Tam Metin - Marmara Medical Journal

Transkript

2009 , Cilt 22, Sayı 3
Marmara
Medical
Journal
Marmara Üniversitesi
Tıp Fakültesi
Dergisi
ISSN: 1309-9469
Marmara Medical Journal
Marmara Üniversitesi Tıp Fakültesi Dergisi
Sahibi
Marmara Üniversitesi Tıp Fakültesi adına
Dekan
Prof. Dr. Davut Tüney
Editör
Prof Dr Emel Demiralp
Editör Yardımcıları
Doç. Dr. Dilek Gogas Yavuz
Doç Dr. Önder Ergönül
İstatistik Editörü
Doç. Dr. Nural Bekiroğlu
Seza Arbay, MA
Koordinatörler
Dr. Vera Bulgurlu
Editörler Kurulu
Prof. Dr. Mehmet Ağırbaşlı
Prof. Dr. Serpil Bilsel
Prof. Dr. Safiye Çavdar
Prof. Dr. Tolga Dağlı
Prof. Dr. Haner Direskeneli
Prof. Dr. Kaya Emerk
Prof. Dr. Mithat Erenus
Prof. Dr. Zeynep Eti
Prof. Dr. Rainer W. Guillery
Prof. Dr. Oya Gürbüz
Prof. Dr. Hande Harmancı
Prof. Dr. Hızır Kurtel
Prof. Dr. Ayşe Özer
Prof. Dr. Tülin Tanrıdağ
Prof. Dr. Tufan Tarcan
Prof. Dr. Cihangir Tetik
Prof. Dr. Ferruh Şimşek
Prof. Dr. Dr. Ayşegül Yağcı
Prof. Dr. Berrak Yeğen
Doç. Dr. İpek Akman
Doç. Dr. Gül Başaran
Doç. Dr. Hasan Batırel
Doç. Dr. Nural Bekiroğlu
Doç. Dr. Şule Çetinel
Doç. Dr. Mustafa Çetiner
Doç. Dr. Arzu Denizbaşı
Doç. Dr. Gazanfer Ekinci
Doç. Dr. Dilek Gogas
Doç. Dr. Sibel Kalaça
Doç. Dr. Atila Karaalp
Doç. Dr. Bülent Karadağ
Doç. Dr. Handan Kaya
Doç. Dr. Gürsu Kıyan
Doç. Dr. Şule Yavuz
Asist. Dr. Asım Cingi
Asist. Dr. Arzu Uzuner
Marmara Medical Journal
DERGİ HAKKINDA
Marmara Medical Journal, Marmara Üniversitesi Tıp Fakültesi tarafından
yayımlanan multidisipliner ulusal ve uluslararası tüm tıbbi kurum ve personele
ulaşmayı hedefleyen bilimsel bir dergidir. Marmara Üniversitesi Tıp Fakültesi
Dergisi, tıbbın her alanını içeren özgün klinik ve deneysel çalışmaları, ilginç olgu
bildirimlerini, derlemeleri,
davet edilmiş derlemeleri, Editöre mektupları,
toplantı, haber ve duyuruları, klinik haberleri ve ilginç araştırmaların özetlerini ,
ayırıcı tanı, tanınız nedir başlıklı olgu sunumlarını, , ilginç, fotoğraflı soru-cevap
yazıları (photo-quiz) ,toplantı, haber ve duyuruları, klinik haberleri ve tıp
gündemini belirleyen güncel konuları yayınlar.
Periyodu: Marmara Medical Journal -Marmara Üniversitesi Tıp Fakültesi Dergisi
yılda 3 sayı olarak OCAK,MAYIS VE EKİM AYLARINDA yayınlanmaktadır.
Yayına başlama tarihi:1988
2004 Yılından itibaren yanlızca elektronik olarak
yayınlanmaktadır
Yayın Dili: Türkçe, İngilizce
eISSN: 1309-9469
Temel Hedef Kitlesi: Tıp alanında tüm branşlardaki hekimler, uzman ve öğretim
üyeleri, tıp öğrencileri
İndekslendiği dizinler: EMBASE - Excerpta Medica ,TUBITAK - Türkiye Bilimsel
ve Teknik Araştırma Kurumu , Türk Sağlık Bilimleri İndeksi, Turk Medline,Türkiye
Makaleler Bibliyografyası ,DOAJ (Directory of Open Access Journals)
Makalelerin ortalama değerlendirme süresi: 8 haftadır
Makale takibi -iletişim
Seza Arbay
Marmara Medical Journal (Marmara Üniversitesi Tıp Fakültesi Dergisi)
Marmara Üniversitesi Tıp Fakültesi Dekanlığı,
Tıbbiye cad No:.49 Haydarpaşa 34668, İSTANBUL
Tel: +90 0 216 4144734
Faks: +90 O 216 4144731
e-posta: [email protected]
Yayıncı
Plexus BilişimTeknolojileri A.Ş.
Tahran Caddesi. No:6/8, Kavaklıdere, Ankara
Tel: +90 0 312 4272608
Faks: +90 0312 4272602
Yayın Hakları: Marmara Medical Journal ‘in basılı ve web ortamında yayınlanan yazı, resim,
şekil, tablo ve uygulamalar yazılı izin alınmadan kısmen veya tamamen herhangi bir vasıtayla
basılamaz. Bilimsel amaçlarla kaynak göstermek kaydıyla özetleme ve alıntı yapılabilir.
www.marmaramedicaljournal.or
Marmara Medical
Journal
YAZARLARA BİLGİ
Marmara Medical Journal – Marmara
Üniversitesi Tıp Fakültesi Dergisine ilginize
teşekkür ederiz.
Derginin elektronik ortamdaki yayınına
erişim www.marmaramedicaljournal.org
adresinden serbesttir.
Marmara Medical Journal tıbbın
klinik
ve
deneysel
alanlarında
özgün
araştırmalar, olgu sunumları, derlemeler,
davet edilmiş derlemeler, mektuplar, ilginç,
fotoğraflı soru-cevap yazıları (photo-quiz),
editöre mektup , toplantı, haber ve
duyuruları,
klinik
haberleri
ve
ilginç
araştırmaların özetlerini yayınlamaktadır.
Yılda 3 sayı olarak Ocak, Mayıs ve Ekim
aylarında
yayınlanan
Marmara
Medical
Journal
hakemli
ve
multidisipliner
bir
dergidir.Gönderilen
yazılar
Türkçe
veya
İngilizce olabilir.
Değerlendirme süreci
Dergiye gönderilen yazılar, ilk olarak
dergi standartları açısından incelenir. Derginin
istediği forma uymayan yazılar, daha ileri bir
incelemeye gerek görülmeksizin yazarlarına
iade edilir. Zaman ve emek kaybına yol
açılmaması için, yazarlar
dergi kurallarını
dikkatli incelemeleri önerilir.
Dergi kurallarına uygunluğuna karar
verilen yazılar Editörler Kurulu tarafından
incelenir ve en az biri başka kurumdan olmak
üzere iki ya da daha fazla hakeme gönderilir.
Editör, Kurulu yazıyı reddetme ya da
yazara(lara) ek değişiklikler için gönderme
veya
yazarları
bilgilendirerek
kısaltma
yapmak hakkına sahiptir.
Yazarlardan
istenen değişiklik ve düzeltmeler yapılana
kadar,
yazılar
yayın
programına
alınmamaktadır.
Marmara Medical Journal gönderilen
yazıları
sadece
online
olarak
http://marmaramedicaljournal.org/submit.
adresinden kabul etmektedir.
Yazıların bilimsel sorumluluğu yazarlara
aittir. Marmara Medical Journal yazıların
bilimsel sorumluluğunu kabul etmez. Makale
yayına kabul edildiği takdirde Yayın Hakkı
Devir Formu imzalanıp dergiye iletilmelidir.
Gönderilen yazıların dergide yayınlanabilmesi
için daha önce başka bir bilimsel yayın
organında yayınlanmamış olması gerekir.
Daha önce sözlü ya da poster olarak
sunulmuş
çalışmalar,
yazının
başlık
sayfasında
tarihi
ve
yeri
ile
birlikte
belirtilmelidir. Yayınlanması için başvuruda
bulunulan makalelerin, adı geçen tüm
yazarlar tarafından onaylanmış olması ve
çalışmanın başka bir yerde yayınlanmamış
olması
ya
da
yayınlanmak
üzere
değerlendirmede olmaması gerekmektedir.
Yazının son halinin bütün yazarlar tarafından
onaylandığı ve çalışmanın yürtüldüğü kurum
sorumluları
tarafından
onaylandığı
belirtilmelidir.Yazarlar tarafından imzalanarak
onaylanan üst yazıda ayrıca tüm yazarların
makale
ile
ilgili
bilimsel
katkı
ve
sorumlulukları yer almalı, çalışma ile ilgili
herhangi bir mali ya da diğer çıkar çatışması
var ise bildirilmelidir.( * )
( * ) Orijinal araştırma makalesi veya vaka
sunumu ile başvuran yazarlar için üst yazı
örneği:
"Marmara Medical Journal'de yayımlanmak
üzere sunduğum (sunduğumuz) "…-" başlıklı
makale,
çalışmanın
yapıldığı
laboratuvar/kurum
yetkilileri
tarafından
onaylanmıştır. Bu çalışma daha önce başka
bir dergide yayımlanmamıştır (400 sözcük –
ya da daha az – özet şekli hariç) veya
yayınlanmak
üzere
başka
bir
dergide
değerlendirmede bulunmamaktadır.
Yazıların hazırlanması
Derginin
yayın
dili
İngilizce
veya
Türkçe’dir. Türkçe yazılarda Türk Dil Kurumu
Türkçe
Sözlüğü
(http://tdk.org.tr) esas
alınmalıdır. Anatomik terimlerin ve diğer tıp
terimlerinin
adları
Latince
olmalıdır.
Gönderilen yazılar, yazım kuralları açısından
Uluslararası Tıp Editörleri Komitesi tarafından
hazırlanan “Biomedikal Dergilere Gönderilen
Makalelerde Bulunması Gereken Standartlar “
a ( Uniform Requirements For Manuscripts
Submittted to Biomedical Journals ) uygun
olarak hazırlanmalıdır.
(http://www. ulakbim.gov.tr /cabim/vt)
Makale içinde kullanılan kısaltmalar
Uluslararası kabul edilen şeklide olmalıdır
(http..//www.journals.tubitak.gov.tr/kitap/ma
www.marmaramedicaljourna
knasyaz/)
kaynağına
başvurulabilir.
Birimler, Ağırlıklar ve Ölçüler 11. Genel
Konferansı'nda
kabul
edildiği
şekilde
Uluslararası Sistem (SI) ile uyumlu olmalıdır.
Makaleler
Word,
WordPerfect,
EPS,
LaTeX, text, Postscript veya RTF formatında
hazırlanmalı, şekil ve fotoğraflar ayrı dosyalar
halinde TIFF, GIF, JPG, BMP, Postscript, veya
EPS formatında kabul edilmektedir.
Yazı kategorileri
Yazının gönderildiği metin dosyasının
içinde sırasıyla, Türkçe başlık, özet, anahtar
sözcükler, İngilizce başlık, özet,
İngilizce
anahtar
sözcükler,
makalenin
metini,
kaynaklar, her sayfaya bir tablo olmak üzere
tablolar ve son sayfada şekillerin (varsa) alt
yazıları şeklinde olmalıdır. Metin dosyanızın
içinde, yazar isimleri ve kurumlara ait bilgi,
makalede
kullanılan
şekil
ve
resimler
olmamalıdır.
Özgün Araştırma Makaleleri
Türkçe ve İngilizce özetler yazı başlığı
ile birlikte verilmelidir.
(i)özetler: Amaç (Objectives), Gereç ve
Yöntem
(Materials and Methods) ya da
Hastalar
ve
Yöntemler
(Patients
and
Methods), Bulgular (Results) ve Sonuç
(Conclusion) bölümlerine ayrılmalı ve 200
sözcüğü geçmemelidir.
(ii) Anahtar Sözcükler Index Medicus
Medical Subject Headings (MeSH) ‘e uygun
seçilmelidir.
Yazının diğer bölümleri, (iii) Giriş, (iv)
Gereç
ve
Yöntem
/
Hastalar
ve
Yöntemler, (v) Bulgular, (vi) Tartışma ve
(vii) Kaynaklar'dır. Başlık sayfası dışında
yazının hiçbir bölümünün ayrı sayfalarda
başlatılması zorunluluğu yoktur.
Maddi kaynak , çalışmayı destekleyen
burslar, kuruluşlar, fonlar, metnin sonunda
teşekkürler kısmında belirtilmelidir.
Olgu sunumları
İngilizce ve Türkçe özetleri kısa ve tek
paragraflık olmalıdır. Olgu sunumu özetleri
ağırlıklı olarak mutlaka olgu hakkında bilgileri
içermektedir. Anahtar sözcüklerinden sonra
giriş, olgu(lar) tartışma ve kaynaklar şeklinde
düzenlenmelidir.
Derleme yazıları
İngilizce ve Türkçe başlık, İngilizce ve
Türkçe özet ve İngilizce ve Türkçe anahtar
kelimeler yer almalıdır. Kaynak sayısı 50 ile
sınırlanması önerilmektedir.
Kaynaklar
Kaynaklar yazıda kullanılış sırasına göre
numaralanmalıdır.
Kaynaklarda
verilen
makale yazarlarının sayısı 6 dan fazla ise ilk
3 yazar belirtilmeli ve İngilizce kaynaklarda
ilk 3 yazar isminden sonra “ et al.”, Türkçe
kaynaklarda ise ilk 3 yazar isminden sonra “
ve ark. “ ibaresi kullanılmalıdır.
Noktalamalara birden çok yazarlı bir
çalışmayı tek yazar adıyla kısaltmamaya ve
kaynak sayfalarının başlangıç ve bitimlerinin
belirtilmesine dikkat edilmelidir. Kaynaklarda
verilen dergi isimleri
Index Medicus'a
(http://www.ncbi.nim.nih.gov/sites/entrez/qu
ery.fcgi?db=nlmcatalog) veya Ulakbim/Türk
Tıp Dizini’ne uygun olarak kısaltılmalıdır.
Makale: Tuna H, Avcı Ş, Tükenmez Ö,
Kokino
S.
İnmeli
olguların
sublukse
omuzlarında kas-sinir elektrik uyarımının
etkinliği.
Trakya
Univ
Tıp
Fak
Derg
2005;22:70-5.
Kitap: Norman IJ, Redfern SJ, (editors).
Mental health care for elderly people. New
York: Churchill Livingstone, 1996.
Kitaptan Bölüm: Phillips SJ, Whisnant JP
Hypertension and stroke. In: Laragh JH,
Brenner
BM,
editors.
Hypertension:
Pathophysiology,
Diagnosis,
and
Management. 2nd ed. New York: Raven Pres,
1995:465-78.
Kaynak web sitesi ise:
Kaynak
makalerdeki gibi istenilen bilgiler verildikten
sonra erişim olarak web sitesi adresi ve
erişim tarihi bildirilmelidir.
Kaynak internet ortamında basılan
bir dergi ise:
Kaynak makaledeki gibi
istenilen bilgiler verildikten sonra erişim
olarak URL adresi ve erişim tarihi verilmelidir.
Kongre
Bildirileri:
Bengtsson
S,
Solheim BG. Enforcement of data protection,
privacy and security in medical informatics.
In: Lun KC, Degoulet P, Piemme TE, Rienhoff
O, editors. MEDINFO 92. Proceedings of the
7th World Congress on Medical Informatics;
1992 Sep 6-10; Geneva, Switzerland.
Amsterdam: North-Holland; 1992:1561-5.
Tablo, şekil, grafik ve fotoğraf
Tablo, şekil grafik ve fotoğraflar yazının
içine yerleştirilmiş halde gönderilmemeli.
Tablolar, her sayfaya bir tablo olmak üzere
yazının gönderildiği dosya içinde olmalı ancak
yazıya ait şekil, grafik ve fotografların her biri
ayrı bir imaj dosyası (jpeg yada gif) olarak
gönderilmelidir.
Tablo başlıkları ve şekil altyazıları eksik
bırakılmamalıdır. Şekillere ait açıklamalar
yazının gönderildiği dosyanın en sonuna
yazılmalıdır. Tablo, şekil ve grafiklerin
numaralanarak
yazı
içinde
yerleri
belirtilmelidir. Tablolar yazı içindeki bilginin
tekrarı olmamalıdır.
Makale yazarlarının, makalede eğer daha
önce yayınlanmış alıntı yazı, tablo, şekil,
grafik, resim vb var ise yayın hakkı sahibi ve
yazarlardan yazılı izin almaları ve makale üst
yazısına ekleyerek dergiye ulaştırmaları
gerekmektedir.
Tablolar Metin içinde atıfta bulunulan
sıraya
göre
romen
rakkamı
ile
numaralanmalıdır. Her tablo ayrı bir sayfaya
ve tablonun üst kısmına kısa ancak anlaşılır
bir başlık verilerek hazırlanmalıdır. Başlık ve
dipnot açıklayıcı olmalıdır.
Sütun başlıkları kısa ve ölçüm değerleri
parantez
içinde
verilmelidir.
Bütün
kısaltmalar
ve
semboller
dipnotta
açıklanmalıdır. Dipnotlarda şu semboller:
(†‡¶§) ve P değerleri için ise *, **, ***
kullanılmalıdır.
SD veya SEM gibi istatistiksel değerler
tablo veya şekildin altında not olarak
belirtilmelidir.
Grafik, fotoğraf ve çizimler ŞEKİL olarak
adlandırılmalı, makalede geçtiği sıraya gore
numaralanmalı ve açıklamaları şekil altına
yazılmalıdır Şekil alt yazıları, ayrıca metinin
son sayfasına da eklenmelidir. Büyütmeler,
şekilde uzunluk birimi (bar çubuğu içinde) ile
belirtilmelidir.
Mikroskopik
resimlerde
büyütme
oranı
ve
boyama
tekniği
açıklanmalıdır.
Etik
Marmara Medical Journal’a yayınlanması
amacı
ile
gönderilen
yazılar
Helsinki
Bildirgesi, İyi Klinik Uygulamalar Kılavuzu,İyi
Laboratuar Uygulamaları Kılavuzu esaslarına
uymalıdır. Gerek insanlar gerekse hayvanlar
açısından etik koşullara uygun olmayan
yazılar yayınlanmak üzere kabul edilemez.
Marmara Medical Journal, insanlar üzerinde
yapılan araştırmaların önceden Araştırma Etik
Kurulu tarafından onayının alınması şartını
arar. Yazarlardan, yazının detaylarını ve
tarihini bildirecek şekilde imzalı bir beyan ile
başvurmaları istenir.
Çalışmalar deney hayvanı kullanımını
içeriyorsa, hayvan bakımı ve kullanımında
yapılan
işlemler
yazı
içinde
kısaca
tanımlanmalıdır. Deney hayvanlarında özel
derişimlerde ilaç kullanıldıysa, yazar bu
derişimin kullanılma mantığını belirtmelidir.
İnsanlar
üzerinde
yapılan
deneysel
çalışmaların sonuçlarını bildiren yazılarda,
Kurumsal Etik Kurul onayı alındığını ve bu
çalışmanın yapıldığı gönüllü ya da hastalara
uygulanacak prosedürlerin özelliği tümüyle
kendilerine anlatıldıktan sonra, onaylarının
alındığını gösterir cümleler yer almalıdır.
Yazarlar, bu tür bir çalışma söz konusu
olduğunda, uluslararası alanda kabul edilen
kılavuzlara ve TC. Sağlık Bakanlığı tarafından
getirilen ve 28 Aralık 2008 tarih ve 27089
sayılı Resmi Gazete'de yayınlanan "Klinik
araştırmaları Hakkında Yönetmelik" ve daha
sonra yayınlanan 11 Mart 2010 tarihli resmi
gazete ve 25518 sayılı “Klinik Araştırmalar
Hakkında Yönetmelikte Değişiklik Yapıldığına
Dair Yönetmelik” hükümlerine uyulduğunu
belirtmeli ve kurumdan aldıkları Etik Komitesi
onayını göndermelidir. Hayvanlar üzerinde
yapılan çalışmalar için de gereken izin
alınmalı; yazıda deneklere ağrı, acı ve
rahatsızlık verilmemesi için neler yapıldığı
açık bir şekilde belirtilmelidir.
Hasta
kimliğini
tanıtacak
fotoğraf
kullanıldığında,
hastanın
yazılı
onayı
gönderilmelidir.
Yazı takip ve sorularınız için iletişim:
Seza Arbay
Marmara Universitesi Tıp Fakültesi
Dekanlığı,
Tıbbiye Caddesi, No: 49, Haydarpaşa
34668, İstanbul
Tel:+90 0 216 4144734
Faks:+90 0 216 4144731
e-posta: [email protected]
İÇİNDEKİLER
Orjinal Araştırma
FACTORS EFFECTING MORTALITY IN PATIENTS WITH GUNSHOT INJURIES
Savaş Eriş, Murat Orak, Behçet Al, Cahfer Güloğlu, Mustafa Aldemir…………………………………181
D VİTAMİNİ TEDAVİSİNİN ETKİNLİĞİ FALANGEAL RADYOGFRAFİK
ABSORPSİYOMETRİ İLE İZLENEBİLİR Mİ? Ümran Kaya, Evrim Karadağ Saygı, Işıl Üstün,
Gülseren Akyüz………………………………………………………………………………………………….192
INCIDENTAL DETECTION OF CORONARY ARTERY CALCIFICATIONS ON NONCARDIAC THORACIC CT EXAMINATIONS Kadriye Orta Kılıçkesmez, Özgür Kılıçkesmez,
Neslihan Taşdelen, Duygu Kara, Yüksel Işık, Arda Kayhan, Bengi Gürses, Nevzat Gürmen………..197
RADİKAL PROSTATEKTOMİ SPESMENLERİNDEKİ VEGF’İN, E-CADHERİN’İN VE
BIM’İN İMMÜNOHİSTOKİMYASAL EKSPRESYONLARININ PROGNOSTİK DEĞERİ
Erem Kaan Başok, Asıf Yıldırım, Adnan Başaran, Ebru Zemheri, Reşit Tokuç………………………..203
CYTOGENETIC ANALYSIS IN INFERTILE MALES WITH SPERM ANOMALIES Ebru
Önalan Etem, Hüseyin Yüce, Deniz Erol, Şükriye Derya Deveci, Gülay Güleç Ceylan,
Halit Elyas………………………………………………………………………………………………………217
THE COMPARISON OF THE RECOVERY CHARACTERISTICS OF EITHER SPINAL OR
EPIDURAL ANESTHESIA WITH PRILOCAINE FOR KNEE ARTHROSCOPY Hatice Türe,
Binnaz Ay, Zeynep Eti, F. Yılmaz Göğüş…………………………………………………………………….225
Olgu Sunumu
ABDOMINAL TUBERCULOSIS IN A 3-YEAR-OLD CHILD Atilla Şenaylı, Taner Sezer, İsmail
Hakkı Göl, Ünal Bıçakçı……………………………………………………………………………………….233
GIANT EPIDERMAL CYST OF THE FOREARM Elif Karadeli, Esra Meltem Kayahan Ulu,
Ahmet Fevzi Ozgur, Emine Tosun…………………………………………………………………………….237
POST-CAESAREAN RECTUS SHEATH HAEMATOMA: A CASE REPORT Imtiaz Wani...240
RETROPERITONEAL CASTLEMAN’S DISEASE: REPORT OF FOUR CASES Pinar Yazıcı,
Ünal Aydin, Oktay Tekesin, Murat Zeytunlu, Murat Kılıç, Mine Hekimgil, Ahmet Coker…………….243
ENDOVASCULAR TREATMENT OF A VERTEBRAL ARTERIOVENOUS FISTULA: CASE
REPORT Feyyaz Baltacıoğlu…………………………………………………………………………………248
BEHÇET OLGUSUNDA DİŞ ÇEKİMİ SONRASI GELİŞEN EKSTERNAL KAROTİD
ARTER PSEUDOANEVRİZMASI VE İNTERNAL JUGULER VEN TROMBOZU Figen
Palabıyık, Arda Kayhan, Esra Karaçay, Ercan İnci, Tan Cimilli………………………………………...252
ORIGINAL RESEARCH
FACTORS AFFECTING MORTALITY IN PATIENTS WITH GUNSHOT INJURIES
Savaş Eriş1, Murat Orak2, Behçet Al3, Cahfer Güloğlu2, Mustafa Aldemir2
1
Adıyaman Devlet Hastanesi, Acil Tıp, Adıyaman, Türkiye 2Dicle Universitesi Tıp Fakültesi, Acil
Tıp, Diyarbakır, Türkiye 3Gaziantep Universitesi Tıp Fakültesi, Acil Tıp, Gaziantep, Türkiye
ABSTRACT
Objective: We planned this study in order to determine the factors affecting mortality in patients with
gunshot injuries in more than one organ.
Methods: We retrospectively reviewed the hospital records of 714 patients admitted to the Emergency
Department of Dicle University, between January 2000 and December 2004. The factors that we considered
would affect mortality such as age, sex, attempts suicide, long barrelled gun injuries, pellet injuries,
contact/near contact shot, delayed admission time, presence of serious anemia and shock during admission,
more than four entrance wounds, injury areas, serious cranial, thorax and abdominal injuries, vascular
injuries in the extremities, administration of multiple transfusion, and trauma scores as GCS, RTS, PATI
were analyzed.
Results: As a result of unvaried statistical analyses, we determined that suicide attempts (p=0.001), presence
of serious anemia (p=0.001) and shock (p=0.001) during admission, presence of serious cranial (p=0.001),
thorax (p=0.001) and abdominal (p=0.001) injury, femoral artery injury (p=0.001), multiple blood
transfusion (p=0.009), , GCS 0-7, GCS 8-12 (p=0.001) and low RTS (p=0.001)were significant factors
affecting mortality.
Conclusion: Multivariate analysis showed that serious anemia during admission, serious cranial injury,
serious abdominal injury and low RTS were independently significant in predicting mortality (p<0.05).
Keywords: Factors, Gunshot, Mortality, Injury, Serious anemia, Suicide
İletişim Bilgileri:
Behçet Al, M.D.
Gaziantep Universitesi Tıp Fakültesi, Acil Tıp, Gaziantep, Türkiye
e-mail: [email protected]
181
Marmara Medical Journal 2009;22(3);000-000
Savaş Eriş, et al.
Factors affecting mortality in patients with gunshot injuries
ATEŞLİ SİLAH YARALANMALI HASTALARDA MORTALİTEYİ ETKİLEYEN
FAKTÖRLER
ÖZET
Amaç: Bu çalışmada birden fazla organda silah yaralanmasına maruz kalan hastalarda mortalitede etkili
faktörleri tespit etmeyi amaçladık.
Yöntem: Dicle Üniversitesi Tıp Fakültesi Acil Tıp Kliniğine Ocak 2000 ile Aralık 2004 arasında ASY
nedeniyle başvuran 714 hastanın kayıtları geriye dönük olarak incelendi. Sağ kalanlar ve ölenler arasında
mortalite üzerine etkisi olabileceğini düşündüğümüz; ileri yaş, cinsiyet, öz kıyım amaçlı olması, uzun
namlulu silahla yaralanma, saçma atan silahlarla yaralanma, yakın atış, gecikmiş başvuru zamanı, başvuruda
derin anemi ve şok varlığı, ateşli silah giriş sayısı ≥4 olması, yaralanma bölgeleri, ciddi kafa, toraks ve batın
yaralanmasının olması, ekstremite vasküler yaralanması, multiple kan transfüzyonu yapılması, GKS, RTS ve
PATİ değerleri analiz edildi.
Bulgular: Ünivariete istatistiksel analizler neticesinde; öz kıyım amaçlı yaralanma (p=0.001), başvuruda
derin anemi (p=0.001) ve şok varlığı (p=0.001), ciddi kafa yaralanması (p=0.001), ciddi toraks yaralanması
(p=0.001) ve ciddi batın yaralanmasının olması (p=0.001), femoral arter yaralanması (p=0.001), multiple kan
transfüzyonu (p=0.009), GKS’nın 0–7 ve 8–12 olması (p=0.001) ve düşük RTS skoru (p=0.001)’nun
mortalite üzerinde anlamlı etkisinin olduğunu tespit ettik.
Sonuç: Multivarite analiz sonucunda; başvuruda derin anemi varlığı, ciddi kafa travması varlığı, ciddi batın
travması olması ve düşük RTS skoru mortaliteyi etkileyen en önemli bağımsız değişkenler olarak bulundu
(p<0.05).
Anahtar Kelimeler: Faktörler, Silah atışı, Mortalite, Yaralanma, Ciddi anemi, Öz kıyım
INTRODUCTION
Nowadays, independent of how socially or
economically developed the country is,
trauma is one of the main public health
problems. In USA, trauma is the leading
cause of death among 1 – 44 year-old
people1-4. In order to decrease the death rates
related to trauma, factors effecting mortality
should be determined and the patients should
be evaluated accordingly. Recent studies are
aimed at determining deaths due to trauma
which could have been prevented4.
Many studies have been made on patients
exposed to gunshot injuries. But the main
factor affecting the mortality is still
controversial. Although, there are mortality
studies related to one system, we have not
come across studies related to the factors
affecting mortality in patients with gunshot
injuries in multiple organs and systems in the
literature. We planned this study in order to
determine the factors affecting mortality in
patients with gunshot injuries in more than
one organ.
Gunshot injuries are one of the leading cause
of high mortality and morbidity in the
hospitals related to trauma surgery in Turkey,
as in all over the world5. Damage is
proportional to the energy transferred to the
tissue, properties of the tissue and how the
tissue distributes the energy1. Damage is
made by the cavitation effect and
fragmentation3. The bullet causes damage not
only in the organ it enters but also in the
nearby tissues because of the blasting effect,
changing direction in the body. Organ injuries
apart from the entrance trace cause the
difficulties in the diagnosis and treatment of
the injuries1,5,6.
MATERIAL AND METHOD
Nine hundred and twenty-two patients were
admitted to the Emergency Department of
Dicle University for gunshot injuries, between
January 2000 and December 2004. Seven
hundred and fourteen of these patients’
hospital
records
were
reviewed
retrospectively. Patient data were recorded to
the standard forms. The parameters used in
the form were age, gender, cause of the
injury, type of gun used, distance of injury,
admittance time, hematocrit, blood pressure,
pulse rate, respiration rate, consciousness
status, entrance number of gunshot, entrance
182
region of gunshot, grade of injured organs,
applied treatment, number of blood
transfusions, period of hospitalization, period
of intensive care and results of treatment.
Glasgow Coma Scale (GCS), revised trauma
score (RTS) and penetrating abdominal
trauma indexes (PATI) were evaluated
independently for each patient. Patients with
missing data in their hospital records, who
were dead on arrival at the hospital, and
penetrating injuries not caused by guns were
not included in this study.
Seven hundred and fourteen patients used in
this study were divided into two groups as
alive (Group 1; n=606) and dead (Group 2;
n=108). The reasons we considered as
affecting mortality between Group 1 and
Group 2 such as old age, gender, aimed of
suicide, long barrelled injuries, pellet injuries,
contact/near contact shot, delayed admission
time, serious anemia during admission,
presence of shock during admission, more
than four entrance wounds, injury regions (1,
2, 3), serious cranial injury, serious thorax
injury, serious abdominal injury, vascular
injury in the extremities, femoral artery
injury, administration of multiple transfusion,
hospitalization time and trauma scores as
GCS, RTS, PATI were analyzed.
While preparing the statistical data; old age
(≥55 years old), gender, cuase of the injury
(murder, suicide, accident), type of gun used
(long barrelled guns, pellet guns, shell guns,
shrapnel or mine), contact/near contact shot (0
– 10 m), delayed admission time (longer than
2 hours after the injury), serious anemia
during admission (hematocrit <20%),
presence of shock during admission (systolic
blood pressure <90 mmHg and heart beat rate
>100 beats/min ) were evaluated. The
entrance regions to the body were determined
as: first region: region covered by the frontal,
parietal, occipital and temporal bones; second
region: region between the left clavicula,
sternum, left rib arc and left medium axillary
line; third region: upper abdominal region
between the horizontal line passing through
the umbilical cord and the rib arcs.
Suicide attempts, serious anemia during
admission, presence of shock during
admission, serious cranial injury, serious
thorax injury, serious abdominal injury,
femoral artery injury, administration of
multiple transfusion, GCS score of 0 – 7,
GCS score of 8 – 12 and RTS score were
evaluated in the multivariable analysis.
Univariable analyses were made by using chisquare test (χ2) for categorical variables and
Student t test for continuous variables. Mann
Whitney U test was applied for the nonhomogenous continuous variables. To
determine the predictive factors affecting
mortality, multivariable analyses were made
by using the Backward Stepwise (Wald)
Logistic Regression method. Mean values
were calculated as Mean ± SEM (Standart
Error Mean). Values of p<0.05 were
considered as statistically significant.
Serious cranial injury (basilar skull fracture,
cerebral contusion/ intracerebral hemorrhage,
subarachnoid
hemorrhage,
epidural
hematoma, subdural hematoma, diffuse
axonal injury, cerebral laceration and
contusion, diffuse cerebral edema), serious
thorax injury (hemothorax, pneumothorax,
hemopneumothorax, pulmonary contusions,
cardiac injury, diaphragm and mediastinal
injuries), serious abdominal injury (solid
visceral injuries, major vascular injuries),
vascular injury in the extremities, femoral
artery injury, administration of multiple blood
transfusion(≥4 Unite), hospitalization time
and trauma scores as GCS, RTS, PATI were
evaluated as probable risk factors for
mortality in gunshot injuries.
RESULTS
Seven hundred and fourteen patients (616
males and 98 females) were included in the
study. Of these patients, 84.9% (n=606) lived
(Group 1), 15.1% (n=108) died (Group 2).
There was no statistical significant difference
between the patients who died or lived
according to gender (p=0.335). While mean
age was 27.25±0.48 (1–82) among all
patients, it was 26.81± 0.51 (1–82) in group 1
and 29.71±1.32 (1–65) in group 2. Seven
183
(6.5%) of the patients who died and 22 (3.6%)
of the patients who lived were old age
patients, but there were no statistical
differences related to old age between the
group 1 and 2 (p=0.167) (Table I).
Table I: Distribution according to gender and old age.
Gender
Male
Female
Old age
≥55
<55
Total
Group 1
n (%)
Group 2
n (%)
Total
n
Statistics
χ2
P value
526 (86.8)
80 (13.2)
90 (83.3)
18 (16.7)
616 (86.3)
98 (13.7)
0.930
0.335
22 (3.6)
584 (96.4)
7 (6.5)
101 (93.5)
29 (4.1)
685 (95.9)
1.912
0.167
606 (84.9)
108 (15.1)
714 (100)
Table II: Distribution of clinical properties of the patients, multiple gunshot injuries and serious organ
injuries.
P value
Group 1
Group 2
Total
Statistics
n(%)
n(%)
n(%)
χ2
Contact/near contact shot
512 (84.5)
102 (94.5)
614 (86)
7.544
0.006
Delayed admission time
271 (44.7)
39 (36.1)
310 (43.4)
2.765
0.096
Severe anemia
16 (3.0)
55 (51.0
71 (10.0)
238.650
0.001
Presence of shock
92 (15.0)
89 (82.0))
181 (25.4)
218.908
0.001
138 (22.8)
30 (27.7)
168(23.7)
1.276
0.259
1.region (Head region)
22 (3.6)
44 (40.7)
66(9.2)
150.476
0.001
2.region (Left thorax region)
36 (5.9)
19 (17.6)
55(7.7)
17.504
0.001
3.region (Upper abdomen region)
95 (15.7)
26 (24.1)
121(16.9)
4.593
0.032
Cranial injury
18 (3.0)
45 (41.7)
63 (8.8)
170.614
0.001
Thorax injury
89 (14.7)
30 (27.8)
119 (16.7)
11.311
0.001
Abdominal injury
50 (8.3)
33 (30.5)
83 (11.6)
44.390
0.001
Vascular injury in the extremities
62 (10.2)
15 (13.9)
77( 10.8)
1.275
0.259
Femoral artery injury
14 (2.3)
9 (8.3)
23 (3.2)
10.667
0.001
Clinical properties of the patients
Multiple gunshot injuries and regions
Multiple gun shot injury
Serious organ injuries
184
Of the injuries, 45 (6.3%) occurred due to
suicide, 184 (25.8%) due to accidents and 485
(67.9%) due to violence. The suicide rate in
group 2 (n=27, 25%) was significantly higher
than in group 1(n=18, 3%) (χ2=75.331,
p=0.001) (Figure 1).
were admitted with delay, for which the
difference between the groups was not
significant (p=0.096). Sevent-one (10%) of
the patients had hematocrit values of 20 mg/dl
or less. Of the patients, who had severe
anemia during admission, 55 (51%) died and
16 (3%) lived. This was statistically
significant for the mortality (χ2=238.650,
P=0.001). Presence of shock during admission
was 15% (n=92) in group 1 and 82% (n=89)
in group 2. That was significant as well
(χ2=218.908, p=0.001) (Table II).
Of the gun types, 172 (24.1%) were pellet,
445 (62.3%) were bullet, 41 (5.7%) were guns
with long barrells, 47 (6.6%) were mines or
shrapnel and 9 (1.3%) were something else.
There was no statistical difference related to
guns with long barrells and pellet guns
between the group 1 and group 2 (p=0.928
and p=0.327, respectively) (Figure 2).
One hundred and sixty eight (23.5%) of the
patients had more than four entrance wounds.
Increase in the number of entrance wounds
did not have a significant effect on the
mortality rate (p=0.259). Distributions of
injuries to the three regions were found to be
statistically significant (Table II).
When Group 2 and Group 1 were compared;
it was determined that, head, thorax and
abdomen region injuries were significantly
higher in Group 1. Sixty two patients (10.2%)
in Group 1 and 15 patients in Group 2
(13.9%) had vascular injury in the
extremities. While vascular injury in the
extremities did not have a significant effect
on the mortality (χ2=1.275, p=0.259), femoral
artery injury did (χ2=10.667, p=0.001) (Table
II).
Figure 1: Distribution of gunshot exposure
because of suicide, accident and violence in the
groups.
Of the patients with abdominal injuries
(n=220), 37 (16.8%) died, while 183 (83.2%)
survived. 55 (25%) of the injuries did not
penetrate to the abdomen. The most
commonly injured organs were the small
bowel and the large intestine. The average
PATI value calculated was 14.31±1.03 for
Group 1, while it was 39.51±2.99 for Group
2. The effect of PATI on the mortality was
found to be extremely important. Of the
patients with ≥25 PATI value, 40 (21.8%)
survived, while 29 (78.4%) died. The
difference between the groups was found to
be significant (χ2=45.673, p=0.001).
Figure 2: Distribution of the guns’ type that
were used.
Five hundred and twelve (84.5% ) patients
from group 1 and 102 (94.5%) patients from
group 2 were exposed to contact/near contact
shots. Contact/near contact shots affected
mortality significantly (χ2=7.544, p=0.006).
Three hundred and ten (43.4%) of the patients
One hundred and seventy six (24.6%) of the
patients had thorax trauma. While 144
(81.8%) of them survived, 32 (18.2%) died.
104 of the patients had hemopneumothorax,
185
was 14.60±0.045 in group 1 and 5.73±0.285
in group 2, which was found to be statistically
significant (p=0.001). The mean RTS value of
the patients was 11.75±2.94 in group 1 and
5.45±0.32 in group 2. We found out that, the
effect of low RTS value had a statistically
significant effect on the mortality (p=0.001).
76 had pulmonary contusions, 13 had major
vascular injury, 15 had cardiac injury, and 57
patients had extrathoracic injury. In 119
(16.7%) patients, the wounds had penetrated
the thorax. Twenty seven (15.3%) patients
underwent thoracotomy and 86 (48.9%)
patients had a chest tube installed. The heart
injury ratio was 8.5% (n=15).
The following factors were found to have
significant effect on mortality by using
invariable statistical analyses: suicide
attempts (p=0.001), serious anemia during
admission (p=0.001), presence of shock
during admission (p=0.001), serious cranial
injury (p=0.001), serious thorax injury
(p=0.001),
serious
abdominal
injury
(p=0.001), femoral artery injury (p=0.001),
administration of multiple transfusion
(p=0.009), GCS score of 0 – 7 (p=0.001),
GCS score of 8 – 12 (p=0.001) and low RTS
score (p=0.001). These variables were entered
into the logistic regression model for
revealing the risk factors causing mortality.
Twenty one (19.4%) of the patients who died
and 64 (10.6%) of the patients who survived
received blood transfusions ≥4 Unite, and the
effect of multiple blood transfusion was found
to be significant (χ2=6.897, p=0.009). While
365 (51.1%) patients were operated, 349
(48.9%) were medically treated. Mean
hospitalization duration was 1.65±0.23 (1–15)
and 11.15±0.51 (1–80) days for the dead and
alive groups, respectively. The hospitalization
duration had a significant effect on the
mortality (p=0.001).
Four (0.7%) patients from the alive group and
89 (82.4%) patients from the dead group had
0 – 7 GCS values and were evaluated as being
in the severe group. Twenty one (3.5%)
patients from the alive group and 13 (12%)
patients from the dead group had 8 – 12 GCS
values which were evaluated as being in the
medium group. We found that, having 0 – 7
GCS value and 8 – 12 GCS value had a very
significant
effect
on
the
mortality
(χ2=540.714, p=0.001 and χ2=14.850,
p=0.001; respectively). The mean GCS value
In the multivariate analyses, serious anemia
during admission [Odds ratio (OR)=0.085,
%95 confidence interval (CI) =0.019–0.369,
p=0.001], serious cranial injury (OR=0.006,
CI=0.001–0.038, p=0.001), serious abdominal
injury (OR=0.130, CI=0.026–0.640, p=0.012)
and low RTS score (OR=0.199, CI=0.121–
0.328, p=0.001) were found as significantly
important for mortality (Table III).
Table III: Logistic Regression analysis results of the risk factors.
Factors
Odds Ratio
(OR)
%95 Confidence interval
(CI)
P value
Anemia during admission
0.085
0.019–0.369
0.001
Serious cranial injury
0.006
0.001–0.038
0.001
Serious abdominal injury
0.130
0.026–0.640
0.012
Low RTS
0.199
0.121–0.328
0.001
186
common23-25. Suicide cases accounted for
6.3% in our study and were found to have an
effect on mortality by invariable analysis. The
reason for the high mortality rate in the
suicide cases were shots in the head region
and late arrival to the hospital.
DISCUSSION
Trauma is one of the main public health
problems in every country. Injuries occur in
all age groups and in both genders, but are
more often observed in young men1-4. 25% of
all the deaths in the United States of America
occur as a result of trauma4. Gunshot injuries
are one of the leading factors causing high
mortality and morbidity in the hospitals
dealing with trauma surgery in our country
and all over the world5. In the study of Gören
et al.7, a 5.6/100000 death rate was found to
be caused by gunshot injuries in 1996 – 2001;
which is fairly high compared to the other
studies8,9. 14.3% of the autopsies in
Diyarbakir are the result of gunshot injury
cases7. We did not come across a general
mortality rate in the literature because there
are no gunshot injury studies related to the
whole body. But in some series, cranial
injuries the mortality rates were 23 – 92% and
considering the neurological conditions, the
mortality rates increased to 87 – 100%10-14.
The mortality rates in which the thorax region
was exposed to the gunshot injuries varied
between 14.3% and 36.8%15,16. And the
mortality rates in which the abdominal region
was exposed to the gunshot injuries varied
between 3% and 31.4% in different studies1721
. The general mortality rate for our study
was 15.1%.
The type of gun used is one of the effective
factors on mortality and morbidity for
gunshot injuries. Mortality and complication
rates are especially higher for the injuries
which are caused by high-accelerated guns
and hunting guns15,23. It is stated in the
literature that mortality and morbidity rates
differ highly in the bullet and pellet
injuries5,17,24,25. For the contact shot pellet
injuries, the whole kinetic energy of the gun is
diffused into the tissue and causes effects like
those of high-accelerated guns26. For the
injuries of distant pellet shots, each pellet
behaves as a low kinetic energized particle
before arriving at the tissue27. In a study of
Glezer et al.24, the mortality rates caused by
pellet injuries were 20 – 38%. In the study of
Feliciano et al.17, the mortality rates caused by
bullet injuries were 5 – 12%. The type of gun
used was not found to be effective on
mortality in our study. The reason for this
may be due to patients who had solely
abdominal region injuries in the abovementioned studies. It might be stated that the
type of gun used is effective on the mortality
rate for the abdominal region. But when the
whole body and other factors are considered,
the effect of the type of gun used decreases. In
our study, cases shot from 0 – 15 m had a
high mortality rate. This might be because of
the high probability of having mortal injuries
in the vital organs from contact shots and the
decreasing kinetic energy of the gun while the
distance increases.
The age of the patient with trauma is an
effective factor in mortality. For patients over
50, mortality rate increases significantly4,22.
4.1% of the patients in our study were over 50
(≥55). 86.3% of the patients in our study were
men and the average age was 27.2. Gender
and old age were not found to affect
mortality. The reason was that young and
active people carry guns, argue and fight more
often. Most of the patients in our study were
young and active people and the number of
old patients in our study was low.
In the study of Baker et al.28, it is stated that
the duration between injury and treatment is
effective on the mortality. Some other
studies19,20 support this statement. In studies
with a smaller number of cases5,29, the
situation is adverse. A longer duration causes
the duration of shock to be longer and
deeper28. Parallel to this, it is stated in most of
the studies that the most common cause of
In the study of Gören et al7 which was carried
out in our geographic region, it was found that
66.7% of the gunshot injury cases were due to
murder. In our study, gunshot injury cases
caused by violence accounted to 67.9%. But
in some societies, suicide cases are more
187
death is the hypovolemic shock4,17,18,30,31.
Britt et al.32 stated that hypovolemic shock
has a 5.5% to 100% role in patients who died
because of trauma. In our study, 82% of the
patients who died were in shock during
admittance, which is statistically meaningful.
Also, there are studies which state the
relationship between continuing hypotension
and increasing mortality33. Losing blood and
not substituting the blood, being unable to
control the bleeding are important problems
for the patients with trauma. According to
Carillo et al.34, 4 – 5 l of early blood loss is
very effective on the mortality rate and is a
valid parameter for deciding on the type of
surgery for the patient. 51% of the patients in
the dead group and 3% of the patients in the
alive group had less than or equal to 20 mg/dl
hematocrit value. This situation had an effect
on the mortality independent of the delayed
admittance or presence of shock during
admittance. If the hematocrit value of the
patient is less than or equal to 20 mg/dl during
admission, bleeding should be controlled and
replacement therapy should be applied very
urgently. We have also observed in our study
that, ≥4 Unite blood transfusions increased
the rate of mortality.
very frequently used scoring system for the
evaluation of the neurologic condition in
cranial traumas, usually in emergency
services41,42 and is a good indication of
prognosis10. This scoring system is simple and
very useful for the evaluation of mortality and
morbidity of the patient. It is in good
correlation with the severity of the cranial
trauma43. Of the GCS scores in our patients
who died, 82.4% were 0–7 and 12% were 8–
12 GCS. Decreasing GCS score is one of the
factors affecting mortality, according to the
literature. We have found out in our study that
both low scores (0 – 7) and moderate scores
(8 – 12) affect mortality. However, by using
multivariable analyses, we observed that the
most important factor was the presence of
severe cranial damage. Presence of severe
cranial injury is an important factor which
increases the mortality rate.
Thorax injuries are still dangerous and they
constitute 20 – 25% of the deaths caused by
trauma in the first four decades of human
life44. Thorax injuries are more common
among
young
people.
Except
for
thoracotomy, treatment methods are sufficient
for most of the thorax injuries45. Parenchymal
injuries such as pulmonary contusion have an
important effect on the mortality for most of
the patients with thorax injuries46,47. Mortality
varies between 14.3% and 36.8% in thorax
injury cases15,16. Right thorax region injuries
are more common, while left thorax injuries
are more vital48,49. The mortality rate for 176
patients with thorax injuries in our study was
18.2%. While the thoracotomy frequency was
15.3%, chest tube was placed in 48.9% of the
patients with thorax injuries in our study. 119
patients had severe thorax trauma.
Hemopneumothoraks took the first place as
59.1% while contusion was in the second
place. In our study, the hearth injury ratio was
8.5%. By using invariable analysis, it was
found that severe thorax trauma affected the
mortality rate. Multivariable analysis showed
that it did not affect mortality as much as the
cranial and abdominal injuries.
Lower extremity, the abdominal region and
upper extremity regions are the most frequent
injury regions for the gunshot injuries,
respectively35. The frequency order was
similar in our study 33.6% in the lower
extremity, 30.8% in the abdominal region and
24.9% in the upper extremity. Regarding the
entrance regions, there were three. Of the
injury regions of patients who died in our
study, 40.7% were cranial, 17.6% were in the
left thorax region and 24.1% were upper
abdominal. Injuries in these regions
significantly affected the mortality rate.
Entrance wounds in these three regions
should alert the clinician.
Deaths caused by cranial region traumas take
first place among all the deaths caused by
The
mortality
rate
for
trauma36-38.
craniocerebral gunshot injuries is declared as
23% - 92% in different studies11-14,38-40. The
mortality rate of patients with cranial gunshot
injuries in our study was 71.4%. GCS is a
Establishing sufficient ambulance services,
blood banks and regional trauma centers
decreased mortality rates to 9.5% in the
188
1990s31,50,51. Delayed admission time,
insufficient blood support and the high rate of
large intestine injuries affected the postoperative infectious complications and the
death incidence52,53. The risk factors related to
post-operative infections for abdominal
gunshot injuries are uncontrolled shock,
duration of surgery, transfusion requirement,
number of injured organs and the PATI54,55. It
was stated in the literature that mortality rate
for the abdominal region gunshot injuries was
3% to 31.4% in different studies18,21,56. The
mortality rate for the abdominal injuries in
our study was 16.8%. The high mortality rate
in our study might be due to the insufficient
pre-hospital services. It was found out in
different studies that there is a direct
relationship between the number of injured
organs and the mortality and morbidity18-21,57.
According to the literature concerning injured
organs; the small bowel, large intestine and
liver take the first three places5,17,21,56.
Frequencies of organ injuries in our study are
similar. The morbidity rate for cases with
abdominal trauma index greater than or equal
to 25 is 42%, while it is 7% for the cases with
abdominal trauma index less than 25
according to Thomsen and friends58. The
average PATI was 14.3 for group 1 and 39.5
for group 2 in our study. Mortality was found
to be 78% for patients with >25 PATI score.
PATI is an independent factor affecting
mortality significantly in abdominal injuries,
as compatible with the literature. The
presence of severe abdominal trauma has
significantly affected mortality in our
multivariable analyses.
artery injury affected mortality in our study.
This result might be explained by the
excessive loss of blood from the femoral
artery. The other veins or arteries of the
extremity are narrower and between the
compartments, so they can be easily affected
by thromboses and the patient can gain time.
Vascular examination on the part of the
clinician in extremity gun shot injuries is very
important.
Revised trauma score is the indicative factor
of mortality for patients with trauma, as stated
in many studies60,61. Low RTS affected
mortality in our study, as in the literature.
CONCLUSION
We have established the factors affecting
mortality in gunshot injuries in all body
regions. As a result of invariable statistical
analyses, we determined that attempted
suicide, presence of serious anemia during
admission, shock, serious cranial trauma,
serious thorax injury, serious abdominal
injury, femoral artery injury, multiple blood
transfusion, GCS 0-7, GCS 8-12, low RTS
were significant factors affecting mortality.
While these results were evaluated by using
multivariable analysis; we found out that
serious anemia during admission, serious
cranial injury, serious abdominal injury and
low RTS were independently significant in
predicting mortality. It can be stated by using
these results that; taking the surgery decision
at the emergency service without losing time,
promptly starting treatment for patients in
shock and with serious anemia and examining
carefully the cranial and abdominal injuries
lead to a decrease in mortality rates.
The emergency treatment of penetrating
extremity trauma is gaining importance
nowadays, as compared with the past. The
most frequent cause of the vascular injuries in
the extremities was penetrating injuries
(82%). Sixty five percent of these injuries
were related to hunting rifles and pistols. The
percent of complications in extremity injuries
is related to the amount of energy transferred
to the tissue. Complications are wound
infection,
neurovascular
injury
and
compartment syndrome, ununion and
malunion59. While vascular extremity injuries
had no significant effect on mortality, femoral
Acklowledgement
The work has been funded by the Institutional
recources of Emergency Department of Dicle
University.
REFERENCES
1.
189
Hoyt DB, Potenza BM, Cryer HG, et al. Trauma. In:
Greenfield LJ, Mullholland MW, Oldham KT, Zelenock
GB, Lilimoe KD eds. Surgery:Scientific Principles and
Practise. 2nd edn. Philadelphia: Lippincott-Raven,
1997:267–421.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Burch JM, Franciosa RJ, Moore EE. Trauma. In:
Schwartz SI, ed. Principles of Surgery. 7th edn.
Singapore: McGraw-Hill, 1999:155–222.
Taviloğlu K. Travmaya genel yaklaşım. In: Kalaycı G,
Acarlı K, Demirkol K, Ertekin C, Mercan S, Özmen V,
eds. Sökücü N. Genel Cerrahi. 1. Baskı. İstanbul: Nobel
Tıp Kitabevleri Ltd, 2002:297–312.
Feliciano DV. Patterns of injury. In: Feliciano DV,
Moore E, Mattox KL, eds. Trauma. Connecticut:
Stamford, 1996:85-l05.
Oymacı E, Kapkaç M, Uçar Y,Ertan H, Özdedeli
E,Tokat Y. The effects of gunshot and shotgun wounds
to mortality and morbidity. Turkish J Trauma & Emerg
Surg 1997; 3:132–136.
Grimes WR, Deitch EA, McDonald JC. A clinical
review of shotgun wounds to the chest and abdomen.
Surg Gynecol Obst 1985; 160:148–152.
Gören S, Subaşı M, Tıraşcı Y, Kemaloğlu S. Firearm
releated mortality: a review of 444 deaths in Diyarbakir,
Turkey between 1996 and 2001. Tohoku J Exp Med
2003; 201:139–145.
Elfawal MA, Awad OA. Firearm fatalities in Eastern
Saudi Arabia, impact of culture and legislation. Am J
Forensic Med Pathol 1997; 18: 391–396.
Azmak D, Altun G, Bilge S, Yılmaz A. Firearm
fatalities in Edirne, 1984–1997. Forensic Sci Int 1998;
95: 231–239.
Martins RS, Siqueira MG, Santos MTS, Zanon-Collange
N, Moraes OJS. Prognostic factors and treatment of
penetrating gunshot wounds to the head. Surg Neurol
2003; 60: 98–104.
Aarabi B. Surgical outcome in 435 patients who
sustained missile head wounds during the Iran-Iraq war.
Neurosurgery 1990; 27: 692–695.
Levy ML, Masri LS, Levy KM, et al. Penetrating
craniocerebral injuries resultant from gunshot wounds:
gangrelated injury in children and adolescents.
Neurosurgery 1993; 33: 1018 –1026.
Rosenfeld JV. Gunshot injury to the head and spine. J
Clin Neurosci 2002; 9: 9–16.
Semple PL, Domingo Z. Craniocerebral gunshot injuries
in South Africa’a suggested management strategy. S Afr
Med J 2001; 91: 141–145.
İnci İ, Özçelik C, Taçyıldız İ, Nizam Ö, Eren N, Özgen
G. Penetrating chest injuries: Unusually high incidence
of high velocity gunshot wounds in civilian practice.
World J Surg 1998; 22: 438–442.
Mandal AK, Oparah SS. Unusually low mortality of
wounds of the chest: twelve years experience. J Thorac
Cardiovasc Surg 1989; 97: 119–125.
Feliciano DV, Burch JM, Patrinel VS, Mattox KL,
Jordan GL. Abdominal gunshot wounds. An urban
trauma center’s experience with 300 consecutive
patients. Ann Surg 1988; 208: 362–370.
Adesanya AA, da Rocha-Afodu JT, Ekanem EE,
Afolabi IR. Factors affecting mortality and morbidity in
patients with abdominal gunshot wounds. Injury 2000;
31: 397–404.
Taçyıldız IH, Aban N, Öztürk A, Arslan Y, Akgün Y.
Factors effecting mortality in penetrating abdominal
trauma. Turkish Journal of Trauma & Emergency
Surgery. 1997; 3: 213-217.
Aldemir M, Taçyıldız IH, Girgin S. Predicting factors
for mortality in the penetrating abdominal trauma. Acta
Chir Belg 2004; 104:429–434.
Coupland R. Abdominal wounds in war. Br J Surg 1996;
83: 1505–1511.
22. Morris JA, McKenzie EJ, Edelstein SL. The effect of
preexisting conditions on mortality in trauma patients.
JAMA 1990; 263:1942–1946.
23. Çıkırıkçıoğlu M, Çağırıcı U, Atay Y, Yağdı T, Telli A,
Bilkay Ö. Thoracic gunshot injuries. Turkish Journal of
Trauma & Emergency Surgery. 1999; 5: 266–269.
24. Glezer JA, Minard G, Croce MA, Fabian TC, Kudsk
KA. Shot gun wounds to the abdomen. Am Surg 1993;
59: 129–132.
25. Dawidson I, Miller E, Litwin MS. Gunshot wounds of
the abdomen. A review of 277 cases. Arch Surg 1976;
111: 862–865.
26. Ordog GJ, Wasserberger J, Balasubramaniam S.
Shotgun wound ballistics. J Trauma 1988; 28: 624-631.
27. Deitch EA, Grimes WR. Experience with 112 shotgun
wounds of the extremities. J Trauma 1984; 24: 600–603.
28. Baker CC, Degutis LC. Predicting outcome in multiple
trauma patients. Infect Surg 1986; 5: 243–245.
29. Çelen O, Oğuz S, Doğan M. Abdominal gunshots
wounds: Retrospective analysis of 164 patients. Turkish
Journal of Trauma & Emergency Surgery. 2001; 4: 258
– 261.
30. Demetriades D,Velmahos G, Cornwell E. Selective
nonoperative management of gunshot wounds of the
anterior abdomen. Arch Surg 1997; 132: 178–183.
31. Fiedler MD, Jones LM, Miller SF, Finley RK. A
correlation of response time and the results of abdominal
gunshot wounds. Arch Surg 1986; 121: 902–904.
32. Britt LD, Weireter LJ, Riblet JL, Asensio JA, Maull K.
Priorities in the management of profound shock. Surg
Clin North Am 1996; 76: 645–660.
33. MacKenzie EJ. Injury severity scales: Overview and
directions for future research. Am J Emerg Med 1984; 2:
537–549.
34. Carillo C, Fogler RJ, Shaftan GW. Delayed
gastrointestinal reconstruction following massive
abdominal trauma. J Trauma 1993; 34: 233–235.
35. Boon JM, Asobayire WM. Gun shot injuries-an analysis
of an epidemic in a South African secondary level public
sector hospital, Geneeskunde. The Medicine Journel.
2001: 43: 16-19.
36. Rakunt C, İyigün Ö. Kafa travmaları. In: Şahinoğlu AH
ed. Yoğun Bakım Sorunları ve Tedavi İlkeleri. 2. baskı.
Ankara: Türkiye Klinikleri, 2003: 347–406.
37. Yagmur Y, Guloglu C, Aldemir M, Orak M. Falls from
flat-roofed houses: a surgical experience of 1643
patients. Injury 2004; 35: 425–428.
38. Kennedy F, Gonzalez P, Dang C, Fleming A, SterlingScott R. The Glasgow coma scale and prognosis in
gunshot wounds to the brain. J Trauma 1993; 35: 75–77.
39. Benzel EC, Day WT, Kesterson L, et al. Civilian
craniocerebral gunshot wounds. Neurosurgery 1991; 29:
67–71.
40. Dove DB, Stahl WM, DelGuercio LRM. A five year
review of deaths following urban trauma. J Trauma
1980; 20: 760–766.
41. Danne P, Brazenor G, Cade R, et al. The major trauma
management study: an analysis of the efficacy of current
trauma care. Anz J Surg 1998: 68: 50–57.
42. Gabble BJ, Cameron PA, Finch CF. The status of the
Glasgow
Coma
Scale.
Emerg
Med
(fremantle).2003;15:353–560.
43. Özgüç H. Travmada skorlama sistemleri. In: Şahinoğlu
AH, ed. Yoğun Bakım Sorunları ve Tedavi İlkeleri. 2.
baskı. Ankara: Türkiye Klinikleri, 2003: 430–433.
44. LoCicero J, Mattox KL. Epidemiolojy of chest trauma.
Surg Clin North Am 1989; 69: 15–19.
190
45. Er M, Işık AF, Kurnaz M. Çobanoğlu U. Sağay S.
Yalçınkaya İ. Clinical results of four hundred and
twenty-four cases with chest trauma. Turkish Journal of
Trauma & Emergency Surgery. 2003; 4: 267–274.
46. Crawford WO. Pulmonary injury in thoracic and
nonthoracic trauma. Radiol Clin North Am 1973; 11:
527–541.
47. Nast-Kolb D, Waydhas C, Gippner-Steppert C, et al.
Indicators of the posttraumatic inflammatory response
correlate with organ failure in patients with multiple
injuries. J Trauma 1997; 42: 446–455.
48. Fasol R, Zilla P, Irvine S, Von Oppell U. Thoracoabdominal injuries in combat casualties on the
Cambodian border. Thorax Cardiovasc Surg 1988; 36:
33–6.
49. Mattox KL. Indications for thoracotomy: deciding to
operate. Surg Clin North Am 1989; 69: 47–58.
50. Zalstein S, Cameron PA. Helicopter emergency medical
services: their role in integrated trauma care. Aust N Z J
Surg 1997; 67: 593–598.
51. McCullough J. The nation\'s changing blood supply
system. JAMA 1993; 269: 2239–2245.
52. Adesanya AA, Afolabi IR, da Rocha-Afodu JT. Civilian
abdominal gunshot wounds in Lagos. J R Coll Surg
Edinb 1998; 43: 230–234.
53. Tegegne A. Abdominal missile injuries at Gonder
Hospital, Northwestern Ethiopia. Ethiop Med J 1991;
29: 81–86.
54. Dellinger EP, Oreskovich MR, Wertz MJ, Hamasaki V,
Lennard ES. Risk of infection following laparotomy for
penetrating abdominal injury. Archives of Surgery 1984;
119: 20–27.
55. Nichols RL, Smith JW, Klein DB, Trunkey DD, Cooper
RH, Adinolfi MF, Mills J. Risk of infection after
penetrating abdominal trauma. N Engl J Med 1984;
311:1065–1070.
56. Çetinkaya Z, İlhan SY, Bülbüller N, Doğru O, Akkuş
MA, Caboğlu S. Abdominal firearm injuries. Turkish
Journal of Trauma & Emergency Surgery. 1998; 3: 206210.
57. Dawidson I, Miller E, Litwin MS. Gunshot wounds of
the abdomen. Archives of Surgery 1976; 111: 862–865.
58. Thomsen JL, Albrektsen SB. An investigation of the
pattern of firearm fatalities before and after the
introduction of New Legislation in Denmark. Med Sci
Law 1991; 31: 162-166.
59. Persad IJ, Reddy RS, Saunders MA, Patel J. Gunshot
injuries to the extremities: experience of a U.K. trauma
centre. Injury 2005; 36: 407–411.
60. Eftekhar B, Zarei MR, Ghodsi M, MoezArdalan K,
Zargar M, Ketabchi E. Comparing logistic models based
on modified GCS motor component with other
prognostic tools in prediction of mortality: Results of
study in 7226 trauma patients. Injury. 2005; 36: 900–
904.
61. Kuhls DA, Malone DL, McCarter RJ, Napolitano LM.
Predictors of mortality in adult trauma patients: the
Physiologic Trauma Score is equivalent to the Trauma
and Injury Severity Score. J Am Coll Surg 2002:194:
695–704.
191
ARAŞTIRMA YAZISI
D VİTAMİNİ TEDAVİSİNİN ETKİNLİĞİ FALANGEAL RADYOGFRAFİK ABSORPSİYOMETRİ
İLE İZLENEBİLİR Mİ?
Ümran Kaya, Evrim Karadağ Saygı, Işıl Üstün, Gülseren Akyüz
Marmara Üniversitesi Hastanesi, Fiziksel Tıp ve Rehabilitasyon AD, İstanbul, Türkiye
ÖZET
Amaç: Radyografik absorpsiyometri (RA) 2, 3 ve 4. parmakların orta falankslarından kemik mineral
yoğunluğu (KMY) ölçümü yapan ucuz ve uygulaması kolay bir tekniktir. Bu çalışmada D vitamini eksikliği
bulunan ileri yaştaki hastalarda kısa süreli D vitamini tedavisinin falangeal RA ile izleminin yapılıp
yapılamayacağı ve dual enerji x-ışını absorpsiometri (DXA) ile ölçüm sonuçlarının uyumunun
karşılaştırılması amaçlanmaktadır.
Gereç ve Yöntem: Çalışmaya 65 yaş ve üzerinde D vitamini eksikliği saptanan (<50nmol/l) 57 osteopenik
hasta alındı. 30 hastaya günde 1 µg alfakalsidol ve 500 mg elemanter kalsiyum, kontrol grubuna ise günde
500 mg elemanter kalsiyum verildi. Tüm hastaların tedavi başlangıcında ve 6. ayda el falangeal KMY;
lomber omurga ve kalça KMY ölçümleri yapıldı. Serumda D vitamini düzeyindeki yüzde değişim ile RA ve
DXA sonuçlarının uyumluluğu istatistiksel olarak karşılaştırıldı.
Bulgular: Tüm hastaların başlangıçta yapılan DXA KMY ölçümleri ile RA ölçüm sonuçları uyumlu idi. 6
aylık alfakalsidol tedavisi sonucunda D vitamini düzeylerindeki değişim hem DXA hem de RA ile
istatistiksel ilgileşim göstermedi.
Sonuç: Falangeal radyografik absorpsiyometri güvenilir ve pratik bir yöntem olmakla birlikte D vitamini
tedavisinin kısa dönemli takibinde kullanımının sınırlı olacağı düşünülmektedir.
Anahtar sözcükler: D vitamini, Dual enerji x-ışını absorpsiyometri (DXA), Falangeal radyografik
absorpsiyometri (RA)
IS IT POSSIBLE TO FOLLOW-UP THE EFFICACY OF VITAMIN D TREATMENT BY
PHALANGEAL RADIOGRAPHIC ABSORPSIOMETRY?
ABSTRACT
Aim: Radiographic absorptiometry (RA) is a cheap and easily applicable technique for measuring bone
mineral density (BMD) of the medium phalanges of fingers 2, 3 and 4. In this trial with elderly patients
suffering from vitamin D deficiency, the aim is to investigate whether it is possible to follow short-term
vitamin D treatment with phalangeal RA or not and to compare the consistency of measurement results with
dual energy x-ray absorptiometry (DXA).
Materials and Methods: Fifty-seven patients over 65 years old who had been determined as vitamin D
deficiency (<50nmol/l) were included in this trial. Thirty patients received 1 µg of alphacalcidol and 500 mg
elemenatry calcium once a day and the control group received 500 mg elementary calcium. Hand phalangeal,
lumbar spinal and hip BMD measurements of all patients were performed at the beginning and the 6th month
of the treatment. The consistency of percentage change of serum levels of vitamin D with RA and DXA
results were statistically compared.
Results: Baseline DXA BMD measurements of all of the patients were consistent with the RA measurement
values. After 6 months of alphacalcidol and elementary calcium treatment, the difference in the levels of
vitamin D was not statistically relevant, neither with DXA nor with RA.
Conclusion: Although phalangeal radiographic absorptiometry is a reliable and practical method, its use in
the short term follow-up of vitamin D treatment is thought to be limited.
Keywords: Vitamin D, Dual energy x-ray absorptiometry (DXA), Phalangeal radiographic absorptiometry
(RA)
Dr. Evrim Karadağ Saygı
Marmara Üniversitesi Hastanesi, Fiziksel Tıp ve Rehabilitasyon AD, İstanbul,
Türkiye
192
Ümran Kaya, ark.
D vitamini tedavisinin etkinliği falangeal radyogfrafik absorpsiyometri ile izlenebilir mi?
GİRİŞ
Osteoporoz kemik gücünü etkileyerek kırık
riskinde artma ile karakterize, ilerleyici bir
iskelet sistemi hastalığıdır. D vitamini
eksikliği yaşlanmaya bağlı olarak gelişen
senil
osteoporozun
en
önemli
risk
faktörlerindendir1.
Osteoporoz
tanısında
günümüzde en geçerli teknik çift-enerji x-ışın
absorpsiyometridir (DXA). Buna karşın,
osteoporoz tanı ve tedavi izleminde DXA’nın
pahalı bir yöntem olması, taşınabilme ve
uygulama
zorluğu
kullanımını
kısıtlamaktadır2.
Toplumda
osteoporoz
hastalarını belirlemek için tarama amaçlı
kullanılan
falangeal
radyografik
absorbsiyometri (RA) ise ucuz ve hızlı bir
yöntemdir3. Bu çalışmada, D vitamini
eksikliği bulunan ileri yaştaki hastalarda kısa
süreli D vitamini tedavisinin RA ile takibinin
yapılıp yapılamayacağı ve DXA ile ölçüm
sonuçlarının uyumunun karşılaştırılması
amaçlanmaktadır.
kontrol grubuna ise günde 500 mg kalsiyum
verildi. Tüm hastaların tedavi başlangıcında
ve 6. ayda falangeal (dominant olmayan elin,
2.,3.,4. parmaklarının orta falankslarından)
kemik mineral yoğunluğu (KMY) RA
(Metriscan-ALARA) ile; lomber omurga ve
kalça KMY ölçümleri DXA (Lunar) ile
yapıldı. DXA sonuçlarından lomber bölgeye
ait değerlerin L1,2,3,4 vertebraların ortalama
KMY’leri, T ve Z skorları değerlendirmeye
alındı. Başlangıçtaki DXA ve RA skorları
(KMY, T ve Z skorları) arasındaki uyumun
yanı sıra, tedavi sonrası serumda D vitamini
düzeyindeki yüzde değişim ile RA ve DXA
sonuçlarının uyumluluğu istatistiksel olarak
karşılaştırıldı.
GEREÇ-YÖNTEM
Çalışmaya
Marmara
Üniversitesi
Tıp
Fakültesi Fiziksel Tıp ve Rehabilitasyon
Anabilim Dalı polikliniklerine başvuran, 65
yaş ve üzerinde D vitamini eksikliği
saptanmış (<50nmol/l), 57 osteopenik (lomber
ve/veya femoral bölge T skoru -1,5 ile -2,5
arasında) hasta dahil edildi. D vitamini
metabolizmasını etkileyen hastalık varlığı,
tiroid ve/veya paratiroid bozukluğu, malignite
varlığı, ciddi renal yetmezlik (kreatinin
klirensi < 30ml/dk) ve D vitamini
metabolizmasını bozabilecek ilaç kullanımı
(hipnotikler, sedatifler veya antikonvülzanlar
gibi) ve eli tutan hastalık varlığı (romatoid
artrit, el osteoartriti gibi) çalışma dışı
bırakılma nedenleri olarak belirlendi. .
Çalışmamız randomize kontrollü bir araştırma
olup, çalışma için hastanemiz Etik
Kurul’undan onay alındı. Hastalar, çalışmanın
içeriği hakkında sözlü ve yazılı olarak
bilgilendirildi ve onayları alındıktan sonra
çalışmaya dahil edildi. 30 hastaya günde 1 µg
alfakalsidol ve 500 mg elemanter kalsiyum,
BULGULAR
D vitamini grubundaki hastaların yaş
ortalaması 70,03±6,04; kalsiyum grubundaki
hastaların ise 69,48±4,27 idi. Gruplar arasında
demografik veriler açısından istatistiksel
farklılık saptanmadı (p>0,05) (Tablo I). Her
iki grubun da başlangıçtaki 25(OH) Vitamin
D3 düzeyleri arasında farklılık yoktu.
Başlangıçtaki lomber, femoral bölgelerden
yapılan DXA ölçümleri ile RA ölçüm
sonuçları uyumlu idi (Tablo II). D
vitamini+kalsiyum ve kalsiyum tedavisi alan
gruplarda 3. ve 6. ay sonunda başlangıca göre
serum D vitamini düzeylerindeki yüzde
değişim oranları hesaplandı. 3. ayda D
vitamini düzeyleri her iki grupta da
yükselirken, 6. ayda alfacalcidol alan grupta
anlamlı artış göze çarptı (Şekil 1). Gruplarda
D vitamini değişim oranları ile RA sonuçları
arasında uyum tespit edilmedi. Benzer şekilde
başlangıca göre 6. ay D vitamini yüzde
değişim oranları DXA ile istatistiksel
ilgileşim göstermedi (Tablo III).
Verilerin değerlendirmesi SPSS for Windows
11,5 istatistik paket programında yapıldı.
Karşılaştırmalarda Mann Whitney U, Ki-kare
testleri kullanıldı. Pearson korelasyon analizi
ile ilişikiler değerlendirildi. P<0,05 anlamlı
kabul edildi.
193
Ümran Kaya, ark.
Tablo I: Demografik özellikler
Yaş (ort±SS) (yıl)
Ağırlık (kg)
Boy (cm)
Vücut kütle indeksi
(kg/cm2) (ort±SS)
D vitamini ve
kalsiyum grubu
(n=30)
Ortalama
70,03±6,04
67,90±10,68
153,27±7,06
28,94±4,42
Kalsiyum grubu
(n= 27)
Ortalama
69,48±4,27
70,33±10,10
153,93±5,79
29,75±4,5
P
,695
,382
,703
,501
Tablo II: Tedavi öncesi hastaların RA ve DXA ölçümlerinin uyumlulukları
Falangeal RA
KMY
T skoru
Z skoru
DXA
KMY lomber
KMY femur
KMY total
T skor lomber
T skor femur
T skor total
Z skor lomber
Z skor femur
Z skor total
Korelasyon
r=0,43 (p<0,01)
r=0,42 (p<0,01)
r=0,4 (p<0,01)
r= 0,45 (p<0,01)
r=0,38 (p<0,05)
r=0,38 (p<0,05)
r=0,43 (p<0,01)
r=0,49 (p<0,01)
r=0,86 (p<0,001)
Tablo III: D vitamini+kalsiyum ve Kalsiyum gruplarında başlangıca göre 6. ay sonunda serum vitamin D
düzeylerindeki % değişim oranları ile DXA, RA değerlerinin uyumu
DXA ve RA
% değişim oranları
(başlangıç-6. ay)
Gruplar
D vitamini serum
düzeyleri % değişim
oranları (başlangıç–
6. ay)
D vitamini ve
kalsiyum grubu
Kalsiyum grubu
KMY
T skoru
Z skoru
KMY
T skoru
Z skoru
Korelasyon
p>0,05
p>0,05
p>0,05
p>0,05
p>0,05
p>0,05
Şekil 1: 25-hidroksi vitamin D3 düzeylerinin başlangıç, 3. ve 6. aylarda karşılaştırması
194
Ümran Kaya, ark.
Bizim çalışmamızda ise 6 aylık alfakalsidol
tedavisi sonucunda serumda D vitamini
düzeylerindeki değişim ne DXA ne de RA ile
istatistiksel ilgileşim gösterdi. Bu sonucun
hasta takip süremizin kısa olmasına verilen D
vitamini tedavisi ne kadar uzunsa KMY
üzerinde yaratacağı pozitif etki de o kadar
belirgin olacaktır) ve hasta sayımızın az
oluşuna bağlı olarak geliştiği kanısındayız.
TARTIŞMA
D vitamini eksikliği tüm geriyatrik yaş
grubunda önemli bir sağlık sorunudur ve bu
dönemde görülen osteoporozun en sık
nedenidir1,4. Senil osteoporozun tanı ve tedavi
izleminde en çok tercih edilen yöntem
DXA’dır. Falangeal RA gibi periferik ölçümü
değerlendiren
yöntemler,
daha
çok
osteoporozun toplum içi taramalarında
kullanılmaktadır.
Yapılan
çalışmalarda
RA’nın periferik KMY’yi doğru ve hassas
olarak ölçebildiği gösterilmiştir5,6. RA ile
yapılan periferik KMY ölçümü ile lomber ve
kalça bölgesi KMY ölçümünün uyumunun
incelendiği çalışmalar bulunmaktadır7,8. Aktaş
ve ark. yaptığı bir tarama çalışmasında lomber
vertebra DXA sonuçları, RA ile yüksek
derecede uyumlu bulunmuştur7. Ayrıca
Swezey ve ark. lomber-femoral DXA ve RA
ile anlamlı korelasyon saptamıştır8. Bizim
çalışmamızda da D vitamini eksikliği bulunan
yaşlı hastalarda başlangıçtaki DXA KMY
ölçümleri ile RA ölçüm sonuçları uyumlu
bulunmuştur. Bu sonuca göre RA D vitamini
eksikliği bulunan hastalarda osteoporoz
tanısında kullanılabilir güvenli ve pratik bir
yöntemdir.
Sonuç
olarak,
falangeal
radyografik
absorpsiyometri, D vitamini eksikliğine bağlı
osteoporoz tanısında güvenilir ve pratik bir
yöntem olmakla birlikte D vitamini
tedavisinin
kısa
dönemli
takibinde
kullanımının sınırlı olacağı düşünülmektedir.
KAYNAKLAR
1.
2.
3.
D vitamini eksikliğine bağlı olarak gelişen
osteoporoz tedavisinde de kemik kaybı DXA
ile takip edilmektedir. Yapılan çalışmalarda
alfakalsidol ile tedavi edilen osteoporoz
hastalarında KMY’nin artış gösterdiği tespit
edilmiştir9,10. Fenkçi ve ark.larının 1 yıl
süreyle
alfakalsidol
alan
osteoporoz
hastalarında DXA ile yapılan ölçümlerinde
femur boynunda %0,07, L2-4’te %0,09 ve
totalde %0,08’lik artış saptanmıştır9. Başka
bir çalışmada, Orimo ve ark.ları, senil
osteoporozlu hastalarda 1 yıl süre ile 1mcg
alfakalsidol tedavisi sonucunda DXA’da
KMY’nda artış tespit etmişlerdir10. Menczel
ve ark.’nın yaptığı bir çalışmada ise 3 yıl
süreyle
alfakalsidol
alan
osteoporoz
hastalarının distal radius KMY ölçümlerinde,
plaseboya göre %2’lik artış saptanmıştır11.
Literatürde, osteoporoz tedavisinin takibinde
RA’nın kullanıldığı herhangi bir çalışmaya
rastlanmamıştır.
4.
5.
6.
7.
8.
9.
195
Eriksen EF, Glerup H. Vitamin D deficiency and aging:
implication for general health and osteoporosis.
Biogerontology 2002; 3: 73-77.
Cadarette SM, Jaglal SB, Murray TM, et al. Canadian
Multicentre Osteoporosis Study. Evaluation of decision
rules for referring women for bone densitometry by
dual-energy x-ray absorptiometry. JAMA 2001:286:5763.
Boonen S, Nijs J, Peeters H, et al. Identifying
postmenopausal women with osteoporosis by calcaneal
ultrasound, metacarpal digital X-ray radiogrammetry
and phalangeal radiographic absorptiometry: a
comparative study. Osteoporos Int 2005:16:93-100.
Atlı T, Erdoğan G, Güllü S. The prevalance of vitamin
D deficiency and effects of ultraviolet light on vitamin D
levels of elderly Turkish population. Arch Gerontol
Geriatr.2005;40: 53-60
Yang SO, Hagiwara S, Engelke K, et al. Radiographic
absorptiometry for bone mineral measurement of the
phalanges: precision and accuracy study. Radiology
1994:192:857-859.
Elliot JR, Fenton AJ, Young T, et al. The precision of
digital X-ray radiogrammetry compared with DXA in
subjects with normal bone density or osteoporosis. J
Clin Densitom 2005:8:187-190.
Aktaş İ, Akgün K, Sarıdopan M.E. Kalkaneal kantitatif
ultrason ve falangeal radyografik absorpsiometrinin
osteoporoz tanısındaki değeri: karşılaştırmalı çalışma.
Osteoporoz Dünyasından. 2006;12:43-46
Swezey RL, Draper D, Swezey AM. Bone densitometry:
Comparison of dual energy x-ray absorptiometry to
radiographic absorptiometry. J Rheumatol 1996:23:
1734-1438.
Fenkci I V, Doğanay M, Tanrıöver S, Gökmen O.
Effects of alfacalcidol treatment on bone mineral density
and
calcium
metabolism
in
postmenopausal
osteoporosis. J Gynecol Obst 2001;28:243-246.
Ümran Kaya, ark.
10. Orimo H, Shiraki M, Hayashi Y. Effects of 1αhydroxyvitamin D3 on lumbar bone mineral density and
vertebral fractures in patients with postmenopausal
osteoporosis. Calcif Tissue Int 1994; 54: 370-376.
11. Menczel J, Foldes J. Alfacalcidol (alpha D3) and
calcium in osteoporosis. Clin Orthop 1994;300: 241247.
196
ORIGINAL RESEARCH
INCIDENTAL DETECTION OF CORONARY ARTERY CALCIFICATIONS ON
NON-CARDIAC THORACIC CT EXAMINATIONS
Kadriye Orta Kılıçkesmez1, Özgür Kılıçkesmez2, Neslihan Taşdelen2, Duygu Kara2, Yüksel Işık2,
Arda Kayhan3, Bengi Gürses2, Nevzat Gürmen2
1
İstanbul Üniversitesi Kardiyoloji Enstitüsü, Kardiyoloji, İstanbul, Türkiye 2Yeditepe Üniversitesi,
Radyoloji, İstanbul, Türkiye 3Namık Kemal Üniversitesi, Radyoloji, Tekirdağ, Türkiye
ABSTRACT
Objective: Strong relationships have been demonstrated between the presence of occlusive coronary artery
disease and coronary artery calcifications detected at autopsy, fluoroscopy, or computed tomography (CT).
The aim of our study was to evaluate the frequency of incidental coronary artery calcifications during
thoracic CT examinations and to correlate them with cardiac risk factors.
Materials and Methods: Thoracic CT scans obtained over a period of 6 months from 113 patients (72 male
and 41 female) with a mean age of 62,7 (31-92 years) were retrospectively evaluated. The thoracic scans
were performed using standard 9 mm consecutive slices from the apex to the base of the thorax, using a
standard thoracic protocol, on a Siemens 16 channel multislice CT scanner. Coronary arteries were evaluated
for calcifications.
Results: Thirty-seven patients (32.7%) had coronary calcifications.18 patients (15.9%) had one, 9 patients
(7.9%) two, 7 patients (6.2%) three, and 3 patients (2.6%) had four vessels with calcifications. The frequency
of coronary calcifications was correlated with hypertension, diabetes mellitus, hypercholesterolemia, nicotine
abuse, and cardiomegaly. Diabetes mellitus, hypercholesterolemia, cardiomegaly and male gender were
significantly associated with coronary calcifications (p<0.05).
Conclusion: With the advent of multislice faster CT scanners, coronary artery calcifications are more
frequently and easily detectable during non-cardiac thoracic CT examinations. This retrospective study
showed increased incidence of coronary calcifications in patients with cardiac risk factors. Among these
factors diabetes mellitus, hypercholesterolemia, cardiomegaly and male gender were statistically significant.
Keywords: Multidetector computed tomography, Heart, Coronary calcification
Kadriye Orta Kılıçkesmez, M.D.
İstanbul Üniversitesi Kardiyoloji Enstitüsü, Kardiyoloji, İstanbul, Türkiye
197
Kadriye Orta Kılıçkesmez, et al.
Incidental detection of coronary artery calcifications on non-cardiac thoracic CF examinations
NON-KARDİYAK TORAKS BT İNCELEMELERİNDE RASTLANTISAL OLARAK
SAPTANAN KORONER ARTER KALSİFİKASYONLARI
ÖZET
Amaç: Bilgisayarlı tomografi (BT), floroskopi veya otopside saptanan koroner arter kalsifikasyonları ile
okluzif koroner arter hastalığı arasında güçlü ilişkiler tanımlanmıştır. Bu çalışmanın amacı, toraks BT
incelemeleri esnasında insidental olarak saptanan koroner kalsifikasyonların sıklığını belirlemek ve risk
faktörleri ile korele etmekti.
Gereç ve Yöntem: Altı ay süresince toraks BT uygulanan ve ortalama yaşları 62,7 (31-92) olan 113 olgu (72
erkek, 41 kadın hasta) retrospektif olarak değerlendirilmiştir. Toraks BT incelemeleri Siemens Somatom
Sensation 16 dedektörlü BT cihazında apeksten toraks bazaline dek, 9 mmlik ardışık kesitlerle elde olunmuş
ve koroner arterler kalsifikasyonlar açısından değerlendirilmiştir.
Bulgular: On sekiz hastada (15.9%) tek damar, 9 hastada (7.9%) çift damar, 7 hastada (6.2%) üç damar ve 3
hastada (2.6%) dört damar kalsifikasyonu olmak üzere toplam 37 hastada (32.7%) koroner kalsifikasyon
belirlendi.
Koroner kalsifikasyonların sıklığı hipertansiyon, diabetes mellitus, hiperkolesterolemi, nikotin bağımlılığı ve
kardiyomegali ile karşılaştırıldı. Hiperkolesterolemi, kardiyomegali ve erkek cinsiyet ile koroner arter
kalsifikasyonları arasında istatistiksel anlamlı farklılık bulundu (p<0.05).
Sonuç: Daha hızlı, çok dedektörlü BT cihazlarının geliştirilmesiyle, non kardiyak BT incelemeleri esnasında
koroner kalsifikasyonlar daha kolay ve sık tespit edilmeye başlandı. Bu retrospektif çalışma kardiyak risk
faktörleri olan hastalarda koroner arter kalsifikasyonlarında artmış insidansı gösterdi. Bu faktörler arasında
diabetes mellitus, hiperkolesterolemi, kardiyomegali ve erkek cinsiyet istatistiksel anlamlı farklılık bulundu.
Anahtar Kelimeler: Multidedektör bilgisayarlı tomografi, Kalp, Koroner kalsifikasyon
stents, a history of previous bypass surgery, or
non-diagnostic scans with poor resolutions.
The thoracic scans were performed using
standard 9 mm consecutive slices from the
apex to the base of the thorax, using a
standard thoracic protocol, on a Siemens 16
channel multislice CT scanner. A standard
tissue window was used (WL: 50, WW: 500)
for the assessment of slices.
INTRODUCTION
The presence of coronary artery calcification
is a significant indicator of atheromatous
disease and it may indicate the presence of
severe stenosis. While the absence of
calcification does not correlate with the
absence of coronary artery disease, an
incidental finding of calcium has important
prognostic implications. Most of the previous
work documenting calcification has been
observed in patients with a known history of
heart disease undergoing further cardiac
investigations1,2.
The coronary arteries were evaluated for
calcifications. The number and location of
coronary calcifications were noted for each
patient. The investigated cardiac risk factors
were gender, hypertension, diabetes mellitus,
hypercholesterolemia, and nicotine abuse. The
diagnosis of cardiomegaly was achieved with
the calculation of transverse heart ratio (>0,5)
on plain thoracic x-rays.
Early diagnosis of atherosclerosis is therefore
highly important in predicting and preventing
myocardial infarction. Imaging modalities
especially CT scans have been proved to be
helpful1. The aim of this study was to evaluate
the frequency of incidental coronary artery
calcifications
during
thoracic
CT
examinations, and to correlate this with
cardiac risk factors.
Medical records were reviewed and the data
related to age, sex, smoking history, risk
factors for vascular disease, and general
medical condition were noted in a
standardized form. Evidence of previous
cardiac disease was determined on the basis
of
electrocardiographic
evidence
of
arrhytmias, ischemia or previous myocardial
infarction. Prior infarctions were documented
by evaluation of enzyme levels, history of
MATERIAL AND METHOD
Thoracic CT scans obtained over a period of 6
months from 113 patients (72 male and 41
female) with a mean age of 62,7 (31-92 years)
were retrospectively evaluated. The exclusion
criteria were existing implanted coronary
198
Incidental detection of coronary artery calcifications on non-cardiac thoracic CT examinations
four vessel calcifications (left main coronary,
circumflex, LAD and RCA).
treatment for angina or congestive heart
failure, and findings of any available studies
of cardiac function such as cardiac
echocardiography,
exercise
thallium
myocardial perfusion imaging and exercise
tolerance testing.
The incidence of calcifications were
significantly higher in males (p<0.05), as well
as in patients with diabetes mellitus (12.3%),
hypercholesterolemia
(16.8%)
and
cardiomegaly (20.3%) (p<0.05). Although
nicotine abuse, and hypertension are
associated with increased risk of calcification,
these were not statistically significant. (TableI).
Image interpretation
CT scans were transferred to an independent
Workstation (Leonardo console, software
version 2.0; Siemens) for postprocessing, and
the 3D multiplanar reconstruction (MPR)
images were reconstructed in the coronal and
sagittal planes in addition to the axial source
slices. The left anterior descending (LAD),
circumflex and right coronary arteries (RCA)
were evaluated for presence of calcifications
by two radiologists on the basis of the
knowledge of the CT anatomy of the coronary
arteries in consensus. The readers were
experienced in reading images of the coronary
anatomy. The presence of coronary
calcifications was evaluated with a
contiguous-slice method. A calcified lesion
was defined as a hyperdense area inside the
artery with a Hounsfield unit (HU) of greater
than 90 and that measured 0.5 mm2 or larger.
Figure 1: Axial thorax CT image at the level of
heart demonstrates left main coronary and
circumflex artery calcifications.
Statistical Analysis
All statistical analysis were performed using
Statistical Package for Social Sciences (SPSS)
for Windows 10.0. The number of
calcifications, locations, and the risk factors
of the patients were reported as the mean ±
standard deviation. Student’s t test was
performed to compare the subgroups with and
without calcifications. A p value of less than
0.05 was considered to indicate a statistically
significant difference.
RESULTS
A total of 113 thoracic CT scans were
reviewed. The scans were performed with
various clinical indications. The most
common indication was for identification of
primary or secondary lung carcinomas,
followed by airway disease evaluation.
Figure 2: Coronal 3D MPR CT image of
the thorax at the level of heart
demonstrates
left
main,
anterior
descending and circumflex coronary
artery calcifications.
Thirty-seven patients (32.7%) had coronary
calcifications. Of the 37, 18 patients (15.9%)
had one, 9 patients (7.9%) had two, 7 patients
(6.2%) had three, and 3 patients (2.6%) had
199
Table I: Association of cardiac risk factors with coronary calcifications.
The group with
coronary
calcifications
62,5% male
Gender
45,7% female
15(13,2%)
Nicotine abuse
21(18,3%)
Hypertension
14 (12,3%)
Diabetes Mellitus
Hypercholesterolemia 19 (16,8%)
23 (20,3%)
Cardiomegaly
13 (11,5%)
Known cardiac
disease
The group without
coronary
calcifications
37,5% male
54,3% female
14(12,3%)
15 (13,2%)
6 (5,3 %)
7 (6,1%)
12 (10,6%)
10 (8,8%)
Statistical
difference (p)
p<0.05
p>0.05
p>0.05
p>0.05
p<0.05
P<0.05
P<0.05
p>0.05
calcium score had a 100% predictive value in
the exclusion of angiographic evidence of
obstructive epicardial coronary lesions. The
higher the calcium score, the more likely the
presence
of
angiographic
obstructive
10
disease .
DISCUSSION
Autopsy studies have shown that there is a
close link between coronary artery
calcification and the extent of vascular
stenosis with a subsequent risk of myocardial
infarction. A variety of imaging modalities
have been used for detecting coronary artery
calcifications of which, plain chest
radiography and fluoroscopy have the lowest
sensitivity. CT imaging is superior to
fluoroscopy
for
detecting
coronary
calcifications1.
Results of autopsy studies indicate that
coronary artery calcification is invariably
associated with the presence of atherosclerotic
plaques11. In a previous study performed with
450 consecutive patients, Callaway et al.,
found atherosclerotic plaques in 26% of male
and 15.6% of female scans. When they
limited their sample to those over 40 years for
age, the incidence increased to 48% from
41.6% 12.
Ultrafast CT has high-resolution contrast, a
rapid image acquisition, and allows
elimination of the image blurring caused by
heart movement. Due to these features,
ultrafast CT has a high sensitivity for
detecting calcium in the coronary arteries3. In
different series, the sensitivity and specificity
of the examination ranged from 88 to 100%
and 43 to 100%, respectively2,4,5.
Coronary calcification is strongly associated
with the prognosis. Indeed, the extent of
coronary atherosclerosis (total calcium score)
is the most powerful predictor of subsequent
or recurrent cardiac events. This was true in
the former years when calcium was detected
with fluoroscopy and conventional CT13.
Arterial calcification occurs in the intima of
the blood vessels, as a part of atherosclerosis.
In general population, coronary artery
calcification
correlates
with
the
atherosclerotic plaque burden and with
coronary vessel stenosis, and has consistently
been shown to be predictive for future cardiac
events6-9.
Janowitz et al., analyzed the evolution of the
amount of calcium in atherosclerotic plaques
by ultrafast CT in patients with and without
coronary artery disease3. Ninety-eight percent
of the calcium deposits identified on the
initial examination were confirmed in
consequent imagings, and there was a
significant increase in the calcification
volume and in the total calcified area of the
atherosclerotic plaque in the evolution.
Patients with coronary artery disease have a
Coronary segments with a luminal obstruction
greater than 50% are likely to have some
calcification that is detectable with electronbeam CT. In a trial, it was shown that, a 0
200
large amount of new calcium deposits, which
are not found in asymptomatic patients. In
patients with no evidence of calcification,
both in the first approach and later, the
prevalence of ischemic heart disease is
extremely low.
accurate event predictor
asymptomatic adults16.
in
high-risk
The present study had some limitations. Our
sample size was small and a relatively old CT
technology was used. Moreover, there was no
gold standard angiographic demonstration of
stenotic effects of the calcium deposits.
In a study searching the presumptive
detection of coronary stenosis on the basis of
existing calcification by means of CT, higher
sensitivities have been found in the calcified
arteries (78% for LAD, 63% for the
circumflex and 16% for RCA). Specificities
were 78%, 80% and 100%, and positive
predictive values (PPV) were 88%, 83% and
100%, respectively. The high PPV suggested
that significant coronary artery disease was
likely to be present when coronary
calcification was seen on CT14. In a study
performed by Shirazi et al., of the total 100
patients (62 males), 69 had coronary artery
obstruction (>50% stenosis was detected by
angiography). Angiography was normal in the
rest. For the diagnosis of coronary artery
disease, a spiral CT scan had a sensitivity of
94% and a specificity of 61%. PPV and
negative predictive value (NPV) were 84%
and 79%, respectively1.
In conclusion, coronary calcifications were
easily discernible with CT. Our study showed
that calcified deposits were more frequently
encountered with increasing age and male
gender. In addition, to the increased
association of coronary calcification with the
male gender, a relationship to diabetes
mellitus,
hypercholesterolemia
and
cardiomegaly was detected.
Acknowledgement:
There was no financial support for this study.
REFERENCES
1.
2.
3.
In their series performed with double-helix
CT, Shemesh et al., stated that calcification
was significantly more prevalant in patients
with obstructive coronary artery disease
(>83%) than in patients with normal coronary
arteries (27%) or in healthy control subjects
(34%, p<0.1). The researchers found a high
sensitivity (91%), however, the specificity
was low (52%) due to calcification in nonobstructive lesions15. When CT and
angiographic findings were compared, CT
was found to have 84% accuracy with PPV
and NPVof 89% and 59%, respectively15.
4.
5.
6.
In contrast, some investigators claim that the
technique is useless16. Detrano et al., in their
series performed with 1196 asymptomatic
high-coronary-risk subjects that underwent
risk-factor assessment and cardiac CT,
showed that CT calcium score did not add
significant incremental information to risk
factors in clinical screening. The researchers
claimed that neither risk-factor assessment
nor the calcium detected with CT was an
7.
8.
9.
201
Shirazi AS, Nasehi N, Sametzadah M, Saberi H,
Shabani MA. Spiral CT scan for detecting coronary
artery stenosis. Iran. J Radiol 2005; 3:11-15.
Feldman C, Vitola D, Schiavo N. Detection of coronary
artery disease based on the calcification index obtained
by helical computed tomography. Arq Bras Cardiol
2000;75:471-480.
Janowitz WR, Agatston S, Kaplan G, Viamonte M.
Differences in prevalence and extent of coronary artery
calcium detected by ultrafast computed tomography in
asymptomatic men and women. Am J Cardiol 1993; 72:
247-254.
Tanenbaum SR, Kondos GT, Veselick KE, Prendergast
MR, Brundage BH, Choomka EV. Detection of calcific
deposits in coronary arteries by ultrafast computed
tomography and correlation with angiography. Am J
Cardiol 1989; 63: 870-871.
Wong ND, Abrahamson D, Tobis JM, Eisenberg H,
Detrano RC. Detection of coronary artery calcium by
ultrafast computed tomography and its relation to
clinical evidence of coronary artery disease. Am J
Cardiol 1994; 73: 223-227.
Wexler L, Brundage B, Crouse J, et al. Coronary artery
calcification: Pathophysiology, epidemiology, imaging
methods, and clinical implications. A statement for
health professionals from the American Heart
Association. Writing Group. Circulation 1996; 94:1175–
1192.
Keelan PC, Bielak LF, Ashai K, et al. Long-term
prognostic value of coronary calcification detected by
electron-beam computed tomography in patients
undergoing coronary angiography. Circulation 2001;
104:412– 417.
Budoff MJ. Prognostic value of coronary artery
calcification. JCOM 2001; 8:42–48.
Greenland P, LaBree L, Azen SP, et al. Coronary Artery
Calcium Score combined with Framingham Score for
risk prediction in asymptomatic individuals. JAMA
2003; 291:210–215.
10. Rumberger JA, Brundage BH, Rader DJ. Electron beam
computed tomographic coronary calcium scanning: a
review and guidelines for use in asymptomatic persons.
Mayo Clin Proc 1999;74:243-252.
11. McNamara JJ, Molot MA, Stremple JF, Cutting RT.
Coronary artery disease in combat casualties in
Vietnam. JAMA 1971; 216: 1185-1187.
12. Callaway MP, Richards P, Goddard P, Rees M. The
incidence of coronary artery calcification on standard
thoracic CT scans. Br J Radiol 1997; 70: 572-574.
13. Selby JB, Morris PB. Coronary Artery Calcification –
CT. url:http://emedicine.medscape.com/article/352189overview
14. Timins ME, Pinsk R, Sider L, Bear G. The functional
significance of calcification of coronary arteries as
detected on CT. J Thorac Imaging 1991;7:79-82.
15. Shemesh J, Apter S, Rozenman J, et al. Calcification of
coronary arteries: detection and quantification with
double-helix CT. Radiology 1995;197:779-783.
16. Detrano RC, Wong ND, Doherty TM, et al. Coronary
calcium does not accurately predict near-term future
coronary events in high-risk adults. Circulation. 1999
May 25;99:2633-2638.
202
ARAŞTIRMA YAZISI
RADİKAL PROSTATEKTOMİ SPESMENLERİNDEKİ VEGF’İN, E-CADHERİN’İN VE
BIM’İN İMMÜNOHİSTOKİMYASAL EKSPRESYONLARININ PROGNOSTİK DEĞERİ
Erem Kaan Başok1, Asıf Yıldırım1, Adnan Başaran1, Ebru Zemheri2, Reşit Tokuç1
1
SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, 1. Üroloji, İstanbul, Türkiye 2SB İstanbul
Göztepe Eğitim ve Araştırma Hastanesi, Patoloji, İstanbul, Türkiye
ÖZET
Giriş: Bu çalışmanın amacı radikal prostatektomi spesmenlerindeki vasküler büyüme faktörü (VEGF), ECadherin ve Bim ekspresyonlarını değerlendirmek ve prognoz üzerine etkisini araştırmaktır.
Gereç ve Yöntem: Radikal prostatektomi uygulanan 66 hastanın (51 hasta pT2, 13 hasta pT3, 2 hasta pT4)
spesmenleri VEGF, E-Cadherin ve Bim antikorları ile boyandı. VEGF, E-Cadherin ve Bim immünoreaktivite
sonuçlarının Gleason skoru ve biyokimyasal nüks ile olan ilişkileri araştırıldı. İmmünohistokimyasal ve
klinik verilere göre istatistiksel analiz yapıldı.
Bulgular: Hastalar Gleason skoruna (Gleason score <7 and Gleason ≥7) ve biyokimyasal nükse (Prostat
spesifik antijen (PSA) >0,2 ng/ml) göre gruplara ayrıldı. Gruplar arasında VEGF, E-Cadherin ve Bim
ekspresyonlarında anlamlı fark olmamasına rağmen, biyokimyasal nüks saptanan hastalarda VEGF
ekspresyonu %59,74 ve biyokimyasal nüks saptanmayan hastalarda %44,47 bulundu (p=0,058). Spearman
korelasyon testi uygulandığında, VEGF ve E-Cadherin arasında anlamlı bir ilişki tespit edildi (p=0,05).
Sonuç: Tedaviye karar aşamasında yüksek riskli hasta grubunun belirlenmesinde kullanılabilecek
biyobelirteçe henüz sahip değiliz. Düşüncemiz daha büyük sayılı çalışmalarda bu biyobelirteçlerin
araştırılması ve immünohistokimyasal değerlendirmede imaj analiz yönteminin kullanılmasıdır.
Anahtar sözcükler: Prostat kanseri, VEGF, E-Cadherin, Bim
PROGNOSTIC VALUE OF IMMUNOHISTOCHEMICAL EXPRESSION OF VEGF, ECADHERIN AND BIM IN RADICAL PROSTATECTOMY SPECIMENS
ABSTRACT
Objective: The aim of this study was to evaluate the expressions of vascular endothelial growth factor
(VEGF), E-Cadherin and Bim in radical prostatectomy specimens and to assess their prognostic value.
Materials and Methods: Sixty-six radical prostatectomy specimens from prostate cancer (51 stage pT2, 13
pT3, 2 pT4) were stained using VEGF, E-cadherin and Bim antibody. The correlations of VEGF, E-Cadherin
and Bim immunoreactivity levels with Gleason scores and biochemical recurrence were examined. A
statistical analysis was then performed according to the immunohistochemical and clinical data.
Results: Patients were grouped according to the Gleason score (Gleason score <7 and Gleason ≥7) and
biochemical recurrence (Prostate specific antigen (PSA)>0.2 ng/ml). Although there were insignificant
differences in the expressions of VEGF, E-Cadherin and Bim in these groups, the expressions of VEGF were
59.74% in patients with biochemical recurrence and 44.47% in patients without biochemical recurrence
(p=0,058). In a Spearman correlation test, there was a significant correlation between expressions of VEGF
and E-Cadherin (p=0.05).
Conclusion: We currently have no useful biomarker for the early identification of high risk patients and for
deciding on treatment. These biomarkers should be studied in larger series of patients and
immunohistochemical staining could be examined with quantitative image analysis method.
Keywords: Prostate cancer, VEGF, E-Cadherin, Bim
Dr. Asıf Yıldırım
SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, 1. Üroloji, İstanbul, Türkiye
203
Erem Kaan Başok, ark.
Radikal prostatektomi spesmenlerindeki VEGF’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının
prognostik değeri
ve hücre-dışı matriks yıkımından sorumlu
olan matriks metalloproteazların, ürokinazın,
doku tipi plasminojen aktivatörlerinin
salınımını da uyarır. Böylelikle invazyon ve
metastazı da kolaylaştırır9.
GİRİŞ
Prostat kanseri erkeklerde en sık görülen ve
insidansı yaş ile artan bir hastalıktır.
Avrupa’da erkek kanserlerinin %11’ini ve
erkekler arasında kanser ölümlerinin %9’unu
oluşturmaktadır1. Prostat spesifik antijen’in
(PSA) tarama amaçlı kullanılmasından sonra
organa sınırlı prostat kanseri insidansında
belirgin bir artış görülmüştür2,3. Prostat
kanserlerinin büyük çoğunluğu oldukça yavaş
seyirlidir ve oldukça büyük bir kısmı hastanın
yaşamına tehdit oluşturmaz, fakat hızla
ilerleme gösterip hastanın sağlığına ve
yaşamına ciddi tehdit oluşturabilecek olanları
da ayırt etmek gereklidir. Organa sınırlı
prostat kanseri tedavi alternatiflerinden olan
radikal prostatektomi sırasında lenf nodu
pozitifliği veya postoperatif erken ve geç
dönemde
rekürrens
görülebilmektedir.
Preoperatif PSA, transrektal ultrasonografibiyopsi Gleason skoru, parmakla rektal
muayene kullanarak hazırlanan nomogramlar
ve bunlara patolojik Gleason skoru, cerrahi
sınır tutulumu, ekstraprostatik yayılım,
kapsüler ve seminal vezikül invazyon gibi
histopatolojik bulgular ile hastalığın klinik
progresyonunun
önceden
belirlenmesini
amaçlanmaktadır3-5. Patolojik Gleason skoru
progresyonu
belirlemede
en
kuvvetli
prognostik faktördür6. Henüz patolojik
Gleason skorundan daha iyi prognostik bilgi
veren parametre bulunmamasına rağmen,
birçok yeni biyobelirteçin prognostik önemi
araştırılma aşamasındadır. Prostat kanserinde
prognostik
faktör
olarak
kullanılması
gündemde olan p53, p27, p21, insülin benzeri
büyüme faktörü (IGF), androjen reseptör
durumu ve mikrodamar dansitesi yakın
zamanda
bu
konuda
araştırılan
biyobelirteçlerin en önemlilerindendir6.
E-Cadherin epitelyal hücrelerdeki önemli
adezyon molekülüdür ve hücreler arasındaki
moleküler bağlantıyı, yapışma kavşaklarında
fermuara benzer yapılar oluşturarak sağlarlar.
Tümör
hücrelerinde
E-Cadherin
ekspresyonunun
azaldığı
ve
epitel
hücrelerinin göç kabiliyetlerinin arttığı
belirlenmiştir. Böylece, E-Cadherin’in invaziv
özelliğe karşı koruyucu olduğu sonucuna
varılmıştır6.
Apoptozisi tetikleyen stres faktörlerinin
kaspaz aktivasyonu yoluyla hücre ölümünde
Bcl-2 proteinleri önemli rol oynamaktadır.
Bcl-2 proteinleri, mitokondri dış zarının
geçirgenliğini değiştirmek suretiyle etki
göstermektedir. Bcl-2 ailesindeki üç alt
gruptan biri olan ‘BH3-only’ Bcl-2 ailesinde
Bad, Bik, Hrk, Noxa, Bid, Bmf, p53
upregulated modifier of apoptosis (PUMA) ve
Bim yer alır10-12.
Bu çalışmada amaç, radikal prostatektomi
uygulanmış hastaların doku örneklerinde
VEGF, E-Cadherin, ve Bim biyobelirteçlerini
immünohistokimyasal
yöntemlerle
değerlendirmek ve
prostat kanserinin
prognozu üzerine öngörü değerlerini ortaya
koymaktır.
GEREÇ-YÖNTEM
Hastane Etik Kurulundan onay alındıktan
sonra S.B. İstanbul Göztepe Eğitim ve
Araştırma Hastanesi 1.Üroloji Kliniği’nde
2002–2007 tarihleri arasında klinik organa
sınırlı prostat kanseri tanısı ile radikal
prostatektomi operasyonu uygulanmış ve
günümüze kadar takiplerine düzenli olarak
gelmiş olan 66 hastanın patoloji örnekleri
çalışmaya alınmıştır (onay tarihi: 26.09.2007,
karar no: 39/A). Olguların yaş, preoperatif ve
postoperatif prostat spesifik antijen (PSA),
klinik ve patolojik evre, transrektal
ultrasonografi-prostat biyopsi ve radikal
prostatektomi Gleason skoru, tümör çapı,
Vasküler endotelyal büyüme faktörü (VEGF)
endotel
hücrelerinin
proliferasyonunu,
migrasyonunu
ve
diferansiyasyonunu
sağlamaktadır7,8. Ayrıca, VEGF muhtemel
temel anjiyojenik faktör olmanın yanında,
VEGF’e maruz kalan damarlarda, endotel
hücreleri arasında fenestrasyon, veziküler
organeller ve transsellüler aralık oluşumuna
olanak sağlayarak damar geçirgenliğini arttırır
204
Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının
prognostik değeri
sinir, kapsül ve seminal vezikül tutulumu,
ekstrakapsüler
uzanım
(ekstraprostatik
yayılım), cerrahi sınır pozitifliği, lenf nodu
metastazı, biyokimyasal rekürrens, klinik
progresyon verileri değerlendirildi (Tablo I).
Hastaların klinik ve patolojik evrelemesi için
TNM evreleme sistemi (2002) kullanıldı5.
Hastalarda izlem sırasında ölçülebilen PSA
değerinin 0,2 ng/ml ve üzerinde olması
biyokimyasal rekürrens, kemik sintigrafisi
veya diğer görüntüleme yöntemleri ile
metastaz saptanması progresyon olarak
değerlendirildi3,5.
Patoloji örnekleri tek bir patoloji uzmanı
tarafından
önceki
patoloji
sonucu
bilinmeksizin tekrar değerlendirildi. Bu 66
olguya ait patoloji örneklerinin hematoksilineosin boyalı kesitleri incelenerek, olgulara ait
bloklar arasından her bir olgu için tümörü en
iyi
örnekleyen,
immünohistokimyasal
çalışması için uygun yeterlilikte doku
bulunduran, 66 parafin blok çalışma için
seçildi. Çalışmaya seçilen bloklardaki doku
örnekleri tümöral ve nontümöral alanları
birlikte içermekteydi. Seçilen her parafin
bloğa VEGF, E-Cadherin ve Bim boyaları
immünohistokimyasal olarak uygulandı.
Tablo I. Hastaların klinik ve histopatolojik özellikleri.
<4
4,1-10
10,1-20
>20
<7
≥7
T1
T2
T2
T3
T4
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Preoperatif PSA (ng/ml)
Gleason skoru
Klinik evre
Patolojik evre
Kapsüler invazyon
Cerrahi sınır tutulumu
Ekstraprostatik yayılım
Seminal vezikül invazyonu
Perinöral invazyon
Vasküler invazyon
Lenf nodu metastazı
205
n
6
25
23
12
47
19
29
37
51
13
2
42
24
42
24
55
11
57
9
20
46
61
5
61
5
(%)
9
38
35
18
71
29
44
56
77
20
3
64
36
64
36
83
17
86
14
33
67
92
8
92
8
prognostik değeri
gözlemlemek için AEC kromojen sistemi
(AEC Substrate system, Thermo Fisher
Scientific Anatomical Pathology, CA USA)
kullanıldı. Yirmi mikrolitre AEC kromojen, 1
ml AEC substrat ile karıştırıldıktan sonra
kesitlere 10 dakika süre ile uygulandı. Daha
sonra kesitler distile su ile yıkanıp zıt boya
olarak 1,5 dakika hematoksilen ile boyandı.
Su bazlı kapama maddesi damlatılarak
kesitler kapatıldı.
İmmünhistokimyasal boyama işlemleri:
Seçilen parafin bloklardan elde edilen 5
mikrometre kalınlıktaki kesitler, önceden
poly-L-Lysin ile kaplanmış lamlara alındı.
Kesitler bir gece önce 57 C º’lik sıcaklıkta
etüvde bekletildi. Deparafinizasyon işlemi
için etüvden alınan kesitler 30 dakika
süresince 3 ayrı şale ile ksilolden geçirildi.
Daha sonra derecesi azalan alkollerden 20
dakikada geçirilen kesitler distile su ile
yıkandı. Antijen retrieval amacıyla plastik
taşıyıcıya alınan kesitler, kesit yüzeyini
örtecek şekilde pH6 sitrat buffer solusyonu
içine yerleştirildi. Üç kez 5’er dakikalık
sürelerle toplam 15 dakika mikrodalga fırında
şoklandı. Oda sıcaklığında 10 dakika
bekletildikten sonra kesitler distile su ile
yıkandı. Dokuların etrafı hidrofobik kalem ile
çizildi ve kesitler PBS (phosphate buffered
saline) ile yıkandı. Dokudaki endojen
peroksidaz aktivitesini ortadan kaldırmak
amacıyla,
kesitlerin
üzerine
hidrojen
peroksidin %0,3’lük çözeltisi damlatılarak 15
dakika bekletildi. Kesitler tekrar PBS ile
yıkandı.
Nonspesifik
bağlanmaları
engellemek amacıyla kesitler üzerine Ultra V
Block Nonspesific Blocking Reagent (Lab
Vision Corporation, CA, USA ) 10 dakika
uygulandı. Ardından VEGF (Epitope Spesific
Rabbit Antibody, Thermo Fisher Scientific
Anatomical Pathology, CA USA), E-Cadherin
(Epitope Spesific Rabbit Antibody, Thermo
Fisher Scientific Anatomical Pathology, CA
USA), BIM/BOD (bcl-2-related Ovarian
Death Gene) Ab-1 (Rabbit polyclonal
antibody,
Thermo
Fisher
Scientific
Anatomical Pathology, CA USA) damlatılıp
60 dakika bekletildi. Dört ayrı PBS
banyosunda 10 dakika yıkandı. Sekonder
antikor olarak Biotinylated Goat AntiPolyvalent (Lab Vision Corporation, CA
USA) uygulandı ve 15 dakika bekletildi.
Kesitler tekrar 4 ayrı PBS banyosunda
yıkandı ve kesitlerin üzerine immün
reaksiyonu gözlemlemek için işaretleyici
(label) olarak Streptavidin Peroxidase (Lab
Vision Corporation, 47790 CA, USA)
damlatılarak 15 dakika beklendi. PBS ile
yıkanan kesitlerin üzerine immün reaksiyonu
İmmunreaktivitenin değerlendirilmesi
Bu çalışmada pozitif kontrol için çevre
malign olmayan prostat dokusu dikkate alındı.
VEGF, E-Cadherin, Bim immünreaktivitesi
sitoplazmik boyanmanın varlığında pozitif
kabul edildi. Boyanma yaygınlık ve boyanma
şiddeti açısından değerlendirildi. VEGF
boyanma şiddetinin değerlendirilmesinde
sitoplazmik
boyanma
dikkate
alındı.
Boyanma yok ise (-), hafif boyanma (+), orta
derecede boyanma (++), kuvvetli boyanma
(+++) ve VEGF boyanma yaygınlığı boyanma
yok (-), %0-%25 (+), %25-%50 (++) ve
%50’nin üstünde (+++) kabul edildi. ECadherin
ile
boyanmanın
değerlendirilmesinde
ise
membranöz
boyanma dikkate alındı. Boyanma yok (-),
hafif boyanma (+), orta derecede boyanma
(++) ve kuvvetli boyanma (+++) kabul edildi.
Bim ile boyanmanın değerlendirilmesinde
nükleer boyanma dikkate alındı ve
boyanmanın olmaması (-), %10’un altında
boyanma (+), %10-%25 boyanma (++) ve
%25’in üstünde boyanma (+++) olarak
değerlendirildi (Resim 1)13.
İstatistiksel değerlendirme:
İstatistiksel analizler NCSS 2007 paket
programı
ile
yapılmıştır.
Verilerin
değerlendirilmesinde tanımlayıcı istatistiksel
metotların (ortalama, standart sapma) yanı
sıra
ikili
grupların
karşılaştırmasında
bağımsız
t
testi,
nitel
verilerin
karşılaştırmalarında
ki-kare
testi
kullanılmıştır. Biyobelirteçlerin (VEGF, ECadherin ve Bim) immünohistokimyasal
çalışmalarından elde edilen verilerin birbirleri
ile
ilişkilerinin
değerlendirilmesinde
Spearman korelasyon testi kullanıldı.
206
prognostik değeri
Sonuçlar, anlamlılık
değerlendirilmiştir.
p<0,05
düzeyinde
BULGULAR
Tüm olgular Gleason skoru <7 ve Gleason
skoru ≥7 olmak üzere gruplandırıldı. Bu iki
grubun operasyon öncesi verileri, patoloji
örnekleri ve izlem sonuçları karşılaştırıldı.
Yaş, tümör çapı, izlem süresi ve prostatik
intraepitelyal neoplazi (PİN) dışında kalan
tüm veriler arasında istatistiksel olarak
anlamlı fark saptandı (p<0.05) (Tablo II ve
III). Yapılan immünhistokimyasal boyama
sonucunda VEGF ve E-Cadherin ekspresyon
yüzdeleri karşılaştırıldığında her iki grup
arasında istatistiksel olarak anlamlı fark
görülmedi (p>0.05) (Tablo II).
Resim 1: Boyanma dereceleri: I-VEGF
(sitoplazmik) kuvvetli [A] ve orta [B], II-E –
Cadherin (membranöz) orta [A] ve kuvvetli [B],
III-Bim (nükleer) %10-25(++) [A] ve %25’in
üstünde (+++) boyanma [B].
Tablo II. Hastaların radikal prostatektomi Gleason skoruna göre dağılımları.
Gleason <7 Gleason ≥7
t
p
Yaş (yıl)
63,02±5,89
64,63±6,46
-0,98
0,332
10,37±8,42 25,86±17,69
-3,66
0,001
TRUS-biyopsi Gleason skoru
5,68±0,75
6,11±1,05
-1,84
0,07
Tümör çapı (cm)
1,46±0,89
1,85±0,81
-1,67
0,1
İzlem süresi (ay)
40,89±12,26 39,21±15,62
0,47
0,643
VEGF en şiddetlinin %si
44,79±26,88 58,95±34,46
-1,78
0,079
E-cadherin en şiddetlinin %si
47,98±30,67 38,16±29,78
1,19
0,239
E-cadherin en yaygın şiddetin %si 72,02±12,58 69,47±13,93
0,72
0,473
207
prognostik değeri
PSA rekürrensi gözlenen hasta sayısı 19
(%29) iken rekürrens saptanmayan hasta
sayısı 47 (%71) idi. Rekürrens durumuna göre
hastaların verileri karşılaştırıldığında, tümör
çapı, histopatolojik Gleason skoru ve
preoperative PSA arasında istatistiksel olarak
anlamlı fark saptandı (p<0.05). Yapılan
immünhistokimyasal boyama sonucunda
VEGF en şiddetli ekspresyonunun PSA
rekürrensi olanlarda %59,74 ve rekürrens
saptanmayanlarda %44,47 olduğu gözlendi
(p=0,058). E-Cadherin en şiddetli düzeyde
ekspresyonu rekürrens olanlarda %45,21 ve
rekürrens olmayanlarda %45,27 (p=0,98)
iken, E-Cadherin en yaygın şiddetinde
ekspresyonunun rekürrens olanlarda %72,2 ve
rekürrens olmayanlarda %68,9 olduğu izlendi.
Tüm veriler karşılaştırıldığında, aradaki farkın
istatistiksel olarak anlamlı olmadığı belirlendi
(p=0,354) (Tablo IV).
ve %42,1 (p=0,29), E-Cadherin kuvvetli
immünreaktivite gösterme oranlarının %91,5
ve %78,9 (p=0,157), E-Cadherin kuvvetli
yaygınlık
immünreaktivite
gösterme
oranlarının %46,8 ve %26,3 olduğu gözlendi
(p=0,303). Ayrıca Gleason 7’nin altında
olanlarda Bim kuvvetli immünreaktivite
gösterme oranı %12,8 iken Gleason 7 ve
üzerinde olanlarda bu oran %21,1 idi
(p=0,657). Tüm biyobelirteçler arasında
istatistiksel olarak anlamlı fark saptanmadı
(Tablo VI).
PSA
rekürrensi
gözlenen
olgularda
immünhistokimyasal boyamalar yapıldıktan
sonra
sırası
ile
VEGF
kuvvetli
immünreaktivite gösterme oranı %52,6
(p=0,161),
VEGF
kuvvetli
yaygınlık
(p=0,099),
E-Cadherin
kuvvetli
(p=0,157), E-Cadherin kuvvetli yaygınlık
(p=0,896) ve Bim kuvvetli immünreaktivite
gösterme oranı %31,6 idi (p=0,895). Hiçbir
biyobelirteçin
kuvvetli
immünreaktivite
gösterme oranlarında istatistiksel olarak
anlamlı fark saptanmadı (Tablo VII).
PSA rekürrensi gözlenen ile rekürrens
gözlenmeyen olguların operasyon öncesi
verilerinin, patoloji örneklerinin ve izlem
sonuçlarının kendi aralarında karşılaştırılması
Tablo V’te gösterilmiştir. Klinik evre, PİN,
sağkalım ve hastalığa bağlı mortalite dışında
tüm veriler arasında istatistiksel olarak
anlamlı fark saptandı (p<0.05)
Gleason skoru ve rekürrens gelişimi açısından
biyobelirteçlerde
istatistiksel
anlam
görülmemesine karşın immünohistokimyasal
çalışmalarından elde edilen verilerin birbirleri
ile
ilişkilerini
belirlemede
Spearman
korelasyon testi kullanıldığında E-Cadherin
ve VEGF arasında istatistiksel anlamda
korelasyon saptandı (p=0,05) (Tablo VIII ve
IX).
Patoloji
örneklerinin
biyobelirteçlerle
boyanma şiddetleri Gleason skoru ve PSA
rekürrensine göre değerlendirildi. Gleason
skoru <7 ve ≥7 olarak ayrılan her iki grupta
sırası ile VEGF kuvvetli immünreaktivite
gösterme oranlarının %27,7 ve %47,4
(p=0,196),
VEGF
kuvvetli
yaygınlık
immünreaktivite gösterme oranlarının %21,3
208
prognostik değeri
Tablo III. Histopatolojik Gleason skoruna göre prognostik faktörlerin karşılaştırması.
TRUS-biyopsi
Klinik evre
Patolojik evre
Kapsüler invazyon
Ekstraprostatik yayılım
Perinöral invazyon
Vasküler invazyonu
PİN
Klinik progresyon
Yaşam
Ölüm nedeni
PSA rekürrensi
<4
4,1-10
10,1-20
>20
<7
≥7
T1
T2
T2
T3
T4
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Yok
Var
Eksitus
Hayatta
Prostat kanseri
Diğer
Yok
Var
Gleason <7
%12,8
%48,9
%27,7
%10,6
%91,5
%8,5
%53,2
%46,8
%91,5
%8,5
%0,0
35
%74,5
12
%25,5
35
%74,5
12
%25,5
44
%93,6
3
%6,4
45
%95,7
2
%4,3
19
%40,4
28
%59,6
46
%97,9
1
%2,1
28
%59,6
19
%40,4
46
%97,9
1
%2,1
47
%100,0
0
%0,0
2
%4,3
45
%95,7
0
%0,0
2
%4,3
42
%89,4
5
%10,6
6
23
13
5
43
4
25
22
43
4
0
2
10
7
11
8
4
15
8
9
2
7
12
7
12
11
8
12
7
1
18
15
4
14
5
15
4
17
2
4
15
2
2
5
14
Gleason ≥7
%0,0
%10,5
%52,6
%36,8
%57,9
%42,1
%21,1
%78,9
%42,1
%47,4
%10,5
%36,8
%63,2
%36,8
%63,2
%55,6
%44,4
%63,2
%36,8
%5,3
%94,7
%78,9
%21,1
%73,7
%26,3
%78,9
%21,1
%89,5
%10,5
%21,1
%78,9
%10,5
%10,6
%26,3
%73,7
χ²:15,2
p=0,002
χ²:10,2
p=0,001
χ²:5,67
p=0,017
χ²:19,5
p=0,0001
χ²:8,27
p=0,004
χ²:8,27
p=0,004
χ²:13,4
p=0,0001
χ²:12,2
p=0,0001
χ²:7,92
p=0,005
χ²:6,92
p=0,009
χ²:1,16
p=0,281
χ²:6,92
p=0,009
χ²:5,1
p=0,024
χ²:4,61
p=0,032
χ²:5,47
p=0,019
χ²:26,2
p=0,0001
Tablo IV. Hastaların PSA rekürrensi durumuna göre dağılımları.
Yaş (yıl)
TRUS-biyopsi Gleason skoru
Histopatolojik Gleason skoru
Tümör çapı (cm)
İzlem süresi (ay)
VEGF en şiddetlinin %si
E-cadherin en şiddetlinin %si
E-cadherin en yaygın şiddetin %si
Nüks (-)
63,13±5,98
10,29±8,32
5,7±0,75
5,89±0,56
1,41±0,84
41,43±13,18
44,47±28,54
45,21±31,79
72,23±12,46
209
Nüks (+)
64,37±6,32
26,05±17,62
6,05±1,08
7,42±1,35
1,96±0,86
37,89±13,29
59,74±30,48
45±27,94
68,95±14,1
t
-0,75
-3,74
-1,51
-4,78
-2,41
0,98
-1,93
0,03
0,93
p
0,455
0,001
0,136
0,0001
0,019
0,329
0,058
0,98
0,354
prognostik değeri
Tablo V. PSA rekürrensi olup olmamasına göre diğer prognostik faktörlerin karşılaştırması.
<4
4,1-10
10,1-20
>20
<7
TRUS-biyopsi skoru
≥7
T1
Klinik evre
T2
T2
Patolojik evre
T3
T4
<7
Patolojik Gleason skoru
≥7
Yok
Kapsül invazyonu
Var
Yok
Var
Yok
Ekstra prostatik yayılım
Var
Yok
Var
Yok
Perinöral invazyon
Var
Yok
Vasküler invazyon
Var
Yok
PİN
Var
Yok
Var
Yok
Klinik progresyon
Var
Eksitus
Yaşam
Hayatta
Prostat kanseri
Ölüm nedeni
Diğer
Rekürrens (-) %
6
12,8
24
51,1
12
25,5
5
10,6
42
89,4
5
10,6
24
51,1
23
48,9
43
91,5
4
8,5
0,0
42
89,4
5
10,6
34
72,3
13
27,7
34
72,3
13
27,7
44
93,6
3
6,4
46
97,9
1
2,1
18
38,3
29
61,7
46
97,9
1
2,1
27
57,4
20
42,6
47
100,0
0,0
47
100,0
0,0
3
6,4
44
93,6
0
0,0
3
6,4
210
Rekürrens (+) %
0,0
1
5,3
11
57,9
7
36,8
12
63,2
7
36,8
5
26,3
14
73,7
8
42,1
9
47,4
2
10,5
5
26,3
14
73,7
8
42,1
11
57,9
8
42,1
11
57,9
10
55,6
8
44,4
11
57,9
8
42,1
2
10,5
17
89,5
15
78,9
4
21,1
15
78,9
4
21,1
14
73,7
5
26,3
17
89,5
2
10,5
3
15,8
16
84,2
2
10,5
1
5,3
χ²:19
p=0,0001
χ²:6,24
p=0,012
χ²:3,36
p=0,067
χ²:19,5
p=0,0001
χ²:26,23
p=0,0001
χ²:5,34
p=0,021
χ²:5,34
p=0,021
χ²:13,4
p=0,0001
χ²:18,3
p=0,0001
χ²:4,94
p=0,026
χ²:6,92
p=0,009
χ²:2,7
p=0,1
χ²:13,3
p=0,0001
χ²:5,1
p=0,024
χ²:1,44
p=0,229
χ²:6,32
p=0,097
prognostik değeri
Tablo VI. Hastaların Gleason skoruna göre biyobelirteçlerin dağılımları.
Biyobelirteç
VEGF şiddet
VEGF yaygınlık
E-Cadherin en
şiddetli
E-Cadherin en
yaygın şiddet
Bim
Şiddet
(-)
(+)
(++)
(+++)
(-)
(+)
(++)
(+++)
(++)
(+++)
(+)
(++)
(+++)
(-)
(+)
(++)
(+++)
Gleason <7
n
%
5
10,6
9
19,1
20
42,6
13
27,7
5
10,6
8
17,0
24
51,1
10
21,3
4
8,5
43
91,5
6
12,8
19
40,4
22
46,8
21
44,7
18
38,3
2
4,3
6
12,8
Gleason ≥7
n
%
2
10,5
5
26,3
3
15,8
9
47,4
2
10,5
1
5,3
8
42,1
8
42,1
4
21,1
15
78,9
3
15,8
11
57,9
5
26,3
9
47,4
6
31,6
0
0,0
4
21,1
χ²:4,68
p=0,196
χ²:3,74
p=0,29
χ²:1,99
p=0,157
χ²:2,38
p=0,303
χ²:1,61
p=0,657
Tablo VII. Hastalarda PSA rekürrensi saptanmasına göre biyobelirteçlerin dağılımları.
Biyobelirteç
VEGF
Şiddet
VEGF
yaygınlık
E-Cadherin en
şiddetli
E-Cadherin
en yaygın şiddet
Bim
Şiddet
(-)
(+)
(++)
(+++)
(-)
(+)
(++)
(+++)
(++)
(+++)
(+)
(++)
(+++)
(-)
(+)
(++)
(+++)
Rekürrens (-)
n
%
6
12,8
10
21,3
19
40,4
12
25,5
6
12,8
8
17,0
24
51,1
9
19,1
4
8,5
43
91,5
6
12,8
21
44,7
20
42,6
22
46,8
19
40,4
2
4,3
4
8,5
211
Rekürrens (+)
n
%
1
5,3
4
21,1
4
21,1
10
52,6
1
5,3
1
5,3
8
42,1
9
47,4
4
21,1
15
78,9
3
15,8
9
47,4
7
36,8
8
42,1
5
26,3
0
0,0
6
31,6
χ²:5,15
p=0,161
χ²:6,26
p=0,099
χ²:1,99
p=0,157
χ²:0,22
p=0,896
χ²:6,36
p=0,095
prognostik değeri
Tablo VIII. E-Cadherin ve VEGF’ nin Spearman korelasyon testi ile karşılaştırılması
Gleason skoru
E-Cadherin en şiddetli
E-Cadherin en yaygın şiddetli
Bim
VEGF şiddet
0,128
0,307
0,243
0,05
0,161
0,196
0,185
0,136
r
p
r
p
r
p
r
p
VEGF yaygınlık
0,176
0,156
0,093
0,457
0,099
0,429
0,137
0,273
Tablo IX. E-Cadherin ve VEGF’ nin Spearman korelasyon testi ile karşılaştırılması
Gleason skoru
VEGF Şiddet
VEGF yaygınlık
r
p
r
p
r
p
E-Cadherin en şiddetli
-0,04
0,749
0,243
0,05
0,093
0,457
E-Cadherin en yaygın şiddetli
-0,067
0,591
0,161
0,196
0,099
0,429
Bim
0,037
0,769
0,185
0,136
0,137
0,273
Yapılan
çalışmalarda,
bu
prognostik
faktörlere ilave olarak insülin benzeri büyüme
faktörü (IGF), androjen reseptör durumu,
mikrodamar dansitesi, Ki-67 indeksi ve p53
geni mutasyonu gibi tümöre ait histopatolojik
biyobelirteçlerin de hastalık progresyonun
önceden belirlenmesinde faydalı olabileceği
belirtilmektedir6.
TARTIŞMA
Prostat kanserinin biyolojik heterojenitesi, her
hastaya
özgü
bir
karar
almayı
gerektirmektedir. Prognoz hakkında bilgi
sahibi olmak, prostat kanseri tedavi
alternatifleri arasında seçim yapmak ve daha
sonraki dönemdeki riskleri belirlemek
açısından önemlidir. Prognostik parametreler
ve bunlar üzerinden oluşturulan birçok
nomogram yardımıyla patolojik evrenin ve
izlemde
olası
senaryoların
önceden
3-5
belirlenmesi amaçlanmıştır . Buna rağmen,
literatürde organa sınırlı prostat kanseri tanısı
ile radikal prostatektomi uygulanan hastaların
%30-45’inde, bizim çalışmamızda % 17’sinde
patolojik olarak ekstraprostatik yayılım
gözlenmiştir14. Bu nedenle, kısa sürede
progresyon gösterecek yüksek riskli hasta
gruplarının önceden belirlenmesi amacıyla
birçok yeni patolojik faktörün prognostik
önemi
araştırılmaktadır.
Ancak
bu
faktörlerden hiçbirisi henüz Gleason skorunun
ötesinde prognostik bilgi verememektedir3-6.
Prostat kanseri progresyonu, anjiyogenez
sayesinde yeterli vaskülarizasyon ve bölgesel
lenf nodu, kemik metastazları ile ilişkilidir.
Tümör hücreleri anjiyojenik faktörleri
salgılayarak neovaskularizasyonu uyarır. Bu
faktörler olmadan tümör hücreleri besin
maddeleri ve oksijeni yeterli düzeyde
alamayacağı için 2-3 mm’den fazla
büyüyemeyecektir. Anjiyojenik faktörlerden
biri olan VEGF’in hipoksi ile indüklenerek
sentezinin artması neovaskularizasyona giden
yolda çok önemli bir adımdır15. Artmış VEGF
ekspresyonu progresyon ile yakından
ilişkilidir. VEGF anjiyogenezi stimüle eder ve
mikrodamar yoğunluğunu arttırır; böylece
212
prognostik değeri
tümör dokusunun büyümesi kolaylaşır16.
VEGF prostat kanseri progresyonunu, nöroendokrin
farklılaşmış
prostat
kanser
hücrelerinden
salıverilerek
anjiyogenezi
uyarması ve mikrodamar yoğunluğunu
arttırmasının yanı sıra doğrudan prostat
kanser hücrelerinde büyümeyi uyardığı
düşünülmektedir6,16. Tüm bu verilere rağmen
güncel literatürde prostat kanseri ile VEGF
ekspresyonu arasındaki ilişki tartışmalıdır.
Daha önceki çalışmalarda, prostat kanser
epitelyumunda normal ve benign prostat
dokusuna göre VEGF ekspresyonunun daha
yüksek
olduğu
gösterilmiştir15,16.
Bu
bulguların aksine, Wu ve ark. çalışmalarında
malign ve benign prostatik epitelyum arasında
VEGF immünreaktivitesi açısından fark
saptamamışlardır17. Joseph ve Isaacs,
androjen tarafından kontrol edilen VEGF’in
prostat kanseri büyümesinde etkili olduğunu
bildirirken, West ve ark. tümör epitelindeki
artmış VEGF immünreaktivitesinin daha
yüksek serum PSA seviyesi ile anlamlı oranda
ilişkisinin olduğunu göstermişlerdir18,19.
E-Cadherin epitelyal hücrelerdeki önemli
adezyon molekülüdür. E- Cadherin bağımlı
adezyonun kaybı, birçok kanser için kötü
progresyon
belirtisidir.
E-Cadherin
ekspresyonundaki azalmanın uzak metastaz,
rekürrens ve azalmış toplam sağkalım ile
ilişkili
olduğunu
bildiren
çalışmalar
25,26
.
vardır
Çok yeni bir çalışmada; klinik önemli prostat
kanserinde E-Cadherin anormal şekilde
boyanmış iken klinik önemsiz prostat
kanserinde E-Cadherin boyanmasının normal
olduğunu
göstermişlerdir26.
İmmunohistokimyasal E-Cadherin seviyesi
üzerine yapılan bir çalışmada malign prostat
dokusunda %50 oranında azalma ve hatta bazı
örneklerde E-Cadherin’in tamamen ortadan
kalktığı, benign prostat dokusunun ise
homojen kuvvetli pozitif boyandığını
belirlemişlerdir27. Yine 89 prostat kanseri
olgusunda
düşük
E-Cadherin
immunohistokimyasal
ekspresyonu
saptananlarda yüksek ekspresyon saptananlara
oranla
daha
kısa
sağkalım
süresi
gözlenmiştir27,28. Van Oort ve ark. prostat
kanserinde E-Cadherin ekspresyonu ile
progresyon ve sağkalım arasındaki ilişkiyi
incelemişlerdir.
Altmış
beş
radikal
prostatektomi olgusunun histopatoloji örneği
incelendiğinde; 36 olguda (%55,4) normal ECadherin boyanması izlenirken E-Cadherin
ile normal boyananlarda 5 yıllık sağkalımın
%79,2, boyanmayanlarda ise bu oranın %
26,8 olduğu saptadılar (p<0.05)29. Musial ve
ark. E-Cadherin anormal boyanmasının
sağkalım süresi üzerinde negatif etkisi olan
bağımsız bir prediktör faktör olduğunu
bulmuşlardır30. De Marzo ve ark. azalmış ECadherin seviyesinin RP sonrası Gleason
skoru yüksekliği (p=0.003) ve patolojik evre
(p=0.008) ile ilişkili olduğunu, ve ECadherin’in progresyonu belirleyen bir
biyobelirteç
olarak
kullanılabileceğini
31
bildirdiler . Aynı zamanda E-Cadherin’in
metastazla
ilişkisi
de
çalışmalarda
bildirilmiştir. Yapılan bir çalışmada Junior ve
ark. 28 kemik metastazlı hastada prostat
kanseri ve kemik örneklerini histopatolojik
olarak incelediklerinde kemik metastazı olan
örneklerde E-Cadherin ekspresyonundaki
Birçok hayvan çalışmasında VEGF aşırı
ekspresyonu ile lenfanjiyogenez ve lenf
metastazı arasındaki ilişki tespit edilmiştir.
VEGF lenf damarlarında hiperplazi ve yeni
lenf
damarı
oluşumundan
sorumlu
tutulmuştur20,21. Ancak, prostat kanseri için bu
bulgular da tartışmalıdır. Tsurusaki ve ark.
VEGF ve lenf nodu metastazı arasında
anlamlı bir ilişki olduğunu bildirirken, Zeng
ve ark. tam tersine anlamlı bir ilişki
saptamamışlardır22,23.
Yine,
VEGF
ekspresyonu ve yüksek Gleason skoruna sahip
tümörler arasındaki ilişki bazı çalışmalarda
bildirilmiş, bazılarında bildirilmemiştir17-23.
Ferer ve arkadaşları iyi diferansiye tümörlerde
daha
yoğun
VEGF
boyanmasını
göstermişlerdir24. Bizim çalışmamızda bu
belirsizliği destekler şekilde; Gleason skoru
ve rekürrens verilerine göre gruplandırıldıktan
sonra kendi aralarında immünohistokimyasal
boyanma
özelliklerine
göre
karşılaştırıldıklarında VEGF ile boyanma
oranları Gleason skoru yüksek ve rekürrens
gözlenen grupta daha fazla bulunmasına
rağmen aradaki fark istatistiksel olarak
anlamlı değildi.
213
prognostik değeri
kaybın %86 olduğunu, primer prostat
kanserinde ise %83 oranında E-Cadherin
ekspresyonunun
normal
olduğunu
gösterdiler32. Bizim çalışmamızda E-Cadherin
ile anormal boyanma oranları Gleason skoru
yüksek ve rekürrens saptanan grupta daha
fazla bulunmasına rağmen aradaki fark
istatistiksel olarak anlamlı değildi.
sırasında kanser hücrelerinin androjensiz
ortamda
kalmaları
yoğun
Bcl-2
ekspresyonuyla
hücreleri
apoptozisten
korumakta ve androjen duyarlı hücreler
hormona dirençli hale gelmektedir40.
Bim’in prostat kanserindeki prognostik
değerini araştıran çalışma sayısı sınırlıdır33.
Bim’in klinik önemi tedavide hedef olarak
kullanılabilmesindendir.
Yapılan
bir
çalışmada invivo ortamda 1,3-thiazolidione
(DBPT) maddesinin Bim fosforilasyonu
yaparak Bcl-2 ekspresyonu fazla olan
hücrelerde de apoptozisi, indüklediği ve
VEGF
ekspresyonunu
azalttığı
41
gösterilmiştir . Bizim çalışmamızda yine
Bim seviyesinin de radikal prostatektomi
sonrası prognozu belirlemede Gleason skoru
ile kıyaslandığında ek bir katkı sağlamadığı
görüldü.
Birçok tümörde anti-apoptotik proteinler,
yüksek düzeyde pro-apoptotik moleküllerle
beraber bulunur. İlk bakışta çelişkili görünen
bu durum 30’dan fazla proteini içeren ve bir
kısmı apoptozisi indükleyen bir kısmı da
baskılayan Bcl-2 ailesi ile açıklanabilir. Bcl-2
ailesinden biri olan Bim’in apoptozisi uyarıcı
etkisi olduğu düşünülmektedir. Tümör
baskılayıcı bir protein olan p53 ile
antiapoptotik etkili Bcl-2 kompleks oluşturur.
Böylece proapoptotik etkisi olan Bim
antiapoptotik proteinden ayrılır ve aktivasyon
gerçekleşir33.
Çalışmamızda boyanma özellikleri açısından
gruplar arasında istatistiksel anlamlı fark
olmamasına rağmen biyobelirteçler arasında
spearman korelasyon testi ile karşılaştırma
yapıldığında bazı alanlarda kendi aralarında
anlamlı ilişki saptandı. E-Cadherin en şiddetli
boyanması ile VEGF şiddeti arasında
istatistiksel olarak anlamlı ilişki bulundu.
Howard ve ark. E-Cadherin’in azalmış ve
Bcl-2’nin aşırı ekspresyonunun dolaşımdaki
tümör hücreleri ile ilişkili olduğunu
göstermişlerdir34. Hipoksi ile indüklenen
streste
Bcl-2
aşırı
ekspresyonu
ve
anjiogenezin uyarılması, tümör hücrelerinin
apoptozisten kaçarak yaşam sürelerini uzatır.
Yapılan invivo bir çalışmada hipoksi koşulları
oluşturulduktan sonra Bcl-2 aşırı ekspresyonu
olan prostat kanser hücrelerinde daha yüksek
oranda VEGF olduğunu göstermişlerdir35.
Sinha ve ark. hormonal tedavi alan lokal ileri
veya metastatik prostat kanserli hastalarda
Bcl-2 aşırı ekspresyonunun sağkalım ile ters
ilişkili olduğunu göstermişlerdir36. Diğer bir
çalışmada da Bcl-2 ve mikrodamar
yoğunluğunun prostat kanserli hastalardaki
ölümü gösteren bağımsız prediktör faktörler
olduğu
bulunmuştur37.
Bcl-2
aşırı
ekspresyonunun erken evre tümörlerde de
görülebilmesine karşın ileri evre prostat
kanserlerinde ekspresyon artışına çok daha sık
saptanır38. Ayrıca McDonnell ve ark. androjen
bağımsız olan prostat kanserinde yaygın ve
yüksek
oranda
Bcl-2
boyanması
gösterilmiştir. Bcl-2 ekspresyonunun prostat
kanserinin androjen bağımlı halden androjen
bağımsız duruma geçişi ile ilişkisi olduğu
gösterilmiştir39. Androjen ablasyonu tedavisi
Son yıllarda bizim çalışmamızda da olduğu
gibi
prostat
kanserinin
anjiyogenez,
proliferasyon ve genetik özelliklerinin beraber
değerlendirildiği çalışmalar planlanarak pratik
uygulamada kullanılabilecek veriler elde
edilmek istenmektedir. Ancak bu çalışmalarda
da farklı sonuçlar elde edilmektedir.
Çalışmamızın sonucunda VEGF ve ECadherin’in biri birleri ile ilişkili olmalarına
rağmen Gleason skoru ve PSA rekürrensi ile
ilişkisi bulunamamıştır. Böylece, VEGF, ECadherin ve Bim biyobelirteçlerinin radikal
prostatektomi
sonrası
progresyonu
belirlemede ek bir katkı sağlamadığını
düşünmekteyiz. Bu nedenle patolojik evre ve
Gleason
skoru
gibi
histopatolojik
parametreler bugün için en iyi prognostik
belirteçlerdir.
İmmünohistokimyasal
boyamanın
değerlendirilmesinde bilgisayar programı ile
yapılan imaj analiz yöntemi günümüzde
yaygın olarak kullanılmaktadır. Bu yöntemde
214
prognostik değeri
immünohistokimyasal reaksiyon sonucu
oluşan boyamanın derecesi objektif olarak
bilgisayar
programı
ile
değerlendirilmektedir42. İmaj analiz bilgisayar
programının pahalı olması ve hastanemizde
olmamasından dolayı imaj analiz yöntemi
çalışmamızda kullanılmadı.
Gleason skoru halen en önemli prognostik
faktör olmasına rağmen, klinik lokalize
prostat kanseri tanısı ile radikal prostatektomi
operasyonu olan hastaların yaklaşık üçte
birinde
gözlenen
rekürrensi,
önceden
belirlememize yetmemektedir. Bu nedenle
hastanın prognozunu önceden ortaya koyacak
yeni biyobelirteçlere ihtiyaç vardır. Radikal
prostatektomi patoloji örneklerinin Gleason
skorları literatürdeki verilerle uyumlu olarak
daha agresif tümörlerle ve daha kötü
progresyon ile uyumlu idi. Preoperatif ve
postoperatif veriler de incelendiğinde nüks
gözlenen hastalarda daha olumsuz veriler
saptandı. Biyobelirteçlerin (VEGF, ECadherin ve Bim) immünohistokimyasal
çalışmalarla
elde
edilen
verileri
değerlendirildiğinde;
gruplar
arasında
istatistiksel anlamda fark olmamasına karşın
özellikle VEGF’de anlamlılığa yakın derecede
fark gözlendi. Bu durum olgu sayısının az
olması ile açıklanabilir. Daha çok sayıda olgu
ile immünohistokimyasal boyanın ‘İmaj
Analiz’ yöntemi ile değerlendirilmesinin
biyobelirteçlerin prognostik değerini daha net
ortaya koyacağı düşüncesindeyiz.
KAYNAKLAR
1.
2.
3.
4.
5.
Bray F, Sankila R, Ferlay J, Parkin DM. Estimates of
cancer incidence and mortality in Europe in 1995. Eur J
Cancer 2002; 38: 99-166.
Terakawa T, Miyake H, Kanomata N, et al. Inverse
association between histologic inflammation in needle
biopsy specimens and prostate cancer in men with serum
PSA of 10-50 ng/mL. Urology 2008; 72: 1194-1197.
Acar C, Sözen S, Erdem Ö, ve ark. Prostat kanserinde
mikrodamar yoğunluğu, Kİ-67 ve p53 ekspresyonu ile
klinikopatolojik ölçütler ve hasta prognozu arasındaki
ilişki. Türk Üroloji Dergisi 2006; 32: 478-485.
Partin AW, Kattan MW, Subong EN, et al. Combination
of prostate-specific antigen, clinical stage, and Gleason
score to predict pathological stage of localized prostate
cancer. A multi-institutional update. JAMA 1997; 277:
1445-1451.
Him HH, Cho SY, Park DS, et al. Prognostic factors of
biochemical recurrence after radical prostatectomy in
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
215
Korean men with high-risk prostate cancer. EJSO,
article in press.
Eskiçorapçı SY. Prostat kanseri doğal seyri, prognostik
faktörler ve nomogramlar. In:Özen H, Türkeri L, eds.
Üroonkoloji Kitabı. Üroonkoloji Derneği; Ankara,
Ertem Basım Yayın, 2007. 593-603.
Klagsbrun M, D’Amore PA. Vascular endothelial
growth factor and its receptors. Cytokine Growt Factor
Rev 1996; 7: 259-270.
Dvorak HF, Brown LF, Detmar M, Dvorak AM.
Vascular permeability factor/vascular endothelial
growth factor, microvascular hyperpermeability, and
angiogenesis. Am J Pathol 1995; 146: 1029-1039.
Ferrara N, Davis-Smyth T. The biology of vascular
endothelial growth factor. Endocr Rev 1997; 18: 4-25.
Shibue T, Taniguchi T. BH3-only proteins: integrated
control points of apoptosis. Int J Cancer 2006; 119:
2036-2043.
Yee KS, Vousden KH. Complicating the complexity of
p53. Carcinogenesis 2005; 26: 1317-1322.
Chipuk JE, Bouchier-Hayes L, Kuwana T, et al. PUMA
couples the nuclear and cytoplasmic proapoptotic
function of p53. Science 2005; 309: 1732-1735.
Mungan MU, Gurel D, Canda AE, ve ark. Expression of
COX-2 in normal and pyelonephritic kidney, renal
intraepithelial neoplasia, and renal cell carcinoma. Eur
Urol 2006; 50: 92-97.
Noldus J, Graefen M, Haese A, et al. Stage migration in
clinically localized prostate cancer. Eur Urol 2000; 38:
74-78.
Nicholson B, Theoderescu D. Angiogenesis and prostate
cancer tumor growth, J Cell Biochem 2004; 91: 125150.
Claffey KP, Brown LF, Del Aguila LF, et al. Expression
of vascular endothelial growth factor by melanoma cells
increases tumor growth angiogenesis and experimental
metastasis. Cancer Res 1996; 56: 172-177.
Wu TT, Wang JS, Jiann BP, et al. Expression of
vascular endothelial growth factor in Taiwanese benign
and malignant prostate tissues. J Chin Med Assoc 2007;
70: 380-384.
Joseph IB, Isaacs JT. Potentiation of the antiangiogenic
ability of linomide by androgen ablation involves downregulation of vascular endothelial growth factor in
human androgen-responsive prostatic cancers. Cancer
Res 1997; 57: 1054-1057.
West AF, O'Donnell M, Charlton RG, et al. Correlation
of vascular endothelial growth factor expression with
fibroblast growth factor-8 expression and clinicopathologic parameters in human prostate cancer. Br J
Cancer 2001; 85: 576-583.
Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of
lymphatic vessels in VEGF-C transgenic mice. Science
1997; 276: 1423-1425.
Oh SJ, Jeltsch MM, Birkenhäger R, et al. VEGF and
VEGF-C: specific induction of angiogenesis and
lymphangiogenesis in the differentiated avian
chorioallantoic membrane. Dev Biol 1997; 188: 96-109.
Tsurusaki T, Kanda S, Sakai H, et al. Vascular
endothelial growth factor-C expression in human
prostatic carcinoma and its relationship to lymph node
metastasis. Br J Cancer 1999; 80: 309-313.
Zeng Y, Opeskin K, Baldwin ME, et al. Expression of
vascular endothelial growth factor receptor-3 by
lymphatic endothelial cells is associated with lymph
node metastasis in prostate cancer. Clin Cancer Res
2004; 10: 5137-5144.
prognostik değeri
24. Ferrer FA, Miller LJ, Andrawis RI, et al. Vascular
endothelial growth factor (VEGF) expression in human
prostate cancer: in situ and in vitro expression of VEGF
by human prostate cancer cells. J Urol 1997; 157: 23292333.
25. Otto T, Birchmeier W, Schmidt U, et al. Inverse relation
of E-Cadherin and autocrine motility factor receptor
expression as a prognostic factor in patient with bladder
carcinomas. Cancer Res 1994; 54: 3120-3123.
26. van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, et
al. Detailed analysis of histopathological parameters in
radical prostatectomy specimens and PCA3 urine test
results. Prostate 2008; 6811: 1215-1222.
27. Buhmeida A, Pyrhönen S, Laato M, Collan Y.
Prognostic factors in prostate cancer. Diagn Pathol
2006; 1: 1-15.
28. Umbas R, Isaacs WB, Bringuier PP, et al. Decreased Ecadherin expression is associated with poor prognosis in
patients with prostate cancer. Cancer Res 1994; 54:
3929-3933.
29. van Oort IM, Tomita K, van Bokhoven A, et al. The
prognostic value of E-cadherin and the cadherinassociated molecules alpha-, beta-, gamma-catenin and
p120ctn in prostate cancer specific survival: a long-term
follow-up study. Prostate 2007; 67: 1432-1438.
30. Musiał J, Sporny S, Nowicki A. Prognostic significance
of E-cadherin and ezrin immunohistochemical
expression in prostate cancer. Pol J Pathol 2007; 58:
235-243.
31. De Marzo AM, Knudsen B, Chan-Tack K, Epstein JI. Ecadherin expression as a marker of tumor aggressiveness
in routinely processed radical prostatectomy specimens.
Urology 1999; 53: 707-713.
32. Junior JP, Srougi M, Borra PM, et al. E-cadherin and
beta-catenin Loss of Expression Related to Bone
Metastasis in Prostate Cancer. Appl Immunohistochem
Mol Morphol 2008 Aug 5. [Epub ahead of print]
33. Liu JW, Chandra D, Tang SH, et al. Identification and
characterization of Bimgamma, a novel proapoptotic
BH3-only splice variant of Bim. Cancer Res 2002; 62:
2976-2981.
34. Howard EW, Leung SC, Yuen HF, et al. Decreased
adhesiveness, resistance to anoikis and suppression of
GRP94 are integral to the survival of circulating tumor
cells in prostate cancer. Clin Exp Metastasis 2008; 25:
497-508.
35. Fernandez A, Udagawa T, Schwesinger C, et al.
Angiogenic potential of prostate carcinoma cells
overexpressing bcl-2. J Natl Cancer Inst 2001; 93: 208213.
36. Sinha BK, Yamazaki H, Eliot HM, et al. Relationships
between proto-oncogene expression and apoptosis
induced by anticancer drugs in human prostate tumor
cells. Biochim Biophys Acta 1995; 1270: 12-18.
37. Concato J, Jain D, Li WW, et al. Molecular markers and
mortality in prostate cancer. BJU Int 2007; 100: 12591263.
38. Çal Ç, Şimşir A. Prostat kanseri hücrelerinde androjen
baskılama tedavisinde direnç gelişiminin mekanizmaları.
Türk Üroloji Dergisi 2005; 31: 21-30.
39. McDonnell TJ, Troncoso P, Brisbay SM, et al.
Expression of the protooncogene bcl-2 in the prostate
and its association with emergence of androgenindependent prostate cancer. Cancer Res 1992; 52:
6940-6944.
40. Colombel M, Olsson CA, Ng PY, Buttyan R. Hormoneregulated apoptosis results from reentry of differentiated
prostate cells onto a defective cell cycle. Cancer Res
1992; 52: 4313–4319.
41. Teraishi F, Wu S, Inoue S, et al. Antitumor activity and
downregulation of pro-angiogenic molecules in human
prostate cancer cells by a novel thiazolidione compound.
Prostate 2006; 66: 430-438.
42. Kuniyasu H, Troncoso P, Johnston D, et al. Relative
expession of Type IV collagenase, E-cadherin, and
vascular endothelial growth factor/vascular permeability
factor in prostatectomy specimens distinguishes organconfined from pathologically advanced prostate cancer.
Clin Cancer Res 2000; 6: 2295-2308.
216
ORIGINAL RESEARCH
CYTOGENETIC ANALYSIS IN INFERTILE MALES WITH SPERM ANOMALIES
Ebru Önalan Etem, Hüseyin Yüce, Deniz Erol, Şükriye Derya Deveci, Gülay Güleç Ceylan,
Halit Elyas
Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik, Elazığ, Türkiye
ABSTRACT
Objective: In a half of all childless partnerships the infertility is caused by the male. Chromosomal
abnormalities are more prevalent in infertile men compared to fertile men. Chromosomal abnormalities are
known to be associated with spermatogenetic failure. The present study investigates the frequency and types
of major chromosomal abnormalities by using standard cytogenetic methods in infertile men with sperm
anomalies.
Materials and Methods: A total of 214 infertile males (138 were azoospermic, 76 oligospermic) were
studied for the cytogenetic evaluation. Chromosomal analysis of peripheral blood lymphocytes was
performed according to standard protocols.
Results: Of the 214 infertile men, 24 (11.2%) had a chromosomal abnormality in the form of a Klinefelter
syndrome/variant (16/24; 7.5%), XYY syndrome (1/24; 0.5%), XX male syndrome (1/24; 0.5%), 45,X,
mar(Y) (1/24; 0.5%), 46,XX, inv(Y)(p11q11) (1/24; 0.5%), 46,XY, der(1)t(1;5)(p33;qter) (1/24; 0.5%),
46,XY, t(15;15) (1/24; 0.5%) or 46,XY,t(14;21) (1/24; 0.5%).
Conclusions: This study shows that chromosomal anomalies were found in 11.2% of the infertile men. The
potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile
men prior to intra cytoplasmic sperm injection (ICSI). In addition, genetic screening and counseling should
be offered to infertile patients routinely.
Keywords: Infertility, Chromosome, Cytogenetic, Azoospermia, Oligoospermia
SPERM ANOMALİSİ GÖSTEREN ERKEKLERDE SİTOGENETİK ANALİZLER
ÖZET
Amaç: Erkek infertilitesi çocuk sahibi olamayan çiftlerin yarısından sorumludur. Kromozomal
abnormaliteler fertil erkeklerle karşılaştırıldığında infertil erkeklerde daha sıktır. Kromozomal anomalilerin
spermotogenezde başarısızlığa neden olarak erkek infertilitesine neden olduğu bilinmektedir. Çalışmada
sperm anomalisi gösteren infertil erkeklerde major kromozomal anomalilerin tipleri ve sıklığının
araştırılması amaçlanmıştır.
Gereç ve Yöntem: Toplam 214 (138 azospermik, 76 oligospermik) infertil erkek bireye sitogenetik
inceleme yapıldı. Tüm hastaların periferik kan lenfositlerinin kromozomal analizleri sdandart yöntemlere
göre yapıldı.
Bulgular: Toplam 214 infertil erkeğin 24 (%11.2)’ünde klinifelter sendromu (16/24; %7.5), XYY sendromu
(1/24; %0.5), XX erkek sendromu (1/24; %0.5), 45,X, mar (Y) (1/24; %0.5), 46,XX, inv(Y)(p11q11) (1/24;
%0.5), 46,XY, der(1)t(1;5)(p33;qter) (1/24; %0.5), 46,XY, t(15;15) (1/24; %0.5) ve 46,XY,t(14;21) (1/24;
%0.5) kromozomal anomalileri tespit edildi.
Sonuçlar: Bu çalışma infertil erkeklerde kromozomal anomalilerin sıklığı %11.2 olduğunu göstermektedir.
Bu genetik bozuklukların yeni nesillere aktarılmasındaki potansiyel risk infertil erkeklerin ICSI’dan önce
taranması için bir sebep oluşturmaktadır. Ayrıca, genetik tarama ve danışmanın infertil hastalara rutin olarak
yapılması gerekmektedir.
Anahtar Kelimeler: İnfertilite, Kromozom,Sitogenetik, Azospermi, Oligospermi
Ebru Önalan Etem, M.D.
Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik, Elazığ,
Türkiye
217
Ebru Önalan Etem, et al.
Cytogenetic analysis in infertile males with sperm anomalies
causes of azoospermia and oligozoospermia
among infertile Turkish men. The prevalence
and types of cytogenetic abnormalities were
analyzed using standard cytogenetic methods.
INTRODUCTION
Infertility affects about 15 per cent of all
couples attempting pregnancy, with a malefactor identified in approximately half of the
cases1. Numerous factors contribute to male
infertility,
genetic
factors
including
chromosomal abnormalities and genetic
syndromes cause gene defects, and other
factors include the hormonal milieu, genital
infections, chemical and physical agents.
infection,
varicose,
spermatic
duct
obstruction,
antisperm
antibodies,
cryptorchidism,
retrograde
ejaculation,
systemic diseases, testicular cancer, testicular
trauma, etc. Male infertility can also be
caused by a variety of other factors, apart
from these, and in 30–40% of male infertile
cases that are referred to as idiopathic, a
genetic abnormality is suspected2.
MATERIAL AND METHOD
Patients
The study was conducted retrospectively
according to the records of the patients
referred to the Department of Medical
Biology and Genetics at Fırat University.
From January 1998 to August 2009, 214
infertile Turkish men were enrolled in the
study. Among these 214 men, 138 had
azoospermia and 76 had oligoospermia. The
average age was 33, ranging from 18 to 51
years. A complete semen analysis was
performed in all patients according to the
guidelines of the World Health Organization
(1999). Semen was collected by masturbation
at the laboratory after 3–5 days of sexual
abstinence, and examined as soon as
liquefied. Cases were classified into groups
using sperm counts. Azoospermia was
defined as the total absence of sperm cells and
oligozoospermia was defined as a sperm cell
count of less than 5×106 cells/ml in seminal
liquid.
The examination of male infertility should be
complex, including a detailed history,
physical examination, semen analysis,
hormonal screening, and chromosomal and
genetic analysis of somatic cells3. The fact
that chromosomal abnormalities are increased
in infertile men relative to fertile men is well
established. Most studies report a wide range
of frequencies of chromosomal abnormalities,
from 2.2% to 10.3%, due to different
cytogenetic procedures and case inclusion
criteria1. In cases of non-obstructive
azoospermia, there is a 15% risk of an
associated
chromosome
abnormality
including both aneuploidies and structural
rearrangements4. Nevertheless, all of them
point to an increasing percentage of
chromosomal abnormalities concomitant with
a decreasing sperm count. In addition, the
nature of chromosomal abnormalities differs
depending on whether a patient has
oligoospermia or azoospermia. An early
mutational event in the stem cells could
produce
structural
rearrangements
(translocations, inversions, or small deletions)
during spermatogenesis, persisting through
mitotic and meiotic divisions to the mature
sperm stage1.
Cytogenetic Analysis
Chromosomal analysis of peripheral blood
lymphocytes was performed according to
standard protocols5. Peripheral blood (2 ml)
was collected in heparin vacutainers (Becton
Dickinson, USA). For every subject whole
blood (0.5 ml) cultures were set up in 5 ml
Roswell Park Memorial Institute (RPMI)
1640 media (GIBCO BRL, USA) containing
15% fetal calf serum (Biological Industries,
KBH, Israel), antibiotic mixture and
phytohemagglutinin P (DIFCO Lab, USA) for
72 h. Chromosome preparations were
obtained from lymphocyte cultures and
analyzed
after
Giemsa-Trypsin-Giemsa
(GTG) -banding6. In all cases, at least 20
metaphases were analyzed. In cases of
suspected mosaicism, 50 cells were counted.
The karyotypes were interpreted using the
recommendation of the International System
for Human Cytogenetic Nomenclature7.
The main purpose of this study was the
investigation of the possible cytogenetic
218
frequency of 11.2%. The frequency of
abnormalities was 13.7% in the cases of
azoospermia, and 6.5% in men with
oligoospermia (Table III). Numerical and
structural chromosomal abnormalities, which
were detected in 24 patients, are summarized
in Table I. Patients with Klinefelter Syndrome
had azoospermia. The frequency of autosomal
chromosome anomalies detected in the
present study was 1.9% (4/214 patients), one
patient who was a t(15;15) carrier was
azoospermic (138/1), other translocation
carriers were oligoospermic (3/76). There was
a statistically significant difference in the
autosomal translocation carrier between
oligoospermic and azoopermic infertile male
goups (p<0.05).
Fluorescence in situ hybrizidation (FISH)
Analysis
FISH for 46,XX and 47,XYY male patients,
to exclude mosaicism was performed on
lymphocyte metaphase spreads using the Y
centromere-specific DNA probe: CEP Y
alpha-satellite spectrum orange (32-130025)
(Vysis, Illinois, USA). It was also performed
using the X centromere and sex-determining
region Y gene (SRY)-specific DNA probe:
LSI SRY Yp11.3 spectrum orange/CEP X
spectrum green (32-191007) (Vysis, Illinois,
USA). The Y centromere-specific DNA
single color probe was labeled with biotin and
detected by FITC avidin. The chromosomal
DNA was then counterstained with propidium
iodide (PI). FISH using the locus specific
identifier (LSI) SRY/CEP X DNA dual color
probe was performed following the
manufacturer’s instructions (VYSIS) and
chromosomal DNA was counterstained with
4’,6-diamidino-2-phenylindole
(DAPI).
Statistical analysis was carried out by the
Statistical Package for Social Science for
Windows, version 11.0 (SPSS; Chicago, IL,
USA). The unpaired t-test, Mann-Whitney Utest and Chi-squared test were used. P < 0.05
was considered significant.
Polymorphisms were detected in 25 (11,6%)
patients (Table II). Abnormality in the
heterochromatin region of the Y chromosome
and inv(9) was the most frequently identified
polymorphism in 10/214 (4.6%) and 9/214
(4.2%) in infertile men, respectively.
For patients with a 47,XYY karyotype
mosaicism was shown by FISH in Y
chromosome content: 47,XYY (76%)/46,XY
(24%). Hybridization with the Y centromereSRY specific DNA dual probe in 46,XX male
patients was positive, ruling out any hidden
mosaicism with a Y-bearing cell line in
peripheral blood cells.
RESULTS
Among the 214 infertile men studied, 24
showed some kind of constitutional
chromosomal abnormality corresponding to a
Table I: Chromosomal abnormalities in azoospermic and oligospermic men.
Chromosomal Finding
46,XX male
Numerical
47,XXY
47,XYY
45,X, mar(Y)
Structural
Inversion
46,XX,inv(Y)(p11q11)
Translocation
46,XY,der(1)t(1;5)(p33;qter)
46,XY,t(15;15)
46,XY,t(14;21)
46,XY,t(9;15)(q21.1:q11.1)
Total (n=214)
0.5 % (1)
7.5 % (16)
0.5 % (1)
0.5 % (1)
0.5 % (1)
0.5 % (1)
0.5 % (1)
0.5 % (1)
0.5% (1)
11.2 % (24)
219
Table II: Chromosomal polymorphisms
Chromosomal polymorphism
Frequency
46,XY, inv(9)
46,XY, 9qh+
46,XY,16qh+
46,XY,Yqh(-)
46,XY, Yqh(+)
4.2 % (9)
0.5 % (1)
0.5 % (1)
1.8 % (4)
4.6 % (10)
11.6 % (25)
Table III: The cytogenetic findings in the literature
Author
Vincert et al
(8)
Zuffardi and
Tiepolo et al
(9)
Chandley et al
(10)
Clementini et
al (11)
Tuerlings et al
(12)
Nakamura et
al (13)
Yoshida et al
(14)
Koulischer et
al (15)
Salahshourifar
et al (16)
Şamlı et al
(17)
Mohammed et
al (18)
Akgul et al
(19)
Vutyavanic et
al (20)
Nagvankar et
al (21)
Balkan et al
(22)
Our study
Total
Patient
Number/chromosomal Azoospermia Oligospermia CytogeneticAbnormalities Frequencies
Structural Numerical
frequencies
2651/204
111/792
(14%)
-
93/1859
(5%)
-
2542/215
2372/51
2078/42
1792/62
1790/225
1007/65
-
-
-
-
-
-
-
-
-
-
-
819/52
289/23
179/18
130/6
88/9
80/9
214/24
17.905/1174
131
40
175
33
18
6
36
6
24
64
126
24
41
6
27
7.69%
8.6%
2.1%
2.02%
3.45%
12.5%
6.5%
-
1000/33
874/136
73
106/444
(23.8%)
42/383
(10.9%)
-
11/175
(6.2%)
10/436
(2.2%)
-
15/86
(17.4%)
-
5/73
(6.85%)
-
6/42
(%14.3)
-
3/46
(%6.5)
-
19/138
(13.7%)
299/1885
(15.8%)
5/76
(6.5%)
127/2665
(4.7%)
220
20
116
13
39
3
20
2
16
2
4
5
4
2
7
6
18
305(1.7%) 802 (4.4%)
3.3%
15.5%
5.9%
7.9%
11.74%
4,6%
10.2%
11.2%
11.2%
6.5 %
SRY gene is translocated on the X
chromosome. The SRY gene is present in this
case (SRY+ XX males), but such patients
have azoospermia.
DISCUSSION
Male infertility may be caused by a variety of
chromosomal
abnormalities,
including
abnormalities in the sex chromosomes and
autosomes, gain or loss of an entire single
chromosome resulting in aneuploidy or
structural abnormalities, as in balanced and
unbalanced tranlocations. The frequency of an
abnormal karyotype in this study was within
the previously reported range of 2.2–14.3%
for infertile men (Table III) 8-22. The incidence
of cytogenetic abnormalities has been
estimated at 5.8% in infertile men and only
0.5% in the normal population1. Possible
explanations for the divergent frequencies of
chromosomal abnormalities in infertile males
may
be
populational,
geographical,
environmental or genetic heterogeneities,
methodological
detection
problems
(expecially
for
minor
chromosomal
abnormalities), patients’ inclusion criteria or
various chromosomal abnormality frequencies
including the absence or the presence of
chromosomal polymorphisms.
A relationship between balanced autosomal
translocations and infertility has been reported
among severely oligozoospermic and
azoospermic men26-29. In our study, reciprocal
translocations t(1;5), t(9;15) and t(14;21)
were seen in oligoospermic males and
t(15;15) was seen in one azoospermic male.
The exact mechanism by which chromosomal
anomalies induce infertility is not clear.
Sperm karyotyping studies of 37 reciprocal
translocation heterozygotes have shown that
19–77% of spermatozoa are unbalanced29.
When delineating the genetic basis of male
infertility, it is very important to emphasize
that about 50% of all translocations found in
sterile men involved an acrocentric
chromosome, which implicates their role in
male hypofertility30. Guichaoua et al.
emphasized the correlation between the
involvement of the acrocentric chromosome
in infertile translocation carriers and the
severity of the spermatogenic defect31. It has
been
hypothesized
that
balanced
translocations
interfere
with
normal
chromosome pairing and segregation at
meiosis I, thus providing a potential for
formation of unbalanced gametes and
subsequent unbalanced abnormal offspring32.
Another hypothesis is based on the
assumption of potential autosomal genes
involved in male gametogenesis that might be
deregulated by chromosome breakpoints. The
relation between chromosomal breakpoints
and male infertility has been investigated, and
it has been found that there is a nonrandom
distribution of breakpoints associated with
infertility32,33. The presence of abnormally
distributed chromatin interferes with meiotic
division and thus reduces sperm production.
Spermatozoa bearing abnormal chromosomes
may cause abnormal embryonic development,
which can in turn, cause early pregnancy
loss26. Further research in this direction is
necessary. Vincent et al., reported that
autosomal structural anomalies (Table III)
were encountered primarily in severe
In the total population, aneuploidy (10.8%)
was the most frequent chromosome-related
cause among infertile males. The most
common abnormality was Klinefelter’s
syndrome (16/24), which was in agreement
with a previous study by Foresta et al.23. Men
with a 47,XYY karyotype are generally
fertile, but they are seen more frequently in
infertile populations. There have been a few
reports of 47,XYY syndromes in azoospermic
males as in our study23,24. Since many
47,XYY men have normal semen parameters,
the severe oligoospermia observed in these
men may indicate more perturbations during
meiotic pairing, subsequent loss of germ cells
and the production of aneuploid sperm24.
The clinical features of male sex reversal
syndrome patients are azoospermia associated
with one or more of the following: abnormal
external genitalia, gynecomastia, short stature,
and pelvic cyst25. Males with a 46, XX
karyotype were mainly found in the group of
azoospermic males (Table I). Most XX males
originate from a crossing over between Xp
and Yp during paternal meiosis, so that the
221
oligoospermia8. Our study confirms this
finding because of detected three autosomal
translocation in oligospermic males.
syndrome (KALIG1) and A-kinase anchor
proteins (AKAP82) etc., but cytogenetic
examinations should be made prior to
molecular studies42.
Common
cytogenetic
polymorphisms
detected by G banding are considered as
heteromorphisms
and
include
heterochromatin regions of chromosomes 1,
9, 16 and Y34. The role of chromosome
heteromorphisms in infertility has been
studied previously35-37. Şahin et al., reported
that the chromosomal polymorphisms
frequency is 7.9% in infertile males. We
found that the polymorphism frequency is
11.6%38. The occurrence of long Y (Yqh+)
and short Y (Yqh-) in our study was 4,6% and
1,8% respectively. These frequencies were
remarkably close to the frequencies of 4.4 and
1.6 per cent reported in literature39,40. Inv (9)
is commonly seen in normal humans and the
frequency has been estimated to be 1 to 3% in
the general population41. As the frequency of
inv(9) (4.2%) in infertile men was similar to
that in the general population, these
inversions definitely have role in the
development of infertility especially in cases
with de novo inversions. We advise parent’s
karyotyping for inv(9) carriers because the
determination of unbalanced chromosomal
content is important for the detection of de
novo or familial inv(9) carriers.The
contribution of variants to alter the carrier’s
fertility is still a controversial topic and
further studies are required to understand this.
In conclusion, cytogenetic investigations in
infertile men undoubtedly confirm previous
reports in spite of differences in the incidence
of chromosomal abnormalities in literature
and they point to a risk of chromosomal
abnormalities that is 20-fold higher in patients
with severe oligoospermia or nonobstructive
azoospermia, than in the general population.
Consequently, high resolution chromosome
preparations are crucial for a group with low
sperm quality to detect complicated
rearrangements. Therefore, genetic testing and
counselling can provide support for patterns
of inheritance, recurrence risks, natural
history of diseases, increased risk for birth
defects and genetic testing options when
planning a pregnancy in patients with
abnormal karyotypes. These patients can be
advised as regards in vitro fertilization (IVF)
and genetic screening of embryos in relation
to assisted reproductive techniques.
Acknowledgement
The authors express their heartfelt gratitude to
the staff and members of the Department of
Medical Biology and Genetic for their
assistance in various experiments, other
organizational aspects of this study and Firat
University Hospital. We are grateful to all
volunteers who participated in this study.
Among numerous etiologic factors, genetic
factors play a primary role in male infertility.
The creation of a specific model for the
interpretation of male infertility data may lead
to different results. For example, many
patients with azoospermia show no
chromozomomal abnormality because they
may have vas deferens aplasia, which is often
the result of a gene defect. However, the gene
defect is invisible on a karyotype and requires
a genetic diagnosis and counseling. It is clear
that there are many genetic factors leading to
infertility such as microdeletions of
chromosome Y, some mutations of the cystic
fibrosis transmembrane conductance regulator
(CFTR) gene, mutations in Sry-related
transcription factor (SOX9), Kallmann
REFERENCES
1.
2.
3.
4.
5.
222
Bhasin S, de Kretser DM, Baker HW. Clinical review
64: Pathophysiology and natural history of male
infertility. J Clin Endocrinol Metab 1994; 79 : 15251529.
Griffin DK, Finch KA. The genetic and cytogenetic
basis of male infertility. Hum Fertil (Camb). 2005
Mar;8:19-26
Van Assch E, Bonduelle M, Tournaye H, et al.
Cytogenetics of infertile men. Hum Reprod 1996;11:1–
26.
Hook EB. Chromosomal abnormalities: prevalence,
risks and recurrence. In Prenatal Diagnosis and
Screening. Edinburgh: Churchill Livingstone 1992; 351392.
Moorhead PS, Nowell PC, Mellman WJ, et al.
Chromosome preparations of leukocytes cultured from
human peripheral blood. Exp Cell Res 1960; 20: 613616.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
Seabright M. A rapid banding technique for human
chromosomes. Lancet 1971; 2: 971-972.
Shaffer LG, Tommerup N. An International System for
Human
Cytogenetic
Nomenclature.
Karger
,
Farmington. 2005.
Vincent MC, Daudin M, De MP, et al. Cytogenetic
investigations of mini review: infertile men with low
sperm counts: A 25-Year Experience. J Androl
2002;23:18-22.
Zuffardi O, Tiepolo, L. Frequencies and types of
chromosome abnormalities associated with human male
infertility. In: Crosignani PG and B.L. Rubsin BL, eds.
Genetic Control of Gamete Production and Function.
Serono Clinical Colloquia on Reproduction III.
Academic Press and Guine and Stratton, London, UK.
1982; 261-273.
Chandley AC. The chromosomal basis of human
infertility. Br Med Bull 1979; 35: 181-186.
Clementini E, Palka C, Iezzi I, Stuppia L, GuancialiFranchi P, Tiboni GM. Prevalence of chromosomal
abnormalities in 2078 infertile couples referred for
assisted reproductive techniques. Hum Reprod 2005;
20:437-442.
Tuerlings JH, de France HF, Hamers A, et al.
Chromosome studies in 1792 males prior to intracytoplasmic sperm injection: the Dutch experience. Eur
J Hum Genet 1998; 6:194-200.
Nakamura Y, Kitamura M, Nishimura K, et al.
Chromosomal variants among 1790 infertile men. Int J
Urol 2001; 8:49-52.
Yoshida A, Tamayama T, Nagao K, et al. A cytogenetic
survey of 1007 infertile males. Contracept Fertil Sex
1995; 23: 103a.
Koulischer L, Schoysman R. Chromosomes and human
infertility. I. Mitotic and meiotic chromosome studies in
202 consecutive male patients. Clin Genet 1974; 5: 116126.
Salahshourifar I, Gilani MAS, Masoudi NS, Gourabi H.
Chromosomal abnormalities in Iranian infertile males
who are candidates for assissted reproductive
techniques. IJFS 2007;1: 75-79.
Şamlı H, Solak M, İmirzalioğlu N, Şamlı MM.
Nonobstruktif azoospermik ve siddetli oligozoospermik
erkeklerde saptanan kromozomal anomaliler. Kocatepe
Tıp Dergisi 2005; 6:7-11.
Mohammed F, Al-Yatama F, Al-Bader M, Tayel SM,
Gouda S,Naguib KK. Primary male infertility in Kuwait:
a cytogenetic and molecular study of 289 infertile
Kuwaiti patients. Andrologia 2007;39:87–92.
Akgul M, Ozkinay F, Ercal D, et al. Cytogenetic
abnormalities in 179 cases with male infertility in
Western Region of Turkey: Report and review. J Assist
Reprod Genet 2009; 26:119–122.
Vutyavanich T, Piromlertamorn W, Sirirungsi W,
Sirisukkasem S. Frequency of Y chromosome
microdeletions and chromosomal abnormalities in
infertile Thai men with oligozoospermia and
azoospermia. Asian J Androl 2007;9:68–75.
Nagvenkar P, Desai K, Hinduja I, Zaveri K.
Chromosomal studies in infertile men with
oligozoospermia and non-obstructive azoospermia.
Indian J Med Res 2005;122:34–42.
Balkan M, Tekes S, Gedik A. Cytogenetic and Y
chromosome microdeletion screening studies in infertile
males with oligozoospermia and azoospermia in
Southeast Turkey. J Assist Reprod Genet 2008; 25:559–
565.
23. Foresta C, Garolla A, Bartoloni L, Bettella A, Ferlin A.
Genetic abnormalities among severely oligospermic men
who are candidates for intracytoplasmic sperm injection.
J Clin Endocrinol Metab 2005; 90: 152–156.
24. El-Dahtory F, Elsheikha HM. Male infertility related to
an aberrant karyotype, 47,XYY: four case reports. Cases
J 2009 8;2: 28.
25. Hackstein JH, Hochstenbach R and Pearson PL.
Towards an understanding of the genetics of human
male infertility: lessons from flies. Trends Genet 2000;
16: 565-572.
26. Pandiyan N, Jequier AM. Mitotic chromosomal
anomalies among 1210 infertile men. Hum Reprod
1996; 11:2604–2608.
27. Vicdan A, Vicdan K, Gunalp S, et al. Genetic aspects of
human male infertility: the frequency of chromosomal
abnormalities and Y chromosome microdeletions in
severe male factor infertility. Eur J Obstet Gynecol
Reprod Biol 2004; 117: 49–54.
28. Hellani A, Al-Hassan S, Iqbal M, Coskun S. Y
chromosome microdeletions in infertile men with
idiopathic oligo-or azoospermia. J Exp Clin Assist
Reprod 2006; 30:1–6.
29. Martin RH. Cytogenetic determinants of male fertility.
Hum Reprod Update 2008; 14:379–390.
30. Gabriel-Robez O, Ratomponirina C, Dutrillaux B,
Carre-Pigeon F, Rumpler Y. Meiotic association
between the XY chromosomes and the autosomal
quadrivalent of a reciprocal translocation in two infertile
men, 46,XY,t(19;22) and 46,XY,t(17;21). Cytogenet
Cell Genet 1986;43:154–160.
31. Guichaoua MR, Quack B, Speed RM, Noel B, Chandley
AC, Luciani JM. Infertility in human males with
autosomal translocations: meiotic study of a 14;22
Robertsonian translocation. Hum Genet 1990;86: 162–
166.
32. Zhou-Cun A, Yang Y, Zhang SZ, Zhang W, Lin L.
Chromosomal abnormality and Y chromosome
microdeletion in Chinese patients with azoospermia or
severe oligozoospermia. Yi Chuan Xue Bao 2006;
33:111–116.
33. Bache I, Van Assche E, Cingoz S, et al. An excess of
chromosome 1 breakpoints in male infertility. Eur J Med
Genet. 2004;12:993–1000.
34. Brothman AR, Schneider NR, Saikevych I, et al.
Cytogenetics Resource Committee, College of American
Pathologists/American College of Medical Genetics.
Cytogenetic heteromorphisms: Survey results and
reporting practices of Giemsa-band regions that we have
pondered for years. Arch Pathol Lab Med
2006;130:947–949.
35. Cortés-Gutiérrez EI, Cerda-Flores RM, DávilaRodríguez MI, Hernández-Herrera R, Vargas-Villarreal
J, Leal-Garza CH. Chromosomal abnormalities and
polymorphisms in Mexican infertile men. Arch Androl
2004;50:261–265.
36. Nakamura Y, Kitamura M, Nishimura K, et al.
Chromosomal variants among 1790 infertile men. Int J
Urol 2001;8:49–52.
37. Yakin K, Balaban B, Urman B. Is there a possible
correlation between chromosomal variants and
spermatogenesis? Int J Urol 2005;12:984–989.
38. Sahin FI, Yilmaz Z, Yuregir OO, Bulakbasi T, Ozer O,
Zeyneloglu HB. Chromosome heteromorphisms: an
impact on infertility. J Assist Reprod Genet 2008;
25:191–195.
223
39. Abramsson L, Beckman G, Duchek M, Nordenson I.
Chromosomal aberrations and male infertility. J Urol
1982; 128 : 52-53.
40. Retief AE, Van Zyl JA, Menkveld R, Fox MR, Kotze
GM, Brusnicky J. Chromosome studies in 496 infertile
males with a sperm count below 10 million/ml. Hum
Genet 1984; 66 : 162-164.
41. Rao BV, Kerketta L, Korgaonkar S, Ghosh K Pericentric
inversion of chromosome 9[inv(9)(p12q13)]: Its
association with genetic diseases. Indian J Hum Genet
2006; 12: 129-132.
42. Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin
DK. The genetic basis of infertility. Reproduction
2003;126:13-25.
224
ORIGINAL RESEARCH
THE COMPARISON OF THE RECOVERY CHARACTERISTICS OF EITHER SPINAL OR
EPIDURAL ANESTHESIA WITH PRILOCAINE FOR KNEE ARTHROSCOPY
Hatice Türe, Binnaz Ay, Zeynep Eti, F. Yılmaz Göğüş
Marmara Üniversitesi, Tip Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İstanbul,
Türkiye
ABSTRACT
Objective: The aim of our study was to compare the recovery characteristics of single-dose spinal and
epidural anesthesia with 2 % prilocaine for outpatient knee arthroscopy.
Methods: Forty patients were randomly assigned to receive either spinal or epidural anesthesia with
prilocaine. Maximum sensory level, recovery of the motor and sensorial functions, time to ambulate, time to
voiding, side effects, and medications used for the treatment were recorded. After 48 hours, the patients were
questioned for pain and need for analgesia, their opinion about the quality of anesthesia, side effects such as
nausea, vomiting, pruritus, backache, post-dural puncture headache (PDPH), urinary difficulties and transient
neurological symptoms (TNS).
Results: Maximum sensory level was similar in the groups. The time from injection to recovery of motor
and sensory functions and ambulation time were significantly shorter in the epidural group than the spinal
group (p < 0.05). The percentage of patients who required additional analgesic was 9 versus 6% in spinal
versus epidural groups. One of the patients in the spinal group had PDPH postoperatively. None of the
patients had postoperative nausea, vomiting, pruritus, backache, urinary difficulties or TNS.
Conclusion: Relatively fast recovery time make epidural anesthesia with prilocaine a good alternative for
outpatient knee arthroscopy.
Keywords: Spinal, Epidural, Prilocaine
DİZ ARTROSKOPİSİ CERRAHİSİNDE PRİLOKAİN İLE YAPILAN SPİNAL VE EPİDURAL
ANESTEZİNİN DERLENME ÖZELLİKLERİNİN KARŞILAŞTIRILMASI
ÖZET
Amaç: Bu çalışma spinal ve epidural anestezide kullanılan tek doz prilokainin hastanın derlenme özellikleri
üzerine etkisinin karşılaştırılması amacıyla planlanmıştır.
Yöntem: Diz artroskopisi geçirecek 40 hasta, 2 mL %2 prilokain ile spinal ya da 15-20 mL %2 prilokain ile
epidural anestezi yapılacak şekilde randomize olarak 2 gruba ayrıldı. Hastaların maksimum duyu bloğu
seviyeleri, motor ve duyu bloğunun geri dönüş süreleri, ayağa kalkma zamanları, ilk idrar yapma zamanları,
yan etkiler ve tedavisinde kullanılan ilaçlar kaydedildiler. Hastalar taburcu olduktan 48 saat sonra, telefonla
aranarak, operasyon sonrası ağrıları, analjezik ihtiyaçları, anestezi yönteminden memnuniyetleri, bulantı,
kusma, kaşıntı, belağrısı, dura delinmesine bağlı baş ağrısı, idrar yaparken zorlanma ve geçici nörolojik
semptomlar açısından sorgulandılar.
Bulgular: Maksimum duyu bloğu seviyesi her iki grupta benzerdi. İlacın verilişinden duyu ve motor bloğun
sonlanmasına dek geçen süre ve ayağa kalkma süresi epidural anestezi sonrası belirgin kısa bulundu (p <
0.05). Ek analjezik kullanan hasta sayısı, spinal anestezi sonrası %9 iken, epidural anestezi sonrası %6 idi.
Spinal gruptan bir hastada dura delinmesine bağlı başağrısı görüldü. Hastaların hiçbirinde postoperatif
bulantı, kusma, kaşıntı, bel ağrısı, idrar zorluğu ya da gecici norolojik semptomlar görülmedi. Hasta
memnuniyeti açısından gruplar arasında fark bulunmadı.
Sonuç: Hızlı derlenme süresi nedeniyle prilokain ile epidural anestezi diz artroskopilerinde iyi bir
alternatiftir.
Anahtar Kelimeler: Spinal, Epidural, Prilokain
Hatice Türe, M.D.
Yeditepe Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon
A.D., İstanbul, Türkiye
Hatice Türe was recently affiliated to Yeditepe University School of
Medicine, Department of Anesthesiology and Reanimation, İstanbul,
Türkiye.
225
Hatice Türe, et al.
The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee
arthroscopy
(allergy,
coagulopathy,
infection,
or
neurologic disease) and pregnant patients
were excluded from the study. Each patient’s
age, sex, weight, and height were recorded
prospectively by the anesthesiologist on a
preprinted form. All patients in both groups
received 500 mL of intravenous isotonic
saline before anesthesia was induced.
Monitors for routine measurements were as
follows: pulse oximeter, electrocardiogram,
and noninvasive systolic/diastolic and mean
arterial blood pressure.
INTRODUCTION
Knee arthroscopy is a common procedure of
orthopaedic surgery. Recent advances in this
surgical practice combined with “fasttracking”
anesthetic
techniques
have
increased the number of patients discharged
on an outpatient basis after knee arthroscopic
surgery1. Complete recovery from sensory
and motor blocks is a critical discharge
criterion for outpatient surgery. Any
deficiencies in these areas limit the patient’s
ability to be self-caring after discharge2,3. The
discharge time, that is, the length of time from
the end of surgery until the patient is
discharged, is greatly affected by the
anesthetic technique used4. The ideal
anesthetic technique for outpatient surgery
should be easily administered, should have a
quick onset of action and should provide good
surgical conditions with a rapid recovery and
minimal side effects5. There are several
published studies citing advantages of
different anesthetic techniques2,3,5-13. Spinal or
epidural anesthesia may provide many of
these advantages; however, comparison of the
single dose spinal and epidural techniques
each with a short acting local anesthetic,
prilocaine, is not well documented.
We performed a prospective, randomized
clinical study to compare the recovery
characteristics of single dose spinal and
epidural anesthesia each with 2% prilocaine
for outpatient knee arthroscopy.
Spinal anesthesia (Group S) (n=20) was
administered at the L4-5 intervertebral space
using a 25-gauge pencil point spinal needle
through the midline approach with the patient
placed in the lateral decubitus position. After
the free flow of cerebrospinal fluid was
observed, 2 mL of prilocaine 2% (Citanest,
AstraZenaca Ltd, Istanbul, TR) was injected.
Patients were then immediately turned to the
supine position. Epidural anesthesia (Group
E) (n=20) was performed after cutaneous
anesthesia with 1.5 mL of 2% lidocaine. An
18-gauge Tuohy epidural needle was
introduced midline at the L4-5 intervertebral
space, using a loss-of-resistance to saline
technique with the patient placed in the lateral
decubitus position and the operative knee
dependent. If no blood or cerebrospinal fluid
was aspirated, 15-20 mL of 2% prilocaine
was given in 5-mL increments. Patients were
immediately turned to supine position.
MATERIAL AND METHOD
Following the Institutional Ethics Committee
approval and written informed patient
consent, forty patients scheduled for knee
arthroscopy (no prior medication, American
Society of Anesthesiologists (ASA) score I-II,
age between 20-60 years) were randomly
assigned to receive either epidural or spinal
anesthesia. This study was performed
according to the recommendation for conduct
of clinical research of the Declaration of
Helsinki. Patients with respiratory or cardiac
disease, diabetes, those receiving chronic
analgesic
therapy,
those
with
contraindications to regional anesthesia
Sensory block level was assessed with
bilateral pinprick testing in the midclavicular
line in all the patients. Motor block was
assessed with modified Bromage score (0=
full flexion of knee and ankles; 1= partial
flexion of knees, full flexion of ankles; 2=
inability to flex knees, partial flexion of
ankles; 3= inability to flex knees and ankles).
The maximum level of the sensory block and
duration of surgery were recorded. All the
patients were transferred to the postanesthesia
care unit (PACU) after the operation and
clinical observations were made by same
investigators who were blinded to the groups.
Side effects such as bradicardia (>30%
decreases from baseline); hypotension (>30%
226
arthroscopy
decrease from baseline), drowsiness, nausea,
vomiting, pruritus, shivering, pain, and
medications used for the treatment were
noted. Sensory and motor block levels were
measured at 10-min intervals during the
PACU period. Sensory block resolution
occurred when the dermatomal level receded
to S1. Motor recovery was defined as a
Bromage score 0 and the ability to do a deep
knee bend. When the patients’ vital signs
were stable and sensory and motor blocks
were resolved, they were transferred to their
beds.
RESULTS
Demographic data were similar between the
groups (Table I). Anesthesia was found to be
satisfactory for surgical incision in all the
patients. After the injection of prilocaine,
maximum sensory level was similar and T9
(T7- T10) in group S, T10 (T6- T11) in group E
(Table II). No differences were observed
between the groups regarding the incidence of
hypotension or the number of the patients
requiring ephedrine.
The maximum level of the sensory block was
above the T12 dermatome in all the patients.
The time from local anesthetic injection to
recovery of motor function was significantly
longer [119± 42 min] in group S compared to
[85±10 min] in group E (p< 0.05). Prolonged
recovery of the sensory block time (< S1) was
also observed in group S [143±39 min]
compared to group E (110±2 min, p< 0.05).
Time to first urination was reported as
272±97 min in group S and 203±63 min in
group E (p< 0.05). During the follow-up
report, none of the patients noted voiding
difficulty. Early postoperative side effects
during the PACU period are shown in Table
III. None of the patients noted hypotension,
bradycardia, nausea, vomiting, pruritis,
shivering, pain or respiratory depression and
there were no major surgical or anesthetic
complications (Table III). All the surgeons
described their opinion about the anesthetic
quality as good.
Time to sensorial (< S1) and motor block
resolution, time to first urination, time to
ambulation were recorded. All times were
defined as the time from injection of the drugs
to the time to the sensorial or motor block
resolution.
Patients were asked to score the degree of
pain themselves and to write down the
respective times and severity on a follow-up
form they were given after the surgery
(Appendix). Patients were discharged with a
prescription for paracetamol as required, up to
six tablets a day. Forty-eight hours after
discharge, the patients were contacted by
telephone and questioned for the side effects,
medication requirement, and their opinion
about the quality of anesthesia (good,
satisfactory or poor). The data collected, such
as pain, nausea, vomiting, backache, post
dural puncture headache (PDPH), urinary
difficulties, transient neurological signs
(TNS), need for analgesia, and patient
satisfaction about the quality of anesthesia
were recorded. TNS was defined as pain or
dysesthesia in the buttocks, thighs or calves
occurring within 24 hrs and resolving within
72 hrs.
A power analysis indicated that a sample size
of 18 patients per group was required to show
a 30 min difference in discharge time among
groups at a p value <0.05 with 80% power. A
statistical analysis of the data recorded from
the two groups was carried out with the Chisquare test, unpaired t-test and Mann
Whitney-U test where appropriate.
The number of patients who needed an
additional analgesic during the first 48 hrs
after surgery was lower in group E than in
group S (p< 0.05). Postoperative pain relief
was adequate with acetaminophen in these
patients (Table II). The quality of anesthesia
as determined by the patients was either
satisfactory or good (Table II). None of the
patients had symptoms of postoperative
nausea,
vomiting,
pruritus,
urinary
difficulties, or TNS following discharge from
the hospital. Only one patient in group S had
postoperative mild PDPH which resolved
within 2 days without treatment.
227
arthroscopy
Table I. Demographic data (mean ± SD).
Spinal (n=20)
Epidural (n=20)
Age (yrs)
47 ± 14
47 ± 14
Weight (kg)
76 ± 10
76 ± 9
Height (cm)
168 ± 7
171 ± 11
Sex (male/female) 8/12
11/9
No significant difference was observed between the groups (p> 0.05).
Table II. Duration of surgery and anesthetic characteristics (mean± SD) (min).
Spinal(n=20)
Epidural (n=20)
Duration of surgery
38 ± 14
44 ± 12
Maximum sensory level
T9 [T7- T10]
T10 [T6- T11]
Recovery of motor function (Bromage 0)
119 ± 42
85 ± 10*
Recovery of sensation (<S1)
143 ± 39
110 ± 2*
Time to ambulate
167± 14
123± 10*
Time to void
272± 97
203± 63*
Postoperative analgesic use (%)
9 (45%)
6 (10%)*
*There were significant differences between the groups (p< 0.05).
228
arthroscopy
Appendix. Patient Questionnaire
Please note down time
1. You feel pain when you get back home………………
2. How much pain are you in
(0: no pain, 1: mild pain, 2: moderate pain, 3: severe pain)
3. Please also note down if you have to take painkillers, how many and approximately at what
time.
4. Please note down when you were able to void the first time after the surgery………… .
5. Do you have any of following side effects after your surgery:
None
Mild
Moderate
Severe
Treatment
/Time
Nausea, Vomiting
Pruritus
Backache
Headache
Inable to void
Transient neurological
symptoms*
* Transient neurological symptoms may be defined as pain or dysesthesia in your buttocks,
thighs or calves occuring within 24 hrs.
6. Your satisfaction with the whole procedure ranging from 1 (poor), 2 (satisfactory) or 3
(good)…….
You will be phoned forty-eight hours after discharge from hospital and you will be asked these
questions.
Any further comments you wish to make. We thank you for your time!
229
arthroscopy
for transurethral resection of the prostate in
elderly patients and prilocaine appeared to be
a safe local anesthetic for either method.
Since patients undergoing knee arthroscopy
are mostly younger patients than the patients
scheduled for prostate resection, incremental
dosing of local anesthetics to avoid their toxic
and untoward effects is unlikely to be as
important as in an elderly population. A
younger population needs to be discharged
and ready to work as soon as possible.
Prilocaine, one of the short acting local
anesthetics, is known as having lower
incidence of transient neurological symptoms
when applied intrathechally and is therefore
recommended for use in surgical procedures
of short duration18. Recovery of motor and
sensorial
functions
was
significantly
prolonged after spinal anesthesia compared to
epidural anesthesia as expected.
DISCUSSION
The main finding in this study is that, both
single dose spinal and epidural anesthesia
with 2% prilocaine provided satisfactory
surgical and anesthetic conditions; However,
epidural anesthesia provided faster recovery
compared to spinal anesthesia following
outpatient arthroscopic surgery.
The optimum anesthetic technique for
outpatient knee arthroscopy should provide
rapid onset and recovery from anaesthesia.
Complete recovery from sensory and motor
block is of critical importance as discharge
criteria in outpatient surgery, because it limits
the ability of patients’ self-caring after
discharge12. Some authors have pointed out
that regional anesthesia provides rapid
discharge times comparable to that of general
anesthesia2,13. However, recent data suggest
that both spinal and epidural anesthesia
require longer discharge times than new
short-acting general anesthetic drugs and
opioids, propofol and sevoflurane4,12.
Epidural anesthesia is advocated for
outpatient surgery because of the minimal
side effects and excellent patient acceptance14.
There are also studies comparing the spinal
technique with the epidural during outpatient
surgery showing similar discharge times5,15.
Local anesthetics were not standardized in
some of the studies comparing spinal and
epidural techniques5,10,16. Mulroy and
colleagues have compared epidural 2chloroprocaine to procaine combined with
fentanyl for spinal anesthesia16. Neal17 and
Pollock5 have compared epidural 2chloroprocaine to lidocaine with fentanyl for
spinal anesthesia. We compared recovery and
discharge characteristics of spinal and
epidural anesthesia with 2% prilocaine for
ambulatory arthroscopic knee surgery,
therefore this study gives important results
about the behavior of the same drug used with
two different regional anesthesia techniques.
However, prilocaine has previously been
scantily documented15,18. Reisli et al18
concluded that both continuous spinal and
continuous epidural anesthesia were reliable
Prilocaine is not a popular local anesthetic
today in anesthesia practice, due to a wellknown side effect, methemoglobinemia. This
side effect is usually of clinical importance
with larger doses. The maximum prilocaine
dose used in our study was 400 [20 mLx 20
mg/ml]
mg,
below
the
maximum
recommended dose, and therefore this agent
may be safely used for single dose epidural
anesthesia in adult patients. However, care
must be taken during repeated doses and
continuous infusion for regional anesthesia.
In clinical practice there are many choices of
local anaesthetics with intermediate duration
of action for outpatient regional anaesthesia
such as lidocaine, prilocaine and mepivacaine.
Although prilocaine is preferred, with less
risk of neurotoxicity, it was recently
suggested that intrathecal mepivacaine and
prilocaine are less neurotoxic than highly
concentrated lidocaine in a rat intrathecal
model18. Our study was designed to search for
an optimal central block type (spinal or
epidural) in outpatients, not to document the
recovery charactheristics or side effects of
prilocaine. However, in clinical settings other
local anesthestics may be preferable to
prilocaine for short surgical procedures.
230
arthroscopy
A potential limitation of this finding is the
sample size studied. In clinical settings, a
recovery difference of 30 minutes is unlikely
to be clinically significant, as institutional
costs may not appear to be affected by such
differences19,20. However, discharge from
hospital is not the end of the recovery process,
as far as the patient is concerned. The patients
in whom the side effects extend to 24 hour
postoperatively have less functional recovery.
Probable complications following regional
anesthesia include postoperative pain,
backache, PDPH and TNS. None of the
patients reported backache or TNS in this
study. Only one patient in the spinal group
had symptoms of mild PDPH in this study.
The incidence of PDPH can be reduced to 1%
or less in hospitalized patients through
meticulous selection of patients, needles, and
technique21. The use of a thinner spinal needle
with a pencil-point tip design has the
advantage of being associated with low
incidence of PDPH21.
TNS is another postoperative side effect of
regional anaesthesia. Lidocaine, lithotomy
position, knee arthroscopy and outpatient
status have been implicated as risk factors for
TNS22. In a recent study, the incidence of
TNS using prilocaine for spinal anaesthesia
has been reported as 4% and was not
significantly different between the patients
given prilocaine or lidocaine23. However,
there were no reports of TNS in our study
with prilocaine. Recent studies suggest that
the frequency of TNS with a small dose of the
agent is decreased; therefore we chose a
relatively small dose of prilocaine to reduce
the probability of TNS2,24. However, further
studies are needed to determine the etiology
and significance of TNS in such a practice
with higher doses.
Pain is one of the most important problems
following the regional anesthesia after
outpatient surgery. Local anesthetics with
long duration of action are useful in an
outpatient setting because of their prolonged
analgesic effects. On the other hand, a longer
duration of action may lead to prolonged
ambulation and recovery times. We found that
the percentage of patients who needed
additional analgesic was 9% in the spinal
group, and 6% in the epidural group with
prilocaine. Postoperative pain relief was
satisfactory with acetaminophen in these
patients. These results were probably related
to the relatively painless type of surgery
chosen in our study.
In conclusion, our study supports the
hypothesis that epidural anesthesia with 2%
prilocaine is suitable for outpatient knee
arthroscopy due to its short-duration of action.
Furthermore, both spinal and single dose
epidural anesthesia provided satisfactory
surgical, anesthetic conditions for surgeons
and patients.
Acknowlegement
There has been no financial support for his
study.
REFERENCES
1.
Jenkins K, Grady D, Wong J, Correa R, Armanious S,
Chung F. Post-operative recovery: day surgery
patients’preferences. Br J Anaesth 2001; 86: 272-274.
2. Ben David B, Levin H, Solomon E, Admoni H, Vaida S.
Spinal bupivacaine in ambulatory surgery: The effect of
saline dilution. Anesth Analg 1996; 83: 716-720.
3. Patel NJ, Flashburg MH, Paskin S, Grossman R.
Regional anesthetic technique compared to general
anesthesia for outpatient knee arthroscopy. Anesth
Analg 1986; 65: 185-187.
4. Pavlin DJ, Rapp SE, Polissar NL, Malmgren JA,
Koerschgen M, Keyes H. Factors affecting discharge
time in adult outpatients. Anesth Analg 1998; 87: 816826.
5. Pollock Je, Mulroy MF, Bent E, Polissar NL. A
comparison of two regional anesthetic techniques for
outpatient knee arthroscopy. Anesth Analg 2003; 97:
397-401.
6. Casati A, Cappelleri G, Fanelli G, Borghi B, Anelati D,
Berti M, et al. Regional anaesthesia for outpatient knee
arthroscopy: a randomized clinical comparison of two
different anaesthetic techniques. Acta Anaesthesiol
Scand 2000; 44: 543-547.
7. Heidvall M, Hein A, Davidson S, Jakobsson J. Cost
comparison between three different general anaesthetic
techniques for elective arthroscopy of knee. Acta
Anaesthesiol Scan 2000; 44: 157-162.
8. Jacobson E, Forssblad M, Rosenberg J, Westman L,
Weidenhielm L. Can local anesthesia be recommended
for routine use in elective knee arthroscopy? A
comparison between local, spinal, and general
anesthesia. Arthroscopy 2000; 16: 183-190.
9. Forssblad M, Weidenhielm L. Knee arthroscopy in local
versus general anaesthesia: the incidence of reartroscopy. Knee Surg Sports Traumatol Arthrosc 1999;
7: 323-326.
10. Dahl V, Gierloff C, Omland E, Raeder JC. Spinal,
epidural or propofol anaesthesia for outpatient knee
231
arthroscopy
11.
12.
13.
14.
15.
16.
17.
arthroscopy? Acta Anaesthesiol Scand 1997; 41: 13411345.
Trieshmann H. Knee arthroscopy: a cost analysis of
general and local anesthesia. Arthroscopy 1996; 12: 6063.
Mulroy MF. Local and regional anesthesia. In: White
PF, ed. Ambulatory Anesthesia& Surgery. London:
W.B. Saunders Company Ltd, 1993:406-433.
Parnass SM, McCarthy RJ, Bach BR, et al. Beneficial
impact of epidural anesthesia on recovery after
outpatient arthroscopy. Arthroscopy 1993; 9: 91-95.
Fisher A, Bryce-Smith R. Spinal analgesic agents. A
comparison of cinchocaine, lignocaine and prilocaine.
Anaesthesia 1971; 26: 324-329.
Kuusniemi KS, Pihlajamäki KK, Irjala JK, Jaakkola
PW, Pitkänen MT, Korkeila JE. Restricted spinal
anaesthesia for ambulatory surgery: a pilot study. Eur J
Anaesthesiol 1999; 16: 2-6.
Mulroy M, Larkin KL, Hodgson PS, Helman JD,
Pollock JE, Liu SS. A comparison of spinal, epidural
and general anesthesia for outpatient knee arthroscopy.
Anesth Analg 2000; 91: 860-864.
Neal JM, Deck JJ, Kopacz DJ, Lewis MA. Hospital
discharge after ambulatory knee arthroscopy: A
comparison of epidural 2-chloroprocaine versus
lidocaine. Reg Anesth and Pain Med 2001; 26: 35-40.
18. Reisli R, Celik J, Tuncer S, Yosunkaya A, Otelcioglu S.
Anaesthetic and haemodynamic effects of continuous
spinal versus continuous epidural anaesthesia with
prilocaine. Eur J Anaesthesiol. 2003; 20: 26-30.
19. Takenami T, Yagishita S, Nara Y, Hoka S. Intrathecal
mepivacaine and prilocaine are less neurotoxic than
lidocaine in a rat intrathecal model. Reg Anesth Pain
Med 2004; 29: 446-453.
20. Lubarsky DA. Understanding cost analysis. Part I. A
practitioners guide to cost behavior. J Clin Anesth 1995;
7: 519-521.
21. Halpern S, Preston R. Postdural puncture headache and
spinal needle design. Metaanalyses. Anesthesiology
1994; 81:1376-1383.
22. Freedman J, Li De-Kun, Drasner K, Jaskela M, Larsen
B, Wi S. Transient neurologic symptoms after spinal
anesthesia. An epidemiologic study of 1.863 patients.
Anesthesiology 1998; 89: 633-641.
23. Østgaard G, Hallaråker O, Ulveseth OK, Flaatten H. A
randomised study of lidocaine and prilocaine for spinal
anaesthesia. Acta Anaesthesiol Scand 2000; 44: 436440.
24. Ben David B, DeMeo PJ, Lucyk C, Solosko D. A
comparison of minidose lidocaine-fentanyl spinal
anesthesia and local anesthesia/propofol infusion for
outpatient knee arthroscopy. Anesth Analg 2001; 93:
319-25.
232
CASE REPORT
ABDOMINAL TUBERCULOSIS IN A 3-YEAR-OLD CHILD
Atilla Şenaylı1, Taner Sezer2, İsmail Hakkı Göl1, Ünal Bıçakçı3
1
Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Çocuk Cerrahisi Anabilim Dalı, Tokat, Türkiye 2Gaziosmanpaşa
Üniversitesi, Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Tokat, Türkiye 3Nafiz Kurt Devlet
Hastanesi-Bafra, Çocuk Cerrahisi Bölümü, Samsun, Türkiye
ABSTRACT
We report the first case of abdominal tuberculosis in our region, deciding to share our experience in the
diagnosis and treatment. In our report, we discussed the diagnostic and treatment criteria of the abdominal
tuberculosis case. A multiple drug regimen might be useful for abdominal tuberculosis and at least 9 months
of follow-up is needed. In the light of the literature, we found out that laboratory and radiological
examinations might have been confusing and the real diagnosis could be reached through explorative
laparotomy or laparoscopy
Keywords: Tuberculosis, Extrapulmonary, Abdominal, Children
ÜÇ YAŞINDAKİ BİR ÇOCUKTA ABDOMİNAL TÜBERKULOZ
ÖZET
Bölgemizdeki ilk abdominal Tüberkuloz vakası rapor edilmiştir ve teşhis ve tedavideki tecrübemizin
paylaşılması düşünülmüştür. Yazımızda, teşhis ve tedavi kriterleri tartışılmıştır. Çoklu ilaç uygulaması
abdominal tüberkuloz tedavisi için uygun görülmektedir ve en az 9 ay tedavi gerekmektedir. Literatür
ışığında laboratuar ve radyolojik değerlendirmelerin karışıklığa sebep olabileceği ve gerçek teşhisin sadece
eksploratif laparotomi ile yapılabileceği düşünülmüştür.
Anahtar Kelimeler: Tüberkuloz, Ekstrapulmoner, Abdominal,Çocuk
pediatric patients were from Turkey. In a
study, it was reported that five of 1700
pediatric tuberculosis patients were defined
with abdominal tuberculosis in Centers for
Disease Control and Prevention (CDC)
reports in 19923. Two reports from Turkey
were about abdominal tuberculosis and one of
them contained adult patients too.2,4.
INTRODUCTION
Abdominal
tuberculosis
is
a
rare
manifestation of tuberculosis1. Treatment may
be delayed because diagnosis is difficult due
to lack of specific symptoms and
pathognomonic findings. However, early
diagnosis is important in order to perform an
effective management and to decrease
morbidity and mortality.
As it is a rare disease, we aimed to discuss the
diagnosis and treatment of the abdominal
tuberculosis in the light of the literature and
In Turkey, abdominal tuberculosis has been
seen in 27/100 000 people2. A few of the
Atilla Şenaylı, M.D.
Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Çocuk Cerrahisi Anabilim
Dalı, Tokat, Türkiye
233
Atilla Şenaylı, et al.
Abdominal tuberculosis in a 3-year-old child
mg/kg) P.O., for one year, streptomycin (20
mg/kg) I.M., for two months and isoniazid
(10 mg/kg) P.O., for one year.
to report our difficulties and experiences with
a 3-year-old patient.
CASE REPORT
A three-year-old patient was referred to our
pediatric surgery clinic after suffering from
abdominal distention for a month. He had
lack of appetite, breathing difficulties and
drowsiness. Blood chemistry and urinary
analyses were normal. The erythrocyte
sedimentation rate (ESR) and blood counts
were non-specific. Blood smear revealed
lymphoid activity. Tumor markers were
normal. Abdominal X-ray seemed to be
normal. The tuberculin skin test was not
performed because tuberculosis was not
considered as the cause. In the abdominal
ultrasound examination (USG), ascites was
defined and multiple polypoid lesions were
seen in the parietal and visceral peritoneum.
The computerized tomography (CT) findings
were the same as the USG, and nothing
additional
was
reported.
Explorative
laparotomy was performed to evaluate the
peritoneal carcinomatosis-like lesions (Fig.1).
There were dense adhesions between the
intestinal segments and multiple polyps were
detected on the peritoneum and on the
intestines. Peroperatively, tuberculosis was
suspected because of the granulomatous
lesions. Biopsies from the mesentery and the
peritoneum were obtained, but biopsies from
the intestine were not obtained because of the
high risk of fistula formation.
Treatment was concluded with remission in a
year. No complications occurred during this
period. After the treatment, abdominal
computerized
tomography
and
USG
evaluations were performed and no lesions on
the mesenteric, intestinal and peritoneal
regions were detected.
Figure 1: Peroperative photograph showing
multiple polypoid lesions on the small intestine.
DISCUSSION
Abdominal tuberculosis is a rare disease that
can be challenging in diagnosis even for a
reference hospital. Routine evaluations may
be done for tuberculosis but pathognomonic
laboratory or radiodiagnostic tests are
absent2,4. In our institute, this patient was the
first case of abdominal tuberculosis, causing
another difficulty in diagnosis. There were
differences in the laboratory findings
according to the literature.
Pathological evaluation of the specimens
revealed fibroblastic proliferation with
histiocytes,
lymphocytes
and
polymorphonuclear
leucocytes
in
all
specimens. Langhans cells were defined in
granulomatous lesions. Acid-Fast bacilli
(AFB) were not detected.
Bacillus Calmette-Guerin (BCG) vaccine had
been administered to the patient through
Ministry of Health Vaccination Program.
In the literature, patients of different ages
were reported. The pediatric patients were
between 6 months and 16 years old. There
were two series for all ages reported from
Turkey for abdominal tuberculosis2,4. In these
reports, a high percentage was from the
pediatric population and median ages were
reported as 7 years and 16.2 years.
The patient was diagnosed as abdominal
tuberculosis with mesenteric, intestinal and
peritoneal invasion and given a treatment
protocol consisting of pyrazinamide (30
mg/kg) P.O., for 2 months, prednisolone
(1/mg/kg) P.O., for 15 days, rifampisin (20
234
Our patient had had the BCG vaccination in
his history. Progressive primary complex
among the BCG vaccinated group has been
increasing5. However, the prevalence of
abdominal tuberculosis is reported to be
almost same over the last 16 years and occurs
more in the BCG non-vaccinated children5.
Disseminated mycobacterial infection after
bacillus Calmette-Guerin vaccination is a very
rare disorder, and often occurs in patients
with immunologic deficiency6. Patients with
abdominal tuberculosis may be treated with
chemotherapy if they have had the BCG
vaccination and if other findings are
obviously targeting the disease2.
amplification using real-time polymerase
chain reaction (PCR) testing in the peritoneal
fluid sample8. For appropriate treatment, PCR
is a rapid diagnosis of abdominal
tuberculosis9.
Granulomas constitute the characteristic
lesions of tuberculosis3. In our case, as the
biopsies revealed granulomatous lesions and
the clinical progression differentiated some of
the other granulomatous lesions like Crohn’s
disease, we started chemotherapy without
PCR evaluation.
Chemotherapy is defined as multiple
antituberculosis drugs for at least one year of
therapy. In a study, isoniasid (10 mg/kg P.O.,
for one year), rifampicin (20 mg/kg P.O., for
one year), pyrazinamide (30 mg/kg P.O., for
the first 2 months), and streptomycin ( 20
mg/kg I.M., for the first month was used for
treatment4. In another study, ethambutol (20
mg/kg per day) was also used2. We also used
prednisolone, 1mg/kg/day for 15 days. The
recommended antituberculous treatment of
extrapulmonary TB in children includes the
use of a three-drug regimen( ısoniazide,
rifampin, and pyrazinamide)3,4,10. Also
streptomycin can be used in this
combination4. Some clinicians administer
corticosteroids routinely for the first 2 or 3
months against fibrosis3. Mortality has
decreased from 50 to 3% with the
introduction of anti-TB drugs1.
Erythrocyte sedimentation rate can be helpful
in evaluating the tuberculosis2. ESR was
reported to be high in the literature, but not in
our patient. If suspected, ESR may be a guide
for the diagnosis, but, as in our patient, it may
be within the normal range.
Ultrasonography and computed tomography
may be used for the diagnosis2. The most
common findings have been reported to be
ascites, lymphadenopathy, thickness of the
mesenterium and the peritoneum2,3,7. In a
study, thickness and fine septation was found
to be the most common findings2. USG and
CT may be added to the BCG vaccination,
ESR elevation, positive tuberculin test and
family story to treat the tuberculosis, if biopsy
is not possible2.
Peritoneal biopsy with explorative laparotomy
or laparoscopy may be indicated2,4,7. If the
treatment is planned without biopsy, careful
evaluation of the laboratory findings have to
be performed2. In biopsy evaluations,
mycobacterium tuberculosis may not be
detected but granulomatous lesions with
caseous necrosis are almost always revealed
with the disease. Cytological evaluation of the
organism is not always helpful for the
microorganisms.
We followed-up the patient for a year with the
therapy. The patient is healthy and has no
symptoms of the disease now. We will
continue to evaluate the patient with clinical
and radiological examinations. In one of
series reported from Turkey, patients were
followed-up for 9 months and all of them
recovered from the disease. We also followed
up our patient for a year and evaluated the
progress of the disease.
In our region, this is the first patient reported
and there are some clinical and laboratory
differences from the other patients reported in
the literature. Our patient was admitted to our
clinic with abdominal distention and he did
not suffer from abdominal pain. Also it was
reported that ESR would be high in reported
As the culture and AFB positivity of the
peritoneal fluid are rarely seen, histological
and bacteriologic confirmation may be the
only way to make a diagnosis2,3. In a study, it
was reported that Mycobacterium tuberculosis
DNA was detected by nucleic acid
235
5.
patients but in our patient ESR was within the
normal range. We experienced that
exploration of the abdomen and peritoneal
and mesenteric biopsies were the only ways to
help make a diagnosis.
6.
7.
REFERENCES
1.
2.
3.
4.
Tawfik R, Thomas A, Bruce J, Mandal B. Smallbowel obstruction caused by tuberculous strictures in
an infant. J Pediatr Gastroenterol Nutr 1996; 23: 324325.
Tanrıkulu AC, Aldemir M, Gurkan F, Suner A, Dağlı
CE, Ece A. Clinical review of tuberculous peritonitis
in 39 patients in Diyarbakır, Turkey. J Gastroenterol
Hepatol 2005; 20: 906-909.
Veeragandham RS, Lynch FP, Canty TG, Collins DL,
Dankner WM. Abdominal tuberculosis in children:
review of 26 cases. J Ped Surg 1996; 31: 170-176.
Özbey H, Tireli GA, Salman T. Abdominal
tuberculosis in children. Eur J Ped Surg 2003; 13:
116-119.
8.
9.
10.
236
Somu N, Vijayasekaran D, Ravikumar T,
Balachandran A, Subramanyam L. Tuberculous
disease in a pediatric referral centre: 16 years
experience. Indian Pediatr 1994;10:1245-1249.
Chandrabhushanam A, Han TI, Kim IO, Kim WS,
Yeon KM. Disseminated BCG infection in a patient
with severe combined immunodeficiency. Korean J
Radiol 2000; 2:114-117.
Saczek KB, Schaaf HS, Voos M, Cotton MF, Moore
SW. Diagnostic dilemmas in abdominal tuberculosis
in children. Ped Surg Int 2001; 17: 111-115.
Dervisoglu E, Sayan M, Sengul E, Yilmaz A. Rapid
diagnosis of Mycobacterium tuberculous peritonitis
with real-time PCR in a peritoneal dialysis patient.
APMIS 2006 ;114:656-658.
Gilroy D, Sherigar J. Concurrent small bowel
lymphoma and mycobacterial infection: use of
adenosine deaminase activity and polymerase chain
reaction to facilitate rapid diagnosis and treatment.
Eur J Gastroenterol Hepatol 2006;3:305-307.
Balasubramanian R, Nagarajan M, Balambal R, et al.
Randomised controlled clinical trial of short course
chemotherapy in abdominal tuberculosis: a five-year
report. Int J Tuberc Lung Dis 1997;1:44-51.
CASE REPORT
GIANT EPIDERMAL CYST OF THE FOREARM
Elif Karadeli1, Esra Meltem Kayahan Ulu1, Ahmet Fevzi Ozgur2, Emine Tosun3
1
Başkent Üniversitesi Tıp Fakültesi, Radyoloji Ana Bilim Dalı, Ankara, Türkiye 2Başkent Üniversitesi Tıp
Fakültesi, Ortopedi ve Travmatoloji Ana Bilim Dalı, Ankara, Türkiye 3Başkent Üniversitesi Tıp Fakültesi,
Patoloji Ana Bilim Dalı, Ankara, Türkiye
ABSTRACT
An epidermoid cyst is a benign, intradermal subcutaneous soft tissue tumor. Subcutaneous epidermal cysts
commonly involve the scalp, face, neck, trunk and back: fewer than 10 % occur in the extremities. We
reported clinical, magnetic resonance imaging (MRI) and pathologic findings of a big epidermal cyst in the
forearm.
Keywords: Forearm, Giant epidermal cyst, MRI
ÖN KOLUN DEV EPİDERMAL KİSTİ
ÖZET
Epidermoid kist benign, intradermal subkutanoz yumuşak doku tümörüdür. Subkutanöz epidermal kistler
sıklıkla kranium derisi, yüz, boyun, gövde ve sırtta yerleşir. Ekstremitelerde %10'dan azı yerleşim gösterir.
Biz ön kolun büyük epidermal kistinin klinik, patolojik ve manyetik rezonans görüntüleme bulgularını
sunduk.
Anahtar Kelimeler: Ön kol, Dev epidermal kist, MRG
and pathologic findings of a big epidermal
cyst in the forearm.
INTRODUCTION
An epidermoid cyst is a benign, intradermal
subcutaneous soft tissue tumor. The tumor is
considered to be a migration of an epidermal
component into the dermis1. The diagnosis is
clinical without imaging. Subcutaneous
epidermal cysts commonly involve the scalp,
face, neck, trunk and back: fewer than 10 %
occur in the extremities2. We reported
clinical, magnetic resonance imaging (MRI)
CASE REPORT
A 30-year-old man presented with a right
forearm mass, which had been slowly
growing for 5 years. The patient had no
trauma or pain. Physical examination
demonstrated a big, firm, subcutaneous mass
of the right forearm (Figure 1). In
Elif Karadeli, M.D.
Başkent Üniversitesi Tıp Fakültesi, Radyoloji Ana Bilim Dalı, Ankara,
Türkiye
237
Elif Karadeli, et al.
Giant epidermal cyst of the forearm
ultrasonographic examination, the tumor had
a regular contour, and was heterogenously
hypoechoic. Some vascularity was noted in
the color Doppler sonography, mimicking a
solid mass. Then, MRI was performed (1.5
Tesla, Philips Gyroscan) for detailed
investigation. The MRI showed a large, welldefined, oval, homogeneous mass measuring
3.5x3x2 cm in diameter. The lesion was
hypointense on T1- weighted images and
hyperintense on T2- weighted images relative
to the muscle. The lesion had some low signal
intensity foci and serpiginous structures in it
on T2-weighted images. After intravenous
injection of gadolinium, there was no
enhancement of the lesion (Figure 2). The
excisional biopsy of the mass was performed
under local anesthesia. The gross pathological
examination showed that the mass was welldefined, nodular and cystic in nature. The
histopathological examination showed that
the lumen of the cyst was filled with keratin
materials arranged in laminated layers. The
wall of the cyst was composed of stratified
squamous epithelium with keratohyalin
granules (Figure 3). The pathologic diagnosis
was keratinous cyst (epidermoid type).
Figure 2: MR imaging. Axial T1(A), T2(B),
coronal T1(D) and fat supressed T2(E) images
showed lobulated mass in the subcutaneous fat of
the forearm, which had low signal intensity on T1
and high signal intensity on T2 images.
Postcontrast axial T1(C) and fat suppressed T1(F)
images show no enhancement of the tumor.
Figure 3: The histopathological examination
showed that the lumen of cyst was filled with
keratin materials arranged in laminated layers.
Figure 1: A round lobulated mass in the forearm is
evident.
238
Elif Karadeli, et al.
Giant epidermal cyst of the forearm
DISCUSSION
Epidermoid cysts probably occur from
inflammation of pilosebaceous structures. The
second theory is that the formation of an
epidermoid cyst is related to the implantation
of epidermis into the dermis through trauma
(example: intramuscular injection) and
migration during embryogenesis. A later
theory frequently valid is for intracranial
lesions3. The epidermoid cyst of our case is
located on the forearm but the patient had no
trauma or injection history. Lee et al4 showed
the sonographic findings of epidermoid cysts,
which can have lobulated contours and show
color Doppler signals, mimicking a solid
mass. Similar to his study we showed that the
mass was not anechoic as a cyst, instead it
was hypoechoic, heterogeneous and showed
color Doppler signals as solid masses.
Unfortunately, we did not record the
ultrasonographic images of our patient.
Hong et al reported that MRI findings of
unruptured epidermal cysts were hypointense
on T1 and hyperintense on T2-weighted
images relative to the muscle5. On
postcontrast T1- weighted images, peripheral
rim enhancement was seen. Epidermoid cysts
may have hyperintense regions on T1weighted images compared to muscle6, and
may be hypointense on T1 and T2-weighted
images related to dense debris and
calcification components7. Shibata et al
reported that no enhancement was observed
inside the tumors and the variety of signal
intensities on T1 and T2-weighted images
reflects differences in chemical components
of the epidermoid cysts2.
Our case was hypointense on T1-weighted
images, hyperintense on T2-weighted images
compared to muscle. This case had a variable
amount of serpiginous lower signal foci on
T2- weighted images. We thought that
heterogeneity on T2-weighted images related
to the cyst lumen was filled with keratin
arranged in laminated layers.
The differential diagnosis of an epidermal
cyst contains a fibrous tissue tumor, such as
benign fibroma, xanthoma, malignant fibrous
histiocytoma
or
fibrosarcoma,
other
subcutaneous cystic masses, vascular lesions,
cystic
degeneration
and
hemorrhage,
lymphangioma with hemorrhage, cystic
teratoma,
large
ganglion
cyst
and
echinococcal cyst5,6 Ganglion cysts are
hyperintense on T2-weighted images, and
show peripheral rim enhancement on
postcontrast images. The heterogeneous
signals of epidermoid cysts on T2-weighted
images may help differentiation of epidermal
cysts from other fluid cysts (ganglion cyst,
bursitis). Some solid tumors such as
neurogenic tumors, nodular fasciitis, myxoid
tumors may be hyperintense on T2-weighted
images, so they mimic cystic masses. The
enhancement pattern of these solid masses
can be used to differentiate epidermal cysts5.
In conclusion, an epidermal cyst should be
thought in the differential diagnosis of a
cystic soft tissue masses. Useful features for
the diagnosis of an epidermoid cyst of the
extremity are a well-defined border, round or
oval
lesion,
subcutaneous
location,
hypointense on T1- weighted images,
hypointense foci in the hyperintense
background on T2- weighted images, and no
enhancement on postcontrast images.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
239
Shimizu Y, Sakita K, Arai E, et al. Clinicopathologic
features of epidermal cysts of the sole: comparison
with traditional epidermal cysts and trichilemmal cyst.
J Cutan Pathol 2005, 32:280-285
Shibata T, Hatori M, Satoh T, Ehara S, Kokubun S.
Magnetic resonance imaging features of epidermoid
cyst in the extremities. Arch Orthop Trauma Surg
2003; 123:239-241.
Bostroem E. Ueber die pialen epidermoide, dermoide
and duralen dermoide. Zentbl allg Path Anat 1897;
8:1-98.
Lee HS, Joo KB, Song HT, et al. Relationship
between sonographic and pathologic findings in
epidermal inclusion cysts. J Clin Ultrasound 2001; 29:
374-383.
Hong S, Chung H, Choi J, et al. MRI findings of
subcutaneous epidermal cysts: Emphasis on the
presence of rupture. AJR 2006; 186:961-966.
Fujimoto T, Murakami K, Kashimada A, et al. Large
epidermoid cyst involving the ischiorectal fossa: MR
demonstration. Clin Imaging 1993; 17:146-148.
Fu YT, Wang HH, Yang TH, et al. Epidermoid cysts
of the testis: diagnosis by ultrasonography and
magnetic resonance imaging resultin in organpreserving surgery. Br J Urol 1996;78:116-118.
CASE REPORT
POST-CAESAREAN RECTUS SHEATH HAEMATOMA: A CASE REPORT
Imtiaz Wani
S.M.H.S Hospital , Srinagar, Surgery, Srinagar, India
ABSTRACT
The author reports a case of rectus sheath haematoma after lower segment caesarean section (LSCS).The
haematoma extended to the pelvic wall. The aberrant course of vessels or injudicious dissection may
contribute to this catastrophe. Clinical suspicion, Carnett’s test and ultrasonography were used to confirm the
diagnosis. The management was conservative.
Keywords: Rectus sheath hematoma, Post caesarean
SEZARYAN OPERASYONU SONRASI GELİŞEN REKTUS KILIFI HEMATOMU: VAKA
SUNUMU
ÖZET
Alt segment sezaryen operasyonu sonrasında rektus kılıfı hematomu saptanan bir olgu sunulmuştur.
Hematom, pelvis duvarına kadar uzanmakta idi. Damar yapısı veya diseksiyon hataları bu olumsuz tabloya
neden olmaktadır. Klinik şüphe nedeni ile Carnett’s testi ve ultrasonografi kesin tanı için kullanılmıştır.
Hastaya konservatif tedavi uygulanmıştır.
Anahtar Kelimeler: Rektus kılıfı hematomu, Sezaryan operasyonu
INTRODUCTION
In developing countries, where simple
diagnostic facilities are not available all times,
diagnosis of rectus sheath haematoma remains
elusive and has to rely on the doctors clinical
judgment to diagnose this uncommon, but
well-documented mimic of acute abdominal
pain1. A keen clinical sense, ultrasound and
the invaluable Carnett’s test for diagnosis is
available in developing countries. Prompt
consideration of this rare mimic of acute
abdominal pain may reduce the burden of
performing expensive and invasive diagnostic
tests and in some cases unnecessary
hospitalization and laparotomy2.
CASE REPORT
A 26-year-old female was referred to our
surgical services with persistent lower
abdominal pain of two days duration .She had
undergone LSCS three days previously. She
was primi. The patient has already received
pain killers. Initially, the pain was attributed
to the wound site pain of LSCS. Tachyardia
was present. The rest of parameters were
normal. Perabdominal examination revealed
tenderness on palpation of lower abdomen.
Due to the tenderness, no swelling could be
assessed. Carnett’s test was positive.
Haemoglobin was 10 gm%. There was no
significant finding on the abdomen X-ray.
Imtiaz Wani, M.D.
S.M.H.S Hospital , Srinagar, Surgery, Srinagar, Hindistan
240
Imtiaz Wani, et al.
Post-caesarean rectus sheath haematoma: a case report
Abdominal sonography showed a multiseptate
cystic swelling of 11.4×8.1 cm. in front of
the bladder extending int the anterior
abdominal wall, as shown in Fig.1 suggestive
of rectus sheath haematoma. In our case, the
abnormal course of vessels in the rectus
sheath, abnormal insertion of the rectus
muscle which was torn during insertion with
lax and thinned out abdominal wall layers
may account for rectus sheath haematoma.
The patient was managed conservatively,
discharged on the seventh day and is routinely
attending our follow up clinics.
DISCUSSION
Rectus sheath hematoma has been a wellknown entity from the ruin of ancient Greece3
Rectus sheath presents as acute abdominal
pain. Females are more prone to develop
rectus sheath haematoma.The presentation is a
painful, tender abdominal swelling of sudden
onset. This haematoma results from bleeding
into the rectus sheath due to damage to the
superior and the inferior epigastric arteries or
their branches, or a direct tear of the rectus
muscle when small branches bleed.
Sometimes it can expand and lead to
hypovolemic shock and subsequent death.
This haematoma usually lies posterior to the
muscle. Haematomas near the umbilicus are
rare. Considered causes for rectus sheath are
severe
exertion4,
pregnancy5,
insulin
6,
injection laparoscopy and cholecystectomy7.
Berna et al, proposed that rectus sheath
haematoma should be suspected in women of
advancing age undergoing treatment with
anticoagulants who present with triad of acute
abdominal pain, infraumbilical mass and
anemic syndrome8. Other causes being
coughing, thrombocytopenia and contusion9.
Ultrasound is a good investigation for
diagnosis10, showing the mass of mixed
echogenicity with no internal vascularity5. CT
abdomen in particular is more useful, permits
a more correct diagnosis and is considered the
investigation of choice11. Technetium -99
labeled red blood cell (RBC) scintigraphy
confirms the presence of the haematoma, site
of bleeding and reveals continued bleeding6.
Selective percutaneous transcatheter arterial
embolisation is considered an effective
haemostatic in the treatment of a patient with
a large haematoma12. Because of the
diagnostic dilemma of differentiating this
condition from other acute abdominal
conditions the majority of cases are treated
with operative procedures3. Non-surgical
therapy is considered appropriate, but leads to
a greater need for analgesics. Surgical
intervention is necessary in cases with large
haematomas or free intra operational
ruptures10.
Early
diagnosis
permits
conservative management even in large
haematomas.
Figure 1: A multiseptate cystic swelling in
front of the bladder extending into the
anterior abdominal wall, suggestive of rectus
sheath hematoma.
241
Imtiaz Wani, et al.
Post-caesarean rectus sheath haematoma: a case report
6.
Stress is laid on clinical examination,
Carnett’s test and ultrasonography in the
diagnosis of rectus sheath haematoma. A
persistent pain in the lower abdomen should
arouse suspicion of rectus sheath hematoma
in post LSCS. Management is most of the
time by conservative measures.
7.
8.
9.
REFERENCES
1.
2.
3.
4.
5.
10.
Maharaj D, Ramdass M, Teelucksingh S. Rectus
sheath haematoma :a new set of diagnostic features.
PMJ 2002;78:755-758.
Edlow JA, Juang P, Margulies S, et al. Rectus sheath
hematoma. Ann Emerg Med 1999;34:671–675.
Miyauchi T, Ishikawa M, Miki H. Rectus sheath
hematoma in an elderly woman under anti-coagulant
therapy. J Med Invest 2001;48:216–220.
Hecker RB, Bradshaw WH, Pinkerton SF. Rectus
sheath hematoma: report of a case. Tex Med
1990;86:68–70.
Humphrey R, Carlan SJ, Greenbaum L. Rectus sheath
hematoma in pregnancy. J Clin Ultrasound
2001;29:306–311.
11.
12.
242
Monsein LH, Davis M. Radionuclide imaging of a
rectus sheath hematoma caused by insulin injections.
Clin Nucl Med 1990;15:539–541
Neufeld D, Jessel J, Freund U. Rectus sheath
hematoma: a complication of laparoscopic
cholecystectomy. Surg Laparosc Endosc 1992;2:344–
345.
Berna JD, Zuazu I, Madrigal M, et al. Conservative
treatment of large rectus sheath hematoma in patients
undergoing anticoagulant therapy. Abdom Imaging
2000;25:230–234.
Hegenbarth R, Reiser C, Leib P.The sonographic
diagnosis of a spontaneous rectus sheath hematoma.
Aktuelle Radiol 1991;1:201–203.
Klingler PJ, Wetscher G, Glaser K, et al. Use of
ultrasound to differentiate rectus sheath hematoma
from other acute abdominal disorders. Surg Endosc
1999;13:1129–1134.
Berna JD, Garcia-Medina V, Guirao J, et al. Rectus
sheath hematoma: diagnostic classification by CT.
Abdom Imaging 1996;21:62–64.
Rimola J, Pirendru J, Falco J. Clinical observations.
Percutaneous arterial embolisation in the management
of rectus sheath haematoma. AJR 2007;188: W497W502.
ORIGINAL RESEARCH
RETROPERITONEAL CASTLEMAN’S DISEASE: REPORT OF FOUR CASES
Pinar Yazıcı1, Ünal Aydin1, Oktay Tekesin2, Murat Zeytunlu1, Murat Kılıç1, Mine Hekimgil3
Ahmet Coker1
1
Ege University, School of Medicine, Department of General Surgery, Izmir, Türkiye
2
Ege University, School of Medicine, Gastroenterology Division, Izmir, Türkiye
3
Ege University, School of Medicine, Department of Pathology,, Izmir, Türkiye
ABSTRACT
Castleman’s Disease (CD) located in the retroperitoneum is a rare entity which has both benign and
malignant potential. We presented our series of four patients with retroperitoneal neoplasm of the lymphatic
chain and evaluated the management of these patients.
Over a five-year period, all patients who had intraabdominal lymphadenomegaly with an unknown etiology
or were diagnosed with Castleman’s Disease of the retroperitoneum were retrospectively reviewed. Data
included demographic features, surgical management and outcomes.
Four patients with CD were detected, three males and one female with a mean age of 54 years. All patients
had a unicentric mass located in the retroperitoneal area. Three cases complete excision of the mass and one
with a mass associated to the pancreatic head underwent a pancreaticoduodenectomy. Three of the
histological examinations were revealed to be of the hyaline vascular type and one was a mixed type
microscopically. The recovery period was uneventful for all the patients. In the follow-up period, no
recurrence was detected.
This unusual anomaly of the lymphatic chain, particularly in the retroperitoneal area, should be kept in mind
in the differential diagnosis of retroperitoneal tumors. The histological examination can reveal a mixed type
CD even in this location. For unicentric tumors, surgical excision is the effective curative management and
our series proved the efficacy of this method.
Keywords: Intraabdominal lymphadenomegaly, Castleman’s disease, Total excision
RETROPERİTONEAL CASTLEMAN HASTALIĞI: DÖRT OLGU SUNUMU
ÖZET
Castleman Hastalığı hem malign hem de benign olma riski olan retroperitoneal yerleşimli olan nadir bir
patolojidir. Biz bu çalışmada retroperitoneal lenfatik zincirde malignitesi olan dört hastayı ve tedavi
yaklaşımlarını değerlendireceğiz.
Beş yılı aşkın bir süredir etiyolojisi bilinmeyen karın içi lenfadenopatisi ya da Castleman hastalığı tanılı
hastalar retrospektif olarak tarandı. Cerrahi tedavileri ve sonuçlar değerlendirildi.
Castleman hastalığı tanılı, yaş ortalaması 54 olan üç erkek bir kadın hasta bulundu. Tüm hastalarda
retroperitoneal alanda yerleşimli izole bir kitle mevcuttu. Üç hastaya total eksizyon uygulanırken pankreas
başı ile ilişkili bir kitleye pankreatikoduodenektomi uygulandı. Bir tane mikst tip haricinde tüm patolojik
değerlendirmeler hiyalin vasküler tip olarak rapor edildi. Tüm hastaların iyileşme periyodu sorunsuz geçti ve
takip periyodunda nüks saptanmadı.
Özellikle retroperitoneal alan yerleşimli lenfatik zincirdeki bu nadir anomali retroperitoneal tümörlerin
ayırıcı tanısında mutlaka akılda bulundurulmalıdır. Bu bölge yerleşimli Castleman hastalığı mikst tip de
olabilir. Tek odaklı tümörlerde etkin küratif tedavi için cerrahi eksizyon yeterlidir ve bu yazı sonuçları bunu
desteklemektedir.
Anahtar Kelimeler: Karın içi lenfadenopatiler, Castleman Hastalığı, Total eksizyon
Pinar Yazici, M.D.
Ege University, School of Medicine, General Surgery, Izmir, Türkiye
243
Pınar Yazıcı, et al.
Retroperitoneal Castleman’s Disease: Report of four Cases
ultrasonography and computed tomography
(CT) of the abdomen. All of the masses were
found in unicentric localization and the most
frequent localization of the masses was the
retroperitoneal area (Figure 2a) and next to
the pancreatic head, mostly at the posterior
side. In case no 2, CT revealed a solid mass
arising from the mesentery of the transverse
colon and extending to the infero-posterior of
the pancreatic head (Figure 2b). Mean
diameter of the tumors was 4,1 cm ranging
between 3cm and 5,5 cm. Three patients
underwent only total excision of the mass,
whereas
one
patient
required
pancreticoduodenectomy.
Pathological
examinations revealed hyaline-vascular type
lymphadenomegaly (Figure 3, case no. 3) in
all patients except one patient (case no.2)
whose histological findings demonstrated
mixed cellular type including both hyalinevascular and plasmacytic type cell features
(Figures 4a-b). All patients had an uneventful
recovery period. Mean hospital stay and
follow-up was 6 days (range: 3-14 days) and
34.5 months (13-72 months), respectively. No
recurrence was revealed by radiological
studies in the follow-up period.
INTRODUCTION
Castleman’s disease (CD), or angiofollicular
lymph node hyperplasia, is a rare entity
characterized by formation of benign lymph
node masses, first described by Castleman et
al. in 19561. It is mostly recognized in the
mediastinum, but it rarely manifests clinically
within the retroperitoneum. CD in the
retroperitoneum is especially unusual,
accounting for only 7% of all reported cases
(400 patients so far)2. The importance of
localization is that there is a relatively high
potential risk for the development of
malignancy with the retroperitoneal tumors.
CD can be histologically divided into two
types: the plasma cell type, and the hyalinevascular type which is more common,
accounting for 90% of all cases3. Isolated case
reports have described the plasma cell type
and rare hyaline vascular type arising in the
retroperitoneum4-6. To our knowledge, a
mixed type of plasma cell and hyalinevascular
types
occurring
in
the
retroperitoneum has not been previously
reported. In this series of four patients with
retroperitoneal CD, we also presented a case
of mixed type tumor arising in this location,
which was diagnosed due to periodical
abdominal pain.
CASE REPORTS
Between May 1999 and March 2006, four
patients were detected with CD after a
retrospective review of the case records.
Demographic variables, clinical features,
diagnostic methods, operative procedures
were evaluated. Data also included the
postoperative complications, hospital stay,
pathological examination and follow-up
period. The informed consent form was
obtained from the patients in question.
Three male and one female with a mean age
of 54 (46-62) were detected. Two patients
were asymptomatic whereas other two had
abdominal pain. Laboratory evaluation and
hematological parameters were within normal
ranges. C-reactive protein, one of the acute
phase reactants, was also normal. All patients
had routinely performed chest X-rays,
Figure 1: Isolated solid mass, 24x32mm in
size, (lymphadenomegaly) located between
vena cava inferior and aorta (case no 3).
244
Pinar Yazici, et al.
Retroperitoneal Castleman’s disease: report of four cases
Figure 2: a) solid mass (about 3 cm in diameter) located posterior to the vena cava
inferior, b) right paraaortic mass arising from the mesentery of the transverse colon
Figure 3: Concentric layering of mantle zone cells
around the hyalinized germinal centers in case no. 3
Figure 4: a) Glomerulization of germinal centers and plasma cell infiltration of the interfollicular
area in case no. 2 (H&E, x20) b) Immunohistochemical staining of plasma cells with CD138
(DAB, x20).
245
Table 1. Demographic characteristics and treatment modalities of the patients
Patient
number
P1-FY
Age
Gender
Clinical
features
Abdominal
pain, weight
loss
Diagnostic
methods
USG, CT
Localization and
diameter of LAM
Pancreatic head
30*18mm
Operative
procedure
Pancreaticoduodenectomy
Pathological
Examination
Hyalinevascular
Hospital
stay(days)
14
Follow-up
(months)
72
62
F
P2-NT
53
M
Abdominal
pain, fatigue
USG,
CT**
Arising from
mesentery of the
transverse colon,
posterior of the
pancreatic head,
right paraaortic
area, 55*31mm
Total excision
of the mass
Mixed type;
Hyalinevascular type
+ plasma cell
type
3
13
P3-GG
46
M
asymptomatic
USG,
CT*, MRI
Posterior to the
uncinat process,
interaortocaval
LAM, 24x37 mm
Total excision
of the mass
6
18
P4-RA
57
M
asymptomatic
USG, CT
Posterior to the
inferior vena cava
32x45mm
Total excision
of the mass
4
36
P:patient , USG: ultrasonography, CT: computed tomography, MRI: magnetic resonance imaging, LAM:
lymphadenomegaly
* picture 1, ** picture 2b
characteristics of this rare entity make it
difficult to obtain the precise diagnosis prior
to surgery. The usual appearance of this entity
by CT is that of a nonspecific homogeneous
mass and homogeneously hypoechoic feature
on US. In our patients, US and CT imaging
demonstrated almost typical characteristics,
but no remarkable evidence of malignancy.
Additionally, magnetic resonance imaging
(MRI) is also one of the diagnostic
techniques. Although MRI has some
advantages like higher soft tissue contrast, the
intensity characteristic is not specific for CD.
DISCUSSION
Tumors located in the retroperitoneum
include various groups of neoplasms of
benign or malignant origin. However,
malignant potential is considerable for
retroperitoneal masses. On the other hand,
benign retroperitoneal tumors comprise only
about 20% of all primary retroperitoneal
neoplasms7. Because of deeper location on the
lymphatic chain, clinical presentation of these
patients with retroperitoneal CD constitutes a
real problem for the physician to diagnose. As
with the patients presented in our study,
patients with the plasma cell type tumor of
CD usually present some symptoms, whereas
those with the other types are generally
asymptomatic. In our series, only one patient
had symptoms related to the abdomen and it
was considered due to close relationship of
the tumor with the pancreatic head,
preoperatively.
The
hyaline
vascular
histological subtype is the most common,
accounting for 90% of cases whereas the
plasma cell type (10%) is less common and
less vascular8. In addition, CD is mostly
indistinguishable from other diseases despite
preoperative radiographic work-ups and even
after operative observation. These two
Once localized CD is removed, the prognosis
is very good, but not for multicentric disease.
Unicentric CD has generally no progression
or association with other tumors and simple
resection is curative in 90-95% of cases,
whereas multicentric CD can progress to
lymphoma (5%) and usually requires systemic
therapy. Those patients generally follow an
aggressive, often fatal clinical course
associated
with
hepatosplenomegaly,
multifocal lymphadenopathy, and abnormal
liver/renal function, mostly caused by
infectious complications or the development
of malignancies3. In some cases, the surgeon
cannot safely remove all the disease, but this
246
does not necessarily mean it will come back.
Because partial removal may help the
prognosis and the disease may not return, the
tumoral mass should be extracted as much as
possible. These recommendations are not
conforming
for both the patients with
multicentric disease or associated HIV
infection. In one study, 50% of the people
with multicentric CD had died by the end
of2½ years. In our series, fortunately, none of
them had multicentric masses. All but one
underwent total excision without remnant
tissue in the abdomen. One had to have
advanced resectional procedure due to close
relation with the pancreatic head and
suspicious frozen section results.If the frozen
section is feasible intraoperatively, it should
be used to determine the operative strategy
and the resection margins.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
In conclusion, although retroperitoneal CD is
a rare entity, it should be included in the
differential diagnosis. We suggest that when
CD is clinically suspected for retroperitoneal
solid masses after meticulous preoperative
evaluation, only total excision of the mass is
curative with a good outcome.
8.
247
Castleman B, Iverson L, Menendez VP. Localized
mediastinal lymph node hyperplasia resembling
thymoma. Cancer 1956; 9:822- 830
Rare
diseases
in
numbers.
[http://ec.europa.eu/health/ph_threats/non_com/docs] it
is available from this website.
Ziv Y, Shikiar S, Segat M, Orda O. Bilateral localized
Castleman disease of the retroperitoneum. Eur J Surg
Oncol 1993; 19:188-191
Moon WK, Kim WS, Kim IO, Yeon KM, Han MC.
Castleman disease in the child: CT and ultrasound
findings. Pediatr Radiol 1994;24:182–184
Joseph N, Vogelzang RL, Hidveg D, Neiman HL.
Computed tomography of retroperitoneal Castleman
disease (plasma cell type) with sonographic and
angiographic correlation. J Comput Assist Tomogr
1985;9:570–572
Singletary L. A, Karcnik T. J, Abujudeh H. Hyaline
vascular-type Castleman disease: a rare cause of a
hypervascular retroperitoneal mass. Abdom Imaging
2000; 25:207–209
Okada S, Maeta H, Maeba T, Goda F, Mori S.
Castleman Disease of the Pararenal Retroperitoneum:
Report of a Case. Surg Today 1999; 29:178-181
Keller AR, Hochholzer L, Castleman B. Hyaline
vascular and plasma cell types of giant lymphnode
hyperplasia of the mediastinum and other locations.
Cancer 1972;29:670–683.
CASE REPORT
ENDOVASCULAR TREATMENT OF A VERTEBRAL ARTERIOVENOUS FISTULA:
CASE REPORT
Feyyaz Baltacıoğlu
Marmara Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul, Türkiye
ABSTRACT
In this report, we present a patient with high flow vertebral arteriovenous fistula and its endovascular
treatment. The patient was a 25-year-old female with neurofibromatosis type I, presenting with quadriparesis
due to the compression of highly dilated epidural venous pouches to cervical spinal cord, and treated with
endovascular stent-graft.
Keywords: Vertebral, Arteriovenous, Fistula, Endovascular
VERTEBRAL ARTERİOVENÖZ FİSTÜLÜ VE ENDOVASKÜLER TEDAVİSİ: VAKA
SUNUMU
ÖZET
Bu yazıda yüksek debili bir vertebral arteriovenöz fistülü ve endovasküler tedavisini sunduk. Hasta
nörofibromatozis tip-I nedeni ile takip edilen 25 yaşında bayandır.Genişlemiş epidural venlerin yol açtığı
servikal spinal kord basısı nedeni ile ortaya çıkan kuadriparezi ile başvurmuştur.
Anahtar Kelimeler: Vertebral, Arteriovenöz, Fistül, Endovasküler
with coil or baloon embolization or with
stent-graft were reported for treatment2,3.
INTRODUCTION
Vertebral arteriovenous (AV) fistulas are
defined as abnormal communications between
the extracranial vertebral artery and an
adjacent vein. Most of these lesions are
traumatic in origin, due either to blunt or
penetrating trauma or iatrogenic trauma1.
Spontaneous cases may be congenital or may
be associated with abnormal vessels. In the
treatment, preservation of the parent artery is
important, and must be attempted, but it is
hardly ever achieved by surgical means.
Endovascular treatment is a minimally
invasive treatment modality, and does not
have the disadvantages of open surgery.
Different types of endovascular approaches,
via both transvenous and transarterial routes,
CASE REPORT
The patient was a 25-year-old female with a
neurofibromatosis (NF) type I. She had
presented to another hospital with sudden
onset of quadriparesis. Her past medical
history was uneventful up to two weeks prior
to admission. During the last two weeks, she
experienced numbness and weakness at all
four extremities progressing slowly to
quadriparesis. There was no clearly defined
trauma in her history. There was a strong
thrill over her left neck. Cervical MR
examination revealed a left sided mass lesion
of 2x4 cm in size at C3 level. The lesion was
Feyyaz Baltacıoğlu, M.D.
Marmara Üniversitesi Tıp Fakültesi, Radyoloji Anabilim
Dalı,Altunizade, İstanbul, Türkiye
248
Feyyaz Baltacıoğlu, et al.
Endovascular treatment of a vertebral arteriovenous fistula: case report
vertebral artery distal to the fistula site did not
fill efficiently. Since there was a single hole,
the fistula site was clearly defined, and there
was no apparent difference between the size
of the vertebral artery proximal and distal to
the fistula site, endovascular treatment with
stent-graft was decided to preserve the
patency of the parent artery. Under local
anesthesia, a baloon expandable Jomed
coronary stent graft (Jomed International AB,
Helsingborg, Sweden) of 4x25 mm in size
was placed across the fistula site. Control
angiography revealed that the fistula was fully
filled with contrast material. After that, the
proximal part of the stent was overdilated
with a 5x20 mm baloon. The last control
angiogram showed no residual filling of the
fistula. The distal filling of the vertebral
artery became normal. The neck thrill
disappeared immediately after the procedure.
The patient was discharged with aspirin 300
mg (life-long) and clopidrogel 75 mg (1
month) the next day. She underwent a surgery
for cervical neurinoma about one month later.
an extradural mass, compressed the spinal
cord, and passed through the left neural
foramen to outside the spinal canal. It was
hypo/isointense with spinal cord on T1W
images, hyperintense on T2W images and
showed dense contrast enhancement. The
lesion was diagnosed as neurinoma. Beside
this, there were dilated signal void epidural
venous pouches severely compressing the
spinal cord and filling the spinal canal at the
level of C5-C6. At this level, it communicated
with the left vertebral artery through the left
intervertebral foramen. The patient underwent
a digital subtraction angiography (DSA)
examination to clear up the architecture of the
arteriovenous fistula, and to plan the
treatment. Left vertebral artery injection
showed a single high flow side-to-side fistula
between the left vertebral artery and an
epidural vein. The size of the fistula site was
about 15 mm, and immediate post-fistula vein
showed aneurysmatic dilatation. The large
epidural venous pouch drained further to
paravertebral veins bilaterally. Due to the
steal of the fistula, the segment of the left
Figure 1: A. Axial T1W, contrast enhanced cervical MR imaging. An extradural, highly contrast enhanced mass
lesion (white arrows) compressing the spinal cord, and passing through the left neural foramen to outside the
spinal canal. B. Axial T2W, cervical MR imaging. A dilated signal void epidural venous pouch (white arrows) that
severely compressing the spinal cord (curved arrow) is seen. It passes through the left foramina and communicates
with the left vertebral artery (large arrow). C. Sagittal T2W, cervical MR imaging. Note the hyperintense
neurinoma at C2 level (white arrow) and, signal void venous pouch at C5-6 level (curved arrow). D. Left vertebral
artery DSA examination. A-P view. A single high flow side-to-side fistula between the left vertebral artery and an
epidural vein is seen (curved arrow). The large epidural venous pouch draines further to bilateral paravertebral
veins. Distal left vertebral artery does not fill efficiently (white arrow). E. Post-embolization control DSA
examination after placement of stent graft (between white arrows). No residual filling of the fistula is seen. Distal
filling of the vertebral artery becomes normal.
249
essential during the treatment procedure. The
fistula site must be well visualized.
Sometimes, contralateral vertebral artery
injection with or without ipsilateral proximal
vertebral artery occlusion with balloon is
better for detecting the exact fistula site. The
bilateral carotis system should also, be studied
in order to reveal the probable concomitant
injuries, which are important in the planning
of the therapy.
DISCUSSION
Extracranial vertebral arteriovenous fistulas
are rare lesions and they are usually traumatic
in origin. Traumatic fistulas are most
commonly of iatrogenic cause, secondary to
internal jugular vein puncture or to neck
surgery. Beaujeux et al reported that, most of
the traumatic fistulas affect the lower portion
of the vertebral artery (below C5), while
spontenous ones involve the upper portion (at
or above C2), which is contrary to both of our
patients4. Non-traumatic fistulas can be
congenital or spontaneous. Spontaneous ones
can complicate primary vascular pathologies
like neurofibromatosis type I, fibromuscular
dysplasia, Marfan’s syndrome or EhlerDanlos syndrome type IV5,6. There has been
an increasing awareness of vascular lesions in
patients with NF I. Dysplastic smooth muscle
or neurofibromatosis proliferation in the
vessel wall lead to vasculopathy, aneurysm
formation, leakage, and ultimately rupture
into the adjacent vein7. The AVF’s in NF type
I were reported to be more common in
women more often left-sided, as in our case 8.
The goal of treatment should be occlusion of
the fistula site, and preservation of the
patency of the vertebral artery. These lesions
are difficult to treat by surgical means,
because of the anatomic location, the critical
condition of the patient especially in the cases
with hematoma, and the difficulty in
localizing the exact site of the fistula.
Endovascular
intervention
has
been
increasingly used to treat AV fistulas. If the
contralateral vertebral artery can supply
sufficient vertebrobasiler circulation despite
the steal effect, transarterial occlusion of the
affected vertebral artery with detachable
balloons or coils can be an effective way of
treatment. For the complete elimination of the
fistula, the embolic material should be placed
both proximal and distal to the fistula site, in
order to prevent the retrograde filling of the
fistula. To preserve the vertebral artery
perfusion, not the parent artery, but the fistula
site itself can also be selectively embolized
with coils or balloons. On the other hand,
both coils and balloons have some
disadvantages. Coils may not produce
occlusion of the fistula, because of their poor
thrombogenicity and the difficulty in
achieving dense coil packing. Also they may
migrate intracranially causing inadvertent
arterial occlusion, or flow through the
draining veins, because of the high flow
fistula. In such cases, balloon aided coil
embolization can be applied, in order to
prevent coil migration and achieve a dense
coil packing9. Sometimes it is impossible to
pass a balloon through the narrow orrifice of
the fistula. The balloon, on the other hand, is
a flow guided device and, in the case of a
large bore high flow fistula, it is hard to pass
Symptomatology differs according to the site
of the fistula and the flow patterns.
Sometimes a neck bruit may be the only
presenting sign. In the case of a proximal
fistula, due to the effects on cardiac funtion,
cardiac failure is seen. In cases with central
venous occlusion of the superior vena cava,
reversal of increased internal jugular vein
flow causes increase in cerebral venous
pressure, which in turn, causes cerebral edema
and headache. Severe life-threatening neck
hematoma is another important sequela, due
to the rupture of a pseudoaneurysm. Finally,
with the enlargement of the fistula, dilated
epidural venous pouches cause neuronal
compression syndrome, which in turn cause
motor and sensory deficits, as in our case.
In the evaluation of the vertebral fistulas, all
possible vascular pedicles should be
angiographically assessed, including both
carotid, costo-cervical, and thyro-cervical
arteries which probably supply the fistula.
Knowledge of the hemodynamics of the
contralateral vertebral artery circulation is
250
the balloon distal to the fistula site for the
parent artery occlusion.
Sealing of the fistula with a stent graft is the
treatment of choice to preserve the vertebral
artery. Stent grafts are of two types: balloon
expandable and self-expandable. Both of
them have advantages and disadvantages. Self
expandable stent grafts have thick shafts of 810 French in size, and they are stiff. That is
why, it is hard to propagate them to the distal
segments of the vertebral artery. They are
more suitable for the proximal lesions. They
are also better in cases at where the vessel
diameter is different at the proximal and distal
end of the fistula. Balloon expandable stent
grafts, on the other hand, have thinner
catheter shafts. Jomed coronary stent graft is
premounted on a monorail balloon system of
4 French catheter size. It is easier to navigate
distal vasculature. The main disadvantages is
that, it is not firmly fixed in the vessel at
where the proximal and distal end of the
fistula show great mismatch in diameter.
Generally the proximal diameter is larger than
the distal one. If any leak is observed after the
deployment of the stent-graft, the proximal
half of the stent may be overdilated with a
balloon of larger diameter, as in our case.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
In conclusion, endovascular treatment of the
vertebral arteriovenous fistulas is safe and
efficacious. Different types of endovascular
means, like coils, balloons or stent-grafts can
be used for this purpose. Preservation of the
parent artery should be aimed for when
possible.
251
Cosgrove G, Theron J. Vertebral arteriovenous fistula
following anterior cervical spine surgery. J Neurosurg
1987;66:297-299.
Barkhordarian S. Stent graft repair of traumatic
vertebral pseudoaneurysm and arteriovenous fistula.
Vascular and Endovascular Surgery 2007;41:153-157.
Guglielmi G, Vinuela F, Duckwiler G, Dion J,
Stocker A. High-flow, small-holes arteriovenous
fistulas: treatment with electrodetachable coils. AJNR
1995;16:325-328.
Beaujeux RL, Reizine DC, Casasco A, et al.
Endovascular treatment of vertebral arteriovenous
fistula. Radiology 1992;183:361-367.
Bahar S, Chiras J, Carpena JF, Bories J. Spontenous
vertebro-vertebral arteriovenous fistula associated
with fibromuscular dysplasia. Report of two cases.
Neuroradiology 1984;26:45-49.
Kahara V, Lehto U, Ryymin P, Helen P. Vertebral
epidural arteriovenous fistula and radicular pain in
neurofibromatosis
type
I.
Acta
Neorochir
2002;144:493-496.
Schievink WI, Piepgras DG. Cervical vertebral artery
aneurysms
and
arteriovenous
fistulae
in
neurofibromatosis type I. Case reports. Neurosurgery
1991;29:760-765.
Hasegawa H, Bitoh S, Katoh A, Tamura K. Bilateral
vertebral arteriovenous fistulas and atlantoaxial
dislocation associated with neurofibromatosis. Neurol
Med Chir 1989;29:55-59.
Yılmaz MH, Kantarcı F, Gülşen F, et al. Yüksek
akımlı vertebrojuguler fistül endovasküler tedavisinde
eş zamanlı transarteryel ve transvenöz yaklaşım. Olgu
sunumu. Bilgisayarlı Tomografi Bülteni 2005;8:177180.
OLGU SUNUMU
BEHÇET OLGUSUNDA DİŞ ÇEKİMİ SONRASI GELİŞEN EKSTERNAL KAROTİD
ARTER PSEUDOANEVRİZMASI VE İNTERNAL JUGULER VEN TROMBOZU
Figen Palabıyık, Arda Kayhan, Esra Karaçay, Ercan İnci, Tan Cimilli
Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Radyoloji, İstanbul, Türkiye
ÖZET
Behçet hastalığı nedeni bilinmeyen, vaskülit ile seyreden multisistemik enflamatuar bir hastalıktır. Klinik
bulgulardan sorumlu küçük damar vaskülitine ek olarak olgularda büyük ven ve arter tutulumu ve buna bağlı
psödoanevrizma, tromboz gibi komplikasyonlar gelişebilir. Büyük arter komplikasyonları sıklık sırasına göre
aort, pulmoner , femoral, subklavian ve karotid arterlerde meydana gelir. Literatürde ekstrakranial yerleşim
ve özellikle eksternal karotid arter tutulumu ve bu lokalizasyonda gelişen komplikasyon nadir olarak
bildirilmiştir. Ayrıca literatürde Behçet hastasında diş çekimi sonrası oral aftöz lezyon oluşumu mevcut iken
büyük damar tutulumu bildirilmemiştir.Olgu sunumumuzda, erkek Behçet hastasında diş çekimi sonrası
meydana gelen eksternal karotid arter psödoanevrizması ve internal juguler ven trombozu klinik ve
radyolojik bulgular eşliğinde değerlendirilmiştir.
Anahtar Kelimeler: Behçet hastalığı, Dental manipulasyon, Eksternal karotid arter pseudoanevrizması,
Internal juguler ven trombozu
EXTERNAL CAROTID ARTERY PSEUDOANEURYSM AND INTERNAL JUGULAR
VEIN THROMBOSIS FOLLOWING TOOTH EXTRACTION IN A CASE OF
BEHÇET’S DISEASE
ABSTRACT
Behçet’s disease is a multisystemic inflammatory disease of unknown cause, presenting with vasculitis.
Complications such as pseudoaneurysm or thrombosis may be seen due to major vein and artery involvement
in addition to vasculitis causing clinical manifestations. Major artery complications are seen most commonly
in the aorta, pulmonary, femoral, subclavian or carotid artery. The involvement of an extracranial artery,
particularly the external carotid artery is uncommon in the literature. In our case, the clinical and radiologic
findings of a young male Behçet patient with an external carotid artery pseudoaneurysm and internal jugular
vein thrombosis following tooth extraction is presented together with the relevant literature. No such
complication of Behçet’s disease following a dental manipulation has previously been reported in the
literature.
Keywords: Behçet’s disease, Dental manipulation, External carotid artery pseudoaneurysm, Internal jugular
vein thrombosis
Dr. Arda Kayhan,
Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Radyoloji,
İstanbul, Türkiye
252
Figen Palabıyık, Ark.
Behçet olgusunda diş çekimi sonrası gelişen eksternal karotid arter pseudoanevrizması ve internal juguler ven trombozu
üst kısmına ve yüze doğru uzanım gösteren
pulsatil ve dokunmakla hassas düzgün
konturlu, yuvarlak bir şişlik saptandı. Behçet
hastalığı anamnezi veren olgunun, 6 gün önce
bir diş hekimi tarafından sol üst 2. molar
dişinin çekildiği öğrenildi. Hasta öyküsünde,
işlemden 2 gün sonra boynunda oluşan
şişliğin diş çekimi sonrasında geliştiğini
düşünerek önce diş hekimine başvurduğunu,
olası abse gelişimine yönelik 4 gün boyunca
antibiyotik tedavisi aldığını ancak yakınması
geçmeyince diş hekiminin bunun yapılan
işlemle ilgisi olmadığını söyleyerek kendisini
hastaneye yönlendirdiğini bildirdi.
GİRİŞ
Behçet hastalığı, tekrarlayan oral ve genital
aftöz ülserler, oküler lezyonlar ve cilt
lezyonları, ayrıca eklem, damar ve sinir
sistemi tutulumu ile seyreden nedeni
bilinmeyen enflamatuar bir hastalıktır. Behçet
olgularının yaklaşık %7-37’sinde, hastalığın
bir döneminde vasküler lezyonlara bağlı
yakınmalar
ortaya
çıkmaktadır1.
Kardiyovasküler tutulum hem arterleri hem de
venleri içermekte, arteriyel oklüzyondan
anevrizmaya, yüzeyel trombozdan süperior
vena kava oklüzyonuna kadar uzanan geniş
bir spektrumu içine almaktadır. Vasküler
ölümler genellikle anevrizma rüptürleri
sonucu ortaya çıkarlar2,3. Türkiye’de yapılan
çalışmalarda vasküler tutulum oranının
%24.3-38.4 arasında değiştiği bildirilmiştir4.
Behçet hastalığında venöz lezyonlar büyük
arter tutulumuna göre daha sık izlenmektedir.
Ayrıca oral hijyenin bozuk olması, yapılan
dental manipulasyonlarda oral aftöz lezyon
oluşumunu tetiklemekte olup relaps ve
komplikasyonlara yol açmaktadır5,6. Olgu
sunumumuzda, diş çekimi sonrası gelişen
eksternal karotid arter ( EKA) anevrizması ve
internal jugular ven (İJV) trombozu saptanan
genç erkek Behçet hastasında, klinik ve
radyolojik bulguları literatür eşliğinde
tartışmayı amaçladık.
Olguya, kliniğimizde gri skala ve renkli
Doppler US ( RDUS) uygulandı. Gri skala US
incelemede boynun sol yarımında, yüzün sol
kısmı ve anterior servikal bölgeden posterior
servikal bölgeye uzanım gösteren, sol ana
karotid arteri (AKA) anteriora deplase eden,
yaklaşık 90x68 mm boyutlu, yuvarlak şekilli,
heterojen eko yapısında, öncelikle hematom
olarak değerlendirilen kitle izlendi. RDUS
incelemede bu kitlenin içerisinde 29x25 mm
boyutlarında, sol EKA’nın superior tiroid
dalını verdikten sonraki ana gövdesi ile ilişkili
(Şekil 1), ying-yang paterni (Şekil 2) ve EKA
ile arasındaki fistül hattında ileri-geri akım
paterni izlenen (Şekil 3) pseudoanevrizma
olduğu saptandı. Fistül hattı 5 mm uzunlukta
olup çapı 3.2 mm idi. Debisi 190ml/dk olarak
ölçüldü. Ayrıca sol İJV lümenini tamamen
dolduran trombüs saptandı.
OLGU SUNUMU
29 yaşında, yaklaşık 7 yıldır Behçet hastalığı
tanısı ile izlenen, düzensiz kortikosteroid ve
immunosupresyon tedavisi alan erkek hasta,
boynun sol yarımında ani gelişen şişlik
yakınması ile hastanemize başvurdu. Genel
durumu
stabil
olan
olgunun
fizik
muayenesinde boynun sol yarımında boynun
Olgu kendi isteği ile başka bir merkezde
izlenmek istediği için, vasküler değerlendirme
için bilgisayarlı tomografi anjiyografi ya da
digital subtraksiyon anjiyografi incelemesi
yapılamadı.
253
Şekil 1: RDUS incelemede pseudoanevrizmanın ECA ile olan ilişkisi
Şekil 2: RDUS incelemede pseudoanevrizmada ying-yang görünümü
Şekil 3: Spektral incelemede pseudoanevrizma boynunda ileri geri akım paterni
254
kalınlaşma ve fibrozis ile perivasküler
lenfositik infiltrasyon, mediada elastik ve kas
liflerinin kaybı, intimada düz kas ve
fibroblastik hücre artışıdır.
TARTIŞMA
Behçet hastalığı oral ve genital ülserler, deri
ve göz tutulumu ile seyreden sistemik
inflamatuar bir hastalıktır. Behçet hastalığının
patogenezinde genetik ve mikrobiyolojik
ajanlar sorumlu tutulmaktadır. HLA51 varlığı
ana genetik faktör olup Streptococcus sanguis
gibi
enfeksiyon
ajanların
hastalığın
patogenezinde önemli rol oynadığı klinik
çalışmalar ile gösterilmiştir. Behçet hastalığı
%70 oranında oral aftöz lezyonlar ile
başlamakta olup oral mikrobiyal flora
patogenezde rol oynamaktadır. Olgularda oral
streptekok kolonizasyonunda artış ve oral
florada
atipik
sterptekokal
ajanlara
rastlanmıştır. Behçet hastalığının streptekok
enfeksiyonları ile ilişkisi dental tedaviler
sonrası oral ülserlerin oluşması, streptekokal
deri testlerine karşı hipersensivite, streptekok
antijenlerine karşı pro-inflamatuar cevapta
artış ve tedavide anti-bakteriyal ilaçların
yararlı olması ile açıklanmaktadır. Olgularda
kötü ağız hijyeni, multiple çürüklere bağlı diş
çekimleri, oral pH değişiklikleri izlenmekte
olup
bunlar
hastalığın
şiddetini
arttırmaktadır5,6. Behçet olgularında, oral
aftların dental manipulasyonlardan sonra
arttığıda
bilinmektedir7.
Epidemiyolojik
çalışmalar ise, Behçet hastalığı olan
olgularda,
sağlıklı
olgular
ile
karşılaştırıldığında, yüksek oranda tonsilit ve
dental manipulasyon öyküsü varlığını ortaya
koymuştur8,9.
Behçet hastalığında arteriyel oklüzyon,
anevrizma, venöz oklüzyon ve varis olmak
üzere
dört
büyük
vasküler
lezyon
12
bildirilmiştir . Hastalığın bilinen en önemli
vasküler
komplikasyonları
anevrizma
gelişimi, arteriyel oklüzyon ve venöz
trombozdur13.
Oklüzyon
özellikle
alt
ekstremitelerde sık izlenir. Arterlerde
anevrizma oklüzyona göre daha iyi prognoz
gösterir14. Vasküler tutulum oranı %7-29 olup
büyük ven tutulumu %14, arteriyel tutulum
%1.5 dur3. Büyük arter komplikasyonları
genç erkeklerde %2-6 oranında olup sıklık
sırasına göre aort, pulmoner, femoral,
subklavian ve karotid arterlerde meydana
gelir11. Karotid arter pseudoanevrizması nadir
bir komplikasyondur15,16.
Kuzu ve arkadaşları 1200 vakalık geniş bir
seride yaptıkları çalışmada 173(%14.4)
hastada venöz tutulum, 19 (%1.6) hastada
arteriyal tutulum bildirmişlerdir. Aynı
çalışmada, venöz tutulum izlenen olgularda
154(%12.8) venöz tromboz, 17(%1.4)
superior vena kava sendromu, 5(%0.4)
inferior vena kava sendromu, 5(%0.4) varis, 2
üst ekstremite ven trombozu, 1 kavernöz sinüs
trombozu,1 internal juguler ven trombozu ve
1 hepatik ven trombozu saptanmıştır.
Arteriyel tutulum izlenen olguların 7’sinde
femoral, 3’ünde abdominal, 3’ünde popliteal,
2’sinde iliak, 2’sinde pulmoner, 1’inde
aksiller arter anevrizması ve 3’ünde arteriyel
oklüzyon izlendiği belirtilmiştir12. Behçet
olgularında , neredeyse tüm majör damarların
tutulumu rapor edilmekle birlikte, en sık
büyük damar tutulumu izlenmekte olup,
visseral
damar
tutulumu
nadir
17
görülmektedir .
Santral sinir sistemi ve vasküler tutulum ise
hastalığın ileri evrelerinde görülür ve ölüme
yol açabilir. Vasküler tutulum erkeklerde
kadınlara göre daha sıktır ve venöz sistem
daha sıklıkla etkilenmektedir. Arteriyel
tutulum nadir ama Behçet hastalığının ciddi
ve önemli bir komplikasyonudur10. Behçet
hastalığında büyük arter lezyonlarının
nedeninin
media
ve
adventisyadaki
enflamasyon
olduğu
düşünülmektedir.
Arteriyel duvarda vaza vazorumlarda
enflamatuar obliterasyona bağlı akım
kesilmesi
sonucu
perforasyon
ve
pseudoanevrizma
gelişir11.
Behçet
hastalarında anevrizma duvarında saptanan
patolojik
değişiklikler,
adventisyada
Literatürde Behçet hastalığında ekstrakranial
tutulum internal karotid arterde bildirilmiş
olup9,13,14, eksternal karotid arter tutulumu ve
komplikasyonu bildirilmemiştir. Ayrıca diş
çekimi sonrası oral aftöz ülser oluşumu
bildirilmiş olmasına rağmen literatürde büyük
255
damar komplikasyonuna rastlanmamıştır. Bu
olgu ile Behçet hastalarında eksternal karotid
arter tutulumu olabileceği; sadece oral aftöz
ülserlerin değil, ciddi ve önemli büyük arter
ve/veya ven tutulumunun klinik olarak dental
girişimlerden sonra bir komplikasyon olarak
karşımıza gelebileceği akılda tutulmalıdır.
2.
3.
4.
Aoki K, Ohno S. Studies on the constitution and
past history of patients with Behcet’s disease. Acta
Soc Ophthalmol Jpn 1972; 76: 1608-1612.
9.
Mizushima Y, Matsuda T, Hoshi K, Ohno S.
Induction of Behçet’s disease symptoms after
dental treatment and streptococcal antigen skin test.
J Rheumatol 1988; 15:1029-1030.
10. Saba D, Saricaoglu H, Bayram AS, Erdoğan C, et
al. Arterial lesions in Behcet’s disease. Vasa 2003;
32:75-81.
KAYNAKLAR
1.
8.
11. Posacıoglu H, Apaydın AZ, Parildar M, Buket S.
Large pseudoaneurism of the carotid artery in
Behcet’s disease. Tex Heart Inst J 2005; 32:95-98.
Chajek T, Fainaru M. Behcet’s disease. Report of
41 cases and a review of the literature. Medicine
1975; 54:179-182.
12. Kuzu MA, Ozaslan C, Koksoy C, Gurler A,
Tuzuner A. Vascular involvement in Behcet’s
disease: 8-year audit. World J Surgery 1994;
18:948-953.
Venkatasubramaniam KV, Swinehart D. Behcet’s
syndrome: case report and literature review. Henry
Ford Hosp Med J 1981; 29:153-159.
13. Bartlett ST, McCarthy WJ , Palmer AS, et al.
Multiple aneurysms in Behcet’s disease. Arch Surg
1988 ; 123:1004-1008.
James DG, Thomson A. Recognition of the diverse
cardiovascular manifestations in Behcet’s disease.
Am Heart J 1982; 103:457-458.
14. Agrawal S, Jagadeesh R, Aggarwal A, et al.
Aneurysm of the internal carotid artery in a female
patient of Behcet\'s disease: a rare presentation.
Clin Rheumatol 2007; 26:994-995.
Müftüoğlu AU, Yurdakul S, Yazini H, et al.
Vascular involvement in Behcet\'s disease: A
review of 129 cases. In: Lehner T, Barnes CG, eds.
Recent Advances in Behcet\'s Disease. London:
Royal Society of Medicine Services Limited,
1986:1:255-260.
15. Ozyazicioglu A, Kocak H, Vural U. Carotid artery
pseudoaneurysm in Behcet’s disease. Eur J
Cardiothroc Surg 2001; 19:938-939.
5.
Mumcu G, Ergun E, Inanc N, et al. Oral health is
impaired in Behcet’s disease and is associataed
with disease severity. Rheumatology 2004;
43:1028-1033.
16. Suzuki J, Akashi K, Shimada M, Abe S, Kawakami
Y. A case of Behcet’s disease with a rapidly
enlarging aneurysm in the common carotid artery.
Jpn J Med 1991; 30:251-254.
6.
Direskeneli H. Autoimmunity vs autoinflammation
in Behcet’s disease: do we oversimplify a complex
disorder? Rheumatology 2006; 45:1461-1465.
17. Park J, Han M, Bettrnann M. Arterial
manifestations of Behcet disease. AJR 1984;
143:821-825.
7.
The Behcet\'s Disease Research Committee of
Japan. Skin hypersensitivity to streptococcal
antigens and the induction of systemic symptoms
by the antigens in Behcet\'s disease-a multicenter
study. J Rheumatol 1989; 16:506-511.
256

Tam Metin - Marmara Medical Journal

Transkript

Benzer belgeler

PDF ( 49 )

mr grıll kozyatağı franchıseetahsin sönmez - Mr.GRILL

12. Ünite Simple past to be

Cilt 52 Sayı 3 Aralık 2014

Excavations and Restoration Work at Kelenderis in 2008

boğaziçi tıp dergisi

Refik Duru "Hacılar Büyük Höyük 2011 Yılı Kazıları"