May 2010
The Comparison of the Efficacy of Three Different Treatment Protocols on the Type 3 Chronic Prostatitis (Chronic Pelvic Pain Syndrome)
Fikret Erdemir, Fatih Fırat, Doğan Atılgan, Nihat Uluocak, Bekir Süha Parlaktaş, Adem Yaşar
Üroloji Anabilim Dalı, Gaziosmanpaşa Üniversitesi, Tıp Fakültesi, Tokat, Türkiye
DOI: 10.4328/JCAM.10.2.17 Received: 11.10.2009 Accepted: 11.12.2009 Printed: 01.05.2010J.Clin.Anal.Med. 2010;1(2):26-30
Corresponding author: Fatih Fırat, Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Üroloji Anabilim Dalı, 60100, Merkez, Tokat, Türkiye. Phone: 0 5057953112, E-mail: ffrat60@yahoo.com, ffrat60@gmail.com
Aim: In this study, the effect of three different treatment protocols on the type 3 chronic prostatitis was evaluated. In addition to our knowledge, the comparative studies which related CPPS are limited in Turkish literature.
Material and Methods: Between January 2004 and December 2008 a total of 87 male patients with diagnosed of type 3 chronic prostatitis, were evaluated in our clinic. According to treatment protocols patients with type 3 chronic prostatitis, were randomized into three groups as fallows group 1; antibiotic+anti- inflammatory+α-blocker, group 2; α-blocker and group 3; antibiotic+anti- inflammatory. Pretreatment and post treatment results were compared.
Results: The mean age of all patients was 34.14±7.68 years. The mean age of the patients was 34.13±7.39 years, 34.76±7.99 years, and 33.72±8.25 years in group 1, group 2 and group 3, respectively (p>0.05). While the improvement rates after treatment was detected 68% in group 1, these rates were found as 35.3% and 52% in group 2 and group 3, respectively. This difference was statitistically significant in combined group when compared to other groups (p=0.047).
Conclusion: Although alternative treatment researches have still been continue in type 3 chronic prostatitis which consist of 90-95% of all prostatitis. It is seen that combined treatment is beneficial. However, studies in larger, randomized and controlled series are needed to prove the effect of treatment on type 3 chronic prostatitis.
Keywords: Prostatitis, Chronic Pelvic Pain Syndrome, Treatment, Antibiotic, Αlfa-Blocker.
Giriş
Prostatitler patolojik tanım açısından prostat bezinin enflamasyonu olarak bilinse de geleneksel olarak üriner sistem semptomları, enflamasyon, prostat kökenli ağrı ve etiyopatogenezi tam olarak anlaşılamayan klinik tabloyu ifade etmek için kullanılmaktadır [1-3]. Tüm yaş gruplarında %8-14 oranında saptanan prostatitler erkeklerde 50 yaş altında en sık, 50 yaş üzerinde ise benign prostat hiperplazisi (BPH) ve prostat kanseri sonrası üçüncü sıklıkta tanı konulan üriner sistem hastalığıdır. Ürogenital sistem hastalıkları içinde üroloji uzmanlarının hastalarının %8-20’sini oluşturmaları dolayısı ile prostatitler ayrı bir önem taşımaktadır [2,4]. Ulusal Sağlık Enstitüsü tarafından (NIH) 1998 yılından itibaren akut bakteriyel prostatit, kronik bakteriyel prostatit, kronik pelvik ağrı sendromu (tip 3 kronik prostatit) ve asemptomatik enflamatuvar prostatit olmak üzere dört gruba ayrılarak tanımlanan prostatitler içerisinde en sık (%95) kronik pelvik ağrı sendromu (KPAS) olarak bilinen tip 3 kronik prostatit görülmektedir [5].
Tip 3 kronik prostatitli olgularda çeşitli tedavi yaklaşımlarının olduğu bildirilmektedir. Bununla birlikte, olguların yaklaşık %30’unun herhangi bir tedaviden fayda görmediği %30’unda düzelme olduğu ve sadece üçte birinin tedaviden yüksek oranda faydalandığı bilinmektedir [6, 7]. Bir başka önemli konu ise hangi tedavinin daha etkin olduğu konusundadır. Buna göre günümüzde, tip 3 kronik prostatit tedavisinin temelini oluşturan antibiyotikler, alfa blokörler ve antienflamatuvar ilaçlar ile bunların kombine kullanımlarının etkinliklerinin derecesi ve birbirlerine olan üstünlüklerinin tartışmalı olarak kaldığı ve bu konuda özellikle Türkçe yazılan literatürde karşılaştırmalı çalışmaların son derece sınırlı olduğu görülmektedir.
Bu çalışmada, prostatitlerle ilişkili çeşitli yakınmalarla kliniğimize başvuran hastalar arasında tip 3 kronik prostatit tanısı konulan erkek olgularda antibiyotik, antienflamatuvar, alfa blokör ve kombine tedavi kullanımının etkinlikleri değerlendirilmiştir.
Gereç ve Yöntemler
Çalışmaya Ocak 2004 ile Aralık 2008 tarihleri arasında kliniğimize perine, suprapubik ve skrotal ağrı, depolama ve boşaltım gibi işeme şikâyetleri ile başvuran hastalardan yapılan değerlendirmeler sonucu tip 3 kronik prostatit tanısı konulan toplam 87 erkek olgu alındı. Tip 3 kronik prostatit tanısı konulan olgular 3 gruba ayrıldı. Buna göre antibiyotik+antienflamatuvar+alfa blokör kullanan olgular grup 1’i (n=45) oluştururken yalnızca alfa blokör kullanan olgular grup 2’yi (n=17) ve antibiyotik+antienflamatuvar ilaç kullananlarda grup 3’ü (n=25) oluşturdular. Antibiyotik olarak kinolon grubu bir ajan 500 mg 4-6 hafta, alfa blokör olarak terazosin 5 mg 12 hafta, antienflamatuvar olarak ise ibuprofen 400 mg 4 hafta süreyle verildi. Hastalar kliniğimizde, ayrıntılı öykü, fizik muayene, kronik prostatit semptom indeksi (NIH-CPSI), rutin hematolojik ve biyokimyasal tetkikler, idrar akım hızı, ürodinamik inceleme, üriner ultrasonografi, gerekli durumda sistoskopi ve manyetik rezonans inceleme (MRI) ile değerlendirildiler. Çalışmamıza nörolojik hastalığı olanlar, üretra darlığı olanlar, kronik karaciğer, böbrek yetmezliği ve diabetes mellitus gibi kronik sistemik bir hastalığı olan olgular, geçirilmiş pelvik cerrahi öyküsü olanlar, daha önceden psikiyatrik bozukluk tanısı ile antidepresan, antipsikotik ve anksiyolitik ilaç alan olgular ile antikonvülzan gibi kronik ilaç tedavisi alan olgular ve yakın zamanda geçirilmiş üriner trakt infeksiyonu olan olgular dahil edilmedi. Prostatitlerin tanısı için yapılan değerlendirmeye göre; prostat masajı sonrası prostat sekresyonunda belirgin (>10) lökosit bulunması tip 3A olarak kabul edilirken, prostat masajı sonrası prostat sekresyonunda önemsiz sayıda (<10) lökosit bulunması da tip 3B olarak kabul edildi (5). Hastaların tedaviye yanıtları Ulusal Sağlık Enstütüsü Kronik Prostatit Semptom İndeksi (NIH-CPSI)’ne göre değerlendirilmiş olup, NIH- CPSI’de ağrı şikayeti skalası 1 ile 21 arasında, işeme şikayeti skalası 0 ile 10 arasında, semptomların günlük hayata etkisi (yaşam kalitesi) skalası 0 ile 12 arasında puanlanmaktadır. Bu indeks tedaviye yanıtı ve hastalığın progresyonunu değerlendiren uluslar arası bir sorgulama formudur.
Tedavi öncesine göre tedavi sonrası fayda görme durumu sonuçlarının karşılaştırılmasında Ki-Kare testi kullanıldı. P<0.05 değeri istatistiksel olarak anlamlı kabul edildi. İstatistiksel değerlendirme SPSS 14® programı ile yapıldı.
Bulgular
Çalışmaya alınan bütün hastaların yaş ortalaması 34.14±7.68 yıl idi. Hastaların ortalama yaşları grup 1, grup 2 ve grup 3’te sırasıyla 34.13±7.39 yıl, 34.76±7.99 yıl ve 33.72±8.25 yıl olarak saptanırken gruplar arasında bu sonuçlara göre yaş açısından istatistiksel olarak anlamlı fark olmadığı tespit edildi (p>0.05). Ortalama takip süreleri grup 1, grup 2 ve grup 3’te sırasıyla 7.13±2.51 ay, 6.01±1.52 ay ve 6.93±2.12 ay olarak saptandı. Uygulanan tedavilerden fayda görme oranları grup 1’de %68 (n=31) olarak tespit edilirken bu oranlar grup 2 ve grup 3’te sırası ile %35.3 (n=6) ve %52 (n=13) olarak saptandı (Tablo 1). Gruplar arasındaki bu fark üçlü tedavi alan kombine kolda diğerlerine göre istatistiksel olarak daha anlamlı bulundu (p=0.047). Gruplara göre NIH-CPSI indeksi total skoruna bakıldığında tedavi öncesi grup 1, grup 2 ve grup 3’te sırasıyla 23.92±5.3, 24.11±4.2, 23.72±3.2 değerleri elde edilirken tedavi sonrasında bu değerler grup 1, grup 2 ve grup 3’te sırasıyla 12.12±5.9, 18.48±5.1, 14.31±3.9 olarak saptanmıştır. Çalışmaya dahil edilen olguların hiç birinde tedaviyi bırakma durumu olmamıştır. Bununla birlikte yapılan retrospektif incelemede yalnızca alfa
blokör kullanan grupta %5.8 (n=1) oranında retrograd ejakülasyon ve baş dönmesi gibi yan etkiler görülürken, antibiyotik+antienflamatuvar ilaç kullanan grupta %8 (n=2) oranında ejakülasyon bozukluğu ve gastrointestinal sistem ile ilgili yan etkiler görüldü, kombine tedavi verilen grupta ise %8.8 (n=4) oranında gastrointestinal sistem ile ilgili yan etkiler görüldü.
Tartışma
Amerika Birleşik Devletleri’nde her yıl yaklaşık 2 milyon ka- dar hastanın prostatit benzeri yakınmalarla kliniklere baş- vurduğu ve her yıl bu sayıya yaklaşık 267 000 hastanın ek- lendiği bilinmektedir [2, 8]. Bu sayılar prostatit yakınma- sının neredeyse kalp hastalıkları ve diabetes mellitus gibi kronik hastalıklarla benzer prevalans oranlarına sahip ol- duğunu göstermektedir. Bununla ilişkili olarak tüm erkek- lerin %50’sinin hayatlarının bir döneminde prostatit ben- zeri bir atak geçirdiği bildirilmektedir [4]. Erkeklerde üriner sistemde taş hastalıkları ve prostat hastalıkları ile birlikte en sık görülen hastalık grubu olan enfeksiyonlar içinde en sık görülen kronik prostatitlerin ilk tanımlandığı 1815 yılın- dan günümüze kadar yaklaşık 200 yıl geçmesine rağmen nedenleri, uygulanan tedaviler ve etiyopatogenezinin hala tartışmalı olarak kaldığı görülmektedir.
Tüm prostatitlerin %90-95’ini oluşturan tip 3 kronik pros- tatit, tedavi ve etiyopatogenezindeki zorluklar ve belirsiz- likler nedeniyle zor bir grubu oluşturmaktadır [9]. Bu grup- ta sistemik enfeksiyon bulguları ya da tekrarlayan üriner enfeksiyon öyküsü bulunmamaktadır. Ağrı en önemli ya- kınma olup en sık perine ve suprapubik bölgede, ikinci sık- lıkla ise testis, inguinal bölge, penis ve gluteal bölgede tarif edilmektedir. Bu grupta depolama ve boşaltım gibi işeme semptomları azalıp artma eğilimindedir. Hastala- rın hayat kaliteleri ciddi olarak bozulmuştur [10]. Pato- genezde disfonksiyonel yüksek basınçlı işeme [%5-33] ve buna bağlı olarak intraprostatik duktal reflünün oluştuğu ve sonuçta mikroorganizmalar, antijenler, lökosit, sper- matozoa, ürat metabolitleri ve kreatinin aracılığının eşlik ettiği enflamatuvar reaksiyon oluşarak ağrı reseptörleri ile patogenezin başlatılmış olduğu bildirilmektedir [3, 11]. Diğer nedenler detrusor-sfinkter uyumsuzluğu, pelvik ta- ban kaslarında bozukluk, otoimmün mekanizma, nitrik ok- sit, psikolojik nedenler, fosfogliserat kinaz-1 [PGK1] geni, androjen reseptör geni Xq11 ve Xq13, sıcak bölgeler ve gün ışığına fazla maruz kalma ve çok oturma olarak bilin- mektedir [12, 13]. Tip 3 kronik prostatitte mikroorganiz- malar ile ilgili çalışmalarda bakteri elde edilmesinin son derece zor olduğu belirtilmektedir. Özellikle proinflama- tuvar IL-8, TNF ve interferonun artması ile doku onarı- mı ve rejenerasyonunu sağlayan antienflamatuvar sito- kinler olan IL-10 ve IL-1ra’nın azalmasının tanı ve pato- genezden sorumlu olabileceği bildirilmiştir [14, 15]. Araş- tırmacılar üretral sendrom, interstisyel sistit ve tip 3 kro- nik prostatitin benzer klinik bulguları gösterdiğini dolayısı ile etiyoloji ve patogenezlerininde aynı olabileceğini ifade etmektedirler [16]. Tip 3 kronik prostatitte ağrı nedenle- ri doku basıncının yüksek olması, semende ürat kristalle-
ri olması ve Nerve Growth Faktör [NGF] olarak sıralanabi- lir [17,18]. NGF, IL-6, 10, mast hücreleri degranülasyonu, TNF- α, IL1-β, TGF- α ve TGF-β 1 tarafından artırılır. So- nuçta bu artış nörojenik enflamasyon yapar, C fiberleri- ni duyarlı hale getirir ve duyusal nöronlarda substans P ile CGRP [Calcitonin gene related peptide] seviyelerini artırır. Nerve Growth Faktör ayrıca periferdeki NMDA [N-methyl D-aspartate] reseptörleri aracılığı ile santral afferent nö- ronları etkileyip uzun süreli depolarizasyon yapar. Tip 3 kronik prostatit’te inflamasyona ikincil oluşan oksida- tif stres nedeniyle artan PGE2’nin de endorfin seviyeleri- ni azaltarak ağrıya neden olduğu bildirilmektedir [17-19]. Yukarıda görüldüğü gibi etiyolojisi bu kadar kompleks olan tip 3 kronik prostatitin tedaviside oldukça karışık ve komplekstir. Günümüze kadar literatürde tip 3 kro- nik prostatit ile ilgili olarak antibiyotik, alfa-blokör, non- steroid antienflamatuvar ilaçlar [NSAİD], interstisyel sis- tit tedavisinde de kullanılan mukopolisakkarit yapıda olan ve bu özelliği nedeniyle üriner epiteli koruyan pentosan sülfat, immün modülatör ve sitokin inhibitörleri, fitotera- pötik ajanlar, allopurinol, fizik tedavi, perineal ya da pelvik taban masajı ve myofasial tetik noktaların tedavisi, biyo- feedback, nöromodülasyon, akapunktur, çinko, gabapen- tin gibi yaklaşımlarla birlikte, antiandrojenler [20-24] gibi yaklaşımların değişik başarı oranları ile bildirildiği görül- se de bu tedaviler içinde Avrupa Üroloji Derneği [EAU] kı- lavuzlarında sadece alfa blokörler, antibiyotikler ve anti- enflamatuvarların kullanımının öne çıktığı bilinmektedir [25]. Antibiyotik tedavisinin özellikle tip 1 ve tip 2 pros- tatitte ilk tedavi yaklaşımı olduğu iyi bilinirken, tip 3 kro- nik prostatitte de kullanımı halen sorgulanmasına rağmen bu grup hastalarda yerinin olduğunu bildiren çalışmalar bulunmaktadır. Antibiyotik tedavisi özellikle tip 3A’da dü- şünülmekte ve etkinliği %40 olarak bildirilmektedir. An- tibiyotikler tip 3 kronik prostatitte plasebo etkileri, kül- türü yapılamayan mikroorganizmaların eradikasyonu ya da supresyonu ile antienflamatuvar etkilerine dayanıla- rak toplam 4-6 hafta verilmektedir. Çalışmalarda tip 2, tip 3A ve tip 3B’de kültür, lökosit sayısı ve antikor düzey- lerinin antibiyotik etkinliği ile korele olmadığı bildirilmek- tedir [26, 27]. Bununla ilgili olarak, Nickel ve arkadaşları tarafından 102 hasta ile yapılan bir çalışmada, kültür, lö- kosit sayısı ve antikor düzeylerinin antibiyotik etkinliği ile korele olmadığını fakat NIH kronik prostatit semptom in- deksinde, semptom şiddet indeksinde, semptom sıklık in- deksinde ve yaşam kalitesi skorunda önceki durumla kar- şılaştırıldığında önemli oranda gelişme olduğu gösteril- miştir [28]. Wagenlehner ve arkadaşları tarafından yapı- lan bir çalışmada tip 3A kronik prostatitte antibiyotiklerin başlangıçta denenebileceği ve gerekirse devam edilebile- ceği bildirilirken tip 3B’de ise antibiyotik kullanımının yeri- nin olmadığı bildirilmiştir. Yine Nickel ve arkadaşları tara- fından tip 3 kronik prostatitli 80 hasta ile yapılan bir ça- lışmada 45 hastaya sadece levofloksasin, 35 hastaya ise plasebo verilmiş olup levofloksasin verilen grupta semp- tomlarda düzelme gözlenirken plaseboya göre önemli bir
fark bulunmadığı bildirilmiştir [29]. Çalışmamızda da an- tibiyotik verilen grupta tek başına alfa blokör verilen gru- ba göre semptomlarda düzelme oranının daha fazla oldu- ğu görülmektedir. Tip 3 kronik prostatitte alfa blokörlerin etkinliği ise %33-57 arasında olup en az 12-14 haftalık tedavi verilmesi önerilmektedir [30-34]. Bu grup ilaçların özellikle tip 3B’de etkin olduğu bildirilmektedir. Prostatik epitelin ve mesane boynunun alfa adrenerjik reseptörler- den zengin olduğu bilinmektedir. Alfa blokörlerin verilme- si ile çıkım obstrüksiyonunun düzelebileceği, idrar akımı- nın kolaylaşacağı ve dolayısı ile reflü oluşmayacağı düşü- nülebilir. Yine prostatit patofizyolojisinde sempatik aktivi- tenin artışının olduğu göz önüne alındığında alfa blokörle- rin etkili olacağı düşünülmelidir. Ayrıca bu tedavinin ağrı patolojisine indirekt ya da spinal korddaki α-1A ve α-1D adrenerjik reseptörleri antagonize ederek ağrıdan sorum- lu Substans P’yi inhibe edip direk etki edeceği bildirilmek- tedir [35]. Öte yandan Cheah ve arkadaşları tarafından alfa blokör [terazosin] verilerek yapılan bir çalışmada alfa blokörlerin idrar akım hızını değiştirmeden üriner semp- tomlarda düzelme sağladığı bildirilmiştir [36]. Yine ben- zer şekilde, Yang ve arkadaşları tarafından yapılan 734 hastanın değerlendirildiği 9 çalışmayı içeren bir metaa- nalizde alfa adrenerjik blokörlerin tip 3 kronik prostatit ve kronik bakteriyel prostatitte kullanımının NIH-CPSI ya da IPSS skorunda önemli oranda düzelme sağladığı, üri- ner semptomların azalmasında faydalı olduğu bildirilmiş- tir [37]. Bizim çalışmamızda ise tek başına alfa blokör ve- rilen grupta benzer şekilde üriner semptomlarda düzelme sağlandığı görülmektedir. Diğer tedavilerle kombine ola- rak NSAİ ve steroidler verilmesi özellikle dizüri, idrar ya- parken zorlanma ve ağrılı ejakülasyonu azaltabilmektedir. Antienflamatuvar ilaçların kronik prostatitteki enflamatu- var parametreleri iyileştirdiği ve semptomlarda düzelme- ye yol açabileceği düşünülebilir. Canale ve arkadaşları ta- rafından yapılan bir çalışmada nimesulidin tip 3A’daki di- züri, işeme zorluğu ve ağrılı ejakülasyonu azalttığı bildiril- mektedir [38]. Bizim çalışmamızda ise hastalara en az 4 hafta boyunca ibuprofen ve siprofloksasin 500 mg veril- miştir ve sadece alfa blokör alan gruba göre semptomlar- da düzelme oranın yüksek olduğu ortaya konulmuştur. Ge- nellikle florokinolonları tercih etmemizin sebebi bakteri- yel spektrumunun geniş olması ve prostat kompartman- larına en iyi şekilde penetrasyon göstermesinden kaynak- lanmaktadır [39].
Son yıllarda tek başına antibiyotik, tek başına alfa blo- kör ya da tek başına antienflamatuvar tedavi yaklaşımı yerine etiyopatogenezdeki kompleks yapıdan hareket- le kombine tedavi verilmesinin daha etkili olabileceği dü- şünülerek çok sayıda araştırma yapılıp sonuçları bildiril- miştir. Bu çalışmaların bir kısmında verilen kombine te- davinin monoterapiye göre etkin olmadığı belirtilmekte- dir. Bununla ilgili olarak Alexander ve arkadaşları tarafın- dan tip 3B prostatit tanısı olan 196 hasta ile yapılan bir çalışmada hastalar 4 gruba ayrılarak incelenmişler. Çalış- mada, grup 1; siprofloksasin, grup 2; tamsulosin, grup 3;
siprofloksasin + tamsulosin ve grup 4 ise plasebo grup- ları olarak ayrılmış olup hastaların gruplara göre cevap oranları sırasıyla %22, %24, %10 ve %22 olarak saptan- mıştır. Gruplara göre tedavi sonuçları karşılaştırıldığın- da NIH-CPSI total skorunda ve ağrı skorunda başlangıca göre önemli derecede düşme saptanırken gruplar arasın- da benzer oranların olduğu görülmektedir [40]. Ülkemiz- den bir çalışmada ise Tuğcu ve arkadaşları tarafından tip 3B prostatit tanısı olan 90 hasta 3 gruba ayrılarak ince- lenmiştir. Çalışmada, grup 1; alfabloker, grup 2; alfablo- ker, antienflamatuvar, kas gevşetici ve grup 3 ise plase- bo grupları olarak ayrılmış olup alfabloker kullanan grup ve kombine grup, plasebo verilen grupla karşılaştırıldığın- da, NIH-CPSI total skorunda ve ağrı skorunda başlangı- ca göre önemli derecede düşme saptanırken üçlü tedavi- nin alfa bloker tedaviye üstünlük sağlamadığı bildirilmiş- tir [41]. Yukarıdaki çalışmaların aksine Ye ve arkadaşları tarafından tip 3A ve tip 3B prostatit tanısı olan 105 has- ta ile yapılan bir başka çalışmada ise hastalar 21’er kişi- lik 5 gruba ayrılmıştır. Bu çalışmada grup 1 tip 3A prosta- titi olan ve sadece tamsulosin verilen grup, grup 2, tip 3A prostatiti olan ve tamsulosin+levofloksasin verilen grup, grup 3, tip 3A prostatiti olan ve sadece levofloksasin ve- rilen grup, grup 4 tip 3B prostatiti olan ve sadece tam- sulosin verilen grup ve grup 5 ise tip 3B prostatiti olan ve tamsulosin+levofloksasin verilen grup olarak sınıflan- mış olup kombinasyon tedavisi verilenlerde, monoterapi alanlara göre daha olumlu sonuçların alındığı ve bu et- kinin tamsulosin ve levofloksasinin bakteriyel olmayan prostatit tedavisinde sinerjistik etkisinden kaynaklanabi- leceği bildirilmektedir [42]. Yine ülkemizden istanbulluoğ- lu ve arkadaşları tarafından yapılan bir çalışmada has- talar; plasebo grubu, antibiyotik + antienflamatuvar alan grup ve antibiyotik + alfa-bloker alan gruplar olmak üze- re üç gruba ayrılmışlardır ve antibiyotik ile kombine edi- len alfa-bloker ve antienflamatuvar tedavilerinin etkili ol- duğunu ancak alfa-bloker ve antibiyotik birlikteliğinin di- ğer tedavilere göre daha da etkili olduğu sonucuna va- rıldığını bildirmişlerdir [43]. Bizim çalışmamızda da üçlü kombine tedavi alan grupta diğerlerine göre istatistiksel olarak anlamlı olacak şekilde semptom şiddetinde azalma olduğu gösterilmiştir. Benzer şekilde, Woong ve arkadaş- larının tip 3 kronik prostatit tanısı olan 69 hasta ile yapı- lan bir çalışmada hastalar iki gruba ayrılarak grup 1’e sa- dece gatifloksasin (n=35), grup 2’ye gatifloksasin ve dok- sazosin (n=34) tedavileri verilerek sonuçlarına bakıldığın- da grup 2’de grup 1’e göre ağrı skorunda, işeme semptom skorunda ve yaşam kalitesinde önemli derecede düzel- me olduğu, kombine tedavinin tek başına verilenlere göre daha üstün olduğu gösterilmiştir [44].
Sonuç olarak tüm prostatitlerin %90-95’ini oluşturan ve etiyopatogenezi oldukça kompleks olup hem hekim hem de hasta için zor bir grubu oluşturan tip 3 kronik prosta- titte alternatif tedavi arayışları hala sürmesine rağmen kombine tedavinin prostatit semptomlarını düzeltmede daha yararlı olduğu görülmektedir. Bununla birlikte bu durumla ilgili çok sayıda karşıt çalışma olduğu bildirilmekte olup bu konuda daha net ifadelerin söylenebilmesi için geniş olgu sayısına sahip kanıt düzeyi yüksek randomize kontrollü çalışmalarla metaanalizlere ihtiyaç bulunduğu söylenebilir.
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The Ligament of Head of Femur and Its Arteries
Yalçın Kırıcı 1, Cenk Kılıç 1, Emin Öztaş 2
1 Departments of Anatomy, 2 Histology-Embryology, Gulhane Military Medical Academy, Ankara, Turkey
DOI: 10.4328/JCAM.10.2.16 Received: 11.10.2009 Accepted: 04.01.2010 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2): 22-25
Corresponding author: Cenk Kılıç, Gulhane Military Medical Academy Faculty of Medicine, Department of Anatomy, 06018, Ankara, Turkey. Phone: +90 312 304 35 08 Fax: +90 312 381 06 02 E-mail: ckilicmd@yahoo.com
Aim: The artery supply to head of femur and running along with the ligament of head of femur (ligamentum capitis femoris) is important for the clinician in preventing aseptic avascular necrosis disease. The purpose of this study was to investigate the course and number of the artery and the anatomic and histologic structures of the ligament.
Material and Methods: The study was conducted on 26 ligaments of head of femur taken from 13 cadavers (8 males, 5 females). Shape and length of the ligament were examined. Then, it was investigated under light microscope.
Results: The ligament was found in all cases. Although, the study was conducted on elderly cadavers, all ligaments included dense collagen fibers and several arteries. These arteries were thick. On histological evaluation, outer surfaces of all ligaments were included dense collagen fibers and synovial membrane.
Conclusion: The arteries did not run into the ligament. Furthermore, they ran into superoanterior region of the ligament. Thus, we thought that the ligament was not injured at the adduction movement and blood stream was not interrupted.
Keywords: Head of Femur, Ligamentum Capitis Femoris, Foveolar Artery.
Introduction
Acetabular branch of the obturator artery supplies to head of femur. This artery running along with the ligamentum capitis femoris is important for the clinician. Thus, we aimed to investigate the course and number of the artery. In addition, the anatomic and histologic structures of the ligament were characterized.
The ligamentum capitis femoris is an intracapsular ligament approximately 3.5 cm long. It is weak and appears to be of little importance in strengthening the hip joint [1]. It is a triangular flat band and its apex is attached in the pit on head of femur. Its base is principally attached on both sides of the acetabular notch, and blenders with the transverse ligament [2].
It varies in strength; occasionally its synovial sheath alone exists, without a core, rarely both ligament and sheath are absent [2]. The contribution coming from the artery of the ligamentum capitis femoris may be negligible or absent in some cases [3]. The ligamentum capitis femoris is located inside of the hip joint and is surrounded by a sleeve of synovial membrane [1].
Even though Catterall [4] reported that the arteries running along with the ligament supplied head of femur at preadolescent stage, Trueta and Harrison [3] demonstrated that epiphyseal and metaphyseal circulations were present in advanced years. Epiphysial and metaphysial arteries supply to head of femur. The epiphysis and the metaphysis usually receive blood from separate sources. The lateral epiphysial and both groups of metaphysial arteries usually arise from the medial femoral circumflex artery; the medial epiphysial artery is a continuation of the artery within the ligamentum capitis femoris which comes from the acetabular branch of the obturator artery [3].
According to Trueta [5] the foveolar artery (in the blood supply of head of femur) does not penetrate head of femur until the age of eight or nine.
The blood supply to the capital femoral epiphysis is interrupted. Bone infarction occurs, especially in the subchondral cortical bone, while articular cartilage continues to grow. Articular cartilage grows because its nutrients come from the synovial fluid [6].
The subsynovial layer consists of dense connective tissue containing numerous large cells. The major central portion of the ligament is formed by dense regular connective tissue. The blood vessels of the ligament are always surrounded by a layer of loose connective tissue. Adipose tissue firstly starts to spread in the postnatal period mainly occurring around the vessels. In the newborn child dense connective tissue is most abundant within the ligamentum capitis femoris. Thus it is considered to be especially strong. The artery of ligamentum capitis femoris is already present in 9 week- old fetuses. In 13 week-old fetuses, branches of the artery enter head of femur through cartilaginous channels and continuously maintain within head of femur during further development. With the growing age of the fetuses the number of branches of the artery increases. Anastomoses between the cartilaginous channels of this artery and the medial and lateral circumflexal femoral artery can be found neither prenatally nor postnatally [6].
Material and Methods
The ligamentum capitis femoris was studied in 13 subjects (8 males and 5 females) in Department of Anatomy, Faculty of Medicine, Gulhane Military Medical Academy, aged from 64 to 83 years by macroscopic and microscopic methods over a two-year period. Permission for cadavers had been obtained from the local ethics committee of Ankara Maternity and Health Academic and Research Hospital (Ref. No:5/16.10.03). Teratologic and secondary hip dislocations (4 subjects) were not included in this study. All muscles covering hip joints in all lower extremities were dissected. The ligaments, fatty tissue filling acetabular notch and acetabular fossa, and synovial membrane covering fatty tissue were removed. Then, the length of the ligamentum capitis femoris was measured in each specimen using a 0.1 mm sensitive caliper and the shape of the ligament was noted. The arterioles were examined under a stereomicroscope (Stemi 2000; Carl Zeiss, Jena, Germany). Their anatomic peculiarities were described, photographed and illustrated.
After photographical documentation, ligaments were removed and immediately immersed in a buffered 10% formalin solution. Each ligament from all cadavers was cut into 4 pieces. Four specimens were embedded in paraffin blocks. Tissues were then sectioned at 5 micron and stained with hematoxylin-eosin (H&E) and Masson’s trichrome stain to assess the light microscopic structure. Vessels and fiber structures were evaluated by their morphologic appearance. Histologic studies showed differences in the amount of organized collagen and components of subsynovial tissue.
Results
The ligament was shown to be variable in length, diameter and shape. We measured that length of the ligament was 1.5-3.5 cm (mean 2.55 cm). We found that this length was 3.5 cm in only one case and the length was 1.5 cm another case. The length of the ligamentum capitis femoris was mostly 2.5-3.0 cm. We found that the twenty ligaments were thick. Shapes of 17 of the 26 ligaments (65.4%) were rectangular and shapes of remaining 9 ligaments (34.6%) were triangular. Shape of the ligament was different between left and right sides in three cadavers (Figure 1).
There was not any variation in this ligament related to its attachment point. The ligament and synovial sheath were present in all cadavers on each side. We showed that the vessels ran in hilar region (superoanterior) (Figure 2). Connective tissue of collagen fibers of the ligament was separated to septums.
Number of vessels was 3-4 semi-quantitatively. Vessels did not run into the ligament. Arterioles located in the superior and inferior region of the ligament ran under the synovial membrane (Figure 3).
Vessels forming capillaries ran in septums between collagen fibers of the ligament (Figure 4). High amount of fatty tissue and several arteries and arterioles were present in acetabular fossa and acetabular notch.
Discussion
This study contributed to the knowledge regarding dense collagen fibers of the ligament, existence of synovial membrane covering it, its shape and artery running along with it.
The ligament was present in both sides of all cadavers. Rarely both ligament and sheath were absent [2]. Tan and Wong [7] reported that ligamentum capitis femoris was absent in 4 of the cadavers. In 3 of them, the ligament was absent unilaterally.
It was reported that length of this ligament was about 3.5 cm [1]. We found that this length was to be mean 2.5- 3.0 cm with only one exceptional case of 3.5 cm. Although it was reported that shape of this ligament was triangular [2]. We found that rate of rectangular shape was 65.4%. Shape of the ligament was different between left and right sides in three cadavers.
It was reported that this ligament appears to be of limited value in strengthening the hip joint [1]. Fritsch and Hegeman [6] reported that this ligament included plenty and dense collagen fibers. Tan and Wong [7] found that the ligament was strong in 26 of the 36 cadavers, weak in 9 and was torn in one. In our study, all ligaments included dense collagen fibers suggesting that all ligaments observed were strong.
Synovial membrane covering this ligament was present in all cadavers. It varies in strength; occasionally its synovial sheath alone exists, without a core, rarely both ligament and sheath are absent [2].
Tan and Wong [7] suggested that although the ligament transmits an artery to head of femur in the young, it does not appear to have any important mechanismed function in maintaining the stability of the hip joint. Arteries and arterioles ran between synovial membrane and the ligament, rather they ran into the ligament.Whereas Crelin [8] found the ligamentum capitis femoris to be very important in stabilizing the hip joint in fetuses and neonates. This ligament must play a role in fetal and neonatal hip joint stability [1].
The artery to head of femur is a branch of the posterior division of the obturator artery [1]. Chung [10] saw the artery of the ligamentum capitis femoris in 113 of 123 specimens, and there was no artery in 10 specimens (78 specimens the
artery only in the ligament, 20 specimens provided 1 deep vessel to the center of the head, 15 specimens 2 or more vessels to center of the head). We found that 3-4 arteries and arterioles underlying synovial membrane were present in all cadavers. One hundred and thirty-four stillborn specimens were arterially injected with latex and dissected to determine the origin of the foveolar artery. The obturator artery supplied this branch in 54.5% and the medial femoral circumflex artery in 14.9%. Separate foveolar branches arose from both these vessels in 6.7%, while in the remaining 23.9% an anastomotic connection between the obturator and medial femoral circumflex gave origin to the foveolar artery [11]. Arteries supplied head of femur are sourced from different arteries, and its anastomosis is important in preventing aseptic avascular necrosis disease.
Fritsch and Hegeman [1] reported that vessels of the ligament are surrounded to loose collagen fibers, which is in conformity with our study.
Although Trueta [5] reported that this ligament was not penetrated to head of femur until 8-9 year, Fritsch and Hegeman [6] reported that artery of this ligament was present at ninth week and this artery ran into head of femur at thirteenth week. We found that plenty arteries and arterioles running along with the ligament were present and these arteries ran into head of femur. It was reported that number of arteries running into the ligament is increased while fetus growth [6] and the artery was present at elderly ages [3].
There is a temporary interruption in the blood supply to the epiphyseal, physeal, and sometimes metaphyseal portion of the femur of the hip joint [4].
In venograms obtained in the early stage, Iwasaki [12] found several abnormalities in the morphology and course of the vein. It appeared that the blood vessels within
Ligamentum Capitis Femoris / The Ligament of Head of Femur
the ligamentum capitis femoris play a compensatory role in reestablishing blood flow to the head. In order to examine the significance of the blood flow through the ligamentum capitis femoris in Perthes’ disease, intraosseous venography was performed on 81 hips [12]. Atsumi et al. [13] concluded that normal vascular anatomy of the artery of the ligamentum capitis femoris was not related to the onset of Perthes’ disease. Fractures of the femoral neck close to the head often disturb the blood supply to the head. In some cases the blood supplied via the artery in the ligament of the head may be the only blood received by the proximal fragment of the head.
We found that the ligament and synovial membrane covering it were present in all cases. The arteries and arterioles running along with the ligament were present in between synovial membrane and the ligament. Arteries did not run into the ligament, further they ran into superoanterior region of the ligament. Thus, we thought that the ligament was not injured at the adduction movement and blood stream was not interrupted. Fractures of the femoral neck rapidly undergo aseptic avascular necrosis. Therefore, the patients should be operated at most within 12 hours. The arteries supplying head of femur is present and is functional even at elderly ages. We maintain that this condition prevents from aseptic avascular necrosis. The structure of the ligament and courses of arteries supplying head of femur are important. For this reason resources and courses of these arteries should be identified by arteriography priorty, and the patient should be informed about this condition. We think that additional studies are necessary in order to understand the blood supply to the head in the hip joint. The results confirmed the crucial role of radiography in the clinical evaluation.
References
1. Moore KL. Clinically Oriented Anatomy. Baltimore: Williams and Wilkins; 1992. p. 475-77.
2. Williams PL, Bannister LH, Berry MM, Collins P, Dyson M, Dessek JE, Ferguson MWJ, editors. Gray’s anatomy. New York: Churchill Livingstone; 1995. p. 681, 685, 1560.
3. Trueta J, Harrison MH. The normal vascular anatomy of the femoral head in adult man. J Bone Joint Surg Br. 1953;35:442-61.
4. Catterall A. Legg-Calve-Perthes’ Disease. New York: Churchill- Livingstone; 1982. p. 3-33.
5. Trueta J. The normal vascular anatomy of the femoral head in adult man. Clin Orthop Relat Res. 1997;334:6-14.
6. Fritsch H, Hegemann L. Development of the ligamentum capitis femoris and the artery with the same name. Z Orthop Ihre Grenzgeb. 1991;129:447-52.
7. Tan CK, Wong WC. Absence of the ligament of head of femur in the human hip joint. Singapore Med J. 1990;31:360-3.
8. Crelin ES. An experimental study of hip stability in human newborn cadavers. Yale J Biol Med. 1976;49:109-21.
9. Walker JM. Growth characteristics of the fetal ligament of the head of femur: significance in congenital hip disease. Yale J Biol Med. 1980;53:307- 16.
10. Chung SM. The arterial supply of the developing proximal end of the human femur. J Bone Joint Surg Am. 1976;58:961-70.
11. Weathersby HT. The origin of the artery of the ligamentum teres femoris. J Bone Joint Surg Am. 1959;41:261-3.
12. Iwasaki K. The role of blood vessels within the ligamentum teres in Perthes’ disease. Clin Orthop Relat Res. 1981;159:248-56.
13. Atsumi T, Yoshihara S, Hiranuma Y. Revascularization of the artery of the ligamentum teres in Perthes disease. Clin Orthop Relat Res. 2001;386:210-7.
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Invitro Effects of our Spring Water on the Solubility of Uric Acid Stones: a Pilot Study
Mustafa Burak Hoşcan 1, Cem Dilmen 2, Mehmet Ekinci 1, Taylan Oksay 2, Sıtkı Orak 3, Selahattin Bedir 4, Tekin Ahmet Serel 2
1 Department of Urology, Başkent University, School of Medicine, Alanya,Antalya, 2 Department of Urology, Süleyman Demirel University, School of Medicine, Isparta, 3 Burdur Medical High School, Isparta, 4 Department of Urology, Gülhane Military Medical Academy, Ankara, Turkey
DOI: 10.4328/JCAM.10.2.14 Received: 23.09.2009 Accepted: 18.11.2009 Printed: 01.05.2010J.Clin.Anal.Med. 2010;1(2): 15-17
Corresponding author: Mustafa Burak Hoşcan, Başkent University Alanya Research and Practice Hospital 07400 Alanya, Antalya, Turkey. GSM: +905324364855 Fax: +90 242 5112350 E-mail: drburakhoscan@yahoo.com
Aim: The aim of this study was to evaluate the influence of our spring water on urinary analytes and stone samples in (patient with) uric acid stone.
Material and Methods: Twenty patients with uric acid stones underwent a nutritional and metabolic evaluation at baseline and after a controlled diet including our spring water. Stone samples were also left in the usual water and in the spring water. The weights of stones were measured before and 7 days after incubation.
Results: In patients who drank spring water, there was a tendency for the mean urine pH to increase, the change was significant statistically. On the other hand, urine citrate excretion significantly also increased in these patients (p<0.005). The differences between initial and end-dry weights of stone examples were significant statistically (p<0.05).
Conclusion: The results of our pilot study may help us to reduce uric acid stone formation and recurrence with the alkaline spring waters.
Keywords: Uric Acid Stone, Solubility of Stones, Spring Water.
Introduction
Urolithiasis is still a disease with a high morbidity, the annual percent frequency increasing with the improvement in socioeconomic indices in the various countries through-out the world. In western society, due to the high standard of living, the incidence of urinary stones is progressively increasing. With the introduction of extracorporeal shock wave lithotripsy, the approach to the treatment of urolithiasis has changed. However, this treatment of choice because of safety and efficacy, we are still faced with the problem of possible recurrence. The solubility of uric acid stones has been studied in water solutions containing ammonium ions, alkaline ions and alkaline earth metals [1]. Oligomineral and spring waters were based upon historical studies which have shown its effect upon renal metabolism and the physiology of the urinary tract [2, 3]; diuretic effect, elimination in the same period of time of a larger amount of water and solutes than with usual water, effect upon the supersaturation of solutes, and effect upon crystallization inhibitors.
From the indications emerging from the studies [4 ,5], and considering that the risk of recurrence appeared to be correlated to the urinary dissoluble urate levels not only in patients presenting with the first episode of urolithiasis, but also in those who had experienced several episodes of recurrence, we attempted, in the present investigation, to evaluated whether urinary uric acid stones might be susceptible to statistically significant variations following in vitro treatment with our local a spring water.
Material and Methods
20 idiopathic uric acid formers were enrolled in this study. 15 men a mean 49.7±10.4 years old with a mean body mass index 25.4±3.1 and 5 women a mean 48.3±11.5 years old with a mean body mass index 26.2±4.3 participated in the study. No patients had a history of a pathological condition, such as gout disease, hyperuricaemia or urinary tract infection. All patients had normal renal function. The standard protocol of this study included physical examination, a nutritional investigation, including a detailed 3-day food record and an interview by a dietician to determine customary dietary habits, and a metabolic evaluation [6]. The metabolic study was performed, and dietary records and interviews were obtained while patients adhered to their original diet as well as after 20-day periods of controlled diet during which they were asked to drink 2 L of spring water. The controlled diet provided a normal daily intake of calories, 1 g/kg protein. The diet was prepared by the dietetics serviced in our hospital. Patients were assigned to a random sequence of home diet with the usual amount and type of water ingested at home, and controlled diets with 2 L of spring water. Metabolic studies included measurement of plasma and urine creatinine, uric acid, sodium, potassium, chloride, calcium, phosphate and magnesium. The excretion of citrate was also determined in urine as well as pH and volume. Patients collected urine for 24h on 2 consecutive days. Crystalluria study was performed on a sample of fasting morning urine in all cases. Citrate was evaluated by enzymatic methods using commercially available kits. The stone samples (17 surgically removed, 3 spontaneously passed away) were pounded with pestle on a porcelain mortar in order to determine its chemical compositions. The stone samples were treated with the spring water and usual water (FS: 26, pH: 6.5). Concentration of components in the spring and usual water are given in Table 1. The stone examples were placed into bottles containing 100 millilitres of water and kept in room temperature for one week. They were mixed manually 3-4 for times a day and the initial and end-dry weights of the stones were calculated.
The statistical analysis was calculated by using student’s t test.
Results
During the study period patient clinical characteristics, including weight, body index and age, did not differ significantly from those at baseline. The results of analytes in the plasma and urine evaluated at baseline and after the period of controlled diet showed no significant differences between the two groups. When patients drank the spring water, there were no statistically significant differences in plasma analyte values. More modifications of some urinary parameters were observed when they drank spring water. There was a tendency for the mean urine pH to increase after the ingestion of the spring water the change was significant statistically. In fact, citrate excretion increased after ingesting the spring water (statistically significant, Table 2).
The distribution of initial and end-dry weights of urate stone examples in usual water and the spring water are shown in Figure 1. According to these results, statistically significant differences were observed between initial and end-dry weights of stone examples (p<0.05).
Discussion
In current medical practice urinary stone formers are usually advised to drink a large amount of water whether or not medical treatment is given. The various types of spring water can be advised to the patients with urolithiasis [7, 8]. Their therapeutic efficacy is attributed, fundamentally, to the important diuretic effect, the litholytic effect, the modification in urinary pH and to the effect upon ureteric contractility [19, 10]. Of the various spring water available in our region, the choice of our spring water which contains bicarbonate, sodium, chloride and sulphur has been examined for possible effects on reducing recurrence of uric acid stone. It has been shown that the solubility of uric acid stones depends on the concentration of alkaline ions [11].
The results of this study show the influence of our spring water on some urinary factors for stone formation independent of the diluting effect of increased water intake. In fact, in our patients the urinary volume throughout the study period remained similar to high baseline values. Citrate excretion was increased during the initial controlled diet period, when patients drank the spring water. To avoid the possible influence of different dietary regimens, patients remained on a controlled diet during the study. In our series the spring water which has particularly rich in bicarbonate caused significantly increased urinary citrate excretion compared with baseline. This increase in citrate excretion may be modulated by gastrointestinal alkali absorption. Thus, evaluation of net gastrointestinal absorption of alkali may useful for this conclusion. On the other hand, after drinking the water, the urine seemed to be more alkaline, which was significant statistically. In addition to this, the solubility of the stone examples increased when the examples were treated with spring water significantly. These observations indicate that the spring waters rich in alkaline ions may increase the urinary excretion of citrate increasing the inhibitory power of urine against the risk of uric acide stone formation and even also decrease stone recurrence.
In conclusion, the results of our study help us to reduce uric acid stone formation and recurrence with the alkaline spring waters. However, this pilot study may stimulate other studies in a fairly large group of patients with uric acid urolithiasis to establish a true correlation between possible risk factors and recurrence.
References
1. Bilobrov VM, Bogdan NM, Bilobrov S, Roy A. Influence of cations and total protein of urine on the solubility and probability of urate stone formation in kidneys. Urol Int 2002;68:118-21.
2. Messina B. Fisiopatologia del rene e cure idropiniche. Clin Ter 1970;23:11-25.
3. Messina M. Ricerche sulle acque oligo- minerali di Fiuggi 1968-1976. Rome, Ente Fiuggi,1977.
4. Di Silverio F, D’Angelo AR, Gallucci M, Casanelli A, Lorenzi L, Seccareccia F, Menotti A. Incidence and prediction of stone recurrence after lithotripsy in idiopathic calcium stone patients:A multivariate approach. Eur Urol 1996;29:41-6.
5. Di Silverio F, Ricciuti GP, D’Angelo AR, Fraioli A, Simeoni G. Stone recurrence after lithotripsy in patients with recur- rent idiopathic calcium urolithiasis: Ef- ficacy of treatment with Fiuggi water. Eur Urol 2000;37:145-8.
6. Caudarella R, Rizzoli E, Bufa A, Bottura A, Stefoni S. Comparative study of the influence of 3 types of mineral water in patients with idipathic calcium lithi- asis. Journal of Urol 1998;159:658-63.
7. Pytel’ IuA, Aliaev IuG, Rapoport LM, Ru- denko VL. Mineral water Volzhanka from Undorovski spring in combined therapy of patients with nephrolithi- asis and chronic pyelonephritis. Urologia 1999;5:12-4.
8. Trinchieri A, Boccafoschi C, Chisena S, De Angelis M, Seveso M. Study of the diuretic efficacy and tolreability of therapy with Rocchetta mineral water in patients with reccurent calcium kidney stones. Arch Ital Urol Androl 1999;71:121-4.
9. Di Silverio F, Zaio A, Gallucci G. Trea- pia idropinica con acqua di Fiuggi nella calcolosi renale metabolica. Act Med Roma 1991;1:53-73.
10. Spada S, Cordelli A, Grassi M. Modifi- cazioni del tempo di transito attraverso l’uretere di pseudocalcoli in conigli trat- tati con un’acqua oligominerale. Clin Ter 1968;21:559-65.
11. Bilobrov VM, Fedotova OO. Uric acid stones dissolution in water solutions. Dokl An UkrSSR 1990;B5:60-1.
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Comparative Evaluation of Microleakage for Different Root Canal Sealers and Irrigation Solutions
Tülin Ertan 1, Yaşar Meriç Tunca 2
1 Department of Endodontics, Turkish Naval Headquarters Infirmary, 2 Department of Endodontics, Gulhane Military Medical Academy Dental Science Center, Ankara, Turkey
DOI: 10.4328/JCAM.10.2.13 Received: 08.09.2009 Accepted: 22.11.2009 Printed: 01.05.2010J.Clin.Anal.Med. 2010;1(2): 9-14
Corresponding author: Tülin Ertan, Department of Endodontics, Turkish Naval Headquarters Infirmary, Ankara, Turkey. Phone: +090 312 4032411 E-mail: tedelibas@gmail.com
Aim: The aim of the study was to examine the sealing ability of a root-canal sealer using different endodontic irrigants and to measure the microleakage using a fluid transport model.
Material and Methods: 170 maxillary and mandibular anterior human teeth with single bilnded were selected for this study. The root canals were instrumented using the crown-down technique with HERO- Shaper and were irrigated with 5.25 % NaOCl. The smear layer was removed by washing in 10 ml of 17% EDTA. The specimens randomly divided into 16 groups (root-canal sealings; Sealite- Ultra, Diaket, AH-Plus, Ketac-Endo and irrigation solutions; NaOCl, 2 % CHX, 1% CHX gel+NaOCl, 1% CHX gel+SS ) of ten teeth and two control groups of five teeth and obturated by lateral condensation. In order to measure the microleakage, a fluid transport model was used and leakage value for each group was calculated and recorded. Four specimens from each group were used for SEM examinations (scanning electron microscopy).
Results: The best results are taken when Ketac-Endo with 2% CHX solution used. The results proved that there is no significant difference between root-canal sealers. As for irrigant solutions, NaOCl solution caused more microleakage than 1% CHX Gel+SS and 1% CHX Gel+NaOCl solutions and the results are statistically significant.
Conclusion: The study shows that the best irrigant solutions for all root- canal sealers are 1% CHX+SS and 1% CHX+NaOCl.
Keywords: Microleakage, Fluid Transport Model, Irrigation Solutions, Root Canal Sealer, Scanning Electron Microscopy, CHX Gel.
Introduction
The aim of the endodontic treatment is to prevent microleakage by filling the canals with nontoxic seals, after mechanical removal of all organic materials inside the root canal system and cleaning with nonirritant bactericide solutions [1].
For the removal of organic materials, the most commonly used instruments are canal files and chemical irrigation materials. Irrigation is the most effective method for removal of residual tissue and dentin debris during the instrumentation. Sodium Hypochlorite (NaOCl) and Chlorhexidine Gluconate (CHX) solutions are the most commonly used irrigation solutions [2]. NaOCl is an irrigant especially preferred for its antimicrobial effect, and lubrication and tissue dissolving properties; but it is found that it causes strong inflammatory reaction when come into contact with vital tissues [3].
CHX is a cationic bisbiguanide agent with pH between 5.5 and 7.0, low toxicity. Despite its routine usage at periodontal treatment and cavity prevention, its gel and liquid forms are used as irrigation solutions at endodontic treatment [4]. Gel form of CHX has low toxicity on periapical tissues. Its viscosity helps to maintain its activity when come into contact with the walls of root canals and dentine tubules. It is also fully soluble in water [5].
There are many endodontic filling materials with different property that are used as canal sealer. Those provide apical sealing to be successful via different filling techniques [6]. Although the most commonly used filling material is gutta-percha, it is used together with different canal sealers in order to hermetically seal the space between gutta-percha and root walls, and dentine canals [2]. Among those, the ones gained common acceptance are glass ionomer-based sealers [Ketac-Endo], calcium hydroxide-based sealers [Kalsin, Sealapex], zinc oxide- eugenol-based sealers [Sealite-Ultra] and polymer sealers [AH-Plus, Diaket].
As the penetration property of root canal sealer increases, the sealing ability also increases [3]. There are many methods used to assess the sealing ability of root canal sealers, some are impermeability test [7], liquid transport method [8], radioactive isotope method [9] and bacterial penetration test [10]. Among these, the liquid transport method is an accurate method, which allows the assessment of microleakage levels at different times, because it can measure microleakage without disturbing the original sample [10].
The aim of this study is to determine the best canal root sealer and irrigant solution combination in order to achieve the least microleakage. To do this, we compared the results of possible combinations.
Material and Methods
During this study, 170 maxillary anterior human teeth, extracted cause of orthodontics and periodontics, with single and straight root canals, were selected.
Root canal preparation and filling: Selected teeth with open roots apices, cracks and resorptive defects were excluded. The teeth were carefully cleaned with curettes to remove soft-tissue remnants and were stored in saline solution before instrumentation. The crowns of the teeth were sectioned at the cemento-enamel junction using water-cooled diamond disks. A #15 K file (Antaeos, VDW GmbH, München, Germany) was inserted into the canal to measure the working length and to verify the apical patency. The working length was established 1 mm short of the apex. The root canals were prepared by using crown-down technique with HERO Shaper (Micro-Mega, Besancon Cedex, France). The coronal third of each root was flared up to a 2-4 Gates Glidden bur (Dentsply, Maillefer, Switzerland) with a low-speed hand- piece. The canals were irrigated with 5.25 % NaOCl that was delivered with a dental syringe, using 2ml between each file size. After instrumentation, the smear layer was removed with 10 ml 5.25 % NaOCl, 10 ml 17 % EDTA (Hacettepe University, School of Pharmacy) and 10 ml 5.25 % NaOCl for 2 min in the respective sequence. Final irrigation of all root sections was carried out with 10 ml saline solution (SS), and the canals were dried with sterile paper points (Meta Dental Co., Ltd., Korea). 160 prepared teeth were randomly divided into 16 groups (n=10/ groups) and the remaining 10 teeth were divided into 2 groups of negative and positive controls (n=5/groups).
The groups were treated with the following irrigant solutions and root-canal sealers:
In groups 1-4, 2ml of 5.25% NaOCl was applied as an irrigation solution while in group 2 specimens were irrigated with 2 ml of 2 % CHX solution (Drogsan, Ankara, Turkey).
In groups 9-16, 1% CHX gel (Hacettepe University, School of Pharmacy) was applied into the root canals as an intra-canal medicament. Root canals were filled with gel using a lentulo. Root canal openings were sealed with cotton pellets and a temporary filling material. Specimens were then stored at 37C° and 100% humidity for 1 week. Following the period, in groups 9-12 10 ml of 5.25% NaOCl was applied for 2 minutes to remove CHX gel from root canals, while 10 ml sterile saline solution was applied for groups 13-16.
Root canals of the samples were obturated using cold lateral condensation technique with gutta-percha cones (Diadent ML. 029, Korea) and 4 different sealers Sealite-Ultra (Produits Dentaires Pierre Rolland, Cedex, France), AH-Plus (Dentsply DeTrey, Konstanz, Germany), Diaket (3M ESPE AG, Seefeld, Germany) and Ketac- Endo (3M ESPE AG, Seefeld, Germany) was applied into channel after mixing with lentulo as recommended by the producer. After obturation, hot pluggers were used to remove the excess gutta-percha from the orifices of the root-canal. Five roots obturated with gutta-percha without any sealer were completely coated with two layers of nail varnish except for the apex of the root and the coronal access and were used as the positive controls. Five root sections obturated with gutta-percha cones and sealers were completely coated with two layers of nail varnish and served as negative controls. All samples were stored in sterile saline solution at 37 oC for 2 weeks. The irrigation solutions used in the experimental groups are listed in Table I.
Evaluation of Microleakage by Fluid transport model: The method is fluid transport model used. The coronal end of the obturated root was then connected to a plastic tube filled with deionized water. Water was sucked back with the syringe for approximately 3 mm in the open end of the glass capillary and then connected to a piece of plastic tube filled with water. In this way, an air bubble was created in the capillary. A head-space pressure of 10 kPa (0.1 atm) from the coronal side was applied and the water was forced through the voids along the root canal filling, displacing the air bubble in capillary tube by transport of water. The volume of the fluid transport was measured in millimeters by observing the movement of this air bubble, and the mean leakage value for each group was calculated and recorded.
Evaluation of Scanning Electron Microscope (SEM): Four specimens from each group were used for SEM examinations (Jeol, JSM-6400, Tokyo, Japan). Longitudinal grooves were cut at the buccal and lingual surfaces of the roots. The roots sections were carefully separated from each other with a sharpened blade. The specimens were mounted on stubs, put in a vacuum chamber, sputter- coated with gold-palladium for SEM evaluation. These samples were examined using SEM to assess dentin tubule penetration at magnifications of 2.500 times. SEM values of examination groups were not evaluated by any statistical test.
Statistical Analysis: A 95% confidence interval was adopted for the descriptive statistics. The effects of irrigant solutions and root-channel sealers on microleakage were measured using General Linear Model–GLM. Pairwise comparisons made using Bonferroni post-hoc test to measure effect of irrigant solutions on microleakage. For statistical analyses, SPSS for Win. Ver. 15.00 (SPSS Inc. Chicago, IL., USA) package program was used. The required level for statistical significance is taken as p≤0.05.
and %1 CHX+NaOCl.
When pairwise comparisons was made via Bonferroni post-hoc test to reveal the cause of microleakage differences between irrigant solutions; the difference between NaOCl, 1% CHX gel+SS and 1% CHX gel+NaOCl is statistically significant (p<0.05). But, the microleakage difference between other solutions are insignificant (p>0.05). The results are given in Table 2. When results in Table 2 analyzed, it was seen that although NaOCl 0.338 caused more microleakage, the statistical relevancy between the results of NaOCl and 2% CHX is higher (p= 0.434). NaOCl solution caused more leakage than 1% CHX gel+SF and 1% CHX gel+NaOCl solutions, and the difference shows statistical significance (p= 0.001, p= 0.002). No statistical relation was found between other solutions in context of microleakage.
When the amount of microleakage is taken as dependent variable, and sealers and solutions are taken as independent variables, Univarite GLM analysis shows that there really is a statistically significant relation (p<0.001) between solutions and the amount of microleakage. Yet there is no meaningful relation (p>0.05) between microleakage and sealer or sealer-solution combination. The model designed with univarite GLM analysis explains the changes at the amount of microleakage with 60% relativity (R2=0.599).
The SEM evaluation showed that both irrigation solutions have better adaptation and penetration in coronal and middle thirds compared to the apical third of root canal. SEM evaluation also showed that AH-Plus performs better than other root-canal sealers as dentin tubule penetrator (Figure 2). As for irrigant solutions, 1% CHX gel had performed better penetration to dentin tubule (Figure 3), but NaOCl and SS solutions, which was used to infuse the solution into canal, were failed to completely remove the gel from tubule.
Discussion
Our study is more widely than former studies, since we compared different combinations of four irrigant solutions and four root canal sealers. As CHX gel is soluble in water, it can easily be removed from canals when washed with distilled water [5]. Practical properties of CHX gel, such as antimicrobial activity, low toxicity, solubility and removal of smear layer, increases its preferability as endodontic irrigant [11,12].
Ferraz et al. [5] stated that when used for irrigation, CHX gel provides long-term antimicrobial effect and lubricates root canals. Besides they stated that tissue dissolving effect, which is nonexistent in CHX solution, can be compensated by gel implementation owing to the increased viscosity, thus dentine debris inside root canals can removed more easily. During the study, CHX gel was applied to root canals with 26 gauge needle. They observed that gel does not penetrate and stays on wall, and when washed with distilled water, it can easily be removed from canal.
Yet Çal [13] used distilled water and NaOCl to remove the CHX gel applied to root canal via lentulo tubule during tubular penetration experiment he conducted. He stated that distilled water is far more effective than NaOCl at removing gel from canal, but he also stated that both solutions are inadequate.
But we preferred saline solution and NaOCl to remove the gel applied to root canal via lentulo. Although serum physiologic proved to be more successful than NaOCl at removing the CHX gel from root canals, both irrigant failed to completely remove the gel from canals.
Kruvilla and Kamath [14] observed during their study on 1% NaOCl and 2% CHX gel [viscous form] combination that NaOCl first disintegrated to H+, O-2 and Cl- ions and then formed chlorhexidine chloride (N+ Cl-) after reaction of chloride group with chlorhexidine. Gomes et al. [12] stated that viscous dark-brown production is fast during this reaction. They stated that, since viscous dark brown can easily adhere to dentine and root walls, it can not be completely removed from root canals, so it creates a residual film and that can increase microleakage by marring the filling property of sealer.
We also observed the reaction and formation of viscous dark-brown, when we mixed 1cc CHX gel and 0.1cc NaOCl in an injector. This formation remained unchanged for 10 days, afterwards viscous formation decomposed. Former studies [12,14] explained the inadequacy of serum physiologic and NaOCl at removal of CHX gel with viscous dark-brown formation. So our study supports former results.
Various studies speculated that irrigant solutions as well as canal sealers causes microleakage. Gomes et al. [2] used five different irrigant solutions (I-1% NaOCl, II- 1% NaOCl+17% EDTA, III- 2% CHX gel, IV- 2% CHX gel+1% NaOCl, V-distilled water) during their study on the effect of irrigant solutions on microleakage. According to their results, the best results were recorded with 2nd and 3rd group solutions and worst results were recorded with 4th group solutions. But they couldn’t find statistically significant difference between groups. In short, they reported that CHX gel doesn’t damage the sealing ability of root canal sealers.
During our study, we observed the minimum microleakage levels in CHX gel-SS and CHX gel-NaOCl groups. Although the results of SEM and microleakage experiments are consistent with previous literature [2], the results recorded in CHX gel-SS group were better that CHX gel- NaOCl group. But the difference between the groups was not statistically significant.
There are studies in the literature, in which various canal sealers were inspected for microleakage. Miletić et al. [15] compared five different root canal sealers [Ketac- Endo, AH-26, AH-Plus, Apexit and Diaket]. Although they observed the microleakage levels were best in Ketac- Endo group, the difference with other sealers was not statistically significant. Çobankara et al. [16] studied four different root canal sealers [AH-Plus, Ketac-Endo, RoekoSeal, Sultan]. The microleakage experiment conducted using liquid filtration model showed that Sultan causes much more microleakage than RoekoSeal
[polydimethylsiloxane], Ketac-Endo and AH-Plus, and the difference was statistically significant. Koch et al. [17] stated that Ketac-Endo has better filling property than zincoxide eugenol-based filling materials [sultan, sealite- ultra]. The microleakage study conducted by Rohde et al. [18] showed that zinc oxide eugenol based filling materials causes more apical leakage that Ketac-Endo. Finally De Gee et al. [19] stated that the impermeability property of epoxy resin based filling materials [Diaket] are better than glass ionomer based canal filling materials [Ketac-Endo].
The best results were observed in Ketac-Endo group and the worst results were observed in Sealite-Ultra group. But the hermetic property of Ketac-Endo was not statistically significant respective to AH-Plus and Diaket. Ketac-Endo has better hermetic property than other canal sealers [17]. Also our study confirms the results of prior studies. Better results recorded in Ketac-Endo group may be related more to better chemical binding to dentine than better tubular penetration. We believe that AH-Plus resulted worse because of short implementation time and high shrinkage stress.
The penetration of root canal sealers is crucial in contest of coronal and apical microleakage for the success of endodontic treatment [20]. The study of Leblebicioğlu et al. [21] explored whether dentine tubule penetration and microleakage are relevant. They observed that the removal of smear layer facilitates the penetration of root canal sealer into dentine tubule and also increases the effectiveness of sealing, consequently decreasing coronal and apical leakage. In the study of Şen et al. [22], where the effect of the tubule penetration of sealings on paint leakage, they found a reverse correlation with low quality between penetration and microleakage.
Similarly our study also showed bad tubular penetration but highest microleakage results for Sealite-Ultra. But although Ketac-Endo did not present so good tubular penetration results, it presented the lowest microleakage results.
In the study of Leblebicioğlu et.al [21], where the tubular penetration of Ketac-Endo was examined, they observed that the tubular penetration was bad for lateral condensation group whereas adaptation to canal walls and penetration to dentine tubules was good for single cone group. They stated that they believed this is due to short hardening time for Ketac-Endo. Also in our study, tubular penetration was quite bad when canals were filled using lateral condensation technique.
Pecora et al. [2 3] stated that AH-Plus has a good value for adhesion but low value for tubular penetration. Differently than others, in our study, AH-Plus homogeneously spread to dentine canals despite its granular composition. Big particles couldn’t penetrated whereas small particles penetrated into almost every dentine tubule up to 30- 40μm deep. We believe this is due to implementation technique.
Okşan et al. [24] examined the tubular penetration of four different canal sealer [Diaket, Forfenan, SPAD, N2 Universal] and concluded Diaket to be better than SPAD and N2, and Forfenan to be the worst. Şen et al. [22] studied the correlation between microleakage and dentine tubular penetration for four different root canal sealer [Diaket, CRCS, Endomethasone, Ketac- Endo], during the study they filled canals with vertical condensation technique after removing smear layer. The paint leakage evaluation showed that Diaket presents least leakage, and Diaket, CRCS and Endomethasone have good tubular penetration. Contrary our study showed that although Diaket has low microleakage, its tubular penetration is low. We believe these contradictive results to be due to different canal filling techniques and leakage measurement methods.
In our SEM study, CHX gel could penetrate into root canals up to 40 μm deep when applied with lentulo and the reaction between CHX gel and NaOCl was minimal. This is why; we didn’t observe any viscous dark-brown formation inside dentine tubules. But as CHX gel groups filled dentine tubules well, they couldn’t be removed after the last wash with NaOCl or SS. Besides, these groups presented relatively less microleakage because of better
tubular penetration ability of root canal filling material. Among different solution and filling material combinations, the best results for microleakage were observed in Ketac Endo-2% CHX group, and the worst results were observed in Diaket-NaOCl and Sealite Ultra-NaOCl groups. The SEM study of the same groups presented better results for Sealite Ultra-NaOCl group than Ketac Endo-2%-CHX and Diaket-NaOCl groups. Furthermore the best results in context of tubule penetration were observed in AH-Plus groups.
Conclusion
We conclude that the effectiveness of irrigant solutions and root canal sealers in context of microleakage and tubular penetration is affected by implementation technique as well as their chemical and physical properties. Our study proves that the best solutions for all sealers are 1% CHX+SS and 1% CHX+NaOCl. According to the results, NaOCl and 2% CHX causes more microleakage and should be used with caution.
Acknowledgements
This study was approved by the Gülhane Military Medical Academy Scientific and Technical Research Institution (Project No: AR-2005-23).
References
1. King KT, Anderson RW, Pashley DH, Pantera EA. Longitudinal evaluation of the seal of endodontic retrofillings. J Endod 1990; 16: 307-310.
2. Gomes NV, Ferraz CCR, Gomes BPFA, Zaia AA, Teixeira FB, Filho FJS. Influence of irrigants on the coronal microleakage of laterally condensed gutta-percha root fillings. Int Endod J 2002; 35: 791-795.
3. Sassone LM, Fidel R, Fidel S, Vieira M, Hirata R. The influence of organic load on the antimicrobial activity of different concentrations of NaOCl and chlorhexidine in vitro. Int Endod J 2003; 36: 848-852.
4. Ferguson DB, Marley JT, Harwell GR. The effect of chlorhexidine gluconate as an endodontic irrigant on the apical seal: long- term study. J Endod 2003; 29: 91-94.
5. Ferraz CCR, Gomes BPFA, Zaia AA, Teixeira FB, Souza-Filho FJ. Invitro assessment of the antimicrobial action and the mechanical ability of chlorhexidine gel as an endodontic irrigant. J Endod 2001; 27: 452-455.
6. Pommel L, About I, Pashley D, Camps J. Apical leakage of four endodontic sealers. J Endod 2003; 29: 208-210.
7. Bodrumlu E, Tunga U. Apical leakage of resilion obturation material JCDP 2006; 7: 45- 52.
8. Wu MK, Wesselink PR. Endodontic leakage studies reconsidered Part 1. Methodology, application and relevance. Int Endod J 1993; 26: 37-43.
9. Haikel Y, Wittenmeyer W, Bateman G, Bentaleb A, Allemann C. A new method for the quantitative analysis of endodontic microleakage. J Endod 1999; 25: 172-177.
10. Wu MK, De Gee J, Wesselink PR, Moorer WR. Fluid transport and bacterial penetration along root canal fillings. Int Endod J 1993; 26: 203-208.
11. Wuerch RMW, Apicella MJ, Mines P, Yancich PJ, Pashley DH. Effect of 2 % chlorhexidine gel as an intracanal medication on the apical seal of the root-canal system. J Endod 2004; 30: 788-791.
12. Gomes BPFA, Ferraz CCR, Vianna ME, Berber VE, Teixeira FB, Souza-Filho FJ. Invitro antimicrobial activity of several consentrations of sodium hypoclorite and chlorhexidine gluconate in the elimination of Enterococcus faecalis. Int Endod J 2001; 34: 424-428.
13. Çal C. “Klorheksidinin kök kanal dolgu patlarının dentin adezyonu ve tübüler penetrasyonuna etkisinin araştırılması” (PhD thesis). Ankara, TR: University of Hacettepe, 2005.
14. Kruvilla JR, Kamath MP. Antimicrobial activity of 2,5 % sodium hypochlorite and 0,2 % chlorhexidine gluconate separately and combined, as endodontic irrigants. J Endod 1998; 24: 472-476.
15. Miletić I, Anić I, Ribarić SP, Jukić S. Leakage of five root canal sealers Int Endod J 1999; 32: 415-418.
16. Çobankara FK, Adanır N, Belli S, Pashley DH. A quantitative evaluation of apikal leakage of four root canal sealers. Int Endod J 2002; 35: 979-984.
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23. Pecora JD, Cussioli AL, Guerisoli DMZ, Marchesan MA, Souza-Neto MD, Brugnera- Junıor A. Evaluation ER-YAG laser and EDTAC on dentin adhesion of six endodontic sealers. Braz Dent J 2001; 12: 27-30.
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Tulin Ertan, Yasar Meric Tunca. Comparative Evaluation of Microleakage for Different Root Canal Sealers and Irrigation Solutions. J Clin Anal Med. 2010;1(2):9-14
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Anaerobic Glycolysis is the Main Pathway for Energy Generation in Hl-60 Acute Promyelocytic Leukemia Cells
Hakan Boyunaga 1, Hatice Keles 2, Levent Kenar 3, Ali Ugur Ural 4, Ferit Avcu 4
1 Department of Biochemistry and Clinical Biochemistry, Kırıkkale University Faculty of Medicine, Kırıkkale, 2 Departments of Internal Medicine, Kırıkkale University Faculty of Medicine, Kırıkkale, 3 Department of Biochemistry and Medical NBC Defense, Gulhane School of Medicine, Ankara, 4 Department of Hematology, Gulhane School of Medicine, Ankara, Turkey
DOI: 10.4328/JCAM.10.2.12 Received: 02.09.2009 Accepted: 15.10.2009 Printed: 01.05.2010J.Clin.Anal.Med. 2010;1(2): 5-8
Corresponding author: Hakan Boyunaga. Department of Biochemistry and Clinical Biochemistry, Kırıkkale University Faculty of Medicine, Kırıkkale, Turkey. Phone: +90 312 304 33 29, E-mail: hboyunaga@kku.edu.tr
Aim: In physiological conditions, normal cells use mainly the glycolytic aerobic pathway to provide energy. However, most cancer cells utilize anaerobic glycolytic way for energy generation. Aim of this study was to investigate the carbohydrate metabolic pathways of HL-60 acute promyelocytic leukemia cells for energy production.
Material and Methods: Leukemia cells as well as normal leukocytes were incubated with radiolabelled glucose in aerobic and anaerobic conditions and glycogen consumptions and the ratios of radiolabelled glucose catabolized into CO2 or lactate, that is, the rates of aerobic or anaerobic glycolysis, were determined.
Results: The glycogen consumption was significantly higher in aerobic leukemia cell culture than normal leukocyte culture (p<0.01). The rate of anaerobic glycolysis was 93.8% in leukemia cells in aerobic conditions and it increased to 96.6% while utilization of glycogen increased by 7.31% in anaerobic conditions.
Conclusion: In conclusion, principally anaerobic glycolysis is effective for energy generation in HL-60 promyelocytic leukemia cells. This result may be important for the development of new therapeutic approaches in the treatment of promyelocytic leukemia, requiring further comprehensive studies.
Keywords: Energy Metabolism, HL-60 Promyelocytic Leukemia Cell, Glycogen Degradation.
Introduction
Some structural and metabolic alterations can occur with malign transformation of a normal living cell [1]. Metabolic changes may appear primarily in pathways of energy formation for the cell. Glucose and glutamine are the common sources of energy for both normal and malign cells [2].
Glycolysis and cell respiration function in both ATP synthesis and metabolic pathways of carbohydrates and other compounds. Both normal and cancer cells use similar metabolic pathways for energy production but in varying rates [3]. In 1930, it was firstly reported by the Warburg that anaerobic glycolysis rate was increased in cancer cells [4]. Some recent studies also indicated that cancer cells predominantly use anaerobic glycolysis rather than aerobic one for their energy generation but the rates differ [5-7]. For the increased protein synthesis and cell division, tumor cells function to provide energy by metabolizing the nutrients at an increased rate. To meet the requirements of increased metabolism, it may be beneficial for tumor cells to use the anaerobic glycolytic pathway, a quicker way to generate energy. But, on the other hand, they consume the organism’s supplies in a short period of time resulting in cashectia.
The main way through which cells metabolize is mostly dependent on oxygen level in the medium. In the case of high oxygen level, glucose is catabolized via aerobic glycolytic pathway followed by the insertion of degradation products into the Krebs cycle. Then, phosphate with high energy is included into the electron transport chain resulting in energy gain [8,9]. When oxygen concentration is inadequate, the anaerobic glycolytic pathway, which is less efficient than aerobic glycolysis, is completely activated, and cells maintain their viabilities even under low oxygen conditions [8]. Depending on the oxygen level, the selection of either the aerobic or anaerobic pathway in ATP synthesis is called “Pasteur Effect” [10-14]. The possession of this effect by tumor cells may provide them to maintain their viabilities, thus may influence the success of the treatment with anti-neoplastic agents which block energy metabolism of tumor cells. So, this study aimed to investigate the carbohydrate metabolic pathways of HL-60 acute promyelocytic leukemia cells for energy production, thus to provide appropriate selection and development of antineoplastic agents targeting energy metabolism of these cells to increase the effectiveness of the treatment.
Material and Methods
This study was performed within the collaboration of Departments of “Biochemistry and Clinical Biochemistry” and “Internal Medicine” of Kırıkkale University School of Medicine and Departments of “Hematology” and “Biochemistry and Clinical Biochemistry” of Gulhane School of Medicine.
Chemicals and biomaterials
D-[6-C14] glucose was purchased from Amersham Company and hexokinase and glucose-6-phosphate dehydrogenase enzymes were from Boehringer. All other chemicals used were in analytical grade. HL- 60 acute promyelocytic leukemia cells were provided from Memorial Sloan-Kettering Cancer Center NY, NY and maintained at 37 °C in the medium of 5% CO2 and medium of RPMI 1640 supported by fetal calf serum 10%, 2 μM L-Glutamine, 100 μg/mL streptomycine and 100 U/ml penicilline. A total of seven cultures from HL- 60 acute promyelocytic leukemia cells were prepared. For the preparation of normal leukocyte cultures blood sample was obtained from a healthy subject and put in tubes with acid-citrate-dextrose (ACD). Then leukocyte isolation was performed by the method described previously by English and Anderson [15] and a total of seven cultures from normal leukocytes were prepared. Radioactive incubations and analysis of excreted end products
Radioactive incubations were performed by glucose in which sixth carbon was labelled with radioactive Carbon 14 (D-[6-C14] glucose). Amount of labelled glucose added to each culture was 25μCi D-[6-C14] glucose. Before the incubation procedure, both the normal leukocyte cultures and the HL-60 cell cultures were made up to adequate concentrations and each cell culture was separated into three groups. The first one was for the aerobic culture the second one was for the anaerobic culture after KCN addition defined by Tielens [9] and the last one was for the determination of the initial glycogen and protein contents of the cells. Both aerobic and anaerobic cell cultures were immediately incubated with radiolabelled glucose for 4 hours in a specially designed chamber at 37 °C. The cultures which were separated for the determination of zero time glycogen and protein levels were not incubated with radiolabelled glucose. Incubated cell cultures which catabolize externally given radioactive glucose through glycolysis convert it into products including lactate, acetate and propionic acid. Following incubation, the generated radioactive CO2 was collected in scintillation vials via nitrogen gas. Then, the content was separated as supernatant and pellets. By using supernatant layer, end-products of glycolysis (lactate, acetate and piruvate) were collected in scintillation vials by anion-exchange chromatography, and were calculated on standard graphics in Microsoft Excel program.
In pellets, protein was determined by modified Lowry method and glycogen by Hassid and Abraham’s enzymatic method. Glucose in supernatant was measured enzymatically by glucose oxidase method. Glycogen consumption and CO2 production for each gram of protein were calculated by using data obtained by the measurement of glycogen and protein found in the pellets. Statistical Analyses
Statistical analysis of the data was done with 9.0 SPSS Package programme for computer. Kruskal-Wallis and Mann Wittney U tests were used for the difference between groups. P<0.05 was assumed to be significant.
Results
Table1 shows the amounts of glycogen consumption, labelled and total end products of glycogen metabolism, CO2 and lactate, and external glucose degradation as percentage of internal glycogen degradation in normal and leukemic cell lines in both aerobic and anaerobic media. Glycogen consumption was significantly higher in anaerobic leukocyte culture than aerobic one (p<0.01). Labelled and total amounts of end product lactate were higher (p<0.01 and p<0.01, respectively) and labelled and total amounts of end product CO2 were lower (p<0.01 and p<0.01, respectively) in anaerobic leukocyte culture when compared to aerobic one.
When aerobic HL-60 promyelocytic leukemia cell culture was compared with aerobic normal leukocyte culture, glycogen consumption was found to be significantly higher (p<0.01), labelled and total end product lactate was found to be higher (p<0.01) and labelled and total end product CO2 was found to be lower in leukemia cell culture (p<0.01). When aerobic HL-60 promyelocytic leukemia cell culture was compared with anaerobic normal leukocyte culture, glycogen consumption was still significantly higher (p<0.01) but both labelled end products lactate and CO2 were lower (p<0.01 and p<0.01, respectively) while both total end products lactate and CO2 were higher (p<0.01 and p<0.01, respectively) in leukemia cell culture.
In anaerobic HL-60 promyelocytic leukemia cell culture glycogen consumption was significantly higher (p<0.05) and both labelled and total amounts of end product CO2 were lower (p<0.01 and p<0.01, respectively) while both total and labelled amounts of end product lactate were higher (p<0.01 and p<0.01, respectively) than the ones in aerobic HL-60 promyelocytic leukemia cell culture. The findings were the same for the comparison of anaerobic HL-60 promyelocytic leukemia cell culture with aerobic and anaerobic normal leukocyte cultures.
Discussion
In the present study analysis of excreted end-products demonstrated that normal leukocytes use primarily the aerobic glycolysis in aerobic conditions but they shift their energy metabolism predominately to anaerobic glycolysis in anaerobic conditions. The results of this study also indicated that HL-60 promyelocytic leukemia cells use primarily the anaerobic glycolytic pathway which gets more predominant in anaerobic conditions.
Warburg first reported in 1930 that cancer cells possess anaerobic glycolysis in high rate [4]. Later on numerous studies were performed to investigate in details how carcinogenic cells use the metabolic pathways to generate ATP when compared to the function of original stem cells [16]. Indeed, the purpose of these studies was to develop more efficient chemotherapeutic agents. The findings indicated that cancer cells often use different metabolic ways as compared to those used by original cells. But, it was also found that a majority of cancer types use essentially anaerobic glycolysis in different rates, and their cell division frequency is quite high [17,18]. The metabolic rate of some cancer cells may be increased up to approximately 400 times [7]. This increase in metabolism also causes increases in enzyme activities of control points in glycolysis like hexokinase, phosphofructokinase and piruvate kinase [19]. Similar increases may also be seen in glucose carrier molecules [18]. Moreover, as addressed by Warburg [4], high rate of anaerobic glycolysis might not be associated with all types of cancer cells and a rather low cell division rate with a normal glycolysis could be seen in some cancer types like Morris hepatoma [20, 21]. The rates of metabolic pathways the cells use can be different although they function on some common ways in principal.
Oxygen level and nutrient concentration are normally the main biological indicators which determine the exact metabolic pathway the cell can use to obtain ATP [8]. The main advantage of the use of anaerobic glycolysis with respect to tumor cell is to obtain ATP easier but it is an ineffective pathway. While 36-38 moles of ATP per mole of glucose are obtained through aerobic glycolysis only 2 moles of ATP per mole of glucose are obtained through anaerobic glycolysis. Therefore 19 times more substrate is utilized in anaerobic glycolysis to obtain the same amount of ATP obtained through aerobic glycolysis.
The conversion of the metabolism of normal or cancer cells from aerobic glycolysis into anaerobic glycolysis in reduced level of ambient oxygen, the so called Pasteur Effect, can accelerate the consumption of glycogen and lipid stores [22, 23]. Moreover, as a result of this alteration, the effect of chemotherapy used to regulate the energy metabolism of cancer cells remains limited [24-26].
In our study, as it was reflected by the level of radiolabelled end product CO2 aerobic glycolysis was the predominant way of metabolism (96%) in aerobic leukocyte culture. But in anaerobic media leukocytes shifted their energy to mainly anaerobic glycolysis (90%) with an increase in consumption of glycogen by 73.8%, showing prominent Pasteur Effect. The ratios of radiolabelled glucose catabolized into CO2 or lactate, that is, the rates it was directed to either anaerobic or aerobic way were also investigated on aerobic HL-60 leukemia cell line and significant differences were found when compared to anaerobic and aerobic control leukocyte cultures. The rate of aerobic glycolysis was only 6.2% in aerobic conditions that is the main way of glycolysis was anaerobic (93.8%) in HL-60 promyelocytic leukemia cells. The level of anaerobic glycolysis increased to 96.6%, and utilization of glycogen increased by 7.31%, when oxygen use of HL- 60 promyelocytic leukemia cells was inhibited by KCN. These results indicate that HL-60 acute promyelocytic leukemia cells metabolize glucose prominently through the anaerobic glycolysis and endogenous glycogen degradation is the main pathway for energy generation. These results also indicate that the Pasteur Effect is also validated in HL-60 promyelocytic leukemia cells.
In conclusion, it is evident that principally anaerobic glycolysis is effective for energy generation in HL-60 promyelocytic leukemia cells in aerobic conditions. On the other hand, the rate of anaerobic glycolysis gets more prominent in anaerobic conditions. This result may be important for the development of new therapeutic approaches in the treatment of acute promyelocytic leukemia, requiring further comprehensive studies.
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4. Warburg O, Metabolism of Tumors. London: Arnold Constable., 1930
5. Rossignol R, Gilkerson R, Aggeler R, Yamagata K, Remington SJ, Capaldi RA. Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res, 2004, 64, 985-993.
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Hakan Boyunaga, Hatice Keles, Levent Kenar, Ali Ugur Ural, Ferit Avcu. Anaerobic Glycolysis is the Main Pathway for Energy Generation in HL-60 Acute Promyelocytic Leukemia Cells. J Clin Anal Med. 2010;1(2):5-8
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The Impact of Co-Existing Prostate Adenocarcinoma with Bladder Carcinoma on Disease Specific Survival of the Patients in Our Radical Cystoprostatectomy Series
Özgür Uğurlu, Volkan Öztekin, Murat Koşan, Ömer Gökhan Doluoğlu, Öztuğ Adsan, Mesut Çetinkaya
2. Üroloji Kliniği, Ankara Numune Eğitim ve Araştırma Hastanesi, Ankara, Türkiye
DOI: 10.4328/JCAM.10.2.11 Received: 27.08.2009 Accepted: 12.11.2009 Printed: 01.05.2010J.Clin.Anal.Med. 2010;1(2):1-4
Corresponding author: Ömer Gökhan Doluoğlu, Ankara Numune Eğitim ve Araştırma Hastanesi 2. Üroloji Kliniği, Ceyhun Atıf Kansu Cd. Cevizlidere Mah. 158/11, Balgat, Ankara, Türkiye. Phone: +90312 508 52 85 E-mail: drdoluoglu@yahoo.com.tr
Aim: The aim of this study was to compare the patients with and without histologically proven prostate carcinoma who underwent radical cystectomy for muscle invasive bladder cancer in terms of bladder tumor properties and survival rates.
Material and Methods: A total of 149 male patients who had undergone radical cystectomy and urinary diversion between 1994-2007 in our institution were included in our study. Medical records of the patients were analyzed retrospectively. Fourteen (9.3%) patients had co-existing prostate carcinoma, while remaining 135 (90.7%) did not. The two groups were compared to each other with respect to the oncological properties of the bladder tumors (stage and grade) and disease specifific mortality rates.
Results: The mean ages for the patients with and without co-existing prostate carcinoma were 64.2±8.4 and 57.7±10.8, respectively. There was a signifificant difffference between the ages of the two groups (p=0.029). There were not any signifificant difffferences among the two groups regarding bladder cancer pathological stage (p=0.199) and grade (p=0.544). The disease specifific survival rates of the two groups for three years were: 61.76% and 81.82% for the patients with and without coexisting prostate carcinoma respectively. No signifificant difffference was observed between the disease specifific survival rates of the two groups (p=0.325).
Conclusion: The co-existing prostate carcinoma had no signifificant effffect on tumor stage, grade and disease specifific survival rates of patients who underwent radical cystectomy for muscle invasive bladder cancer.
Keywords: Prostate Adenocarcinoma, Cystoprostatectomy, Survival.
Giriş
Batı ülkelerinde Prostat karsinomu (PCa) 50 yaşından sonra ortaya çıkan en yaygın malignitelerden biridir. PCa mortalitesi 1994’den bu yana her yıl için %4 azalmaktadır [1]. PCa günümüzde erkeklerde akciğer kanserinden sonra ikincil ölüm nedenidir [2-3]. Latent PCa prevalansının klinik saptanabilen PCa prevalansından çok daha yüksek olduğu otopsi çalışmalarıyla gösterilmiştir [4]. Otopsi çalışmalarında erkeklerde 5. dekatta insidental PCa yaklaşık %30 olarak bulunmuştur. Bu oran 90 yaşını geçmiş erkeklerde yaklaşık %90 lara çıkmaktadır. PCa’dan ölüm oranı ise yaklaşık %3 tür. İnsidental olarak saptanan tümörler genellikle küçük, iyi ya da orta diferansiye ve prostata sınırlı tümörlerdir [5].
Sistoprostatektomi kas invaziv nonmetastatik mesane tümörünün en etkili tedavi şeklidir [6]. Mesane kanseri nedeniyle yapılan radikal sistoprostatektomi esnasında çıkarılan prostatın değerlendirilmesi, insidental PCa’nın klinik ve morfolojik özelliklerinin belirlenmesi için eşsiz bir olanak sağlar [7-14]. PCa nin erken teşhisi gereksiz tedavilerden kaçınıldığı zaman mantıklı bir amaç gibi görünse de böyle hastalarda günümüz metodları ile tedavi gerekliliği bakımından bu saptamayı yapabilmek yetersizdir.
Bu çalışmanın amacı invaziv mesane tümörü nedeniyle radikal sistoprostatektomi uygulanan hastalardan patolojik inceleme neticesinde prostat kanseri saptanan ve saptanmayan hastaları mesane tümörü özellikleri ve mortalite oranları açısından karşılaştırmaktır.
Gereç ve Yöntemler
1994-2007 tarihleri arasında kliniğimizde mesane tümörü nedeniyle radikal sistoprostatektomi ve üriner diversiyon uygulanan toplam 149 erkek hasta çalışmaya dahil edildi ve verileri retrospektif olarak gözden geçirildi. Sistoprostatektomi için endikasyonlar kas invaziv üretelyal karsinoma, yaygın yüksek gradeli karsinoma insitu (CIS) ya da rekürrent yüzeyel üretelyal karsinomayı içeriyordu. Tüm hastalara radikal sistoprostatektomiden önce parmakla rektal muayene (DRE) yapıldı. Prostat spesfik antijen (PSA) bakıldı (Tablo1). Tüm hastalar preoperatif abdominal ve pelvik bilgisayarlı tomografi (BT) ile değerlendirildi.
Standart radikal sistoprostatektomi prosedürü ile birlikte bilateral pelvik lenfadenektomi prosedürü 149 hastanın tümüne uygulandı. Çalışmaya alınan hastaların hiçbirinde cerrahi sınır pozitifliği yoktu. Üriner diversiyon olarak 93 hastaya ileal loop, 31 hastaya ortotopik neobladder, 14 hastaya Maintz poş, 6 hastaya üreterokutaneostomi, 1 hastaya Coeffey, 1 hastaya İndiana poş, 3 hastaya Stanford poş uygulandı. Hastaların hiçbirinde digital rektal muayenede prostat Ca şüphesi ya da bulgusu yoktu. Patolojik kesitler prostatın apeksinden tabanına doğru 5mm lik aralıklar ile uygulandı. Total tümör volümün < 0,5ml, Gleason grade < 4, ekstrakapsüler yayılım olmayan, seminal vezikül invazyonu olmayan, lenf nodu metastazı ya da pozitif cerrahi sınır olmayan hastalarda PCa klinik önemsiz olarak değerlendirildi. Yapılan patolojik değerlendirme neticesinde 149 hastanın 14’ünde (%9.39) prostat kanseri saptandı. Beraberinde prostat kanseri olmayan 135 hasta ile prostat kanseri olan 14 hasta mesane tümörünün özellikleri (evre, grade) ve mortalite oranları açısından birbirleriyle karşılaştırıldı. Hem prostat hem de mesane tümörünün patolojik evrelendirilmesinde 2002 TNM sınıflaması kullanıldı.
İstatistiksel yöntem olarak Mann Whitney U ve Ki-Kare testleri kullanıldı. Gruplar arasında yaş ve takip süresi yönünden farkın anlamlılığı, veriler normal dağılmadığı için Mann Whitney U testiyle araştırıldı. Mesane tümörü ile beraberinde prostat kanseri bulunmasının sağkalım üzerine etkisi Log-Rank testi kullanılarak Kaplan Meier sağkalım analizi ile değerlendirildi. p<0,05 için sonuçlar istatistiksel olarak anlamlı kabul edildi.
Bulgular
Çalışmamızda mesane tümörü nedeni ile radikal sistoprostatektomi yapılan 149 hastanın 14’ünde (%9.39) insidental PCa saptandı. PCa saptanan 14 hastanın 12 ‘si yukarıda belirtilen kriterlere göre klinik önemsiz olarak, 2’si tümör volümü > 0,5cm olduğundan klinik önemli olarak değerlendirildi. PCa saptanan hastaların ortalama PSA düzeyleri 3.26 ±3.61 idi ve hastaların radikal sistektomiden önce yapılan parmakla rektal muayeneleri normaldi. Bir hastanın PSA değeri 15,2 idi. Bu hastada tedavi seçeneğini değiştirmeyeceği için transrektal ultrason eşliğinde prostat biyopsisi yapılmadı. Hastanın radikal sistoprostatektomi sonrası Gleason skoru 3+2 olarak geldi. PCa saptanan hastaların karakteristik özellikleri tablo 1 de görülmektedir.
Prostat patolojisi benign olan hastaların yaş ortalaması 57.7, adenokarsinoma olan hastaların yaş ortalaması 64.2 idi. İki grup arasında yaş açısından istatistiksel olarak anlamlı fark vardı (p=0.029). Prostat patolojisi benign ve adenokarsinoma olan hastaların tablo 2’de mesane tümörü evresine, tablo 3’de mesane tümörü grade’ine göre dağılımı görülmektedir. Buna göre iki grup arasında mesane tümörünün patolojik evresi (p=0.199) ve grade (p=0.544) açılarından istatistiksel olarak anlamlı fark saptanmadı. Ortalama 22.8 aylık takip sonucunda hastalığa bağlı sağkalım prostat patolojisi benign olanlar için % 61.76, adenokarsinoma olanlar için % 81.82 idi. İki grup arasında hastalığa bağlı sağkalım açısından istatistiksel fark yoktu (p=0.325).
Tartışma
Literatürde sistoprostatektomi spesmenlerinde insidenital PCa oranı %10 ile %60 arasında verilmiştir [15,16]. Bu konuda en önemli çalışma Pritchett ve arkadaşlarına aittir [17]. Sistoprostatektomi geçirmiş 165 serilik hastada PCa ve mesane kanseri birlikteliğini %27 olarak bulmuşlardır. Delongchamps ve ark. radikal sistoprostatektomi geçiren 141 hastada PCa oranını %14.2 olarak bulmuşlardır [18]. Bizim serimizde ise insidental PCa oranı %9.39 olarak bulunmuştur. Literatürdeki bu farklılık farklı patolojik değerlendirme yöntemlerinin kullanılması ve farklı hasta dahil etme kriterleri ile açıklanabilir. Prostat değerlendirilirken apeksten tabana doğru yapılan kesitler ne kadar kısa aralıklarla olursa PCa saptama oranı artabilmektedir. Abbas ve ark. prostatı apeksten tabana 2 ila 3 mm lik kesitler ile incelediklerinde serilerinde PCa’yı 40 hastanın 18’inde (%40) bulmuşlardır[8]. Ayrıca Abbas ve arkadaşlarının PCa saptadıkları 18 hastanın 3’ünde sistoprostatektomiden önce yapılan parmakla rektal muayenede PCa şüphesi saptanmıştır. Bu da bize hasta seçim kriterlerinin PCa saptama oranını etkilediğini düşündürebilir. Bizim çalışmamızda ise saptanan düşük oran patolojik inceleme tekniği ve hasta seçim kriterleri ile açıklanabilir. Spesmen üzerinde yapılan daha detaylı incelemeler klinik önemsiz PCa oranını arttırabilmektedir.
Radikal sistoprostatektomi spesmeninde daha önce yayınlanan serilerde klinik önemli PCa oranı %10 ile %70 arasında bildirilmiştir [14,18-22]. Bu değişiklik patolojik değerlendirme işleminin farklılığına, klinik önemli PCa tanımlama kriterlerinin farklılığına ve araştırma altındaki popülasyona bağlı olabilir. Buna rağmen daha önce yapılan çalışmalar arasındaki karşılaştırmalar zor olmaktadır. Çünkü yayınlanan çalışmaların çoğu retrospektif olduğundan parmakla rektal muayene ve preoperatif PSA değerleri hastaların yalnızca çok küçük bir kısmında ulaşılır olmaktadır. Prange ve arkadaşları vakalarının %48’inde insidental PCa saptarken bunların yalnızca %10’nunda klinik önemli PCa saptamışlardır [23]. Delongchamps ve arkadaşları saptadıkları 20 PCa’nın 14’ünde (%70) PCa’yı klinik önemli olarak değerlendirmişlerdir [18]. Mazzucchelli ve ark. da 248 hastalık serilerinde saptadıkları insidental PCa ların %81.3’ünün klinik önemsiz olduğunu bulurken yalnızca %18.7 sinde klinik önemli PCa saptamışlardır [24]. Bizim çalışmamızda insidental saptanan 14 hastanın 2’sinde (%14.2) PCa klinik önemli olarak değerlendirilmiştir. 2 hastada da yalnızca tümör volümü >0.5cc olduğu için klinik önemli PCa tanısı konmuştur. Androulakakis ve arkadaşları PCa ve mesane kanserinin birlikte bulunmasının prognozu her iki hastalık içinde etkilemediğini bulmuşlardır [9]. Hasta prognozu ayrı ayrı her bir tümörün özelliği ile ilişkili gibi görünmektedir. Pritchett ve ark. her iki kansere sahip hastalarda yalnızca mesane tümörü olanlara göre sağkalım açısından fark bulmamışlardır [17]. Delongchamps ve arkadaşlarının serisinde ortalama 13 aylık takip süresinde hastaların 10’nu mesane kanserinden ölmüş, 8 hasta ise 64.5 aylık izlemde hastalıksız olarak yaşamını sürdürmüştür. Hastaların çoğunda kötü sağkalım oranı insidental PCa’lı hastalar ile karşılaştırıldığında mesane tümörünün evresinin ileri olması ile ilişkili bulunmuştur [18]. Moutzouris ve arkadaşlarının yaptığı çalışmada 1 hastada PCa rekürrensi gözlenmiştir. Bu hastada PCa apeks yerleşimlidir ve rekürrens ileoüretral anastomoz üzerinde olmuştur. Ortalama takip süresi 39 aydır ve 7 hasta metastatik mesane kanserinden ölürken rekürrens PCa’lı hasta halen hayatta bulunmaktadır [25].
Bizim çalışmamızda da benzer şekilde ortalama 22.8 aylık takip sonucunda hastalığa bağlı sağkalım prostat patolojisi benign olanlar için % 61.76, adenokarsinoma olanlar için % 81.82 idi. İki grup arasında hastalığa bağlı sağkalım açısından istatistiksel fark yoktu (p=0.325). Hiçbir hastada PCa rekürrensi gelişmedi ve hiçbir ölüm PCa ile ilişkili değildi. Ölümler mesane tümörünün evresi ve komorbid faktörler ile ilişkiliydi.
Sonuç
Radikal sistoprostatektomi spesmeninde prostatın PCa ile tutulması yaygın bir olaydır. Bizim çalışmamızda bu oran %9.39 olarak bulunmuştur. İnsidental PCa’ların çoğu bizim çalışmamızda da olduğu gibi organa sınırlı durumdadır. Çalışmamızda beraberinde prostat kanseri olan ya da olmayan invaziv mesane tümörlü hastaların
mesane tümörü evre, grade ve hastalığa bağlı sağkalım oranları benzerdi. Saptanan insidental PCa klinik önemli olarak değerlendirildiği zaman PSA testi postoperatif izlem protokolüne eklenmelidir. Bize göre radikal sistoprostatektomiden sonra saptanan insidental PCa sağkalımı etkilememektedir ve sağkalım mesane tümörünün prognozuna bağlıdır.
References
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8. Abbas F, Hochberg D, Civantos F, Soloway M. Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Eur Urol 1996;30:322-6
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10. Babaian RJ, Troncoso P, Ayala A. Transurethral-resection zone prostate cancer detected at cystoprostatectomy. A detailed histologic analysis and clinical implications. Cancer 1991;67:1418-22
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Ozgur Ugurlu, Volkan Oztekin, Murat Kosan, Omer Gokhan Doluoglu, Oztug Adsan, Mesut Cetinkaya. The Impact of Co-Existing Prostate Adenocarcinoma with Bladder Carcinoma on Disease Specific Survival of The Patients in Our Radical Cystoprostatectomy Series. J Clin Anal Med. 2010;1(2):1-4
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A Leser-Trelat Syndrome Associated with Renal Adenocarsinoma and Benign Prostat Hypertrophia
Tuncer Saçar 1, Handan Saçar 2
1 Dermatoloji servisi, Özel BucaDoruk Tıp Merkezi, 2 Dermatoloji Servisi, Bornova Şifa Hastanesi, İzmir, Türkiye
DOI: 10.4328/JCAM.10.2.25 Received: 12.11.2009 Accepted: 02.01.2010 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2): 44-46
Corresponding author: Tuncer Saçar, Mehmet Akif Caddesi, İnkılap Mah. No:107, Şirinyer, İzmir, Türkiye. Phone: +90 232 487 60 60 E-mail: tuncersacar@hotmail.com
Lesser-Trelat is generally known to be one of the cutaneous findings of vicceral occult cancer and is associated with diffuse seboreic ceratosis. That finding is an important clue for a clini-cian and when is noticed it has to be cleared up whether there is a vicceral occult cancer. We report a case with leser-trelat syn-drome, thought to be associated both with renal adenocarsino-ma and benign prostat hypertrophia present in a same patient.
Keywords: Leser-Trelat, Occult Cancer, Renal Adenocarcinoma, Benign Prostat Hypertrophy.
Giriş
1890 yılında Leser ve Trelat tarafından tanımlanan, özel- likle yaşlı popülasyonda aniden kaşıntılı seboreik keratoz- ların sayı ve büyüklüklerinin artışı ile karakterize, iç or- gan kanserlerinin göstergesi olabilen deri bulgusudur [1]. Literatürde böbrek adenokarsinom ilişkili Leser-Trelat sendromu oldukça nadir görülmektedir.
Olgu
75 yaşında erkek hasta sırtında şiddetli kaşıntılı ka- buklanmalar şikâyeti ile kliniğimize başvurdu. Hastanın şikâyetleri 4,5 yıl önce aniden başlamış ve 4 yıl önce de böbrek tümörü nedeniyle nefrektomi yapılmış. Son altı ay içinde gövdedeki lezyonlarında artış görülen hasta son 6 aydır benign prostat hiperplazisi tanısı ile izlenmektedir. Testlerinde total prostat spesik antijenin hafif yüksekliği dışında başka bir özelliği yoktu.
Dermatolojik muayenesinde sırtta kaşıntıya bağlı eksko- riye papüller, sağ lomber bölgede 20 cm’lik lineer nefrek- tomi insizyon skarı gözlendi (Resim 1a). Boyun, gövde ön, arka ve yan yüzlerde yaklaşık 500 adet 1 mm ile 2 cm çapları arasında değişen sarı-kahve renkli, sarı skuamlı, deriden kabarık papül ve plakları mevcuttu (Resim 1b,c,d).
Tartışma
İleri yaşlarda aniden kaşıntılı seboreik keratozların sayı ve çaplarındaki artış bir internal malignite belirtisi ola- bilir. Etyolojisinde sorumlu tutulan tümörlerin salgılamış olduğu büyüme faktörleri olan transforming growth fak- tör alfa (TGF-alfa) ve epidermal growth faktör (EGF), se- boreik keratoz gelişimini arttırmaktadır [2, 3]. Olguların %60’ında gastrointestinal kanala ait bir malignite, özel- likle de mide adenokarsinomu saptanmaktadır. Bunun ya- nında meme karsinomları, lenfoma, lösemi, melanom, nö- rofibrosarkom, hepatoma, osteojenik sarkom, pankre- as, over, uterus adeno karsinomları, akciğer kanseri, öze- fagus kanseri, sezary sendromu, prostat adenokarsino- mu, porfirya kutena tarda, malign hepatoma, renal hüc- reli karsinom, ampulla vateri tümörü, lenfoma, mikozis fungoides olguları ile de birlikteliğini bildiren çalışmalar mevcuttur. Olguların çoğunda dermatoz ve kanser geli- şimi birlikte başlar ve klinik olarak paralel seyir gösterir. Tümörün cerrahi çıkarımı ile tam iyileşme gözlenen has- talarda deri lezyonlarında gerileme olduğu bildirilmekte- dir [4-8].
Kutanöz paraneoplastik sendromlar altta yatan tümör- le ilişkili olabilmektedir. Bunlar; çomak parmak, hipertro- fik osteoartropati, dermatomiyozit, multisentrik retikülo- histiyositoz, eritema giratum repens, nekrolitik migatuvar
eritem, Trousseasu’s sendromu, akantozis nigrikans, pal- mar hiperkeratoz, akkiz iktiyoz, pitiriyazis rotunda, Bazex’s sendromu, extramammar paget, leser-trelat sendromu ve akkiz hipertrikozis lanoginosadır. Kutanöz paraneoplastik sendromun bulunması sıklıkla kötü prognoz belirtisidir [9]. İleri yaş bir hastada ani ortaya çıkışlı yaygın seboreik ke- ratozları gördüğümüzde Leser-Trelat sendromunu akla getirerek gizli internal malignite açısından hastanın sor- gulanması gerekmektedir. En kısa sürede; rutin hematolo- jik ve biyokimyasal analizler, akciğer röntgeni, mammog- rafi, servikal sitoloji, prostat spesifik antijen, gastrointes- tinal sistemin endoskopisi, ultrasonografi ve tomografik tetkikler yapılmalıdır [10, 11].
Hastamız böbrek kanseri tanısı almadan 6 ay önce sebo-
reik keratozlarının arttığını ifade etmekteydi. Nefrektomi sonrası dönemde seboreik keratozlarında artış olmayan hastanın son 6 aydır lezyonlarında tekrar artış olması ve yine 6 ay önce benign prostat hipertrofisi tanısı almış ol- ması yeni lezyonların benign prostat hipertrofisi ile ilişki- li olabileceğini düşündürmektedir. Metastazı ve nüksü ol- mayan hastada benign prostat hipertrofisi dışında başka bir rahatsızlık yoktu.
Literatür araştırmamızda ve textbooklarda benign pros- tat hipertrofisi ile ilişkili Leser-Trelat olgusunun bulun- maması, şu ana kadar bildirilmiş ikinci böbrek adenokar- sinom ilişkili Leser-Trelat sendromu olması ve ikinci kez aynı hastanın Leser-Trelat sendromu tanısı alması nede- niyle bu olgumuzu sunmayı uygun gördük.
Kaynaklar
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10. Scully C, Barret WA, Gilkes J. Oral acanthosis nigricans, the sign of Leser-Trélat and cholangiocarcinoma. British Journal of Dermatology 145 (3), 506–507.
11. Ceylan C, Alper S, Kılıc I. Leser-Trelat sign. Int J Dermatol 2002;41:687-688.
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Tuncer Sacar, Handan Sacar. A Leser-Trelat Syndrome Associated with Renal Adenocarsinoma and Benign Prostat Hypertrophia. J Clin Anal Med. 2010;1(2):44-46
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Primary “Lymphoepithelioma-Like Carcinoma” of the Lung
Ülkü Yazıcı, Erkmen Gülhan, Ertan Aydın, Pınar Yaran, İrfan Taştepe
Göğüs Cerrahisi Kliniği, Atatürk Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi, Ankara, Türkiye
DOI: 10.4328/JCAM.10.2.24 Received: 10.11.2009 Accepted: 05.12.2009 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2): 40-43
Corresponding author: Ülkü Yazıcı, Department of Thoracic Surgery, Atatürk Training and Research Hospital for Chest Disease and Chest Surgery, Sanatoryum Caddesi Keçiören, Ankara 06280 Turkey. Phone: +90312 355 21 10 Fax :+9 0312 355 21 35 E-mail: ulku_yazici@yahoo.com
Primary Lymphoepithelioma-like Carcinoma of the lung is commonly encountered in the nasopharyngeal region. The oral cavity, salivary glands, lung and stomach are other sites of localization. Primary Lymphoepithelioma-like Carcinoma of the lung is very rare. In our clinic 3 male and 1 female patients have been diagnosed as Lymphoepithelioma-like Carcinoma between 2000-2007. Mean age was 33. 25 years (range from 22 to 49). 2 patients presented as left hilar, 1 as right hilar, and 1 as tracheal mass. One patient was given radiotherapy after a left pneumonectomy. The remaining 3 patients received chemotherapy: 1 due to esophageal invasion, and the other 2 after biopsy via thoracotomy. All patients are still under follow-up.Lymphoepithelioma-like Carcinoma is common in the Asian population. Publications including long-term follow-up such patients are limited and the issue needs more research. Current articles state that the optimal median survival is 2 years.
Keywords: Lymphoepithelioma-Like Carcinoma, Lung, Epstein-Barr Virus, Surgery.
Giriş
Akciğerin Lemfoepiteliyoma-like karsinomu (LELC) ilk kez 1987 yılında Begin ve arkadaşları tarafından tanımlanmıştır ve akciğerin large hücreli andifferansiye karsinomundan histolojik bir antite olarak ayrılmıştır [1]. Son derece az görülmekle beraber asya nüfusunda insidansı oldukça fazladır [2]. Epstein-Barr virus (EBV) ile ilişkisi değişkendir, anlamlı coğrafik ve etnik varyasyonlar içermektedir. EBV nun nazofaringeal karsinoma ile ilişkisi uzun yıllardır bilinmektedir. Son yıllarda bu virusun nazofarinks dışında mide, timus, tükrük bezi ve akciğerde de yerleştiği bilinmektedir [3-5]. Deri, serviks, oral kavite ve diğer nadir bölgelerde de izlenebilen LELC olgularında ise EBV ilişkisi gösterilememiştir.
Olgular
2000-2007 yılları arasında kliniğimizde 4 LELC olgusu takip edilmiştir.
Olgu grubumuzun 3’ü erkek, 1’i kadın olup, yaş dağılımla- rı 22-49 idi (ortalama yaş: 33.2). 3 olgumuzda sigara içi- cisiydi. En sık karşılaşılan semptomlar sırt ağrısı, kilo kay- bı ve öksürüktü.
Olgularımızın tamamına posterior anterior ve yan akci- ğer grafisi, bilgisayarlı akciğer tomografisi, manyetik re- zonans görüntüleme (MR), kraniyal tomografi, batın ultra- sonografisi yapıldı. 1 numaralı olgumuzda trakeayı sağ- dan çevreleyen, prevasküler alandan subkarinal düzeye kadar uzanan, MR özefagus ile sınırları net ayrılamayan kitle lezyonu görünümü mevcuttu (Resim1), 2 numaralı ol- gumuzda sol hiler kitle, sol akciğerde atelektazi, medias- tinal yapılarda sola deviasyon (Resim2), 3 numaralı olgu- muzda sol hiler kitle ve 4 numaralı olgumuzda sağ hiler kitle görünümü mevcuttu.
4 olgumuza bronkoskopi yapılmış, 3 olgumuza tanı konu- labilmiştir. Histolojik olarak primer akciğer LELC tanısı konulan tüm olgularımız nazofaringeal karsinom yönün- den değerlendirilmiştir. 3 olgumuza nazofarinks biyopsisi yapılmış, tümör hücresine rastlanılmamış- tır. 1 no’lu olgumuzda bronkosko- pik olarak trakea alt ucunda karinaya 1 cm uzaklıkta endobron- şial lezyon (EBL) izlendi. MR in- celemesinde trakea ve özefagus invazyonu tespit edildi. T4 NxM1 (Evre IV) olarak değerlendirildi, 4 kür KT verildi. 2 no’lu olgumu- zun sol ana bronşunda karinaya 2 cm den daha uzak yerleşimde EBL görünümü mevcuttu. Pnömonektomi yapıldı. Subkarinal lenfnodunda tümöral infiltrasyon izlendi. T2N2Mo (Evre III A) olarak kabul edildi. Postope- ratif KT tedavisi verildi. 3 nolu olgumuzun sol alt lob giri- şini kapatan EBL u mevcuttu. Sol torakotomi yapıldı. İnt- raperikardial inferior pulmoner ven invaze idi. Paryetal, diyafragmatik, mediastinal plevra örneklerinde ve aorti- kopulmoner pencere lenf nodunda tümör tutulumu tespit edildi. T4N2Mo (Evre III B) olarak değerlendirildi. KT te- davisi verildi. 4 no’lu olgumuzun bronkoskopik değerlen- dirilmesi normaldi. Torakotomisinde orta lobda kitle, orta lobda ve üst lobda multible noduller tespit edilmesi üze- rine, orta lobdan biyopsi alındı. T4NoM1 (Evre IV) ola- rak değerlendirilerek KT tedavisi verilmiştir (Tablo1). Ta- kip edebildiğimiz 2 olgumuz postoperatif 24. ve 32. aylarda kaybedilmiştir.
Tartışma
Akciğerin LELC sı dünya çapın- da oldukça az görülen bir tümör- dür. Beyaz ırka oranla Asyalılar- da, özellikle çin nüfusunda daha fazla görülmektedir [1]. İlk kez 1987 yılında tariflenmiştir. Akci- ğerin large hücreli undifferansiye karsinomundan histolojik bir antite olarak ayrılmıştır. Olgularımızın patolojik değerlendi- rilmesinde tümör lemfosit ve plasma hücrelerinden zen- gin bir stroma içinde yerleşmiş veziküler ve belirgin nükle- uslu, geniş sitoplazmalı hücrelerden oluşmaktaydı.
LELC major olarak foregut kökenli olan farenks, mide, ak- ciğer, tükrük bezi ve timus gibi organlarda görülmektedir. Bu bölge lokalizsayonlarında EBV enfeksiyonu ile ilişkisi gösterilmiştir [6-8]. LELC nun daha az görüldüğü deri, va- gen, serviks, mesane tutulumlarında EBV enfeksiyonu ile ilişki gösterilememiştir [9,10].
Olgularımızda olduğu gibi tümör sıklıkla adult yaş grubunda görülmektedir[11]. Cinsiyet yatkınlığı gösterilememiş- tir. Sigara kullanımı ile ilişkisi ile ilgili olarak %25-40 ara- sında değişen oranlar bildirilmektedir, oysa akciğerin di- ğer tümörlerinde bu oran %90 ve üzerindedir [12]. Bizim 3 olgumuzda sigara kullanma hikayesi mevcuttur.
Hastalık soliter pulmoner nodül görünümünde tesadüfen tespit edilebileceği gibi, ciddi yaygın hastalık devresinde de bulunabilmektedir. Bizim 1 olgumuz evre III A, 1 olgu- muz evre III B, 2 olgumuz da evre IV aşamasındadır. Tes
pit yapılan aşamaya göre semptomlar gelişmektedir. Bi- zim hasta grubumuzda en sık göğüs ağrısı ve kilo kaybı gözlenmekteydi.
Primer akciğer LELC tanısı konulan olgularda nazofaringe- al bölgenin araştırılması aşamasında nazofarengeal böl- gede şüpheli bir lezyon yoksa ve lezyon bilgisayarlı tomog- rafi ile gösterilemiyorsa nazofaringeal bölgeden biyopsi alınması önerilmemektedir [1]. 2 no’lu olgumuzda nazofa- ringeal bölgede kitle görünümü vardı, biyopsisinde tümör hücresine rastlanmadı. Bildirici ve arkadaşları T2N0M0 ev- resinde tanı koydukları primer LELK olgularında nazofarin- geal bölgenin temiz, EBV yönünden negatif olarak değer- lendirildiğini bildirmişlerdir [12].
Nazofarengeal LELC yüksek oranda radyosensitif bir tü- mördür ve son yıllarda kemosensitif olduğuna dair yayın- lar mevcuttur [12]. Fakat akciğerin LELC da RT ve KT nin tedavideki başarıları belirsizdir. Bununla beraber hasta- lık klinik olarak operabl ise cerrahi uygulanmalıdır. İnope- rabl olgularda KT, RT veya her ikisinin kombinasyonu ve- rilebilir. Adjuvan RT veya KT opere olabilecek hastalarda avantajlar sağlamaktadır [1]. (Olgularımıza KT protokolü olarak sisplatin 80 mg/m2 1. gün, Vinoralbin 30 mg/m2 1.ve 8. günlerde 21 günlük periyotlar halinde verilmiştir. ) Akciğerin LELC u yüksek oranda sistemik metastaz ya- pabilmektedir ve akciğerin diğer nonsmall akciğer malig- nitelerine göre metastazları ciddi oranda kemosensitifdir [1]. Akciğerin LELC’nin diğer akciğer maligniteleri arasın- da %0.87 ile % 3.6 arasında değişen oranlarda görüldüğü ifade edilmektedir [2].
Dünya çapında oldukça az görülen akciğerin LELC nın uzun dönem takip bilgileri oldukça sınırlıdır ve bu konuda daha çok çalışmaya gereksinim vardır. En iyi yaşam süre- sinin ortalama 2 yıl olduğunu ifade eden çalışmalar var- dır [2 ]. Bizim takip edebildiğimiz iki olgumuzda yaşam sü- releri 24 ve 32 ay olup bu konu ile ilgili literatür bilgileri ile uyum göstermektedir. Yazımızda, ülkemizde de olduk- ça nadir olarak izlenen bu tümöre yönelik klinik tecrübele- rimizi paylaşmayı amaçladık.
Kaynaklar
1. Anthony TCC, Peter MLT, Kwok CL, et al. Multimodality treatment of primary Lymphoepithelioma-Like Carcinoma of the lung. Cancer 1998 ; 83:925-9.
2. An-jia H, Min X, Young-shen Z. Association of Epstein-Barr virus with Lymphoepithelioma-Like Carcinoma of the lung in southern china. Am J Clin Pathol 2000; 114:220-6.
3. BurkeAP, Yen TSB, Shekitka KM, et al. Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstarated by polymerase chain reaction. Mod Pathol 1990; 3:377-80.
4. Dimery IW, Lee JS, Blick M, et al. Association of the Epstein-Barr virus with lymphoepithelioma of the thymus. Cancer 1988; 61:2475-80.
5. Hamilton-Dutoit SJ, Hamilton TM, Nielsen NH, et al. Undifferantiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of the Epstein-Barr virus DNA by in situ nuclei acid hybridization. Hum Pathol 1991; 22:811-5.
6. Chan JKC, Hui PK, Tsang WYW, et al. Primary lymphoepithelioma-like carcinoma of the lung. Cancer 1995; 76:413-22.
7. Iezzoni IC; Gaffey MJ, Weiss LM. The role of Epstein-Barr virus in lymphoepithelioma-like carcinomas.
Am J Clin Pathol 1995; 103:308-15.
8. Oda K, Tamara J, Takenouchi T, et al. Association of Epstein-Barr virus gasric carcinoma with lhymphoid stroma. Am J Pathol 1993; 143:1063-74
9. Land AC, Breer WA, Wick MR. Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis: A pattern or an entity? A case report. Cancer 1999; 85:884-890.
10. Weiss LM, Mohaved LA, Butler A, et al. Analysis of lymphoepithelioma and lymphoepithelioma-like carcinomas of different organs for Epstein-Barr viral genomes by in situ hybridization. Am J Surg Pathol. 1989; 13:625-31.
11. John K.C.C, Pak-kwain H, William Y.W, et al. Primary lymphoepithelioma-like carcinoma of the lung. Cancer 1995; 76:413-22.
12. Hammar SP. Common neoplasms. In: Dail DH, Hammar SP, editors. Pulmonary pathology. 2nd ed. New York: Springer-verlag. 1994; 1123-278.
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Ulku Yazici, Erkmen Gulhan, Ertan Aydin, Pinar Yaran, Irfan Tastepe. Primary Lymphoepithelioma Like Carcinoma of the Lung. J Clin Anal Med. 2010;1(2):40-43
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Tracheobronchopathia Osteochondroplastica: Owing to a Case
Burçin Çelik 1, Salih Bilgin 2
1 Göğüs Cerrahisi Anabilim Dalı, Ondokuz Mayıs Mayıs Üniversitesi Tıp Fakültesi, 2 Göğüs Hastalıkları Kliniği, Samsun Göğüs Hastalıkları ve Göğüs Cerrahisi Hastanesi, Samsun, Türkiye
DOI: 10.4328/JCAM.10.2.23 Received: 07.11.2009 Accepted: 22.12.2009 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2):37-39
Corresponding author: Burçin Çelik, 19 Mayıs Üniversitesi Tıp Fakültesi Göğüs Cerrahisi AD, Kurupelit, 55139, Samsun, Türkiye. Phone: +90 362 312 19 19/2701 Fax: +90 362 457 60 41 E-mail: cburcin@hotmail.com
Tracheobronchopathia osteochondroplastica (TBO) is a rare be-nign disease characterized by the presence of the submucosal nodules projecting into the tracheobronchial tree. This disease is usually asymptomatic and has a benign course. A 61-year old man was admitted with cough and hemoptysis for further evalu-ation. A chest computed tomography demonstrated emphysema and subpleural bullea in both upper lobes, and consalidation in the left lower lobe. A fiberoptic bronchoscopy revealed multiple white, irregular nodules on the anterior and lateral walls of the trachea extending to the level of the carina. The patient was dis-charged with medical therapy. TBO should be considered in the differential diagnosis as an unusual cause of persistent cough, hemoptysis, persistent atelectasis and recurrent segmental or lobar infection. There is no specific therapy for this entity. The prognosis of TBO is generally good and depends on the extent and the location of the lesions.
Keywords: Tracheobronchopathia Osteochondroplastica, Bronchoscopy, Diagnosis.
Giriş
Trakeobronkopatia osteokondroplastika (TBO) trakea ve bronşların lümenine doğru uzanan, kemik ve kıkırdak do- kusu içeren submukozal nodüllerle karakterize benign bir patolojidir. Bu nodüller genellikle trakeada, subglottik la- rinkste ve bronş ağacında bulunurlar [1–4]. İlk olarak Wilks [5] tarafından 1857 yılında tüberkülozdan ölen bir has- tanın otopsisi sırasında tanımlanmıştır. Genellikle 50 yaş üstünde tanı konulur ve cinsiyet farkı izlenmez. Olgula- rın çoğunluğunda yakınma yoktur, klinik belirtiler obstrük- tif ve infeksiyöz komplikasyonlar olunca ortaya çıkar [2, 3]. Çalışmanın amacı bronkoskopi ile tanı koyduğumuz bir trakeobronkopatia osteokondroplastika olgusunu sun- maktır.
Olgu
Altmış bir yaşında erkek hasta son bir haftadır devam eden öksürük ve beraberinde kanlı balgam şikayetinin değerlendirilmesi amacıyla başvurdu. Hastanın soy geçmişinde herhangi bir özellik yok iken öz geçmişinde solunum yolu enfeksiyonu ile hastaneye birçok kere başvurduğu saptandı. Dinlemekle akciğer sesleri özellikle sol alt lobda azalmıştı. Direkt akciğer grafisinde sol alt zonda infiltrasyon, parankimde yaygın amfizem alanları mevcuttu (Resim 1). Hastanın laboratuar incelemelerinde sadece sedimentasyon değeri yüksekti (62 mm/saat). Solunum fonksiyon testinde FVC 3.88 L (%107), FEV1 3.84 L (%113), FEV1/FVC %98.4 olarak saptandı.
Toraks bilgisayarlı tomografide (BT) her iki akciğer üst zonlarda amfizem alanları ve subplevral büller, sol üst lob alt zonda konsolide alan tespit edilirken TBO’yu destek- leyici bir bulgu izlenmedi (Resim 2). Tanı amaçlı lokal an- estezi altında yapılan fleksibl bronkoskopide trakea ön ve yan duvarlarında karinaya kadar devam eden çok sayıda beyaz renkte, düzensiz nodüler lezyonlar saptandı (Resim 3). Bronkoskopide herhangi bir kanama odağı ve başka bir patoloji saptanmadı, bronşiyal biyopsiler ve bronkoa- lveoler lavaj alındı. Sol akciğerdeki enfeksiyona yönelik medikal tedavi verilen hastanın bronş biyopsisinde ve lavajında herhangi bir patoloji saptanmadı. Klinik ve rady- olojik bulgularla trakeobronkopatia osteokondroplastika tanısı konulan hasta medikal tedavi ve önerilerle taburcu edildi. Yaklaşık 2 yıldır poliklinik takibi altında olan hasta dönem dönem kronik obstrüktif akciğer hastalığına bağlı şikayetlerle başvurmaktadır.
Tartışma
Trakeobronkopatia osteokondroplastikanın etiyolojisi bi- linmemektedir. Kronik enfeksiyonlar, kimyasal ve mekanik iritasyonlar, dejeneratif ve metabolik bozukluklar, konje- nital ve genetik faktörler etiyolojiden sorumlu tutulmak- tadır. Geçmişte tanı genellikle otopsi çalışmaları sıra- sında konulurken günümüzde bronkoskopi ve bilgisayar- lı tomografinin kullanımın artmasıyla kolay tanı koyulur hale gelmiştir [1–4]. TBO insidansının otopsi çalışmala- rında 1:400 ila 3:1000 arasında, bronkoskopi çalışmala- rında 1:125 ila 1:6000 arasında olduğu bildirilmiştir [6, 7]. Bu oranlara göre %0.12 gibi daha düşük insidans bildiren bronkoskopi çalışmaları da mevcuttur [8].
TBO’da genellikle trakeanın alt 2/3’lük kısmı tutulurken larinskten bronşlara kadar tüm bölgelerde tutulabilir. Lobar bronşların distalinde yani segmental bronşlarda lezyon izlenmez. TBO tanıyı destekleyici karakteristik semptom ve bulgulara neden olmamaktadır. Genellikle hastalarda ilk olarak astma ya da kronik bronşit tanısı konulur. Hastanın hikayesinde kronik öksürük, egzersiz dispnesi ve solunum yolu enfeksiyonları genellikle uzun zamandan beri mev- cuttur. Büyüyen nodüller hava yoluna doğru uzandıklarında kronik öksürük, hemoptizi, ısrar eden atelektazi, rekür- ren segmental veya lober enfeksiyonlar ortaya çıkmakta- dır, stridor nadirdir [1, 4, 9].
En önemli tanısal yöntemler bronkoskopi ve BT’dir. BT’de trakea arka duvarını tutmayan dens submukozal nodü- ler lezyonlar saptanırken BT’nin normal olduğu olgular da mevcuttur. Bronkoskopide trakea 2/3 alt bölümde ön ve yan duvarları tutan, sert, beyaz renkli, düzensiz, 1–6 mm ebadında ve çok sayıda nodüllerin izlenmesi ile tanı kesinleşir, bronkoskopik biyopsi genellikle gerekli değildir [3, 4, 9].
Olgumuz kliniğimize alt solunum yolu enfeksiyonu ve hemoptizi bulguları ile başvurdu. Direk akciğer grafisinde ve toraks BT’de TBO’yu destekleyecek bir bulgu izlenmedi. Sol alt zondaki konsolidasyon alanının araştırılması ama- cıyla yapılan bronkoskopide TBO’yu destekleyen tipik submukozal nodüller izlendi, bu nodüller dışında herhangi bir patoloji saptanmadı. Medikal tedavi verilen hasta öneri- lerle taburcu edildi ve halen poliklinik takibi altındadır. TBO tanısı alan hastalar asemptomatik kalabilecekle- ri gibi öksürük, balgam çıkarma, hemoptizi gibi kronik ve tekrarlayan semptomlarla kliniklere başvurabilirler [9]. Bu hastalarda ayrıca literatürde belirtildiği gibi entübasyon güçlüğü ile karşılaşılabilinir. Entübasyon gereken durum- larda hastada TBO tanısı olduğu göz önünde bulundurul- malıdır [10].
Hastalığın spesifik bir tedavisi yoktur, semptomlara yö- nelik konservatif tedavi yöntemleri uygulanır. Prognoz ge- nellikle iyidir ve lezyonların yaygınlığına bağlıdır. Havayo- lu obstrüksiyonu söz konusu olduğunda, lazer uygulaması, bronkoskopik olarak nodüllerin çıkarılması, stent ve rad- yoterapi uygulanmaktadır [1, 2, 4]. Tüm bu palyatif yön- temlerin uygulanamadığı ciddi darlıklarda Grillo ve arka- daşlarının [11] önerdiği linear anterior trakeoplasti uygu- lanabilinir. Lezyonların malignleşme riski yoktur.
Sonuç olarak, trakeobronkopatia osteokondroplastika kronik persistan öksürük, hemoptizi, persistan atelektazi- nin ayırıcı tanısında düşünülmelidir. BT ile her zaman tanıya ulaşılamayabilinir ancak bronkoskopi bu tür şikayet- leri olan hastalarda tanı koydurucudur.
Kaynaklar
1. Abu-Hijleh M, Lee D, Braman SS.Tracheobronchopathia osteochondroplastica: a rare large airway disorder. Lung 2008;186:353–359.
2. Kart L, Kiraz K, Büyüloğlan H, Özesmi M, Şentürk Z, Gülmez İ ve ark. Tracheobronchopathia osteochondroplastica: two cases and review of literature. Tub Toraks Derg 2004;52:268–271.
3. Baran A, Güngör S, Ünver E, Yılmaz A. Trakeobronkopatia osteokondroplastika: bir olgu nedeniyle. Tub Toraks Derg 2004;52:183–185.
4. Prakash UB. Tracheobronchopathia osteochondroplastica. Semin Respir Crit Care Med 2002;23:167–175.
5. Wilks S. Ossific deposits on the larynx, trachea and bronchi. Trans Pathol Soc Lond 1857;8:88.
6. Pounder D, Pieterse A. Tracheopathia osteoplastica: report of four cases. Pathology 1982;14:429–433.
7. Smith D, Pillai R, Gillbe C. Tracheopathia osteoplastica: a cause of unexpected difficulty in tracheal intubation. Anaesthesia 1987;42:536– 538.
8. Bioque JC, Feu N, Rubio JM, Martin MA, Garcia FL, Bravo JM, et al. Tracheobronchopathia osteochondroplastica: clinical study and follow-up in nine cases. J Bronchology 2001;8:78–83.
9. Leske V, Lazor R, Coetmeur D, Crestani B, Chatté G, Cordier JF; Groupe d’Etudes et de Recherche sur les Maladies ”Orphelines” Pulmonaires. Tracheobronchopathia osteochondroplastica: a study of 41 patients. Medicine (Baltimore) 2001;80:378–90.
10. Tadjeddien A, Khorgami Z, Akhlaghi H. Tracheobronchopathia osteoplastica: cause of difficult tracheal intubation. Ann Thorac Surg 2006;81:1480–2.
11. Grillo HC, Wright CD. Airway obstruction owing to tracheopathia osteoplastica: treatment by linear tracheoplasty. Ann Thorac Surg 2005;79:1676–81.
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Burcin Celik, Salih Bilgin. Tracheobronchopathia Osteochondroplastica: Owing to a Case. J Clin Anal Med. 2010;1(2):37-39
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Bifid Rib ; Report of Two Cases and the Efficacy of 3-Dimensional Computed Tomography
Hasan Volkan Kara¹, Kadir Ağladıoğlu¹, Mehmet Deniz Bulut² ,Ufuk Çobanoğlu³, Serhat Oğuz¹
¹Göğüs Cerrahisi Kliniği, Van Asker Hastanesi, ²Radyoloji Kliniği, Yüzüncü Yıl Üniversitesi Tıp Fakültesi, ³Göğüs Cerrahisi Kliniği, Yüzüncü Yıl Üniversitesi Tıp Fakültesi, Van, Türkiye
DOI: 10.4328/JCAM.10.2.21 Received: 27.02.2009 Accepted: 16.10.2009 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2): 31-33
Corresponding author: Hasan Volkan Kara, Göğüs Cerrahisi Uzmanı, Van Asker Hastanesi, Van, Türkiye. GSM: 0 532 409 74 44 • 0 505 237 90 10, E-mail: drvolkankara@yahoo.com.
Congenital anomalies of ribs exist between 0.15% to 30%. These patients have minor symptoms or totally symptom-free. They are generally diagnosed accidentally. There are case report of bifid (forked) ribs in the literature. Bifid rib should be differ-enciated from other pathological situation of lung and chest wall including malignancies. 3-dimensional(3-D) computed to-mography (CT) is a very effective diagnostic tool in differencial diagnosis of bifid rib . We present 2 cases of bifid rib that had the diagnosis by f 3 dimentional (3-D)computed tomography (CT) with the demonstrative images .
Keywords: Bifid Rib; Forked Rib; 3D CT.
Giriş
Kostaların birçok yapısal konjenital anomalisi bulunmakta- dır. Bunlardan literatürde yer alanlar ; servikal , intratora- sik, pelvik kosta , iki veya daha fazla kostanın füzyonu , iki kostanın köprüleşmesi, bifid [çatallanan] kosta ve birinci kostanın psödoartrozudur [1, 2]. Tüm bu yapısal farklılık- ların toplamı nüfusun %0.15-%0.30 unda görüldüğünden nadir vakalar olarak kabul edilirler [1]. Kadınlarda ve gö- ğüs kafesinin sağ tarafında daha fazla görüldüğü bildiril- miştir [3]. Bu yapısal farklılık durumları klinik olarak ge- nellikle hafif şikayetler veya semptomsuz seyretmekte olup dahaçok başkanedenlerileyapılangörüntülemeyöntem- lerinde rastlantısal olarak teşhis edilirler [1, 2]. Konjenital kosta anomalilerinden bifid kosta olguları literatürde vaka takdimi şeklinde yer almıştır.
Kliniğimize başvuruları sonrası bifid kosta tanısı konu- lan 2 olguyu, teşhiste kullanılan 3 boyutlu bilgisayarlı to- mografinin bu durumlardaki etkinliğini değinerek mevcut görüntüleriyle sunmak istedik
Olgu 1
20 yasında erkek hasta, sağ dizinden planlanmış artros- kopik ortopedik cerrahi öncesi anestezi tarafından de- ğerlendirme amaçlı çekilen Postero Anterior (PA) akciğer grafisinde sol 4. kosta anterior yayında şüpheli çatallan- ma görüntüsü üzerine (Resim 1) polikliniğimize konsülte edildi. Hastanın öz ve soygeçmişinde bilinen bir özellik yok idi. Fizik muayenesinde her iki akciğer sesleri tüm alanlarda doğaldı. Sol 4. kostanın ön yayında midklavi- küler hatta net tanımlanamayan bir kostanın şekil bozuk- luğu palpe edildi. Bu bölgede hastanın hassasiyet ya da ağrı şikayeti mevcut değildi.
Diğer sistem muayene ve değerlendirmeleri normal tespit
edildi. Hastanın tüm kan laboratuvar değerleri normal sınırlarda idi. Hastanın olası bifid kosta tanısının netleştiril- mesi için 3 boyutlu (3-D) toraks bilgisayarlı tomografisi (BT) çekildi. Görüntülerde sol 4. kaburga ön yayında kıkır- dak kesime uzanım gösteren çatallanma izlendi (Resim2). Diğer göğüs duvarı bölgeleri ve akciğer parankim kesim- lerinde ek patolojik bulguya rastlanılmadı.
Olgu 2
21 yaşında erkek hasta, sağ hemitoraksın ön yüzünde dışa doğru şekil bozukluğu ve ağrı şikayetiyle polikliniğimize başvurdu. Hikayesinde bu oluşumun küçüklüğünden bu yana var olduğu, zaman zaman ağrıya yol açtığı, ancak bu dönemde kadar herhangi bir tıbbi değerlendirme yapıl- madığını ifade etti. Hastanın yapılan fizik muayenesinde her iki akciğer sesleri tüm alanlarda doğal idi. Sağda 5. kostosternal bileşke lokalizasyonunda dışa ekspansiyon gözlendi. Palpasyonda bu kesimde kosta ön yayının ikiye ayrıldığı (çatallandığı) saptandı. Diğer sistem muayeneleri doğal , yapılan kan laboratuvar değerlendirmeleri normal sınırlarda tespit dildi. Çekilen dijital P-A akciğer grafisin- de sağ 5 . kosta ön sınırında çatallanma görüntüsü izlendi (Resim 3). Hastanın ağrı şikayetlerinin olması sebebiyle muhtemel bir tümöral hadisenin netleştirilmesi için 3 bo- yutlu toraks BT planlandı . Görüntülerde sağ 5. kosta ön yayına çatallanma izlendi (Resim 4). Diğer göğüs duvarı bölgeleri ve akciğer parankim kesimlerinde başka pato- lojik bulguya rastlanılmadı.
Fizik muayene ve 3 boyutlu toraks BT sonuçları eşliğinde her iki vakadaki kaburga durumunun , konjenital bir var- yasyon olan bifid kosta olduğuna karar verildi. Olgulara müdahale planlanmadı , ağrı şikayeti mevcut 2. olguya non spesifik analjezik tedavi sonrası ağrı şikayetleri geriledi , gerekli bilgilendirmeleri yapılan olgular takibe alındı.
Tartışma
Bifid kosta hakkında literatürde az sayıda vaka takdimi mevcuttur. Vaka sunumları ağırlıkla rastlantısal tespit edi- len olgular [4] ve rutin kadavra diseksiyonlarında ortaya çıkan anatomik varyasyonlardır [5]. Bifid kostanın klinik olarak Bazal Nevus Sendromu ile ispatlanmış bağlantısı mevcuttur [6] . Bazal Nevus Sendromu yada Gorlin –Goltz sendromu, toplumda 1/600.000 sıklıkta izlenen otosomal dominant geçişli bir sendromdur. Hastalarda ciltte epider- mal kistler, palmoplantar oyuklar, fasyal milia ve cilt altı kalsifikasyonlar bulunur [6, 7] . İskelet sisteminde bifid , si- nostotik kostalar ve servikal vertebralarla ilişkili kostalar bulunabilmektedir. Her iki hastanında fizik muayenesinde ve tetkilerinde ek patolojik bulgu mevcut olmadığından bu tanıdan uzaklaşılmıştır.
Çocuk çağı kanserlerinden akut lenfoblastik lösemi, ast- rositom, ve germ hücreli tümörlerin servikal kaburga ano- malilerinde yüksek oranda tespit edildiği bilinmektedir[8]. Nöroblastoma olgularında özellikle bifid kaburga oranının arttığı bildirilmiştir [ 9]. Tümor tespit edilen hastalarda mezenkimal defektlerin artmış oranda bulunması tumörün ortaya çıkışında değişmiş morfogenezin ipucu olabileceği halen bir tartışma konusudur [9] .
Osteomyelit, hemanjiomatoziz, özonofilik granülom, anev- rizmal kemik kisti , enkondrom gibi iyi huylu kemik patoloji- lerini tanımlamakta toraks BT sinin yüksek klinik başarısı mevcuttur [10]. Bilgisayarlı tomografi sayesinde kabur- gadaki lezyonun destrüksiyon durumu , plevral efüzyon varlığı, olası bir yumuşak doku invazyonu net şekilde de- ğerlendirilebilir [10]. Her iki hastada olası diğer ön tanıların ekarte edilmesine yardımcı olmak için 3 boyutlu toraks BT uygulanmıştır.
Bifid kosta ve diğer konjenital kosta anomalilerinin birço- ğu belirginbirsemptomasahipdeğildirvebaşkanedenler ile çekilen akciğer grafilerinde ortaya çıkan rastlantısal klinik durumlardır. Konjenital kaburga anomalilerinin diğer malign ve benign kaburga patolojilerinden ayrılmasında 3 boyutlu Toraks BT etkin bir görüntüleme ve tanı metodu- dur [10, 11] . Klinisyenlerin ve radyoloji uzmanları akciğer grafilerinde şüphelendikleri ancak net tanı koymakta güç- lük çektikleri bifid kosta olgularında 3 boyutlu toraks BT ile tanıyı netleştirebilirler.
Kaynaklar
1. Kurihara Y, Yakushiji YK, Matsumoto J, Ishikawa T, Hirata K. The ribs: anatomic and radiologic considerations. Radiographics. 1999 Jan-Feb;19(1):105-19; quiz 151-2.
2. Guttentag AR, Salwen JK Keep your eyes on the ribs: the spectrum of normal variants and diseases thatinvolve the ribs. Radiographics. 1999;19(5):1125- 42.
3. Kohler A., Zimmer EA. Borderlands of normal and early and early pathological findings in skeletal radiology . 3 rd ed . New York , NY: Grune &Straton 1968
4. Batra D, Lawner BJ. Bifid fifth rib in a 9-year-old girl with chest pain. J Am Osteopath Assoc. 2006;106(6):359-60.
5. Osawa T, Sasaki T, Matsumoto Y, Tsukamoto A, Onodera M, Nara E, Chen JK, FujimuraA, Nozaka Y. Bifid ribs observed in the third and the fourth ribs. Kaibogaku Zasshi. 1998 ; 73(6):633-5.
6. Ratcliffe JF, Shanley S, Chenevix- Trench G. The prevalence of cervical and thoracic congenital skeletal abnormalities in basal cell naevus syndrome; a review of cervical and chest radiographs in 80 patients with BCNS. Br J Radiol. 1995;68(810):596-9.
7. Crutchfield CE, Geiger J, Gorlin RJ, Ahmed I. What syndrome is this? Pediatr Dermatol. 2000;17(6):484-6.
8. Merks JH, Smets AM, Van Rijn RR Prevalence of rib anomalies in normal Caucasian children and childhood cancer patients. Eur J Med Genet. 2005 ;48(2):113-29.
9. Schumacher R, Mai A, Gutjahr P. Association of rib anomalies and malignancy in childhood. Eur J Pediatr. 1992;151(6):432-4.
10. Faro SH, Mahboubi S, Ortega W. T diagnosis of rib anomalies, tumors, and infection in children Clin Imaging. 1993;17(1):1-7.
11. Bottosso N,Ghaye B. Bifidintrathoracic rib. JBR-BTR. 2008;91(3):86-7
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Hasan Volkan Kara, Kadir Agladioglu, Mehmet Deniz, Bulut, Ufuk Cobanoglu, Serhat Oguz. Bifid Rib ; Report of Two Cases and the Efficacy of 3-Dimensional Computed Tomography. J Clin Anal Med. 2010;1(2):31-33
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Multiple Intestinal Perforation Due to Wegener’s Granulotamosis: Case Report
Nazif Zeybek 1, Özcan Altınel 1, Faik Yaylak 1,Özgür Albuz 1, Ayper Kaya 2
1 Genel Cerrahi Anabilim Dalı, 2 Patoloji Anabilim Dalı, Gülhane Askeri Tıp Akademisi, Askeri Tıp Fakültesi, Etlik, Ankara, Türkiye
DOI: 10.4328/JCAM.10.2.22 Received: 30.09.2009 Accepted: 12.11.2009 Printed: 01.05.2010 J.Clin.Anal.Med. 2010 ; 1(2): 34-36
Corresponding author: Faik Yaylak, Gülhane Askesi Tıp Akademisi, Askeri Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Etlik, Ankara, Türkiye. GSM: +90 533 338 68 99, E-mail: faikyaylak@lycos.com
Wegener’s granulomatosis is one of the well known vasculitis, which results with necrotizing granulomatous lesions in the upper and lower respiratuary system and glomerulonephritis. Vasculitis is also observed in several other tissues and organ systems including gastrointestinal system. However, gastrointestinal involvement in Wegener’s granulomatosis is extremely rare. This report presents a patient with Wegener’s granulomatosis, who was diagnosed to have multiple intestinal perforations.
Keywords: Wegener’s Granulomatosis, Vasculitis, Acute Abdomen, Intestinal Perforation.
Giriş
İlk kez 1936’da Wegener tarafından tanımlanan ve nede- ni bilinmeyen Wegener Granülomatozis’i birden fazla or- ganı etkileyebilen bir sistemik vaskülit hastalığıdır. We- gener granülomatozisi’nin en sık 4. ve 5. dekatda görül- düğü ve kadın/erkek oranının 2/3 olduğu bildirilmiştir [1]. Etkilediği organların tutulum sıklığı ise sırasıyla akciğer- ler [%94], böbrekler [%85], eklemler [%67], göz [%58], deri [%45], sinir sistemi [%22] ve kalp [%12] olarak bildirilmiş- tir [1,2]. Siklofosfamidin tek başına ya da diğer kortikos- teroidlerle beraber kullanımından önce Wegener granülo- matozisi son derece ölümcül bir hastalık olarak kabul edil- mekteydi [2]. İmmünosüpresiflerin kullanımından önce or- talama yaşam süresi % 82 hastada 5 ay olup, hastala- rın %90’ında yaşam süresi en fazla iki yıldı [1]. Siklofos- fomid ve kortikosteroidlerin kullanıma girmesi ile 10 yıl- lık yaşam süresinin %75 olduğu daha sonraki çalışmalar- da bildirilmiştir [3].
Hastalığın, birçok organ ve dokuyu tutan klasik formu ve izole böbrek tutulumu ile karakterize iki formu bulunur. Tanı, lezyonlardan alınan biyopsi ve/veya Wegener ve ar- kadaşlarının GARK klasifikasyonundaki bulguların, biyopsi ya da c-ANCA pozitifliği ile desteklenmesi ile konulmak- tadır [1]. Gastrointestinal tutulum nadir gözlenir. Akciğer ve böbrek
tutulumu olmadan da gastroin- testinal tutulum olabileceği ve bu tutulumun perforasyonlara yol
açabileceği bilinmektedir [4]. Ayrıca gastrointestinal tutulum olsa bile belirti ve bulgular yaygın olmayıp, saptanmaları zordur [5,6].
Gastrointestinal tutulum, nadiren perforasyona kadar ilerleyen cerrahi problemlere sebep olur.
Skaife ve arkadaşları, Wegener granülomatozis’li bir hastanın medikal tedavi almadan önce, ince barsak iskemisi ve perforasyonu olan bir olgu bildirmişlerdir
[6]. Wegener granülomatozisi’nin
neden gastrointestinal sistemi tuttuğu konusunda deği- şik görüşler mevcuttur. Bazı yayınlarda immunosupressif tedavinin gastrointestinal tutuluma neden olduğu belirtil- miştir [1, 7]. Gastrointestinal tutulum; orofaringeal muko- zal lezyonlardan, gingivitis, gastrik ülser, ince barsak per- forasyonu, kolonik ülserasyon, nükseden peri anal ülserler, kolesistitis, rekürren akut pankreatitis, ekstrahepatik biliyer obstrüksiyonlu, pankreatik kitle ve splenik nekrozi- se kadar geniş bir yelpaze içinde gözlenebilir.
Olgu
Özgeçmişinde 12 yıldır kronik böbrek yetmezliği ve kronik hepatit C hikâyesi olan 52 yaşındaki erkek hasta olup 12 yıldır kronik böbrek yetmezliği ve kronik hepatit C hikâyesi
mevcuttur. Dört yıl önce başlayan öksürük, kanlı balgam şikâyetleri nedeniyle yapılan bronkoskopik biyopsisinde nekrozitan vaskülitis tespit edildi. Alınan cilt biyopsis- inde lökoklastik vaskülitis, immün floresan incelemede üst dermisteki damarların duvarlarında C3(+++), IgG(++), IgM(++) ve fibrinojen(++) birikimi saptandı. Hastada cilt, böbrek, solunum yolu ve barsak tutulumunun da olması Wegener Granülomatozisi’ni düşündürmüştür. Ocak 2006’da tüm vücutta vaskülitik döküntüler, sol elde yara, peri anal bölgede akıntı şikâyetleri ile acil cer- rahi polikliniğine müracaat eden hastaya peri anal apse drenajı ve antibiyotik tedavisi uygulandı. Cerrahi drena- jdan 6 gün sonra karın ağrısı, iki gündür defekasyon ya- pamama şikâyetleri ile tekrar müracaat eden hastanın fizik muayenesinde; barsak sesleri hipoaktif, karında dört kadranda da yaygın defans ve rebaund tespit edildi. Tam kan tetkikinde; lökosit sayısı, 6000/mm3 idi. Hastanın düz karın grafisinde, diafragma altında serbest hava gözlendi. Batın ultrasonografisinde ve batın bilgisayarlı tomografisinde barsak ansları arasında sıvama tarzında mayii gözlendi. Akut batın ön tanısı ile ameliyata alınan hastanın batın eksplorasyonunda; jejunum, ileum ve çe- kumda multiple perforasyonlar gözlendi (Resim 1). Acilen
ameliyata alınan hastaya; sağ hemikolektomi + parsiyel ileum rezeksiyonu + uç ileostomi + multipl jejunal wedge rezeksiyon + jejunum primer tamiri yapıldı. Sefazolin so- dyum 3×1 gr /gün iv + metranidazol 2×500 mg IV 5 gün uygulandı. Ateşin 390C üzerinde seyretmesi nedeniyle antibiyotik komitesi tarafından imipenem silastatin so- dyum 4×500 mg /gün iv, tedaviye eklendi. Rezeke edilen piyeslerin patolojik incelemesinde ince barsakta; iskemik nekroz ve perforasyon, kalın barsakta; transmural inflamasyon gözlendi ve bulguların Wegener Granülomatozisi ile uyumlu olabileceği düşünüldü (Resim 2). Olgu postoperatif onbeşinci günde sepsis nedeniyle kaybedildi.
Tartışma
Wegener Granülomatozisi’nin etiyolojisi tam bilinmemek- le birlikte, vaskülitik lezyonlarda granülom oluşumunun belirleyici özellik oluşu ve makrofaj/CD4 hücrelerinin bas- kın hücreler olarak görülmesi, etiyopatogenezde T hüc- re aracılı gecikmiş aşırı duyarlılık reaksiyonunu suçlan- maktadır [1]. Wegener Granülomatozis’li hastalarda en sık gözlenen patoloji bulgusu; lökositoklastik vaskülittir.
[5]. Olguların %14 ünde cilt tutulumu mevcuttur. Hemop- tizi hastalığın sık görülen bir bulgusudur [1, 5]. Tanı aktif lezyonlardan alınan biyopsi ile konur. Solunum sisteminden alınan biyopsi örneklerinde granülomatöz nekrozitan vas- külit bulguları, böbrek biyopsi materyalinde ise fokal segmental glomerülonefrit tespit edilir [1]. Laboratuar bulgu- ları açısından c-ANCA pozitifliği [özellikle geniş tutulumlar- da] çok önemlidir. Bununla birlikte yayınlanmış 3 perforas- yon olgusunda c-ANCA negatif olarak saptanmıştır [5, 8]. Sunduğumuz olgu, akut batın nedeni ile yapılan operas- yonda alınan biyopsi ve doku piyesleri, daha önce Wegener Granülomatozisi tanısı alan hastanın tanısını des- tekler nitelikte idi. Biz bu vakada gastrointestinal sis- temdeki multiple perforasyonların nedeninin Wegener Granülomatozisi’nde görülen vaskülit sonucu oluşan iske- miye bağlı olabileceğini düşündük.
Sonuç olarak Wegener Granülomatozisi’ne bağlı ince barsak perforasyonunun nadir görülmesi nedeniyle; bu has- talıktan tedavi edilen olguların karın ağrısı şikâyetlerinde, perforasyona kadar ilerleyen barsak lezyonlarının olabi- leceği, akut batın nedeniyle eksplorasyonda ise multiple barsak perforasyonlarıyla karşılaşıldığında postoperatif tedavinin doğru yapılması yönünden romatolojik patolojilerin barsak tutulumlarının da olabileceği göz önünde bulundurulmalıdır.
Kaynaklar
1. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s Granulomatozis Prospective clinical and therapeutic experience with 85 patients for 21 years Ann Intern Med. 1983; 98:76-85.
2. Regan MJ, Hellmann DB, Stone JH. Treatment of Wegener’s Granulomatosis Rheum Dis Clin North Am. 2001; 27: 865-886.
3. Koldingness W, Nossent H. Predictors of survival and organ damage in Wegener’s Granulomatosis. Rheumatology. 2002; 41: 572-581.
4. Shaikh FM, Sabu CB, Peirce TH, Naqvi SA. Extensive intestinal ischaemic necrosis in Wegener’s Granulomatosis. Gut. 2006;55: 1368-1369.
5. Lie JT. Wegener’s Granulomatosis: histological documentation of common and uncommon manifestations in 216 patients. Vasa. 1997; 26: 261-270.
6. Skaife P, Lee S, Ramadwar M, Maitra D, Edwardson KF. Intestinal perforation as a presentation of Wegener’s Granulomatosis. Hosp Med. 2000; 61: 286-87.
7. Takwoingi YM, Dempster JH. Wegener’s Granulomatosis: an analysis of 33 patients seen over a 10 year period. Clin Otolaryngol. 2003; 28: 187-194.
8. Özbalkan Z, Kiraz S, Öztürk MA, Ertenli Aİ, Apras S, Calguneri M. Wegener’s Granulomatosis: clinical and laboratory results of a university hospital study of 20 patients from Turkey. Clin Rheumatol. 2006; 25:358–363.
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Nazif Zeybek, Faik Yaylak, Ozcan Altinel, Ozgur Albuz, Ayper Kaya, Yusuf Peker. Multiple Intestinal Perforation Due To Wegener Granulotamosis: Case Report. J Clin Anal Med. 2010;1(2):34-36
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Management of Parapneumonic Effusions
Richard W. Light
Professor of MedicineVanderbilt University, Nashville, Tennessee, USA
DOI: 10.4328/JCAM.10.2.41 Received: 17.01.2010 Accepted: 30.01.2010 Printed: 01.05.2010 J.Clin.Anal.Med. 2010;1(2).47-50
Corresponding Author: Richard W. Light, Professor of Medicine, Vanderbilt University, Nashville, Tennessee, USA. E-mail: richard.w.light@vanderbilt.edu
Pleural effusions associated with pneumonia (parapneu-monic effusions) are one of the most common causes of exudative pleural effusions in the world [1]. Approximately 20 to 40% of patients hospitalized with pneumonia will have an accompanying pleural effusion [1]. The presence of a pleural effusion is associated with worse outcomes in patients with pneumonia. In one study of patients hospitalized with pneumonia the mortality risk was 6.5 times higher if the patient had bilateral pleural effusion and 3.7 times higher if the effusion was unilateral than if the patient had no pleural effusion [2]. At least part of the increased mortality with parapneumonic effusions is due to mismanagement of the pleural effusion.The likelihood of developing a pleural effusion with a bacterial pneumonia is dependent upon the organism re-sponsible for the pneumonia. The distribution of organisms responsible for parapneumonic effusions is quite different from the distribution of organisms responsible for pneumonia in general. Organisms responsible for community and hospital acquired pneumonia with complicated parapneumonic effusions also differed consider-ably in a recent multicenter study from the United King-dom [3]. For the 336 patients with community acquired pneumonias with parapneumonic effusions in whom the responsible bacteria were identified, the most common organisms were Strept. Milleri group 32%, anaerobes 16%, Strep. pneumoniae 13% and Staph. aueus 11%. For the 60 patients with hospital-acquired pneumonia, the most common organisms were multiple resistant Staph. aureus 28%, other Staph. 18%, Enterobacteriacea 15% and Enterococci 13% [3]. These numbers should be kept in mind when selecting antibiotics for patients with parapneumonic effusions.
Any patient with pneumonia should be assessed for the possibility of a parapneumonic effusion. Patients with pneumonia have similar symptoms whether or not they have a pleural effusion [4]. All pneumonia patients should have a lateral chest x-ray in addition to the posterioan- terior chest x-ray. If both diaphragms are not visible throughout their course, the possibility of a pleural effu- sion should be assessed with a CT scan, ultrasound or a lateral decubitus radiograph.
There are several pleural fluid findings that are sugges- tive that a patient will need more invasive therapy (at least tube thoracostomy) for their pleural effusion (Table 1). Therefore, if the patient has more than a minimal pleural effusion, the pleural fluid should be sampled to see if any of the factors in Table 1 are present. The pleural fluid with parapneumonic effusion is an exudate and the differential cell count reveals predominantly neutrophils. If mononuclear cells predominate in the pleural fluid, an alternative diagnosis should be sought [1]. The lower the pH and the glucose and the higher the LDH, the more likely that the patient will need an invasive procedure for their parapneumonic effusion [1]. The low pleural fluid pH and glucose and the higher LDH are more effective at identifying complicated parapneumonic effusions than are procalcitonin, lipopolysaccharide-binding protein, C- reactive protein and triggering receptor express on my- eloid cells (sTREM-1) [5].
When faced with a patient with a parapneumonic effu- sion, it is important to realize that not all effusions need to be treated in identical manners. The American College of Chest Physicians (ACCP) [6] developed the classifica- tion shown in Table 2 to assist the practicing physician in managing patients with pleural effusions. Several com- ments should be made about this classification. (a) With category 1 effusions, no thoracentesis is indicated and no chemistries or bacteriology are obtained because ef- fusions this small virtually always resolve without diffi- culty. (b) If the pH is used for the classification it must be measured with a blood gas machine – pH meters and indicator strips are not sufficiently accurate [7]. (c) If a pH measurement is not available, an alternative to the pH is a glucose level of 60 mg/dl. (d) There is nothing magic about a pH measurement of 7.20 or a glucose level of 60 mg/dl– the lower the worse with both measurements. (e) The ACCP recommended that categories 3 and 4 be treated with drainage. Although they stated that thera- peutic thoracentesis or chest tube alone is insufficient for most patients with category 3 or 4, many patients are cured with one of these methods [1]. (f) The ACCP recommended that fibrinolytics, thoracoscopy or thoraco- tomy are acceptable approaches for managing patients with category 3 or 4 without indicating which patient should receive which treatment [6].
In order to categorize patients who have pleural effusion other than category 1, the pleural fluid must be sampled. There are three possible means to do this: (a) a diagnos- tic thoracentesis, (b) a therapeutic thoracentesis or (c) the insertion of a small chest tube. Although there are no studies comparing the three methods, I prefer either a therapeutic thoracentesis or the insertion of a small chest tube. The advantage of inserting a small chest tube is that if the fluid continues to be formed, it can be removed as it is formed. The advantage of a therapeutic thoracentesis is that if all of the fluid is removed and if it does not recur, then one need not worry about the pleural fluid. If the fluid recurs, a repeat thoracentesis or a small chest tube should be inserted if the patient has any of the characteristics listed in Table 1.
In most instances when the pleural fluid is loculated with a parapneumonic effusion, the patient will not recover unless the fluid is drained. The loculation is produced by fibrous membranes that partition the pleural space. Frequently when the pleural fluid is loculated, the lung is also encased with a fibrin membrane which prevents the lung from re-expanding. If the pleural fluid is infected, the pleural infec- tion cannot be eradicated unless the fibrin membrane encasing the lung is removed so that the lung can expand and the fill the pleural space. Five procedures have been proposed to remove the loculated
pleural fluid: the insertion of multiple chest tubes, the in- trapleural administration of fibrinolytics, thoracoscopy with the breakdown of fibrin membranes and sometimes decortication, thoracotomy with decortication, and an open drainage procedure. I do not recommend multiple chest tubes because there are frequently multiple locules of the pleural fluid. With thoracoscopy or thoracotomy, the fibrous membrane encasing the lung can also be re- moved which allows the lung to expand.
There have been many articles attesting to the effica- cy of fibrinolytics in the treatment of loculated parap- neumonic effusions [1]. The theory behind their use is that the loculations are produced by fibrin membranes and the fibrinolytics could destroy these membranes and facilitate drainage of the pleural fluid. However, a large multicenter, randomized, placebo controlled, double-blind study cast doubt on the effectiveness of fibrinolytics in reducing hospital stays, mortality or the need for surgi- cal intervention [8]. In this study 454 patients were ran- domized to receive 250,000 IU of streptokinase or saline, twice daily for three days, both in a total volume of 30 ml [8]. In this study the patients receiving placebo had a slightly higher likelihood of surviving without surgery than the patients receiving streptokinase and had nearly identical hospitalization times. In our empyema model in rabbits the intrapleural administration of tissue plas- minogen activator (tPA) did not significantly improve the empyema scores [9].
In view of the above studies, what is the rightful place of fibrinolytics in the management of complicated parap- neumonic effusions? It is my recommendation that fibrin- olytics should be reserved for patients in centers without access to video assisted thoracic surgery (VATS) and for patients who are not surgical candidates.
What is the future of fibrinolytics in the management of loculated parapneumonic effusions? It is possible that the newer fibrinolytics such as tPA or the combination of a fibrinolytic plus a DNAse may be efficacious. Indeed in our rabbit empyema model the intrapleural administra- tion of the combination of tPA plus a DNAse significantly reduced the empyema scores [9]. Moreover, a large mul- ticenter randomized double blind study has recently been completed that compared the effectiveness of 10 mg tPA, 4 mg DNAse, 10 mg tPA plus 4 mg DNAse and saline in patients with complicated parapneumonic effusions [10]. In this study the combination of tPA and DNAase was significantly more effective in reducing the amount of the hemithorax occupied by pleural fluid than were any of the other three regimens [10]. Indeed as in the previ- ous study, the results with saline and with the two agents individually were virtually identical [10]. Accordingly, if fibrinolytics are used in loculated parapneumonic effu- sions, it is recommended that they should be combined with DNAse.
Probably the best management of patients with loculated pleural fluid is the performance of VATS with the break-
down of adhesions, the optimal placement of chest tubes and decortication if necessary. When four studies [11-14] with a total of 232 patients are combined, VATS was the definitive procedure in 77% of the patients, the overall mortality rate was 3% and the median time for chest tube drainage after the procedure ranged from 3.3 to 7.1 days. In many of these patients decortication was also performed. In general, patients who require open tho- racotomy had their complicated parapneumonic effusion for a longer period before thoracoscopy was attempted. At the time of VATS it is important to make certain that the lung has completely expanded. If the lung is encased by a fibrous peel, decortication (the removal of the fi- brous peel) should be attempted. If this cannot be ac- complished by VATS, then a full thoracotomy should be performed in order to do the decortication. In general VATS is preferred to full thoracotomy as the initial proce- dure since it is associated with a shorter hospitalization and less postoperative pain.
VATS or open thoracotomy should only be performed for pleural sepsis. If the patient has no signs of a systemic infection and has only pleural thickening, neither proce- dure is indicated as the pleural thickening will improve markedly over time without any intervention [15, 16].
If a patient has an infected pleural space that is not re- sponding to therapy, one therapeutic option is an open drainage procedure. With an open drainage procedure portions of one or more ribs are resected and large tubes are inserted into the empyema cavity. The cavity is then allowed to heal from within. The disadvantage of this procedure is that the median time for the drainage site to heal is several months [1].
In summary, the possibility of a parapneumonic effusion should be considered anytime that a patient with pneu- monia is evaluated. If the diaphragms cannot be seen throughout their entirety on a lateral chest radiograph, the possibility of a parapneumonic effusion should be evaluated with ultrasound, CT scan or lateral decubitus radiographs. If there is more than minimal fluid, the fluid should be sampled preferably with a therapeutic thora- centesis or the insertion of a small chest tube. If the fluid is loculated and cannot be removed, the next step is thoracoscopy. If thoracoscopy does not result in com- plete expansion of the lung, thoracotomy with decortica- tion should be performed. Fibrinolytics are reserved for those institutions where thoracoscopy is not available or for patients who refuse or cannot tolerate surgery. When fibrinolytics are used, they should be used in combination with DNAse. An open drainage procedure can also be performed on patients who are not surgical candidates.
References
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Richard W. Light. Management of Parapneumonic Effusions. J Clin Anal Med. 2010;1(2):47-50
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Giant Dissecting Aortic Aneurysm Imitating Pleural Effusion
Göktürk Fındık, Seray Kalaycıoğlu Hazer, Sadi Kaya
Department of Thoracic Surgery, Ataturk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey
DOI: 10.4328/JCAM.10.2.31 Received: 26.11.2009 Accepted: 17.12.2009 Printed: 01.05.2010
Corresponding author: Göktürk Fındık, Department of Thoracic Surgery, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey. Phone: +90 312 355 21 10 Email: gokturkfindik@hotmail.com
62 years old male patient, was admitted to our clinic suffering severe dyspnea. Breath sounds are absent on the left side. The chest graphy, pleural effusion was seen on the left hemythorax (Figure 1). Thoracoabdominal computed tomography showed giant aortic ane-urysm that filled half of the left hemythorax and bilateral polycystic kidney (Figure 2-3).
62 years old male patient, was admitted to our clinic suffering severe dyspnea. Breath sounds are absent on the left side. The chest graphy, pleural effusion was seen on the left hemythorax (Figure 1). Thoracoabdominal computed tomography showed giant aortic ane-urysm that filled half of the left hemythorax and bilateral polycystic kidney (Figure 2-3).
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Gokturk Findik, Seray Hazer, Sadi Kaya. Giant Dissecting Aortic Aneurysm Imitating Pleural Effusion. J Clin Anal Med. 2010;1(2):10.4328/JCAM.10.2.31
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