c-MYC ve EZH-2 ekspresyonu ve Merlin kaybının klinik önemi

Aim:&nbsp;Malignant mesothelioma&nbsp;(MM) is an aggressive tumor originating from pleural, peritoneal or perikardiyal cavities. Although the most powerful&nbsp;prognostic factors&nbsp;are stage and histologic sybtypes there is need to find prognostic and/or predicitve factors for targeted treatment. The aim of this study is to explore the association between known prognostic factors and also prognostic significance of EZH-2, c-MYC and&nbsp;Merlin&nbsp;in MM.Patients and methods:&nbsp;Sixty seven patients with&nbsp;MM&nbsp;followed by Çukurova University Faculty of Medicine Dept of Oncology were evaluated retrospectively. Demographic properties of the 67 patients including asbest exposure, smoker history,&nbsp;tumor localization, histopathologic type, treatment modalities,&nbsp;ECOG&nbsp;performance status and disease stage were evaluated. EZH-2, c-MYC and&nbsp;Merlin&nbsp;expressions were evaluated by&nbsp;immunohistochemistry&nbsp;(IHC) Expression and/or loss of EZH-2, c-MYC and Merlin were compared with demographic/clinical findings and survival times. IBM&nbsp;SPSS&nbsp;version 20.0 was used for statistical analyses. Cut off level for XH-2 was 30%. c-MYC and Merlin were evaluated according to&nbsp;staining&nbsp;intensity as weak (1-19%), moderate (20–59%), strong (60–100%).Findings:&nbsp;Female/male ratio was 38/29, mean age was 60,3 ± 10,5. The majority of the cases had epitheloid type&nbsp;MM&nbsp;(54 cases), 11 had biphasic and 2 had&nbsp;sarcomatoid&nbsp;type. Median overall survival was longer in women, in early stage disease, in non-smokers, in good performance status and in cases with epitheloid type MM.Merlin&nbsp;loss was not found to be associated with overall survival (OS) and&nbsp;progression free survival&nbsp;(PFS). Strong EZH-2 expression with 30% cut off level was found to be associated with shorter overall survival. Strong c-MYC expression was found to be associated with shorter overall survival. Interestingly double expression for EZH-2 and c-MYC was found to be asociated with shortest survival while double negative cases had longest survival. Histologic subtype, stage,&nbsp;ECOG&nbsp;performance status and EZH-2 were found to be prognostic in&nbsp;multivariate analysis.Conclusion:&nbsp;EZH-2, c-MYC and&nbsp;Merlin&nbsp;expressions were detected by&nbsp;IHC&nbsp;in biopsy specimens. EZH-2 and c-MYC expressions were found to be associated with shorter&nbsp;PFS&nbsp;and OS times. However our results must be validated with further studies. It is well known that EZH-2 inhibitors and also c-MYC inhibitors have been found to be successfull in some types of tumors. We can propose that inhibition of EZH-2 and/or c-MYC may be an important therapeutic alternative in cases with&nbsp;MM.</p

Clinical significance of c-MYC and EZH-2 Expressions and loss of Merlin and BAP-1.

TEZ12293Tez (Uzmanlık) -- Çukurova Üniversitesi, Adana, 2019.Kaynakça (s. 111-134) var.XII, 156 s. :_res. (bzs. rnk.), tablo ;_29 cm.Amaç: Malign mezotelyoma (MM), plevral, peritoneal veya perikardiyal boşluklardan kaynaklanan agresif bir tümördür. MM için en güçlü prognostik faktörler evre ve histoloji olmakla birlikte, hassas tıp için MM için prognostik ve / veya öngörücü faktörlerin bulunmasına ihtiyaç vardır. Bu çalışmanın amacı MM'de demografik değişkenler ile BAP-1, EZH-2, c-MYC ve Merlin'in prognostik önemi arasındaki ilişkiyi araştırmaktır. Hasta Seçimi ve Yöntem: Çukurova Üniversitesi Tıp Fakültesi Onkoloji Anabilim Dalı tarafından takip edilen 75 MM hastası retrospektif olarak değerlendirildi. Asbest maruziyeti, sigara içme öyküsü, tümör yerleşim yeri, histopatolojik tip, tedavi yöntemleri, ECOG performans durumu ve hastalık evresi de dahil olmak üzere 75 hastanın demografik özellikleri değerlendirildi. BAP-1, EZH-2, c-MYC ve Merlin ifadeleri 67 vakada immünohistokimya ile değerlendirildi ve ekspresyon düzeyleri ve / veya ekspresyon kaybı ve sonuçları sağkalım süreleri ile karşılaştırıldı. İstatistiksel analizler için IBM SPSS 20.0 sürümü kullanıldı. Bulgular: Kadın / erkek oranı 42/32, yaş ortalaması 60 ± 10,8 idi. Olguların çoğunda epiteloid tip MM (60 olgu), 12'sinde bifazik tip MM ve 3'ünde sarkomatoid tip MM vardı. Ortanca toplam sağkalım, kadınlarda, erken evre hastalığı olanlarda, sigara içmeyenlerde, iyi performans gösteren ve epiteloid tip MM' li olgularda daha uzundu. BAP-1 kaybı ile progresyonsuz sağkalım ve toplam sağkalım arasında ilişkili bulunmadı. Merlin kaybının toplam ve hastalıksız sağkalım ile ilişkili olduğu saptandı. Güçlü EZH-2 ekspresyonunun daha kısa toplam sağkalım ile ilişkili olduğu saptandı. Güçlü c-MYC ekpresyonunun daha kısa toplam sağkalım ile ilişkili olduğu saptandı. EZH-2 ve c-MYC için kombine yüksek ekspresyonun, en kısa sağkalım ile ilişkili olduğu, ikisinin de negatif olduğu vakaların en kısa sağkalıma sahip olduğu saptandı. Çok değişkenli analizlerde histolojik alt tip, evre, ECOG performans durumu ve EZH-2 prognostik faktör olarak bulundu. Sonuç: BAP-1, EZH-2, c-MYC ve Merlin ifadeleri biyopsi örneklerinde veya cerrahi örneklerde immünohistokimya ile tespit edilebilir. Özellikle EZH-2 ve c-MYC ifadelerinin daha kısa hastalıksız ve toplam sağkalım ile ilişkili olduğu bulunmuştur. EZH-2 ve / veya c-MYC'yi hedef almak, MM'li olgularda önemli bir tedavi seçeneği olabilir. Bu sonuçları doğrulamak için daha fazla çalışmaya ihtiyaç vardır.Aim: Malignant mesothelioma (MM) is an aggressive tumor originating from pleural, peritoneal or perikardiyal cavities. Although the most powerful prognostic factors are stage and histology in MM, there is need to find prognostic and/or predicitve factors for MM for precision medicine. The aim of this study is to explore the association between demographic variables and also prognostic significance of BAP-1, EZH-2, c-MYC and Merlin in MM. Patients and methods: 75 patients with MM followed by Çukurova University Faculty of Medicine Dept of Oncology were evaluated retrospectively. Demographic properties of the 75 patients including asbest exposure, smoker history, tumor localization, histopathologic type, treatment modalities, ECOG performance status and disease stage were evaluated. BAP-1, EZH-2, c-MYC and Merlin expressions were evaluated by immunohistochemistry in 67 cases and expression levels and/or loss of expression and results were compared with survival times. IBM SPSS version 20.0 was used for statistical analyses. Findings: Female/male ratio was 42/32, mean age was 60 ± 10,8. The majority of the cases had epitheloid type MM (60 cases), 12 had biphasic and 3 had sarcomatoid type. Median overall survival was longer in women, in cases with early stage disease, in non-smokers, in cases with good performance status and in cases with epitheloid type MM. BAP-1 loss was not found to be associated with progression free survival and overall survival. Merlin loss was not found to be associated with overall and progression free survival. Strong EZH-2 expression with two cut off levels was found to be associated with shorter overall survival. Strong c-MYC expression was found to be associated with shorter overall survival. Double expression for EZH-2 and c-MYC was found to be asociated with shortest survival while double negative cases had shortest survival. Histologic subtype, stage, ECOG performance status and EZH-2 were found to be prognostic in multivariate analysis. Conclusion: BAP-1, EZH-2, c-MYC and Merlin expressions may be detected by immunohistochemistry in biopsy samples or surgical specimens. Especially EZH-2 and c-MYC expressions have been found to be associated with shorter progression and overall survival times. Targeting EZH-2 and/or c-MYC may be an important therapeutic choice in cases with MM. We need further studies to validate these results.Bu Çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: TTU-2018-10795

Böbrek yetmezliği, karaciğer yetmezliği ve ateşin farklı bir nedeni: Leptospirosis

Leptospirosis is the most common bacterial zoonosis globally, especially intropical and temperate regions with heavy rainfall. Infection into humans occursin direct contact with the urine of the sick animals' contact with the environmentcontaminated with urine. The clinical spectrum of leptospirosis is quite broad.It is subclinical in 90% of cases. Multiple organ failure, especially kidney, liver,and lung, can be seen in 5-10% of cases [1-2]. Weil's disease is the most severeform of leptospirosis. It progresses with liver dysfunction, acute renal failure,thrombocytopenia, and fever; If left untreated, it can be fatal at 1-5% [3]. In ourcase, a 60-year-old patient with fever, hyperbilirubinemia, acute renal failure, andthrombocytopenia will be discussed.</p

Ailevi akdeniz ateşli çocuklarda ortalama trombosit hacmi ve trombosit dağılım genişliğinin değerlendirilmesi

Platelet activation plays a key part in the process of atherosclerosis. The risk of atherosclerosis increased in familial Mediterranean fever (FMF). Mean platelet volume (MPV), platelet distribution width (PDW) and platelet counts are important in platelet activation. The aim of present study was to evaluate the relationship between the MPV, PDW, PLT counts and mutation types of FMF in children in attack free period. PLT counts, MPV, PDW, age, sex and mutation types of patients were recorded retrospectively from medical records of patients. Three hundred sixty-eight children with FMF in attack-free period and 379 healthy children were included in the study. MPV of the patients were lower than those of control (p0.05). Of 368 patients; homozygous, heterozygous, and compound mutations were seen, respectively, in 51, 267, and 51 patients. The MPV of patients with homozygous (p=0.029) and heterozygous(p=0.041) mutations were found higher than that of patients with compound mutations. There was no difference between heterozygous and homozygous mutation in terms of MPV (p>0.05). In addition, there was no difference between heterozygous, homozygous and compound mutations in terms of PDW and PLT counts (p>0.05). The most common mutations were M694V (n=131), E148Q (n=82), M680I, (n=37), and V726A (n=32). There wasn’t seen significant difference among these mutations in terms of MPV, PDW and PLT counts (p > 0.05). Although, atherosclerosis risk is increased in high MPV levels, we couldn’t find this relationship in current study. It may be due to all the patients were under colchicine treatment. On the other hand PDW levels were found higher in patients than control group. To verify this relationship between PDW and MPV values, further investigations are needed.Trombosit aktivasyonu ateroskleroz sürecinde anahtar rol oynamaktadır. Ateroskleroz riski ailevi Akdeniz ateşi (AAA) hastalığında artmıştır. Ortalama trombosit hacmi, trombosit dağılım genişliği ve trombosit sayısı, trombosit aktivasyonunda önemlidir. Çalışmanın amacı ortalama trombosit hacmi, trombosit dağılım genişliği ve trombosit sayılarıyla ataksız dönemdeki AAA’lı çocukların mutasyon tipinin arasındaki ilişkiyi incelemektir. Ortalama trombosit hacmi, trombosit dağılım genişliği ve trombosit sayıları, yaş, cinsiyet ve mutasyon tipleri, hastaların tıbbi kayıtları geriye dönük incelenerek kaydedilmiştir. Çalışmaya atak döneminde olmayan 368 AAA’lı çocuk hasta ve 379 sağlıklı çocuk dahil edilmiştir. BULGULAR: Ortalama trombosit hacmi (MPV), hastalarda kontrol grubuna göre daha düşüktür (p0.05). Homozigot, heterozigot, birleşik mutasyonlar 368 hastanın sırasıyla 51, 267 ve 51’inde saptanmıştır. OTH; homozigot mutasyonlu (p=0.029) ve heterozigot mutasyonlu hastalarda (p=0.041) birleşik mutasyonlu hastalardan daha yüksek bulunmuştur. Homozigot mutasyonlu hastalarla, heterozigot mutasyonlu hastalarda ortalama trombosit hacmi açısından fark bulunmamıştır (p>0.05). Ayrıca, trombosit dağılım genişliği ve trombosit sayılar açısından heterozigot, homozigot ve birleşik mutasyonlar arasında fark saptanmamıştır (p>0.05). En sık görülen mutasyonlar M694V (131), E148Q (82), M680I, (37), and V726A (32) olarak saptanmıştır. Bu mutasyonlar arasında MPV, trombosit dağılım genişliği ve trombosit sayıları açısından anlamlı fark saptanmamıştır (p > 0.05). Ateroskleroz riski yüksek MPV değerlerinde artmış olsa da, şimdiki çalışmada bu ilişkiyi bulamadık. Bu, belki de tüm hastaların kolşisin tedavisi altında olduğundan kaynaklanmış olabilir. Diğer yandan PDW değerleri kontrol grubuna göre daha yüksek saptanmıştır. PDW ve MPV arasındaki ilişkiyi açıklığa kavuşturmak için daha fazla çalışmaya ihtiyaç vardır

The Prognostic Role of Inflammatory Biomarkers in Metastatic Castration Sensitive Prostate Carcinoma

Objectives: Due to limited data in the literature on the prognostic value of inflammatory markers neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and derived NLR (dNLR) in metastatic castration-sensitive prostate cancer (mCSPC), we aimed to determine the role of this markers in the prognosis of mCSPC. Methods: In this study, inflammatory marker values in mCSPC (NLR0, PLR0, dNLR0) and mCRPC (NLR1, PLR1, dNLR1) were calculated. Characteristics of the patients and the effects of inflammatory markers on overall survival (OS) and cancer-specific survival (CSS) were evaluated using appropriate statistical methods. Results: The median age of 124 patients was 68.71 years. No significant difference was found OS in mCSPC NLR0, dNLR0 and PLR0 groups (p&gt;0,05). While the median CSS was statistically longer in the NLR0, dNLR0 and PLR0 low groups (Median:45.9 vs 35.7 months for NLR0, 47.0 vs 34.6 months for dNLR and 46.2 vs 33.9 months, p=0.037, p=0.036, p=0.041 respectively). There was no significant difference in terms of OS and CSS in NLR1 and dNLR1 groups (p&gt;0.05). The patients with low PLR1 showed statistical significantly better OS and CSS (p=0.027 for OS and p=0.006 for CSS). Conclusion: Although inflammatory markers have prognostic value in many cancers, mCSPC which have heterogeneous and complex structures, are still controversial, and more studies are needed for their routine use. Keywords: Castration, inflammation, prostate cancer, prognosis</p

Mitral valve replacement with bileaflet preservation for complex annular calcification

Extensive calcification of mitral apparatus may preclude optimal valve repair, thus requiring debridement. We performed mitral valve replacement in a 55-year-old woman with a modified bileaflet preservation technique to avoid complications related to extensive debridement. Posterior transposition of the anterior leaflet as a buttress over the posterior ventricular wall provided extra support for the weakened tissues and covered the decalcified areas, which protected against debris embolism. This technique is safe and reproducible, especially for elderly patients who have complex calcification that requires extensive debridement, enables better preservation of ventricular function, and avoids disruption of the mechanical left ventricular wall