Haluk Demiryürek

G-308A TNF-α polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: case-control study.

BACKGROUND Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha gene at position -308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. METHODS To determine the association of the TNF-alpha gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS The distribution G-308A genotype was significantly associated with the risk of HCC (p<0.001, odds ratio [OR]=4.75, 95% confidence interval [CI]=2.25-9.82 for -308 AA/GA genotypes versus GG genotype). CONCLUSION We suggested that the presence of the high producer allele -308A in the TNF-alpha gene appears to be associated with an increased risk for the development of HCC in Turkish population.

Endoscopic Retrograde Cholangiopancreatography in the Diagnosis and Management of Choledochal Cysts

Choledochal cysts are an uncommon anomaly of the biliary system manifested by cystic dilatation of the extra or intrahepatic biliary tree or both. It is most frequently found in Orientals and in females. Endoscopic retrograde cholangiopancreatography is a valuable imaging technique in the diagnosis of choledochal cysts in adults. Additionaly, in selected cases, a choledochocele may be effectively managed by endoscopic sphincterotomy. We present clinical and endoscopic findings of six adult patients with choledochal cysts. Clinical symptoms were characterized by abdominal pain, jaundice and cholangitis. Associated hepatobiliary pathologic findings included cholelithiasis, recurrent acute pancreatitis, gallbladder carcinoma, Cystolithiasis, choledocholithiasis, biliary stricture and hepatic abscess.

Neurofibromatosis type 1, gastrointestinal stromal tumor, leiomyosarcoma and osteosarcoma: Four cases of rare tumors and a review of the literature

BACKGROUND Neurofibromatosis type 1 (NF1) is a genetic syndrome that predisposes patients to benign and malignant tumor development. Patients with NF1 develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors. In contrast, malignant tumors unrelated to the nervous system rarely coexist with neurofibromatosis. The aim of this article was to present four cases of adult NF1 patients with malignant tumors unrelated to the nervous system as well as a bibliographic search for papers describing these tumors in NF1, focusing on osteosarcomas, gastrointestinal stromal tumors (GISTs), leiomyosarcomas and somatostatinomas and their genetic alterations in NF1. METHODS Search engines such as PubMed and MEDLINE were browsed for English-language articles since 1989 using a list of keywords, as well as references from review articles. Search terms were NF1, osteosarcoma, leiomyosarcoma, somatostatinoma and GIST. Data were summarized in a table at the end of the Results section. RESULTS In our four NF1 cases, there were one osteosarcoma, one leiomyosarcoma, one somatostatinoma and GIST and one GIST. NF1 was diagnosed at an adult age when these patients were admitted to our oncology department. The results generated by the literature search yielded 75 articles about NF and GIST. We summarized the clinical characteristics of 43 patients with NF1 and somatostatinoma. Forty-five articles involving NF and osteosarcoma were found, and of these, 26 involved NF1; from these articles, we identified the clinical features of 8 patients. Twenty-five articles were found concerning NF1 and leiomyosarcoma, and of those, we summarized the clinical features of 15 patients. CONCLUSIONS Here we reviewed somatostatinomas, GISTs, osteosarcomas and leiomyosarcomas occurring in NF1 patients. Patients with NF1 who present with gastrointestinal symptoms, should be carefully evaluated carefully with a high index of suspicion of potential GISTs, periampullary and duodenal tumors. Patients with pathological fractures or bone pain along with NF1 should be carefully screened for malignant bone tumors. Patients with NF1 can develop leiomyosarcoma less frequently than other malignancies, but the association of uterine leiomyoma and NF1 may not be fortuitous. Somatic mutations were defined for frequent tumors, including neurogenic tumors and GISTs but not for sarcomas due to the complexity of underlying mechanisms of the disease and tumorigenesis. Based on the findings; all NF patients can develop malignant tumors, including the less frequently observed ones. Therefore, we recommend that new genetic studies should be performed for rare malignancies in cases of NF1.

Antiviral Combination Therapy With Low-Dose Hepatitis B Immunoglobulin for the Prevention of Hepatitis B Virus Recurrence in Liver Transplant Recipients: A Single-Center Experience.

OBJECTIVES This study presents the overall long-term hepatitis B virus (HBV) recurrence rate with possible associated factors after hepatitis B immunoglobulin (HBIG) was given in combination with 4 different antiviral (lamivudine, adefovir, entecavir, and tenofovir) drugs. PATIENTS AND METHODS Between September 2000 and October 2013, the medical records of 42 adult patients who underwent liver transplantation at the Cukurova University Medical Hospital for chronic liver failure or hepatocellular carcinoma (HCC) secondary to chronic HBV were reviewed retrospectively. The analyses of risk factors for recurrence were performed based on the efficacy of hepatitis B envelope antigen (HBeAg), hepatitis B core antibody (anti-HBc), HBV DNA, preoperative prophylaxis, and the presence of HCC. Posttransplantation HBV recurrence was defined as persistence of hepatitis B surface antigen (HBsAg) positivity after orthotopic liver transplantation, or the reappearance of HBsAg and HBV DNA after initial HBsAg undetectability despite prophylaxis. RESULTS The mean follow-up of 28 patients having HBIG and lamivudine prophylaxis was 73.25 ± 37.5 months with a recurrence rate of 3.5%. The mean follow-up of 2 patients having HBIG and adefovir prophylaxis was 90 ± 46.6 months with a 50% recurrence rate. The mean follow-up of each 6 patients who received prophylaxis with entecavir and tenofovir groups were 27.5 ± 16.1 and 16.17 ± 5.3 respectively, with no posttransplantation recurrence for both groups. On univariate analysis, preoperative factors such as anti-HBc, HBV DNA, preoperative prophylaxis, and the presence of HCC did not show any correlation with recurrence. However, HBeAg showed statistical significance for recurrence. CONCLUSIONS Low-dose HBIG in combination with antiviral agents (lamivudine, entecavir, and tenofovir) is efficacious in preventing recurrence of HBV in posttransplantation patients.

Renal Function in Patients with Orthotopic Liver Transplantation

Due to multiple reasons, acute renal failure (ARF) commonly develops in the early postoperative period of orthotopic liver transplantation (OLT) recipients. The records of OLT recipients between 1999 and 2004 were evaluated. Age, gender, primary disease, history of diabetes, immunosuppressive drugs, pre- and postoperative renal function tests, serum electrolytes, dialysis, liver functions tests, and renal function tests in follow-up period were noted. We followed 16 patients with OLT in our center. ARF developed in 8 patients. Dialysis was performed in only 2 patients, and other patients with ARF were managed with conservative measures. Hypertensive crisis and cerebrovascular stroke developed in 1 diabetic hypertensive patient.

A rare cause of bile duct obstruction in adolescence: Neuroendocrine tumor.

Extrahepatic bile duct is one of the rare places for neuroendocrine tumors which comprise 0.2-2% off all neuroendocrine tumors of gastrointestinal tract. The aim of this paper is to report a case of a 16-year-old boy with a neuroendocrine tumor of extra hepatic bile duct. Laboratory and imaging findings is supported obstructive jaundice. After a pre-operative detailed evaluation, the common bile and common hepatic duct with gallbladder were resected and Roux-en-Y hepaticojejunostomy was performed. After a 36 months follow up, no locoregional recurrence or metastatic disease was observed. Pre-operative diagnosis of neuroendocrine tumors are extremely difficult and often confused with cholangiocarcinoma. Treatment modality of this rare entity depends on the location of the tumor and aggressive surgery is still the best chocie of treatment. It should be kept in mind that disease-free survival for patients with neuroendocrine tumor depends on success of surgery.

18F-FDG activitiy PET/CT and CA-19.9 levels for the prediction of histopathological features and localization of peri- ampullary tumors

BACKGROUND/AIMS We sought to investigate the roles of maximum standardized uptake value (SUVmax) and serum carbohydrate antigen 19-9 (CA 19-9) in predicting the histopathological features of periampullary tumors. MATERIALS AND METHODS Thirty-four patients with histologically confirmed periampullary tumors were classified into two groups, according to the localizations of their tumors (ampulla Vateri or pancreas). SUVmax was obtained from [(18)F]-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT). SUVmax and CA 19-9 levels were measured and compared with histopathological features of the tumors. Logistic regression was used to assess the significance and independence of predictive factors. RESULTS 18F-FDG PET/CT SUVmax (<2.5 vs. ≥2.5; p=0.031) and CA 19-9 level (normal vs. elevated; p=0.045) were significantly and independently predictive of the histopathological origin of the tumors (ampulla Vateri vs. pancreas). The ratio of CA 19-9 levels and SUVmax were found to be higher in cases of poorly differentiated tumors and tumors greater than 2 cm in diameter. CONCLUSION A surgical approach to treatment may be considered for patients who have both i) an established or suspected diagnosis of periampullary tumors and ii) low SUVmax and CA 19-9 levels.

A case of uneventful ABO-incompatible liver transplantation from a deceased donor managed with routine immunosuppressive treatment.

ABO-incompatible liver transplantation (ILT) was formerly contraindicated because of the increased risk of antibody-mediated humoral graft rejection due to preformed anti-A/-B antibodies on recipient endothelial cells. A 2.5-year-old girl with end-stage liver disease underwent cadaveric donation ILT because of acute liver failure and esophageal variceal bleeding before transplantation. The patients blood type was A Rh (-) and the donors blood type B Rh (+). The operation and postoperative course were uneventful. The immunosuppression consisted of steroids, and tacrolimus was initiated on the day of the surgery. The patients hemoglobin level did not change, and direct Coombs test performed daily was consistently negative. Anti-B titer was observed at a maximum of 1/8. The patient was followed up during the first year. This case of ILT from a cadaveric donor is significant because the 2.5-year-old recipient did not experience any complications after undergoing routine immunosuppressive treatment.