A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

In Silico Analysis of a De Novo OTC Variant as a Cause of Ornithine Transcarbamylase Deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common X-linked hereditary disorder of urea cycle disorders that is caused by neonatal hyperammonemia. OTC gene sequence variations are common causes of OTCD. The current study presents a 28-month-old baby girl proband with phenotypical characteristics of OTCD such as irritability, somnolence, intermittent vomiting, and high levels of serum ammonium. Whole-exome sequencing revealed a de novo c.275G>A p.(Arg92Gln) variant within the OTC gene. In silico analysis revealed a possible differential affinity between wild-type and mutant OTCase, while Arg92Gln decreases the binding ability of OTCase to the substrate, which can disrupt the urea cycle and explains the molecular pathogenicity of clinical hyperammonemia. In light of the fact that the genotype and phenotype correlation of OTCD is still uncertain, the present in silico analysis outcome can enhance our knowledge on this complicated, rare, and severe genetic disorder.

The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers.

OBJECTIVE: It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. METHODS: A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. RESULTS: The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). CONCLUSION: We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.

Hepatitis C recurrence after liver transplantation: has the human leukocyte antigen mismatching at individual loci a role?

BACKGROUND AND AIM: The objective of this 11-year cohort retrospective study conducted in adult patients with chronic hepatitis C virus (HCV) who underwent liver transplantation (LT) was to identify whether human leukocyte antigen (HLA) mismatching is associated with the recurrence of HCV and with the time to recurrence of HCV. METHODS: Among the 181 patients (74% men; mean age: 54 years, range 25-71) who underwent a LT between 1995 and 2006 in the study center, 163 had relevant data in their medical chart documenting HCV recurrence, and 107 (65.64%) reported a histological evidence of HCV recurrence. RESULTS: Survival was 78% at 5 years. There was no significant relationship between the total score of HLA-mismatches and the recurrence of HCV. Similarly, there was no significant relationship between the total score of HLA mismatches and the time to recurrence of HCV. For the analyses at each individual locus, a significant relationship between the individual scores of HLA-mismatches and the recurrence of HCV were observed. Out of the 40 patients who experienced a rejection, the rate of recurrence was not different according to the severity of the rejection (75% mild, 64% moderate and 64% for severe rejection). CONCLUSIONS: In conclusion, this large study did not demonstrate any relationship between the total score of HLA mismatches and HCV-recurrence. Contrarily a significant relationship between the individual scores of HLA mismatches (HLA-A3, HLA-B35, HLA-DR3, HLA-DR7, HLA-DQ2, HLA-DQ2-0) and the recurrence of HCV were observed.

Robotic liver resection as a bridge to liver transplantation.

BACKGROUND: The surgical robotic system is superior to traditional laparoscopy in regards to 3-dimensional images and better instrumentation. Robotic surgery for hepatic resection has not yet been extensively reported. The aim of this article is to report the first known case of liver resection with the use of a robot in France. METHODS: A 61-year-old male with hepatitis C liver cirrhosis and hepatocellular carcinoma was referred for surgical treatment. Preoperative clinical evaluation and laboratory data disclosed a Child-Pugh class A5 patient. Magnetic resonance imaging showed a 3.4-cm tumor in segment III. Liver size was normal, and there were not signs of portal hypertension. Five trocars were used. RESULTS: Liver transection was achieved with Harmonic scalpel and bipolar forceps without pedicle clamping. Hemostasis of raw surface areas was accomplished with interrupted stitches. Operative time was 180 minutes. Blood loss was minimal, and the patient did not receive transfusion. The recovery was uneventful, and the patient was discharged on the fifth postoperative day without ascites formation. CONCLUSION: The robotic approach may enable liver resection in patients with cirrhosis. The da Vinci robotic system allowed for technical refinements of laparoscopic liver resection due to 3-dimensional visualization of the operative field and instruments with wrist-type end-effectors.

Successful liver transplantation for Rendu-Weber-Osler disease, a single centre experience.

UNLABELLED: BACKROUNDS/PURPOSE: Hereditary hemorrhagic telangiectasia or Rendu-Weber-Osler is an autosomal dominant inherited disorder characterized by arteriovenous malformations and telangiectasia that may affect the nose, skin, lungs, brain and gastrointestinal tract. Liver involvement of the disease has been described to be responsible of biliary tract necrosis, high cardiac output and portal hypertension, due to intra-hepatic vascular shunts. We aimed to present four cases of successful orthotopic liver transplantations in this indication performing our modified Piggy-back technique. PATIENTS AND METHODS: Between 2002 and 2008, four patients have been diagnosed for Rendu-Weber-Osler disease and underwent liver transplantation. Three of them suffered from high cardiac output with heart failure, two presented HBV infection and one patient suffered from renal failure requiring a liver-kidney transplantation. We performed our modified Piggy-back technique for liver implantation, which consists to clamp selectively the hepatic veins during the hepatectomy, without venous bypass, the retro-hepatic vena cava is preserved. RESULTS: No hemodynamic concerns disturbed the surgery and no massive transfusions were needed. The liver replacement corrected the cardiac insufficiency due to high cardiac output for the three patients. At present, the four patients are getting well. CONCLUSIONS: Despite new advances in immunotherapy for the medical treatment of Rendu-Weber-Osler disease, liver transplantation remains the curative option for hepatic based-hereditary hemorrhagic telangiectasia.

Reye syndrome and liver transplantation.

Reye syndrome is a rare, but severe and often fatal disease. The etiology of the classical Reye syndrome is unknown, but it is typically preceded by a viral infection with a free interval of three to five days. The main physiopathological hypothesis is a mitochondrial metabolism insult causing acute liver failure and encephalopathy. Survivors present serious neurological sequelae. The treatment of Reye syndrome is usually medical with intensive care management. Herein, we present the clinical case of a six-month-old baby diagnosed with Reye syndrome with a fulminant hepatitis, who was successfully liver transplanted with an auxiliary partial orthotopic liver transplantation.

Four hundred and twenty-three consecutive adults piggy-back liver transplantations with the three suprahepatic veins: was the portal systemic shunt required?

BACKGROUND AND AIMS: The aim of this study is to analyze a single-center experience in orthotopic liver transplantation with the piggy-back technique (PB) realized with a cuff of three veins without temporary portacaval shunt. Outcome parameters were graft and patient survival and the surgical complications. METHODS: The records of 423 liver transplantation in 396 adult recipients were reviewed. PB was performed in all cases also in patients with transjugular intrahepatic portosystemic shunts and redo transplants without temporary portacaval shunt. No hemodynamic instability was observed during venous reconstruction. RESULTS: Operation time, cold ischemia time and anhepatic phase were, respectively, 316, 606 and 82 min, respectively. The mean intraoperative transfusion of packed red blood cells was 3.2 (range 1-48). Surgical complications were observed in 25% of the orthotopic liver transplantation and 2% of these was related to caval anastomosis. No case of caval thrombosis was observed; a stenosis was noted in seven patients, always treated with an endovascular approach. A postoperative ascites was observed in seven cases. Retransplantation was required in 6.3% patients. Overall in-hospital mortality was 5.3%, but no patient died through technical problems or complications related to PB procedure. One-, 3- and 5-year grafts and patients were 94%, 83% and 75%, and 92%, 86% and 79%, respectively. CONCLUSION: This experience indicates that our approach is feasible with a low specific risk and can be performed without portacaval shunt, with minimal outflow venous complications.

Passenger lymphocyte syndrome and liver transplantation.

The authors reviewed the passenger lymphocyte syndrome (PLS) that has appeared after transplantation. The definition, mechanism, serological, clinical features, and treatment for PLS after solid organ transplantation, especially liver transplantation, are described. The PLS refers to the clinical phenomenon of alloimmune hemolysis resulting from the adoptive transfer of viable lymphocytes from donor during solid organ or hematopoietic stem cell transplant. Sometimes, it is very severe and may cause "unexplained" hemolysis during the postoperative period. The authors reviewed literature about the PLS in liver transplantation.