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.

Objectives: Obesity is one of the most common diseases of children across the globe with repercussion because of comorbidities like diabetes for the future followed by premature deaths. We aimed to report the world first case of robotic-assisted mini-gastric by-pass in 15 years old boy to treat diabetes and obesity. Surgical technique and review of the literature has been presented. Patient and Methods: Fifteen years old male with Body Mass Index (BMI) 58.6 at 125 percentile, and the patient was followed by dietetic counseling and with increasing metformin dosage treatment because of insulin resistance in his country. After 3 years of follow up the patient’s treatment was not successful and therefore the family addressed to our obesity council. Our genetic consultant assured the boy doesn’t have MC4R mutation. Other endocrinologic comorbidities was evaluated by a pediatrician specialist on obesity and referred to a pediatric endocrinologist. The Type 2 diabetes was diagnosed. Robotic assisted mini-gastric by-pass was planned. Under general anesthesia five instrument ports were placed. Then the robot was docked. The stomach was divided with stapler at the junction of the body and antrum, at a location where the jejunal loop can be brought up comfortably. The jejunal loop is brought up antecolic, and the stapler is used to anatomose the stomach and the small bowel at this point. The distal end of the gastric tube is anastomosed to the side of the small bowel. Methylene blue was given to ensure there was no leakage at the anastomosis and the stapling sites. The antidiabetics were stopped by the operation. The patient was followed for a month with a normalization of blood glucose levels and without medical nor surgical complication. Results: Operative time was 105 minutes. No intraoperative complication was encountered. The patient started walking 6 hours postoperatively. The first postoperative day glucose levels were within the normal limits. Oral contrast CT demonstrated neither leakage nor obstruction on the first day. Patient started oral intake within 24 hours and was discharged in 3 days without any postoperative complication. After 1 month of follow up we didn`t saw any perturbation on blood glucose level. Conclusion: Robotic-assisted mini gastric by-pass is feasible in diabetic children. The main postoperative advantages are early recovery, less pain and better cosmesis with a easily revisable and reversible operation.

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.

Objective: The aim of this retrospective cohort study is to evaluate the carrier frequency of spinal muscular atrophy (SMA) among pregnant women and their partners admitted to our clinic for routine pregnancy follow-up. Methods: The study included pregnant women and their partners who were informed about SMA disease and screening at first trimester and who accepted to undergo screening for SMA. Carrier screening for SMA was carried out using DNA extracted from peripheral blood with a quantitative real-time polymerase chain reaction (qPCR) assay targeting the recurrent SMN1 exon 7-8 gene deletion. The data of the study were analyzed by SPPS version 15.0 statistical software package. Descriptive statistical analyses were carried out. Fisher’s exact test was used for intergroup comparisons. Results: The study included a total of 250 subjects, of whom 182 were female and 68 were male. The carrier frequency of SMN1 deletion was 3.6% (9/250) (95% CI: 1.66–5.54) in the entire study population, with a carrier frequency of SMN1 deletion of 1/27.8. Of 182 female participants, 6 had SMN1 deletion, with a carrier frequency of SMN1 deletion of 3.3% (95% CI: 1.3–6.2). Of 68 male participants, 3 had SMN1 deletion, with a carrier frequency of SMN1 deletion of 4.4% (95% CI: 0.35–9.4). There was no significant difference between female and male participants in terms of SMN 1 deletion frequencies (p=0.712). SMN1 duplication frequency was 8% (95% CI: 5.18–10.8) in all gender. Conclusion: The results of this study demonstrated a carrier frequency of SMN1 deletion of 1/27.7 in the Turkish population, which is higher than in many other countries. The results of the study will be useful for genetic counseling for SMA.

Purpose: Colorectal cancers, which are one of the most common types of cancer, take the first ranks in terms of mortality. Various factors, such as smoking, are considered risk factors in CRC. In this study, germline mutations in 18 genes were examined by Next Generation Sequencing analysis and the role played by smoking and genetic effects in colon cancers were compared. Materials and Methods: In this retrospective study, paraffin blocks of 50 patients with colon cancer that were followed up in between 2010 and 2018 were included. The bioinformatics program SOPHiA DDM® was used for next-generation sequencing. The data of the study were evaluated by the IBM SPSS Statistics Standard Concurrent User V 25 (IBM Corp, Armonk, New York, USA) statistics program. Results: In the study, it was concluded that the presence of APC and MUTYH genetic mutations was 3.083 times more common in patients with distant organ metastasis compared to patients without metastasis and these patients exhibited 6.364 times more TP53 genetic mutations. Also, a relationship was found between APC, MUTYH, and MSH2 and tumor stage. There was no statistically significant relationship between smoking status and Colon Ca patients with and without distant organ metastasis. Conclusion: APC and MUTYH were found to have a bad effect on overall survival. It was determined that there was a significant relationship between the patients' grade, stage, and overall survival status. A significant relationship was found between the expected survey of age and grade in patients with distant organ metastasis.

Smith-Kingsmore Syndrome is a very rare autosomal dominant intellectual disability syndrome characterized by macrocephaly, seizures, umbilical hernia, and facial dysmorphic features. The prevalence of SKS, with 27 patients reported so far, is still unknown. Rubinstein Taybi Syndrome Type 2 (RSTS2) is another rare genetic condition that prevalance is <1/1.000.000. It is characterized by mental and developmental retardation, dysmorphic findings. We present a seven-year-old girl who was diagnosed with SKS and RSTS2 based on identification of a novel de novo pathogenic variant in the MTOR and EP300 genes (MIM #616638 and #613684) by Whole Exome Sequencing and supported by some characteristic clinical features. In our patient, pathogenic mutations belonging to two different ultra-rare syndromes were found. However, the patient had clinical findings of only Smith Kingmore Syndrome among the syndromes. Although he had a pathogenic mutation, she did not have the clinical findings of Rubinstein Taybi Syndrome. This the first case presenting two different mutation of these two ultra-rare syndromes.

In this study, pathogenic, likely pathogenic and variant of uncertain significance/variant unknown significance (VUS) identified in the Hereditary Cancer Panel Genes between 2016 and 2017 and specified in the report are re-examined in 2022 and shown whether they have changed over time. METHODSContaining 26 genes in 2016-2017 variants of patients with pathogenic/likely pathogenic/VUS detected in the Hereditary Cancer Panel were analyzed again in 2022 on Clinvar (https://www.ncbi.nlm.nih.gov/clinvar/) and other databases. RESULTSThe results of a total of 137 patients, 137 women and 2 men, were evaluated.While no pathogenic/ likely pathogenic/VUS variant was detected in the results of 95 patients, at least 1 variant was detected in 42 female patients.A total of 58 variants were detected in 42 patients, and we found that 24 variants among them fell into a different class.While 12 more variants were included in the lower pathogenicity subgroup, 5 of them were higher in pathogenicity.We saw that 6 variants that were not yet identified in 2016-2017 were identified, except for 1 of them. CONCLUSIONWe have seen that the pathogenicity of the variants written in patient reports, which can cause serious changes in the patient's life, can change over time.While giving genetic counseling about these variants, it should be stated that much more comprehensive research and information should be given to the patient, this information was given to the patient under the current conditions and that there may be a possibility of change in the future.

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.

Amaç: En yaygın kanser türlerinden biri olan kolorektal kanserler ölüm oranı açısından da ilk sıralarda yer almaktadır.Bu oranı azaltmak için sıklık ve risklerin iyi tanımlanması önem taşır.KRK'da sigara kullanımı gibi birçok faktör polip veya kolorektal kanser gelişme olasılığını artırdıkları için risk faktörü olarak kabul edilir.Bu çalışmada, Yeni Nesil Dizileme analizi ile 18 gendeki germline mutasyonları incelenmiş olup kolon kanserlerinde genetik etki ile sigaranın oynadıkları

Amaç Karaciğer transplantasyonu sonrası tolerans kavramı son yıllarda giderek popülarite kazanmaktadır. Bu çalışmada amacımız çok özenli parametrelerle seçilmiş yaklaşık on yıllık bir seride düşük doz immünosupressif kullanan bir grupta toleransın varlığını CD3+ hücrelerde mikrokimerizmin yokluğu ile kanıtlamaya çalışmaktır. Gereç ve Yöntem Mikrokimerizm yokluğunu araştırma yöntemi; retrospektif olarak donör kanlarından cross match yapılarak DNA izolasyonunun ardından, mikrosatellit markerlarının PCR ile amplifikasyonu ve dönör ve alıcı allellerinin karşılaştırılması ilkesine dayanıyordu. Bulgular Postoperatif takiplerinde organ reddi ya da buna bağlı komplikasyonları olmayan alkole bağlı sirozu olan 12 hastadan bir izogrup oluşturuldu. Bu hastalar immunsüpresif olarak takrolimus ve mikofenolat mofetil kullanıyordu ve ilaç kan düzeyleri 5 ng/l yani kabul edilebilir sınırın altında idi. Çalışmamızda hiçbir hastamızda kimerizm gözlemlemedik. Sonuç Biyokimyasal stabiliteyi koruyan mikrokimerizmin yokluğu yani transplantasyona tolerans olması durumunda immunsupressif tedavilerin kesilebilir olmasının düşünülebilirliği gündeme gelmektedir.Böylelikle immünsüpressif tedavilerin yan etkileri azalacak ve hastalar böbrek yetmezliği, metabolik bozukluklar, diyabet ve kanserlerin artmış riskinden korunacak, dolayısı ile yaşam kalitesi artmış ve transplantasyon sonrası kullanılan ilaçların ülke ekonomisine yükü azalmış olacaktır.

OBJECTIVE Breast cancer, which basically is the unchecked proliferation of the epithelial cells covering the ductus and the lobules of the breast, is the most common form of cancer in women and ranks second after lung cancer among total deaths from that disease. As all other carcinomas, mamarian cancer results from the progressive accumulation of genetic anomalies. Several genes exist that have been associated positively with breast cancer. We aimed to research the molecular markers about breast cancer’s etiology, screening, treatment, and its follow-up.

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.

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.

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.

Introduction. Sirolimus is a potent immunosuppressant with a mechanism of action different from calcineurin inhibitors (CNIs). It has increasing importance for liver transplant (OLT) patients, in particular if when there is decreased renal function. We evaluated the efficacy and the causes for discontinuation of sirolimus-based immunosuppression among OLT recipients.Objective. We retrospectively analyzed 97 liver transplanted patients who were prescribed sirolimus as the principal immunosuppressant. Of these, 61 patients discontinued treatment. Herein we have reported the causes, the timing, and the effects of sirolimus discontinuation.Results. The overall patient survival at 3 years follow-up was 89%. Hepatotoxicity and blood disorders were the most frequent, severe reported side effects. Acute cellular rejection episodes appeared in seven patients and was relieved in 1 to 2 weeks after the sirolimus administration. In 10 patients, the cholestasis associated with chronic rejection was sharply reduced after the introduction of sirolimus. No increase in vascular thrombosis and/or poor wound healing were reported.Conclusion. Sirolimus given alone or in combination with CNIs appears to be an effective primary immunosuppressant regimen for OLT patients. However, in the late postoperative period (>3 months) the drug is associated with a relatively high rate of side effects.

M. Audet, T. Piardi, F. Panaro, E. Ghislotti, F. Gheza, M. Cag, T.M. Jarzembowski, H. Flicoteaux, P. Wolf, J. Cinqualbre. Incidence and clinical significance of bacterial and fungal contamination of the preservation solution in liver transplantation. Transpl Infect Dis 2011: 13: 84–88. All rights reserved Abstract: A perfusion fluid used in the preservation of the grafted liver represents a medium suitable for microorganism growth. In this observational study, a sample of 232 transplanted livers was collected. Perfusion fluid samples were stored for microbiological analysis from harvested donors. Bacteria were isolated in 91 out of 232 samples, post‐operative infections related to contaminated perfusion solution occurred in 13 cases. The contamination rate of the preservation medium appears to be high, but postoperative infections occurs rarely. We suggest periodic detection and a protocol in place designed for antibiotic use for transplanted patients exposed to contaminated perfusion solution.

INTRODUCTION:The advanced age of the recipient is considered a "relative contraindication" to liver transplantation (LT). However, recently some studies reported a morbidity rate and an overall survival comparable with those of younger patients. Here, we reported the outcome after LT in recipients aged >65 yr.METHODS:Between January 2000 and December 2006, 565 LT was performed in 502 recipients in our institution. Of these, 34 were recipients of >65 yr old (aged group). We focused our study comparing: donor age, co-morbidities, model for end-stage liver disease (MELD) and American Society of Anesthesiologists (ASA) score, duration of operation, transfusions and outcome between the two groups (young/aged).RESULTS:For the group aged >65: the mean donor age was 52.5 (range 16-75) yr and the graft weight 1339 g (890-1880 g). Co-morbidity was recorded in 25 (73.5%), coronary artery disease (CAD) in 17 (50%), diabetes mellitus (DM) and chronic renal insufficiency in four (11.7%) and chronic obstructive pulmonary disease (COPD) in three patients (8.8%). Mean MELD score was 14.9 (range 12-29) and ASA score was two in 15 (44.1%); and three in 19 (55.8%) recipients. Mean operation time was four h 45 min, three patients also received combined kidney transplantation. Twenty-five (73.5%) recipients received blood transfusions (mean 3.2). Morbidity was observed in 20 patients (58.8%); of these two had hepatic artery thrombosis requiring re-LT. Overall survival was 80% (40 months of follow-up), in particularly, at 30-d, one yr, three yr was 91%, 84%, 80%, respectively. The only two statistical differences reported (p = 0.02) are: the lower rate of CAD in the younger group of recipients (12%), compared with the aged group (50%) and the subsequently lower mortality rate secondary to cardiac causes in the younger group (1.4%) compared with aged group (8.8%).CONCLUSION:Our results suggest that the recipient age should not be considered an absolute contraindication for LT when the graft/recipient matching is optimal and when an adequate cardiac assessment is performed.