The use of fully covered self-expandable metal stents in the endoscopic treatment of portal cavernoma cholangiopathy.

BACKGROUND AND AIMS: There are different therapeutic approaches for biliary strictures and reducing portal hypertension in patients with symptomatic portal cavernoma cholangiopathy (PCC). Endoscopic treatment includes endoscopic biliary sphincterotomy (EST), dilation of stricture with a biliary balloon, placement of plastic stent(s) and stone extraction. Fully covered self-expandable metal stent (FCSEMS) is placed as a rescuer in case of haemobilia seen after EST, dilation of stricture and removal of plastic stent rather than the stricture treatment itself. In this retrospective observational study, we sought to assess the clinical outcomes of FCSEMS as the initial treatment for PCC-related biliary strictures. MATERIALS AND METHODS: Twelve symptomatic patients with PCC both clinically and radiologically between July 2009 and February 2019 were examined. Magnetic resonance cholangiopancreatography (MRCP) and cholangiography were employed as the diagnostic imaging methods. Chandra-Sarin classification was used to distinguish between biliary abnormalities in terms of localization. Llop classification was used to group biliary abnormalities associated with PCC. Endoscopic partial sphincterotomy was performed in all the patients. If patients with dominant strictures 6-8-mm balloon dilation was first performed. This was followed by removal of the stones if exist. Finally, FCSEMS placed. The stents were removed 6-12 weeks later. RESULTS: The mean age of the patients was 40.9 ± 10.3 years, and 91.6% of the patients were male. Majority of the patients (n = 9) were noncirrhotic. Endoscopic retrograde cholangiopancreatography (ERCP) findings showed that 11 of the 12 patients were Chandra Type I and one was Chandra Type IIIa. All the 12 patients were Llop Grade 3. All patients had biliary involvement in the form of strictures. Stent placement was successful in all patients. FCSEMSs were retained for a median period of 45 days (30-60). Seven (58.3%) patients developed acute cholecystitis. There was no occurrence of bleeding or other complications associated with FCSEMS replacement or removal. All patients were asymptomatic during median 3 years (1-10) follow up period. CONCLUSIONS: FCSEMS placement is an effective method in biliary strictures in case of PCC. Acute cholecystitis is encountered frequently after FCSEMS, but majority of patients respond to the medical treatment. Patients should be followed in terms of the relapse of biliary strictures.

CHRM3-Associated miRNAs May Play a Role in Bile Acid-Induced Proliferation of H508 Colon Cancer Cells.

BACKGROUND: It was well defined that proliferative effects of bile acids on colon epithelium are through interaction with muscarinic-3 receptors. Recently, microRNA emerged as an important regulator of gene expression and has been implicated in pathogenesis of many malignancies. However, the interaction of CHRM3 and microRNAs and their potential effects on colon carcinogenesis remains to be elucidated. METHODS: In the current study, analysis of cell proliferation for 6 days after treatment with sodium taurolithocholate was analyzed by using WST-1 method. microRNAs which possibly target CHRM3 were identified by in silico analyses. Expression profiling of these microRNAs, expression changes of CHRM3 gene at mRNA level for H508 and SNU-C4 colon cancer cells were analyzed by quantitative polymerase chain reaction; the protein level of CHRM3 was analyzed using Western blot; apoptotic experiments were analyzed using the Annexin V assay. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the miRPath v3.0. RESULTS: It was found that the expression level of CHRM3 gene was 6.133 ± 0.698-fold in H508 cells compared with SNU-C4 cells (P =.004). Treatment of H508 cells with sodium taurolithocholate caused 1.34 ± 0.4156-fold change in the expression level of CHRM3 gene (P =.0448). No apoptotic changes were observed in both colon cancer cells after treatment with sodium taurolithocholate. Different expression changes were detected of hsa-miR-129-5p, hsa-miR-30c-5p, hsa-miR-224-5p, hsa-miR-30b-5p, hsa-miR-522-3p, and hsa-miR-1246. Finally, hsa-miR-1246 and hsa-miR-522-3p could play a critical role in tumor development via bile acid-related genes in colon cancer. CONCLUSION: These findings reflected that CHRM3-dependent oncogenetic pathways might be in charge of colon cancer. We suggest that the microRNA expression profile of each individual colon cancer tissue is a unique digital signature.

Effect of interval between neoadjuvant chemoradiotherapy and surgery on disease recurrence and survival in rectal cancer: long-term results of a randomized clinical trial.

BACKGROUND: The optimal timing of surgery following chemoradiotherapy (CRT) is controversial. This trial aimed to assess disease recurrence and survival rates between patients with locally advanced rectal adenocarcinoma (LARC) who underwent total mesorectal excision (TME) after a waiting interval of 8 weeks or less (classic interval; CI) versus more than 8 weeks (long interval; LI) following preoperative CRT. METHODS: This was a phase III, single-centre, randomized clinical trial. Patients with LARC situated within 12 cm of the anal verge (T3-T4 or N+ disease) were randomized to undergo TME within or after 8 weeks after CRT. RESULTS: Between January 2006 and January 2017, 350 patients were randomized, 175 to each group. As of February 2022, the median follow-up time was 80 (6-174) months. Among the 322 included patients (CI, 159; LI, 163) the cumulative incidence of locoregional recurrence at 5 years was 10.1 per cent in the CI group and 6.9 per cent in the LI group (P = 0.143). The cumulative incidence of distant metastasis at 5 years was 30.8 per cent in the CI group and 18.6 per cent in the LI group (sub-HR = 1.78; 95 per cent c.i. 1.14 to 2.78, P = 0.010). The disease-free survival (DFS) in each group was 59.7 and 69.9 per cent respectively (P = 0.157), and overall survival (OS) rates at 5 years were 73.6 versus 77.9 per cent (P = 0.476). CONCLUSION: Incidence of distant metastasis decreased with an interval between CRT and surgery exceeding 8 weeks, but this did not impact on DFS or OS. REGISTRATION NUMBER: NCT03287843 (http://www.clinicaltrials.gov).

Nonoperative Management of Leaks After Laparoscopic Sleeve Gastrectomy With Endoscopic Stents in a Tertiary Referral Center.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a frequently performed operation. Leaks are formidable complications; however, the optimal management of these leaks is controversial. METHODS: We retrospectively reviewed the medical records of 15 patients referred to our tertiary center between 2012 and 2016 with leaks after LSG. RESULTS: In 12 patients with whom ongoing leaks were identified, stents were inserted with the intent of definitive therapy. In addition to attempts at source control, percutaneous drainage was carried out for intraabdominal collection in 9 patients and pleural effusion in 4 patients. The length of stay in the intensive care unit was significantly shorter in patients referred earlier or in those without any intervention. CONCLUSION: LSG leaks can be treated nonoperatively in well-organized centers under meticulously designed protocols, depending on the clinical condition of the patient.

Autoimmune Pancreatitis after a Seven-Year History of Suspicious Pancreatic Cancer.

In this case report, we present a case of autoimmune pancreatitis (AIP) diagnosis in a patient after a 7-year history of suspicious pancreatic cancer. Kim's and Japanese criteria were used to diagnose AIP. Our case avoided undesirable invasive procedures and recovered thanks to the proper diagnosis and timely treatment with prednisone. Early and accurate diagnosis of AIP, in this case, had a significant impact on the treatment and prognosis process.

Colorectal cancer and dysplasia risk of ulcerative colitis patients in a tertiary referral center in Turkey.

BACKGROUND/AIMS: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). High-grade dysplasia (HGD) and low-grade dysplasia (LGD) are premalignant conditions. The aim of this study is to evaluate the risk of CRC/dysplasia in patients with UC, and the related risk factors. MATERIALS AND METHODS: Medical records of 1659 patients dating between 1993 and 2016 were scanned from an inflammatory bowel disease database. A total of 801 patients with UC who underwent at least one colonoscopic procedure with at least 1-year follow-up period were included in the study. Clinical, endoscopic, and histopathological data were assessed. RESULTS: The mean disease duration was 6.7±6.6 years. The total disease duration was 5334 person-years duration (pyd), and 34% of patients had the disease for 8 years or longer. The prevalence of UC-associated CRC was 0.7%, and the prevalence of dysplasia was 0.85%. The overall incidence of CRC was determined to be 1.1/1000 pyd. The cumulative risk of CRC was 0.3% at 10 years, 1.3% at 20 years, and 5.9% at 30 years. The Cox regression analysis indicated that primary sclerosing cholangitis (HR:13.677, 95% CI:2.6-70.8, p = 0.012) was an independent risk factor for developing UC-associated CRC. CONCLUSION: This study underlined the low risk of CRC and dysplasia in patients with UC in a tertiary referral center in the western part of Turkey. Primary sclerosing cholangitis was found to be the most important risk factor for the development of CRC in patients with UC. Identification of risk factors is important to categorize patients into subgroups to know which patients will require frequent surveillance.

Management of iatrogenic bile duct injuries: Multiple logistic regression analysis of predictive factors affecting morbidity and mortality.

OBJECTIVE: Iatrogenic bile duct injuries remain a challenge for the surgeons to overcome. The predictive factors affecting morbidity and mortality are important for determining the best management modality. MATERIAL AND METHODS: The patients who referred to Ege University Faculty of Medicine after laparoscopy associated iatrogenic bile duct injury are grouped according to Strasberg-Bismuth classification system. The type and number of prior attempts, concomitant complications, and treatment modalities are analyzed using the SPSS version 18 (IBM, Chicago, IL, USA). The variables with p<0.10 were considered for univariate analysis and then evaluated for predictive factors by forward Logistic Regression method using multiple logistic regression analysis. RESULTS: According to the analysis of 105 patients who were referred during 2004-2014, the type and number of prior attempts are considered predictive factors in sepsis. In multiple logistic regression analysis, abscess formation, concomitant vascular injury, and serum bilirubin level are significantly effective in predicting mortality. CONCLUSION: The management of iatrogenic bile duct injuries should be carefully planned with a multidisciplinary approach. The predictive factors affecting morbidity and mortality are important in determining the best modality for managing iatrogenic bile duct injuries. Abscess formation, vascular injury, and serum bilirubin level are the potential risk factors. Therefore, we can strongly recommend immediate assessment of patients for prompt diagnosis and referring to an HPB center, to avoid further injuries.

Association of LCT-13910 C/T Polymorphism and Colorectal Cancer.

PURPOSE: The activity of epithelial lactase (LCT) is associated with a polymorphism 13910 bp upstream in the lactase encoding gene. Because the association between the LCT-13910 polymorphism and the risk for colorectal cancer is not clear, we investigated the role of the LCT-13910 polymorphism as a potential risk factor for colorectal cancer and colorectal polyps in the Turkish population. METHODS: One hundred sixty-six subjects (74 with polyps, 44 with colorectal cancer, 48 controls), who had undergone a total colonoscopy between January 2012 and November 2012 in our endoscopy unit were genotyped for the LCT-13910 polymorphism by using the polymerase chain reaction and minisequencing. RESULTS: The CC genotype in the lactose gene 13910 locus, which is accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had a history of lactose intolerance and 81.5% in those without a history of lactose intolerance (P = 0.236). No difference was detected between the patients who had colorectal polyp(s) and/or cancer and the controls with regard to the LCT-13910 polymorphism. No differences were determined between groups when they were compared with regard to the C or the T allele. CONCLUSION: No differences were detected between the patients who had colorectal polyp(s) and/or cancer and those with normal colonoscopy findings with regard to lactase gene polymorphisms. No differences were determined between the groups when they were compared with regard to the C or the T allele.

The effects of chemoradiotherapy on recurrence and survival in locally advanced rectal cancers with curative total mesorectal excision: a prospective, nonrandomized study.

BACKGROUND: There are only two prospective, randomized studies comparing preoperative long-term chemoradiotherapy and postoperative chemoradiotherapy in locally advanced rectal cancer (LARC); however, conflicting results in terms of locoregional recurrence (LR) and survival rates have been reported. This prospective study aims to compare the effects of preoperative versus postoperative chemoradiotherapy on recurrence and survival rates in LARC patients. METHODS: From January 2003 to January 2016, a total of 336 eligible patients who were clinically diagnosed with LARC (T3-T4 tm or node-positive disease) were prospectively assigned into preoperative chemoradiotherapy (n = 177) and postoperative chemoradiotherapy (n = 159) groups. The preoperative treatment consisted of 50.4 Gy total dose of radiotherapy (delivered in fractions of 1.8 Gy) and concomitant two cycles chemotherapy of 5-fluorouracil and leucovorin. The patients in the preoperative group underwent curative total mesorectal excision (TME) following long-term chemoradiotherapy. Surgery was performed 8 (range 4-12) median weeks after the completion of the chemoradiotherapy. Similar protocol was administered to the postoperative group 4 weeks after the operation. Four cycles of adjuvant chemotherapy were added to the groups. The primary end points were locoregional recurrences and 5-year cancer-specific, overall, and disease-free survivals. RESULTS: The mean follow-up period was 60.4 (range 12 to 168) months. Five-year cumulative incidence of locoregional recurrence (LR) was 7.4% in the preoperative group and 13.4% in the postoperative group (p = 0.021). Five-year cancer-specific survival (CSS) was 87.5% in the preoperative group and 80% in the postoperative group (p = 0.022). Overall survival (OS) was 79.8 versus 74.7% (p = 0.064), disease-free survival (DFS) was 75.2 versus 64.8% (p = 0.062), and severe late toxicity was 7.4 versus 13.2% (p = 0.002), respectively. The rate of patient compliance was higher in the preoperative group (p < 0.001). CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, significantly improved local control, patient compliance, CSS, and late toxicity and suggested a trend toward improved overall and disease-free survival.

Efficacy of simvastatin in reducing postoperative adhesions after thyroidectomy: an experimental study.

BACKGROUND: We aimed to investigate whether simvastatin had any impact on the prevention of adhesion formation after thyroidectomy in a rat model. METHODS: This study was performed in 66 Wistar albino rats randomized into three experimental groups. A right hemithyroidectomy was carried out in all the rats. Simvastatin was administered locally at a dose of 0.5 mg/kg and 0.8 mg/kg. Control rats received a saline solution only. Changes during the 1st week, 1st month and 3rd month were evaluated. Efficacy of the treatment was assessed by using a scoring system. RESULTS: The severity of adhesions in low-dose simvastatin group was significantly less than the control and high-dose groups during the 1st and 3rd month (p < .05). In addition, adhesions were less in the high dose group during the 3rd month, when compared to the control group (p < .05). Moreover, fibrosis and fibroblast scores, which represent adhesions, were significantly lower in low-dose and high-dose groups at 3rd month, compared to controls (p < .05). CONCLUSIONS: We investigated the influence of simvastatin application on post-thyroidectomy adhesion formation in rats. Whether adhesions, causing technical difficulties during neck redo surgery, can be reduced by the use of simvastatin in human, needs to be studied.

Effect of microemulsion formulation on biodistribution of 99mTc-Aprotinin in acute pancreatitis models induced rats.

BACKGROUND: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas. OBJECTIVE: The aim of this study was to evaluate the biodistribution of Technetium-99m (99mTc)-Aprotinin solution (99mTc-Aprotinin-S) and 99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis. METHOD: Aprotinin was radiolabeled with 99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99mTc-Aprotinin-S and 99mTc-Aprotinin loaded microemulsion (99mTc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies. RESULTS: Aprotinin was radiolabeled by 99mTc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of 99mTc-Aprotinin-S distributed mostly in kidneys and bladder, 99mTc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas. CONCLUSION: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.

Seroprevalence of hepatitis A,B, and C viruses in Turkish alcoholic cirrhotics and the impact of hepatitis B on clinical profile.

INTRODUCTION: The aims of this study were to detect the seroprevalence of hepatitis A, B, and C viruses in Turkish alcoholic cirrhotics, and to evaluate the impact of hepatitis B infection on clinical profile at first admittance. METHODOLOGY: Serological markers for hepatitis A, B, and C viruses in 300 alcoholic cirrhotics diagnosed between January 1994 and December 2012 were retrospectively reviewed. Among them, 148 eligible patients were divided into group 1 (HBsAg positive, n = 43) and group 2 (HBsAg and anti-HBc negative, n = 105). Clinical characteristics at first admittance of groups 1 and 2 were compared. RESULTS: The seroprevalence of anti-HAV total, HBsAg, and anti-HCV was found to be 91.5%, 16.3%, and 8.2%, respectively. The prevalence of hepatocellular carcinoma was higher in the HbsAg-positive group compared to HbsAg- and anti-HBc-negative group (16.3% vs. 2.9%, p = 0.007). Other clinical features were similar in the two groups. CONCLUSIONS: Alcoholic cirrhotics have higher frequencies of HBsAg and anti-HCV than the general population. These patients should be investigated for coexistent HBV and HCV infections, and HBV vaccination should not be neglected. Alcoholic cirrhotic patients with concomitant HBV infection should be closely screened for hepatocellular carcinoma.

The prognostic significance of clinicopathological features and apoptosis inhibitor proteins in pancreas ductal adenocarcinoma.

INTRODUCTION: Pancreas ductal adenocarcinoma (PDAC) is among tumors with unfavorable prognosis. The aim of this study was to determine potential prognostic factors in PDAC. MATERIALS AND METHODS: We retrospectively evaluated a total of 117 cases according to clinicopathological parameters and survivin and livin expression. We investigated the relationship between these parameters and their prognostic significance. RESULTS: In univariate analysis, lymph node metastasis, surgical margin positivity, tumor size over 4 cm and survivin expression were associated with poorer survival but livin expression was not correlated with survival-time. In multivariate analysis, only lymph node metastasis was independent factor predicting a poorer outcome. CONCLUSIONS: In present study, the lymph node metastasis was the strongest predictor of survival. Our finding suggest that survivin could be a target for the treatment of advanced stage resectable PDAC. Our results need to be supported by studies on larger series with advanced techniques.

Aurora kinase A (AURKA) and never in mitosis gene A-related kinase 6 (NEK6) genes are upregulated in erosive esophagitis and esophageal adenocarcinoma.

Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT(2) Profiler(™) PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma.