Pancreaticobiliary maljunction in Turkish patients: a multicenter case series.

BACKGROUND AND AIMS: Pancreaticobiliary maljunction (PBM) is a malformation in which the pancreatic and bile ducts join outside the duodenal wall. It is associated with various biliary and pancreatic diseases. In addition, patients with PBM carry a substantial lifetime risk of developing biliary or gallbladder carcinoma. We aimed to present a multicenter case series of PBM from Turkey. METHODS: This study was conducted in adult and pediatric PBM patients who were referred to three tertiary reference centers of Turkey for endoscopic retrograde cholangiopancreatography (ERCP) between July 2007 and May 2020. The clinical presentations, types of PBM, ERCP findings, surgical histories, and the postoperative courses, including the development of biliary malignancies, were retrospectively reviewed. RESULTS: The study group included 47 (31 adult and 16 children) patients. Type D PBM was more frequent (13/41: 27.7%) than that reported in Eastern studies. Type A PBM was more common in the adults (51.6% vs. 12.5%, p < 0.05), whereas type C was more common in pediatric patients (31.3% vs. 13.2%, p < 0.05). Although fusiform anatomy was predominant in both of the groups, cystic dilatation was more common (25.8% vs. 12.5%) in adults and the common bile duct diameter was greater [22 mm (range 11-58) vs. 12 mm (range 5-33)] in adult patients compared to pediatric patients. Resective surgeries were more frequently done in pediatric patients (73.3% vs. 53.6%), whereas cholecystectomy was more frequently performed in adult patients (21.4% vs. 6.7%). CONCLUSION: Although our findings were compatible with Eastern studies, type D PBM (associated with pancreas divisum) was more frequent in our study population.

COVID-19 induced haemobilia: a novel entity.

Hemobilia which is firstly described in 1948 is a rare cause of gastrointestinal bleeding. Since its main clinic takes time to occur and may cause mortality, early diagnosis and management have a great importance. Almost for 3 years, the world has been facing with an unknown viral infection called COVID-19 whose clinic changes from asymptomatic respiratory infection to symptoms associated with multiple system involvement. The clinical presentation of Covid-19 infection varies tremendously depending on the severity of the illness. In this report, we present the first two cases of severe COVID-19 induced hemobilia.

The crosstalk between H. pylori virulence factors and the PD1:PD-L1 immune checkpoint inhibitors in progression to gastric cancer.

BACKGROUND: The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death -ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. METHODS: A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors' (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. RESULTS: The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. CONCLUSION: Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Magnetic resonance image-guided hypofractionated ablative radiation therapy for extrahepatic cholangiocarcinoma: Plan adaptation in changing anatomy.

Extrahepatic cholangiocarcinoma is an aggressive malignancy of biliary duct epithelium which typically has a poor prognosis. Although surgical resection improves overall survival, many patients are deemed medically inoperable or have unresectable tumors. Herein, we report a case of an 84-year-old Caucasian male who was diagnosed with medically inoperable extrahepatic cholangiocarcinoma. Magnetic resonance image-guided hypofractionated ablative radiotherapy was administered which has the advantages of superior soft tissue resolution, better visualization of the target and organ at risk, daily online adaptive planning and continuous cine MR tracking of the target during irradiation. Concomitant chemotherapy was used. On the first fraction the patient presented with a broken arm that forced the patient take a treatment position much different than the one used for simulation CT and planning. The patient was able to finish the treatment without the need of another simulation by adapting the plan according to the new anatomy. The patient is being followed up until today and is alive with no evidence of disease.

Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests?

BACKGROUND/AIMS: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Dealing with the gray zones in the management of gastric cancer: The consensus statement of the Istanbul Group.

The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.

Endoscopic papillectomy of benign ampullary lesions: Outcomes from a multicenter study.

BACKGROUND/AIMS: Endoscopic papillectomy (EP) has emerged as an alternative to surgery in the management of ampullary lesions. The aim of this study is to evaluate feasibility, efficacy, safety, outcome, and impact of EP in the management of benign ampullary lesions. MATERIALS AND METHODS: This is a multicenter, retrospective study of 44 patients who had EP of benign ampullary lesions. RESULTS: Over the 11-year period, 44 (55.7%) of 79 patients underwent EP for benign ampullary lesions. Complete resection was achieved in 40 patients (91%). An underlying adenocarcinoma was the only risk factor for incomplete resection. Twenty-eight lesions (63.6%) were resected en-bloc and 16 lesions (36.4%) were resected in piecemeal fashion. Post-papillectomy histopathologic diagnoses were tubular adenoma in 14 patients (32%), invasive adenocarcinoma in 9 patients (20.5%), tubullovillous adenoma in 7 patients (16%), tubullovillous adenoma with carcinoma limited to the mucosal layer in 5 patients (11.3%), adenoma with high-grade dysplasia in 4 patients (9%), neuroendocrine tumor in 1 patient (2.3%), ganglioneuroma in 1 patient (2.3%), hamartomatous polyp in 1 patient (2.3%), adenofibroma in 1 patients (2.3%), and Brunner gland hyperplasia in 1 patient (2.3%). Seven (15.9%) procedure-related complications occurred: 3 (6.8%) bleeding, 2 (4.5%) pancreatitis, 1 (2.3%) abdominal pain, and 1 (2.3%) stent migration to the pancreatic duct. Seven patients (17%) had recurrence. CONCLUSION: Endoscopic papillectomy is a safe and effective method and can be considered as a first-line approach in patients with benign ampullary lesions with intent for cure. It also allows for correct histological diagnosis and staging.

Analyzing esophageal squamous cell papillomas for the presence of human papilloma virüs.

BACKGROUND/AIMS: Human Papilloma Virus (HPV) infection can be a predisposing condition for the development of squamous cell papilloma (SCP) of the esophagus, which can progress to dysplasia and to carcinoma as a result of chronic infection. The aim of the present study was to search for the presence of HPV in the esophageal SCP, and to genotype the detected HPV. MATERIALS AND METHODS: Data from patients with definite diagnosis of SCP of the esophagus were identified from pathology records for two years period at different Hospitals. Slides from each patient were reviewed and samples with satisfactory papilloma tissues were submitted to molecular analysis. DNA has been isolated. DNA sequencing has been performed for genotyping HPV for all types. RESULTS: Our study group consisted of 21 women and 17 men (a total of 38 patients), mean age was 41 years (range 17-67 years). Most of the papillomas were located at mid-esophagus (68%). Eight out of 38 patients (21%) had associated erosive esophagitis, and fourteen patients (36.8%) had Helicobacter Pylori (H. pylori). Of the 38 SCP analyzed, seven (19%) were positive for HPV DNA. Three of them were of genotype 6, whereas four were of genotype 16, 18, 31, 81 that are known as highly oncogenic. There were no correlations between the presence of HPV and the patient's age, the presence of reflux esophagitis or H. pylori, smoking habit and the location of the papillomas. CONCLUSION: The presence of high-risk type HPV in esophageal SCP may implicate a role of the virus in the pathogenesis of the esophageal tumor.

Hepatitis C virus positive patient diagnosed after detection of atypical cryoglobulin.

A 60-year-old male patient presented with jaundice and dark urine for three days, icteric sclerae and skin rash on his legs for six months. Laboratory investigations revealed an atypical cryoglobulinemia with high hepatitis C virus (HCV)-RNA levels. Imaging studies showed cholestasis was accompanying HCV. Capillary zone electrophoresis using immunosubtraction method revealed a polyclonal immunoglobulin G and immunoglobulin A (IgA) monoclonal cryoglobulin and that IgA lambda was absent in immunofixation electrophoresis. After a liver biopsy, chronic hepatitis C, HCV related mixed cryoglobulinemia and cryoglobulinemic vasculitis were diagnosed and antiviral therapy was initiated. Our HCV patient presented with cryoglobulinemic symptoms with an atypical cryoglobulinemia that was detected by an alternative method: Immunosubtraction by capillary electrophoresis. Different types of cryoglobulins may therefore have a correlation with clinical symptoms and prognosis. Therefore, the accurate immunotyping of cryoglobulins with alternative methods may provide more information about cryoglobulin-generated pathology.

Ki67 as a prognostic factor for long-term outcome following surgery in gastrointestinal stromal tumors.

OBJECTIVE: This study aimed to examine the value of Ki67 expression along with other potential prognostic factors for predicting overall survival and disease-free survival in patients with gastrointestinal stromal tumors who underwent curative resection. PATIENTS AND METHODS: Sixty-eight histologically confirmed and operated patients with gastrointestinal stromal tumors were included. Clinical and follow-up data were retrieved from medical records and patients were contacted at the end of the study. The effects of certain clinical and histopathological parameters on survival outcomes were examined. RESULTS: Sixty-eight patients were followed for a mean duration of follow-up of 2923.3 patient-months. Twelve deaths (17.6%), seven metastasis (10.3%), and two local recurrences (2.9%) occurred. Overall survival was 102.5 months [95% confidence interval (CI), 88.3-116.8] and disease-free survival was 91.8 months (95% CI, 76.5-107.2). Multivariate analyses identified a high Ki67 index (≥ 10%) as an independent predictor of both poor overall survival (hazard ratio, 4.8; 95% CI 1.2-19.2; P=0.027) and poor disease-free survival (hazard ratio, 15.3; 95% CI, 4.7-50.2). CONCLUSION: A high Ki67 expression seems to be a useful prognostic factor that would aid in predicting disease course in gastrointestinal stromal tumors. These findings deserve further investigation in larger studies.

Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

Diverticulum With Papillae: Does Position of Papilla Affect Technical Success?

BASIS AND PURPOSE: The presence of peripapillary diverticulum (PPD) can cause some biliary diseases, especially common bile duct stones, and also, literally, can change the technique of endoscopic retrograde cholangiopancreatography (ERCP) and affect the complication ratio of this procedure. In this study, we investigate the effect of localization and position of the papilla according to the diverticulum on the success of therapeutic ERCP procedures. MATERIALS AND METHODS: The study was conducted prospectively in the patients with naive papillae, who underwent ERCP for a period of 16 months. In all patients, the position of papillae according to the diverticulum (the periphery of the diverticulum is thought as the clock circumference, and the position of papillae is defined as the dials of clock), the success rate of biliary cannulation, total procedure time, overall treatment success rate of ERCP, and the complications are investigated. RESULTS: During this period, 222 (18.5%) of the 1205 enrolled patients who underwent ERCP had PPD. Of the patients with PPD, 123 (55.4%) were female and 99 (44.6%) were male, and the median age was 68.9±10.1 years. According to the position of the papilla by the diverticulum, 90 (40.5%) patients have it on 7 o'clock position, 64 (28.8%) patients have on 6 o'clock position, 63 (28.3%) patients have on 5 o'clock position, and 5 (2.3%) patients have on 1 o'clock position. In the cases of the papilla on 1 o'clock position according to the diverticulum, cannulation procedures were found to be more difficult than other patients (P<0.05). The presence of the diverticulum did not affect the success of therapeutic procedures and did not increase the ratio of complications. CONCLUSIONS: In the presence of PPD, additional cannulation techniques may be required for the procedure. Particularly, the aid of percutaneous techniques may be needed for the papilla on 1 o'clock position.

Isolated hepatic tuberculosis: a rare cause of hepatic mass lesions.

Hepatic tuberculosis usually accompanies pulmonary and extrapulmonary tuberculosis. Although isolated hepatic tuberculosis is a very rare condition, it should be considered in the differential diagnosis of a hepatic mass. Here, we report a 42-year-old woman presenting with weight loss, fever, night sweats, and a hepatic mass on the abdominal ultrasonography and magnetic resonance imaging (MRI). Ultrasonography-guided percutaneous needle biopsy demonstrated a caseating granuloma with epithelioid histiocytes and giant cells compatible with the diagnosis of tuberculosis. The patient was treated with four anti-tuberculous drugs for 1 year. She recovered clinically, and her post-treatment abdominal MRI was normal.

Retraction of the main papilla toward the biliary system in patients with primary sclerosing cholangitis.

BACKGROUND/AIMS: Retraction of the main papilla toward the biliary system was observed in 70% of patients with primary sclerosing cholangitis (PSC). However, this observation was confounded by the fact that all of the patients with this finding had a prior history of sphincterotomy. The aim of the present study was to observe whether main papillary retraction can be seen in patients with naïve papillae and accompanies the progression of the disease. MATERIALS AND METHODS: The study was conducted in a single tertiary reference center and included 4 patients with PSC. RESULTS: Main papillary retraction was seen to emerge with progression of PSC after an initial presentation with intra and extrahepatic involvement in 2 patients and after progression from intrahepatic to extrahepatic bile ducts in 1 patient. Main papillary retraction was seen in 2 patients with naïve papillae and could be detected by magnetic resonance cholangiography in 1 patient. CONCLUSION: Retraction of the main papilla can be seen in patients with PSC regardless of prior sphincterotomy history.

Major predictors for difficult common bile duct stone.

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography has become the standard treatment for common bile duct stones worldwide. However, there are only a few reports with small number of patients concerning the factors that contribute to the technical difficulty of endoscopic retrograde cholangiopancreatography in these patients. In this study we aimed to investigate these factors in a large group of patients. MATERIALS AND METHODS: All patients with a naiïve papilla (n=1850) who underwent endoscopic retrograde cholangiopancreatography during a study period of 2 years were prospectively evaluated. Of these, 757 patients with common bile duct stones were included in the study. Following successful cannulation, patients who needed either more than one episode for stone extraction or mechanical lithotripsy, extracorporeal shock wave lithotripsy, or patients in whom stone extraction could not be achieved endoscopically and underwent surgery were regarded as having "difficult stones". Age, sex, laboratory parameters, endoscopic and cholangiographic findings were recorded in all patients. Predictive factors for difficult stones were investigated using univariate and multivariate analysis. RESULTS: The study group consisted of 432 women and 325 men with a mean age of 60±16 years (range, 4-96). Of the total 757 patients, 654 (86.4%) had easy and 103 (13.6%) had difficult stones. Endoscopic stone extraction was successful in 98.1% of patients. A stricture distal to the stone (OR: 8.248), smaller common bile duct/stone diameter ratio (OR: 0,348), stone diameter (OR: 1,187) stone impaction (OR: 1,117) and higher bilirubin levels (OR: 1,1) were found to be independent predictors of difficult stone extraction on multivariate analysis. CONCLUSION: Endoscopic retrograde cholangiopancreatography is a very effective method for the treatment of common bile duct stones. Presence of a stricture distal to the stone, smaller common bile duct/stone diameter ratio, stone diameter, impacted stone, and higher bilirubin levels are significant predictors of difficult stone.

Groove (paraduodenal) pancreatitis: Report of two cases.

"Groove" pancreatitis is a rare segmental form of chronic pancreatitis that involves the area located between the common bile duct, head of the pancreas and duodenum. It is more common in middle-aged males who have a history of alcohol abuse. The differential diagnosis varies from anatomic variants to malignancies. The most relevant differential diagnosis of groove pancreatitis is adenocarcinoma of the head of the pancreas. Most of the cases were diagnosed after pancreatic resection. Thus, the correct diagnosis of this rarely seen disease is very important to avoid unnecessary tests or procedures and to determine the definitive treatment.

Accuracy of endoscopic ultrasound-guided fine needle aspiration cytology on the differentiation of malignant and benign pancreatic cystic lesions: a single-center experience.

OBJECTIVES: The aim was to compare the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in cytology and the biochemical analysis of cyst fluid, together with the size of the lesion in the differentiation between benign and malignant pancreatic cystic lesions. METHODS: Data of patients who underwent EUS-FNA for pancreatic cystic lesions in our center from January 2006 to October 2010 were retrospectively analyzed. The diagnostic accuracy of EUS-FNA was determined. RESULTS: Of the 56 patients, 37 (66.1%) had evaluable cytology for diagnosis and sufficient cyst fluid was available for biochemical analysis in 58.9% (33/56) of the patients. The sensitivity, specificity, positive predictive value and negative predictive value of EUS-FNA for detecting malignancy were 63%, 100%, 100% and 85%, respectively. EUS-FNA was the most accurate diagnostic method for differentiating malignant and benign pancreatic cystic lesions (88%). Cyst fluid carcinoembryonic antigen (CEA) > 365 ng/mL had a sensitivity of 100% for the detection of malignant cystic lesions. CONCLUSIONS: Although the rate of insufficient cyst fluid aspiration is high, the combination of cytological evaluation and CEA analysis of cyst fluid obtained by EUS-FNA is accurate in differentiating malignant cystic lesions from benign ones. Safe techniques are essential to improve the yield of cyst fluid aspiration by EUS.