An unusual variant of type I common bile duct duplication associated with ampullary carcinoma.

Common bile duct duplications represent exceptionally rare congenital anomalies of the biliary tract. In this case report we document an unusual variant of common bile duct duplication in a 79-year-old man who underwent a pancreaticoduodenectomy for ampullary cancer. The duplication consisted of two unseparated, completely-layered, common bile ducts which originated above the cystic duct junction and terminated prior to the point of insertion into the pancreas, where the two lumens converged into a single duct.

Immunohistochemical inflammation in histologically normal gallbladders containing gallstones.

Background: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders.

Methods: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system.

A recurrent retrohepatic abscess secondary to a dropped appendicolith.

Appendicoliths can drop into the peritoneal cavity during the course of an appendicectomy, or more commonly as a result of perforated appendicitis. We report the case of a patient with a history of recurrent retrohepatic abscesses over 7-year period due to a retained appendicolith and review the literature on perihepatic abscesses caused by retained appendicoliths. The abscess had been drained percutaneously 4 times without retrieval of the appendicolith and eventually the patient needed a laparotomy, drainage of the abscess, and extraction of the appendicolith.

Preclinical evidence for anaplastic lymphoma kinase inhibitors as novel therapeutic treatments for cholangiocarcinoma.

Introduction: Bile duct cancer (cholangiocarcinoma, CCA) has a poor prognosis for patients, and despite recent advances in targeted therapies for other cancer types, it is still treated with standard chemotherapy. Anaplastic lymphoma kinase (ALK) has been shown to be a primary driver of disease progression in lung cancer, and ALK inhibitors are effective therapeutics in aberrant ALK-expressing tumors. Aberrant ALK expression has been documented in CCA, but the use of ALK inhibitors has not been investigated.

The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa.

High-level expression of decay-accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood.

Immunohistochemical Inflammation in Histologically Normal Appendices in Patients with Right Iliac Fossa Pain.

Background: Histologically normal appendices resected for right iliac fossa pain in children demonstrate immunohistochemical markers of inflammation. We aimed to establish if subclinical inflammation was present in histologically normal appendices resected from adults with right iliac fossa pain.

Methods: Immunohistochemistry was performed on formalin-fixed paraffin-embedded appendices for tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R and serotonin in four groups: Group I (n = 120): uncomplicated appendicitis, Group II (n = 118): complicated appendicitis (perforation or gangrene), Group III (n = 104): histologically normal appendices resected for right iliac fossa pain and Group IV (n = 106) appendices resected at elective colectomy.

Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.

Purpose: The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells.

Materials And Methods: ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot.

Monoclonal Antibody Targeting Sialyl-di-Lewis-Containing Internalizing and Noninternalizing Glycoproteins with Cancer Immunotherapy Development Potential.

Tumor glycans constitute attractive targets for therapeutic antibodies. The sialylated glycocalyx plays a prominent role in cancer progression and immune evasion. Here, we describe the characterization of the mAb, FG129, which targets tumor-associated sialylated glycan, and demonstrate its potential for multimodal cancer therapy.

Publisher Correction: SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.

Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved in scar formation and its prevalence in patients with liver fibrosis predicts progression.

A galling disease? Dieulafoy's lesion of the gallbladder.

Introduction: Dieulafoy's lesion is a rare vascular anomaly characterized by an abnormally large and tortuous submucosal arteriole leading to an area of mucosal defect with minimal inflammation. It is most often seen in the stomach but could occur anywhere along the gastrointestinal tract. Only five cases of gallbladder Dieulafoy's lesion have been published so far.

SOX9 predicts progression toward cirrhosis in patients while its loss protects against liver fibrosis.

Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation governing fibrotic matrix deposition by liver myofibroblasts.

Pancreas preserving distal duodenectomy: A versatile operation for a range of infra-papillary pathologies.

Aim: To investigate the range of pathologies treated by pancreas preserving distal duodenectomy (PPDD) and present the outcome of follow-up.

Methods: Neoplastic lesions of the duodenum are treated conventionally by pancreaticoduodenectomy. Lesions distal to the major papilla may be suitable for a pancreas-preserving distal duodenectomy, potentially reducing morbidity and mortality.

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited.

A dangerous loop.

A 76-year-old man developed a hemoperitoneum after ERCP for choledocholithiasis. He underwent a laparotomy and splenectomy for a capsular tear at the splenic hilum, a rare complication of ERCP. "Bowing" of the endoscope with torsion on the greater curvature of the stomach may lead to shear forces causing splenic injury.

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy.

Aims: Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. Here we aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well it predicts gastric pathology.

IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection.

Background & Aims: Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients.

Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases.

Objective: The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM).

Methods: Patients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival.

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays.

Background: Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.

Methods: After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20.

Three cases of concomitant intraductal papillary mucinous neoplasm and pancreatic neuroendocrine tumour.

Context: Intraductal papillary mucinous neoplasms (IPMNs) are uncommon tumours which can be associated with pancreatic and extrapancreatic malignancies. The association of IPMN and neuroendocrine tumours of the pancreas has been reported previously but is exceedingly rare.

Case Report: We report three cases of IPMN treated with total pancreatectomy/extended distal pancreatectomy.

Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla.

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required.

Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla.

The performance of transient elastography compared to clinical acumen and routine tests - what is the incremental diagnostic value?

Background/aims: There is substantial evidence suggesting transient elastography (TE) is a useful tool in assessing liver fibrosis. We aimed to determine whether TE has incremental diagnostic value over clinical acumen and routinely available tests.

Methods: We performed a retrospective study of 130 patients to assess the ability of hepatologists to predict severity of fibrosis using clinical acumen; clinical acumen with routine tests; and elastography in patients with chronic liver disease.