Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation.

Background And Aims: We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT).

Methods: We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings.

A Signature Identifies TIM-3 and VISTA as Potential Immune Checkpoint Targets in a Subgroup of Microsatellite Stable Colorectal Cancer Liver Metastases.

Unlabelled: Disease recurrence and drug resistance are major challenges in the clinical management of patients with colorectal cancer liver metastases (CLM), and because tumors are generally microsatellite stable (MSS), responses to immune therapies are poor. The mesenchymal phenotype is overrepresented in treatment-resistant cancers and is associated with an immunosuppressed microenvironment. The aim of this work was to molecularly identify and characterize a mesenchymal subgroup of MSS CLM to identify novel therapeutic approaches.

Clinical Variables as Indicative Factors for Endoscopy in Adolescents with Esophageal Atresia.

Introduction: Gastro-esophageal reflux disease (GERD) occurs frequently in patients operated for esophageal atresia (EA). Longstanding esophagitis may lead to dysphagia, strictures, columnar metaplasia, and dysplasia with an increased risk of adenocarcinoma. Are clinical factors and non-invasive assessments reliable indicators for follow-up with endoscopy?

Material And Method: A follow-up study with inclusion of EA adolescents in Norway born between 1996 and 2002 was conducted.

Research on the Behavior of Stiffening Walls in Single-Storey Buildings Made of Autoclaved Aerated Concrete (AAC) Masonry Units.

Experimental identification of stiffening walls is often limited to studying single-wall models. However, these samples do not reflect many additional effects-torsion of the building and redistribution of internal forces. This paper presents the results of two full-scale buildings made of autoclaved aerated concrete (AAC) masonry elements.

The Use of NDT Diagnostic Methods and Calculations in Assessing the Masonry Tower Crowned with the Steel Dome.

Non-destructive testing (NDT) methods are a diagnostic tool for evaluating the risk of failure or the need for repair and renovation. In analyzing constructions of high historical value, destructive diagnostic methods should be avoided. This study is a comprehensive NDT investigation of the masonry tower topped with a steel dome, a remnant of the overhead telecommunications network from the end of the 19th century.

Histopathologic reassessment of melanoma and other melanocytic skin lesions excised in 2009 and 2018-2019.

Background: Histopathological assessment of melanoma and other melanocytic skin lesions can be difficult and can vary between pathologists.

Material And Method: Histopathological slides of 196 melanocytic skin lesions from 2009 and 2018-2019 were obtained from the archive of the Department of Pathology at Oslo University Hospital and classified into six diagnostic categories: 1) benign nevus, 2) irregular/dysplastic nevus, i.e.

A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation.

Background And Aims: Several characteristic features of the fecal microbiota have been described in primary sclerosing cholangitis (PSC), whereas data on mucosal microbiota are less consistent. We aimed to use a large colonoscopy cohort to investigate key knowledge gaps, including the role of gut microbiota in PSC with inflammatory bowel disease (IBD), the effect of liver transplantation (LT), and whether recurrent PSC (rPSC) may be used to define consistent microbiota features in PSC irrespective of LT.

Approach And Results: We included 84 PSC and 51 liver transplanted PSC patients (PSC-LT) and 40 healthy controls (HCs) and performed sequencing of the 16S ribosomal RNA gene (V3-V4) from ileocolonic biopsies.

Biliary Adenofibroma: A Rare Liver Tumor with Transition to Invasive Carcinoma.

Biliary adenofibroma is a rare benign liver tumor with potential for malignant transition. It has a bile duct origin characterized by a complex tubulocystic biliary epithelium with fibrous stroma. MRI features may suggest this uncommon entity, and histological findings can be diagnostic.

A man in his fifties with abdominal pain, itching and weight loss.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease which can potentially affect any organ system. IgG4-related sclerosing cholangitis and inflammatory pseudotumour in the hepatobiliary system is rare, but is probably underdiagnosed.

Case Presentation: We present the case of a 52-year-old male who was admitted with obstructive jaundice and weight loss.

Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases.

Patients with colorectal liver metastases (CLM) commonly receive neoadjuvant chemotherapy (NACT) prior to surgical resection. NACT may induce immunogenic cell death with subsequent recruitment of T-cells to the tumor microenvironment, which could be exploited by immune checkpoint inhibition (ICI). In theory, this could expand the use of ICI to obtain responses also in microsatellite stable colorectal cancer, but evidence to suggest optimal treatment schedules are lacking.

Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities.

Background And Aims: Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC).

Approach And Results: We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 patients with PSC-BTC from 11 centers in eight countries with all anatomical locations included.

Neoplastic Transformation of the Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy frequently complicated by cholangiocarcinoma (CCA). Massive proliferation of biliary tree stem/progenitor cells (BTSCs), expansion of peribiliary glands (PBGs), and dysplasia were observed in PSC. The aims of the present study were to evaluate the involvement of PBGs and BTSCs in CCA which emerged in PSC patients.

Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases.

Background: Metastatic colorectal cancer (CRC) is associated with highly variable clinical outcome and response to therapy. The recently identified consensus molecular subtypes (CMS1-4) have prognostic and therapeutic implications in primary CRC, but whether these subtypes are valid for metastatic disease is unclear. We performed multi-level analyses of resectable CRC liver metastases (CLM) to identify molecular characteristics of metastatic disease and evaluate the clinical relevance.

Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study.

Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.

Liver transplantation with deceased ABO-incompatible donors is life-saving but associated with increased risk of rejection and post-transplant complications.

ABO-incompatible (ABOi) liver transplantation (LT) with deceased donor organs is performed occasionally when no ABO-compatible (ABOc) graft is available. From 1996 to 2011, 61 ABOi LTs were performed in Oslo and Gothenburg. Median patient age was 51 years (range 13-75); 33 patients were transplanted on urgent indications, 13 had malignancy-related indications, and eight received ABOi grafts for urgent retransplantations.

Long-term risk of colorectal cancer in individuals with serrated polyps.

Objective: Although serrated polyps may be precursors of colorectal cancer (CRC), prospective data on the long-term CRC risk in individuals with serrated polyps are lacking.

Design: In a population-based randomised trial, 12,955 individuals aged 50-64 years were screened with flexible sigmoidoscopy, while 78 220 individuals comprised the control arm. We used Cox models to estimate HRs with 95% CIs for CRC among individuals with ≥1 large serrated polyp (≥10 mm in diameter), compared with individuals with adenomas at screening, and to population controls, and multivariate logistic regression to assess polyp risk factors for CRC.

Inhibitory effects of prostaglandin E2 on collagen synthesis and cell proliferation in human stellate cells from pancreatic head adenocarcinoma.

Background: Several studies have described an increased cyclooxygenase-2 (COX-2) expression in pancreatic cancer, but the role of COX-2 in tumour development and progression is not clear. The aim of the present study was to examine expression of COX-2 in cancer cells and stromal cells in pancreatic cancer specimens, and to explore the role of PGE2 in pancreatic stellate cell proliferation and collagen synthesis.

Methods: Immunohistochemistry and immunofluorescence was performed on slides from whole sections of tissue blocks using antibodies against COX-2 and α-smooth muscle actin (αSMA).

Laparoscopic resection of exocrine carcinoma in central and distal pancreas results in a high rate of radical resections and long postoperative survival.

Background: The role of laparoscopic resection in patients with pancreatic cancer remains to be clarified, because previous reports have not clearly defined oncologic outcomes. The objective of the present study was to investigate this question with the rate of R0 resection and long-term survival as endpoints.

Methods: This retrospective observational study included prospectively collected data from 40 patients operated laparoscopically with curative intent for exocrine pancreatic malignancies identified among 250 consecutive patients undergoing laparoscopic pancreatic operations since 1997.

Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and nontransplanted patients.

Background: Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) seems to differ from IBD without PSC, but a systematic, prospective study of IBD in PSC has until now not been reported. We aimed to describe the clinical, endoscopic, and histopathologic features of PSC-IBD in liver-transplanted and nontransplanted patients.

Methods: PSC patients (n = 184) were included and underwent ileocolonoscopy with assessment of segmental histopathology.