Acute Liver Injury of Unclear Etiology: A Case of Alcohol-Associated Steatohepatitis.

A 37-year-old female was hospitalized for acute liver injury, presenting a diagnostic challenge that ultimately led to a diagnosis of alcohol-associated steatohepatitis (ASH). Steatohepatitis is a state of liver inflammation with fat accumulation and has several potential etiologies, including metabolic dysfunction-associated, alcohol-associated, drug-induced, autoimmune, and viral causes. A definitive diagnosis often requires a thorough clinical history, laboratory and imaging studies, and, in some cases, a liver biopsy.

Correlation of Fecal, Plasma, Serum, and Salivary Calprotectin to Endoscopic and Histologic Outcomes in Patients With Crohn's Disease: A Pilot Study.

Easily obtained, noninvasive biomarkers are needed for Crohn's disease monitoring. This pilot study compared associations between calprotectin levels in stool, saliva, and blood to assess their correlation with endoscopic and histologic outcomes among patients with Crohn's disease. Participants recruited from an Inflammatory Bowel Disease center provided stool, blood, and saliva samples prior to undergoing scheduled colonoscopy (n = 17).

Discordance between endoscopic and histopathologic assessment in ileal Crohn's disease.

Background: Discordance between endoscopic and histologic assessments in Crohn's disease (CD) have been observed, however the prevalence and cause are unclear.

Aim: To assess if a protocolized approach to biopsy collection facilitates understanding of this discordance in patients with ileal CD.

Methods: Patients with known ileal CD underwent colonoscopy with endoscopic disease activity assessment.

Directionality of endoscopic and histologic healing in ulcerative colitis: a prospective pilot study.

Objective: Endoscopic and histologic healing in ulcerative colitis (UC) is hypothesized to progress proximally to distally, with healing of the distal rectosigmoid occurring last. However, this has not been empirically verified.

Methods: We performed a prospective cohort study in patients with pancolonic UC commencing treatment with a tumor necrosis factor (TNF) antagonist or vedolizumab.

Multidisciplinary Approach for the Management of Metastatic Poorly Differentiated Neuroendocrine Carcinoma of the Pancreas: A Case Report of an Exceptional Responder.

Poorly differentiated pancreatic neuroendocrine carcinomas (pNECs) are rare, highly aggressive neoplasms. Frequently metastatic at diagnosis, prognosis is poor with median overall survival estimated to be less than 1 year. Although multidisciplinary management, including systemic medications and locoregional therapies aimed at reducing and preventing symptoms caused by mass effect, is the mainstay of treatment for patients with metastatic well-differentiated pancreatic neuroendocrine tumors, rapid progression, organ dysfunction, and poor performance status often preclude initiation of even single-modality palliative chemotherapy for patients with metastatic pNEC, limiting the use of and recommendation for multidisciplinary management.

Non-Canonical Activin A Signaling Stimulates Context-Dependent and Cellular-Specific Outcomes in CRC to Promote Tumor Cell Migration and Immune Tolerance.

We have shown that activin A (activin), a TGF-β superfamily member, has pro-metastatic effects in colorectal cancer (CRC). In lung cancer, activin activates pro-metastatic pathways to enhance tumor cell survival and migration while augmenting CD4+ to CD8+ communications to promote cytotoxicity. Here, we hypothesized that activin exerts cell-specific effects in the tumor microenvironment (TME) of CRC to promote anti-tumoral activity of immune cells and the pro-metastatic behavior of tumor cells in a cell-specific and context-dependent manner.

Artificial Intelligence Enabled Histological Prediction of Remission or Activity and Clinical Outcomes in Ulcerative Colitis.

Background & Aims: Microscopic inflammation has significant prognostic value in ulcerative colitis (UC); however, its assessment is complex with high interobserver variability. We aimed to develop and validate an artificial intelligence (AI) computer-aided diagnosis system to evaluate UC biopsies and predict prognosis.

Methods: A total of 535 digitalized biopsies (273 patients) were graded according to the PICaSSO Histologic Remission Index (PHRI), Robarts, and Nancy Histological Index.

Constrained multiple instance learning for ulcerative colitis prediction using histological images.

Background And Objective: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) affecting the colon and the rectum characterized by a remitting-relapsing course. To detect mucosal inflammation associated with UC, histology is considered the most stringent criteria. In turn, histologic remission (HR) correlates with improved clinical outcomes and has been recently recognized as a desirable treatment target.

Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon.

Unlabelled: Although somatic mutations in colorectal cancer are well characterized, little is known about the accumulation of cancer mutations in the normal colon before cancer. Here, we have developed and applied an ultrasensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without colorectal cancer.

PICaSSO virtual electronic chromendoscopy accurately reflects combined endoscopic and histological assessment for prediction of clinical outcomes in ulcerative colitis.

Background And Aims: A composite endoscopic-histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic-histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores.

Methods: Ulcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months.

PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system.

Unlabelled: Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity.

Methods: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI).

An International Multicenter Real-Life Prospective Study of Electronic Chromoendoscopy Score PICaSSO in Ulcerative Colitis.

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes.

Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO.

Interobserver agreement in pathologic evaluation of bile duct biopsies.

Intraductal biopsy is commonly used for preoperative evaluation of the etiology of biliary strictures. Interpretation of intraductal biopsies is frequently challenging. The diagnosis often suffers from interobserver disagreement, which has not been studied in the literature.

Dysregulation of IL6/IL6R-STAT3-SOCS3 signaling pathway in IBD-associated colorectal dysplastic lesions as compared to sporadic colorectal adenomas in non-IBD patients.

Background: IL6-IL6R-STAT3-SOCS3 signaling pathway is known to play important roles in regulating intestinal epithelial homeostasis, in pathogenesis of inflammatory bowel disease (IBD), and in tumorigenesis of colorectal neoplasia. We studied the expressions of these factors in IBD-associated dysplasia and compared to sporadic colorectal adenomas in non-IBD individuals.

Materials And Methods: The expression of IL6, IL6R, STAT3, and SOCS3 within dysplastic as well as background non-dysplastic epithelial cells was evaluated by immunohistochemistry in 26 sporadic colorectal adenomas in non-IBD patients, 32 adenoma-like and 30 non-adenoma-like dysplastic lesions in IBD (41 ulcerative colitis, 21 Crohn's disease) patients.

Macroscopic and microscopic characteristics of low grade appendiceal mucinous neoplasms (LAMN) on appendectomy specimens and correlations with pseudomyxoma peritonei development risk.

Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development.

Chronic inflammation and other changes are significant components of clinically fibrotic strictures in Crohn's disease: a histological study of resected strictures clinically characterized as noninflamed.

Background: Strictures related to Crohn's disease due to fibrosis are a result of an exaggerated tissue remodelling response to inflammation, characterized by accumulation of collagen-rich extracellular matrix produced by mesenchymal cells.

Objectives: The objective of this study was to characterize histological changes seen in resected 'fibrotic' strictures to better understand individual components of intestinal stenosis.

Methods: We identified patients undergoing surgery for ileal Crohn's disease secondary to symptomatic stricturing disease (Montreal B2) using the histopathology database at Queen Elizabeth Hospital in Birmingham, UK, between 2012 and 2017.

Fecal Calprotectin Thresholds to Predict Endoscopic Remission Using Advanced Optical Enhancement Techniques and Histological Remission in IBD Patients.

Background: Fecal calprotectin (FC) is a common surrogate marker of mucosal healing (MH) in patients with ulcerative colitis (UC) and Crohn's disease (CD). We investigated the optimum FC thresholds for defining endoscopic remission (ER) and histological remission (HR) using advanced endoscopic techniques.

Patients And Methods: In this cross-sectional study, we collected clinical, endoscopic, histological data, and FC from 76 UC and 41 CD patients.

Revisiting the distinct histomorphologic features of inflammatory bowel disease-associated neoplastic precursor lesions in the SCENIC and post-DALM Era.

Distinct histomorphologic features of colitis-associated dysplasia (CAD) or neoplastic precursors in inflammatory bowel disease (IBD) have never been clearly identified. In this study, we tried to further explore the differentiating morphologic features of CAD by retrospectively reviewing the lesions that were clearly associated with carcinomas (carcinoma-related lesions) and by comparing between endoscopically nonpolypoid (non-adenoma-like) lesions and polypoid (adenoma-like) lesions and sporadic conventional adenomas found in the noncolitic mucosa and in patients without IBD. Our study results have revealed that (1) precursor lesions related to IBD-associated colorectal carcinomas were almost always nonpolypoid in macroscopic/endoscopic appearance; (2) nearly half of the carcinoma-related lesions and nonpolypoid lesions were similarly nonadenomatous (nonconventional) lesions, largely serrated type, with no or only mild/focal adenomatous dysplasia, and commonly had mixed adenomatous and nonadenomatous features; (3) carcinoma-related and nonpolypoid adenomatous dysplastic lesions frequently showed some peculiar histocytologic features that we observed and described for the first time, including mixed features of inflammatory pseudopolyps or granulation tissue, pleomorphic and disarrayed nuclei, micropapillary or hobnailing surface epithelial cells, and microvesicular or bubbling cytoplasm of dysplastic cells; and (4) polypoid lesions in the colitic mucosa were identical to sporadic adenomas in the noninflamed mucosa and in patients without IBD, and they lacked the aforementioned features.

Assessment of Endoscopic Healing by Using Advanced Technologies Reflects Histological Healing in Ulcerative Colitis.

Background: Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC.

Methods: A prospective study enrolling 82 UC patients [male 66%] was conducted.

Newly recognized non-adenomatous lesions associated with enteric carcinomas in inflammatory bowel disease - Report of six rare and unique cases.

It is the current view that the inflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous (with classic cytologic dysplasia) and non-adenomatous (without frank cytologic dysplasia), and the latter ones are in various histomorphologies including serrated, mucinous, eosinophilic (goblet cell deficient), and differentiated (dysplasia with terminal epithelial differentiation) types. By retrospectively reviewing the surgically resected IBD-associated colorectal and ileal carcinomas (×53), analyzing the background epithelial changes/lesions in the mucosa surrounding and adjacent to invasive carcinomas, and testing the key molecular profile (KRAS, BRAF, PIK3CA, NRAS, p53, mismatch repair proteins, and SAT-B2) known to be involved in colorectal carcinogenesis, we identified 6 representative, rare and unique cases, in which non-adenomatous lesions were clearly in vicinity and in transition to invasive carcinomas. Furthermore, we identified certain colonic carcinoma-related molecular alterations, and thus further confirmed the neoplastic nature of various non-adenomatous lesions.

Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases.

Aims: Inflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous or non-adenomatous with various histomorphologies. We aim to validate the newly proposed classification, to explore the neoplastic nature of the non-adenomatous lesions and to elucidate the molecular mechanisms underlying the different histomorphologies.

Methods: 44 background precursor lesions identified in 53 cases of surgically resected IBD-associated colorectal and ileal carcinomas were reviewed for the histomorphological features (classified into adenomatous, mucinous, sessile serrated adenoma (SSA)-like, traditional serrated adenoma-like, differentiated, eosinophilic and serrated not otherwise specified (NOS)) and analysed for a key panel of colonic cancer-related molecular markers.