Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.

Background & Aims: In Crohn's disease, wrapping of mesenteric fat around the bowel wall, so-called "creeping fat," is highly associated with strictures. The strongest contributor to luminal narrowing in strictures is a thickening of the human intestinal muscularis propria (MP). We investigated creeping fat-derived factors and their effect on mechanisms of human intestinal MP smooth muscle cell (HIMC) hyperplasia.

Stricturing Crohn's Disease Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity and Intercellular Interactions.

Background & Aims: Fibroblasts play a key role in stricture formation in Crohn's disease (CD) but understanding its pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full-thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single-cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation.

Methods: We performed scRNAseq of 13 fresh full-thickness CD resections containing noninvolved, inflamed nonstrictured, and strictured segments as well as 7 normal non-CD bowel segments.

A Different Way to Think About Syndromes of Hereditary Colorectal Cancer.

Background: Hereditary colorectal cancer is an increasingly complex field in which the commoner syndromes are being augmented by rarer genetic presentations contributing to familial polyposis and colorectal cancer. Coming to grips with the complexity is difficult because of the phenotypic and genotypic overlap between syndromes.

Objective: This study aimed to describe a new way of thinking about syndromes of hereditary colorectal cancer based on their embryonic tissue of origin.

Stricturing Crohn's disease single-cell RNA sequencing reveals fibroblast heterogeneity and intercellular interactions.

Background: Fibroblasts play a key role in stricture formation in Crohn's disease (CD) but understanding it's pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation.

Methods: We performed scRNAseq of 13 fresh full thickness CD resections containing non-involved, inflamed non-strictured, and strictured segments as well as 7 normal non-CD bowel segments.

A Review of Autoimmune Enteropathy and Its Associated Syndromes.

Autoimmune enteropathy is an extremely rare condition characterized by an abnormal intestinal immune response which typically manifests within the first 6 months of life as severe, intractable diarrhea that does not respond to dietary modification. Affected individuals frequently present with other signs of autoimmunity. The diagnosis is made based on a characteristic combination of clinical symptoms, laboratory studies, and histological features on small bowel biopsy.

Patterns of polyp histology: predictors of peril in the mucosa.

Background: Precursor colonic polyps of varied subtypes correlate with the known neoplastic pathways. When patients present with synchronous pre-malignant polyps of multiple histologies, multiple genetic mechanisms are likely to be active, potentially resulting in a more unstable, tumourigenic mucosa.

Methods: We hypothesized that patients with a combination of sessile serrated adenomas/polyps (SSA/Ps), hyperplastic (HP) polyps and adenomas would be at highest risk of developing dysplasia/cancer compared to SSA/Ps alone, due to the synergistic effect of multiple active carcinogenic pathways.

Histopathologic Patterns of Recurrent Choroidal Melanoma Following I-125 Plaque Brachytherapy.

Purpose: Histologic correlation of clinical patterns of recurrent choroidal melanoma following I-125 plaque brachytherapy was performed to identify pathologic mechanisms of recurrence.

Methods: We reviewed 7 cases of recurrent choroidal melanoma following I-125 plaque brachytherapy managed with enucleation. Clinical characteristics included tumor dimensions, radiation dose, time to local recurrence, and clinical pattern of recurrence.

The location of premalignant colorectal polyps under age 50: a further rationale for screening sigmoidoscopy.

Purpose: The incidence of colorectal cancer (CRC) among young adults has been dramatically rising, with guidelines for screening recently adjusted to start at age 45. However, knowledge of the precursor lesions is limited. We recently reported that 83% of CRC diagnosed under age 50 are left sided.

Fibrous Extracellular Spheroids in an Endoscopic Ultrasound-Guided Pancreatic Fine Needle Aspiration Correlating to a Gyriform Pancreatic Endocrine Tumor with a Unique Cobblestone Pavement Growth Pattern.

Pancreatic neuroendocrine neoplasms (PanNENs) are uncommon tumors. Fine needle aspiration (FNA) samples from PanNENs are typically of high cellularity and lack necrosis. In cytology slides from these tumors, dyscohesive cells are usually reported with variably round to oval to plasmacytoid forms exhibiting coarsely granular chromatin and showing immunoreactivity for synaptophysin.

Specific Histopathologic Features Aid in Distinguishing Diffuse-type Gastric Adenocarcinoma From Metastatic Lobular Breast Carcinoma.

Metastatic invasive lobular carcinoma (mILC) may masquerade as primary diffuse gastric adenocarcinoma (PDGA) by demonstrating significant clinical and pathologic overlap. Accurate distinction is of therapeutic and prognostic significance. On the basis of anecdotal cases of mILC that lacked estrogen receptor and/or GATA3 expression, we analyzed the cytoarchitectural features of 28 mILC and 44 PDGA specimens obtained from women to assess features that would help in this distinction and prompt ancillary work-up.

Case Report: Primary Orbital Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) of the orbit is almost uniformly the result of local invasion from a cutaneous primary, extension by perineural invasion, or the result of metastasis. This is owed to the lack of native squamous epithelium in the orbit. After review of the literature, to date, only 6 reports of 8 patients with primary orbital SCC exist.

Multifocal Primary Uveal Melanoma: Clinical and Molecular Characteristics.

We report two patients who developed a second distinct choroidal melanoma in the same eye following successful regression of their first choroidal melanoma after iodine-125 plaque brachytherapy. Neither patient demonstrated ocular melanocytosis, local tumor recurrence, or vitreous seeding. One patient had the second tumor arising from a previously documented choroidal nevus, and after undergoing enucleation, there was no detectable connection between the tumors on histopathologic examination.

A rare case of paraganglioma of the cystic duct.

Introduction: Biliary system paragangliomas are rare neuroendocrine tumors of embryonic neural crest origin. The majority is asymptomatic and incidentally found due to gallbladder functional disorders. Herein, we present a non-functional, 2.

Deoxycholic Acid and the Marginal Mandibular Nerve: A Cadaver Study.

Background: One of the rare but serious complications observed with deoxycholic acid administration is damage to the marginal mandibular nerve. In this study, we evaluated if deoxycholic acid directly induces histologic damage to fresh cadaveric marginal mandibular nerve.

Methods: A segment of marginal mandibular nerve was harvested from 12 hemifaces of 6 fresh cadavers.

Isolated Conjunctival Inflammation as a Manifestation of IgG4-Related Disease.

Purpose: To report a unique case of isolated conjunctival inflammation from IgG4-related disease (IgG4-RD) confirmed by pathology.

Methods: A single interventional case of conjunctival IgG4-RD.

Results: A 63-year-old woman presented with a chronic, solitary, vascularized, tan-colored, and raised conjunctival lesion measuring 7.

Multidisciplinary Conference and Clinical Management of Rectal Cancer.

Background: Presentation of rectal cancer cases at a colorectal cancer multidisciplinary conference (CRC-MDC) is a required standard for the newly formed National Accreditation Program for Rectal Cancer administered by the Commission on Cancer. The aim of this study was to determine the frequency and manner in which CRC-MDC changed the management of rectal cancer patients at a tertiary academic center.

Study Design: All rectal cancer cases presented at a weekly CRC-MDC between July 2015 and June 2016 were prospectively included.

Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

Background: The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients.

Objective: The objective of the study was to determine factors associated with poor outcome in young patients with colorectal cancer (≤40 years) and to determine relationships between mucinous histology and oncologic outcomes in this population.

Conjunctival squamous papilloma refractory to interferon α-2b in a patient on systemic immunosuppression (tacrolimus).

Purpose: To describe a case of diffuse conjunctival papilloma in an immunocompromised individual on tacrolimus that was refractory to treatment with interferon α-2b, but responded to topical mitomycin-c.

Observations: A 79-year-old Caucasian female with a history of a liver transplant twenty years ago, who was immunosuppressed with tacrolimus (2 mg daily) presented with a diffuse conjunctival and corneal squamous papilloma. Following treatment with four weekly subconjunctival interferon-α2b injections (3 million units/0.