Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.

Background: Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.

Methods: Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients.

Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs.

Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization.

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event.

Spectrum of Findings Seen in Patients With Cholangiocarcinoma.

Background: Cholangiocarcinoma-with a growing incidence rate and poor prognosis-is not an uncommon cancer. Molecular profiling can reveal actionable aberrations in at least a third of the tumors. This is especially so in the case of intrahepatic cholangiocarcinoma (ICC), where mutations in the isocitrate dehydrogenase 1 and 2 genes () make up 15%-20% of these tumors.

Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis.

Nuclear Bcl-xL is found to promote cancer metastasis independently of its mitochondria-based anti-apoptotic activity. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates histone H3 trimethyl Lys4 (H3K4me3) modification have yet to be understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds to Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus.

Distinct clinical outcomes and biological features of specific KRAS mutants in human pancreatic cancer.

KRAS mutations in pancreatic ductal adenocarcinoma (PDAC) are suggested to vary in oncogenicity but the implications for human patients have not been explored in depth. We examined 1,360 consecutive PDAC patients undergoing surgical resection and find that KRAS mutations are enriched in early-stage (stage I) disease, owing not to smaller tumor size but increased node-negativity. KRAS tumors are associated with decreased distant recurrence and improved survival as compared to KRAS.

Exploring the mysterious mucinous appendiceal neoplasm.

Mucinous neoplasms of the appendix comprise a group of diagnostically challenging lesions that have generated significant controversy and confusion throughout the years, given their potential for aggressive behavior despite very bland cytologic features. Numerous classification schemes have been proposed to characterize and stage these lesions, but confusion remains among pathologists, surgeons, and oncologists regarding diagnostic criteria, therapeutic implications, and overall prognosis. This review summaries the current recommended nomenclature, histologic characteristics of each entity, and helpful features to distinguish neoplasia from benign mimics.

Cytologic Findings and Ancillary Tests Results of Sclerosing Pneumocytoma: Our Institutional Experience.

Introduction: Sclerosing pneumocytoma (SP) is a rare benign tumor and a potential diagnostic pitfall. Our aim was to review the cytologic features of our surgically diagnosed SP cases including the clinical, immunohistochemical and available molecular findings.

Materials And Methods: A computerized search from 2013 to 2020 for surgical cases with corresponding cytology specimens diagnosed as SP was performed.

Integrative Transcriptomic and Single-Cell Protein Characterization of Colorectal Carcinoma Delineates Distinct Tumor Immune Microenvironments Associated with Overall Survival.

Colorectal carcinoma (CRC) is a heterogeneous group of tumors with varying therapeutic response and prognosis, and evidence suggests the tumor immune microenvironment (TIME) plays a pivotal role. Using advanced molecular and spatial biology technologies, we aimed to evaluate the TIME in patients with CRC to determine whether specific alterations in the immune composition correlated with prognosis. We identified primary and metastatic tumor samples from 31 consented patients, which were profiled with whole-exome sequencing and bulk RNA-seq.

Utility of C4d Immunohistochemistry in the Diagnosis of Esophageal Pemphigus Vulgaris.

To assess the utility of C4d immunohistochemistry for esophageal pemphigus vulgaris. We searched for patients with a history of esophageal pemphigus vulgaris who had esophageal biopsies for routine hematoxylin and eosin (H&E) staining. A total of 8 biopsies from 7 patients were available.

Histologic Manifestations of Gastrointestinal Adenovirus Infection After Stem Cell Transplant.

Adenovirus can cause severe disease in hematopoietic stem cell transplant (HSCT) patients. Histopathologic features of this infection in gastrointestinal biopsies and their distinction from graft-versus-host disease (GVHD) have been incompletely studied. We retrospectively identified patients with gastrointestinal adenovirus infection.

A reversible epigenetic memory of inflammatory injury controls lineage plasticity and tumor initiation in the mouse pancreas.

Inflammation is essential to the disruption of tissue homeostasis and can destabilize the identity of lineage-committed epithelial cells. Here, we employ lineage-traced mouse models, single-cell transcriptomic and chromatin analyses, and CUT&TAG to identify an epigenetic memory of inflammatory injury in the pancreatic acinar cell compartment. Despite resolution of pancreatitis, our data show that acinar cells fail to return to their molecular baseline, with retention of elevated chromatin accessibility and H3K4me1 at metaplasia genes, such that memory represents an incomplete cell fate decision.

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer.

EUS-guided liver biopsy using a novel hydrostatic stylet technique.

Video 1Hydrostatic stylet technique for the performance of EUS-guided liver biopsy.

A Rare Exon 15 Germline Mutation Identified in a Patient With Phenotypic Manifestations Concerning for GIST-Plus Syndrome: A Case Report and Review of Literature.

Molecular alterations in are well-described as drivers of sporadic gastrointestinal stromal tumors (GISTs) and inflammatory fibroid polyps (IFPs). However, a small number of families with germline mutations in exons 12, 14, and 18 have been reported, forming the basis of an autosomal dominant inherited disorder with incomplete penetrance and variable expressivity, now referred to as -mutant syndrome or GIST-plus syndrome. Phenotypic manifestations of this rare syndrome include multiple gastrointestinal GISTS, IFPs, fibrous tumors, and other variable features.

Clinicopathologic and Molecular Features of Pancreatic Ductal Adenocarcinomas Harboring Alterations in COMPASS-like Complex Genes.

Context.—: Recent genome-wide sequencing studies have identified a subset of pancreatic ductal adenocarcinomas (PDACs) harboring significant alterations in epigenetic regulation genes, including the COMPASS-like complex genes. Whether this subset of PDACs has specific histologic characteristics or carries prognostic or therapeutic implications is unknown.

Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells.

Low-dose carbon monoxide (CO) is under investigation in clinical trials to treat non-cancerous diseases and has an excellent safety profile. Due to early detection and cancer awareness, an increasing number of cancer patients are diagnosed at early stages, when potentially curative surgical resection can be done. However, many patients ultimately experience recurrence.

Histologic and Clinical Correlates of Multiplex Stool Polymerase Chain Reaction Assay Results.

Context.—: Multiplex stool polymerase chain reaction tests (SPTs) simultaneously test for many enteric pathogens. However, the clinical significance of a positive result, particularly in the context of chronic gastrointestinal disease, remains controversial.

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

Context.—: Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 μm or less is associated with low nodal metastasis rates.

Metastatic Neoplasms Involving the Stomach.

Objectives: Metastatic neoplasms involving the stomach are rare and diagnostically challenging if clinical history of malignancy is absent or unavailable. This study was designed to identify the tumors that most frequently metastasize to the stomach and the morphologic features that can provide clues to investigate the possibility of metastasis and predict the primary sites.

Methods: All patients with metastatic neoplasms involving the stomach were included in the study.

Adenomatoid tumours of the gastrointestinal tract - a case-series and review of the literature.

Aims: Adenomatoid tumours are mesothelial-derived benign neoplasms with a predilection for the genital tract. Extragenital sites are rare and can cause significant diagnostic challenges. Herein, we describe the clinicopathological features of a cohort of adenomatoid tumours involving the gastrointestinal tract and liver in order to more clearly characterise their histological findings and aid in diagnosis.

Use of Selective Arterial Calcium Stimulation Testing in Identification of Insulinoma in a Patient After Bariatric Surgery.

Objective: Insulinomas are rare in the post-bariatric surgery setting. The differential diagnosis for hypoglycemia is broad, requiring laboratory testing to verify endogenous hyperinsulinemic hypoglycemia. Selective arterial calcium stimulation testing (SACST) can help localize abnormal insulin production.