Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years.

Background: Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas.

Analysis of shared variants between cancer biospecimens.

Purpose: Mutational data from multiple solid and liquid biospecimens of a single patient is often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence.

Experimental Design: Utilizing 8,000 patient tumors from The Cancer Genome Atlas (TCGA) across 33 cancer types, we estimated background rates of co-occurrence rates of mutations between discrete pairs of samples across cancers and by cancer type.

Molecular and Clinicopathologic Impact of GNAS Variants Across Solid Tumors.

Purpose: The molecular drivers underlying mucinous tumor pathogenicity are poorly understood. mutations predict metastatic burden and treatment resistance in mucinous appendiceal adenocarcinoma. We investigated the pan-cancer clinicopathologic relevance of variants.

Predicting response to immune checkpoint blockade therapy among mismatch repair-deficient patients using mutational signatures.

Despite the overall efficacy of immune checkpoint blockade (ICB) for mismatch repair deficiency (MMRD) across tumor types, a sizable fraction of patients with MMRD still do not respond to ICB. We performed mutational signature analysis of panel sequencing data (n = 95) from MMRD cases treated with ICB. We discover that T>C-rich single base substitution (SBS) signatures-SBS26 and SBS54 from the COSMIC Mutational Signatures catalog-identify MMRD patients with significantly shorter overall survival.

Ecological structure of diversity-dependent diversification in Phanerozoic marine bivalves.

Rigorous analysis of diversity-dependence-the hypothesis that the rate of proliferation of new species is inversely related to standing diversity-requires consideration of the ecology of the organisms in question. Differences between infaunal marine bivalves (living entirely within the sediment) and epifaunal forms (living partially or completely above the sediment-water interface) predict that these major ecological groups should have different diversity dynamics: epifaunal species may compete more intensely for space and be more susceptible to predation and physical disturbance. By comparing detrended standing diversity with rates of diversification, origination, and extinction in this exceptional fossil record, we find that epifaunal bivalves experienced significant, negative diversity-dependence in origination and net diversification, whereas infaunal forms show little appreciable relationship between diversity and evolutionary rates.

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.

Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38).

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.

Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%.

Metastatic well differentiated serotonin-producing pancreatic neuroendocrine tumor with carcinoid heart disease: a case report.

Background: Less than two percent of pancreatic neuroendocrine tumors (NETs) produce serotonin. Serotonin can cause carcinoid syndrome and less commonly carcinoid heart disease (CHD). CHD is associated with increased mortality and requires a more aggressive approach.

Facts and Hopes in Colorectal Cancer Immunotherapy.

Although a minority of colorectal cancers exhibit mismatch repair deficiency and associated sensitivity to immune checkpoint inhibitors (ICI), the vast majority of colorectal cancers arise in a tolerogenic microenvironment with mismatch repair proficiency, low tumor-intrinsic immunogenicity, and negligible immunotherapy responsiveness. Treatment strategies to augment tumor immunity with combination ICIs and chemotherapy have broadly failed in mismatch repair-proficient tumors. Similarly, although several small single-arm studies have shown that checkpoint blockade plus radiation or select tyrosine kinase inhibition may show improved outcomes compared with historical controls, this finding has not been clearly validated in randomized trials.

The Impact of Germline Alterations in Appendiceal Adenocarcinoma.

Purpose: More than 10% of assessed patients with appendiceal adenocarcinoma have a pathogenic (P) or likely pathogenic (LP) germline variant, including genes implicated in heritable gastrointestinal cancer syndromes, such as Lynch syndrome. We defined the clinical and molecular impact of heritable alterations in appendiceal adenocarcinoma to evaluate the need for dedicated appendiceal screening and prevention strategies in patients with LP/P germline variants.

Experimental Design: We performed an integrated germline and somatic molecular analysis for patients with confirmed appendiceal adenocarcinoma.

Diversity-Dependent Diversification in the History of Marine Animals.

AbstractBy comparing detrended estimates of diversity (taxonomic richness) and rates of origination, extinction, and net diversification, I show that at the global scale over the course of the Phanerozoic eon, rates of diversification and origination are negatively correlated with diversity. By contrast, extinction rates are only weakly correlated with diversity for the most part. These results hold for both genus- and species-level data and for many alternative analytical protocols.

Clinical Outcomes Associated With Pembrolizumab Monotherapy Among Adults With Diffuse Malignant Peritoneal Mesothelioma.

Importance: Diffuse malignant peritoneal mesothelioma (DMPM) represents a rare and clinically distinct entity among malignant mesotheliomas. Pembrolizumab has activity in diffuse pleural mesothelioma but limited data are available for DMPM; thus, DMPM-specific outcome data are needed.

Objective: To evaluate outcomes after the initiation of pembrolizumab monotherapy in the treatment of adults with DMPM.

Clinical Importance of Clonal Hematopoiesis in Metastatic Gastrointestinal Tract Cancers.

Importance: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity.

Objective: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB.

Molecular Classification of Appendiceal Adenocarcinoma.

Purpose: Appendiceal adenocarcinomas (ACs) are rare, histologically diverse malignancies treated as colorectal cancers despite having distinct biology and clinical behavior. To guide clinical decision making, we defined molecular subtypes of AC associated with patient survival, metastatic burden, and chemotherapy response.

Patients And Methods: A comprehensive molecular analysis was performed in patients with AC to define molecular subtypes.

Association of Perceived Role Misidentification With Use of Role Identity Badges Among Resident Physicians.

Importance: Role misidentification of resident physicians occurs frequently and is associated with decreased well-being.

Objective: To evaluate the role misidentification and burnout rates among resident physicians after disbursement of role identity badges.

Design, Setting, And Participants: This quality improvement study was conducted during the 2018 to 2019 academic year.

PD-1 Blockade in Solid Tumors with Defects in Polymerase Epsilon.

Unlabelled: Missense mutations in the polymerase epsilon (POLE) gene have been reported to generate proofreading defects resulting in an ultramutated genome and to sensitize tumors to checkpoint blockade immunotherapy. However, many POLE-mutated tumors do not respond to such treatment. To better understand the link between POLE mutation variants and response to immunotherapy, we prospectively assessed the efficacy of nivolumab in a multicenter clinical trial in patients bearing advanced mismatch repair-proficient POLE-mutated solid tumors.

Treatment of Platinum Nonresponsive Metastatic Malignant Peritoneal Mesothelioma With Combination Chemoimmunotherapy.

Malignant peritoneal mesothelioma is a rare cancer associated with minimal durable disease control with chemotherapy and poor overall survival. The efficacy of combined cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) in malignant peritoneal mesothelioma has not previously been studied. We describe the clinical course of 2 patients with metastatic peritoneal mesothelioma who both relapsed with platinum nonresponsive disease after initial cytoreductive surgery and chemotherapy.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19.

Association of Antineoplastic Therapy With Decreased SARS-CoV-2 Infection Rates in Patients With Cancer.

Importance: Novel therapies for SARS-CoV-2 infection are urgently needed. Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity.

Objectives: To determine whether patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates.