CD93 blockade overcomes sunitinib resistance in pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare malignancies of the pancreas, but their incidence is steadily increasing. Standard therapy with antiangiogenic inhibitors, including sunitinib, has shown clinical benefit for advanced PanNETs; however, its long-term effectiveness is limited due to the development of resistance. In this study, we demonstrate that targeting the CD93-IGFBP7 axis enhances the efficacy of sunitinib by normalizing tumor vasculature in PanNETs.

Treatment Innovations in Pancreatic Cancer: Putting Patient Priorities First.

Pancreatic adenocarcinoma remains one of the most aggressive and difficult-to-treat solid tumor malignancies, with a high mortality-to-incidence ratio. Globally, pancreatic cancer ranks 12th in terms of incidence but sixth for mortality signifying its aggressive behavior and limited treatment options. While the mortality rates for many other solid tumors have substantially improved over the past few decades, temporal trends in pancreatic cancer mortality rates are quite sobering.

GPR182 is a lipoprotein receptor for dietary fat absorption.

The lymphatic system plays a central role in lipid absorption, which transports chylomicrons from the small intestine to the circulation. However, the molecular mechanism by which chylomicrons get into the intestinal lymphatics is unknown. Here we demonstrated that GPR182, a receptor in lymphatic endothelial cells (LECs), mediates dietary fat absorption.

Pancreatectomies with vein resection: Two large institutions' experience of East and West.

Background: The effectiveness and preferred reconstruction methods of pancreatectomy associated with vein resection (PAVR) for pancreatic cancer, especially for the extensive portal vein/superior mesenteric vein (PV/SMV) resections (more than 4 cm), are still subjects of debate. The aim of this study is to evaluate the safety and feasibility of PAVR by analyzing data from two large institutions from different regions.

Methods: From 2008 to 2018, we identified consecutive series of patients with pancreatic cancer who underwent PAVR at Karolinska University Hospital (KUH), Sweden, and Cancer Institute Hospital, Japanese Foundation of Cancer Research (JFCR), Japan.

Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review.

Resectable cholangiocarcinoma (CCA) arising from the middle of the extrahepatic biliary tree has historically been classified as perihilar or distal CCA, depending on the operation contemplated or performed, namely the associated hepatectomy or pancreaticoduodenectomy, respectively. Segmental bile duct resection is a less invasive alternative for select patients harboring true middle extrahepatic CCA (MCC). A small, yet growing body of literature has emerged detailing institutional experiences with bile duct resection versus pancreaticoduodenectomy or concomitant hepatectomy for MCC.

Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

Background: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC.

Methods: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022.

Group XIV C-type lectins: emerging targets in tumor angiogenesis.

C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology.

Unmeasured factors are associated with the use of completion lymph node dissection (CLND) in melanoma.

Background: Completion lymph node dissection (CLND) was the standard treatment for patients with melanoma with positive sentinel lymph nodes (SLN) until 2017 when data from the DeCOG-SLT and MLST-2 randomized trials challenged the survival benefit of this procedure. We assessed the contribution of patient, tumor and facility factors on the use of CLND in patients with surgically resected Stage III melanoma.

Methods: Using the National Cancer Database, patients who underwent surgical excision and were found to have a positive SLN from 2012 to 2017 were included.

Circulating CD8 mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients.

Objectives: While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on the contributions of conventional peptide-specific T cells, the role of unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are an abundant population of innate-like T cells expressing a semi-invariant T-cell receptor restricted to the MHC class I-like molecule, MR1, presenting vitamin B metabolites derived from bacteria. We sought to characterise MAIT cells in melanoma patients and determined their association with treatment responses and clinical outcomes.

GPR182 limits antitumor immunity via chemokine scavenging in mouse melanoma models.

For many solid tumors, immune checkpoint blockade therapy has become first line treatment, yet a large proportion of patients with immunologically cold tumors do not benefit due to the paucity of tumor infiltrating lymphocytes. Here we show that the orphan G Protein-Coupled Receptor 182 (GPR182) contributes to immunotherapy resistance in cancer via scavenging chemokines that are important for lymphocyte recruitment to tumors. GPR182 is primarily upregulated in melanoma-associated lymphatic endothelial cells (LECs) during tumorigenesis, and this atypical chemokine receptor endocytoses chemokines promiscuously.

The GPR171 pathway suppresses T cell activation and limits antitumor immunity.

The recently identified G-protein-coupled receptor GPR171 and its ligand BigLEN are thought to regulate food uptake and anxiety. Though GPR171 is commonly used as a T cell signature gene in transcriptomic studies, its potential role in T cell immunity has not been explored. Here we show that GPR171 is transcribed in T cells and its protein expression is induced upon antigen stimulation.

Adjuvant Therapy for Stage III Melanoma Without Immediate Completion Lymph Node Dissection.

Introduction: For patients with stage III melanoma with occult lymph node metastasis, the use of adjuvant therapy is increasing, and completion lymph node dissection (CLND) is decreasing. We sought to evaluate the use of modern adjuvant therapy and outcomes for patients with stage III melanoma who did not undergo CLND.

Methods: Patients with a positive SLNB from 2015 to 2020 who did not undergo CLND were evaluated retrospectively.

Implementation of Minimally Invasive Pancreaticoduodenectomy at Low and High-Volume Centers.

Background: There is a need to better define the safety of implementing the use of minimally invasive pancreaticoduodenectomy (MIPD) in order to provide evidence for safe application. The objective of this study was to evaluate the mortality associated with the implementation of MIPD across low and high-volume facilities using the National Cancer Database (NCDB).

Methods: Patients in the NCDB with pancreatic cancer diagnosed from 2010-2016 undergoing MIPD were selected.

Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors.

Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites.

Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy.

The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature.

Pancreatic incidentalomas: Investigation and management.

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population.

Induction Chemotherapy Plus Neoadjuvant Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma.

Background: Neoadjuvant chemotherapy with concurrent radiotherapy (nCRT) is an accepted treatment regimen for patients with potentially curable esophageal and gastroesophageal junction (GEJ) adenocarcinoma. The purpose of this study is to evaluate whether induction chemotherapy (IC) before nCRT is associated with improved pathologic complete response (pCR) and overall survival (OS) when compared with patients who received nCRT alone for esophageal and GEJ adenocarcinoma.

Methods: Using the National Cancer Database (NCDB), patients who received nCRT and curative-intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006 to 2015 were included.

De-implementation of Axillary Dissection in Women With Breast Cancer is Largely Driven By Site-level Contextual Effects.

Objective: To assess the contribution of unknown institutional factors (contextual effects) in the de-implementation of cALND in women with breast cancer.

Summary Of Background Data: Women included in the National Cancer Database with invasive breast carcinoma from 2012 to 2016 that underwent upfront lumpectomy and were found to have a positive sentinel node.

Methods: A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and institutional variables on the risk of cALND.

Outcomes After Converted Minimally Invasive to Open Esophagectomy in Patients With Esophageal Cancer.

Background: The objective of this study was to evaluate the impact of unplanned conversion to open esophagectomy during minimally invasive esophagectomy (MIE) on postoperative morbidity and mortality for patients with esophageal cancer, as well as to evaluate the variables that influence the need for conversion.

Methods: This study was a retrospective analysis of patients with esophageal cancer who underwent open esophagectomy or MIE by either a laparothoracoscopic approach or a robotic approach from 2016 to 2018 by using the esophagectomy-specific American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Poisson regression models were used to analyze 30-day outcomes and risk factors for conversion to open esophagectomy during attempted MIE.