Tyrosine Kinase Inhibition Activates Intratumoral γδ T Cells in Gastrointestinal Stromal Tumor.

γδ T cells are a rare but potent subset of T cells with pleiotropic functions. They commonly reside within tumors but the response of γδ T cells to tyrosine kinase inhibition is unknown. To address this, we studied a genetically engineered mouse model of gastrointestinal stromal tumor (GIST) driven by oncogenic Kit signaling that responds to the Kit inhibitor imatinib.

Multiple intratumoral sources of kit ligand promote gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the Kit or PDGFRA receptor. While highly effective, tyrosine kinase inhibitors (TKIs) are not curative. The natural ligand for the Kit receptor is Kit ligand (KitL), which exists in both soluble and membrane-bound forms.

Immunotherapy for GI Malignancies, Ready for Prime Time?

Gastrointestinal (GI) cancers include esophageal, gastric, pancreatic, hepatobiliary, and colorectal malignancies. Immunotherapy has proved to be an important treatment method for cancer, and its use for a wide range of GI malignancies has been evaluated recently. This article discusses the type and mechanism of various immunotherapies under investigation in GI cancer.

Tyrosine Kinase Inhibition Alters Intratumoral CD8+ T-cell Subtype Composition and Activity.

Targeted therapy with a tyrosine kinase inhibitor (TKI) such as imatinib is effective in treating gastrointestinal stromal tumor (GIST), but it is rarely curative. Despite the presence of a robust immune CD8+ T-cell infiltrate, combining a TKI with immune-checkpoint blockade (ICB) in advanced GIST has achieved only modest effects. To identify limitations imposed by imatinib on the antitumor immune response, we performed bulk RNA sequencing (RNA-seq), single-cell RNA-seq, and flow cytometry to phenotype CD8+ T-cell subsets in a genetically engineered mouse model of GIST.

Pulling Back from the Brink: A Multi-Pronged Approach to Address General Surgery Resident Clinical Work Hour Adherence.

Purpose: The conflict between prioritizing education for surgical trainees, promoting trainee wellness, and maintaining optimal patient care has remained challenging since the introduction of the Accreditation Council for Graduate Medical Education (ACGME) work hour restrictions in 2003. There is still a dearth of research examining which interventions successfully enable duty hour adherence. This study assessed the impact of a combination of strategic interventions on improving clinical work hour adherence.

Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the KIT receptor. Across tumor types, numerous mouse models have been developed in order to investigate the next generation of cancer therapies. However, in GIST, most in vivo studies use xenograft mouse models which have inherent limitations.

Hiatal Hernia after Esophagectomy: An Underappreciated Complication?

Background: The natural history of hiatal herniation of small and/or large bowel post-esophagectomy (HHBPE) in the current era of improving long-term survival and evolving surgical technique is unknown. The aim of this study was to describe the rate and risk factors of HHBPE at our hospital.

Methods: Patients undergoing esophagectomy between January 2011 and June 2017 were included if both follow-up information and axial imaging were available beyond 3 months post-esophagectomy.

Relationship between age and likelihood of lymph node metastases in patients with intermediate thickness melanoma (1.01-4.00 mm): A National Cancer Database study.

Background: There is large variability in the risk of sentinel lymph node (SLN) positivity among patients with intermediate thickness melanoma (ITM), with a subgroup of patients exhibiting a low risk of nodal disease.

Objective: To identify a group of patients with ITM for whom the risk of nodal disease is low.

Methods: A retrospective cohort of patients with ITM who underwent wide excision and nodal evaluation from 2010 to 2013 was identified by using the National Cancer Database and analyzed for the presence of nodal disease.

Laparoscopic Heller Myotomy vs Per Oral Endoscopic Myotomy: Patient-Reported Outcomes at a Single Institution.

Background: Although laparoscopic Heller myotomy (LHM) has been the standard of care for achalasia, per oral endoscopic myotomy (POEM) has gained popularity as a viable alternative. This retrospective study aimed to compare patient-reported outcomes between LHM and POEM in a consecutive series of achalasia patients with more than 1 year of follow-up.

Study Design: We reviewed demographic and procedure-related data for patients who underwent either LHM or POEM for achalasia between January 2011 and May 2016.