Impact of American College of Surgeons Geriatric Surgery Verification Program in Patients Undergoing Major Abdominal Oncologic Operation at a Cancer Center.

Background: Patients older than 65 years have unique needs and treatment outcomes goals. The objective of this study was to evaluate the impact of Geriatric Surgery Verification (GSV) initiative in oncology patients ≥65 years undergoing major abdominal surgeries.

Study Design: We implemented the American College of Surgeons' GSV program protocols for patients 65 and older starting in 2022.

Impact of Medicaid Expansion on Screenable versus Non-Screenable Gastrointestinal Cancers.

Background: Medicaid expansion afforded increased healthcare access to low-income Americans contributing to a positive impact on cancer outcomes. However, it is unclear if these benefits were mainly due to enhanced access to cancer screening and earlier diagnosis versus access to cancer treatment METHODS: The National Cancer Database (NCDB) was queried between 2010-2021 for Medicaid and uninsured patients with GI malignancies. Patients were stratified by screenable (SGI) and non-screenable (NGI) cancers and expansion state (ES) categories: early (EES) and late (LES) adopters, and non-expansion state (NES) cohorts.

Negative Impact of Systemic Therapy on Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Low-Grade Metastatic Appendiceal Adenocarcinoma.

Background: Despite studies demonstrating that patients with peritoneal metastases from low-grade appendiceal adenocarcinoma (AA) do not respond well to systemic chemotherapy (SC), patients frequently undergo combination of SC with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) regardless of grade.

Methods: A nationwide retrospective analysis using the National Cancer Database evaluated patients with AA with peritoneal metastasis from 2016 to 2021. Cox proportional hazards model was used to evaluate the impact of SC in addition to CRS/HIPEC on overall survival (OS) stratified by tumor grade.

Decreasing colorectal cancer screening disparities: A culturally tailored patient navigation program for Hispanic patients.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in Hispanic patients. Screening colonoscopy has been shown to reduce the incidence and mortality of CRC. However, utilization among Hispanic patients and other minority groups is low.

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: an evidence-based expert consensus algorithm.

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres].

HITM-SIR: phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA liver metastases.

Effective chimeric antigen receptor-modified T-cell (CAR-T) therapy for liver metastases (LM) will require innovative solutions to ensure efficient delivery and minimization of systemic toxicity. We previously demonstrated the safety of CAR-T hepatic artery infusions (HAI). We subsequently conducted the phase 1b HITM-SIR trial, in which six patients (pts) with CEA LM received anti-CEA CAR-T HAIs and selective internal radiation therapy (SIRT).

Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor: The PERSIST-5 Clinical Trial.

Importance: Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment. The impact of a longer duration of therapy is unknown.

Objective: To determine whether adjuvant treatment for primary GIST with imatinib for 5 years is tolerable and efficacious.

STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells.

Immunosuppressive myeloid-derived suppressor cells (MDSC) subvert antitumor immunity and limit the efficacy of chimeric antigen receptor T cells (CAR-T). Previously, we reported that the GM-CSF/JAK2/STAT3 axis drives liver-associated MDSC (L-MDSC) proliferation and blockade of this axis rescued antitumor immunity. We extended these findings in our murine liver metastasis (LM) model, by treating tumor-bearing mice with STAT3 inhibitors (STATTIC or BBI608) to further our understanding of how STAT3 drives L-MDSC suppressive function.

Association of primary tumor lymph node ratio with burden of liver metastases and survival in stage IV colorectal cancer.

Background: The primary objective of our study was to assess the association of primary tumor lymph node ratio (LNR) in stage IV colorectal adenocarcinomas (CRC) with overall survival (OS) and the extent of metastatic disease in the liver.

Methods: We analyzed data on 53 stage IV CRC patients who underwent surgical resection of the primary tumor. The median LNR of 0.

Frontline Science: Functionally impaired geriatric CAR-T cells rescued by increased α5β1 integrin expression.

Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T.

Predictors of surgical non-referral for colorectal liver metastases.

Background: Surgical resection is the only curative option for patients with colorectal liver metastases (CRLM). The objective of our study was to identify factors associated with failure to refer patients with CRLM to a surgeon with oncologic and hepatobiliary expertise.

Materials And Methods: Data were retrospectively reviewed on 75 patients with CRLM treated at our institution.

Phase I Hepatic Immunotherapy for Metastases Study of Intra-Arterial Chimeric Antigen Receptor-Modified T-cell Therapy for CEA+ Liver Metastases.

Purpose: Chimeric antigen receptor-modified T cells (CAR-T) have demonstrated encouraging results in early-phase clinical trials. Successful adaptation of CAR-T technology for CEA-expressing adenocarcinoma liver metastases, a major cause of death in patients with gastrointestinal cancers, has yet to be achieved. We sought to test intrahepatic delivery of anti-CEA CAR-T through percutaneous hepatic artery infusions (HAIs).

Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T.

Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function.

Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+CD11b+ myeloid cells.

LM escape immune surveillance, in part, as a result of the expansion of CD11b+MC, which alter the intrahepatic microenvironment to promote tumor tolerance. HBC make up a significant proportion of liver lymphocytes and appear to delay tumor progression; however, their significance in the setting of LM is poorly defined. Therefore, we characterized HBC and HBC/CD11b+MC interactions using a murine model of LM.

Regional hepatic therapies: an important component in the management of colorectal cancer liver metastases.

The treatment of colorectal cancer liver metastases (CRLM) has evolved significantly in the last 15 years. Currently, complete surgical resection remains the only potentially curative option; unfortunately, approximately 80% of patients with CRLM are not candidates for complete tumor resection. For patients with unresectable CRLM the available treatment options were historically limited; however, the development of regional hepatic therapies (RHT) and improvement of systemic chemotherapeutic regimens have emerged as viable options to improve overall survival and quality of life for this group of patients.

Biliary obstruction results in PD-1-dependent liver T cell dysfunction and acute inflammation mediated by Th17 cells and neutrophils.

Biliary obstruction is a common clinical problem that is associated with intrahepatic inflammation and impaired immunity. PD-1 is well known to mediate T cell dysfunction but has been reported to promote and attenuate acute inflammation in various injury models. With the use of a well-established murine model of BDL, we studied the effects of intrahepatic PD-1 expression on LTC function, inflammation, and cholestasis.

Lenalidomide for second-line treatment of advanced hepatocellular cancer: a Brown University oncology group phase II study.

Purpose: To assess the activity and toxicity of lenalidomide for patients with advanced hepatocellular cancer (HCC) previously treated with sorafenib.

Materials And Methods: Patients with advanced HCC who progressed on or were intolerant to sorafenib were eligible. Patients received lenalidomide 25 mg orally for 1 to 21 days in a 28-day cycle until disease progression or unacceptable toxicities.

Anti-KIT designer T cells for the treatment of gastrointestinal stromal tumor.

Background: Imatinib mesylate is an effective treatment for metastatic gastrointestinal stromal tumor (GIST). However, most patients eventually develop resistance and there are few other treatment options. Immunotherapy using genetically modified or designer T cells (dTc) has gained increased attention for several malignancies in recent years.

Thermal tumor ablation therapy for colorectal cancer hepatic metastasis.

Surgical resection for colorectal hepatic metastases (CRHM) is the preferred treatment for suitable candidates, and the only potentially curative modality. However, due to various limitations, the majority of patients with CRHM are not candidates for liver resection. In recent years, there has been an increasing interest in the role of thermal tumor ablation (TTA) as a component of combined resection-ablation strategies, staged hepatic resections, or as standalone adjunct treatment for patients with CRHM.

Feasibility of purely laparoscopic resection of locally advanced rectal cancer in obese patients.

Background: Totally laparoscopic (without hand-assist) resection for rectal cancer continues to evolve, and both obesity and locally advanced disease are perceived to add to the complexity of these procedures. There is a paucity of data on the impact of obesity on perioperative and oncologic outcomes for totally-laparoscopic rectal cancer resection (TLRR) for locally advanced disease.

Methods: In order to identify potential limitations of TLRR, a single-institution database was queried and identified 26 patients that underwent TLRR for locally advanced rectal cancers (T3/T4) over a three-year period.

The effects of sorafenib on liver regeneration in a model of partial hepatectomy.

Background: Sorafenib is currently approved for advanced hepatocellular carcinoma (HCC) and is presently being studied as an adjuvant treatment for HCC following resection. The effects of sorafenib on liver regeneration have not been clearly defined. Our objective was to identify the effects of sorafenib on liver regeneration in a murine partial hepatectomy (PH) model.

Safety and efficacy of trans arterial chemoembolization with drug-eluting beads in hepatocellular cancer: a systematic review.

Background/aims: The aim of this review was to compare current conventional TACE to the drug eluting beads loaded with doxorubicin (DEBDOX) device in the treatment of HCC.

Methodology: A recent hepatocellular consensus discussion was convened to review all recent and past literature in the use of hepatic directed therapies to compare the safety, efficacy and overall survival of the available hepatic directed therapies in the management of hepatocellular cancer. A review of all publications in peer review journals in the English Language from 1995 to 2007 was performed.

Total laparoscopic distal pancreatectomy: beyond selected patients.

Laparoscopic distal pancreatectomy (LDP) has emerged as the procedure of choice for selected patients. This study is to evaluate the feasibility of LDP and procedural outcomes in a series of consecutive nonselected patients. All patients undergoing distal pancreatectomy over 18 months were identified from a prospectively maintained database, under institutional review board approval.