Updates in Immunotherapy for Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options. Due to a variety of cancer cell-intrinsic factors, including KRAS mutations, chemokine production, and other mechanisms that elicit a dysregulated host immune response, PDAC is often characterized by poor immune infiltration and an immune-privileged fibrotic stroma. As understanding of the tumor microenvironment (TME) evolves, novel therapies are being developed to target immunosuppressive mechanisms.

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial.

Background: The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading.

Open vs robotic-assisted pancreaticoduodenectomy, cost-effectiveness and long-term oncologic outcomes: a systematic review and meta-analysis.

Background: Whipple pancreaticoduodenectomy (PD) is a complex gastrointestinal surgery that is performed increasingly via minimally invasive approach through robotic platforms. We sought to provide a comparative review of available data regarding robot-assisted vs open PD in terms of cost-effectiveness, overall survival, and other perioperative and long-term oncologic outcomes.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, PubMed, Scopus, and Web of Science databases were searched from 1980 to April 2024 using designated keywords.

Neoadjuvant systemic therapy for hepatocellular carcinoma.

Surgical resection and liver transplant remain the only curative therapies for most patients with hepatocellular carcinoma (HCC). Systemic therapy options have typically been ineffective, but recent advances, such as the combination of immune checkpoint inhibitors and targeted therapies, have shown great promise. Neoadjuvant systemic therapy in resectable or locally advanced HCC is under active investigation with encouraging results in small, early-phase trials.

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

Introduction: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS).

Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results.

Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis.

Background: The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (±granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients.

Modern trends in minimally invasive versus open hepatectomy for colorectal liver metastasis: an analysis of ACS-NSQIP.

Background: Surgical resection of colorectal liver metastasis (CRLM) provides the best opportunity for prolonged survival. Eligibility for metastasectomy has expanded with technical advancements including parenchymal-sparing hepatectomy (PSH). Meanwhile, enthusiasm for minimally invasive surgery (MIS) has increased, though this approach may be preferentially utilized for technically straightforward cases.

Meeting the New Commission on Cancer Operative Standards: Where Do We Stand Now?

Introduction: The 2020 Commission on Cancer accreditation standards 5.7 and 5.8 address total mesorectal excision for rectal cancer and lymph node sampling for lung cancer.

Divergent clinical outcomes in a phase 2B trial of the TLPLDC vaccine in preventing melanoma recurrence and the impact of dendritic cell collection methodology: a randomized clinical trial.

Background: A randomized, double-blind, placebo-controlled phase 2b trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was conducted in patients with resected stage III/IV melanoma. Dendritic cells (DCs) were harvested with and without granulocyte-colony stimulating factor (G-CSF). This analysis investigates differences in clinical outcomes and RNA gene expression between DC harvest methods.

Downstaging of Pancreatic Adenocarcinoma With Either Neoadjuvant Chemotherapy or Chemoradiotherapy Improves Survival.

Background: Neoadjuvant chemotherapy (NAC) or chemoradiation (NAC+XRT) is incorporated into the treatment of localized pancreatic adenocarcinoma (PDAC), often with the goal of downstaging before resection. However, the effect of downstaging on overall survival, particularly the differential effects of NAC and NAC+XRT, remains undefined. This study examined the impact of downstaging from NAC and NAC+XRT on overall survival.

Maximizing Benefit of Virtual Learning: Lessons From the Coronavirus Disease 2019 Pandemic.

Introduction: The coronavirus disease 2019 pandemic has profoundly impacted surgical education. We assessed resident perceptions of our virtual academic program, which consists of daily lectures or case conferences held via a videoconferencing platform.

Methods: A survey evaluating attitudes and practices for virtual academics was administered to general surgery residents.

Using the Flipped Classroom Model in Surgical Education: Efficacy and Trainee Perception.

Objective: To describe the feasibility, efficacy, and learner perception of the flipped classroom model for teaching conferences within surgical training programs.

Design: For the flipped classroom conferences, video lectures were prepared by a faculty member, and sent to all attendees at least 2 days prior to lecture. The conference time was then spent going over cases and questions, rather than traditional lecture.

Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center.

Background: Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center.

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

Background: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups.

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis.

Background: Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient's immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma.

Methods: This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma.

Rates, Predictors, and Outcomes of Portal Lymphadenectomy for Resectable Gallbladder Cancer.

Introduction: Lymphadenectomy (LND) is recommended following surgical resection of ≥ T1b gallbladder cancer (GBC). However, frequency and stage-specific survival benefits of LND remain unclear.

Patients And Methods: The National Cancer Database (NCDB; 2006-15) was queried for resected pathologic stage I-III GBC.

Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression.

No approved medical therapies prevent progression of low-grade prostate cancer. Rapamycin inhibits cell proliferation and augments immune responses, producing an antitumor effect. Encapsulated rapamycin (eRapa) incorporates rapamycin into a pH-sensitive polymer, ensuring consistent dosing.

Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer.

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.

Lymph node sampling in resectable hepatocellular carcinoma: national practice patterns and predictors of positive lymph nodes.

Background And Objectives: Routine lymphadenectomy (LND) for resectable hepatocellular carcinoma (HCC) remains controversial. We evaluated national LND trends to identify pre-operative factors associated with node-positive disease to determine which patients might benefit from LND.

Methods: We identified HCC patients in the National Cancer Database (NCDB) treated with surgical resection between 2004 and 2015.

Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

Background: Colorectal cancer (CRC) tumor microenvironment (TME) characteristics, such as tumor infiltrating lymphocyte (TIL) densities and PD-L1 status, are predictive of recurrence, disease-free survival, and overall survival. In many malignancies, TME characteristics are also predictive of response to immunotherapy. As window of opportunity studies using neoadjuvant immunotherapy become more common and treatment guidelines incorporate TME features, accurate assessment of the pre-treatment TME using the biopsy specimen is critical.

An Educational Intervention Reduces Opioids Prescribed Following General Surgery Procedures.

Background: Variability exists in opioid prescribing practices among surgeons, frequently resulting in the prescription of excessive opioids. This study evaluated the ability of a single educational intervention targeted toward general surgery residents to reduce the quantity of postoperative opioids prescribed.

Materials And Methods: This retrospective cohort study evaluated opioid prescribing practices 12 mo prior to and 6 mo following a 30-min lecture for general surgery residents that discussed prescribing guidelines and multimodal analgesia.

Adjuvant Chemotherapy in Resectable Gallbladder Cancer is Underutilized Despite Benefits in Node-Positive Patients.

Background: Adjuvant chemotherapy (AC) is recommended following surgical resection of gallbladder cancer regardless of stage. However, stage-specific benefits of AC in gallbladder cancer are unclear.

Patients And Methods: Patients with resected pathologic stage I-III gallbladder cancer were identified using the 2006-2015 National Cancer Database.

Chemoprevention in familial adenomatous polyposis: past, present and future.

Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome characterized by colorectal adenomas and a near 100% lifetime risk of colorectal cancer (CRC). Prophylactic colectomy, usually by age 40, is the gold-standard therapy to mitigate this risk. However, colectomy is associated with morbidity and fails to prevent extra-colonic disease manifestations, including gastric polyposis, duodenal polyposis and cancer, thyroid cancer, and desmoid disease.