Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis.

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM

Castleman's disease in the head of the pancreas: report of a rare clinical entity and current perspective on diagnosis, treatment, and outcome

<p>Abstract</p> <p>Background</p> <p>Castleman's disease of the pancreas is a very rare condition that may resemble more common disease entities as well as pancreatic cancer.</p> <p>Case presentation</p> <p>Here we report the case of a 58-year-old African American male with an incidentally discovered lesion in the head of the pancreas. The specimen from his pancreaticoduodectomy contained a protuberant, encapsulated mass, exhibiting microscopic features most consistent with localized/unicentric Castleman's disease. These included florid follicular hyperplasia with mantle/marginal zone hyperplasia along with focal progressive transformation of germinal centers admixed with involuted germinal centers.</p> <p>Conclusion</p> <p>To date, eight cases of Castleman's disease associated with the pancreas have been described in the world literature. We report the first case of unicentric disease situated within the head of the pancreas. In addition, we discuss the diagnostic dilemma Castleman's disease may present to the pancreatic surgeon and review current data on pathogenesis, treatment, and outcome.</p

Retroperitoneal Castleman’s disease: advocating a multidisciplinary approach for a rare clinical entity

BACKGROUND: Castleman’s disease is a rare and poorly understood disease entity that may resemble more common conditions and represents a clinical challenge to the treating surgeon. CASE PRESENTATION: In this report, we describe a case of a 61-year-old Caucasian woman with a symptomatic retroperitoneal mass. The specimen obtained from her resection contained a protuberant encapsulated mass, exhibiting microscopic features consistent with localized, unicentric Castleman’s disease. These characteristics included architectural features and immunohistochemical findings consistent with the hyaline vascular variant of Castleman’s disease. CONCLUSION: We report a very rare case of a retroperitoneal hyaline vascular type of Castleman’s disease. We discuss the diagnostic dilemma Castleman’s disease may present to the surgeon, with an emphasis on multidisciplinary management of these patients. We also review current data on pathogenesis, treatment and outcomes

Non-Thermal Plasma-Induced Immunogenic Cell Death in Cancer: A Topical Review.

Recent advances in biomedical research in cancer immunotherapy have identified the use of an oxidative stress-based approach to treat cancers, which works by inducing immunogenic cell death (ICD) in cancer cells. Since the anti-cancer effects of non-thermal plasma (NTP) are largely attributed to the reactive oxygen and nitrogen species that are delivered to and generated inside the target cancer cells, it is reasonable to postulate that NTP would be an effective modality for ICD induction. NTP treatment of tumors has been shown to destroy cancer cells rapidly and, under specific treatment regimens, this leads to systemic tumor-specific immunity. The translational benefit of NTP for treatment of cancer relies on its ability to enhance the interactions between NTP-exposed tumor cells and local immune cells which initiates subsequent protective immune responses. This review discusses results from recent investigations of NTP application to induce immunogenic cell death in cancer cells. With further optimization of clinical devices and treatment protocols, NTP can become an essential part of the therapeutic armament against cancer

Chronic Obstructive Pulmonary Disease Is Associated with Worse Oncologic Outcomes in Early-Stage Resected Pancreatic and Periampullary Cancers

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer mortality in the United States. Hypoxic and hypercapnic tumor microenvironments have been suggested to promote tumor aggressiveness. The objective of this study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and oncologic survival outcomes in patients with early-stage PDAC and periampullary cancers. In this case-control study, patients who underwent a pancreaticoduodenectomy during 2014–2021 were assessed. Demographic, perioperative, histologic, and oncologic data were collected. A total of 503 PDAC and periampullary adenocarcinoma patients were identified, 257 males and 246 females, with a mean age of 68.1 (±9.8) years and a mean pre-operative BMI of 26.6 (±4.7) kg/m2. Fifty-two percent of patients (N = 262) reported a history of smoking. A total of 42 patients (8.3%) had COPD. The average resected tumor size was 2.9 ± 1.4 cm and 65% of the specimens (N = 329) were positive for lymph-node involvement. Kaplan–Meier analysis showed that COPD was associated with worse overall and disease-specific survival (p \u3c 0.05). Cox regression analysis showed COPD to be an independent prognostic factor (HR = 1.5, 95% CI 1.0–2.3, p = 0.039) along with margin status, lymphovascular invasion, and perineural invasion (p \u3c 0.05 each). A 1:3 nearest neighbor propensity score matching was also employed and revealed COPD to be an independent risk factor for overall and disease-specific survival (OR 1.8 and OR 1.6, respectively; p \u3c 0.05 each). These findings may support the rationale posed by in vitro laboratory studies, suggesting an important impact of hypoxic and hypercapnic tumor respiratory microenvironments in promoting therapy resistance in cancer

Repurposing the FDA-Approved Anthelmintic Pyrvinium Pamoate for Pancreatic Cancer Treatment: Study Protocol for a Phase I Clinical Trial in Early-Stage Pancreatic Ductal Adenocarcinoma

BACKGROUND: Recent reports of the utilisation of pyrvinium pamoate (PP), an FDA-approved anti-helminth, have shown that it inhibits pancreatic ductal adenocarcinoma (PDAC) cell growth and proliferation in-vitro and in-vivo in preclinical models. Here, we report about an ongoing phase I open-label, single-arm, dose escalation clinical trial to determine the safety and tolerability of PP in PDAC surgical candidates. METHODS AND ANALYSIS: In a 3+3 dose design, PP is initiated 3 days prior to surgery. The first three patients will be treated with the initial dose of PP at 5 mg/kg orally for 3 days prior to surgery. Dose doubling will be continued to a reach a maximum of 20 mg/kg orally for 3 days, if the previous two dosages (5 mg/kg and 10 mg/kg) were tolerated. Dose-limiting toxicity grade≥3 is used as the primary endpoint. The pharmacokinetic and pharmacodynamic (PK/PD) profile of PP and bioavailability in humans will be used as the secondary objective. Each participant will be monitored weekly for a total of 30 days from the final dose of PP for any side effects. The purpose of this clinical trial is to examine whether PP is safe and tolerable in patients with pancreatic cancer, as well as assess the drug\u27s PK/PD profile in plasma and fatty tissue. Potential implications include the utilisation of PP in a synergistic manner with chemotherapeutics for the treatment of pancreatic cancer. ETHICS AND DISSEMINATION: This study was approved by the Thomas Jefferson Institutional Review Board. The protocol number for this study is 20F.041 (Version 3.1 as of 27 October 2021). The data collected and analysed from this study will be used to present at local and national conferences, as well as, written into peer-reviewed manuscript publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05055323