A Stauffer, John

PURPOSE Pancreatic cancer (PC) carries a poor prognosis with high rates of unresectable/metastatic disease at diagnosis, recurrence after resection, and few systemic therapy options. Deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) PCs demonstrated uncharacteristically poor outcomes in KEYNOTE-158, evaluating pembrolizumab in MSI-H solid tumors. Our study aggregates the Mayo Clinic experience with dMMR/MSI-H PCs, characterizing the clinical, molecular, and treatment response patterns with a focus on response to immune checkpoint inhibitors (ICIs). METHODS Retrospective data were collected from the electronic medical record from December 2009 to February 2023. Patients were included if they had a pathologically confirmed pancreatic malignancy and had (1) deficient expression of mismatch repair (MMR) proteins by tumor immunohistochemistry, (2) pathogenic mutation of MMR genes on genomic sequencing, and/or (3) MSI-H by polymerase chain reaction. RESULTS Thirty-two patients were identified for inclusion, with all stages of disease represented. Sixteen of these patients underwent surgery or chemoradiotherapy. Of these patients, uncharacteristically favorable responses were seen, with a recurrence rate of only 19% (n = 3) despite a median follow-up of 25 months. In the palliative setting, excellent responses to ICI were seen, with overall response rate (ORR) of 75% (20% complete response). Median time to disease progression was not reached. Response rates to cytotoxic chemotherapy in the palliative setting were poor, with 30% ORR and median time to progression of 4 months. We observed a high rate of discrepancy between MMR and MSI testing methods, representing 19% of the entire cohort and 26% of evaluable cases. CONCLUSION Our data argue for the preferential use of ICI over cytotoxic chemotherapy in any patient with dMMR/MSI-H PC requiring systemic therapy, including in the metastatic and adjuvant/neoadjuvant settings.

Despite advancements in cancer therapy that have occurred over the past several decades, successful treatment of advanced malignancies remains elusive. Substantial resources and significant efforts have been directed toward the development of novel therapeutic modalities to improve patient outcomes. Oncolytic viruses (OVs) are emerging tools with unique characteristics that have attracted great interest in developing effective anticancer treatment. The original attraction was directed toward selective replication and cell-specific toxicity, two unique features that are either inherent to the virus or could be conferred by genetic engineering. However, recent advancements in the knowledge and understanding of OVs are shifting the therapeutic paradigm toward a greater focus on their immunomodulatory role. Nonetheless, there are still significant obstacles that remain to be overcome to enhance the efficiency of OVs as effective therapeutic modalities and potentially establish them as part of standard treatment regimens. In this review, we discuss advances in the design of OVs, strategies to enhance their therapeutic efficacy, functional translation into the clinical settings, and various obstacles that are still encountered in the efforts to establish them as effective anticancer treatments.

Selective oncotropism and cytolytic activity against tumors have made certain viruses subject to investigation as novel treatment modalities. However, monotherapy with oncolytic viruses (OVs) has shown limited success and modest clinical benefit. The capacity to genetically engineer OVs makes them a desirable platform to design complementary treatment modalities to overcome the existing treatment options' shortcomings. In recent years, our knowledge of interactions of the tumors with the immune system has expanded profoundly. There is a growing body of literature supporting immunomodulatory roles for OVs. The concept of bioengineering these platforms to induce the desired immune response and complement the current immunotherapeutic modalities to make immune-resistant tumors responsive to immunotherapy is under investigation in preclinical and early clinical trials. This review provides an overview of attempts to optimize oncolytic virotherapy as essential components of the multimodality anticancer therapeutic approach and discusses the challenges in translation to clinical practice.

Introduction: Minimally invasive major hepatic resection (MIMHR) is increasingly being performed in tertiary centers using either hand-assisted laparoscopic surgery (HALS) or totally laparoscopic surgery (TLS). The outcomes data of MIMHR are scarce, especially in comparison to open major hepatic resection (OMHR). Our aim was to compare 90-day outcomes in major hepatic resections when minimally invasive approaches are attempted. Methods and Procedures: At our institution, minimally invasive liver resection was formally introduced in January 2007, initially using the HALS approach. Since then, the use of TLS approach has increased. We collected data on all patients who underwent major liver resection between January 2007 and December 2017 at our institution. In an intention to treat fashion, we then compared MIMHR to OMHR. Results: From January 2007 to December 2017, 669 patients underwent liver resection. Of these, 203 patients (30%) underwent major hepatic resection and MIMHR and OMHR were performed in 68 (33%) and 135 (67%) patients, respectively. The rate of conversion from minimally invasive to open was 30.9%. Overall, there were no significant differences in 90-day mortality (2.9% versus 1.5%; P = .499) or major complications (14.7% versus 14.8%; P = .985). MIMHR was associated with a shorter average postoperative hospital stay (6.2 days versus 7.9 days; P = .0110) and shorter average ICU stay (0.66 days versus 0.90 days; P = .0299) compared with OMHR. Conclusions: The minimally invasive approach to major liver resection is a safe and reasonable alternative to an open approach when performed by a surgeon experienced with the relevant surgical techniques. MIMHR may be associated with similar outcomes and a shorter postoperative hospital stay with no increase in 90-day postoperative complications to OMHR.

AbstractEfforts to improve mortality associated with locally advanced pancreatic cancer (LAPC) have shown minimal gains despite advances in surgical technique, systemic treatments, and radiation therapy. Locoregional therapy with ablation has not been routinely adopted due to the high risk of complications associated with thermal destruction of the pancreas. Irreversible electroporation (IRE) is an emerging, nonthermal, ablative technology that has demonstrated the ability to generate controlled ablation of LAPC while preserving pancreatic parenchymal integrity. IRE may be performed percutaneously or via laparotomy and will commonly involve multidisciplinary treatment teams. This article will describe the technical aspects of how multidisciplinary IRE is performed during laparotomy at a single tertiary care institution.

Objective: The aim of this study was to develop and externally validate the first evidence-based guidelines on minimally invasive pancreas resection (MIPR) before and during the International Evidence-based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR) meeting in Miami (March 2019). Summary Background Data: MIPR has seen rapid development in the past decade. Promising outcomes have been reported by early adopters from high-volume centers. Subsequently, multicenter series as well as randomized controlled trials were reported; however, guidelines for clinical practice were lacking. Methods: The Scottisch Intercollegiate Guidelines Network (SIGN) methodology was used, incorporating these 4 items: systematic reviews using PubMed, Embase, and Cochrane databases to answer clinical questions, whenever possible in PICO style, the GRADE approach for assessment of the quality of evidence, the Delphi method for establishing consensus on the developed recommendations, and the AGREE-II instrument for the assessment of guideline quality and external validation. The current guidelines are cosponsored by the International Hepato-Pancreato-Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Asian-Pacific Hepato-Pancreato-Biliary Association, the European-African Hepato-Pancreato-Biliary Association, the European Association for Endoscopic Surgery, Pancreas Club, the Society of American Gastrointestinal and Endoscopic Surgery, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology. Results: After screening 16,069 titles, 694 studies were reviewed, and 291 were included. The final 28 recommendations covered 6 topics; laparoscopic and robotic distal pancreatectomy, central pancreatectomy, pancreatoduodenectomy, as well as patient selection, training, learning curve, and minimal annual center volume required to obtain optimal outcomes and patient safety. Conclusion: The IG-MIPR using SIGN methodology give guidance to surgeons, hospital administrators, patients, and medical societies on the use and outcome of MIPR as well as the approach to be taken regarding this challenging type of surgery.

Abstract Objective The Superior Mesenteric Artery Syndrome (SMAS) was first described by Rokitansky in 1842. Clinical symptoms include postprandial pain, nausea, vomiting and weight loss. Duodenojejunostomy is the treatment of choice for patients with SMAS. We now present a case of a young female with SMAS who successfully underwent laparoscopic duodenojejunostomy. Indications The first line treatment for SMAS is medical management, which includes infusion therapy, bowel rest, parenteral nutrition and a nasojejunal feeding tube inserted into the jejunum past the obstruction. If medical therapy fails, surgery is recommended. Procedure A symptomatic patient with body mass index (BMI) of 19.4 kg/m2 underwent laparoscopic duodenojejunostomy. The patient tolerated the procedure well. The post-operative period was uneventful and the patient was discharged after three days. On six month follow up, the patient had gained weight and her symptoms were completely resolved. Conclusion SMAS is still a poorly recognised pathology. A high index of suspicion should be given for patients with unclear causes of postprandial nausea, vomiting and abdominal pain, especially in young females. A laparoscopic approach seems to be safe and effective for patients with SMAS.