Masafumi Nakamura

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.

BACKGROUND: The aim of this study was to compare the long-term outcomes and perioperative outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) between well-matched patient groups. METHODS: Hepatocellular carcinoma patients underwent primary liver resection between 2000 and 2010, were collected from 31 participating institutions in Japan and were divided into LLR (n = 436) and OLR (n = 2969) groups. A one-to-one propensity case-matched analysis was used with covariates of baseline characteristics, including tumor characteristics and surgical procedures of hepatic resections. Long-term and short-term outcomes were compared between the matched two groups. RESULTS: The two groups were well balanced by propensity score matching and 387 patients were matched. There were no significant differences in overall survival and disease-free survival between LLR and OLR. The median blood loss (158 g vs. 400 g, P < 0.001) was significantly less with LLR, and the median postoperative hospital stay (13 days vs. 16 days, P < 0.001) was significantly shorter for LLR. Complication rate (6.7% vs. 13.0%, P = 0.003) was significantly less in LLR. CONCLUSION: Compared with OLR, LLR in selected patients with HCC showed similar long-term outcomes, associated with less blood loss, shorter hospital stay, and fewer postoperative complications.

It has been suggested that immunosuppressive cytokines such as transforming growth factor beta (TGF-beta) and interleukin 10 play an important role in the induction and/or maintenance of regulatory T-cells (Tregs) in patients with cancer. In the present study, whether or not vascular endothelial growth factor (VEGF) contributes to the induction and/or maintenance of Tregs was examined, because of experience with a patient in whom a positive correlation between VEGF concentration and the percentage of Tregs (% Tregs) among the total CD4(+) T-cells in the pleural effusion was found during dendritic cell activated lymphocyte therapy. CD4(+)CD25(high) T-cells were estimated as Tregs in the present study. In an in vitro experimental system, VEGF-containing malignant effusions increased the % Tregs in autologous peripheral blood mononuclear cells (PBMCs), which could be suppressed by the addition of a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]). When VEGF-producing hepatic carcinoma cells were mix-cultured with PBMCs, the % Tregs increased and this increase was also suppressed by the addition of bevacizumab. Whether or not bevacizumab can affect the % Tregs of PBMCs in patients with colon cancer was also examined. Three out of four patients showed a significant decrease of the % Tregs after intravenous injection of bevacizumab. Interestingly, the expression of VEGF receptor-2 (VEGFR-2) was higher in Tregs than in other CD4(+) T-cells. Taken together, the data presented here indicate a contribution of VEGF to induction and/or maintenance of Tregs in patients with cancer.