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Objective: The optimal neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDA) and the impact on surgical outcomes remains unclear., Methods: S1505 (NCT02562716) was a randomized phase II study of perioperative chemotherapy with mFOLFIRINOX (Arm 1) or gemcitabine/nab-paclitaxel (Arm 2). Measured parameters included resection rate, margin positivity, pathologic response, and toxicity., Results: Between 2015 and 2018, 147 patients were randomized. Of these, 44 (30%) were deemed ineligible (43 by central review). Of the 103 eligible patients, 77 (76%) completed preoperative therapy and underwent surgery; reasons patients did not undergo surgery included toxicity related to preoperative therapy (n = 9), progression (n = 9), or other (n = 7). Of the 77, 73 (95%) underwent successful resection; 21 (29%) required vascular reconstruction, 62 (85%) had negative (R0) margins, and 24 (33%) had a complete or major pathologic response to therapy. The grade 3-5 postoperative complication rate was 16%. Of the 73 patients completing surgery, 57 (78%) started and 46 (63%) completed postoperative therapy. This study represents the first prospective trial evaluating modern systemic therapy delivered in a neoadjuvant/perioperative format for resectable PDA., Conclusions: We have demonstrated: (1) Based on the high percentage of enrolled, but ineligible patients, it is clear that adherence to strict definitions of resectable PDA is challenging; (2) Patients can tolerate modern systemic therapy and undergo successful surgical resection without prohibitive perioperative complications; (3) Completion of adjuvant therapy in the perioperative format is difficult; (4) Major pathologic response rate of 33% is encouraging., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Total pancreatectomy and islet cell autotransplantation (TPIAT) has been increasingly utilized for the management of chronic pancreatitis (CP) with early success. However, the long-term durability of this operation remains unclear., Methods: All patients undergoing TPIAT for the treatment of CP with 5-year or greater follow-up were identified for inclusion in this single-center observational study. End points included narcotic requirements, glycemic control, islet function, quality of life (QOL), and survival., Results: Between 2000 and 2013, 166 patients underwent TPIAT; 112 of these patients had 5-year follow-up data to analyze. All patients underwent successful IAT with a mean of 6027 ± 595 islet equivalents per body weight. There was no perioperative mortality and actuarial survival at 5 years was 94.6%. The narcotic independence rate at 1 year was 55% and continued to improve to 73% at 5-year follow-up (P < 0.05). The insulin independence rate declined over time (38% at 1 year vs 27% at more than 5 years), but insulin requirements remained similar (21.4 vs 24.3 units per day, P = 0.6). All patients achieved stable glycemic control with a median hemoglobin A1C (HgA1C) of 6.9% (range: 5.85%-8.3%). The short form 36-item QOL assessment of a subset of patients available for contact demonstrated continued improvements in all tested modules in patients with at least 5-year follow-up. Two patients developed diabetic complications requiring whole organ pancreas transplant for salvage., Conclusions: This represents one of the largest series examining long-term outcomes after TPIAT. This operation produces durable pain relief and improvement in QOL parameters. Insulin independence rates decline over time, but most patients maintain stable glycemic control.

Objectives: To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience., Summary and Background Data: LLP is being performed more commonly with limited data comparing results with outcomes from OLP., Methods: Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression., Results: Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56)., Conclusions: In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.

Objective: In Western populations, long-term survival rates after curative resection of gastric cancer remain extremely poor. The lack of effective adjuvant therapy has prompted the evaluation of neoadjuvant approaches. Since 1988, we have conducted three separate phase II trials using neoadjuvant chemotherapy to treat patients with potentially resectable gastric cancer. The present study was conducted to evaluate whether response to neoadjuvant chemotherapy is predictive of survival in patients with resectable gastric cancer., Methods: Eighty-three patients with pathologically confirmed gastric adenocarcinoma were treated with neoadjuvant chemotherapy before planned surgical resection. Response was assessed by upper gastrointestinal series, endoscopy, computed tomography scan, and pathologic examination., Results: For the three phase II trials, clinical response rates ranged from 24% to 38%. Three patients (4%) had a complete pathologic response. Sixty-one patients (73%) underwent a curative resection. Median follow-up was 26 months. Univariate analysis revealed T stage, number of positive nodes, and response to chemotherapy to be significant predictors of overall survival. However, on multivariate analysis, response to chemotherapy was found to be the only independent prognostic factor., Conclusions: Response to neoadjuvant chemotherapy is the single most important predictor of overall survival after neoadjuvant chemotherapy for gastric cancer. These findings support further evaluation of neoadjuvant approaches in the treatment of this disease.

Objective: This study was conducted to determine whether the perioperative administration of octreotide decreases the incidence of pancreatic anastomotic leak after pancreaticoduodenectomy for malignancy., Summary Background Data: Three multicenter, prospective, randomized trials concluded that patients who receive octreotide during and after pancreatic resection have a reduction in the total number of complications or a decreased incidence of pancreatic fistula. However, in the subset of patients who underwent pancreaticoduodenectomy for malignancy, either no analysis was performed or no benefit from octreotide could be demonstrated., Methods: A single-institution, prospective, randomized trial was conducted between June 1991 and December 1995 involving 120 patients who were randomized to receive octreotide (150 microg subcutaneously every 8 hours through postoperative day 5) or no further treatment after pancreaticoduodenectomy for malignancy. The surgical technique was standardized, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa or invagination technique., Results: The two patient groups were similar with respect to patient demographics, treatment variables, and histologic diagnoses. The rate of clinically significant pancreatic leak was 12% in the octreotide group and 6% in the control group (p = 0.23). Perioperative morbidity was 30% and 25%, respectively. Patients who underwent reoperative pancreaticoduodenectomy had an increased incidence of pancreatic anastomotic leak, whereas those who received preoperative chemoradiation had a decreased incidence of pancreatic anastomotic leak., Conclusions: The routine use of octreotide after pancreaticoduodenectomy for malignancy cannot be recommended.

Objective: The results of preoperative infusional chemoradiation, resection, and selective intraoperative radiation (IORT) boost in 43 previously nonirradiated patients with locally advanced pelvic recurrence of colorectal adenocarcinoma are described., Summary Background Data: After surgery alone 10% to 30% of patients with carcinoma of the distal colon and rectum will develop isolated pelvic recurrence. In most cases, the disease is locally advanced and not amenable to curative resection. Preoperative infusional chemoradiation has been shown to increase resectability and decrease local recurrence in primary locally advanced colorectal cancer. Based on this experience, we initiated a multimodality treatment protocol to treat patients with pelvic recurrence of colorectal adenocarcinoma., Methods: Forty-three consecutive patients with histologically proven pelvic recurrence of colorectal adenocarcinoma were enrolled on a multimodality treatment protocol. The treatment plan consisted of 5 weeks of concurrent pelvic external beam radiotherapy (45 Gy) with continuous intravenous infusion of 5-fluorouracil and/or cisplatin. This was followed by surgery that included IORT boost (10-20 Gy) for 21 patients and brachytherapy for 4 patients., Results: Forty patients (93%) underwent operation and 33 (77%) underwent resection with curative intent. There were 29 (88%) margin-negative resections. Fifteen patients (48%) underwent sphincter-preserving operations. There were no treatment-related deaths. Twenty-two patients experience perioperative complications. Median follow-up for the 43 patients was 26 months. The local recurrence rate was 36%. Median survival for the patients who underwent resection was 34 months, and actuarial 5-year disease-free and overall survival were 37% and 58%, respectively., Conclusions: Tumor cytoreduction by preoperative chemoradiation can increase resectability and enable sphincter-preserving surgery in patients with locally advanced pelvic recurrence of colorectal cancer.