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A positive microscopic margin (R1) following resection of pancreatic ductal adenocarcinoma (PDAC) can occur in up to 80% of patients and is associated with reduced survival and increased recurrence. Our aim was to characterize the impact of neoadjuvant therapy (NAT) on survival and recurrence in patients with PDAC following an R1 resection. A retrospective analysis of patients with PDAC who underwent pancreatectomy from 2008 to 2017 was performed. Patients were staged according to the American Joint Committee on Cancer 8th edition and stratified based on resection margin (R0 vs. R1) and treatment sequence (NAT vs. surgery first [SF]). Conditional survival analysis was performed using Cox regression and inverse probability weighted estimates. Among 580 patients, 59% received NAT and 41% underwent SF. On final pathology, the NAT cohort had smaller tumors and less lymph node (LN) positivity (p

Background Growing evidence for the advantages of robotic pancreatoduodenectomy (RPD) has been demonstrated internationally. However, there has been no structured training program for RPD in Japan. Herein, we present the surgical training model of RPD and a standardized protocol for surgical technique. Methods The surgical training model and surgical technique were standardized in order to implement RPD safely, based on the Dutch training system collaborated with the University of Pittsburgh Medical Center. Results The surgical training model included various trainings such as basic robotic training, simulation training, biotissue training, and a surgical video review. Furthermore, a standardized protocol on the surgical technique was established to understand the tips, tricks, and pitfalls of RPD. Conclusions Safe implementation of RPD can be achieved through the completion of a structured training program and learning surgical technique. A nationwide structured training system should be developed to implement the program safely in Japan.

BACKGROUND. Neoadjuvant therapy is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). It is unknown whether neoadjuvant chemoradiotherapy is more effective than chemotherapy (NCRT vs. NAC). We aim to compare pathological and survival outcomes of NCRT and NAC in patients with PDAC. PATIENTS AND METHODS. Single-center analysis of PDAC patients treated with NCRT or NAC followed by resection between December 2008 and December 2018 was performed. Average treatment effect (ATE) was estimated after case–control matching using Mahalanobis distance nearest-neighbor matching. Inverse probability weighted estimates (IPWE)-based ATE was estimated for disease-free survival (DFS) and overall survival (OS). RESULTS. Among the 418 patients (mean age 66.8 years, 51% female) included in the study, 327 received NAC and 91 received NCRT. NCRT patients had higher rates of locally advanced disease, number of neoadjuvant chemotherapy cycles, more chemotherapy regimen crossover (gemcitabine and 5-FU based), and were more likely to undergo open surgical procedures and/or vascular resection (all p < 0.05). After matched analysis, NCRT was associated with a significant reduction in lymph node positive disease [ATE = (−)0.24, p = 0.007] and lymphovascular invasion [ATE = (−)0.20, p = 0.02]. While NCRT was associated with significantly improved DFS by 9.5 months (p = 0.006), it did not affect OS by IPWE-based ATE after adjusting for adjuvant therapy (ATE = 5.5 months; p = 0.32). CONCLUSION. Compared with NAC alone, NCRT is associated with improved pathologic surrogates and disease-free survival, but not overall survival in patients with PDAC.

761 Background: SMAD4, a tumor suppressor gene, is inactivated or deleted in 60-90% of pancreatic adenocarcinomas (PDA). Loss of SMAD4 allows tumor progression by limiting cell cycle arrest and apoptosis and increasing metastases. SMAD4 deficient PDA cells are resistant to radiotherapy by upregulation of autophagy, a cell survival mechanism that allows intracellular recycling of macromolecules and organelles. Hydroxychloroquine (HCQ) is a known autophagy inhibitor, suggesting that HCQ treatment in SMAD4 deficient PDA may prevent therapeutic resistance induced by autophagy upregulation. Methods: We retrospectively analyzed the SMAD4 status of PDA patients enrolled in two prospective clinical trials evaluating preoperative HCQ. The first dose escalation trial demonstrated the safety of preoperative gemcitabine with HCQ ( NCT01128296 ). More recently, a randomized trial of gemcitabine/nab-paclitaxel +/- HCQ evaluated Evans Grade histopathologic response ( NCT01978184 ). Immunohistochemistry of resected specimens for SMAD4 was previously performed. Patients not treated at the max HCQ dose (n = 5), not resected (n = 2) or with SMAD4 staining unavailable were excluded (n = 10). The effect of SMAD4 loss on response to HCQ and chemotherapy was studied for association with clinical outcome. Fisher’s exact test and log-rank test were used to assess response and survival. Results: 52 patients receiving HCQ with neoadjuvant chemotherapy and 24 patients receiving neoadjuvant chemotherapy alone were studied. Of the HCQ group, 25 patients had SMAD4 loss (48%), compared with 15 control patients (63%, p = 0.32). 76% of HCQ treated patients with SMAD4 loss obtained a histopathologic response ≥2A, compared to only 37% with SMAD4 intact (p = 0.006). In the control group, loss of SMAD4 was associated with a nonsignificant detriment in 3 year OS (25% vs. 78%, p = 0.3) that was less apparent in patients treated with HCQ (46% vs. 47%, p = 0.18). Conclusions: The addition of HCQ to neoadjuvant chemotherapy in PDA may improve treatment response in patients with SMAD4 loss. Further study of the relationship between SMAD4, autophagy and treatment outcomes in PDA is warranted.

727 Background: Neoadjuvant therapy is increasingly used for pancreatic cancer (PDA). The comparative efficacy of neoadjuvant chemotherapy (NC) versus chemoradiation (NCRT) remains uncertain. We aimed to compare NC and NCRT on survival outcomes and pathologic endpoints of PDA. Methods: Single-center analysis of PDAs treated with NC or NCRT between 2008-2018. Average treatment effects (ATE) were estimated after matching cases to controls using Mahalanobis distance nearest-neighbor matching. Competing risk survival analysis and inverse probability weighted estimates (IPWE) were used for disease free survival (DFS) and overall survival (OS) respectively. Results: Of 418 patients (median age 67yrs, 51% females), 327 received NC and 91 received NCRT. NCRT patients had more locally advanced disease, cross-over NC regimens (gemcitabine & 5-FU based), longer neoadjuvant therapy duration, open surgery and vascular resection (all p < 0.05). NCRT was associated with lower LN positivity, LNR, LVI and PNI, higher R0 rates, and higher near complete and complete pathologic responses (all p < 0.05, table). After adjustment, NCRT was associated with a significant reduction in LN positivity [95%CI = (-)0.41-(-)0.07; p = 0.007] and LVI [95%CI = (-)0.36-(-)0.03; p = 0.02]. While NCRT was associated with improved OS on UVA (25.5 vs. 21.6 months; p = 0.04), it was not significantly associated with OS by IPWE after adjusting for adjuvant therapy [95%CI = (-)5.02-16.3; p = 0.3] or DFS on competing risk analysis (95%CI = 0.78-1.31; p = 0.96). Conclusions: Although NCRT is associated with improved pathologic surrogates, it is not associated with improved survival in PDA. [Table: see text]

Aim: Parastomal hernia commonly occurs following the formation of a stoma. This is a review of parastomal hernia repair using a modified lateral approach to access the defect. Patients/methods: A case series of 17 patients, with a median age of 65, who underwent parastomal hernia repair via a lateral approach over a five year period, is presented. Results: Of the 17 repairs, there were four minor complications in the form of a superficial cellulitis and conservatively managed ileus. In total, there were four recurrences, though only one recurrence occurred in 11 cases after slight modification of the technique. The period of follow-up ranged from 6 to 60 months. Discussion: The lateral approach is a viable option for repair of parastomal hernia. It does not necessitate a laparotomy or relocation of the stoma.