Asbun, Horacio J.

AbstractAfter decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced‐based argument for the fundamental role of surgery and anaesthesia within cost‐effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.

365 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense stroma and connective tissue growth factor (CTGF) overexpression. Although prolonged overall survival (OS) can be achieved through resection, only approximately 15% to 20% of patients are treated with surgery. Previously, pamrevlumab (P), a fully human monoclonal antibody blocking CTGF, was combined with gemcitabine/erlotinib (G/E) in a study of advanced PDAC. P plasma levels of > 150 μg/mL and low baseline CTGF levels resulted in prolonged OS. We hypothesize that neoadjuvant (NA) treatment of LAPC with P + G/nab-paclitaxel (NP) may alter LAPC’s stroma, increase R0 resectability, and improve OS similar to that of patients resectable at presentation. Methods: LAPC subjects, confirmed by NCCN criteria and staging laparoscopy, were randomized 2:1 to G/NP ± P for 6-cycle/24-week treatment. Safety and efficacy (resection rate, OS, progression-free survival, tumor response) were assessed. Resection was performed in subjects who met protocol-defined criteria with no contraindications. Results: As of 26 Sep 2016, 25 subjects were enrolled. Of 14 subjects in Arm A (G/NP + P), 7 completed, 2 discontinued. Of 11 subjects in Arm B (G/NP), 4 completed, 4 discontinued. 6 subjects (43%) in Arm A and 4 (36%) in Arm B experienced SAEs; no P-related SAEs were reported. Out of 7 eligible Arm A subjects, 3 were not resected. Successful resection was achieved in 4 Arm A subjects (3 R0, 1 R1) and 1 Arm B subject (R0) (Table). Conclusions: The combination of G/NP + P is feasible and well-tolerated with no incremental safety signals in this study. The addition of P suggests a trend toward increased resectability among LAPC subjects. Clinical trial information: NCT02210559. [Table: see text]

457 Background: Curative therapy for PDAC is currently achievable through resection only, but ≤ 15% of patients are candidates for surgery. FG-3019, a recombinant human mAb to connective tissue growth factor (CTGF), plus gemcitabine (G) significantly reduced tumor growth, increased apoptosis and improved survival vs G alone in the KPC mouse model. Higher FG-3019 exposure and lower baseline (BL) CTGF were independently and significantly associated with improved overall median and 1-year survival (OS) in a Ph2a trial with G and erlotinib in stage 3 or 4 PDAC. Neoadjuvant treatment of LAPC with FG-3019 combined with multidrug therapy may change the fibrotic character of LAPC and thus may make it amenable to surgical resection and potentially improve OS. Methods: Patients with unresectable LAPC (confirmed by laparoscopy) are randomized to G/NP ±FG-3019 for 6-cycle/24-week treatment. Safety, efficacy, PK and changes in CT, PET, & CA19.9 from BL through end of treatment (EOT) are assessed. Up to 4 endoscopic ultrasound (EUS) guided core biopsies are collected at BL. Protein microarrays of pre- and post-treatment biopsies are prepared from tumor and stromal cells isolated by laser capture microdissection. Surgical exploration is performed in subjects who achieved the protocol-defined criteria for possible resection. Results: To date, 11 subjects were enrolled with 5 randomized to +FG-3019 arm. There were no complications from laparoscopy or EUS core biopsies that were clinically significant or delayed dosing. Per investigator assessment, no FG-3019-related SAEs were reported, nor any identified toxicity suspected from combination of FG-3019 with chemotherapy. Overall, CA19.9 mean change from BL was −62.7% at Week 8 (n = 8), and target lesions were reduced by 20.6% (n = 6) at Week 16. Three out of 4 subjects had PET SUVmax reductions of ≥ 30% at EOT. Additional data from protein microarrays will be presented. Conclusions: Based on the limited data collected so far, this trial design is feasible and the G/NP +FG-3019 combination is well-tolerated and appears to be active. Summary results on surgical exploration of subjects will be provided later. Clinical trial information: NCT02210559.

Objectives. Surgery is the most effective treatment for pancreatic cancer. However, present literature varies on outcomes of curative pancreatic resection in the elderly. The objective of the study was to evaluate age as an independent risk factor for 90-day mortality and complications after pancreatic resection. Methods. Nine hundred twenty-nine consecutive patients underwent 934 pancreatic resections between March 1995 and July 2014 in a tertiary care center. Primary analyses focused on outcomes in terms of 90-day mortality and postoperative complications after pancreatic resection in these two age groups. Results. Even though patients aged 75 years or older had significantly more postoperative morbidities compared with the younger patient group, the age group was not associated with increased risk of 90-day mortality after pancreatic resection. Discussion. The study suggests that age alone should not preclude patients from undergoing curative pancreatic resection.

Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complex procedures performed in laparoscopic abdominal surgery, and its practice is still limited to only a few selected centers. Surgeons need to be proficient in advanced laparoscopic techniques and have a thorough understanding of the advantages and disadvantages inherent to the laparoscopic approach. LPD can be divided into the following steps: division of the omentum and colon mobilization; division of the proximal bowel and gastroduodenal artery, and transection of the common bile duct; making a retropancreatic window; dissection of ligament of Treitz and division of the distal bowel; dissection of the uncinate process and superior mesenteric vessels; and reconstruction. In this article, we describe our conventional technique for LPD.

AbstractBackgroundLaparoscopic distal pancreatectomy (LDP) has been shown to have short‐term benefits over open distal pancreatectomy (ODP). Its application for pancreatic ductal adenocarcinoma (PDAC) remains controversial.MethodsFrom 1995 to 2014, 72 patients underwent distal pancreatectomy for PDAC at a single institution and were included in the study. Postoperative and long‐term outcomes of patients undergoing LDP (n = 44) or ODP (n = 28) were compared.ResultsLDP was associated with less blood loss (332 vs. 874 mL, p = 0.0012) and lower transfusion rates than ODP (18.2 vs. 50 %, p = 0.0495). Operative time was similar (254 vs. 266 min) for LDP and ODP; five patients (11.4 %) required conversion to ODP. Pancreatic fistulas (13.6 vs. 7.1 %) and major complications (13.6 vs. 25 %), were similar between LDP and ODP, respectively. Length of hospital stay (5.1 vs. 9.4 days, p = 0.0001) and time to initiate adjuvant therapy (69.4 vs. 95.6 days, p = 0.0441) was shorter for LDP than ODP. Tumor characteristics were similar but LDP was associated with more resected lymph nodes than ODP (25.9 vs. 12.7, p = 0.0001). One‐, three‐, and five‐year survival rates were similar between LDP (69, 41, and 41 %, respectively) and ODP (78, 44, and 32 %, respectively).ConclusionLDP is associated with less blood loss and need for blood transfusion, shorter hospital stay, and faster time to initiate adjuvant therapy than ODP for patients with PDAC. Postoperative outcomes and long‐term survival are similar between the two groups. LDP appears to be safe in the treatment of patients with PDAC.

AbstractBackgroundMinimally invasive surgical techniques for pancreatic cancer are being applied with increasing frequency. With support of the literature, the location of the tumor within the pancreas is the factor which determines if these techniques can be safely used routinely by pancreatic surgeons.MethodsLiterature supporting minimally invasive techniques for all types of resections for pancreatic cancer was reviewed.ResultsMultiple meta‐analysis regarding laparoscopic distal pancreatectomy all support the routine use of laparoscopy for these lesions. There are several case series describing the safety and efficacious use of laparoscopy in pancreaticoduodenectomy, and results have been promising in these highly specialized centers.ConclusionsThe location of the tumor within the pancreas remains the most critical factor in the use of laparoscopy as the standard of care. Lesions in the body and tail, which are readily resected with a distal or subtotal pancreatectomy should be performed laparoscopically unless there is a clear reason why not to do so. Lesions in the head of the pancreas have been shown to be removed safely and effectively with laparoscopy. However, the technical skills necessary and the ability to teach these to trainees are the limiting factors to widespread use. Further series are necessary to assess if the laparoscopic approach to pancreaticoduodenectomy will play a similar role as the one it plays in the surgical treatment for distal lesions.

Background . Glycemic control following total pancreatectomy (TP) has been thought to be difficult to manage. Diffuse intraductal papillary mucinous neoplasm (IPMN) is a potentially curable precursor to pancreatic adenocarcinoma, best treated by TP. Objective . Compare glycemic control in patients undergoing TP for IPMN to patients with type 1 diabetes mellitus (DM). Design/Setting . Retrospective cohort. Outcome Measure . Hemoglobin A1C(HbA1C) at 6, 12, 18, and 24 months after TP. In the control group, baseline was defined as 6 months prior to the first HbA1c measure. Results . Mean HgbA1C at each point of interest was similar between TP and type I DM patients (6 months (7.5% versus 7.7%, P = 0.52 ), 12 months (7.3% versus 8.0%, P = 0.081 ), 18 months (7.7% and 7.6%, P = 0.64 ), and at 24 months (7.3% versus 7.8%, P = 0.10 )). Seven TP patients (50%) experienced a hypoglycemic event compared to 65 type 1 DM patients (65%, P = 0.38 ). Limitations . Small number of TP patients, retrospective design, lack of long-termfollowup. Conclusion . This suggests that glycemic control following TP for IPMNcan be well managed, similar to type 1 DM patients. Fear of DM following TP for IPMN should not preclude surgery when TP is indicated.