The multidisciplinary pancreatic cyst clinic: A collaborative approach to streamlined management.

BACKGROUND: Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. METHODS: To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. CLINIC INFRASTRUCTURE: The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. RESULTS: A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. CONCLUSIONS: The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.

Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Pancreatic ductal adenocarcinoma: tumour regression grading following neoadjuvant FOLFIRINOX and radiation.

AIMS: In the adjuvant setting, when compared to gemcitabine, patients with pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX (Folinic Acid, Fluorouracil, Irinotecan, and Oxaliplatin) show superior survival. In this study, we quantitatively assess the pathological tumour response to chemoradiation in pancreatectomy specimens and reassess guidelines for tumour regression grading. METHODS AND RESULTS: We evaluated 92 patients with borderline resectable/locally advanced PDAC following pancreatectomy and neoadjuvant treatment with FOLFIRINOX and radiation. Demographic data, CAP tumour regression grade (TRG) and overall survival (OS) were recorded. A quantitative analysis of residual tumour was performed on the slide with the highest tumour burden to derive a tumour-to-tumour bed ratio. On univariate analysis, only lymph node status (P = 0.043) and CAP TRG (P = 0.038) correlated with OS. Sixteen per cent of patients showed a complete pathological response. The optimal tumour-to-tumour bed ratio cut-point was 11.6%, and on a multivariate model was the only pathological parameter that correlated with OS (P = 0.016) (hazard ratio = 2.27). CONCLUSIONS: The high proportion of patients with PDAC showing complete and near-complete pathological responses supports the use of FOLFIRINOX and radiation in the neoadjuvant setting. Several traditional pathology parameters fail to predict OS in patients treated with chemoradiation, while a quantitative tumour-to-tumour bed ratio is a powerful predictor of OS. The data support a two-tiered approach to TRG based on tumour-to-tumour bed ratio, and quantitative analysis merits further consideration.

Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: The aim was to evaluate the various operative techniques and outcomes used to manage the pancreatic transection plane (or stump) during a left (distal) pancreatectomy and to develop expert consensus guidelines. METHODS: Evidence-based, clinically relevant questions were discussed and then were circulated among members of the International Study Group of Pancreatic Surgery. After agreement on the questions and statements, voting in a 9-point Likert scale was used to gauge the level of objective support for each. RESULTS: Studies using the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula including 16 randomized trials were reviewed to generate a series of statements set into 14 domains. There was strong consensus in the following statements: there was no difference in the postoperative pancreatic fistula rate after left pancreatectomy between the handsewn and stapler techniques; a stapling technique could not be used in all cases of left pancreatectomy; the use of an energy-based tissue sealant or a chemical sealant device or combinations of these did not impact the postoperative pancreatic fistula rate; there was no difference in the postoperative pancreatic fistula rate between the open, laparoscopic, or robotic approaches; and there are 1 or more clinically important, patient-related risk factors associated with the postoperative pancreatic fistula rate. There was weak or conditional agreement on the use of prophylactic somatostatin analogs, stents, stump closure, stump anastomosis, and the role of abdominal drains. CONCLUSION: Areas of strong consensus suggests a change in clinical practice and priority setting. Eight domains with lower agreement will require novel approaches and large multicenter studies to determine future key areas of practice.

Total Neoadjuvant Therapy With FOLFIRINOX in Combination With Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial.

IMPORTANCE: Patients with locally advanced pancreatic cancer have historically poor outcomes. Evaluation of a total neoadjuvant approach is warranted. OBJECTIVE: To evaluate the margin-negative (R0) resection rate of neoadjuvant FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) and losartan followed by chemoradiotherapy for locally advanced pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTS: A single-arm phase 2 clinical trial was conducted at a large academic hospital from August 22, 2013, to May 22, 2018, among 49 patients with previously untreated locally advanced unresectable pancreatic cancer as determined by multidisciplinary review. Patients had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 17.1 months (range, 5.0-53.7) among 27 patients still alive at study completion. INTERVENTIONS: Patients received FOLFIRINOX and losartan for 8 cycles. Patients with radiographically resectable tumor after chemotherapy received short-course chemoradiotherapy (5 GyE × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy (50.4 Gy with a vascular boost to 58.8 Gy) with fluorouracil or capecitabine. MAIN OUTCOMES AND MEASURES: R0 resection rate. RESULTS: Of the 49 patients (26 women and 23 men; median age 63 years [range, 42-78 years]), 39 completed 8 cycles of FOLFIRINOX and losartan; 10 patients had fewer than 8 cycles due to progression (5 patients), losartan intolerance (3 patients), and toxicity (2 patients). Seven patients (16%) had short-course chemoradiotherapy while 38 (84%) had long-course chemoradiotherapy. Forty-two (86%) patients underwent attempted surgery, with R0 resection achieved in 34 of 49 patients (69%; 95% CI, 55%-82%). Overall median progression-free survival was 17.5 months (95% CI: 13.9-22.7) and median overall survival was 31.4 months (95% CI, 18.1-38.5). Among patients who underwent resection, median progression-free survival was 21.3 months (95% CI, 16.6-28.2), and median overall survival was 33.0 months (95% CI, 31.4 to not reached). CONCLUSIONS AND RELEVANCE: Total neoadjuvant therapy with FOLFIRINOX, losartan, and chemoradiotherapy provides downstaging of locally advanced pancreatic ductal adenocarcinoma and is associated with an R0 resection rate of 61%. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01821729.

Short-term and long-term outcomes for patients with autoimmune pancreatitis after pancreatectomy: a multi-institutional study.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis that may mimic adenocarcinoma of the pancreas. The aim of this study was to evaluate the short-term and long-term outcomes of pancreatectomy for patients with AIP. METHODS: In this multi-institutional study, we identified all patients who underwent pancreatectomy for AIP from 1986 to 2011. AIP was confirmed by pathology review. Clinical presentation, operative details, and postoperative outcomes were analyzed. RESULTS: Seventy-four patients (median age, 60 years; 69 % male) with AIP underwent pancreatectomy. The main indication for operation was concern for malignancy (n = 59, 80 %). No patients were found to have pancreatic adenocarcinoma on final pathology. Major complications occurred in ten (14 %) patients, with one perioperative death (1 %). Clinically relevant (grade B/C) pancreatic fistulae occurred in two patients. No patients required reoperation for AIP and 11 (17 %) patients developed recurrent AIP. CONCLUSION: Although we do not advocate pancreatectomy for AIP, strong suspicion of malignancy may require an operation in selected patients. For patients with AIP, pancreatectomy resulted in few pancreatic fistulae, a low rate of re-intervention, and a 17 % recurrence rate.