The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

Background: Preoperative chemo- or chemoradiotherapy is recommended for borderline-resectable pancreatic cancer. The aim of this study was to determine the impact of preoperative therapy on surgical complications in patients with resected pancreatic cancer. Methods: This systematic review and meta-analysis included studies reporting on the rate of surgical complications after preoperative chemo- or chemoradiotherapy versus immediate surgery in pancreatic cancer patients. The primary endpoint was the rate of grade B/C POPF. Pooled odds ratios were calculated using random-effects models. Results: Forty-one comparative studies including 25,389 patients were included. Vascular resections were more often performed after preoperative therapy (29.4% vs. 15.7%, p < 0.001). Preoperative therapy was associated with a lower rate of grade B/C POPF as compared to immediate surgery (pooled OR 0.47, 95%CI 0.38–0.58). This reduction was mostly obtained by preoperative chemoradiotherapy (OR 0.46, 95%CI 0.29–0.73), but not by preoperative chemotherapy alone (OR 0.83, 95%CI 0.59–1.16). No difference was demonstrated for major morbidity, mortality, postpancreatectomy haemorrhage, delayed gastric emptying and overall morbidity. Conclusion: Preoperative chemo- and chemoradiotherapy in patients with pancreatic cancer appears to be safe with respect to POPF and other surgical complications as compared to immediate surgery. The reduced rate of POPF appears to be attributable to preoperative chemoradiation

The effect of preoperative chemotherapy and chemoradiotherapy on pancreatic fistula and other surgical complications after pancreatic resection: a systematic review and meta-analysis of comparative studies

BACKGROUND: Preoperative chemo- or chemoradiotherapy is recommended for borderline-resectable pancreatic cancer. The aim of this study was to determine the impact of preoperative therapy on surgical complications in patients with resected pancreatic cancer. METHODS: This systematic review and meta-analysis included studies reporting on the rate of surgical complications after preoperative chemo- or chemoradiotherapy versus immediate surgery in pancreatic cancer patients. The primary endpoint was the rate of grade B/C POPF. Pooled odds ratios were calculated using random-effects models. RESULTS: Forty-one comparative studies including 25,389 patients were included. Vascular resections were more often performed after preoperative therapy (29.4% vs. 15.7%, p < 0.001). Preoperative therapy was associated with a lower rate of grade B/C POPF as compared to immediate surgery (pooled OR 0.47, 95%CI 0.38-0.58). This reduction was mostly obtained by preoperative chemoradiotherapy (OR 0.46, 95%CI 0.29-0.73), but not by preoperative chemotherapy alone (OR 0.83, 95%CI 0.59-1.16). No difference was demonstrated for major morbidity, mortality, postpancreatectomy haemorrhage, delayed gastric emptying and overall morbidity. CONCLUSION: Preoperative chemo- and chemoradiotherapy in patients with pancreatic cancer appears to be safe with respect to POPF and other surgical complications as compared to immediate surgery. The reduced rate of POPF appears to be attributable to preoperative chemoradiation

Outcome of pancreatic anastomoses during pancreatoduodenectomy in two national audits

Background: Evidence on the optimal pancreatic anastomosis during pancreatoduodenectomy is inconclusive. Large multicenter and nationwide registries may provide additional insights. The study compared the practice and outcome of different pancreatic anastomoses during pancreatoduodenectomy, focusing on the rate of postoperative pancreatic fistula, in two large audits of pancreatic surgery.Methods: Posthoc analysis of patients after pancreatoduodenectomy in the Dutch Pancreatic Cancer Audit and the German DGAV StuDoQ vertical bar Pancreas registries (January 2014 to December 2017). Postoperative pancreatic fistula (International Study Group of Pancreatic Surgery B/C), postpancreatectomy hemorrhage (International Study Group of Pancreatic Surgery B/C) and Clavien-Dindo >= 3 complications rates were compared for the three most common anastomoses: duct-to-mucosa pancreatojejunostomy, non-duct-to-mucosa pancreatojejunostomy, and non-duct-to-mucosa pancreatogastrostomy. Multivariable adjustment for potential confounders was performed.Results: Overall, 6,149 patients were included. The most common anastomosis was duct-to-mucosa pancreatojejunostomy (duct-to-mucosa pancreatojejunostomy 59.8%, non-duct-to-mucosa pancreatojejunostomy 21.1%, non-duct-to-mucosa pancreatogastrostomy 12.4%). The overall postoperative pancreatic fistula rate was 14%: duct-to-mucosa pancreatojejunostomy 12.9%, non-duct-to-mucosa pancreatojejunostomy 14.4% (P = .162), non-duct-to-mucosa pancreatogastrostomy 18.3% (P = 3 complications was the lowest after duct-to-mucosa pancreatojejunostomy: duct-to-mucosa pancreatojejunostomy 28%, non-duct-to-mucosa pancreatojejunostomy 32.7% (P = .002), non-duct-to-mucosa pancreatogastrostomy 43.1% (P = 3 (odds ratio 1.6, 95% confidence interval 1.2-2.1, P = .001) remained significantly higher only for non-duct-to-mucosa pancreatogastrostomy.Conclusion: Data from two national audits showed no difference in the risk-adjusted postoperative pancreatic fistula rate among the three most used pancreatic anastomoses during pancreatoduodenectomy. Pancreatogastrostomy was inferior to pancreatojejunostomy regarding bleeding and overall major complications. (C) 2021 Elsevier Inc. All rights reserved

Nationwide validation of the ISGPS risk classification for postoperative pancreatic fistula after pancreatoduodenectomy: “Less is more”

Background: The International Study Group of Pancreatic Surgery 4-tier (ie, A–D) risk classification for postoperative pancreatic fistula grade B/C is based on pancreatic texture and pancreatic duct size: A (not-soft texture and pancreatic duct >3 mm), B (not-soft texture and pancreatic duct ≤3 mm), C (soft texture and pancreatic duct >3 mm), and D (soft texture and pancreatic duct ≤3 mm). This study aimed to validate the International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy. Methods: Consecutive patients after pancreatoduodenectomy for all indications (2014–2021) were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. The rate of postoperative pancreatic fistula grade B/C (according to the International Study Group of Pancreatic Surgery 2016 definition) was calculated per risk category. Model performance was assessed using the area under the receiver operating curve (discrimination) and calibration plots. Results: Overall, 3,900 patients were included in risk categories: A (n = 1,046), B (n = 498), C (n = 963), and D (n = 1,393) with corresponding postoperative pancreatic fistula grade B/C rates of 3.8%, 12.2%, 15.6%, and 29.6%. Per category, the in-hospital mortality rates were 1.3%, 3.4%, 2.9%, and 4.1%, P = .001. There was no difference in the rate of postoperative pancreatic fistula between risk categories B and C (12.2% vs 15.6%, P = .101). When simplifying the classification system to a 3-tier classification system (based on 0, 1, and 2 risk factors), the discrimination was not significantly different (area under the receiver operating curve 0.697 vs area under the receiver operating curve 0.701, P = .077). Conclusion: This validation of the 4-tier International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy confirmed its predictive value. However, as the 2 middle risk categories provide no added predictive value, a simplified 3-tier classification with comparable predictive value is proposed and should be validated in future prospective studies

Surgical Outcome After Pancreatoduodenectomy for Duodenal Adenocarcinoma Compared with Other Periampullary Cancers: A Nationwide Audit Study

BACKGROUND: Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. METHODS: After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien-Dindo grade III or higher) was assessed via multivariable regression analysis. RESULTS: Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p < 0.001), postoperative pancreatic fistula (International Study Group of Pancreatic Surgery [ISGPS] grade B/C; 23.1% vs. 13.4%; p < 0.001), complication-related intensive care admission (14.3% vs. 10.3%; p = 0.046), re-interventions (39.8% vs. 26.6%; p < 0.001), in-hospital mortality (5.7% vs. 3.1%; p = 0.025), and longer hospital stay (15 days vs. 11 days; p < 0.001) compared with pancreatoduodenectomy for other cancers. In multivariable analysis, duodenal adenocarcinoma was independently associated with major complications (odds ratio 1.14, 95% confidence interval 1.03-1.27; p = 0.011). CONCLUSION: Pancreatoduodenectomy for duodenal adenocarcinoma is associated with higher rates of major complications, pancreatic fistula, re-interventions, and in-hospital mortality compared with patients undergoing pancreatoduodenectomy for other cancers. These findings should be considered in patient counseling and postoperative management

Outcome of Pancreatic Surgery During the First Six Years of a Mandatory Audit within the Dutch Pancreatic Cancer Group

OBJECTIVE: To describe outcome after pancreatic surgery in the first six years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between three time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after pancreatoduodenectomy and 1118 after distal pancreatectomy. After pancreatoduodenectomy, failure to rescue improved from 13% to 7.4% (OR 0.64, 95%CI 0.50-0.80, P75 years (18% to 22%, P=0.006), ASA score ≥3 (19% to 31%, P<0.001) and Charlson comorbidity score ≥2 (24% to 34%, P<0.001). The rates of textbook outcome (57% to 55%, P=0.283) and major complications remained stable (31% to 33%, P=0.207), whereas complication-related intensive care admission decreased (13% to 9%, P=0.002). After distal pancreatectomy, improvements in failure to rescue from 8.8% to 5.9% (OR 0.65, 95%CI 0.30-1.37, P=0.253) and in-hospital mortality from 1.6% to 1.3% (OR 0.88, 95%CI 0.45-1.72, P=0.711) were not statistically significant. CONCLUSIONS: During the first six years of a nationwide audit, in-hospital mortality and failure to rescue after pancreatoduodenectomy improved despite operating on more high-risk patients. Several collaborative efforts may have contributed to these improvements

Consensus Statement on Mandatory Measurements for Pancreatic Cancer Trials for Patients with Resectable or Borderline Resectable Disease (COMM-PACT-RB): A Systematic Review and Delphi Consensus Statement

Importance: Pancreatic cancer is the third most common cause of cancer death; however, randomized clinical trials (RCTs) of survival in patients with resectable pancreatic cancer lack mandatory measures for reporting baseline and prognostic factors, which hampers comparisons between outcome measures. Objective: To develop a consensus on baseline and prognostic factors to be used as mandatory measurements in RCTs of resectable and borderline resectable pancreatic cancer. Evidence Review: We performed a systematic literature search of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase for RCTs on resectable and borderline resectable pancreatic cancer with overall survival as the primary outcome. We produced a systematic summary of all baseline and prognostic factors identified in the RCTs. A Delphi panel that included 13 experts was surveyed to reach a consensus on mandatory and recommended baseline and prognostic factors. Findings: The 42 RCTs that met inclusion criteria reported a total of 60 baseline and 19 prognostic factors. After 2 Delphi rounds, agreement was reached on 50 mandatory baseline and 20 mandatory prognostic factors for future RCTs, with a distinction between studies of neoadjuvant vs adjuvant treatment. Conclusion and Relevance: This findings of this systematic review and international expert consensus have produced this Consensus Statement on Mandatory Measurements in Pancreatic Cancer Trials for Resectable and Borderline Resectable Disease (COMM-PACT-RB). The baseline and prognostic factors comprising the mandatory measures will facilitate better comparison across RCTs and eventually will enable improved clinical practice among patients with resectable and borderline resectable pancreatic cancer