Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and Subclassification Proposal.

OBJECTIVE: The aim of this study was to describe characteristics and management approaches for grade B pancreatic fistula (B-POPF) and investigate whether it segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined definition of B-POPF is predicated on various postoperative management approaches, ranging from prolonged drainage to interventional procedures, but the spectrum of clinical severity within this entity is yet undefined. METHODS: Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to identify B-POPFs and their treatment strategies. Subclassification of B-POPFs into 3 classes was modeled after the Fistula Accordion Severity Grading System (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional procedures). Clinical and economic outcomes, unique from the ISGPS definition qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of 1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage occurred in 79 patients (24.7%), always in combination with other strategies. Management of B-POPFs was widely heterogeneous with a median of 2 approaches/patient (range 1 to 6) and 38 various strategy combinations used. Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and were associated with progressively worse clinical and economic outcomes. These results were confirmed by multivariable analysis adjusted for clinical and operative factors. Notably, distribution of the B-POPF subclasses was influenced by institution and type of resection (P < 0.001), while clinical/demographic predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3 distinct subclasses with increasing clinical and economic burden can be identified. This classification framework has potential implications for accurate reporting, comparative research, and performance evaluation.

Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.

OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. RESULTS: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. CONCLUSION: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Drain Management after Pancreatoduodenectomy: Reappraisal of a Prospective Randomized Trial Using Risk Stratification.

BACKGROUND: A recent randomized trial used the Fistula Risk Score (FRS) to develop guidelines for selective drainage based on clinically relevant fistula (CR-POPF) risk. Additionally, postoperative day (POD) 1 drain and serum amylase have been identified as accurate postoperative predictors of CR-POPF. This study sought to identify patients who may benefit from selective drainage, as well as the optimal timing for drain removal after pancreatoduodenectomy. STUDY DESIGN: One hundred six pancreatoduodenectomies from a previously reported RCT were assessed using risk-adjustment. The incidence of CR-POPF was compared between FRS risk cohorts. Drain and serum amylase values from POD 1 were evaluated using receiver operating characteristic (ROC) analysis to establish cut-offs predictive of CR-POPF occurrence. A regression analysis compared drain removal randomizations (POD 3 vs POD 5). RESULTS: Three-quarters of patients had moderate/high CR-POPF risk. This group had a CR-POPF rate of 36.3% vs 7.7% among negligible/low risk patients (p = 0.005). The areas under the ROC curve for CR-POPF prediction using POD 1 drain and serum amylase values were 0.800 (p = 0.000001; 95% CI 0.70-0.90) and 0.655 (p = 0.012; 95% CI 0.55-0.77), respectively. No significant serum amylase cut-offs were identified. Moderate/high risk patients with POD 1 drain amylase ≤ 5,000 U/L had significantly lower rates of CR-POPF when randomized to POD 3 drain removal (4.2% vs 38.5%; p = 0.003); moreover, these patients experienced fewer complications and shorter hospital stays. CONCLUSIONS: A clinical care protocol is proposed whereby drains are recommended for moderate/high FRS risk patients, but may be omitted in patients with negligible/low risk. Drain amylase values in moderate/high risk patients should then be evaluated on POD 1 to determine the optimal timing for drain removal. Moderate/high risk patients with POD 1 drain amylase ≤ 5,000 U/L have lower rates of CR-POPF with POD 3 (vs POD ≥ 5) drain removal; early drain removal is recommended for these patients.