Elsevier

Pancreatology

Volume 19, Issue 1, January 2019, Pages 17-25
Pancreatology

Risk stratification for postoperative pancreatic fistula using the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery

https://doi.org/10.1016/j.pan.2018.11.008Get rights and content

Abstract

Background

Postoperative pancreatic fistula (POPF) is a major factor for morbidity and mortality after pancreatic resection. Risk stratification for POPF is important for adjustment of treatment, selection of target groups in trials and quality assessment in pancreatic surgery. In this study, we built a risk-prediction model for POPF based on a large number of predictor variables from the German pancreatic surgery registry StuDoQ|Pancreas.

Methods

StuDoQ|Pancreas was searched for patients, who underwent pancreatoduodenectomy from 2014 to 2016. A multivariable logistic regression model with elastic net regularization was built including 66 preoperative und intraoperative parameters. Cross-validation was used to select the optimal model. The model was assessed via area under the ROC curve (AUC) and calibration slope and intercept.

Results

A total of N = 2488 patients were included. In the optimal model the predictors selected were texture of the pancreatic parenchyma (soft versus hard), body mass index, histological diagnosis pancreatic ductal adenocarcinoma and operation time. The AUC was 0.70 (95% CI 0.69–0.70), the calibration slope 1.67 and intercept 1.12. In the validation set the AUC was 0.65 (95% CI 0.64–0.66), calibration slope and intercept were 1.22 and 0.42, respectively.

Conclusion

The model we present is a valid measurement instrument for POPF risk based on four predictor variables. It can be applied in clinical practice as well as for risk-adjustment in research studies and quality assurance in surgery.

Introduction

Postoperative pancreatic fistula (POPF) is one of the major factors for morbidity and mortality in pancreatic surgery. The International Study Group for Pancreatic Surgery (ISGPS) published in 2005 a definition and a classification of POPF, which have been widely accepted and used [1]. According to this definition, a pancreatic fistula is defined as any amylase-rich drainage fluid (>3 times the upper limit of institutional normal serum amylase activity) starting from the third day after surgery. POPF are then classified in grade A, grade B and grade C, according to the extent of the clinical impact. Grade A POPF have no impact on the postoperative course, grade B POPF alter the normal postoperative course, while the condition of the patient stays stable, and grade C POPF lead to severe complications such as organ failure with the need of intensive care or surgical intervention. In 2016, the ISGPS narrowed the definition of POPF to the clinically relevant POPF B and C [2]. While POPF B does not lead to higher mortality, the in-hospital death rate among patients with POPF C is as high as 35% and over one third of in-hospital deaths after pancreatoduodenectomy are contributed to POPF C [3,4]. Thus, assessing risk for POPF has a pivotal role when estimating overall risk in pancreatic surgery.

There has been considerable effort to develop a measurement tool for risk of POPF [[5], [6], [7], [8]]. In a recent review, Sandini et al. described 10 clinical risk scores for POPF, published between 2008 and 2016 [5]. The most common parameters used in the development of predictive scores for POPF are the consistency of the pancreatic parenchyma and the diameter of the main pancreatic duct (MPD). While usually the consistency of the pancreatic parenchyma is subjectively assessed by the surgeon as soft or hard, the MPD is either used as a continuous or as a multicategorial parameter, measured at the resection plane of the pancreas. Since measurements of the MPD intraoperatively, especially when the pancreatic duct is small, might be impractical and imprecise, in the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery MPD has been recorded as a binary variable <3 mm versus ≥3 mm [9]. Furthermore, there is an association of soft pancreatic parenchyma and small MPD that might cause the problem of multicollinearity in the regression models used to develop the prediction scores, and thus lead to instability of the models [10].

Another issue, when developing a predictive model for POPF, is the parameter selection, which usually has been based on univariable testing for significance or some prior knowledge, which might lead to selection bias and potentiating of uncertainties due to multiple testing.

In this study, we address the problems of parameter selection and multicollinearity using multivariable logistic regression with elastic net regularization [11] to develop a predictive model for POPF, using a large sample from the German pancreatic surgery registry StuDoQ|Pancreas [9].

Section snippets

Study Design and Approval

This is a retrospective, registry-based, explorative study. It was approved by the German Society for General and Visceral Surgery and the local ethics committee of the University of Lübeck.

Software

All data processing and analysis was performed with R version 3.3.1. The following R packages were used: Hmisc, knitr, tables, xtable, stats, pROC, stringr, mice, Amelia, caret, ggplot2, gridExtra. The graphics were produced with the R packages ggplot2 and gridExtra.

Study population and parameters

The study population consisted of all

Descriptive and univariable analysis

A total of N = 2488 patients were identified. Of these, 1671 were assigned to the training set and 817 to the test set. Appendix A, Table A1 displays the descriptive statistics including missing data percentage. In the training set, POPF B rate was 8.2%, POPF C - 6.3% and total POPF B/C - 14.5%. The 30-day mortality was 3.4%, in-hospital mortality - 4.6%. Of the patients, who died during postoperative hospital stay, 34.2% had POPF C and 28.4% of the patients with POPF C died during

Discussion

In the era of precision medicine, estimation and quantification of operative risk is of major importance in surgery. Being able to estimate the operative risk allows for an individual therapy concept but also to develop and target new therapeutics and operative techniques to a specific population at risk as well as for risk adjusted quality assurance.

Postoperative pancreatic fistula has acquired much attention due to its enormous impact on morbidity and mortality in pancreatic surgery.

Conclusion

In conclusion, the model presented here is a valid measurement tool for POPF risk. It can be applied to guide the decision for surgery, drainage management, risk adjustment in research studies as well as quality assurance in surgery.

Conflicts of interest

T. Keck and U. F. Wellner are members of the steering committee of StuDoQ|Pancreas.

Acknowledgements

None.

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