A simple preoperative stratification tool predicting the risk of postoperative pancreatic fistula after pancreatoduodenectomy

BackgroundPostoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) can be associated with severe postoperative morbidity. This study aims to develop a preoperative POPF risk calculator that can be easily implemented in clinical routine.MethodsPatients undergoing PD were identified from a prospectively-maintained database. A total of 11 preoperative baseline and CT-based radiological parameters were used in a binominal logistic regression model. Parameters remaining predictive for grade B/C POPF were entered into the risk calculator and diagnostic accuracy measures and ROC curves were calculated for a training and a test patient cohort. The risk calculator was transformed into a simple nomogram.ResultsA total of 242 patients undergoing PD in the period from 2012 to 2018 were included. CT-imaging-based maximum main pancreatic duct (MPD) diameter (p = 0.047), CT-imaging-based pancreatic gland diameter at the anticipated resection margin (p = 0.002) and gender (p = 0.058) were the parameters most predictive for grade B/C POPF. Based on these parameters, a risk calculator was developed to identify patients at high risk of developing grade B/C POPF. In a training cohort of PD patients this risk calculator was associated with an AUC of 0.808 (95%CI 0.726–0.874) and an AUC of 0.756 (95%CI 0.669-0-830) in the independent test cohort. A nomogram applicable as a visual risk scale for quick assessment of POPF grade B/C risk was developed.ConclusionThe preoperative POPF risk calculator provides a simple tool to stratify patients planned for PD according to the risk of developing postoperative grade B/C POPF. The nomogram visual risk scale can be easily integrated into clinical routine and may be a valuable model to select patients for POPF-preventive therapy or as a stratification tool for clinical trials.     

Surgical techniques and postoperative management to prevent postoperative pancreatic fistula after pancreatic surgery

Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.     

Analysis of risk factors for postoperative pancreatic fistula following pancreaticoduodenectomy

AIM: To explore the morbidity and risk factors of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy.METHODS: The data from 196 consecutive patients who underwent pancreaticoduodenectomy, performed by different surgeons, in the General Hospital of the People’s Liberation Army between January 1^st, 2013 and December 31^st, 2013 were retrospectively collected for analysis. The diagnoses of POPF and clinically relevant (CR)-POPF following pancreaticoduodenectomy were judged strictly by the International Study Group on Pancreatic Fistula Definition. Univariate analysis was performed to analyze the following factors: patient age, sex, body mass index (BMI), hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pancreatic duct diameter, pylorus preserving pancreaticoduodenectomy, pancreatic drainage and pancreaticojejunostomy. Multivariate logistic regression analysis was used to determine the main independent risk factors for POPF.RESULTS: POPF occurred in 126 (64.3%) of the patients, and the incidence of CR-POPF was 32.7% (64/196). Patient characteristics of age, sex, BMI, hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pylorus preserving pancreaticoduodenectomy and pancreaticojejunostomy showed no statistical difference related to the morbidity of POPF or CR-POPF. Pancreatic duct diameter was found to be significantly correlated with POPF rates by univariate analysis and multivariate regression analysis, with a pancreatic duct diameter ≤ 3 mm being an independent risk factor for POPF (OR = 0.291; P = 0.000) and CR-POPF (OR = 0.399; P = 0.004). The CR-POPF rate was higher in patients without external pancreatic stenting, which was found to be an independent risk factor for CR-POPF (OR = 0.394; P = 0.012). Among the entire patient series, there were three postoperative deaths, giving a total mortality rate of 1.5% (3/196), and the mortality associated with pancreatic fistula was 2.4% (3/126).CONCLUSION: A pancreatic duct diameter ≤ 3 mm is an independent risk factor for POPF. External stent drainage of pancreatic secretion may reduce CR-POPF mortality and POPF severity.     

External validation of alternative fistula risk score (a-FRS) for predicting pancreatic fistula after pancreatoduodenectomy

BackgroundThe utility of the proposed alternative fistula risk score (a-FRS) for predicting risk of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) has not been validated widely.MethodsThis retrospective analysis included data of patients undergoing open and laparoscopic PD during March 2012–May 2018 in our institution. The predictive abilities of a-FRS and original-FRS were compared. Risk factors for CR-POPF were also evaluated by multivariate regression analysis.ResultsOf the 370 patients, 80 (21.62%) developed CR-POPF. The incidences of CR-POPF in patients classified as low risk, intermediate risk, and high risk by a-FRS were 5.88%, 24.38%, and 57.69%, respectively (R2 = 0.97). The incidences of CR-POPF in patients classified as negligible risk, low risk, intermediate risk, and high-risk by original-FRS were 0%, 8.62%, 21.51%, and 52.50%, respectively (R2 = 0.92). The area under the ROC curve (AUC) was 0.74 for a-FRS vs. 0.70 for original-FRS. The a-FRS performed better than original-FRS for prediction of CR-POPF in open PD patients (AUC: 0.74 vs. 0.69) and was comparable with original- FRS in laparoscopic PD patients (AUC: 0.70 vs. 0.72).ConclusionsThe a-FRS appears to be an accurate and convenient tool for predicting occurrence of CR-POPF after PD.     

Impact of postoperative pancreatic fistula on long-term oncologic outcomes after pancreatic resection

BackgroundThe short-term morbidity associated with post-operative pancreatic fistula (POPF) is well established, however data regarding the long-term impact are lacking. We aim to characterize long-term oncologic outcomes of POPF after pancreatic resection through a single institution, retrospective study of pancreatic resections performed for adenocarcinoma from 2009 to 2016.MethodsKaplan–Meier survival analysis, logistic regression, and multivariate analysis (MVA) were used to evaluate impact of POPF on overall survival (OS), disease free survival (DFS), and receipt of adjuvant chemotherapy (AC).Results767 patients were included. 82 (10.6%) developed grade B (n = 67) or C (n = 15) POPF. Grade C POPF resulted in decreased OS when compared to no POPF (20.22 vs 26.33 months, p = 0.027) and to grade B POPF (20.22 vs. 26.87 months, p = 0.049). POPF patients were less likely to receive AC than those without POPF (59.5% vs 74.9%, p = 0.003) and grade C POPF were less likely to receive AC than all others (26.7% vs 74.2%, p = 0.0001).ConclusionPOPF patients are less likely to receive AC and more likely to have delay in time to AC. These factors are exacerbated in grade C POPF and likely contribute to decreased OS. These findings validate the clinical significance of the ISGPF definition of POPF.     

Nomogram for predicting survival of patients with metastatic nonfunctioning pancreatic neuroendocrine tumors: A SEER based study

More attention has been placed on nonfunctioning pancreatic neuroendocrine tumors due to the increase in its incidence in recent years. Whether tumor resection at the primary site of metastatic NFpNET is effective remains controversial. Moreover, clinicians need a more precise prognostic tool to estimate the survival of these patients.Patients with metastatic NFpNET were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were identified using a multivariate Cox regression model and included in the nomogram. Coarsened exact matching analysis was used to balance the clinical variables between the non-surgical and surgical groups in our study.A total of 1464 patients with metastatic nonfunctioning pancreatic neuroendocrine tumors (NFpNETs) were included in our cohort. Multivariate analysis identified age, sex, tumor size, differentiated grade, lymph node metastases, resection of primary tumors, and marital status as independent predictors of metastatic NFpNET. The nomogram showed excellent accuracy in predicting 1-, 3-, and 5-year overall survival, with a C-index of 0.812. The calibration curve revealed good consistency between the predicted and actual survival.Coarsened exact matching analysis using SEER data indicated the survival advantages of resection of primary tumors. Our study is the first to build a nomogram model for patients with metastatic NFpNETs. This predictive tool can help clinicians identify high-risk patients and more accurately assess patient survival times.     

Intraoperative acidosis is a new predictor for postoperative pancreatic fistula after pancreaticoduodenectomy

BACKGROUND:Early diagnosis of postoperative pancreatic fistula(POPF) is important for proper interventions.The preoperative,intraoperative and early postoperative biochemical markers have predictive value of POPF.The present study was to evaluate several simple biochemical parameters in the prediction of POPF.METHODS:Patients who underwent pancreaticoduodenectomy in our center between 2006 and 2015 were reviewed retrospectively.Preoperative and early postoperative biochemical parameters were evaluated.Additionally,the relationship between POPF and p H and lactate level at the end of surgery were analyzed,and neutrophil-to-lymphocyte ratio(NLR),plateletto-lymphocyte ratio(PLR),and red cell distribution widthto-platelet ratio(RPR) were calculated for postoperative days(PODs) 1 and 3.Diagnosis and grading of POPF were performed according to the standards of the International Study Group on Pancreatic Fistula.The patients were divided into two groups:Group 1 with no fistula or grade-A fistula; group 2 with grade-B or-C fistula.These simple biochemical markers were then compared between the two groups.RESULTS:Serum amylase level was significantly higher at POD3,and p H level was significantly lower at the end of operation in group 2 compared with those in group 1.However,the serum amylase was below the upper limit of normal serum level and therefore,the difference was not significant in clinical practice.Receiver operating charecteristic curve analysis showed that p H level was a reliable predictor of POPF(area under the curve:0.713; 95% CI:0.573-0.853).CONCLUSIONS:A low p H level at the end of pancreaticoduodenectomy was a risk factor of POPF.NLR,PLR,and RPR had no predictive value of POPF after pancreaticoduodenectomy.     

Risk factors to predict severe postoperative pancreatic fistula following gastrectomy for gastric cancer

AIM:To allow the identification of high-risk postoperative pancreatic fistula(POPF)patients with special reference to the International Study Group on Pancreatic Fistula(ISGPF)classification.METHODS:Between 1997 and 2010,1341 consecutive patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery,Kyoto Prefectural University of Medicine,Japan.Based on the preoperative diagnosis,total or distal gastrectomy and sufficient lymphadenectomy was performed,mainly according to the Japanese guidelines for the treatment of gastric cancer.Of these,35 patients(2.6%)were diagnosed with Grade B or C POPF according to the ISGPF classification and were treated intensively.The hospital records of these patients were reviewed retrospectively.RESULTS:Of 35 patients with severe POPF,17(49%)and 18(51%)patients were classified as Grade B and C POPF,respectively.From several clinical factors,the severity of POPF according to the ISGPF classification was significantly correlated with the duration of intensive POPF treatments(P=0.035).Regarding the clinical factors to distinguish extremely severe POPF,older patients(P=0.035,65 years≤vs<65 years old)and those with lower lymphocyte counts at the diagnosis of POPF(P=0.007,<1400/mm3vs 1400/mm3≤)were significantly correlated with Grade C POPF,and a low lymphocyte count was an independent risk factor by multivariate analysis[P=0.045,OR=10.45(95%CI:1.050-104.1)].CONCLUSION:Caution and intensive care are required for older POPF patients and those with lower lymphocyte counts at the diagnosis of POPF.     

A phase II trial of lanreotide for the prevention of postoperative pancreatic fistula

BackgroundClinically relevant postoperative pancreatic fistula (CR-POPF) is a significant contributor to morbidity after pancreatectomy. Somatostatin analogues have shown variable efficacy in the prevention of CR-POPF. Lanreotide is a somatostatin analogue ideally suited for perioperative use due to its long half-life and favorable side effect profile.MethodsWe conducted a phase II single-arm trial of a single dose of preoperative lanreotide (120 mg) in patients undergoing either pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). The primary outcome was development of CR-POPF or intra-abdominal abscess. Secondary outcomes included biochemical leak and overall morbidity.ResultsA total of 98 patients completed the study. Sixty-two underwent PD (63.3%) and 36 underwent DP (36.7%). The primary outcome was observed in eight (8%) patients in the overall cohort, one from the DP group and seven from the PD group. Biochemical leak was detected in 12 (12.2%) patients in the overall cohort. Twenty-seven (27.5%) patients developed complications, of which 14 (14.2%) were major complications. Drug-related adverse events were limited to mild skin reactions in two (2%) patients.ConclusionPatients who received preoperative lanreotide developed CR-POPF at rates significantly lower than historical controls or published literature. This provides strong justification for a randomized controlled trial.     

Prophylactic octreotide for postoperative pancreatic fistula in patients with pancreatoduodenectomy: Risk-stratified analysis

Background:Postoperative pancreatic fistula is one of the most critical complications following pancreatic surgery. This study aimed to evaluate the utility of selective prophylactic octreotide for patients at high risk of developing postoperative pancreatic fistula.Methods:From June 2019 to July 2020, 263 patients underwent pancreatoduodenectomy with pancreatojejunostomy at Samsung Medical Center. The individual fistula risk scores were calculated using a previously developed nomogram. The clinicopathological data of the patients were retrospectively reviewed.Results:There were 81 patients in the low-risk group and 182 patients in the high-risk group. No statistically significant differences were found in the rates of clinically relevant postoperative pancreatic fistula between octreotide group and the control group in all patients (15.0% vs 14.7%, P = .963) and in the high-risk group (16.1% vs 23.6%, P = .206). In risk factor analysis, postoperative octreotide was not an independent risk factor for clinically relevant pancreatic fistula in all patients and the high-risk group. Drain fluid amylase levels on the first postoperative day were significantly associated with clinically relevant postoperative pancreatic fistula, regardless of the individual risk.Conclusions:The selective use of octreotide, even in high-risk patients, showed no protective effect against pancreatic fistula. Therefore, the routine use of postoperative octreotide is not recommended.     

Pasireotide does not prevent postoperative pancreatic fistula: a prospective study

Background

Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted.

A new pancreaticojejunostomy technique: A battle against postoperative pancreatic fistula

AIM:To present a new technique of end-to-side, ductto-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation, and insertion of a silicone stent. METHODS:We present an end-to-side, duct-to-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation, and the insertion of a silicone stent. This technique was performed in thirty-two consecutive patients who underwent a pancreaticoduodenectomy procedure by the same surgical team, from January 2005 to March 2011. The surgical procedure performed in all cases was classic pancreaticoduodenectomy, without preservation of the pylorus. The diagnosis of pancreatic leakage was defined as a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase concentration greater than three times the serum amylase activity. RESULTS:There were 32 patients who underwent end-to-side, duct-to-mucosa pancreaticojejunostomy with seromuscular jejunal flap formation. Thirteen of them were women and 19 were men. These data correspond to 40.6% and 59.4%, respectively. The mean age was 64.2 years, ranging from 55 to 82 years. The mean operative time was 310.2 ± 40.0 min, and was defined as the time period from the intubation up to the extubation of the patient. Also, the mean time needed to perform the pancreaticojejunostomy was 22.7 min, ranging from 18 to 25 min. Postoperatively, one patient developed a low output pancreatic fistula, three patients developed surgical site infection, and one patient developed pneumonia. The rate of overall morbidity was 15.6%. There was no 30-d postoperative mortality. CONCLUSION:This modification appears to be a significantly safe approach to the pancreaticojejunostomy without adversely affecting operative time.     

Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy

AIM To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy.METHODS We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis.RESULTS A total of 269(49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy,including 71(13.17%) cases of grade A pancreatic fistula,178(33.02%) cases of grade B,and 20(3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula(POPF) and the following factors: age,hypertension,alcohol consumption,smoking,history of upper abdominal surgery,preoperative jaundice management,preoperative bilirubin,preoperative albumin,pancreatic duct drainage,intraoperative blood loss,operative time,intraoperative blood transfusion,Braun anastomosis,and pancreaticoduodenectomy(with or without pylorus preservation). Conversely,a significant correlation was observed between POPF and the following factors: gender(male vs female: 54.23% vs 42.35%,P = 0.008),diabetes(non-diabetic vs diabetic: 51.61% vs 39.19%,P = 0.047),body mass index(BMI)(≤ 25 vs 25: 46.94% vs 57.82%,P = 0.024),blood glucose level(≤ 6.0 mmol/L vs 6.0 mmol/L: 54.75% vs 41.14%,P = 0.002),pancreaticojejunal anastomosis technique(pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-tomucosa anastomosis: 57.54% vs 35.46%,P = 0.000),diameter of the pancreatic duct(≤ 3 mm vs 3 mm: 57.81% vs 38.36%,P = 0.000),and pancreatic texture(soft vs hard: 56.72% vs 29.93%,P = 0.000). Multivariate logistic regression analysis showed that gender(male),BMI 25,pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis,pancreatic duct diameter ≤ 3 mm,and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.CONCLUSION Gender(male),BMI 25,pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis,pancreatic duct diameter ≤ 3 mm,and soft pancreas were risk factors for pancreatic fistula after pancreaticoduodenectomy.