Combination of postoperative C-reactive protein value and computed tomography imaging can predict severe pancreatic fistula after pancreatoduodenectomy

BackgroundRecent management after pancreatoduodenectomy recommends either omission of prophylactic drainage or early removal. This potentially makes the diagnosis of postoperative pancreatic fistula (POPF) difficult because the diagnosis is based on the amylase value of drain effluent. The aim of this study was to determine if severe POPF could be predicted independent of drainage information.MethodsRecords of consecutive patients who underwent pancreatoduodenectomy between 2012 and 2018 were included for further analysis. The presence of a peripancreatic collection (PC) on routine postoperative (day7) computed tomography (early CT) and perioperative characteristics were analyzed.ResultsPC appeared in 82/211 patients (39%) and was associated with clinically relevant POPF (p < 0.001). The C-reactive protein (CRP) on postoperative day5 was a good predictor of severe POPF (needing interventional therapy or Grade C) (area under the receiver operating characteristics curve, 0.802; 95% confidence interval, 0.702–0.875). Presence of a PC and a high CRP value were independent risk factors for severe POPF following multivariate analysis. The combination of CRP<5.0 mg/dL on postoperative day 5 and the absence of a PC had 98% negative predictive value.ConclusionThe combination of CRP measurement and PC evaluation by early CT was useful in predicting severe POPF after pancreatoduodenectomy.     

Pancreatic attenuation on computed tomography predicts pancreatic fistula after pancreaticoduodenectomy

BackgroundSome parameters using preoperative computed tomography (CT) have been evaluated to predict the development of pancreatic fistula (PF) after pancreaticoduodenectomy (PD). The present retrospective study evaluated the predictive value of pancreatic attenuation for PF after PD.MethodsA retrospective review was conducted of the patients who underwent PD between January 2010 and December 2014. The pancreatic attenuation was measured in unenhanced preoperative CT images. Pre- and intraoperative variables were analyzed for the risk of PF after PD.ResultsOf the 346 consecutive patients, PF occurred in 116 (34%). The pancreatic attenuation was significantly greater in patients with PF than in those without PF (median, 40.0 vs. 33.3 Hounsfield units [HU], P < 0.001). A multivariate analysis showed that a pancreatic attenuation ≥30.0 HU (odds ratio [OR], 3.72; P < 0.001), a body mass index ≥25.0 kg/m² (OR, 3.67; P < 0.001) and a diameter of the main pancreatic duct <3.0 mm (OR, 1.84; P = 0.034) were independent risk factors for PF after PD.ConclusionThe degree of pancreatic attenuation on preoperative CT images was significantly associated with PF, and a pancreatic attenuation ≥30.0 HU was an independent risk factor of PF after PD.     

A preoperative predictive score of pancreatic fistula following pancreatoduodenectomy

Background

Various factors are related to the occurrence of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD). Some of the strongest are identified intra- or postoperatively, which limits their utility in predicting this complication. The preoperative prediction of POPF permits an individualized approach to patient consent and selection, and may influence postoperative management. This study sought to develop and test a score to predict POPF.

Methods

A post hoc analysis of a prospectively maintained database was conducted. Consecutive patients were randomly selected to modelling and validation sets at a ratio of 2 : 1, respectively. Patient data, preoperative blood tests and physical characteristics of the gland (assessed from preoperative computed tomography images) were subjected to univariate and multivariate analysis in the modelling set of patients. A score predictive of POPF was designed and tested in the validation set.

Results

Postoperative pancreatic fistula occurred in 77 of 325 (23.7%) patients. The occurrence of POPF was associated with 12 factors. On multivariate analysis, body mass index and pancreatic duct width were independently associated with POPF. A risk score to predict POPF was designed (area under the receiver operating characteristic curve: 0.832, 95% confidence interval 0.768–0.897; P < 0.001) and successfully tested upon the validation set.

Conclusions

Preoperative assessment of a patient''s risk for POPF is possible using simple measurements. The present risk score is a valid tool with which to predict POPF in patients undergoing PD.     

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.     

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.     

A modified alternative fistula risk score (a-FRS) obtained from the computed tomography enhancement pattern of the pancreatic parenchyma predicts pancreatic fistula after pancreatoduodenectomy

BackgroundAlternative fistula risk score (a-FRS) is useful to predict clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD).MethodsClinical data from 239 patients undergoing PD were collected. The CT value of the pancreatic parenchyma was measured in the nonenhanced (N), arterial (A), portal venous (P), and late (L) phases. The A/N, A/P, P/L and A/L ratios were calculated and their correlation with CR-POPF were analyzed. By replacing pancreatic texture with the best CT attenuation ratio, a modified a-FRS was developed.ResultsForty-seven patients developed CR-POPF. The A/P ratio (P < 0.001), P/L ratio (P = 0.002) and A/L ratio (P < 0.001) were significantly higher in the CR-POPF group. The A/L ratio performed best in predicting CR-POPF (AUC: 0.803) and the cut-off value is 1.36. A/L ratio >1.36 (P < 0.001), body mass index (P = 0.005) and duct diameter (P = 0.037) were independently associated with CR-POPF. By replacing soft texture with an A/L ratio >1.36, a modified a-FRS was developed and performed better than the a-FRS (AUC: 0.823 vs 0.748, P = 0.006) in predicting CR-POPF.ConclusionsThe modified a-FRS is an objective and preoperative model for predicting the occurrence of CR-POPF after PD.     

Standardized salvage completion pancreatectomy for grade C postoperative pancreatic fistula after pancreatoduodenectomy (with video)

BackgroundEmergency completion pancreatectomy (CP) after pancreatoduodenectomy (PD) is a technically demanding procedure. We report our experiences with a four-step standardized technique used at our center since 2012.MethodsIn the first step, the gastrojejunostomy is divided with a stapler to quickly access the pancreatic anastomosis and permit adequate exposure, especially in cases of active bleeding. Second, the bowel loops connected to the pancreatic anastomosis is divided in cases of pancreaticojejunostomy. Third, the pancreatectomy is completed with or without the splenic vessels and spleen conservation according to the local conditions. Finally, the fourth step reconstructs in a Roux-en-Y fashion and ensures drainage.ResultsFrom January 2012 to December 2019, 450 patients underwent PD at our center. Reintervention for grade C postoperative pancreatic fistula was decided for 30 patients, and CP was performed in 21 patients. The mean intraoperative blood loss and operative duration were relatively low (600 ml and 240 min, respectively). During the perioperative period, three patients died from multiple organ failure, and two patients died intraoperatively from a cataclysmic hemorrhage originating from the superior mesenteric artery.DiscussionOur standardized procedure appears to be relatively safe, reproducible, and could be particularly useful for young surgeons.     

Density and enhancement of the pancreatic tail on computer tomography predicts acinar score and pancreatic fistula after pancreatoduodenectomy

BackgroundAcinar score calculated at the pancreatic resection margin is associated with postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). The present study evaluates the association between (i) computed tomography (CT) density of the pancreas and the acinar score of the pancreatic resection margin, and (ii) CT density of the pancreas and POPF after PD.MethodsConsecutive patients who underwent PD were included for analysis. CT densities of the pancreatic head, neck, body and tail were measured in non-contrast (NC), arterial (ART) and portal venous (PV) phases. Histologic slides of the pancreatic resection margin were scored for acinar cell density.ResultsNinety patients were included for analysis. Non-contrast density of the pancreatic tail was a good predictor of POPF (AUROC 0.704, p = 0.036), and a cut-off value of >40 Hounsfield units predicted POPF with 70.0% sensitivity and 73.4% specificity. The ratio of densities between PV and NC phases in the pancreatic tail was also a good predictor of POPF (AUROC 0.712, p = 0.030), and a cut-off value of <2.29 predicted POPF with 70.9% sensitivity and 80% specificity.ConclusionNon-contrast CT density of the pancreatic tail correlates with acinar cell density of the pancreatic resection margin and predicts the development of POPF after PD.     

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.     

Pure biliary leak vs. pancreatic fistula associated: non-identical twins following pancreatoduodenectomy

BackgroundBiliary leak (BL) after pancreatoduodenectomy (PD) may have diffrent severity depending on its association with postoperative pancreatic fistula (POPF).MethodsData of 2715 patients undergoing PD between 2011 and 2020 at two European third-level referral Centers for pancreatic surgery were retrospectively reviewed. These included BL incidences, grading, outcomes, specific treatments, and association with POPF.ResultsBL occurred in 6% of patients undergoing PD. Among 143 BL patients, 47% had an associated POPF and 53% a pure BL. Major morbidity (64% vs 36%) and mortality (19% vs 4%) were higher in POPF-associated BL group (all P< 0.01). Day of BL onset was similar between groups (POD 2 vs 3; P = 0.2), while BL closure occurred earlier in pure BL (POD 12 vs 23; P < 0.01). Conservative treatment was more frequent (55% vs 15%; P < 0.01), and the rate of percutaneous and/or trans-hepatic drain placement was lower (30% vs 16%; P = 0.04) in pure BL group. Relaparotomy was more common in POPF-associated BL group (42% VS 17%; P < 0.01) but was performed earlier in pure BL (POD 2 vs 10; P = 0.02).ConclusionsPure BL represents a more benign entity, managed conservatively in half of the cases.     

Lower phosphate levels following pancreatectomy is associated with postoperative pancreatic fistula formation

BackgroundWhereas hypophosphatemia following hepatectomy is associated with decreased morbidity, hypophosphatemia following pancreatectomy may be associated with increased morbidity, including the development of postoperative pancreatic fistula (POPF). This study aimed to evaluate the relationship between postoperative hypophosphatemia and POPF formation.MethodsPatients from our institutional Research Patient Data Registry who underwent pancreatectomy from 2001 to 2017 were included. POPF was defined according to the International Study Group for Pancreatic Fistulas (ISGPF) criteria and according to internal criteria for drain removal. Postoperative serum phosphate levels, demographics, and comorbidities were evaluated. Unadjusted and adjusted analyses were performed.Results2342 patients underwent pancreatic resection. Mean age was 63.0 years (SD 14.3), 51.2% were male, and 58.7% had pancreatic cancer. Of all resections, 67.7% were pancreaticoduodenectomies. In unadjusted analysis, phosphate levels were significantly and persistently lower on POD 0 and POD 2–5 in patients who developed POPF's. In adjusted analysis, POD 2 phosphate <1.75 predicted an additional 46% increased odds of POPF (OR 1.46 95% CI 1.06–2.01; p = 0.02). Distal pancreatectomy was independently associated with POPF formation when compared to pancreaticoduodenectomy (OR 1.72 95% CI 1.18–2.51; p = 0.005).ConclusionLower phosphate levels in the early post-operative period following both proximal and distal pancreatectomies is associated with increased risk of POPF.     

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis

BackgroundMultiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores.MethodsAreas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models.ResultsSystematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%.ConclusionMost risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.     

Drainage fluid and serum amylase levels accurately predict development of postoperative pancreatic fistula

AIM To investigate potential biomarkers for predicting postoperative pancreatic fistula( POPF) after pancreaticoduodenectomy(PD).METHODS We prospectively recruited 83 patients to this study. All patients underwent PD(Child's procedure) at the Division of Hepatobiliary and Pancreas Surgery at the First Bethune Hospital of Jilin University between June 2011 and April 2015. Data pertaining to demographic variables, clinical characteristics, texture of pancreas, surgical approach, histopathological results, white blood cell count, amylase and choline levels in the serum, pancreatic/gastric drainage fluid, and choline and amylase levels in abdominal drainage fluid were included in the analysis. Potential correlations between these parameters and postoperative complications such as, POPF, acute pancreatitis, hemorrhage, delayed gastric emptying, and biliary fistula, were assessed. RESULTS Twenty-eight out of the 83(33.7%) patients developed POPF. The severity of POPF was classified as Grade A in 8(28%) patients, grade B in 16(58%), and grade C in4(14%), according to the pancreatic fistula criteria. On univariate and multivariate logistic regression analyses, higher amylase level in the abdominal drainage fluid on postoperative day(POD)1 and higher serum amylase levels on POD4 showed a significant correlation with POPF(P 0.05). On receiver operating characteristic curve analysis, amylase cut-off level of 2365.5 U/L in the abdominal drainage fluid was associated with a 78.6% sensitivity and 80% specificity [area under the curve(AUC): 0.844; P = 0.009]. A cut-off serum amylase level of 44.2 U/L was associated with a 78.6% sensitivity and 70.9% specificity(AUC: 0.784; P = 0.05).CONCLUSION Amylase level in the abdominal drainage fluid on POD1 and serum amylase level on POD4 represent novel biomarkers associated with POPF development.     

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.     

Cystic pancreatic neoplasms: computed tomography and magnetic resonance imaging findings.

Cystic pancreatic neoplasms include serous cystadenomas (SCA), mucin-producing cystic tumors, cystic islet-cell tumors, and cystic solid and papillary epithelial neoplasms. Imaging techniques are of great value in the demonstration and differential diagnosis of these tumors. In this article we present the computed tomography (CT) and magnetic resonance imaging (MRI) findings of the aforementioned cystic neoplasms. Although the radiological features are in many cases informative, a significant overlap does exist; fine-needle aspiration biopsy and cytology or excisional biopsy and histological examination are necessary to determine a definitive diagnosis.     

External validation and comparison of the original,alternative and updated-alternative fistula risk scores for the prediction of postoperative pancreatic fistula after pancreatoduodenectomy

BackgroundMany postoperative pancreatic fistula (POPF) predictions models were developed and validated in western populations. Direct use of these models in the large Indian/Asian population, however, requires proper validation.ObjectiveTo validate the original, alternative and updated alternative fistula risk score (FRS) models.MethodsA validation study was performed in consecutive patients undergoing pancreatoduodenectomy (PD) from January 2011 to March 2018. The area under the receiver operating curve (ROC) and calibration plots were used to assess the performance of original-FRS (o-FRS), alternative FRS (a-FRS) and updated alternative FRS (ua-FRS) models.ResultsThis cohort consisted of 825 patients of which 66% were males with a median age of 55 years and mean body mass index of 22.6. The majority of tumors (61.8%) were of periampullary origin. Clinically relevant POPF was observed in 16.8% patients. Area under curve (AUC) of ROC for the o-FRS was 0.65, 0.69 for a-FRS and 0.70 for ua-FRS, respectively (p = 0.006).ConclusionsIn this large Indian cohort of predominantly periampullary tumors, the ua-FRS performed better than the a-FRS and o-FRS, although differences were small. Since the AUC value of the ua-FRS is at the accepted threshold there might be room for improvement for a FRS.