Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection.

OBJECTIVE: We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs). SUMMARY BACKGROUND DATA: An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis. METHODS: Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice. RESULTS: Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice. CONCLUSIONS: Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

Impact of the preoperative bone mineral density on the outcomes after resection of pancreatic cancer.

PURPOSE: The aim of this study is to evaluate the correlation between bone mineral density (BMD) and other body composition markers, as well as, the impact of preoperative BMD on the surgical outcomes after resection of pancreatic cancer. METHODS: This retrospective study included 275 patients who underwent surgical resection of pancreatic cancer in our institute between 2003 and 2016. Patients were divided according to BMD into low and normal groups and their postoperative outcomes were compared. Risk factors for mortality and tumor recurrence were also evaluated. RESULTS: Patients with low BMD were older (P < 0.001), had a higher intramuscular adipose tissue content (P = 0.011) and higher visceral fat area (P = 0.003). The incidence of postoperative pancreatic fistula (POPF) (grade ≥ B) was higher in the low BMD group. No significant difference was observed between the two groups regarding overall survival and recurrence-free survival and low BMD was not a risk factor for mortality or tumor recurrence after resection of pancreatic cancer. CONCLUSION: A low preoperative BMD was not found to be a risk factor for mortality or tumor recurrence after resection of pancreatic cancer; however, it was associated with a higher incidence of clinically relevant POPF.

Significance of drain fluid amylase check on day 3 after pancreatectomy.

BACKGROUND: The occurrence of pancreatic fistulae (PF) after pancreatectomy is the main cause of prolonged hospital stay, delayed chemotherapy, poor quality of life and post-operative death. The surgical drainage after pancreatectomy can induce ascending infection, early removal is recommended if the possibility of PF is low. The present study analysed the risk factors and predictors of PF, and confirmed the significance of drain fluid amylase concentration (DFA, U/L) among various factors identified. On the basis of these results, we tried to evaluate the practical clinical applicability of DFA and obtain appropriate baseline values. METHODS: From January 2014 to December 2017, 117 patients underwent major pancreatectomy with pylorus-preserving pancreatoduodenectomy, Whipple procedure, subtotal pancreatectomy or distal pancreatectomy. This study retrospectively collected and analysed demographics, pathological results and prognoses of these patients. RESULTS: Multivariate analysis indicated that the DFA obtained on day 3 after surgery (DFA 3) was the only predictor of PF with statistical significance (P < 0.001). Of all the factors tested, area under the curve was highest for DFA 3 (0.89). In addition, of all the factors tested, DFA 3 with a cut-off value of 1004 U/L had the best sensitivity (92%) and specificity (82%). CONCLUSIONS: DFA 3 of a cut-off value of 1004 U/L might be determined to be the best predictor of PF, and early removal of the surgical drain could be considered if DFA (1004 U/L) is lower than the cut-off value at 3 days after surgery.

Predictive value of drain pancreatic amylase concentration for postoperative pancreatic fistula on postoperative day 1 after pancreatic resection: An updated meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a potentially fatal complication following pancreaticoduodenectomy. Early prediction and exclusion of POPF may be highly advantageous to enhance patient outcomes, and accelerate recovery. In this meta-analysis, we sought to assess the prediction of drain pancreatic amylase concentration on postoperative day 1 (DPA1) for POPF. METHODS: By searching online databases up to April 2018, all researches mentioned DPA1 for detecting POPF were analyzed. STATA 12.0 was used to analyze pooled predictive parameters. RESULTS: Seventeen studies were finally analyzed including 4676 patients in total. The pooled sensitivity and specificity of DPA1 were respectively 0.85 (95% CI: 0.71, 0.93), 0.80 (95% CI: 0.74, 0.85) to predict overall POPF, and 0.70 (95% CI: 0.53, 0.82), 0.88 (95% CI: 0.86, 0.90) to predict CR-POPF. If pretest probability was 50%, corresponding post-test (+) were respectively 81%, 86% for overall POPF and CR-POPF when DPA1 was above cutoffs, while the post-test (-) were respectively 16%, 26% when DPA1 was under cutoffs. In subgroup analysis, sensitivities of cutoff >5000 group, 1000< cutoff <5000 group, and cutoff <1000 group were respectively 0.65 (0.43-0.82), 0.82 (0.71-0.89), 0.87 (0.78-0.92); and specificities were respectively 0.88 (0.83-0.92), 0.83 (0.77-0.88), 0.71 (0.62-0.79). Positive LR was 5.5 (3.4-8.8), 4.8 (3.4-6.7), and 3.0 (2.3-4.0) respectively. Negative LR was 0.40 (0.22-0.72), 0.22 (0.13-0.37), and 0.19 (0.11-0.32) respectively. CONCLUSION: DPA1, which has good sensitivity and specificity, is useful for predicting overall POPF and CR-POPF, according to the present studies. Meanwhile, it should be cautious to apply because there is a wide range in cutoffs between different studies.

EARLY DRAIN FLUID AMYLASE IS USEFUL TO PREDICT PANCREATIC FISTULA AFTER PANCREATODUODENECTOMY: LESSONS LEARNED FROM A SOUTHERN BRAZILIAN CENTER.

BACKGROUND: Pancreatic fistula represents the most feared complication after pancreatoduodenectomies, being the major responsible for the high morbidity and mortality after this operation. Its incidence remains around 10% to 30%. In recent years, several authors have studied the value of amylase in abdominal drains fluid, measured at an early stage after the surgical procedure, as a useful tool to identify patients at risk of developing pancreatic fistula. OBJECTIVE: To analyze the value of early drain fluid amylase as a method to predict the occurrence and severity of postoperative pancreatic fistula in patients undergoing pancreatoduodenectomies. METHODS: We evaluated 102 prospective patients submitted to pancreatoduodenectomies from January 2013 to June 2017. The mensuration of amylase in abdominal drains was performed on days 1, 3, 5 and 7 in all patients. Patients were divided into three groups according to postoperative day 1 (POD1) results: values <270 U/L (group 1); between 271 and 5.000 U/L (group 2); and values >5.000 U/L (group 3). RESULTS: The incidence of pancreatic fistula was 25.5%, being 3.33%, 27.3% and 41.02% in the three groups, respectively. Compared with group 1, the risk of developing pancreatic fistula increased with increasing amylase values on POD1. Amylase values on POD1 and POD3 of patients with pancreatic fistula were higher than in the other ones without this complication (P<0.001). In addition, in group 3, 37.5% of patients with pancreatic fistula evolved to death (P<0.001). Finally, in this group, patients who died had drain fluid amylase values on POD1 significantly higher than the others in the same group (P<0.001). CONCLUSION: Early drain fluid amylase value is a useful test to stratify patients in relation to the risk of developing pancreatic fistula after pancreatoduodenectomies, in addition to correlate with the severity of this complication.

O valor da amilase, obtido precocemente nos drenos abdominais, é teste útil em prever a ocorrência de fístula pancreática após duodenopancreatectomia: lições aprendidas de um centro do Sul do Brasil / Early drain fluid amylase is useful to predict pancreatic fistula after pancreatoduodenectomy: lessons learned from a southern brazilian center

ABSTRACT BACKGROUND: Pancreatic fistula represents the most feared complication after pancreatoduodenectomies, being the major responsible for the high morbidity and mortality after this operation. Its incidence remains around 10% to 30%. In recent years, several authors have studied the value of amylase in abdominal drains fluid, measured at an early stage after the surgical procedure, as a useful tool to identify patients at risk of developing pancreatic fistula. OBJECTIVE: To analyze the value of early drain fluid amylase as a method to predict the occurrence and severity of postoperative pancreatic fistula in patients undergoing pancreatoduodenectomies. METHODS: We evaluated 102 prospective patients submitted to pancreatoduodenectomies from January 2013 to June 2017. The mensuration of amylase in abdominal drains was performed on days 1, 3, 5 and 7 in all patients. Patients were divided into three groups according to postoperative day 1 (POD1) results: values <270 U/L (group 1); between 271 and 5.000 U/L (group 2); and values >5.000 U/L (group 3). RESULTS: The incidence of pancreatic fistula was 25.5%, being 3.33%, 27.3% and 41.02% in the three groups, respectively. Compared with group 1, the risk of developing pancreatic fistula increased with increasing amylase values on POD1. Amylase values on POD1 and POD3 of patients with pancreatic fistula were higher than in the other ones without this complication (P<0.001). In addition, in group 3, 37.5% of patients with pancreatic fistula evolved to death (P<0.001). Finally, in this group, patients who died had drain fluid amylase values on POD1 significantly higher than the others in the same group (P<0.001). CONCLUSION: Early drain fluid amylase value is a useful test to stratify patients in relation to the risk of developing pancreatic fistula after pancreatoduodenectomies, in addition to correlate with the severity of this complication.

RESUMO CONTEXTO: A fístula pancreática representa a complicação mais temida após as duodenopancreatectomias, sendo a grande responsável pela elevada morbi-mortalidade após esta operação. Sua incidência permanece em torno de 10% a 30%. Nos últimos anos, diversos trabalhos têm estudado o valor da amilase nos drenos abdominais, medido de forma precoce após o procedimento cirúrgico, como ferramenta útil para a identificação dos pacientes sob risco de desenvolver fístula pancreática. OBJETIVO: Avaliar o valor da amilase no fluido dos drenos abdominais, obtido precocemente no pós-operatório, como método para prever a ocorrência e severidade da fístula pancreática nos pacientes submetidos a duodenopancreatectomias. MÉTODOS: Foram avaliados 102 pacientes prospectivos submetidos a duodenopancreatectomias no período de janeiro de 2013 a junho de 2017. A dosagem da amilase nos drenos abdominais foi realizada nos dias 1, 3, 5 e 7 em todos os pacientes. Os pacientes foram divididos em três grupos conforme os resultados do 1o PO: valores <270 U/L (grupo 1); entre 271 e 5.000 U/L (grupo 2); e valores >5.000 U/L (grupo 3). RESULTADOS: A incidência de fístula pancreática foi de 25,5%, sendo 3,33%, 27,3% e 41,02% nos três grupos, respectivamente. Comparados ao grupo 1, o risco de desenvolver fístula pancreática foi crescente com o aumento da amilase no 1o PO. Os valores das amilases no 1o PO e 3o PO dos pacientes com fístula pancreática foram maiores do que nos pacientes sem essa complicação (P<0,001). Além disso, no grupo 3, 37,5% dos pacientes com fístula pancreática evoluíram para óbito (P<0,001). Por fim, neste grupo, os pacientes que evoluíram para óbito tiveram valores de amilase no 1o PO significativamente maiores do que os demais pacientes (P<0,001). CONCLUSÃO: O valor da amilase, medido de forma precoce nos drenos abdominais no pós-operatório de duodenopancreatectomias, é teste útil para estratificar pacientes em relação ao risco de apresentar fístula pancreática, além de se correlacionar com a severidade dessa complicação.

Impact of anatomical position of the pancreas on postoperative complications and drain amylase concentrations after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic surgery for gastric cancer requires traction or compression of the pancreas, with the extent depending on the anatomical position of the pancreas. This study investigated the impact of the position of the pancreas on postoperative complications and drain amylase concentrations after laparoscopic distal gastrectomy (LDG). METHODS: Gastric cancer patients who underwent LDG were assessed retrospectively. The following anatomical parameters were measured retrospectively in preoperative computed tomography sagittal projections: the length of the vertical line between the pancreas and the aorta (P-A length), representing the height of the slope looking down the celiac artery from the top of the pancreas, and the angle between a line drawn from the upper border of the pancreas to the root of the celiac artery and the aorta (UP-CA angle), representing the steepness of the slope. Correlations between each parameter and postoperative complications were analyzed by logistic regression analysis. Pearson's product-moment correlation coefficients were calculated for scatter diagrams for each parameter and drain amylase concentration on postoperative day 1. RESULTS: Analyses were performed in 394 patients. P-A length [odds ratio (OR) 1.905; 95% confidence interval (CI) 1.100-3.300; P = 0.021] was significantly correlated with pancreatic fistula. P-A length (OR 2.771; 95% CI 1.506-5.098; P = 0.001), UP-CA angle (OR 2.323; 95% CI 1.251-4.314; P = 0.008), and low preoperative serum albumin (OR 2.082; 95% CI 1.050-4.128; P = 0.036) were significantly correlated with overall postoperative complications defined as Clavien-Dindo ≥ grade II. P-A length and UP-CA angle showed significant positive correlations with drain amylase concentration on postoperative day 1. CONCLUSION: The position of the pancreas is an independent predictor of pancreatic fistula and/or postoperative complications and correlates with drain amylase concentration after LDG for gastric cancer.

Acinar cell density at the pancreatic resection margin is associated with post-pancreatectomy pancreatitis and the development of postoperative pancreatic fistula.

BACKGROUND: There has been recent evidence supporting post-pancreatectomy pancreatitis as a factor in the development of postoperative pancreatic fistula (POPF). The aims of this study were to evaluate: (i) the correlation of the acinar cell density at the pancreatic resection margin with the intra-operative amylase concentration (IOAC) of peri-pancreatic fluid, postoperative pancreatitis, and POPF; and (ii) the association between postoperative pancreatitis on the first postoperative day and POPF. METHODS: Consecutive patients who underwent pancreatic resection between June 2016 and July 2017 were included for analysis. Fluid for IOAC was collected, and amylase concentration was determined in drain fluid on postoperative days 1, 3, and 5. Serum amylase and lipase and urinary trypsinogen-2 concentrations were determined on the first postoperative day. Histology slides of the pancreatic resection margin were scored for acinar cell density. RESULTS: Sixty-one patients were included in the analysis. Acinar cell density significantly correlated with IOAC (r = 0.566, p < 0.001), and was significantly associated with postoperative pancreatitis (p < 0.001), and POPF (p = 0.003). Postoperative pancreatitis was significantly associated with the development of POPF (OR 17.81, 95%CI 2.17-145.9, p = 0.001). DISCUSSION: The development of POPF may involve a complex interaction between acinar cell density, immediate leakage of pancreatic fluid, and postoperative pancreatitis.

[Analysis of the Relationship between the Change of Drain Amylase Value and Postoperative Pancreatic Fistula after Pancreaticoduodenectomy].

To diagnose postoperative pancreatic fistula(POPF)after pancreaticoduodenectomy(PD)during early post operative days, we evaluatedwhether a change in drain amylase value(DAV), WBC value, or CRP value predicted clinically significant POPF. One hundred thirty patients underwent substomach preserving PD(SSPPD)from 2005 to 2016 in our institution andwe examinedDAV, WBC, andCRP values at POD 1, 3, and 5. Seventy-five patients(57.7%)were equivalent to ISGPF grade A at POD 3.We analyzedthese 75 cases by following 5 factors(DAV at POD 3>1,500 U/L, DAV at POD 5>1,000 U/L,WBC value at POD 5≤9,000/mL, DAV of POD 5 decreased to 1/3 from DAV of POD 3, CRP value not improved≥50%from POD 3 to 5) andwere concernedwith the crisis of the grade B/C POPF at final diagnosis after POD 5. In conclusion, DAV of POD 5 decreased to 1/3 from DAV of POD 3, andthe CRP value having not improved(≥50%from POD 3 to 5)were significant risk factors for POPF grade B andC by Cox proportional hazard models.

Pancreatitis After Pancreatoduodenectomy Predicts Clinically Relevant Postoperative Pancreatic Fistula.

BACKGROUND: Morbidity after pancreas resection is still high with postoperative pancreatic fistulas (POPF) being the most frequent complication. However, exocrine insufficiency seems to protect from POPF. In clinical practice, patients showing increased postoperative systemic amylase concentrations appear to frequently develop POPF. We therefore retrospectively examined the occurrence of systemic amylase increase after pancreas resections and its association with the clinical course. PATIENTS AND METHODS: Perioperative data from 739 consecutive pancreas resections were assessed in a prospectively maintained SPSS database. Serum and drain amylase concentrations were determined by routine clinical chemistry. POPFs were graded into A-C according to ISGPF definitions. RESULTS: In patients with reduced serum amylase (n = 89) on day 1 after pancreatoduodenectomy, clinically relevant POPFs were not observed. In patients with normal serum amylase concentrations, clinically relevant POPFs occurred in 9 %, while in 39 % of the patients with more than three times elevated amylase concentrations, a clinically relevant postoperative fistula was observed (p < 0.001). Systemic hyperamylasemia detected on postoperative day 1 after pancreatoduodenectomy was further a good predictor for clinically relevant POPFs (AUROC = 0.797, p < 0.001). CONCLUSION: Patients with a high risk for developing clinically relevant POPFs can be identified on the first postoperative day by determining serum amylase.

Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection.

BACKGROUND: Drain amylase content in the days immediately after major pancreatic resection has been investigated previously as a predictor of postoperative pancreatic fistula (POPF). Its accuracy, however, has not been determined conclusively. The purpose of this study was to evaluate the accuracy of drain amylase content on the first day after major pancreatic resection in predicting the occurrence of POPF. METHODS: A literature search of the MEDLINE, Embase and Scopus(®) databases to 13 May 2015 was performed to identify studies evaluating the accuracy of drain amylase values on day 1 after surgery in predicting the occurrence of POPF. The area under the hierarchical summary receiver operating characteristic (ROC) curve (AUChSROC ) was calculated as an index of accuracy, and pooled estimates of accuracy indices (sensitivity and specificity) were calculated at different cut-off levels. Subgroup and meta-regression analyses were performed to test the robustness of the results. RESULTS: Thirteen studies involving 4416 patients were included. The AUChSROC was 0·89 (95 per cent c.i. 0·86 to 0·92) for clinically significant POPF and 0·88 (0·85 to 0·90) for POPF of any grade. Pooled estimates of sensitivity and specificity were calculated for the different cut-offs: 90-100 units/l (0·96 and 0·54 respectively), 350 units/l (0·91 and 0·84) and 5000 units/l (0·59 and 0·91). Accuracy was independent of the type of operation, type of anastomosis performed and octreotide administration. CONCLUSION: Evaluation of drain amylase content on the first day after surgery is highly accurate in predicting POPF following major pancreatic resection. It may allow early drain removal and institution of an enhanced recovery pathway.

Postoperative drain amylase predicts pancreatic fistula in pancreatic surgery: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: This study to evaluate the utility of drain fluid amylase as a predictor of PF in patients undergoing pancreatic surgery based on the International Study Group of Pancreatic Fistula definitions of pancreatic fistula. METHODS: A comprehensive search was carried out using Pubmed (Medline), Embase, Web of science and Cochrane database for clinical trials, which studied DFA as a diagnostic marker for pancreatic fistula after pancreatic surgery. Sensitivity, specificity and the diagnostic odds ratios with 95% confidence interval were calculated for each study. Summary receiver-operating curves were conducted and the area under the curve was evaluated. RESULTS: A total of 10 studies were included. The pooled sensitivity and specificity of drain fluid amylase Day 1 for the diagnosis of postoperative pancreatic fistula were 81% and 87%, respectively (area under the curve was 0.897, diagnostic odds ratios was 16.83 and 95%CI was 12.66-22.36), the pooled sensitivity and specificity of drain fluid amylase Day 3 for the diagnosis of postoperative pancreatic fistula were 56% and 79%, respectively (area under the curve was 0.668, diagnostic odds ratios was 3.26 and 95%CI was 1.83-5.82) CONCLUSIONS: The drain fluid amylase Day 1, instead of drain fluid amylase Day 3, may be a useful criterion for the early identification of postoperative pancreatic fistula, and a value of drain fluid amylase Day 1 over than 1300 U/L was a risk factor of pancreatic fistula. And the diagnostic accuracy and the proposed cut-off levels of drain fluid amylase Day 1 in predicting the postoperative pancreatic fistula will have to be validated by multicenter prospective studies.

Early Drain Removal--The Middle Ground Between the Drain Versus No Drain Debate in Patients Undergoing Pancreaticoduodenectomy: A Prospective Validation Study.

OBJECTIVE: To perform an unbiased assessment of first postoperative day (POD 1) drain amylase level and pancreatic fistula (PF) after pancreaticoduodenectomy (PD). BACKGROUND: Recent evidence demonstrated that drain abandonment in PD is unsafe. Early drain amylase levels have been proposed as predictors of PF after PD, allowing for selection of patients for early drain removal. METHODS: Daily drain amylase levels were correlated with the development of PF in 2 independent cohorts of patients undergoing PD: training cohort (n = 126; year 2008) and validation cohort (n = 369; years 2009-2012). RESULTS: POD 1 drain amylase level had the highest predictive ability (concordance index: 0.911) for PF in the training cohort. An amylase level of 612 U/L or higher showed the best accuracy (86%), sensitivity (93%), and specificity (79%). Thus, a cutoff value of 600 U/L was utilized. In the validation cohort, 229 (62.1%) patients had a POD 1 drain amylase level of lower than 600 U/L, and PF developed in only 2 (0.9%) cases; whereas in patients with POD 1 drain amylase level of 600 U/L or higher (n = 140) the PF rate was 31.4% (odds ratio [OR] = 52, P < 0.0001). On multivariate analysis, POD 1 drain amylase level of lower than 600 U/L (OR = 0.0192, P < 0.0001) was a stronger predictor of the absence of PF than pancreatic gland texture (OR = 0.193, P = 0.002) and duct diameter (OR = 0.861, P = 0.835). CONCLUSIONS: After PD, the risk of PF is less than 1% if POD 1 drain amylase level is lower than 600 U/L. We propose that in this group, which comprise more than 60% of patients, drains should be removed on POD 1.

Negative predictive value of drain amylase concentration for development of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of morbidity following pancreaticoduodenectomy. A predictive indicator would be highly advantageous. One potential marker is drain amylase concentration (DAC). However, its predictive value has not been fully established. METHODS: 405 patients undergoing pancreaticoduodenectomy at our centre over a 10 year period were reviewed to determine the value of DAC as a predictive indicator for the development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR: 5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal-adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post-operatively were significantly higher in those developing POPF, but with significant overlap. ROC curves revealed optimal threshold values for differentiating POPF and non-POPF patients. A DAC°<°1400 U/ml on day 1 and <768 U/ml on day 2, although having a poor positive predictive value (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our data suggest that post-operative DAC below the determined optimal threshold values on day 1 and 2 following pancreaticoduodenectomy carries high negative predictive value for POPF development and identifies patients in whom early drain removal, and enhanced recovery may be considered, with simultaneous assessment of operative and clinical factors.

Drain amylase value as an early predictor of pancreatic fistula after cephalic duodenopancreatectomy.

AIM: To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period. METHODS: This prospective clinical study included 382 patients with periampullary tumors that were surgically resected at our department between March 2005 and October 2012. A cephalic duodenopancreatectomy (DP) was performed on all patients. Two closed suction drains were placed at the end of the surgery. The highest postoperative DFA value was recorded and analyzed during the first three postoperative days and on subsequent days if the drains were kept longer. Pancreatic fistula (PF) was classified according to the International Study Group of Pancreatic Fistula (ISGPF) criteria. Postoperative complications were defined according to the Dindo-Clavien classification. All data were statistically analyzed. The optimal thresholds of DFA levels on the first, second and third postoperative days were estimated by constructing receiver operating curves, generated by calculating the sensitivities and specificities of the DFA levels. The DFA level limits were used to differentiate between the group without PF and the groups with biochemical pancreatic fistula (BPF) and CRPF. RESULTS: Pylorus-preserving duodenopancreatectomy was performed on 289 (75.6%) patients, while the remaining patients underwent a classic Whipple procedure (CW). The total incidence of PF was 37.7% (grade A 22.8%, grade B 11.0% and grade C 3.9%). Soft pancreatic texture (SPT) was present in 58.3% of patients who developed PF. Mortality was 4.2%. The median DFA value on the first postoperative day (DFA1) in patients who developed PF was 4520 U/L (range 350-99000 U/L) for grade A fistula (BPF) with a SPT and a diameter of the main pancreatic duct (MPD) of ≤ 3 mm. For grade B/C (CRPF), the median DFA1 value was 8501 U/L (range 377-92060 U/L) with a SPT and MPD of ≤ 3 mm. These values were significantly higher when compared to the patients who did not have PF (122; range 5-37875 U/L). The upper limit of DFA values for the first 3 postoperative days in the examined stages of PF were: DFA1 1200 U/L for the BPF and CRPF; DFA3 350 U/L for BPF and DFA3 800 U/L for CRPF. The determined values were highly significant and demonstrated a reliable diagnostic test for both BPF and CRPF. CONCLUSION: DFA1 ≥ 1200 U/L is an important predictive factor for PF of any degree. The trend of DFA3 (decrease of < 50%) compared to DFA1 is a significant factor in the differentiation of CRPF from transient BPF.

Evaluation of a predictive model for pancreatic fistula based on amylase value in drains after pancreatic resection.

BACKGROUND: Amylase value in drains (AVD) is a predictor of pancreatic fistula (PF). We evaluated the accuracy of an AVD-based model. METHODS: Two hundred thirty-one patients underwent pancreatoduodenectomy with pancreaticojejunostomy (PDPJ) or pancreatoduodenectomy with duct-to-mucosa (PDDTM) and distal pancreatectomy (DP). Patients with AVD greater than 5,000 U/L on postoperative day (POD) 1 underwent AVD measurement on POD5. RESULTS: Sensitivity and specificity of POD1 AVD greater than 5,000 in predicting PF were 71% and 90%, respectively. The sensitivity and specificity of POD5 AVD greater than 200 were 90% and 83%, respectively. AVD greater than 1,000 (for PDPJ) and 2,000 U/L (PDDTM and DP) represented the most accurate cutoffs on POD1. AVD greater than 200 (PDPJ), 300 (PDDTM), and 50 U/L (DP) represented the cutoffs with the highest sensitivity in predicting PF on POD5. CONCLUSION: AVD-based model for predicting PF after pancreatic resection is an accurate tool, although AVD cutoffs should be evaluated for each type of operation.

Serum amylase on the night of surgery predicts clinically significant pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVES: Drainage after pancreaticoduodenectomy (PD) remains controversial because the risk for uncontrolled postoperative pancreatic fistula (POPF) must be balanced against the potential morbidity associated with prolonged and possibly unnecessary drainage. This study investigated the utility of the level of serum amylase on the night of surgery [postoperative day (PoD) 0 serum amylase] to predict POPF. METHODS: A total of 185 patients who underwent PD were studied. Occurrences of POPF were graded using the International Study Group on Pancreatic Fistula (ISGPF) classification. Receiver operating characteristic (ROC) analysis identified a threshold value of PoD 0 serum amylase associated with clinically significant POPF (ISGPF Grades B and C) in a test cohort (n = 45). The accuracy of this threshold value was then tested in a validation cohort (n = 140). RESULTS: Overall, 43 (23.2%) patients developed clinically significant POPF. The threshold value of PoD 0 serum amylase for the identification of clinically significant POPF was ≥ 130 IU/l (P = 0.003). Serum amylase of <130 IU/l had a negative predictive value of 88.8% for clinically significant POPF (P < 0.001). Serum amylase of ≥ 130 IU/l on PoD 0 and a soft pancreatic parenchyma were independent risk factors for clinically significant POPF. CONCLUSIONS: Postoperative day 0 serum amylase of <130 IU/l allows for the early and accurate categorization of patients at least risk for clinically significant POPF and may identify patients suitable for early drain removal.

Risk factors of pancreatic fistula after pancreaticoduodenectomy - patients with low drain amylase level on postoperative day 1 are safe from developing pancreatic fistula.

BACKGROUND/AIMS: Based on the criteria of International Study Group on Pancreatic Fistula (ISGPF), the risk factors for grade B/C pancreatic fistula (PF) after pancreaticoduodenectomy (PD) were analyzed in this study. METHODOLOGY: Between October 2006 and August 2010, 114 consecutive patients underwent PD at National Hospital Organization Osaka National Hospital. We compared the clinicopathological features between patients with grade B/C PF and those with PF-free/grade A PF. We also examined the relationship between PF formation and the drain amylase level on post-operative day (POD) 1 and POD 3. RESULTS: Eighteen patients (15.8%) developed grade B/C P. Of these patients, four patients underwent reoperation. The mortality rate in patients with grade B/C PF was 5.6%(1/18). The non-dilated pancreatic duct (≤ 3mm) was the only independent risk factor for grade B/C PF by a multivariate analysis (p=0.026). There were 45 patients who showed low (≤ three times serum amylase level)drain amylase level on POD 1 and none of them developed PF. CONCLUSIONS: Although our study demonstrated that the non-dilated pancreatic duct is significantly correlated with the increased incidence of grade B/CPE patients with low amylase level of drainage fluid on POD 1 are thought to be safe from developing PE.

Elevation of urine trypsinogen 2 is an independent risk factor for pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVES: Previous reports suggested that the urine trypsinogen 2 (U-TRP2) test might be a valuable method for the diagnosis of postoperative pancreatitis after pancreatic surgery. We hypothesize that the elevation of U-TRP2 level after pancreaticoduodenectomy (PD) could be associated with the occurrence of postoperative pancreatic fistula (POPF). METHODS: A total of 130 consecutive patients undergoing PD with duct-to-mucosa pancreaticogastrostomy were included. Urine samples for evaluation of U-TRP2 levels were collected prospectively. Risk factors for POPF were evaluated using univariate and multivariate analyses. RESULTS: Of 130 patients, 19 developed POPF; grade A in 14 (11%), grade B in 3 (2%), and grade C in 1 (1%). Univariate analysis demonstrated that a nonobstructed main pancreatic duct, a pancreatic duct less than 3 mm, soft texture of the pancreatic gland, a PD with antrectomy, PD with hepatic resection, hyperamylasemia, and elevation of U-TRP2 levels (>50 µg/L) were significantly associated with POPF (P < 0.05). By multivariate analysis, elevation of U-TRP2 levels (odds ratio = 4.544, P = 0.029) was the only independent risk factor that correlated with POPF. CONCLUSIONS: Elevation of U-TRP2 level is an independent risk factor for POPF after PD. Elevated U-TRP2 level might be the consequence of the postoperative pancreatitis, and postoperative pancreatitis may play an important role in the pathogenic mechanism of POPF after PD.