Persisting ratio of total amylase output in drain fluid can predict postoperative clinical pancreatic fistula

Background/purpose

A consistent predictor for pancreatic fistula (PF) development in the early period after pancreatic resection is still lacking.

Patients and methods

A total of 54 consecutive patients undergoing pancreatic resection were enrolled between June 2007 and April 2010. Pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) were performed in 38 and 16 patients, respectively. For the purpose of finding an early predictor for PF development, we investigated drain amylase levels (d-Amy, IU/mL), drain output volume (d-Vol, mL/day) and drain amylase output (Amy-V, IU/day) on postoperative days (POD) 1 and 3. Amy-V was calculated as the product of d-Amy and d-Vol, and was expressed as the sum of values obtained from all drains. In addition, the ratio of d-Amy or Amy-V on POD3 to that on POD1 was calculated as the persisting ratio in each patient.

Results

The overall incidence of clinical PF (International Study Group on Pancreatic Fistula Grade B and C) was 16.7%, occurring in 13.1% after PD and 25% after DP. All PF occurred in cases with a remnant pancreas of soft texture. There was no significant difference in d-Amy, d-Vol, or Amy-V on POD1 and POD3 between patients with and without clinical PF. The persisting ratio of Amy-V was significantly lower in patients without clinical PF compared to those with clinical PF (P?=?0.029). Furthermore, the persisting ratio of Amy-V was significantly lower in patients with Grade A PF compared to those with Grade B PF (P?=?0.03).

Conclusion

The persisting ratio of drain amylase output is a new significant predictive factor for clinical PF development.     

Prediction of pancreatic fistula by amylase levels of drainage fluid on the first day after pancreatectomy

BACKGROUND/AIMS: We investigated whether it would be useful to monitor amylase levels of drainage fluid after pancreatic surgery for prediction of pancreatic fistula. METHODOLOGY: Twenty-six cases in which amylase levels of drainage fluid were determined after pancreatic surgery, were divided into 14 cases who did not develop pancreatic fistula and 12 cases who developed pancreatic fistula. Changes in amylase levels of sera and urine as well as drainage fluid were monitored. RESULTS: Amylase levels of drainage fluid were significantly higher in cases with pancreatic fistula than in cases without pancreatic fistula on the first postoperative day, but those levels in both groups decreased until the 7th postoperative day without significant difference. However, those levels in cases with pancreatic fistula significantly increased from the 9th postoperative day whereas the levels in cases without pancreatic fistula further decreased. There was no significant difference in amylase levels of sera or urine. CONCLUSIONS: Amylase levels of drainage fluid on the first postoperative day may be useful to predict development of pancreatic fistula and to plan appropriate management.     

Correlation of serum amylase levels with pancreatic pathology and pancreatitis etiology

Fifty-one patients, 35 men and 16 women, with acute pancreatitis were studied prospectively with early computed tomography (CT). Etiological factors for acute pancreatitis were alcohol abuse (n = 28), gallstones (n = 14), pancreas cancer (n = 3) and miscellaneous (n = 6). Admission serum amylase levels ranged between 68-5,856 U/L with a mean of 1,090 +/- 1,369 U/L. The mean serum amylase level was significantly different between patients with alcoholic pancreatitis (439 +/- 302 U/L) and gallstone pancreatitis (2,480 +/- 1,575) (p less than 0.001). The initial pancreatic CT findings and corresponding mean serum amylase levels were in CT grade A (pancreas normal) 1,499 +/- 1,569 U/L (n = 11), in CT grade B (pancreatic enlargement with inflammation confined to pancreas) 1,144 +/- 1,542 U/L (n = 18), in CT grade C (inflammatory extension into one peripancreatic space) 722 +/- 962 U/L (n = 13) and in CT grade D (inflammatory extension into two or more peripancreatic spaces) 590 +/- 369 U/L (n = 9). However, on separating the etiology subgroups, there was no increase or decrease in the serum amylase level with increasing pancreatic inflammatory involvement. Pancreatic complications (pseudocyst, abscess, necrosis) requiring surgical intervention developed only in patients with CT grades C and D. We conclude that within the etiologic subgroups there is no correlation between the initial serum amylase level and the extent of pancreatic involvement visualized by CT. These findings provide a pathological basis for the clinical observation that the initial serum amylase level cannot predict the outcome in acute pancreatitis.     

Histological pancreatic findings correlate with computed tomography attenuation and predict postoperative pancreatic fistula following pancreatoduodenectomy

BackgroundAlthough a soft pancreas is a widely-accepted reliable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), there is no established preoperative evaluation of pancreatic texture.MethodsTwo hundred thirty-seven patients who underwent PD with histological pancreatic assessment were retrospectively enrolled. The degree of fibrosis and fatty infiltration was scored histologically as seven grades and five grades, respectively. Computed tomography (CT) attenuation of the pancreas was measured on preoperative unenhanced CT images. Correlations between the CT attenuation of the pancreas and the histological pancreatic findings, and the development of POPF were analyzed.ResultsThe fibrosis grade was significantly higher for hard pancreas than for soft pancreas (p < 0.001), whereas the fatty infiltration grade was similar between the two types (p = 0.161). CT attenuation of the pancreas was inversely correlated with both fibrosis grade (Spearman's rank correlation coefficient ([r] = ?0.609, p < 0.001) and fatty infiltration grade (r = ?0.382, p < 0.001). Multivariate analysis showed that body mass index ≥25 kg/m² (odds ratio [OR]: 5.64, p < 0.001) and fibrosis grade ≤2 (OR: 18.0, p < 0.001) were independent risk factors for clinically significant POPF.ConclusionHistological pancreatic texture can be evaluated with CT attenuation and might be helpful in preoperatively predicting the development of POPF after 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.     

Elastase-1 vs trypsin, lipase and amylase serum levels in pancreatic diseases

Serum levels of elastase-1 were measured in 174 patients with pancreatic diseases and in 131 controls and were compared with the circulating levels of trypsin, lipase and amylase and with clinical data. In 48 patients with chronic pancreatitis serum enzyme levels were also compared with the pancreatic exocrine capacity. About 50% of the patients with chronic pancreatic disease showed increased levels of serum elastase, sometimes even in the face of long lasting pain-free periods, and/or of severe pancreatic impairment. On the contrary, serum trypsin and lipase were almost always either normal or below the normal range in the absence of painful relapses and/or in the presence of an impairment of the exocrine pancreatic function. A strict correlation was found between elastase-1 and trypsin (r = 0.778) and lipase (r = 0.834). However, controls and patients with chronic pancreatic diseases behaved differently, an increase in trypsin and in lipase levels being associated in the patients with chronic pancreatitis with an increase in elastase-1 values significantly larger than that observed in controls. These findings raise the hypothesis, at present unproven, that trypsin and lipase serum assays are more reliable indices of pancreatic exocrine function, whereas serum elastase-1 levels may indicate the presence of acute pancreatic episodes, even if subclinical, the importance of which, in the natural history of the disease, remains unknown.     

Elastase-1 vs trypsin, lipase and amylase serum levels in pancreatic diseases

Summary Serum levels of elastase-1 were measured in 174 patients with pancreatic diseases and in 131 controls and were compared with the circulating levels of trypsin, lipase and amylase and with clinical data. In 48 patients with chronic pancreatitis serum enzyme levels were also compared with the pancreatic exocrine capacity. About 50% of the patients with chronic pancreatic disease showed increased levels of serum elastase, sometimes even in the face of long lasting pain-free periods, and/or of severe pancreatic impairment. On the contrary, serum trypsin and lipase were almost always either normal or below the normal range in the absence of painful relapses and/or in the presence of an impairment of the exocrine pancreatic function. A strict correlation was found between elastase-1 and trypsin (r=0.778) and lipase (r=0.834). However, controls and patients with chronic pancreatic diseases behaved differently, an increase in trypsin and in lipase levels being associated in the patients with chronic pancreatitis with an increase in elastase-1 values significantly larger than that observed in controls. These findings raise the hypothesis, at present unproven, that trypsin and lipase serum assays are more reliable indices of pancreatic exocrine function, whereas serum elastase-1 levels may indicate the presence of acute pancreatic episodes, even if subclinical, the importance of which, in the natural history of the disease, remains unknown. *** DIRECT SUPPORT *** A00DX035 00007     

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.     

Pasireotide is not effective in reducing the development of postoperative pancreatic fistula

Background

In a single trial, perioperative pasireotide demonstrated reduction in postoperative pancreatic fistula (POPF) following pancreatectomy, yet recent studies question the efficacy of this drug.

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.     

Nomogram for predicting postoperative pancreatic fistula

BackgroundPrevious studies analyzed risk factors for postoperative pancreatic fistula (POPF) and developed risk prediction tool using scoring system. However, no study has built a nomogram based on individual risk factors. This study aimed to evaluate individual risks of POPF and propose a nomogram for predicting POPF.MethodsFrom 2007 to 2016, medical records of 1771 patients undergoing pancreaticoduodenctomy were reviewed retrospectively. Variables with p < 0.05 in multivariate logistic regression analysis were included in the nomogram. Internal performance validation was executed using a repeated cross validation method.ResultsOf 1771 patients, 222 (12.5%) experienced POPF. In multivariable analysis, sex (p = 0.004), body mass index (BMI) (p < 0.001), ASA score (p = 0.039), preoperative albumin (p = 0.035), pancreatic duct diameter (p = 0.002), and location of tumor (p < 0.001) were identified as independent predictors for POPF. Based on these six variables, a POPF nomogram was developed. The area under the curve (AUC) estimated from the receiver operating characteristic (ROC) graph was 0.709 in the train set and 0.652 in the test set.ConclusionsA POPF nomogram was developed. This nomogram may be useful for selecting patients who need more intensified therapy and establishing customized treatment strategy.     

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.     

Drain data to predict clinically relevant pancreatic fistula

Background

Post-operative pancreatic fistula (POPF) is a common and potentially devastating complication of pancreas resection. Management of this complication is important to the pancreas surgeon.

Objective

The aim of the present study was to evaluate whether drain data accurately predicts clinically significant POPF.

Methods

A prospectively maintained database with daily drain amylase concentrations and output volumes from 177 consecutive pancreatic resections was analysed. Drain data, demographic and operative data were correlated with POPF (ISGPF Grade: A – clinically silent, B – clinically evident, C – severe) to determine predictive factors.

Results

Twenty-six (46.4%) out of 56 patients who underwent distal pancreatectomy and 52 (43.0%) out of 121 patients who underwent a Whipple procedure developed a POPF (Grade A-C). POPFs were classified as A (24, 42.9%) and C (2, 3.6%) after distal pancreatectomy whereas they were graded as A (35, 28.9%), B (15, 12.4%) and C (2, 1.7%) after Whipple procedures. Drain data analysis was limited to Whipple procedures because only two patients developed a clinically significant leak after distal pancreatectomy.The daily total drain output did not differ between patients with a clinical leak (Grades B/C) and patients without a clinical leak (no leak and Grade A) on post-operative day (POD) 1 to 7. Although the median amylase concentration was significantly higher in patients with a clinical leak on POD 1–6, there was no day that amylase concentration predicted a clinical leak better than simply classifying all patients as ‘no leak’ (maximum accuracy =86.1% on POD 1, expected accuracy by chance =85.6%, kappa =10.2%).

Conclusion

Drain amylase data in the early post-operative period are not a sensitive or specific predictor of which patients will develop clinically significant POPF after pancreas resection.     

Intraoperative amylase level of pancreatic juice as a simple predictor of pancreatic fistula after pancreaticoduodenectomy

IntroductionA soft remnant texture of the pancreas is commonly accepted as a risk factor for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). However, its assessment is subjective. The aim of this study was to evaluate the significance of intraoperative amylase level of the pancreatic juice as a risk factor of POPF after PD.MethodThis study included 75 patients who underwent PD between November 2014 and April 2020 at Jikei University Hospital. We investigated the relationship between pancreatic texture, intraoperative amylase level of pancreatic juice, results of the pathological evaluations, and the incidence of POPF.ResultsTwenty-three patients (31%) developed POPF. The significant predictors of POPF were non-ductal adenocarcinoma (p < 0.01), soft pancreatic remnant (p < 0.01), high intraoperative blood loss (p < 0.01), high intraoperative amylase level of pancreatic juice (p < 0.01), and low pancreatic fibrosis (p < 0.01). Multivariate analysis revealed that the significant independent predictors of POPF were high intraoperative blood loss (p < 0.01) and high intraoperative amylase level of pancreatic juice (p = 0.02). Receiver operating characteristic (ROC) analysis showed that the cut-off value for the intraoperative amylase level of pancreatic juice was 2.17 × 10⁵ IU/L (area under the curve = 0.726, sensitivity = 95.7%, and specificity = 50.0%)ConclusionsThe intraoperative amylase level of pancreatic juice is a reliable objective predictor for POPF after PD.     

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.

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.