Beyond Binary Mortality Endpoints: The T-MOD PD Framework (Timing-Mechanism-Opportunity-Disease) for Phenotype-Specific Root Cause Analysis of Mortality after Pancreatoduodenectomy A Retrospective Observational Cohort Study.
To evaluate the T-MOD PD (Timing-Mechanism-Opportunity-Disease) framework for classifying mortality after pancreatoduodenectomy (PD), focusing on preventability and rescue opportunities. Pancreatoduodenectomy mortality (2-10%) is reported as binary endpoints, obscuring distinctions between surgery-related and systemic causes and limiting targeted quality improvement. Retrospective analysis of 1,727 consecutive PDs (2014-2024) at a high-volume centre. All 58 deaths (3.4%) were independently adjudicated across four axes: Timing (T1-T3), Mechanism (M1-M3), Opportunity (O1-O4), and Disease (D1-D3). Deaths were categorized as surgery-attributable potentially preventable (SAPM), surgery-attributable non-preventable (SANPM), or non-surgery-attributable mortality (NSAM). Striking phenotypic clustering emerged: 38% of deaths (22/58) converged in T1M1O1D1 (early, surgery-related, strategically modifiable, resectable disease), with 19% (11/58) in T2M1O1D1. Together, these postoperative pancreatic fistula (POPF)-driven phenotypes accounted for 57% of mortality. Domain analysis revealed 66% early deaths (T1), 74% surgery-related mechanisms (M1), and critically, 72% potentially modifiable opportunities (O1: 72%; O2: 22%; O3: 2%; O4: 3%). Overall, 74% were classified as SAPM. Timeline reconstruction identified median 72-hour delays in recognition and escalation despite warning signs at postoperative day 5-6, with 22-day median interval from clinically relevant POPF diagnosis to death, suggesting 35-40% preventability in the dominant phenotype. Perfect interobserver agreement was achieved (κ=1.0). T-MOD PD provides reproducible mortality phenotyping revealing 72% of deaths are potentially modifiable, with dominant phenotypes sharing POPF pathways and identifiable rescue delays, enabling phenotype-specific quality improvement.
- Front Matter
3
- 10.1016/j.gie.2010.05.016
- Aug 27, 2010
- Gastrointestinal Endoscopy
Distal pancreatectomy: another indication for prophylactic pancreatic stenting?
- Research Article
1
- 10.1177/000313481808400325
- Mar 1, 2018
- The American Surgeon™
Postoperative pancreatic fistula (PF) is a relatively frequent and occasionally fatal complication of pancreatoduodenectomy (PD). Several risk factors for PF have been reported, including high drain amylase level (D-AMY). Among the 140 consecutive patients who underwent PD, we analyzed 110 cases with D-AMY measurements over time after PD. According to the D-AMY change, we divided patients into five patterns and defined delayed PF cases. We analyzed clinical characteristics, including serum amylase and D-AMY, and examined the correlation between the period of drain insertion and PF grade. In 15 delayed PF cases, 12 cases were grade B or C, pancreatic cancer was less frequent, pancreatic ducts were smaller, and soft pancreas texture was more commonly observed. The D-AMY on postoperative day (POD) 1 was higher in cases of delayed PF compared with non-PF cases (P < 0.0001). In 28 cases with drain removal before POD 7, grade B or C PF was not observed afterward. The average D-AMY on POD 1 in cases with drain removal before POD 1 was significantly lower than in delayed PF cases. Although further studies are required to determine the most appropriate timing of drain removal, it is thought that intra-abdominal drains should be removed within seven days of PD in cases without signs of PF. On the other hand, delayed PF should be considered in cases of soft pancreas texture and/or high D-AMY on POD 1, even if D-AMY levels are low on POD 3 or decreasing on POD 5.
- Research Article
137
- 10.1007/s00268-013-1998-5
- Mar 15, 2013
- World Journal of Surgery
Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) remains a challenge even at high-volume centers. This study was designed to analyze perioperative risk factors for POPF after PD and evaluate the factors that predict the extent and severity of leak. Demographic data, preoperative, intraoperative, and postoperative variables were collected. A total of 471 consecutive patients underwent PD in our center. Fifty-seven patients (12.1 %) developed a POPF of any type; 21 patients (4.5 %) had a fistula type A, 22 patients (4.7 %) had a fistula type B, and the remaining 14 patients (3 %) had a POPF type C. Cirrhotic liver (P = 0.05), BMI > 25 kg/m(2) (P = 0.0001), soft pancreas (P = 0.04), pancreatic duct diameter <3 mm (0.0001), pancreatic duct located <3 mm from the posterior border (P = 0.02) were significantly associated with POPF. With the multivariate analysis, both BMI and pancreatic duct diameter were demonstrated to be independent factors. The hospital mortality in this series was 11 patients (2.3 %), and the development of POPF type C was associated with a significantly increased mortality (7/14 patients). The following factors were predictors of clinically evident POPF: a postoperative day (POD) 1 and 5 drain amylase level >4,000 IU/L, WBC, pancreatic duct diameter <3 mm, and pancreatic texture. Cirrhotic liver, BMI, soft pancreas, pancreatic duct diameter <3 mm, pancreatic duct near the posterior border are risk factors for development of POPF. In addition a drain amylase level >4,000 IU/L on POD 1 and 5, WBC, pancreatic duct diameter, pancreatic texture may be predictors of POPF B, C.
- Research Article
125
- 10.1007/s11605-015-2884-2
- Jul 11, 2015
- Journal of Gastrointestinal Surgery
The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy
- Research Article
- 10.3390/medicina62010094
- Jan 1, 2026
- Medicina (Kaunas, Lithuania)
Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45-85) years; mean body mass index (BMI) 26.6 kg/m2). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols.
- Abstract
1
- 10.1016/j.hpb.2020.04.602
- Jan 1, 2020
- HPB
Predictors of prolonged pancreatic fistula in patients undergoing pancreatoduodenectomy (whipple procedure)
- Research Article
61
- 10.1007/s00268-013-2149-8
- Jul 10, 2013
- World Journal of Surgery
Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a worrisome and life-threatening complication. Recently, early drain removal has been recommended as a means of preventing POPF. The present study sought to determine how to distinguish clinical POPF from non-clinical POPF in the early postoperative period after PD to aid in early drain removal. From March 2002 through December 2010, 176 patients underwent PD and were enrolled in this study to examine factors predictive of clinical POPF after PD. POPF was defined and classified according to the International Study Group of Pancreatic Surgery guideline, and grade B/C POPF was defined as clinical POPF. Grade A POPF occurred in 39 (22.2 %) patients, grade B in 19 (10.8 %) patients, and grade C in 11 (6.3 %) patients. Clinical POPF (grade B/C) occurred in 17.1 % of patients. Multivariate analysis revealed male gender and body mass index (BMI) ≥22.5 kg/m(2) to be the independent preoperative risk factors predictive of POPF. Receiver operating characteristic curves showed that the combination of drain amylase ≥750 IU/L, C-reactive protein (CRP) ≥20 mg/dL, and body temperature ≥37.5 °C on postoperative day 3 could effectively distinguish clinical POPF from non-clinical POPF. Sensitivity, specificity, and accuracy were 84.6, 98.2, and 95.7 %, respectively. Male gender and BMI ≥22.5 were the independent preoperative predictive risk factors for POPF. We assume that when amylase is <750 IU/L, serum CRP is <20 mg/dL, and body temperature is <37.5 °C the drain can safely be removed, even if POPF is indicated.
- Research Article
47
- 10.1002/jhbp.11
- Jun 26, 2013
- Journal of Hepato-Biliary-Pancreatic Sciences
Postoperative pancreatic fistula (PF) remains a major complication after pancreaticoduodenectomy (PD). We aimed to investigate the predictors of clinically relevant PF after PD. We retrospectively analyzed the predictive factors of relevant grade B/C PF using logistic regression analysis of 100 consecutive patients who underwent PD. PF was defined in accordance with the International Study Group on PF (ISGPF). White blood cell count (WBC) of 73.6 × 10(2) /μl, C-reactive protein (CRP) of 9.3 mg/dl and amylase value in drains (d-amylase) of 647 U/I on postoperative day (POD) 4 were proposed as the cut-off values for predicting grade B/C PF with high accuracy by the receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis revealed that the three factors as significant predictive factors and the predicted probability of detecting grade B/C PF was calculated by the following formula; P = 1/[1 + exp{-(2.033 × WBC+3.269 × CRP+2.698 × d-amylase-4.122)}]. P > 0.5 indicates the prospective incidence of the PF. When the cut-off values of the three significant predictors were substituted into the formula, P always showed above 0.5 if more than two predictors were above their cut-off values, indicating a high probability of grade B/C PF. White blood cell count, CRP and d-amylase on POD4 were predictive factors for clinically relevant PF after PD. These findings indicate that our formula is useful for management of drain after PD.
- Research Article
58
- 10.1016/j.jamcollsurg.2014.01.048
- Feb 18, 2014
- Journal of the American College of Surgeons
Does Postoperative Drain Amylase Predict Pancreatic Fistula after Pancreatectomy?
- Research Article
- 10.1016/j.hpb.2019.10.2217
- Jan 1, 2019
- HPB
A modified definition of POPF with cost validation for PPPD
- Research Article
2
- 10.55730/1300-0144.5693
- Oct 26, 2023
- Turkish Journal of Medical Sciences
Background/aimEarly identification of patients at risk for developing postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) may facilitate drain management. In this context, it was aimed to examine the efficiency of the serum amylase (SA) value on postoperative day (PoD) 1 in predicting the occurrence of POPF.Materials and methodsA total of 132 patients who underwent PD were studied. Occurrences of POPF were classified according to the International Study Group on Pancreatic Fistula classification as a biochemical leak (BL) or clinically relevant grade b/c POPF (CR-POPF). Receiver operating characteristic analysis identified a threshold value of SA on PoD 1 associated with POPF formation.ResultsOverall, 66 (50%) patients had POPF, including 51 (38.7%) with BL and 15 with CR-POPF (11.3%). The threshold value of SA associated with the development of POPF was 120 IU/L (odds ratio [OR]: 3.20; p = 0.002). In the multivariate analysis, independent POPF risk factors were SA ≥120 IU/L, soft pancreatic texture, and high-risk pathology (i.e., duodenal, biliary, ampullary, islet cell, and benign tumors); SA ≥120 IU/L outperformed soft pancreatic texture and high-risk pathology in predicting POPF, respectively (OR: 2.22; p = 0.004 vs. OR: 1.37; p = 0.012 vs. OR: 1.35; p = 0.018). In a subset analysis according to gland texture (soft vs. hard), patients with soft pancreatic texture exhibited a significantly higher incidence of POPF (63.4% vs. 34.4%) and SA ≥120 IU/L (52.1% vs. 27.9%); SA <120 IU/L had a negative predictive value of 82.5% for developing POPF in patients with hard pancreatic texture (OR: 4.28, p = 0.028).ConclusionA SA value ≥120 IU/L on the day after PD, which is the strongest predictor for POPF, can be used as a biomarker of the occurrence of POPF. The advantage of SA measurement is that it can contribute to identifying suitable patients for early drain removal.
- Research Article
7
- 10.1093/bjsopen/zrac124
- Jan 6, 2023
- BJS Open
Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD). A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD. From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold. NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.
- Research Article
12
- 10.1016/j.jss.2017.08.006
- Dec 9, 2017
- Journal of Surgical Research
Ketorolac use may increase risk of postoperative pancreatic fistula after pancreaticoduodenectomy
- Research Article
12
- 10.1097/md.0000000000000339
- Jan 1, 2015
- Medicine
This article aims to identify risk factors for postoperative pancreatic fistula (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy (PD).POPF significantly contributes to mortality and morbidity in patients who undergo PD. Previously identified predictors for POPF often have low predictive accuracy. Therefore, accurate POPF predictors are needed.In this prospective cohort study, we measured the clinical and biochemical factors of 61 patients who underwent PD and diagnosed POPF according to the definition of the International Study Group of Pancreatic Fistula. We analyzed the association between POPF and various factors, identified POPF risk factors, and evaluated the predictive power of the GPAR on POD3 and the levels of serum and ascites amylase.Of the 61 patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum, POD1 median output of pancreatic drain fluid volume, and GPAR were significantly associated with POPF. The color of the pancreatic drain fluid and high GPAR were independent risk factors. Although serum and ascites amylase did not predict POPF accurately, the cutoff value was 1.24, and GPAR predicted POPF with high sensitivity and specificity.This is the first report demonstrating that high GPAR on POD3 is a risk factor for POPF and showing that GPAR is a more accurate predictor of POPF than the previously reported amylase markers.
- Book Chapter
- 10.1007/978-3-662-47181-4_22
- Jan 1, 2017
Pancreatic anastomosis has always been the Achilles heel of pancreaticoduodenectomy (PD), and postoperative pancreatic fistula (POPF) is the leading cause of morbidity and mortality. Currently, there is no universally accepted standard technique for pancreatic reconstruction after PD. POPF after PD is still unsatisfactorily high, at 5–25%, even in high-volume centers. There are two major variants of pancreatic reconstruction after PD: pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). PG has been claimed to be a better pancreatic reconstruction in reducing the incidence and severity of POPF by most retrospective studies. However, not all of the published randomized controlled trials confirm the superiority of PG. In recent meta-analysis of published randomized controlled trials, PG has been shown to be associated with lower rate of POPF as compared with classic PJ. Blumgart PJ has been reported to decrease the POPF to 4.3–6.9%, significantly lower than the 10–20% of other techniques. Based on the matched historical control study at our institute, the modified Blumgart PJ appears to be superior to PG in reducing the incidence and severity of clinically relevant postoperative pancreatic fistula (CR-POPF). The modified Blumgart PJ can therefore be recommended as a fast, simple, and safe alternative for pancreatic reconstruction after PD.
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