The invisible fluid leaking from a partially resected pancreas is associated with complications including postoperative pancreatic fistula (POPF), calling for strategies to visualize intraoperative leakage. This single-arm, monocentric trial aims to evaluate the usefulness and safety of SmartPAN, a hydrogel that reacts to alkali pancreatic fluids by changing color and thus enables the surgeon to take immediate action to close leakage.

Patients awaiting partial pancreatic resection for any indication were recruited to receive intraoperative SmartPAN application. Trial endpoints covered SmartPAN usability and safety according to reports completed by surgeons after each operation, laboratory measurements of nonbiodegradable compounds in body fluids, and clinical evaluations over 30 days of follow-up.

In total 42 patients were recruited to the trial and 29 received partial pancreatic resection with SmartPAN application according to protocol. All 16 attending surgeons rated SmartPAN as easy to learn and use, mostly agreeing that it was useful and that they intended to use it frequently. No adverse effects or complications were associated with SmartPAN, nor were its compounds detected in blood or abdominal fluids. Positive leakage response was detected in 10/29 surgeries. POPF developed in 7 patients, including 2 intraoperatively detected leakages, thereof 1 with targeted closure as well as 5 with no leakage detected.

This study represents the first-in-human clinical trial of SmartPAN and the precursor to randomized controlled trials. The outcomes support SmartPAN's clinical usability and safety and showcase the device's potential to intraoperatively visualize precursors of POPF.

Postoperative day (POD) 1 drain amylase concentration (DAC) is considered the most accurate predictor for the development of a clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Recent studies have associated drain placement with negative postoperative outcomes. This study aims to evaluate multiple biochemical markers and their associations with CR-POPF development in order to identify a reliable, non-drain dependent alternative to DAC.

This is a review of 53 consecutive PD patients between 2021 and 2022. Albumin, C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), DAC, white blood cell count, and procalcitonin values were compared by CR-POPF status. The discriminatory abilities of CAR, CRP, and DAC for CR-POPF were compared using receiver operating characteristic (ROC) curves.

Six of 51 included patients developed a CR-POPF. Receiver operating characteristic curve analysis produced an area under the curve of .977 for POD 1 DAC (cut-off 5131.0 IU/L, sensitivity 100%, specificity 95.5%), .858 for POD 1 CRP (cut-off 52.5 mg/L, sensitivity 100%, specificity 72.7%), and 1.000 for POD 3 CAR (cut-off 99.2, sensitivity and specificity 100%). POD 3 CAR produced a positive and negative predictive value of 100%.

The CAR and CRP provide early and accurate identification of patients with post-PD CR-POPFs. These markers offer a method of safe CR-POPF detection, when the gold standard DAC is unavailable, ultimately allowing for early intervention and patient rescue.

The aim of this study was to evaluate the predictive value of the first postoperative day (POD1) drain fluid amylase in predicting pancreatic fistula formation following pancreaticoduodenectomy (PD).

One-hundred and eighty-five prospective patients undergoing PD between April 2014 and April 2018 were studied retrospectively. Cut-off point to predict the development of POPF was determined by median values for drain fluid amylase of 1883 U/L. Patients were classified into two groups according to POD1 drain fluid amylase values: <1883 U/L (Group 1) and ≥1883 U/L (Group 2). Differences between the groups with clinically relevant POPF and without POPF were evaluated.

The incidence of POPF was 17.2%. POD1 amylase level was the strongest predictor of POPF, with levels of higher than 1883 U/L demonstrating the best accuracy (87.5%), sensitivity (78.1%), specificity (89.5%), positive predictive value (60.9%), and negative predictive value (95.1%). One-hundred and forty-four patients (77.8%) had a POD1 drain amylase level of less than 1883 U/L, and POPF developed in only seven (3.7%) cases, whereas in patients with POD1 drain amylase level of 1883 U/L or higher (n= 41), the POPF rate was 31.4% [OR: 22.24, 95% CI (7.930-62.396), p<0.001].

The cut-off point of POD1 drain fluid amylase level (1883 U/L) might predict the clinically relevant POPF with adequate sensitivity and specificity rates in patients undergoing pancreatic resection.

Several indicators are recognized in the development of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). However, drain fluid volume (DFV) remains poorly studied. We aimed to discover the predictive effects of DFV and guide clinical management.

We retrospectively reviewed the clinical data of patients that received PD between January 2015 and December 2019 in a high-volume center. DFV was analyzed as a potential risk factor and postoperative short-term outcomes as well as drain removal time were compared stratified by different DFV levels. Receiver operating characteristic curves and area under curves (AUC) were compared for DFV alone and DFV combined with drain fluid amylase (DFA). Subgroup analysis of DFV stratified by DFA evaluated the predictability of CR-POPF.

CR-POPF occurred in 19.7% of 841 patients. Hypertension, postoperative day 3 (POD3) DFA ≥ 300 U/L, and POD3 DFV ≥ 30 mL were independent risk factors, while pancreatic main duct diameter ≥ 3 mm was a protective factor. POD3 DFV ≥ 30 mL increased the overall occurrences of CR-POPF and major complications (P = 0.017; P = 0.029). POD3 DFV alone presented a low predictive value (AUC 0.602), while POD3 DFV combined with DFA had a high predictive value (AUC 0.759) for CR-POPF. Subgroup analysis showed that the combination of POD3 DFV ≥ 30 mL and DFA ≥ 300 U/L led to higher incidences of CR-POPF (P = 0.003).

CR-POPF is common after PD, and high DFV combined with DFA may predict its occurrence and facilitate appropriate management.

Postoperative pancreatic fistula (POPF) represents one of the most severe complications following pancreatic surgery. Despite being a leading cause of morbidity and mortality, its pathophysiology is poorly understood. In recent years, there has been growing evidence to support the role of postoperative or post-pancreatectomy acute pancreatitis (PPAP) in the development of POPF. This article reviews the contemporary literature on POPF pathophysiology, risk factors, and prevention strategies.

A literature search was conducted using electronic databases, including Ovid Medline, EMBASE, and Cochrane Library, to retrieve relevant literature published between 2005 and 2023. A narrative review was planned from the outset.

A total of 104 studies fulfilled criteria for inclusion. Forty-three studies reported on technical factors predisposing to POPF, including resection and reconstruction technique and adjuncts for anastomotic reinforcement. Thirty-four studies reported on POPF pathophysiology. There is compelling evidence to suggest that PPAP plays a critical role in the development of POPF. The acinar component of the remnant pancreas should be regarded as an intrinsic risk factor; meanwhile, operative stress, remnant hypoperfusion, and inflammation represent common mechanisms for acinar cell injury.

The evidence base for PPAP and POPF is evolving. Future POPF prevention strategies should look beyond anastomotic reinforcement and target underlying mechanisms of PPAP development.

Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis.

Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies.

Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1.

The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.

To evaluate whether postoperative serum hyperamylasemia (POH), with drain fluid amylase (DFA) and C-reactive protein (CRP), improves the Fistula Risk Score (FRS) accuracy in assessing the risk of a postoperative pancreatic fistula (POPF).

The FRS predicts POPF occurrence using intraoperative predictors with good accuracy but intrinsic limits.

Outcomes of patients who underwent pancreaticoduodenectomies between 2016 and 2021 were evaluated across FRS-risk zones and POH occurrence. POH consists of serum amylase activity greater than the upper limit of normal (52 U/l), persisting within the first 48 hours postoperatively (postoperative day -POD- 1 and 2).

Out of 905 pancreaticoduodenectomies, some FRS elements, namely soft pancreatic texture (odds ratio (OR) 11.6), pancreatic duct diameter (OR 0.80), high-risk pathologic diagnosis (OR 1.54), but not higher blood loss (OR 0.99), were associated with POH. POH was an independent predictor of POPF, which occurred in 46.8% of POH cases ( P <0.001). Once POH occurs, POPF incidence rises from 3.8% to 42.9%, 22.9% to 41.7%, and 48.9% to 59.2% in patients intraoperatively classified at low, moderate and high FRS risk, respectively. The predictive ability of multivariable models adding POD 1 drain fluid amylase, POD 1-2 POH and POD 3 C-reactive protein to the FRS showed progressively and significantly higher accuracy (AUC FRS=0.82, AUC FRS-DFA=0.85, AUC FRS-DFA-POH=0.87, AUC FRS-DFA-POH-CRP=0.90, DeLong always P <0.05).

POPF risk assessment should follow a dynamic process. The stepwise retrieval of early, postoperative biological markers improves clinical risk stratification by increasing the granularity of POPF risk estimates and affords a possible therapeutic window before the actual morbidity of POPF occurs.

To conduct a systematic review and meta-analysis of randomized controlled trials compared laparoscopic pancreatoduodenectomy (LPD) versus open pancreatoduodenectomy (OPD) in patients with periampullary tumors.

LPD has gained attention; however, its safety and efficacy versus OPD remain debatable.

We searched PubMed and Embase. Primary outcomes were the length of hospital stay (LOS) (day), Clavien-Dindo grade ≥III complications, and 90-day mortality. Secondary outcomes were blood loss (milliliter), blood transfusion, duration of operation (minute), readmission, reoperation, comprehensive complication index score, bile leak, gastrojejunostomy or duodenojejunostomy leak, postoperative pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, surgical site infection, intra-abdominal infection, number of harvested lymph nodes, and R0 resection. Pooled odds ratio (OR) or mean difference (MD) of data was calculated using the random-effect model. The grading of recommendations, assessment, development and evaluation approach was used for grading the level of evidence.

Four randomized controlled trials yielding 818 patients were included, of which 411 and 407 patients underwent LPD and OPD, respectively. The meta-analysis concluded that 2 approaches were similar, except in the LPD group, the LOS tended to be shorter [MD=-2.54 (-5.17, 0.09), P =0.06], LOS in ICU was shorter [MD=-1 (-1.8, -0.2), P =0.01], duration of operation was longer [MD=75.16 (23.29, 127.03), P =0.005], blood loss was lower [MD=-115.40 (-152.13, -78.68), P <0.00001], blood transfusion was lower [OR=0.66 (0.47, 0.92), P =0.01], and surgical site infection was lower [OR=0.35 (0.12, 0.96), P =0.04]. The overall certainty of the evidence was moderate.

Within the hands of highly skilled surgeons in high-volume centers, LPD is feasible and as safe and efficient as OPD.

Postoperative pancreatic fistula (POPF) is a major complication of pancreatic surgery. Drain fluid amylase concentration (DAC) is considered a predictive indicator of POPF. However, other indicators related to postoperative drain fluid amylase status exist, and the most reliable indicator for predicting POPF remains unclear. The object of this study is to identify the single most accurate indicator related to drain fluid amylase status of POPF after distal pancreatectomy (DP).

This single-institution retrospective study included 122 patients who underwent DP. The study was conducted between 2010 and 2022 at Gifu University Hospital. We statistically analyzed DAC, drain fluid amylase amount (DAA) calculated by multiplying DAC and daily drainage volume, and drain and serum amylase concentration ratio (DSACR) to assess the correlation with POPF.

Based on the definition and grading of the International Study Group of Pancreatic Fistula, 24.6 (%) of the 122 patients had Grades B and C POPF. The result of the receiver operating characteristic (ROC) curve for predicting POPF after DP, DSACR had the highest area under curve(AUC) value among DAC, DAA, and DSACR both POD1 and POD3. The cutoff value of DSACR on POD1 was 17 (AUC 0.69, sensitivity 80.0%, specificity 58.2%, and accuracy 63.6%). The cutoff value of DSACR on POD3 was 22 (AUC 0.77, sensitivity 77.7%, specificity 73.3%, and accuracy 73.6%). Overall, DSACR on POD3 had the highest AUC value. Furthermore, a multivariate logistic regression analysis revealed that pancreatic texture (soft; odds ratio [OR] 9.22; 95% confidence interval [CI] 2.22-44.19; p < 0.01) and DSACR on POD3 (> 22; OR 8.76; 95% CI 2.78-31.59; p < 0.001) were independently associated with POPF after DP.

DSACR is the most reliable indicator of drain fluid amylase status for predicting POPF after DP.

Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the major cause of morbidity following pancreaticoduodenectomy (PD). Several model score systems such as the Fistula Risk Score (FRS) have been developed to predict CR-POPF using preoperative and intraoperative data. Machine learning (ML) algorithms are increasingly applied in the medical field and they could be used to assess the risk of CR-POPF, identify clinically meaningful data and guide drain removal.

Data from consecutive patients who underwent PD between January 1, 2010 and March 31, 2021 at a single high-volume center was collected retrospectively in this study. Demographics, clinical features, intraoperative parameters, and laboratory values were used to conduct the ML model. Four different ML algorithms (CatBoost, lightGBM, XGBoost and Random Forest) were used to train this model with cross-validation.

A total of 2421 patients with 62 clinical parameters were enrolled in this ML model. The majority of patients (76.3%) underwent open PD while others underwent robot-assisted PD. CR-POPF occurred in 424 (17.5%) patients. The CatBoost algorithm outperformed other algorithms with a mean area under the receiver operating characteristic curve (AUC) of 0.81 (95% confidence interval: 0.80-0.82) from the 5-fold cross-validation procedure. In the test dataset, the CatBoost algorithm also achieved the best mean-AUC of 0.83. The most important value was mean drain fluid amylase (DFA) in the first seven postoperative days (POD). The performance of models that used only preoperative data and intraoperative data was marginally lower than that of models that used combined data.

Our ML algorithms could be applied as early diagnostic tools for CR-POPF in patients who underwent PD. Such real-time clinical decision support tools can identify patients with a high risk of CR-POPF, help in developing the perioperative management plan and guide the optimal timing of drain removal.

Surgical drains are widely utilized in hepatopancreaticobiliary surgery to prevent intra-abdominal collections and identify postoperative complications. Surgical drain monitoring ranges from simple-output measurements to specific analysis for constituents such as amylase. This systematic review aimed to determine whether surgical drain monitoring can detect postoperative complications and impact on patient outcomes.

A systematic review was performed, and the following databases searched between 02/03/20 and 26/04/20: MEDLINE, EMBASE, The Cochrane Library, and Clinicaltrials.gov. All studies describing surgical drain monitoring of output and content in adult patients undergoing hepatopancreaticobiliary surgery were considered. Other invasive methods of intra-abdominal sampling were excluded.

The search returned 403 articles. Following abstract review, 390 were excluded and 13 articles were included for full review. The studies were classified according to speciality and featured 11 pancreatic surgery and 2 hepatobiliary surgery studies with a total sample of 3262 patients. Postoperative monitoring of drain amylase detected pancreatic fistula formation and drain bilirubin testing facilitated bile leak detection. Both methods enabled early drain removal. Improved patient outcomes were observed through decreased incidence of postoperative complications (pancreatic fistulas, intra-abdominal infections, and surgical-site infections), length of stay, and mortality rate. Isolated monitoring of drain output did not confer any clinical benefits.

Surgical drain monitoring has advantages in the postoperative care for selected patients undergoing hepatopancreaticobiliary surgery. Enhanced surgical drain monitoring involving the testing of drain amylase and bilirubin improves the detection of complications in the immediate postoperative period.

C-reactive protein (CRP) and procalcitonin (PCT) have recently been used to diagnose and screen for postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD), but their reliability is still unclear. Our study aims to assess the efficacy of CRP and PCT in the diagnosis of POPF after PD.

Electronic databases such as PubMed, Excerpta Medica (EMBASE), the Web of Science (WOS) and the China National Knowledge Infrastructure (CNKI) were used to search for studies and full-text articles that assessed the diagnostic efficacy of CRP and PCT for POPF. Review Manager 5.4 and STATA 14.0 were used to estimate the pooled diagnostic value of CRP and PCT. Sensitivity analyses and Deeks' funnel plot tests were conducted on the selected studies.

Twenty studies that satisfied the established selection criteria were chosen. Both CRP and PCT were shown to be highly effective in diagnosing POPF, each with a high area under the curve (AUC). The AUC of CRP on postoperative day (POD) 4 had a value of 0.86, with a sensitivity and specificity of 0.85 and 0.69, respectively. The AUC of PCT on POD 5 had a value of 0.87, with a sensitivity and specificity of 0.84 and 0.74, respectively.

Our research supports the hypothesis that CRP and PCT are valuable diagnostic tools for predicting POPF, especially given the CRP levels on POD 4 and PCT levels on POD 5. Limited by the small number of the studies analyzed herein, we recommend that more randomized controlled trials be performed to verify our conclusions.

Drain fluid amylase concentration (DFAC) has been reported as a predictor of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatectomy. However, the clinical significance of measuring the total drain fluid amylase amount (DFAA) considering the daily drainage volume of CR-POPF remains unclear.

Data from 216 consecutive patients who underwent pancreaticoduodenectomy (PD) (n = 126) or distal pancreatectomy (DP) (n = 90) between August 2014 and November 2020 were reviewed. All drains were closed but not suctioned. DFAA was calculated by multiplying the DFAC and daily drainage fluid volume. DFAC and DFAA were recorded on d 1 and 3 after pancreatectomy. The cutoff value of CR-POPF was determined using the receiver operating characteristic curve.

CR-POPF was found in 75 patients (35%) (PD: 30%, DP: 41%, P = .111); the mortality rate was zero. The cutoff value of DFAC-day 1 was 1757 U/L (sensitivity [SE]: 84%, specificity [SP]: 62%, and accuracy [AC]: 69%). The cutoff value of DFAA-day 1 was 139 U (SE: 71%, SP: 72%, and AC: 71%). The cutoff value of DFAC-day 3 was 1044 U/L (SE: 73%, SP: 79%, and AC: 78%). The cutoff value of DFAA-day 3 was 21 U (SE: 68%, SP: 72%, and AC: 70%). Multivariate analysis indicated that a nondilated pancreatic duct and high DFAC-day 3 were independently associated with CR-POPF after PD, indicating that a prolonged operative duration, massive blood loss, and high DFAC-day 3 are independently associated with CR-POPF after DP.

DFAC is more reliable than DFAA for predicting CR-POPF after both PD and DP.

Enhanced Recovery After Surgery (ERAS) protocols have been successfully instituted for pancreaticoduodenectomy (PD). This study evaluates reasons patients fail to meet length of stay (LOS) and areas for pathway improvement.

A multidisciplinary team developed and implemented an ERAS protocol for open PD in 2017. The study includes a medical record review of all patients who were perioperatively managed with the ERAS protocol and failed to meet LOS after PD procedures. Target LOS was defined as 7 d.

From 2017 to 2020, 44% (93 of 213) of patients using ERAS protocol after PD procedures failed to meet target LOS. The most common reason to fail target LOS was ileus or delayed gastric emptying (47 of 93, LOS 11). Additional reasons included work-up of leukocytosis or pancreatic leak (17 of 93, LOS 14), additional "night" of observation (14 of 93, LOS 8), and orthostatic hypotension (3 of 93, LOS 10). Of these additional 46 patients, 19 patients underwent computed tomography (on or after POD 7) and only four patients received additional inpatient intervention.

The most common reason for PD pathway failure included slow return of gastrointestinal function, a known complication after PD. The remaining patients were often kept for observation without additional intervention. This group represents an actionable cohort to target for improving LOS through surgeon awareness rather than protocol modification.

Several scoring systems predict risks of clinically relevant postoperative pancreatic fistula after pancreatectomy, but none have emerged as the gold standard. This study aimed to evaluate the accuracy of postoperative day 1 drain amylase and serum C-reactive protein levels in predicting clinically relevant postoperative pancreatic fistula compared with intraoperative pancreatic characteristics.

Patients who underwent pancreatectomy between 2017 and 2019 were included prospectively. Cutoff values were determined using receiver operating characteristic curves, and a score combining postoperative day 1 drain amylase and serum C-reactive protein was tested in a multivariate logistic regression model to evaluate clinically relevant postoperative pancreatic fistula risk.

A total of 274 pancreatic resections (182 pancreaticoduodenectomies and 92 distal pancreatectomies) were included. The pancreatic gland texture was "soft" in 47.8% (n = 131), and 55.8% (n = 153) had a small size main pancreatic duct (≤3 mm). Clinically relevant postoperative pancreatic fistula occurred in 58 patients (21.2%). Drain amylase ≥1,000 UI/L and serum C-reactive protein ≥90 mg/L were identified as the optimal cutoffs to predict clinically relevant postoperative pancreatic fistula. On multivariate analysis these cutoffs were independent predictors of clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies (drain amylase: P < .001, serum C-reactive protein: P = .006) and distal pancreatectomies (drain amylase: P = .009, serum C-reactive protein: P = .001). The postoperative day 1 "90-1000" model, a 2-value score relying on these cutoffs, significantly (P < .001) outperformed intraoperative pancreatic parenchymal characteristics in predicting clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies and distal pancreatectomies. A postoperative day 1 "90-1000" score = 0 had a negative predictive value of 97% and 94%, respectively, after pancreaticoduodenectomy and distal pancreatectomies.

A combined score relying on postoperative day 1 values of drain amylase and serum C-reactive protein levels was accurate in predicting risks of clinically relevant postoperative pancreatic fistula after pancreatectomy.

Fistula following leaked pancreatico-enteric anastomosis is a common, potentially lethal complication of pancreaticoduodenectomy (PD). Early assessment and prediction of its occurrence can improve postoperative outcomes. Various perioperative factors were analyzed for its contribution to clinically relevant postoperative pancreatic fistula (crPOPF). Also, the difference in clinical outcomes of patients with and without fistula was studied. Sixty-seven patients undergoing PD for malignancies were analyzed during 3-year period in a dual-institutional study. Various preoperative, intraoperative, and postoperative factors were assessed. The incidence and severity of POPF and its association with the development of other post-PD complications were observed. Patients with and without POPF were divided into groups and compared with univariate and multivariate analyses, to identify significant contributing factors. Clinically relevant POPF was present in 20.9% cases. crPOPF contributed to delayed gastric emptying, albeit insignificant (p = 0.403), but was significantly associated with increased incidence of post-pancreatectomy hemorrhagic (p = 0.005) and infectious complications (p = 0.013). Soft pancreas (p = 0.024), intraoperative blood loss (p = 0.045), blood transfusion (p = 0.024), and fistula risk score (p = 0.001) were significant predictors of crPOPF. First postoperative day (POD1) drain fluid amylase (DFA) values at cut-off of 1336 U/L (AUC = 0.871; p < 0.001) significantly predicted crPOPF with good sensitivity and specificity. POD1 DFA was only factor significant on multivariate analysis (p = 0.014). There was no significant difference in overall survival between groups. crPOPF results in significant post-pancreatectomy hemorrhagic and septic complications, along with increased mortality. It can be accurately predicted by several preoperative and intraoperative factors. POD1 DFA can independently predict crPOPF development.

This study aimed to establish a reliable criterion for early drain removal after pancreaticoduodenectomy (PD) based on predictive factors of clinically relevant postoperative pancreatic fistula (CR-POPF) available on postoperative day 3 (POD3).

A total of 300 consecutive patients who underwent PD with pancreaticojejunostomy at our hospital from 2011 to 2015 were analyzed retrospectively. CR-POPF was defined as POPF grade B or C according to the definition by ISGPF. Clinicopathological factors available on or before POD3 were analyzed to identify predictors of CR-POPF. Using obtained predictors, we developed a criterion for no CR-POPF and internally validated its relevance in 100 consecutive patients.

The incidence rates of CR-POPF, severe complications (Clavien-Dindo ≥ grade IIIa), and postoperative mortality were 35%, 9.6%, and 0.3%, respectively. Multivariate analysis showed that drain amylase (d-AMY) levels ≥ 350 IU/l on POD3, C-reactive protein (CRP) levels ≥ 14 mg/dl on POD3, preoperative endoscopic retrograde biliary drainage, and no portal vein resection were significant predictors of CR-POPF. Using the strongest predictors (i.e., d-AMY and CRP), we established a criterion for no CR-POPF: d-AMY levels < 350 IU/l and CRP levels < 14 mg/dl on POD3. The incidence rates of CR-POPF were 6%, 38%, and 88% in patients who fulfilled both of (n = 149), each of (n = 74), and none of (n = 77) the two factors, respectively. In the internal validation cohort, the positive predictive value of CR-POPF was 89%.

A simple two-factor criterion available on POD3 after PD has a reliable predictive ability. In patients who fulfill this criterion, early drain removal is considered safe.

Postoperative hyperamylasemia is a frequent finding after pancreatoduodenectomy, but its incidence and clinical implications have not yet been analyzed systematically. The aim of this review is to reappraise the concept of postoperative hyperamylasemia with postoperative acute pancreatitis, including its definition, interpretation, and correlation.

Online databases were used to search all available relevant literature published through June 2019. The following search terms were used: "pancreaticoduodenectomy," "amylase," and "pancreatitis." Surgical series reporting data on postoperative hyperamylasemia or postoperative acute pancreatitis were selected and screened.

Among 379 screened studies, 39 papers were included and comprised data from a total of 9,220 patients. Postoperative hyperamylasemia was rarely defined in most of these series, and serum amylase values were measured at different cutoff levels and reported on different postoperative days. The actual levels of serum amylase activity and the representative cutoff levels required to reach a diagnosis of postoperative acute pancreatitis were markedly greater on the first postoperative days and tended to decrease over time. Most studies analyzing postoperative hyperamylasemia focused on its correlation with postoperative pancreatic fistula and other postoperative morbidities. The incidence of postoperative acute pancreatitis varied markedly between studies, with its definition completely lacking in 40% of the analyzed papers. A soft pancreatic parenchyma, a small pancreatic duct, and pathology differing from cancer or chronic pancreatitis were all predisposing factors to the development of postoperative hyperamylasemia.

Postoperative hyperamylasemia has been proposed as the biochemical expression of pancreatic parenchymal injury related to localized ischemia and inflammation of the pancreatic stump. Such phenomena, analogous to those associated with acute pancreatitis, could perhaps be renamed as postoperative acute pancreatitis from a clinical standpoint. Patients with postoperative acute pancreatitis experienced an increased rate of all postoperative complications, particularly postoperative pancreatic fistula. Taken together, the discrepancies among previous studies of postoperative hyperamylasemia and postoperative acute pancreatitis outlined in the present review may provide a basis for stronger evidence necessary for the development of universally accepted definitions for postoperative hyperamylasemia and postoperative acute pancreatitis.

There lacks an ideal model for accurately predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). This study aimed at developing a nomogram with high accuracy in predicting CR-POPF after PD.

A total of 1182 patients undergoing PD in the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU, n = 762) and Fudan University Shanghai Cancer Center (FUSCC, n = 420) between January 2010 and May 2018 were enrolled. The patients from FAHSYSU were assigned as testing cohort, and those from FUSCC were used as external validation cohort. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors for CR-POPF. Nomogram was developed on the basis of significant predictors. The performance of nomogram was evaluated by area under receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis.

In testing cohort, 87 out of 762 patients developed CR-POPF. Three predictors were significantly associated with CR-POPF, including body mass index ≥24.0 kg/m2, pancreatic duct diameter <3 mm, and drainage fluid amylase on postoperative day 1 ≥2484 units/L (all p ≤ 0.001). Prediction of nomogram was accurate with AUC of 0.934 (95% confidence interval [CI]: 0.914-0.950) in testing cohort and 0.744 (95% CI: 0.699-0.785) in external validation cohort. The predictive accuracy of nomogram was better than that of previously proposed fistula risk scores both in testing and external validation cohort (all p < 0.05).

The novel nomogram based on three easily available parameters could accurately predict CR-POPF after PD. It would have high clinical value due to its accuracy and convenience.

Backgound: This study aimed to determine the usefulness of the Controlling Nutritional Status (CONUT) scorescore for predicting postoperative pancreatic fistula (POPF).

Data from 108 consecutive pancreaticoduodenectomy cases performed at the Surgery Department of Iwakuni Clinical Center, from April 2008 to May 2018, were included. Preoperative patient data and postoperative complication data were collected.

Of the 108 patients (male=65; female=43; mean age=70 years), 41 (37.9%) had indication for pancreaticoduodenectomy due to pancreatic carcinoma. Grade B or higher POPF was diagnosed in 32 patients (29.6%). In the multivariate analysis, body mass index ≥22 kg/m2 [odds ratio (OR)=5.24; p=0.005], CONUT score ≥4 (OR=3.28; p=0.042), non-pancreatic carcinoma (OR=47.17; p=0.001), and a low computed tomographic contrast attenuation value (late/early ratio) (OR=4.39; p=0.029) were independent risk factors for POPF.

Patients with high CONUT score are at high risk for POPF. Preoperative nutritional intervention such as immunonutrition might help reduce the POPF risk in these patients.

We evaluated the intuition of expert pancreatic surgeons, in predicting the associated risk of pancreatic resection and compared this "intuition" to actual operative follow-up. The objective was to avoid major complications following pancreatic resection, which remains a challenge.

From January 2015 to February 2018, all patients who were 18 years old or more undergoing a pancreatic resection (pancreaticoduodenectomy [PD], distal pancreatectomy [DP], or central pancreatectomy [CP]) for pancreatic lesions were included. Preoperatively and postoperatively, all surgeons completed a form assessing the expected potential occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF: grade B or C), postoperative hemorrhage, and length of stay.

Preoperative intuition was assessed for 101 patients for 52 PD, 44 DP, and 5 CP cases. Overall mortality and morbidity rates were 6.9% (n = 7) and 67.3% (n = 68), respectively, and 38 patients (37.6%) developed a POPF, including 27 (26.7%) CR-POPF. Concordance between preoperative intuition of CR-POPF occurrence and reality was minimal, with a Cohen's kappa coefficient (κ) of 0.175 (P value = 0.009), and the same result was obtained between postoperative intuition and reality (κ = 0.351; P < 0.001). When the pancreatic parenchyma was hard, surgeons predicted the absence of CR-POPF with a negative predictive value of 91.3%. However, they were not able to predict the occurrence of CR-POPF when the pancreas was soft (positive predictive value 48%).

This study assessed for the first time the surgeon's intuition in pancreatic surgery, and demonstrated that pancreatic surgeons cannot accurately assess outcomes except when the pancreatic parenchyma is hard.

C-reactive protein (CRP) and procalcitonin (PCT) have shown to be reliable predictors of inflammatory complications and anastomotic leak after colorectal surgery. Their predictive value after partial pancreaticoduodenectomy (PD) remains unclear.

All consecutive pancreaticoduodenectomies (2009-2018) at our hospital were included. Drain amylase was evaluated on postoperative day (POD) 1, serum CRP and PCT were evaluated on POD 1-3. Receiver-operating characteristics curves were performed and significant cut-off values were tested using logistic regression.

Among 188 patients who underwent partial PD, clinically relevant pancreatic fistulas (POPF) occurred in 30 (16%) patients, including 20 (10.6%) with Grade B and 10 (5.3%) patients with Grade C. Postoperative complications (Clavien-Dindo ≥ III) were reported in 46 (24.5%) patients, including Grade IIIa in 16 (8.5%), IIIb in 18 (9.6%), IVa in 3 (1.6%), IVb in 2 (1.1%) and V in 7 (3.7%) patients. Drain amylase on POD 1 showed the largest area under the curve (0.872, p < 0.001), followed by CRP (0.803, p < 0.001) and PCT on POD 3 (0.651, p < 0.011). Drain amylase on POD 1 > 303 U/l (OR 0.045, 95% CI 0.010-0.195, p < 0.001), CRP > 203 mg/l (OR 0.098, 95% CI 0.041-0.235, p < 0.001) and PCT > 0.85 μg/l (OR 0.393, 95%CI 0.178-0.869, p = 0.02) were significant predictors of relevant POPF in the univariate analysis. CRP > 203 mg/l (OR 0.098, 95% CI 0.024-0.403, p = 0.001) and drain amylase > 303 U/l (OR 0.064, 95% CI 0.007-0.554, p = 0.01) remained independent predictors in the multivariable analysis. The combination of drain amylase on POD 1 and CRP on POD 3 had a sensitivity and specificity of 87.4% and 90.9% to predict relevant POPF.

Drain amylase on POD 1 and CRP on POD 3 can accurately predict clinically relevant POPF after partial pancreaticoduodenectomy. The accuracy of PCT on POD 3 is limited.

Prediction of complications after pancreatoduodenectomy (PD) remains of interest. Blood parameters and biomarkers during first and second postoperative days (POD1, POD2) may be early indicators of complications.

This case-control study included 50 patients. Baseline, POD1 and POD2 values of leukocytes, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein (CRP), procalcitonin and arterial lactate were compared between individuals presenting Clavien ≥ III morbidity, pancreatic fistula (PF) or clinically relevant PF (CRPF) and those without these morbidities. Common variables reaching significance were further analyzed in order to calculate a predictive score.

Severe morbidity, PF and CRPF rates were 28.0%, 26.0% and 14.0%, respectively. Patients with severe morbidity had lower leukocytes on POD2 (P = 0.04). Patients with PF presented higher CRP on POD2 (P = 0.001), higher lactate on POD1 (P = 0.007) and POD2 (P = 0.008), and lower lymphocytes on POD1 (P = 0.007) and POD2 (P = 0.008). Patients with CRPF had lower leukocytes and neutrophils on POD1 (P = 0.048, P = 0.038), lower lymphocytes on POD1 (P = 0.001) and POD2 (P = 0.003), and higher CRP on POD2 (P = 0.001). Baseline parameters and procalcitonin obtained no statistical associations. Score was defined according to lymphocytes on POD1 < 650/µL and CRP on POD2 ≥ 250 mg/L allocating patients in 3 risk categories. PF and CRPF rates were statistically higher as risk category increased (P<0.001). Receiver operating characteristic curves and Hosmer-Lemeshow tests showed a good accuracy.

Impaired immunological reaction during early postoperative period (lower leukocytes and, particularly, lymphocytes) in response to surgical aggression would favor complications after PD. Likewise, acidosis (higher arterial lactate) could behave as risk factor of PF. An elevated CRP on POD2 is also an early biomarker of PF. Our novel score based on postoperative lymphocyte count and CRP seems reliable for early prediction of PF.

Early recognition of postoperative pancreatic fistula might decrease the risk of subsequent life threatening complications. The aim of this review was to systematically evaluate the accuracy of postoperative clinical, biochemical and radiologic variables for early recognition of clinically relevant postoperative pancreatic fistula.

A systematic literature search was performed up to August 2018. Clinical studies reporting on the association between postoperative variables and clinically relevant postoperative pancreatic fistula were included. Variables were stratified: early prediction (postoperative day 1-2) versus early diagnosis (day 3) and had to be reported in 2 cohorts.

Overall, 37 included studies reported on 17 different diagnostic variables after 8701 pancreatic resections. Clinically relevant postoperative pancreatic fistula occurred in 1532/8701 patients (18%). Early prediction variables included elevated serum and drain amylase (day 1). Identified variables for early diagnosis were: non-serous drain efflux (day 3); positive drain culture (day 3); elevated temperature (any day); elevated C-Reactive Protein (CRP; day 4); elevated white blood cell count (day 4) and peripancreatic collections on computed tomography (CT; day 5-10).

This review provides a comprehensive overview of postoperative variables associated with clinically relevant pancreatic fistula. Incorporation of variables in future algorithms could potentially mitigate the clinical impact of postoperative pancreatic fistula.

Early drain removal after pancreatic resection is encouraged for individuals with low postoperative day 1 drain amylase levels (POD1 DA) to mitigate associated morbidity. Although various protocols for drain management have been published, there is a need to assess the implementation of a standardized protocol.

The Ottawa pancreatic drain algorithm (OPDA), based on POD1 DA and effluent volume, was developed and implemented at our institution. A retrospective cohort analysis was conducted of all patients undergoing pancreatic resection January 1, 2016-October 30, 2017, excluding November and December 2016 (one month before and after OPDA implementation).

42 patients pre-implementation and 53 patients post-implementation were included in the analysis. The median day of drain removal was significantly reduced after implementation of the OPDA (8 vs. 5 days; p = 0.01). Early drain removal appeared safe with no difference in reoperation or readmission rate after protocol implementation (p = 0.39; p = 0.76). On subgroup analysis, median length of stay was significantly shorter following OPDA implementation for patients who underwent DP and did not develop a postoperative pancreatic fistula (POPF) (6 vs 10 days, p = 0.03). Although the incidence of both surgical site infection and POPF were reduced following the intervention, neither reached statistical significance (38.1 to 28.3%, p = 0.31; and 38.1 to 28.3%, p = 0.31 respectively).

Implementing the OPDA was associated with earlier drain removal and decreased length of stay in patients undergoing distal pancreatectomy who did not develop POPF, without increased morbidity. Standardizing drain removal may help facilitate early drain removal after pancreatic resection at other institutions.

The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction.

DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored.

DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables.

In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts.

A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Postoperative pancreatic fistula remains an unsolved challenge after pancreatoduodenectomy. Important in this regard is the presence of a soft pancreatic texture which is a major risk factor. Advances in machine learning and texture analysis of medical images allow identification of features of parenchyma that are invisible to the human eye. The aim of this study was to investigate the potential of machine learning to predict postoperative pancreatic fistula based on preoperative, non-contrast-enhanced computed tomography.

We screened a prospectively assessed database including all patients undergoing pancreatoduodenectomy at a tertiary center from 2008 until 2018 for patients based on the occurrence of postoperative pancreatic fistula. In total, 110 patients were included, consisting of 55 patients who developed a postoperative pancreatic fistula and 55 without postoperative pancreatic fistula. For machine learning-based texture analysis preoperative, non-contrast-enhanced computed tomography axial images were used. Machine learning results were tested using 10-fold cross validation. Previously validated clinical fistula risk scores (original and alternative fistula risk scores) served as reference tests.

Both the original and the alternative fistula risk scores showed good discrimination between patients without and with postoperative pancreatic fistula (area under the curve 0.76 and 0.72, respectively). Machine learning-based texture analysis showed potential to detect histologic fibrosis (area under the curve 0.84, sensitivity 75%; specificity 92%), histologic lipomatosis (area under the curve 0.82, sensitivity 78%; specificity 89%), and intraoperative pancreatic hardness (area under the curve 0.70, sensitivity 78%; specificity 74%). The features of the machine learning-based texture analysis were most accurate in predicting the occurrence of postoperative pancreatic fistula (area under the curve 0.95, sensitivity of 96%; specificity 98%) after pancreatoduodenectomy.

This proof-of-principle study suggests the ability of machine learning in recognizing important features of pancreatic texture associated with an increased risk of postoperative pancreatic fistula based on preoperative computed tomography.

To compare perioperative outcomes of pancreatoduodenectomy (PD) performed through the laparoscopic route or by open surgery.

Laparoscopic PD is being progressively performed in selected patients.

An open-label single-center RCT was conducted between February 2013 and September 2017. The primary endpoint was the length of hospital stay (LOS). Secondary endpoints were operative time, transfusion requirements, specific pancreatic complications (pancreatic or biliary fistula, pancreatic hemorrhage, and delayed gastric emptying), Clavien-Dindo grade ≥ 3 complications, comprehensive complication index (CCI) score, poor quality outcome (PQO), and the quality of pathologic resection. Analyses were performed on an intention to treat basis.

Of 86 patients assessed for PD, 66 were randomized (34 laparoscopic approach, 32 open surgery). Conversion to an open procedure was needed in 8 (23.5%) patients. Laparoscopic versus open PD was associated with a significantly shorter LOS (median 13.5 vs. 17 d; P = 0.024) and longer median operative time (486 vs. 365 min; P = 0.0001). The laparoscopic approach was associated with significantly better outcomes regarding Clavien-Dindo grade ≥ 3 complications (5 vs. 11 patients; P = 0.04), CCI score (20.6 vs. 29.6; P = 0.038), and PQO (10 vs. 14 patients; P = 0.041). No significant differences in transfusion requirements, pancreas-specific complications, the number of lymph nodes retrieved, and resection margins between the two approaches were found.

Laparoscopic PD versus open surgery is associated with a shorter LOS and a more favorable postoperative course while maintaining oncological standards of a curative-intent surgical resection.

ISRCTN93168938.

Postoperative pancreatitis (POP) has recently been shown to be the cause of pancreatic fistula (POPF) following pancreaticoduodenectomy (PD). The aim of the present study was to document the perioperative outcome associated with POP and determine potential risk factors for POP.

Patients undergoing PD between 2009 and 2015 were identified from the prospective data base at a single center. The previous suggested definition of POP by Connor was used. Complications were graded according to the Clavien-Dindo classification and by the grading proposed for POP. Risk factors for POP were analyzed by univariate and multivariate analysis.

Of 190 patients, a total of 100 patients (53%) developed POP of whom 22 (12%) and 13 (7%) had grade B and grade C complications, respectively. Elevated serum CRP-levels on postoperative day (POD) 2 and elevated serum lipase on POD 1 were associated with onset of cr-POP.

The proposed definition of POP constitutes a valuable tool to assess a serious pancreatic-surgery associated complication. Routine serum CRP and serum lipase levels on the first two postoperative days enable sufficient discrimination of clinically relevant POP.

Although the Whipple operation is an essential surgical technique, its high morbidity (30% to 60%) and mortality (5%) are problems to be addressed. The incidence of postoperative hemorrhage has been reported between 5% and 16% in the literature. In this study, the data and results regarding postoperative hemorrhage complications from our clinic were evaluated.

The files of 185 patients who had undergone Whipple operation in our hospital in the last five years were evaluated retrospectively, and the causes of hemorrhage were attempted to be determined.

It was found that 6 out of the 13 (7%) patients who had hemorrhage died. In six of there 13 cases, hemorrhage occurred due to fistulas from the portal vein, gastroduodenal artery, and pancreatic arteries at variable periods. Two cases were found to have developed disseminated intravascular coagulation as a result of sepsis. Early intervention was performed in two cases who bled from the meso veins and in one case who bled from the portal vein. Laparotomy and hemostasis were performed in a patient who bled from the gastric anastomosis line. In a patient who had been taking low molecular weight heparin, bleeding from the drains and nasogastric tube stopped following the cessation of the drug.

Preventive procedures such as connection of the vascular structures, use of vascular sealants, omental patching during surgery, and reducing the risk of complications by using somatostatin analogs were performed to prevent hemorrhages after Whipple operations. In addition to standard methods, angiography and embolization have emerged as effective methods in the diagnosis and treatment of hemorrhages. Furthermore, determination and elimination of independent risk factors, such as jaundice, affecting fistula formation and bleeding in the perioperative period, is important for prevention.

The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor.

Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations.

The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS.

For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05).

The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

The mechanism of infected postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD) is undefined. Drain amylase has been used to predict POPF, whereas little data are available about the value of drain fluid culture. The aim was to investigate the incidence, risk factors and association with surgical outcomes of positive drainage culture (PDC) after PD.

A single-center retrospective analysis was conducted of prospectively collected data from patients who underwent PD between January 2005 and December 2015. Drain fluid samples were obtained for microbiological analysis after surgery. Risk factors for PDC were evaluated, and its influence on surgical outcomes was explored.

Of 768 patients, 261 (34%) had PDC during the postoperative period. Among them, a total of 434 isolates were yielded. One hundred and seven (24.7%) were Gram-positive, 283 (65.2%) Gram-negative, and 44 (10.1%) fungi. Multivariate analysis revealed that body mass index (BMI) ≥25 kg/m2 , preoperative chemoradiation and intra-operative red blood cell transfusion were independent risk factors for PDC. PDC was associated with higher incidences of complications including POPF, major complications and reoperation, but with no correlation between the day of PDC and complications. BMI ≥25 kg/m2 , early PDC (≤3 days), main pancreatic duct <3 mm, and soft pancreas were revealed as independent predictors for POPF. There was a correlation between type of microorganisms and complications.

Considering the correlation between PDC and postoperative complications, preventive measures are crucial to improve outcomes after PD. Whether antibiotic treatment for early PDC will alter the clinical course of POPF needs further evaluation.

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.

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.

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.

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.

This study was designed to analyze the risk factors for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD).Between September 2015 and August 2017, 170 successive patients underwent a radical PD in the Department of Pancreatic Surgery, Union Hospital, Wuhan. We carried out a retrospective study of these cases and the prospective conditions, which might be related to POPF, were examined with univariate and multivariate analysis. POPF was defined as a drain output of any measurable volume of fluid with an amylase level more than 3 times the upper limit of serum amylase activity on postoperative day 3, accompanied by a clinically relevant condition according to the 2016 update of the International Study Group for Pancreatic Surgery (ISGPS) definition. In our study, the POPF was just referred to as grade B and grade C pancreatic fistula in accordance with the ISGPS consensus, because the former grade A pancreatic fistula is now redefined as a biochemical leak, namely no-POPF, which has no clinical impact and needs no other special therapy.Pancreatic fistula occurred in 44 (25.9%) patients after PD, with a mean length of hospital stay of 24.98 ± 14.30 days. Thirty-six patients (21.2%) developed grade B pancreatic fistula, and 8 patients (4.7%) had grade C pancreatic fistula. Among patients with grade C pancreatic fistula, 4 patients died, 3 patients were operated on again, and 3 patients developed multiple organ failure.Univariate analysis showed a significantly important association between POPF and the following factors: pancreas texture (soft vs hard: 39.1% vs 10.3%, P < .0001) and fasting blood glucose level (<108.0 mg/dL vs ≥108.0 mg/dL: 32.5% vs 12.5%, P = .005). Multivariate logistic regression analysis identified 2 independent factors related to POPF: soft pancreas texture and fasting blood glucose level <108.0 mg/dL.A soft pancreas and a fasting blood glucose level of <108.0 mg/dL are risk factors for the development of a POPF.

Postoperative pancreatic fistula and pancreas-specific complications have a significant influence on patient management and outcomes after pancreatoduodenectomy. The aim of the study was to assess the value of serum C-reactive protein on the postoperative day 1 as early predictor of pancreatic fistula and pancreas-specific complications.

Between 2013 and 2016, 110 patients underwent pancreaticoduodenectomy. Clinical, biological, intraoperative, and pathological characteristics were prospectively recorded. Pancreatic fistula was graded according to the International Study Group on Pancreatic Fistula classification. A composite endpoint was defined as pancreas-specific complications including pancreatic fistula, intra-abdominal abscess, postoperative hemorrhage, and bile leak. The diagnostic accuracy of serum C-reactive protein on postoperative day 1 in predicting adverse postoperative outcomes was assessed by ROC curve analysis.

Six patients (5%) died and 87 (79%) experienced postoperative complications (pancreatic-specific complications: n = 58 (53%); pancreatic fistula: n = 48 (44%)). A soft pancreatic gland texture, a main pancreatic duct diameter < 3 mm and serum C-reactive protein ≥ 100 mg/L on postoperative day 1 were independent predictors of pancreas-specific complications (p < 0.01) and pancreatic fistula (p < 0.01). ROC analysis showed that serum C-reactive protein ≥ 100 mg/L on postoperative day 1 was a significant predictor of pancreatic fistula (AUC: 0.70; 95%CI: 0.60-0.79, p < 0.01) and pancreas-specific complications (AUC: 0.72; 95%CI: 0.62-0.82, p < 0.01). ROC analysis showed that serum C-reactive protein ≥ 50 mg/L at discharge was a significant predictor of 90-day hospital readmission (AUC: 0.70; 95%CI: 0.60-0.79, p < 0.01).

C-reactive protein levels reliably predict risks of pancreatic fistula, pancreas-specific complications, and hospital readmission, and should be inserted in risk-stratified management algorithms after pancreaticoduodenectomy.

Many pancreatic surgeons continue to use intraperitoneal drains, but others have limited or avoided their use, believing this improves outcomes. We conducted a systematic review and meta-analysis of the literature assessing outcomes in pancreatectomy without drains, selective drainage, and early drain removal. We searched PubMed, Embase, and the Cochrane Library databases and conducted a systematic review of randomized and nonrandomized studies comparing routine intra-abdominal drainage versus no drainage, selective drain use, and early versus late drain removal after pancreatectomy, with major complications as the primary outcome. A meta-analysis of the literature assessing routine use of drains was conducted using the random-effects model. A total of 461 articles met search criteria from PubMed (168 articles), Embase (263 articles), and the Cochrane Library (30 articles). After case reports and articles without primary data on complications were excluded, 14 studies were identified for systematic review. Definitive evidence-based recommendations cannot be made regarding the management of drains following pancreatectomy because of limitations in the available literature. Based on available evidence, the most conservative approach, pending further data, is routine placement of a drain and early removal unless the patient's clinical course or drain fluid amylase concentration suggests a developing fistula.

The postoperative pancreatic fistula (POPF) rate for duct-to-mucosa and invagination anastomosis after pancreatoduodenectomy is still debated. The aim of this RCT was to investigate the POPF rate for duct-to-mucosa versus invagination pancreaticojejunostomy.

Patients were stratified by pancreatic texture and diameter of the main pancreatic duct and randomized to the duct-to-mucosa or invagination group. The primary endpoint was the rate of clinically relevant POPF (defined as grade B or C). Secondary endpoints were suture material cost for pancreaticojejunostomy, drain insertion duration and duration of postoperative hospital stay.

Some 120 patients undergoing pancreatoduodenectomy were included following consent. Clinically relevant POPF developed in six of 59 patients (10 per cent) in the invagination group and in 14 of 61 patients (23 per cent) in the duct-to-mucosa group (P = 0·077). Duration of drain insertion (6 versus 7 days respectively; P = 0·027) and postoperative hospital stay (19 versus 24 days; P = 0·015) were shorter in the invagination group. Subgroup analysis for 61 patients with a soft pancreas revealed a lower rate of clinically relevant POPF in the invagination group (10 per cent versus 42 per cent in the duct-to-mucosa group; P = 0·010). Among 20 patients with a clinically relevant POPF, the six patients in the invagination group had a shorter duration of drain insertion (38·5 days versus 49 days for 14 patients in the duct-to-mucosa group; P = 0·028) and postoperative hospital stay (42 versus 54·5 days respectively; P = 0·028).

This study did not demonstrate a superiority of invagination over duct-to-mucosa pancreaticojejunostomy in the risk of POPF. However, in high-risk patients with a soft pancreas, invagination may reduce the risk of clinically relevant POPF compared with duct-to-mucosa. Registration number: UMIN000005890 (http://www.umin.ac.jp).