In the past, indications for total pancreatectomy (TP) were rare, with several concerns about patients' postoperative quality of life due to exocrine and endocrine post-pancreatectomy management [...].

Early detection and therapy of pancreatic fistula after pancreaticoduodenectomy is crucial to improve outcomes of this surgery. Since it is not clear if procalcitonin (PCT), can predict the onset of clinically relevant post-operative pancreatic fistula (CR-POPF), we aimed to investigate this ability.

One-hundred-thirty pancreaticoduodenectomies (PD) were analyzed. Receiver Operating Characteristic curves analysis defined the optimal cut-offs for PCT and drains amylase levels (DAL). Complications were compared using chi-square for proportions test.

DAL ≥2,000 U/L in postoperative day (POD) 2 had 71% positive predictive value (PPV) and 91% negative predictive value (NPV) for CR-POPF (P<0.001). In POD2, PCT ≥0.5 ng/mL showed NPV 91% (P<0.045) and increased DAL PPV for CR-POPF to 81%. In POD3, POD4 and POD5, DAL (cut-offs 780, 157 and 330 U/L, respectively) showed NPV for CR-POPF >90% (P<0.0001). PCT ≥0.5 ng/mL showed NPV for CR-POPF of about 90%. In POD5, combining DAL (cut-off 330 U/L) and PCT (cut-off 0.5 ng/mL), a PPV for CR-POPF of 81% was detected. A progressive increased risk of CR-POPF from POD2 [odds ratio (OR) =3.05; P=0.0348] to POD5 (OR =4.589; P=0.0082) was observed. In POD2 and 5, PCT ≥0.5 ng/mL, alone and in combination with DAL, may be a reliable marker for identifying patients at highest risk of CR-POPF after PD.

This association could be proposed to select high risk patients that could benefit of "intensive" postoperative management.

After pancreatojejunostomy for pancreatic head resection, contrast-enhanced computed tomography sometimes reveals a hypoattenuated area at the pancreatojejunostomy site. The clinical impact of this hypoattenuated area, in terms of postoperative pancreatic fistula, is unknown.

Among 309 patients undergoing pancreatic head resection with pancreatojejunostomy reconstruction at Osaka University Hospital from 2012 to 2020, 105 exhibited drain amylase levels over 3× the upper limit of normal. According to contrast-enhanced computed tomography on postoperative days 3-14, these patients were divided into two groups-evident hypoattenuated area group (≥ 5 mm; n = 46) and subtle hypoattenuated area group (< 5 mm; n = 59)-and evaluated for clinically relevant pancreatic fistula.

Clinically relevant pancreatic fistula was significantly more common with the evident hypoattenuated group (80.4%; 37/46) than the subtle hypoattenuated group (40.7%; 24/59) (P < 0.0001). Multivariate analysis identified four factors related to clinically relevant pancreatic fistula formation: male sex (P = 0.0230), main pancreatic duct diameter < 3 mm (P = 0.0007), operative time > 475 min (P = 0.0161), and evident hypoattenuated area group (P = 0.0050). Hypoattenuated area ≥ 5 mm was associated with clinically relevant pancreatic fistula (60.7% sensitivity; 79.6% specificity).

Evident hypoattenuated area on postoperative contrast-enhanced computed tomography was an independent risk factor for clinically relevant pancreatic fistula. Patients experiencing increased drain amylase levels may benefit from contrast-enhanced computed tomography assessment to predict clinically relevant pancreatic fistula formation.

Although the mortality at 90 days has declined, pancreaticoduodenectomy (PD) is an extremely complex surgical procedure, with a non-negligible rate of major postoperative complications [...].

Postoperative pancreatic fistula (POPF) is the most fearful complication after pancreatic surgery and can lead to severe postoperative complications such as surgical site infections, sepsis and bleeding. A previous study which identified cut-offs of drains amylase levels (DALs) determined on postoperative day (POD) 1 and POD3, was able to significantly predict POPF, abdominal collections and biliary fistulas, when related to specific findings detected at the abdominal computerized tomography (CT) scan routinely performed on POD3.

To validate the cut-offs of DALs in POD1 and POD3, established during the previous study, to assess the risk of clinically relevant POPF and confirm the usefulness of abdominal CT scan on POD3 in patients at increased risk of abdominal collection.

The DALCUT trial is an interventional prospective study. All patients who will undergo pancreatoduodenectomy (PD) for periampullary neoplasms will be considered eligible. All patients will receive clinical staging and, if eligible for surgery, will undergo routine preoperative evaluation. After the PD, daily DALs will be evaluated from POD1. Drains removal and possible requirement of abdominal CT scans in POD3 will be managed on the basis of the outcome of DALs in the first three postoperative days.

This prospective study could validate the role of DALs in the management of surgical drains and in assessing the risk or relevant complications after PD. Drains could be removed in POD3 in case of POD1 DALs < 666 U/L and POD3 DALs < 207 U/L. In case of POD3 DALs ≥ 252, abdominal CT scan will be performed in POD3 to identify abdominal collections ≥ 5 cm. In this latter category of patients, drains could be maintained beyond POD3.

The results of this trial will contribute to a better knowledge of POPF and management of surgical drains.

The role of preoperative inflammatory biomarkers (PIBs) in predicting postoperative morbidity has been assessed in colorectal and otorhinolaryngeal surgery. However, data regarding the role that preoperative inflammatory biomarkers have on morbidity after pancreaticoduodenectomiy (PD) are less consistent.

To assess the utility of PIBs in predicting postoperative complications after pancreaticoduodenectomy.

A database of 317 consecutive pancreaticoduodenectomies performed from April 2003 to November 2018 has been retrospectively analyzed. Data regarding preoperative neutrophil-to-lymphocyte ratio (NLR), derived NLR and C-reactive protein (CRP), and postoperative complications of 238 cases have been evaluated. Exclusion criteria were: age < 18-years-old, previous neoadjuvant treatment, absence of data about PIBs, concomitant hematological disorders, and presence of active infections at the moment of the surgery. PIBs were compared using Mann-Whitney's test and receiver operating characteristic (ROC) analysis was performed to define the cutoffs. The positive predictive value (PPV) was computed to evaluate the probability to develop complication. P-values < 0.05 were considered statistically significant.

According to the literature findings, only four papers have been published reporting the relation between the inflammatory biomarkers and PD postoperative morbidity. A combination of preoperative and postoperative inflammatory biomarkers in predicting complications after PD and the utility of preoperative NLR in the development of postoperative pancreatic fistula (POPF) have been reported. The combination of PIBs and postoperative day-1 drains amylase has been reported to predict the incidence of POPF. According to our results, CRP values were significantly different between patients who had/did not have postoperative complications and abdominal collections (P < 0.05). Notably, patients with preoperative CRP > 8.81 mg/dL were at higher risk of both overall complications and abdominal collections (respectively P = 0.0037, PPV = 0.95, negative predictive value [NPV] = 0.27 and P = 0.016, PPV = 0.59, NPV = 0.68). Preoperative derived neutrophil-to-lymphocyte ratio (dNLR) (cut off > 1.47) was also a predictor of abdominal collection (P = 0.021, PPV = 0.48, NPV = 0.71). Combining CRP and dNLR, PPV increased to 0.67. NLR (cut off > 1.65) was significantly associated with postoperative hemorrhage (P = 0.016, PPV = 0.17, NPV = 0.98).

PIBs may predict complications after PD. During postoperative care, PIB levels could influence decisions regarding the timing of drains removal and the selection of patients who might benefit from second level diagnostic exams.

Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD.

An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF).

Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli, Klebsiella pneumoniæ and Enterococcus fæcalis (p < 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli, Klebsiella pneumoniæ, Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF (p < 0.001). Biliary culture positive for Escherichia coli, Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE (p < 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30-6.70); p < 0.01).

Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Postoperative day 1-drains amylase (POD1-DA) values are commonly used to predict the risk of pancreatic fistula (PF) after pancreaticoduodenectomy (PD). Perioperative inflammatory biomarkers have been associated to higher risk of complications in different oncological surgeries. Aim of this study was to investigate the utility of the combination of preoperative inflammatory biomarkers (PIBs) with POD1-DA levels in predicting grade C PF.

From a prospective collected database of 317 consecutive pancreaticoduodenectomies, data regarding POD1-DA levels and PIBs as neutrophil-to-lymphocyte ratio (NRL), derived neutrophil-to-lymphocyte ratio (dNRL), platelet-to-lymphocyte ratio (PLR) were analyzed in 227 cases. P-values <0.05 were considered statistically significant. Receiver operating characteristic (ROC) curves defined the optimal thresholds for biomarkers and drains amylase values and their accuracy to predict PF. Furthermore, the Positive Predictive Value (PPV) was computed to evaluate the probability to develop PF combining PIBs and drains amylase values. Combination of drains amylase and different PIBs cut-offs were used to evaluate the risk of grade C PF.

A POD1-DA level of 351 U/L significantly predicted PF (sensitivity 82.7%, specificity 76%, AUC 0.836; p < 0.001) with a PPV of 76.5% and a NPV of 82.6%.POD1-DA levels ≥807 U/L significantly predicted grade C PF (sensitivity 72.7%, specificity 64.4%, AUC 0.676; p = 0.004) with a PPV of 17.8% and a NPV of 95.6%.Notably, this last PPV increased from 17.8% to 89% when PIBs, at different cut-offs, were combined with POD1-DA at the value ≥ 807 U/L.

PIBs significantly improve POD1-DA ability in predicting grade C PF after PD.