Relevant Postoperative Pancreatic Fistula Research Articles

How I do it. Pancreatojejunostomy: surgical tips to mitigate the severity of postoperative pancreatic fistulas after open or minimally invasive pancreatoduodenectomy.

Pancreatoduodenectomy is the most appropriate technique for the treatment of periampullary tumors. In the past, this procedure was associated with high mortality and morbidity, but with improvements in patient selection, anesthesia, and surgical technique, mortality has decreased to less than 5%. However, morbidity remains increased due to various complications such as delayed gastric emptying, bleeding, abdominal collections, and abscesses, most of which are related to the pancreatojejunostomy leak. Clinically relevant postoperative pancreatic fistula is the most dangerous and is related to other complications including mortality. The incidence of postoperative pancreatic fistula ranges from 5-30%. Various techniques have been developed to reduce the severity of pancreatic fistulas, from the use of an isolated jejunal loop for pancreatojejunostomy to binding and invagination anastomoses. Even total pancreatectomy has been considered to avoid pancreatic fistula, but the late effects of this procedure are unacceptable, especially in relatively young patients. Recent studies on the main techniques of pancreatojejunostomy concluded that duct-to-mucosa anastomosis is advisable, but no technique eliminates the risk of pancreatic fistula. The purpose of this study is to highlight technical details and tips that may reduce the severity of pancreatic fistula after pancreatojejunostomy during open or minimally invasive pancreatoduodenectomy.

Risk factors and nomogram of clinically relevant pancreatic fistula after pancreaticoduodenectomy for periampullary cancer: A prospective multicenter cohort study

Abstract Background Clinically relevant postoperative pancreatic fistula (CRPF) is considered the most dangerous morbidity associated with pancreaticoduodenectomy (PD). The purpose of this study is to evaluate the risk factors and to construct a predicted model for CRPF after PD. Material and Methods Consecutive patients who underwent pancreaticoduodenectomy between August 2021 and October 2023 at Cho Ray Hospital and University Medical Center were included in a multicenter cohort research. Multivariate logistic regression analyses was used to identify the risk factors of CRPF, and a nomogram was built based on these factors. The value of the nomogram in predicting CRPF was evaluated using the area under the receiver operating characteristic (ROC) curve. Results There were 183 eligible patients in this study (mean age: 57.5 ± 12.6 years; 101 males), and the prevalence of CRPF was 13,7% overall. Multivariate analyses showed that, four risk factors related to CRPF, including preoperative serum albumin <3.5 g/dl, body mass index (BMI) ≥ 25 kg/m2, soft texture of the pancreas and estimated blood loss ≥400 ml were prognostic factors for CRPF (p < 0.05). We built a nomogram based on four variables to predict CRPF, and the area under the ROC curve for this nomogram was 0.855 (95% CI: 0,768 – 0,933). Conclusions Nomogram developed from four risk factors shows good performance to predict CRPF after PD. The clinical findings of this study will help surgeons identify perioperative risk factors for high-risk patients with pancreatic fistula who should be managed differently from other patients. Clinical Trial Registry number: ClinicalTrials.gov NCT05017207. Statement of Significance We successfully developed a nomogram to predict the risk of pancreatic fistula using four perioperative factors. By incorporating these risk factors into clinical practice, surgeons can develop appropriate treatment plans and interventions for high-risk patient populations, potentially reducing the morbidity associated with CRPF.

Retromesenteric omental flap as arterial coverage in pancreaticoduodenectomy: A novel technique to prevent postpancreatectomy hemorrhage

BackgroundClinically relevant postpancreatectomy hemorrhage occurs in 10% to 15% of patients after pancreaticoduodenectomy, mainly in association with clinically relevant postoperative pancreatic fistula. Prevention of postpancreatectomy hemorrhage by arterial coverage with a round ligament plasty or an omental flap is controversial. This study assessed the impact of arterial coverage with an original retromesenteric omental flap on postpancreatectomy hemorrhage after pancreaticoduodenectomy. MethodsThis single-center retrospective study included 812 open pancreaticoduodenectomies (2012–2021) and compared 146 procedures with arterial coverage using retromesenteric omental flap to 666 pancreaticoduodenectomies without arterial coverage. The Fistula Risk Score was calculated. The primary endpoint was a 90-day clinically relevant postpancreatectomy hemorrhage rate according to the International Study Group of Pancreatic Surgery classification. ResultsThere were more patients with a Fistula Risk Score ≥7 in the arterial coverage-retromesenteric omental flap group: 18 (12%) versus 48 (7%) (P < .01). Clinically relevant postpancreatectomy hemorrhage was less frequent in the arterial coverage- retromesenteric omental flap group than in the no arterial coverage group: 5 (3%) versus 66 (10%), respectively (P = .01). Clinically relevant postoperative pancreatic fistula occurred in 28 (19%) patients in the arterial coverage- retromesenteric omental flap group compared with 165 (25%) in the no arterial coverage group (P = .001). There were fewer reoperations for postpancreatectomy hemorrhage or postoperative pancreatic fistula in the arterial coverage- retromesenteric omental flap group: 1 (0.7%) versus 32 (5%) in the no arterial coverage group (P = .023). In multivariate analysis, arterial coverage with retromesenteric omental flap was an independent protective factor of clinically relevant postpancreatectomy hemorrhage (odds ratio 0.33; 95% confidence interval [0.12–0.92], P = .034) whereas postoperative pancreatic fistula of any grade (odds ratio = 10.1; 95% confidence interval: 5.1–20.3, P < .001) was predictive of this complication. ConclusionArterial coverage with retromesenteric omental flap can reduce rates of clinically relevant postpancreatectomy hemorrhage after pancreaticoduodenectomy. This easy and costless technique should be prospectively evaluated to confirm these results.

Impact of pancreas transection site on incidence of pancreatic fistula after distal pancreatectomy: a propensity score matched study

IntroductionDistal pancreatectomy (DP) is performed for lesions in the body and tail of the pancreas. The morbidity profile is considerable, mainly due to clinically relevant postoperative pancreatic fistula (CR-POPF). This study aims to investigate potential differences in CR-POPF related to transection site. MethodsAn observational cohort study from a prospectively maintained database was performed. Subtotal distal pancreatectomy (SDP) was defined as transection over the superior mesenteric vein, and DP was defined as transection lateral to this point. Propensity score matching (PSM) in 1:1 fashion was applied based on demographical and perioperative variables. ResultsSix hundred and six patients were included in the analysis (1997–2020). Four hundred twenty (69.3%) underwent DP, while 186 (30.7%) underwent SDP. The rate of CR-POPF was 19.3% after DP and 20.4% after SDP (p = 0.74). SDP was associated with older age (63.1 vs 60.1 years, p = 0.016), higher occurrence of ductal adenocarcinoma (37.1 vs 17.6%, p = 0.001) and more frequent use of neoadjuvant chemotherapy (3.8 vs 0.7%, p = 0.012). After PSM, 155 patients were left in each group. The difference in CR-POPF between DP and SDP remained statistically not significant (20.6 vs 18.7%, p = 0.67). ConclusionThis study found no difference in CR-POPF related to transection site during distal pancreatectomy.

Efficacy of pancreaticojejunostomy of the pancreatic stump during distal or central pancreatectomy.

A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.

Does perioperative hydrocortisone or indomethacin improve pancreatoduodenectomy outcomes? A triple arm, randomized placebo-controlled trial.

This trial evaluated whether anti-inflammatory agents hydrocortisone (H) and indomethacin (I) could reduce major complications after pancreatoduodenectomy (PD). Between June 2018 and June 2020, 105 patients undergoing PD with > 40% of acini on the intraoperative frozen section were randomized into three groups (35 patients per group): 1) intravenous H 100 mg 8 hourly, 2) rectal I suppository 100 mg 12 hourly, and 3) placebo (P) from postoperative day (POD) 0-2. Participants, investigators, and outcome assessors were blinded. The primary outcome was major complications (Clavien-Dindo grades 3-5). Secondary outcomes were overall complications (Clavien-Dindo grades 1-5), Clinically relevant postoperative pancreatic fistula (CR-POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), surgical site infections (SSI), length of stay, POD-3 serum amylase, readmission rate, and mortality. Major complications were comparable (8.6%, 5.7%, and 8.6% in groups H, I, and P, respectively). However, overall complications were significantly lower in group H than in group P (45.7% vs. 80.0%, p = 0.006). CR-POPF (14.3% vs. 25.7%, p = 0.371), PPH (8.6% vs. 14.3%, p = 0.710), DGE (8.6% vs. 22.9%, p = 0.188), and SSI (14.3% vs. 25.7%, p = 0.371) were comparable between groups H and P. Major complications and overall complications in group I were 5.7% and 60.0%, respectively, which were comparable to those in groups P and H. CR-POPF rates in groups H, I, and P were 14.3%, 17.1%, and 25.7%, respectively, which was comparable. H and I did not decrease major complications in PD.

Preoperative ultrasound radiomics for predicting clinically relevant postoperative pancreatic fistula after pancreatectomy.

To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation.

Perioperative textbook outcomes of minimally invasive pancreatoduodenectomy: a multicenter retrospective cohort analysis in a Korean minimally invasive pancreatic surgery registry.

The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD). The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD. Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P<0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P=0.001), lower 90-day mortality (0.5% vs. 2.7%, P=0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P=0.006) than those low-volume centers. MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease.

Stent placement for the prevention of clinically-relevant postoperative pancreatic fistula following pancreaticojejunostomy: A systematic review and meta-analysis

ObjectivesThere remains a lack of consensus regarding the benefits of stent placement following pancreaticojejunostomy in terms of clinically relevant postoperative pancreatic fistulas (CR-POPFs). This study was aimed at analyzing the effects of stent placement, stent technique (internal and external), stent size, and dilation of the main pancreatic duct on CR-POPFs. MethodsOur study comprised a systematic review and meta-analysis of randomized controlled trials involving patients undergoing pancreaticojejunostomy. The primary outcome was defined as the incidence of CR-POPFs. Additionally, subgroup analyses were conducted, and pooled analyses were performed to provide comparative references. ResultsTwelve randomized controlled trials, including a total of 1117 patients, were included. Compared with no stent placement, stenting did not exhibit a significant association with reduced CR-POPF incidence (odds ratio [OR] ​= ​0.60, 95% CI: 0.34–1.04, P ​= ​0.07). Subgroup analysis revealed that only external stents, and not internal stents, were significantly associated with a reduced CR-POPF incidence compared with no stent placement (OR ​= ​0.53, 95% CI: 0.28–0.99, P ​= ​0.05 vs. OR ​= ​0.92, 95% CI: 0.28–3.05, P ​= ​0.89). Furthermore, stent placement in patients with a main pancreatic duct diameter of ≤3 ​mm, and not in those with a main pancreatic duct diameter of >3 ​mm, was associated with a significantly reduced CR-POPF incidence compared with no stent placement (OR ​= ​0.24, 95% CI: 0.07–0.78, P ​= ​0.02 vs. OR ​= ​1.58, 95% CI: 0.41–6.06, P ​= ​0.50). ConclusionsThe findings suggest a potential role for external stent placement in the prevention of CR-POPFs after pancreaticojejunostomy, particularly in patients with undilated pancreatic ducts. The reliability of our findings is constrained by the limited number of studies included. Prospero registration numberCRD42022380103.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. Data for 294 patients (ODP, n=127; LDP, n=167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263U/L vs 4243U/L, p<0.001), while the difference was not significant on POD three (543U/L vs 1221U/L, p=0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697U/L on POD one, 1114U/L on POD three; LDP, 10564U/L on POD one, 6020U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Meta-analysis and trial sequential analysis of pancreatic stump closure using a hand-sewn or stapler technique in distal pancreatectomy.

This study aimed to compare outcomes of hand-sewn and stapler closure techniques of pancreatic stump in patients undergoing distal pancreatectomy (DP). Impact of stapler closure reinforcement using mesh on outcomes was also evaluated. Literature search was carried out using multiple data sources to identify studies that compared hand-sewn and stapler closure techniques in management of pancreatic stump following DP. Odds ratio (OR) was determined for clinically relevant postoperative pancreatic fistula (POPF) via random-effects modelling. Subsequently, trial sequential analysis was performed. Thirty-two studies with a total of 4,022 patients undergoing DP with hand-sewn (n = 1,184) or stapler (n = 2,838) closure technique of pancreatic stump were analyzed. Hand-sewn closure significantly increased the risk of clinically relevant POPF compared to stapler closure (OR: 1.56, p = 0.02). When stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.54, p = 0.002). When only randomized controlled trials were considered, there was no significant difference in clinically relevant POPF between hand-sewn and stapler closure techniques (OR: 1.20, p = 0.64) or between reinforced and standard stapler closure techniques (OR: 0.50, p = 0.08). When observational studies were considered, hand-sewn closure was associated with a significantly higher rate of clinically relevant POPF compared to stapler closure (OR: 1.59, p = 0.03). Moreover, when stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.55, p = 0.02). Trial sequential analysis detected risk of type 2 error. In conclusion, reinforced stapler closure in DP may reduce risk of clinically relevant POPF compared to hand-sewn closure or stapler closure without reinforcement. Future randomized research is needed to provide stronger evidence.

Open distal pancreatectomy stump closure by linear stapling versus continuous suturing: a retrospective–prospective comparative study

Background Distal pancreatectomy (DP), performed for removing pancreatic lesions located to the left of the superior mesenteric vein, accounts for ~25% of all pancreatic resections. Most recently reported overall mortality rate of DP is less than 3%. However, albeit technically simpler to perform than pancreaticoduodenectomy, morbidity rate of DP remains substantial. Postoperative pancreatic fistulas (POPFs), which may result in numerous clinically significant and potentially life-threatening complications such as intraabdominal abscess, hemorrhage, and surgical site infection, is the leading cause of morbidity after DP, with an incidence of ~30–60%. Risk factors associated with POPFs after DP include decreased serum albumin levels, concurrent splenectomy, increased body weight, increased duration of surgery, higher American Society of Anesthesiologists score, and impaired renal function. Furthermore, POPFs often translate to significant increases in hospitalization costs. Objective To compare the technique of DP stump closure in two groups of patients; a group underwent stump closure with linear stapling technique and the other group underwent stump closure with continuous suturing technique. Patients and methods This was a retrospective–prospective clinical trial that was conducted at General Surgery Department, Ain Shams University Hospitals on 30 patients who were admitted to specialized hepatobiliary units in Cairo, Egypt for open DP. Between January 2020 and June 2022 with postoperative follow-up period of 2 months. In our study, there were 30 patients (15 in the continuous suturing technique group and 15 in the linear stapling technique group) with a mean age of 45.37±10.662 years. Groups were similar in demographic and clinical characteristics (P&gt;0.05). Results In our study, 13.33% patients in continuous suturing technique group developed clinically relevant POPF (grade B and grade C POPF), whereas 33.33% patients in stapling technique group develop POPF (P=1.00). The amount of the blood loss which was found to be statistically significant as the P value was found less than 0.05 and the t test was found to be −2.396 which mean that the amount of the blood lost was more in the stapler group. There was no statistically significant difference in the rate of clinically relevant POPF (grade B and grade C POPF) with suture closure compared with stapler closure (13.33 vs. 33.33%). There was no statistically significant difference in the risk of intraabdominal abscess. There were three (20%) patients with a biochemical leak in continuous suturing technique group. In stapling technique group, three (20%) patients developed biochemical leaks. There was no significant in difference between groups in terms of biochemical leak. In our study, mortality rates did not differ between stapler and suture closure techniques. Conclusion Our study showed no significant difference between suture and stapler closure of DP stump with respect to POPF or intraabdominal collection after DP. The amount of the blood lost was more in the stapler group.

A combined score for predicting clinically relevant postoperative pancreatic fistula based on inflammatory parameters and drainage fluid culture results on postoperative day 3.

Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR-POPF remains elusive. We aimed to identify inflammatory parameter- and drainage fluid culture-related risk factors for CR-POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). Data from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR-POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR-POPF was developed. Of the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR-POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1mm were independent risk factors in the DP group. The model for predicting CR-POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups. Inflammatory parameters on POD 3 significantly influence the risk of CR-POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR-POPF after pancreatectomy.

Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a nationwide analysis

BackgroundPostoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. MethodsAll patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014–2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. ResultsOverall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03–0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25–1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P < .001). ConclusionThis nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.

Deep learning-based prediction of post-pancreaticoduodenectomy pancreatic fistula

Postoperative pancreatic fistula is a life-threatening complication with an unmet need for accurate prediction. This study was aimed to develop preoperative artificial intelligence-based prediction models. Patients who underwent pancreaticoduodenectomy were enrolled and stratified into model development and validation sets by surgery between 2016 and 2017 or in 2018, respectively. Machine learning models based on clinical and body composition data, and deep learning models based on computed tomographic data, were developed, combined by ensemble voting, and final models were selected comparison with earlier model. Among the 1333 participants (training, n = 881; test, n = 452), postoperative pancreatic fistula occurred in 421 (47.8%) and 134 (31.8%) and clinically relevant postoperative pancreatic fistula occurred in 59 (6.7%) and 27 (6.0%) participants in the training and test datasets, respectively. In the test dataset, the area under the receiver operating curve [AUC (95% confidence interval)] of the selected preoperative model for predicting all and clinically relevant postoperative pancreatic fistula was 0.75 (0.71–0.80) and 0.68 (0.58–0.78). The ensemble model showed better predictive performance than the individual ML and DL models.

Revealing the role of early peripancreatic bacterial contamination and Enterococcus faecalis in pancreatic fistula development after pancreaticoduodenectomy: Implications for useful antibiotic prophylaxis–An observational cohort study

BackgroundPeripancreatic bacterial contamination (PBC) is a critical factor contributing to the development of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Controlling pathogenic bacteria is essential in preventing CR-POPF; however, the precise relationship between specific bacteria and CR-POPF remains unclear. This study aimed to investigate the relationship between PBC and CR-POPF after PD, with a focus on identifying potentially causative bacteria. MethodsThis prospective observational study enrolled 370 patients who underwent PD. Microbial cultures were routinely collected from peripancreatic drain fluid on postoperative days (PODs) 1, 3, and 6. Predictive factors for CR-POPF and the bacteria involved in PBC were investigated. ResultsCR-POPF occurred in 86 (23.2%) patients. In multivariate analysis, PBC on POD1 (Odds ratio [OR] = 3.59; P = 0.005) was one of the main independent predictive factors for CR-POPF, while prophylactic use of antibiotics other than piperacillin/tazobactam independently influenced PBC on POD1 (OR = 2.95; P = 0.010). Notably, Enterococcus spp., particularly Enterococcus faecalis, were significantly isolated from PBC in patients with CR-POPF compared to those without CR-POPF on PODs 1 and 3 (P < 0.001), and they displayed high resistance to all cephalosporins. ConclusionsEarly PBC plays a pivotal role in the development of CR-POPF following PD. Prophylactic antibiotic administration, specifically targeting Enterococcus faecalis, may effectively mitigate early PBC and subsequently reduce the risk of CR-POPF. This research sheds light on the importance of bacterial control strategies in preventing CR-POPF after PD.

Safety and performance of a synthetic sealant patch aimed to prevent postoperative pancreatic fistula after distal pancreatectomy (SHIELDS) – Prospective international multicenter phase II study

ObjectiveThe incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch. MethodsIn this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers. Following surgical resection, the transection plane was closed according to the standard of care and manually covered with the sealant patch. As primary endpoint the incidence of CR-POPF up to 30-days postoperatively was evaluated. The secondary endpoints included the assessment of complications and device usability. ResultsAmong 40 patients after distal pancreatectomy, CR-POPF occurred in 7 (17.5%) up to postoperative day 30. No type C POPF was observed. There was no intraoperative bleeding observed after patch application. ConclusionThe results of this international phase II study demonstrate promising results of a new sealant patch regarding the rate of CR-POPF. Randomized studies are now needed to confirm the superiority of the current patch as compared to the best current practice.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Proposal of the novel predictive model for postoperative pancreatic fistula in distal pancreatectomy for pancreatic tumor based on preoperative imaging parameters and stapler handling.

Distal pancreatectomy (DP) using linear staplers is widely performed; however, postoperative pancreatic fistulas (POPF) remain an issue. This study aimed to analyze preoperative risk factors for POPF and assess stapler handling. We retrospectively analyzed consecutive patients who underwent DP for pancreatic tumors using a linear stapler between 2014 and 2022. Preoperative measurements included pancreas-to-muscle signal intensity ratio (SIR) on fat-suppressed T1-weighted magnetic resonance imaging (MRI). The main outcome was clinically relevant POPF of the 2016 International Study Group of Pancreatic Fistulas definition. The predictive ability of the model was compared with the distal fistula risk score (D-FRS) by using the area under the receiver operating characteristic curve (AUROC). Among the 81 patients, POPF occurred in 31 (38.2%). Multivariate analysis identified computed tomography-measured pancreatic thickness (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.05-1.61, p=0.009) and SIR on T1-weighted MRI (OR 6.85, 95% CI 1.71-27.4, p=0.002) as preoperative predictors. A novel preoperative model, "Thickness×MRI (TM)"-index, was established by multiplying these two variables. The TM-index exhibited the highest predictability preoperatively (AUROC 0.757, 95% CI 0.649-0.867). In the intraoperative variable analyses, TM-index (p<0.001), thin cartridge application (p=0.032), and short pre-firing compression (p=0.047) were identified as significant risk factors for POPF. The model's AUROC combined with these two stapler handling methods was higher than D-FRS (0.851 vs. 0.660, p=0.006). The novel preoperative model exhibited excellent predictability. Thick cartridge use and long pre-firing compression were protective factors against POPF. This model may facilitate preventive surgical strategy development to reduce POPF.

Association of Postoperative Hyperamylasemia With Clinically Relevant Postoperative Pancreatic Fistula in Pancreatoduodenectomy.

Background In this study, we aimed to determine the association between postoperative hyperamylasemia (POH) and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). Methodology A prospective observational study of 140 consecutive PDs between March 2020 and March 2022 was conducted. POH was defined as an elevation in serum pancreatic amylase levels above the institutional upper limit of normal on postoperative day (POD) 1 (>100 U/L). CR-POPF was defined as the International Study Group of Pancreatic Surgery Grade B or C POPF. The primary outcome was the rate of CR-POPF in the study population. The trial was prospectively registered with Clinicaltrials.gov (NCT04514198). Results In our study, 93 (66.42%) patients had POH (serum amylase >100 U/L). CR-POPF developed in 48 (34.28%) patients: 40 type B and 8 type C. CR-POPF rate was 43.01% (40/93) in patients with POH compared to 17.02% (8/47) in patients without POH (p = 0.0022). Patients with POH had a mean serum amylase of 422.7 ± 358.21 U/L on POD1 compared to 47.2 ± 20.19 U/L in those without POH (p < 0.001). Serum amylase >100 U/L on POD1 was strongly associated with developing CR-POPF (odds ratio = 3.71; 95% confidence interval = 1.31-10.37) on logistic regression, with a sensitivity and specificity of 83.3% and 42.4%, respectively. Blood loss >350 mL, pancreatic duct size <3 mm, and elevated POD1 serum amylase >100 U/L were predictive of CR-POPF on multivariate analysis (p < 0.001). Conclusions An elevated serum amylase on POD1 may help identify patients at risk for developing POPF following PD.