Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Completion pancreatectomy during pancreatoduodenectomy: A lifesaving solution in high-risk patients.

BACKGROUND: Postoperative pancreatic fistula (POPF) is responsible of most major complications and fatalities after PD. By avoiding POPF, TP may improve operative outcomes in high-risk patients. The aim was to compare total pancreatectomy (TP) and pancreatoduodenectomy (PD) in high-risk patients and evaluate results of implementing a risk-tailored strategy in clinical practice. METHODS: Between 2014 and 2023, 139 patients (76 men, median age 67 years) underwent resection of disease located in the head of the pancreas. Starting January 1, 2022, we offered TP to patients at high POPF risks (fistula risk score (FRS) ≥7) and to patients with intermediate POPF risks (FRS: 3-6) and high risks of failure to rescue (age> 75 years, ASA score ≥3). We compared outcomes of TP and PD and evaluated the results of the new strategy implementation on operative outcomes. Propensity score-based analysis was performed to limit bias of between-group comparison. RESULTS: Eventually, 26 (19%) patients underwent TP and 113 (81%) patients underwent PD. Severe complications occurred in 42 (30%) patients and 13 (9%) patients died. TP resulted in shorter lengths of hospital stay (median: 14 days [11; 18] vs. 17 days [13; 24], p = 0.016) and less risks of post-pancreatectomy hemorrhage (PPH) (0% vs. 20%, p < 0.001) compared to PD. Crude and propensity match analysis showed that the implementation of a risk-tailored strategy led to significant reduction of reoperation, POPF, PPH and mortality rates. CONCLUSION: The use of TP as part of a risk-tailored strategy in high-risk patients can be lifesaving.

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

BACKGROUND: Postoperative 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. METHODS: All 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. RESULTS: Overall, 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). CONCLUSION: This 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.

Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Prophylactic passive abdominal drainage is standard practice after distal pancreatectomy. This approach aims to mitigate the consequences of postoperative pancreatic fistula (POPF) but its added value, especially in patients at low risk of POPF, is currently being debated. We aimed to assess the non-inferiority of a no-drain policy in patients after distal pancreatectomy. METHODS: In this international, multicentre, open-label, randomised controlled, non-inferiority trial, we recruited patients aged 18 years or older undergoing open or minimally invasive elective distal pancreatectomy for all indications in 12 centres in the Netherlands and Italy. We excluded patients with an American Society of Anesthesiology (ASA) physical status of 4-5 or WHO performance status of 3-4, added by amendment following the death of a patient with ASA 4 due to a pre-existing cardiac condition. Patients were randomly assigned (1:1) intraoperatively by permuted blocks (size four to eight) to either no drain or prophylactic passive drain placement, stratified by annual centre volume (<40 or ≥40 distal pancreatectomies) and low risk or high risk of grade B or C POPF. High-risk was defined as a pancreatic duct of more than 3 mm in diameter, a pancreatic thickness at the neck of more than 19 mm, or both, based on the Distal Pancreatectomy Fistula Risk Score. Other patients were considered low-risk. The primary outcome was the rate of major morbidity (Clavien-Dindo score ≥III), and the most relevant secondary outcome was grade B or C POPF, grading per the International Study Group for Pancreatic Surgery. Outcomes were assessed up to 90 days postoperatively and analysed in the intention-to-treat population and per-protocol population, which only included patients who received the allocated treatment. A prespecified non-inferiority margin of 8% was compared with the upper limit of the two-sided 95% CI (Wald) of unadjusted risk difference to assess non-inferiority. This trial is closed and registered in the Netherlands Trial Registry, NL9116. FINDINGS: Between Oct 3, 2020, and April 28, 2023, 376 patients were screened for eligibility and 282 patients were randomly assigned to the no-drain group (n=138; 75 [54%] women and 63 [46%] men) or the drain group (n=144; 73 [51%] women and 71 [49%] men). Seven patients in the no-drain group received a drain intraoperatively; consequently, the per-protocol population included 131 patients in the no-drain group and 144 patients in the drain group. The rate of major morbidity was non-inferior in the no-drain group compared with the drain group in the intention-to-treat analysis (21 [15%] vs 29 [20%]; risk difference -4·9 percentage points [95% CI -13·8 to 4·0]; pnon-inferiority=0·0022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference -4·1 percentage points [-13·2 to 5·0]; pnon-inferiority=0·0045). Grade B or C POPF was observed in 16 (12%) patients in the no-drain group and in 39 (27%) patients in the drain group (risk difference -15·5 percentage points [95% CI -24·5 to -6·5]; pnon-inferiority<0·0001) in the intention-to-treat analysis. Three patients in the no-drain group died within 90 days; the cause of death in two was not considered related to the trial. The third death was a patient with an ASA score of 4 who died after sepsis and a watershed cerebral infarction at second admission, leading to multiple organ failure. No patients in the drain group died within 90 days. INTERPRETATION: A no-drain policy is safe in terms of major morbidity and reduced the detection of grade B or C POPF, and should be the new standard approach in eligible patients undergoing distal pancreatectomy. FUNDING: Ethicon UK (Johnson & Johnson Medical, Edinburgh, UK).

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Hand-sewn gastrojejunal anastomosis reduces delayed gastric emptying after pancreaticoduodenectomy: A single-center retrospective clinical study of 1,077 consecutive patients.

BACKGROUND: Hand-sewn anastomosis and stapled anastomosis are the 2 main types of gastrojejunal anastomotic methods in pancreaticoduodenectomy. There is ongoing debate regarding the most effective anastomotic method for reducing delayed gastric emptying after pancreaticoduodenectomy. This study aims to identify factors that influence delayed gastric emptying after pancreaticoduodenectomy and assess the impact of different anastomotic methods on delayed gastric emptying. METHODS: The study included 1,077 patients who had undergone either hand-sewn anastomosis (n = 734) or stapled anastomosis (n = 343) during pancreaticoduodenectomy between December 2016 and November 2021 at our department. We retrospectively analyzed the clinical data, and a 1:1 propensity score matching was performed to balance confounding variables. RESULTS: After propensity score matching, 320 patients were included in each group. Compared with the stapled anastomosis group, the hand-sewn anastomosis group had a significantly lower incidence of delayed gastric emptying (28 [8.8%] vs 55 [17.2%], P = .001) and upper gastrointestinal tract bleeding (6 [1.9%] vs 17 [5.3%], P = .02). Additionally, the hand-sewn anastomosis group had a significantly reduced postoperative length of stay and lower hospitalization expenses. However, the hand-sewn anastomosis group had a significantly longer operative time, which was consistent with the analysis before propensity score matching. Logistic regression analysis showed that stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula were independent prognostic factors for delayed gastric emptying. CONCLUSION: Hand-sewn anastomosis was associated with a lower incidence rate of clinically relevant delayed gastric emptying after pancreaticoduodenectomy. Stapled anastomosis, intra-abdominal infection, and clinically relevant postoperative pancreatic fistula could increase the incidence of postoperative clinically relevant delayed gastric emptying. Hand-sewn anastomosis should be considered by surgeons to reduce the occurrence of postoperative delayed gastric emptying and improve patient outcomes.

Pancreatic stump closure after distal pancreatectomy: Systematic review and meta-analysis of randomized clinical trials comparing non-autologous versus no reinforcement: Value of prediction intervals.

BACKGROUND: This meta-analysis of randomized trials aimed to assess the benefits and harms of non-autologous versus no reinforcement of the pancreatic stump following distal pancreatectomy (DP). METHODS: It was performed in accordance with PRISMA 2020 and AMSTAR 2 Guidelines. (registered in PROSPERO ID: EROCRD42021286863). RESULTS: Nine relevant articles (between 2009 and 2021) were retrieved, comparing non-autologous reinforcement (757 patients) with non-reinforcement (740 patients) after PD. Pooled analysis showed a statistically significant lower rate of postoperative pancreatic fistula (POPF) in the reinforcement group (RR â€‹= â€‹0.677; 95 â€‹% CI [0.479, 0.956], p â€‹= â€‹0.027). The 95 â€‹% predictive interval (0.267-1.718) showed heterogeneity. Non-autologous reinforcement other than with "Tachosil®" was effective (subgroup analysis). No statistically significant differences were found between the two groups with regard to secondary outcomes. CONCLUSIONS: This meta-analysis showed that covering the stump with non-autologous reinforcement other than Tachosil® had a preventive effect on the onset of POPF.

Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy (LPDEXCEPT): protocol for a multicentre superiority randomised controlled trial.

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection. METHODS AND ANALYSIS: The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula. ETHICS AND DISSEMINATION: Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: NCT05808894.

Comparison of manual sutures and laparoscopic stapler for pancreatic stump closure techniques in robotic distal pancreatectomy: a single-center experience.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) are prevalent and major postoperative complications of distal pancreatectomy (DP). There are numerous ways to manage the pancreatic stump. However, no single approach has been shown to be consistently superior. Moreover, the potential role of robotic systems in reducing POPFs has received little attention. METHODS: The clinical data of 119 patients who had consecutively received robotic distal pancreatectomy between January 2019 and December 2022 were retrospectively analyzed. Patients were divided into two groups according to the method of handling the pancreatic stump. The attributes of the patients and the variables during the perioperative period were compared. RESULTS: The analysis included 72 manual sutures and 47 stapler procedures. The manual suture group had a shorter operative time (removing installation time) than the stapler group (125.25 ± 63.04 min vs 153.30 ± 62.03 min, p = 0.019). Additionally, the manual suture group had lower estimated blood loss (50 mL vs 100 mL, p = 0.009) and a shorter postoperative hospital stay. There were no significant differences in the incidence of clinically relevant POPFs between the two groups (18.1% vs 23.4%, P > 0.05). No perioperative death occurred in either group. CONCLUSION: The manual suturing technique was shown to have an incidence of POPFs similar to the stapler technique in robotic distal pancreatectomy and to be safe and feasible.

Reconsidering the role of prophylactic pancreaticojejunostomy in pancreatic enucleation: balancing the benefits and risks.

BACKGROUND: The incidence of postoperative pancreatic fistula (POPF) following enucleation is high, and prophylactic pancreaticojejunostomy (PPJ) is frequently performed. Minimally invasive enucleation (MEN) has been demonstrated to be safe and feasible, leaving most enucleation wounds exposed. METHODS: The clinical data of 40 patients who underwent open enucleation with PPJ at our center between 2012 and 2021 were compared with those of 80 patients who underwent MEN. RESULTS: The MEN group had better outcomes than the PPJ group in terms of intraoperative bleeding (50.0 versus 100.0 mL), postoperative semi-liquid diet recovery (2.0 versus 5.0 days), and postoperative length of stay (7.7 versus 12.5 days). While the MEN group had higher rates of complex enucleation (60.0% versus 40.0%), main pancreatic duct repair (32.5% versus 10.0%), discharge with drains (48.8% versus 25.0%), and grade B POPFs (47.5% versus 17.5%). Both surgical methods effectively preserved pancreatic function; however, two patients in the PPJ group experienced severe haemorrhaging and died. Additionally, during the follow-up period, gastrointestinal bleeding was found and discomfort in the surgical area was reported. CONCLUSION: Pancreatic enucleation combined with PPJ should be avoided, and although a biochemical or grade B POPF may develop after MEN, it can be compensated for by preserving pancreatic function and ensuring a good long-term quality of life in the patients.

Dual-crosslinking immunostimulatory hydrogel synchronously suppresses pancreatic fistula and pancreatic cancer relapse post-resection.

In pancreatic cancer (PC), surgical resection remains the sole curative option, albeit patients undergoing resection are susceptible to postoperative pancreatic fistula (PF) formation and tumor recurrence. An unmet need exists for a unified strategy capable of concomitantly averting PF and tumor relapse to mitigate morbidity in PC patients after surgery. Herein, an original dual crosslinked biological sealant hydrogel (methacrylate-hyaluronic acid-dopamine (MA-HA-DA) and sulfhydryl-hyaluronic acid-dopamine (SH-HA-DA)) was engineered as a drug depot and loaded with polydopamine-cloaked cytokine interleukin-15 and platelets conjugated with anti-TIGIT. In vitro analyses validated favorable tissue adhesion, cytocompatibility, and stability of the hydrogels. In a PF rodent model, the hydrogel effectively adhered to the pancreatic stump, sealing the severed pancreatic end and impeding post-operative elevations in amylase and lipase. In PC murine models, hydrogels potently stimulated CD8+ T and NK cells to deter residual tumor re-growth and distant metastasis. This innovative hydrogel strategy establishes a new framework for concomitant prevention of PF and PC recurrence.

Nationwide validation of the distal fistula risk score (D-FRS).

PURPOSE: Distal pancreatectomy (DP) is associated with a high complication rate of 30-50% with postoperative pancreatic fistula (POPF) as a dominant contributor. Adequate risk estimation for POPF enables surgeons to use a tailor-made approach. Assessment of the risk of POPF prior to DP can lead to the application of preventive strategies. The current study aims to validate the recently published preoperative and intraoperative distal fistula risk score (D-FRS) in a nationwide cohort. METHODS: This nationwide retrospective Dutch cohort study included all patients after DP for any indication, all of whom were registered in the Dutch Pancreatic Cancer Audit (DPCA) database between 2013 and 2021. The D-FRS was validated by filling in the probability equations with data from this cohort. The predictive capacity of the models was represented by an area under the receiver operating characteristic (AUROC) curve. RESULTS: A total of 896 patients underwent DP of which 152 (17%) developed POPF of whom 144 grade B (95%) and 8 grade C (5%). The preoperative D-FRS, consisting of the variables pancreatic neck thickness and pancreatic duct diameter, showed an AUROC of 0.73 (95%CI 0.68-0.78). The intraoperative D-FRS, comprising pancreatic neck, duct diameter, BMI, operating time, and soft pancreatic aspect, showed an AUROC of 0.69 (95%CI 0.64-0.74). CONCLUSION: The current study is the first nationwide validation of the preoperative and intraoperative D-FRS showing acceptable distinguishing capacity for only the preoperative D-FRS for POPF. Therefore, the preoperative score could improve prevention and mitigation strategies such as drain management, which is currently investigated in the multicenter PANDORINA trial.

Efficacy of rectal indomethacin in prevention of post-operative hyperamylasemia following pancreatoduodenectomy: a randomized controlled trial.

BACKGROUND: Post-operative hyperamylasemia (POH) following pancreatoduodenectomy (PD) may play a key role in pathogenesis of post-operative pancreatic fistula (POPF). Aim of the current study was to evaluate efficacy of perioperative administration of indomethacin in preventing POH. METHODS: Single-center, double-blind, randomized controlled trial (RCT) conducted on consecutive patients undergoing PD. Patients received either 100 mg of indomethacin per-rectally at induction of anesthesia or standard care. Primary endpoint was incidence of POH in the two arms. POH was defined as postoperative day (POD) 1 serum amylase (S. amylase) levels greater than the upper limit of normal. RESULTS: After exclusion 44 patients were randomized. The two arms were comparable for preoperative and intraoperative parameters. POH was noted in 20/44 (45.5%) with significantly lower incidence of POH (60.9% vs. 28.6%, p = 0.032) in intervention arm (IA). Median S. amylase, POD 1, 3, and 5 drain amylase, and incidence of clinically relevant POPF (CR-POPF) were lower in IA but failed to reach statistical significance (30.4% vs. 14.3%, p = 0.18). The severity of delayed gastric emptying (DGE) was significantly lower in the IA (grade B/C DGE 23.8% vs. 47.8%, p = 0.023). Evaluation of risk factors for POH showed IA to confer an independent protective effect and increased risk with soft pancreas. CONCLUSION: Perioperative per-rectal indomethacin administration is effective in decreasing the incidence of POH following pancreatoduodenectomy.

The cholinesterase and C-reactive protein score is a potential predictor of pseudoaneurysm formation after pancreaticoduodenectomy in patients with soft pancreas.

BACKGROUND: Pseudoaneurysm (PA) rupture after pancreaticoduodenectomy (PD) is a life-threatening complication. Most PA cases originate from postoperative pancreatic fistulas (POPFs). Although several risk factors for POPF have been identified, specific risk factors for PA formation remain unclear. Therefore, we retrospectively analyzed PD cases with soft pancreas and proposed a novel strategy for early detection of PA formation. METHODS: Overall, 120 patients underwent PD between 2010 and 2020 at our institution; of these, 65 patients with soft pancreas were enrolled. We evaluated the clinicopathological factors influencing PA formation and developed a risk score to predict PA formation. RESULTS: In total, 11 of the 65 patients developed PAs (PA formation group: PAG), and 8 of these 11 PAs ruptured. The median time to PA formation was 15 days, with a minimum of 5 days. The PAG was significantly older than the non-PA formation group, were predominantly men, and had comorbid diabetes mellitus. Pre- and intra-operative findings were similar between the two groups. Importantly, no significant differences were found in postoperative drain amylase levels and total drain amylase content. Cholinesterase and C-reactive protein (CRP) levels on postoperative day (POD) 3 were significantly different between the two groups. Multivariate analysis showed that cholinesterase ≤ 112 U/L and CRP ≥ 16.0 mg/dl on POD 3 were independent predictors of PA formation. CONCLUSIONS: Decreased cholinesterase and elevated CRP on POD 3 (Cho-C score) are useful predictors of PA formation in cases with soft pancreas. In such cases, periodic computed tomography evaluations and strict drain management are necessary to prevent life-threatening hemorrhage.

Reinforced stapling does not reduce postoperative pancreatic fistula in distal pancreatectomy: a systematic review and meta-analysis.

Postoperative pancreatic fistula (POPF) is a severe complication after distal pancreatectomy (DP); however, it is unclear how to effectively reduce the incidence. The purpose of this meta-analysis is to determine whether reinforced stapling reduces POPF after DP. From February 2007 to April 2023, a comprehensive search of electronic data and references was conducted in PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. In this study, the perioperative outcomes were evaluated for the reinforced stapler (RS) group and the standard stapler (SS) group in DP using Review Manager Software. Using fixed- or random-effects models, pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. In total, three randomized clinical trials (RCTs) with 425 patients and five observational clinical studies (OCS) with 318 patients were included. In pooled meta-analyses from RCTs, there was no difference between the two groups in the incidence of POPF (OR = 0.79; 95% CI [0.47,1.35]; P = 0.39), intraoperative blood loss (MD = 10.66; 95% CI [- 28.83,50.16]; P = 0.6), operative time (MD = 9.88; 95% CI [- 8.92,28.67]; P = 0.3), major morbidity (OR = 1.12; 95% CI [0.67,1.90]; P = 0.66), reoperation (OR = 0.97; 95% CI [0.41,2.32]; P = 0.95), readmission (OR = 0.99; 95% CI [0.57,1.72]; P = 0.97) or hospital stay (MD = - 0.95; 95% CI [- 5.22,3.31]; P = 0.66). However, the results of POPF and readmission were favorable for RS in the OCS group.

Wrapping pancreaticojejunostomy using the ligamentum teres hepatis during laparoscopic pancreaticoduodenectomy: a propensity score matching analysis.

BACKGROUND AND OBJECTIVE: It is controversial whether wrapping around the pancreaticojejunostomy (PJ) could reduce the rate of postoperative pancreatic fistula (POPF), especially in laparoscopic pancreaticoduodenectomy (LPD). This study aims to summarize our single-center initial experience in wrapping around PJ using the ligamentum teres hepatis (LTH) and demonstrate the feasibility and safety of this method. METHODS: Patients who underwent LPD applying the procedure of wrapping around the PJ were identified. The cohort was compared to the cohort with standard non-wrapping PJ. A 1:1 propensity score matching (PSM) was performed to compare the early postoperative outcomes of the two cohorts. Risk factors for POPF were determined by using univariate and multivariate logistic regression analysis. RESULTS: Overall, 143 patients were analyzed (LPD without wrapping (n = 91) and LPD with wrapping (n = 52)). After 1:1 PSM, 48 patients in each cohort were selected for further analysis. Bile leakage, DGE, intra-abdominal infection, postoperative hospital stays, harvested lymph nodes, and R0 resection were comparable between the two cohorts. However, the wrapping cohort was associated with significantly less POPF B (1 vs 18, P = 0.003), POPF C (0 vs 8, P = 0.043), and Clavien-Dindo classification level III-V (5 vs 26, P = 0.010). No patients died due to the clinically relevant POPF in the two cohorts. No patients who underwent the LTH wrapping procedure developed complications directly related to the wrapping procedure. After PSM, whether wrapping was an independent risk factor for POPF (OR = 0.202; 95%CI:0.080-0.513; P = 0.001). CONCLUSIONS: Wrapping the LTH around the PJ technique for LPD was safe, efficient, and reproducible with favorable perioperative outcomes in selected patients. However, further validations using high-quality RCTs are still required to confirm the findings of this study.

Retroperitonealization of the pancreatic stump in distal pancreatectomy: a novel technique to reduce postoperative pancreatic fistula.

PURPOSE: To evaluate the efficacy and safety of retroperitonealization of the pancreatic stump in distal pancreatectomy. METHODS: Clinical data from the Tongji Hospital pancreatic database were retrospectively reviewed in this study. The data of 68 patients who underwent retroperitonealized distal pancreatectomy from January, 2019, to April, 2021, were collected and analyzed. Sixty-four patients who underwent conventional distal pancreatectomy during the same period were matched. We compared and analyzed the operative outcomes and postoperative complications between the patients in the two groups before and after propensity score matching (PSM). RESULTS: Before PSM, the operative outcomes and postoperative complications were comparable between the two groups. After PSM, the retroperitonealized group had a lower incidence of postoperative pancreatic fistula (POPF) (10.53% vs 31.58%, P = 0.047) and shorter time until drainage removal (10.00, 8.00-13.00 days vs 13.00, 10.00-18.00 days, P = 0.005). In the univariate and multivariate regression analyses, non-retroperitonealization and intra-abdominal infection were found to be independent risk factors for postoperative pancreatic fistula (POPF). CONCLUSION: Retroperitonealization of the pancreatic stump can reduce the incidence of POPF after distal pancreatectomy.