Sealing the Pandora's vase of pancreatic fistula through entrapping the digestive enzymes within a dextrorotary (D)-peptide hydrogel.

A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases.

Early postoperative fever as a predictor of pancreatic fistula after pancreaticoduodenectomy: a single-center retrospective observational study.

BACKGROUND: The connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF. METHODS: This retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF. RESULTS: Of the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34-2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42-2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73-0.79) and 0.75 (95% CI, 0.72-0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00-0.03; DeLong's test, P = 0.005). CONCLUSIONS: Early postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker.

The Potential Clinical Benefits of Direct Surgical Transgastric Pancreatic Necrosectomy for Patients With Infected Necrotizing Pancreatitis.

OBJECTIVE: Surgical transgastric pancreatic necrosectomy (STGN) has the potential to overcome the shortcomings (ie, repeat interventions, prolonged hospitalization) of the step-up approach for infected necrotizing pancreatitis. We aimed to determine the outcomes of STGN for infected necrotizing pancreatitis. MATERIALS AND METHODS: This observational cohort study included adult patients who underwent STGN for infected necrosis at two centers from 2008 to 2022. Patients with a procedure for pancreatic necrosis before STGN were excluded. Primary outcomes included mortality, length of hospital and intensive care unit (ICU) stay, new-onset organ failure, repeat interventions, pancreatic fistulas, readmissions, and time to episode closure. RESULTS: Forty-three patients underwent STGN at a median of 48 days (interquartile range [IQR] 32-70) after disease onset. Mortality rate was 7% (n = 3). After STGN, the median length of hospital was 8 days (IQR 6-17), 23 patients (53.5%) required ICU admission (2 days [IQR 1-7]), and new-onset organ failure occurred in 8 patients (18.6%). Three patients (7%) required a reintervention, 1 (2.3%) developed a pancreatic fistula, and 11 (25.6%) were readmitted. The median time to episode closure was 11 days (IQR 6-22). CONCLUSIONS: STGN allows for treatment of retrogastric infected necrosis in one procedure and with rapid episode resolution. With these advantages and few pancreatic fistulas, direct STGN challenges the step-up approach.

Efficacy of Reinforced Stapler for Preventing Postoperative Pancreatic Fistula After Minimally Invasive Distal Pancreatectomy.

BACKGROUND/AIM: Although minimally invasive distal pancreatectomy (MIDP) has become a treatment option for benign and malignant pancreatic tumors, the safety and efficacy of reinforced staplers in MIDP remain controversial. The present study was performed to evaluate the safety of reinforced staplers in MIDP and identify the risk factors for postoperative pancreatic fistula (POPF) after MIDP with reinforced staplers. PATIENTS AND METHODS: In total, 92 consecutive patients who underwent MIDP at NHO Kyushu Medical Center from July 2016 to August 2023 were enrolled in this retrospective study. In all patients, a reinforced black cartridge triple-row stapler (Covidien Japan, Tokyo, Japan) was used during MIDP. The primary endpoint was the incidence of clinically relevant POPF. The risk factors for POPF were evaluated using multivariate analysis. RESULTS: Among the 92 patients, 74 underwent laparoscopic distal pancreatectomy and 18 underwent robot-assisted distal pancreatectomy. Clinically relevant POPF occurred in seven (7.6%) of 92 patients. The rate of severe complications (Clavien-Dindo grade ≥III) was 10.8%, and the mortality rate was 0%. The median postoperative hospital stay was 14 days. Multivariate logistic regression analysis showed that the independent risk factor for clinically relevant POPF after MIDP with a reinforced stapler was a body mass index of ≥22.6 kg/m2 (p=0.050, odds ratio=7.60). CONCLUSION: This study confirmed the safety and efficacy of reinforced staplers for preventing POPF after MIDP. A high body mass index was the only risk factor for clinically relevant POPF after MIDP with a reinforced stapler.

Perioperative and oncologic outcomes of robot-assisted versus open surgery for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare perioperative and oncologic outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) treated with robotic-assisted surgery versus open laparotomy. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and cohort studies up to June 15, 2024, were identified using PubMed, EMBASE, and Google Scholar. Additionally, reference lists of included studies, relevant review articles, and clinical guidelines were manually searched. The primary outcomes evaluated were length of stay, 90-day mortality, postoperative pancreatic fistula (POPF), and Post-pancreatectomy haemorrhage (PPH). Secondary outcomes included estimated blood loss, reoperation rate, lymph node yield, and operative time. The final analysis included 10 retrospective cohort studies involving 23,272 patients (2,179 robotic-assisted and 21,093 open surgery). There were no significant differences between the two procedures in terms of postoperative pancreatic fistula, Post-pancreatectomy haemorrhage, lymph node yield, and operative time. However, patients undergoing robotic-assisted surgery had shorter lengths of stay, lower 90-day mortality, and less estimated blood loss compared to those undergoing open surgery. The reoperation rate was higher for the robotic-assisted group. Robotic-assisted surgery for pancreatic ductal adenocarcinoma is safe and feasible. Compared to open surgery, it offers better perioperative and short-term oncologic outcomes, but with a higher risk of reoperation.

Efficacy of the two-parts wrapping technique in reducing postoperative complications in laparoscopic pancreaticoduodenectomy.

BACKGROUND: The advancement of laparoscopic technology has broadened the application of laparoscopic pancreaticoduodenectomy (LPD) for treating pancreatic head and ampullary tumors. Despite its benefits, postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) remain significant complications. Ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) stump show limitations in reducing POPF and PPH. METHODS: This study retrospectively analyzed patients undergoing LPD from January 2016 to October 2023, We compared the effectiveness of the two-parts wrapping (the ligamentum teres hepatis wrapping of the gastroduodenal artery stump and the omentum flap wrapping of the pancreatojejunal anastomosis) and ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) in reducing postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH), using propensity score matching for the analysis. RESULTS: A total of 172 patients were analyzed, showing that the two-parts wrapping group significantly reduced the rates of overall and severe complications, POPF, and PPH compared to ligamentum teres hepatis wrapping around the GDA group. Specifically, the study found lower rates of grade B/C POPF and no instances of PPH in the two-parts wrapping group, alongside shorter postoperative hospital stays and drainage removal times. These benefits were particularly notable in patients with soft pancreatic textures and pancreatic duct diameters of < 3 mm. CONCLUSION: The two-parts wrapping technique significantly reduce the risks of POPF and PPH in LPD, offering a promising approach for patients with soft pancreas and pancreatic duct diameter of < 3 mm.

Clinical significance of postoperative complications after pancreatic surgery in time-to-complication and length of postoperative hospital stay: a retrospective study.

PURPOSE: We retrospectively analyzed pancreatectomy patients and examined the occurrence rate and timing of postoperative complications (time-to-complication; TTC) and their impact on the length of postoperative hospital stay (POHS) to clarify their characteristics, provide appropriate postoperative management, and improve short-term outcomes in the future. METHODS: A total of 227 patients, composed of 118 pancreaticoduodenectomy (PD) and 109 distal pancreatectomy (DP) cases, were analyzed. We examined the frequency of occurrence, TTC, and POHS of each type of postoperative complication, and these were analyzed for each surgical procedure. Complications of the Clavien-Dindo (CD) classification Grade II or higher were considered clinically significant. RESULTS: Clinically significant complications were observed in 70.3% and 36.7% of the patients with PD and DP, respectively. Complications occurred at a median of 10 days in patients with PD and 6 days in patients with DP. Postoperative pancreatic fistula (POPF) occurred approximately 7 days postoperatively in both groups. For the POHS, in cases without significant postoperative complications (CD ≤ I), it was approximately 22 days for PD and 11 days for DP. In contrast, when any complications occurred, POHS increased to 30 days for PD and 19 days for DP (each with additional 8 days), respectively. In particular, POPF prolonged the hospital stay by approximately 11 days for both procedures. CONCLUSION: Each postoperative complication after pancreatectomy has its own characteristics in terms of the frequency of occurrence, TTC, and impact on POHS. A correct understanding of these factors will enable timely therapeutic intervention and improve short-term outcomes after pancreatectomy.

Omental Flap Technique in Pancreaticojejunostomy: Does it Prevent Pancreatic Fistula Development after Pancreaticoduodenectomy?

AIM: The aim of our study was to investigate the clinical results of omental flap application during pancreaticojejunostomy (PJ) anastomosis in pancreatoduodenectomy (PD) surgeries. METHODS: The data of patients who underwent pancreaticoduodenectomy in our hospital were evaluated retrospectively. The patients were divided into two groups; patients with an omental flap (Group 1) and those without an omental flap (Group 2). The demographic and other characteristics of the groups and the incidence of postoperative pancreatic fistula (POPF) development were compared. RESULTS: One hundred patients were included (39 females, 61 males) Group 1 consisted of 20 patients with omental flaps and Group 2 consisted of 80 patients without omental flaps. While no clinically significant (Grade B and C) leaks were observed in Group 1, both biochemical and clinically significant leak rates were lower in Group 1 compared to 4 patients (5%) in Group 2. There was no statistically significant difference compared with Group 2 (p > 0.05). CONCLUSIONS: Although not statistically significant in this study, postoperative complication rates and the incidence of POPF tended to decrease in patients who underwent omental flaps.

[Our innovations for the reduction of postoperative pancreatic fistula output]. / A posztoperatív pancreasfistula csökkentésére bevezetett innovációink.

Bevezetés: A posztoperatív pancreasfistula mind proximalis, mind distalis pancreatectomia után a legjelentosebb sebészi szövodménynek számít. A szakirodalomban nincs egyértelmuen ajánlott, megbízható módszer ezen probléma kiküszöbölésére, emiatt történnek újítások szerte a világon. Jelen közleményünkben a technikai innovációinkról számolunk be. Anyag és módszerek: 2013. január 1-jétol 2023. november 30-ig terjedo idoszakban 205 Whipple-mutétet végeztünk nyitottan, mely során a pancreatojejunalis anastomosist az általunk módosított dohányzacskó-öltéses módszerrel készítettük el. 2019. január 1. és 2023. november 30. között pedig 30 betegnél történt nyitott distalis pancreatectomia, amikor a pancreascsonkot az általunk kifejlesztett technikával, szabad rectus fascia-peritoneum grafttal fedtük, majd azt cirkuláris öltéssel rögzítettük. Közleményünkben ezen két módszerrel elért eredményeket ismertetjük. Eredmények: a demográfiai adatok megfeleltek a betegségnél szokásosnak. A posztoperatív ápolási ido és a transzfúzió igény terén észlelt különbségek tükrözték a kétféle beavatkozás eltéro invazivitását. A releváns pancreasfistula kialakulási rátája kedvezo képet mutatott, Whipple-mutét után 7,3% volt, míg distalis pancreatectomát követoen nem fejlodött ki. A reoperációs és a halálozási arányok megfeleltek az elvártaknak és korreláltak a mutétek kiterjedtségével. Következtetés: pancreas resectiók utáni komplikációk csökkentésére tett törekvéseink során a módosított dohányzacskó-öltéses pancreatojejunostomia és a pancreascsonk fedésére kidolgozott módszerünk egyaránt kedvezo eredményekkel járt.

Association of preoperative CT-scan features and clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy: a meta-analysis.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a significant complication after pancreaticoduodenectomy. CR-POPF is associated with various adverse outcomes, including high mortality rates. Identifying complication predictors for CR-POPF, such as preoperative CT scan features, including pancreatic attenuation index (PAI) and pancreatic duct diameter (PDD), is critical. This systematic review and meta-analysis consolidate existing literature to assess the impact of these variables on CR-POPF risk. METHODS: Our comprehensive search, conducted in May 2023, covered PubMed, Scopus, Embase, and Web of Science databases. Inclusion criteria encompassed peer-reviewed cohort studies on pancreaticoduodenectomy, focusing on preoperative CT scan data. Case reports, case series, and studies reporting distal pancreatectomy were excluded. The quality assessment of included articles was done using New-Castle Ottawa Scale for cohort studies. Statistical analysis was carried out using Review Manager 5. This study was registered at the International Prospective Register of Systematic Reviews database (PROSPERO) on 12 May 2023 (registration number: CRD42023414139). RESULTS: We conducted a detailed analysis of 38 studies with 7393 participants. The overall incidence of CR-POPF was 24%. Multiple linear regression analyses revealed that PDD and pancreatic parenchymal thickness were significantly associated with CR-POPF. CONCLUSION: Our systematic review and meta-analysis shed light on CT scan findings for predicting CR-POPF after Whipple surgery. Age, PDD, and pancreatic parenchymal thickness significantly correlate with CR-POPF.

One hundred consecutive pancreatic resections using a novel pancreatico-jejunostomy technique.

BACKGROUND: No single technique of remnant pancreas reconstruction after pancreaticoduodenectomy (PD) has been demonstrated to be superior to the others in the prevention of post-operative pancreatic fistula (POPF), and the accumulation of surgical experience is closely related to the quality of this anastomosis. The aim of the current study was to evaluate the feasibility and patient outcomes of a simplified technique involving a single-layer continuous pancreaticojejunostomy (PJA) with Falciform ligament reinforcement that can be used with all types of pancreases. METHODS: A single-centre and single-surgeon study was performed. One hundred consecutive patients undergoing pancreatic resection with subsequent PJA using a novel technique performed by a single surgeon were included in the study. Patient demographics, pre-operative treatments, risk factors for POPF, and post-operative morbidity and mortality and long-term patient outcome were prospectively recorded and reported. RESULTS: From March 2018 to March 2022, 59 male and 41 female patients were included. 91 patients underwent PD for malignancy with 32 receiving neoadjuvant treatment. 59 patients were classified as intermediate/high risk for POPF according to validated fistula prediction models. There were 12 POPF Type B and 2 POPF Type C. The overall morbidity rate was 16% with no 90-day mortality. 3 patients underwent reoperation. The median length of hospitalisation was 12.6 days and 82% of eligible patients commenced and completed adjuvant chemotherapy. CONCLUSION: Single-layer continuous dunking PJA with Falciform ligament reinforcement is a simplified and feasible method for PJA with a low associated complication rate.

Evaluation of postoperative pancreatic fistula prediction scales following pancreatoduodenectomies based on magnetic resonance imaging: A diagnostic test study.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most feared and common complications following pancreatoduodenectomies. This study aims to evaluate the performance of different scales in predicting POPF using magnetic resonance imaging (MRI), including estimation of the pancreatic duct diameter, pancreatic texture, main duct index, relation to the portal vein, and intra-abdominal fat thickness. MATERIALS AND METHODS: A retrospective diagnostic test study was designed. Between January 2017 and December 2021, 133 pancreatoduodenectomies were performed at our institution. The performance for predicting overall POPF and clinically relevant POPF (CR-POPF) was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: A total of 96 patients were included in the study, of whom 26 patients experienced overall POPF, and 8 patients had CR-POPF. When analyzing the predictive value of each of the different scores applied, the Birmingham score showed the highest performance for predicting overall POPF and CR-POPF with an AUC (area under the curve) of 0.815 (95 % CI 0.725-0.906) and 0.813 (0.679-0.947), respectively. CONCLUSION: The Birmingham scale demonstrated the highest predictive performance for POPF. It is a simple scale with only two variables that can be obtained preoperatively using MRI. Based on these results, we recommend its use in patients undergoing pancreatoduodenectomy.

Prolonged pre-firing pancreatic compression with linear staplers in distal pancreatectomy: a valuable technique for post-operative pancreatic fistula prevention.

PURPOSE: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. METHODS: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. RESULTS: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). CONCLUSION: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland.

Effect of artificial or autologous coverage of the pancreatic remnant or anastomosis on postoperative pancreatic fistulas after partial pancreatectomy: meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic remnant can reduce the incidence of postoperative pancreatic fistulas. The aim of this study was to evaluate the effect of autologous or artificial coverage of the pancreatic remnant or anastomosis on outcomes after partial pancreatectomy. METHODS: A systematic literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2024. All RCTs analysing a coverage method in patients undergoing partial pancreatoduodenectomy or distal pancreatectomy were included. The primary outcome was postoperative pancreatic fistula development. Subgroup analyses for pancreatoduodenectomy or distal pancreatectomy and artificial or autologous coverage were conducted. RESULTS: A total of 18 RCTs with 2326 patients were included. In the overall analysis, coverage decreased the incidence of postoperative pancreatic fistulas by 29% (OR 0.71, 95% c.i. 0.54 to 0.93, P < 0.01). This decrease was also seen in the 12 RCTs covering the remnant after distal pancreatectomy (OR 0.69, 95% c.i. 0.51 to 0.94, P < 0.02) and the 4 RCTs applying autologous coverage after pancreatoduodenectomy and distal pancreatectomy (OR 0.53, 95% c.i. 0.29 to 0.96, P < 0.04). Other subgroup analyses (artificial coverage or pancreatoduodenectomy) showed no statistically significant differences. The secondary endpoints of mortality, reoperations, and re-interventions were each affected positively by the use of coverage techniques. The certainty of evidence was very low to moderate. CONCLUSION: The implementation of coverage, whether artificial or autologous, is beneficial after partial pancreatectomy, especially in patients undergoing distal pancreatectomy with autologous coverage.

Technical details of robotic pancreatojejunostomy using a modified Blumgart anastomosis: Thread manipulation using gauze and an assisted port.

BACKGROUNDS: Pancreatojejunostomy is a technically demanding procedure during robotic pancreaticoduodenectomy (RPD). Modified Blumgart anastomosis (mBA) is a common method for the pancreatojejunostomy; however, the technical details for robotic mBA are not well established. During RPD, we performed a mBA for the pancreatojejunostomy using thread manipulation with gauze and an additional assist port. METHODS: Patients who underwent robotic pancreatoduodenectomy at Fujita Health University from November 2009 to May 2023 were retrospectively investigated, and technical details for the robotic-modified Blumgart anastomosis were demonstrated. RESULTS: Among 78 patients who underwent RPD during the study period, 33 underwent robotic mBA. Postoperative pancreatic fistula (POPF) occurred in six patients (18%). None of the patients suffered POPF Grade C according to the international study group of pancreatic surgery definition. The anastomotic time for mBA was 80 min (54-125 min). CONCLUSION: Robotic mBA resulted in reasonable outcomes. We propose that mBA could be used as one of the standard methods for robotic pancreatojejunosotomy.