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Background: Somatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of different SA protocols on the incidence of POPF after pancreatoduodenectomy in a nationwide population., Methods: All patients undergoing elective open pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2014-2017). Patients were divided into six groups: no SA, octreotide, lanreotide, pasireotide, octreotide only in high-risk (HR) patients and lanreotide only in HR patients. Primary endpoint was POPF grade B/C. The updated alternative Fistula Risk Score was used to compare POPF rates across various risk scenarios., Results: 1992 patients were included. Overall POPF rate was 13.1%. Lanreotide (10.0%), octreotide-HR (9.4%) and no protocol (12.7%) POPF rates were lower compared to the other protocols (varying from 15.1 to 19.1%, p = 0.001) in crude analysis. Sub-analysis in patients with HR of POPF showed a significantly lower rate of POPF when treated with lanreotide (10.0%) compared to no protocol, octreotide and pasireotide protocol (21.6-26.9%, p = 0.006). Octreotide-HR and lanreotide-HR protocol POPF rates were comparable to lanreotide protocol, however not significantly different from the other protocols. Multivariable regression analysis demonstrated lanreotide protocol to be positively associated with a low odds-ratio (OR) for POPF (OR 0.387, 95% CI 0.180-0.834, p = 0.015). In-hospital mortality rates were not affected., Conclusion: Use of lanreotide in all patients undergoing pancreatoduodenectomy has a potential protective effect on POPF development. Protocols for HR patients only might be favorable too. However, future studies are warranted to confirm these findings., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We developed a jejunal and colonic experimental human ischemia-reperfusion (IR) model to study pathophysiological intestinal IR mechanisms and potential new intestinal ischemia biomarkers. Our objective was to evaluate the safety of these IR models by comparing patients undergoing surgery with and without in vivo intestinal IR., Methods: A retrospective study was performed comparing complication rates and severity, based on the Clavien-Dindo classification system, in patients undergoing pancreatoduodenectomy with (n = 10) and without (n = 20 matched controls) jejunal IR or colorectal surgery with (n = 10) and without (n = 20 matched controls) colon IR. Secondary outcome parameters were operative time, blood loss, 90-day mortality and length of hospital stay., Results: Following pancreatic surgery, 63% of the patients experienced one or more postoperative complications. There was no significant difference in incidence or severity of complications between patients undergoing pancreatic surgery with (70%) or without (60%, P = 0.7) jejunal IR. Following colorectal surgery, 60% of the patients experienced one or more postoperative complication. Complication rate and severity were similar in patients with (50%) and without (65%, P = 0.46) colonic IR. Operative time, amount of blood loss, postoperative C-reactive protein, length of hospital stay or mortality were equal in both intervention and control groups for jejunal and colon IR., Conclusion: This study showed that human experimental intestinal IR models are safe in patients undergoing pancreatic or colorectal surgery., Competing Interests: The authors have declared that no competing interests exist.

Background: Enhanced recovery after surgery (ERAS) pathways are now implemented worldwide with strong evidence that adhesion to such protocol reduces medical complications, costs and hospital stay. This concept has been applied for pancreatic surgery since the first published guidelines in 2012. This study presents the updated ERAS recommendations for pancreatoduodenectomy (PD) based on the best available evidence and on expert consensus., Methods: A systematic literature search was conducted in three databases (Embase, Medline Ovid and Cochrane Library Wiley) for the 27 developed ERAS items. Quality of randomized trials was assessed using the Consolidated Standards of Reporting Trials statement checklist. The level of evidence for each item was determined using the Grading of Recommendations Assessment Development and Evaluation system. The Delphi method was used to validate the final recommendations., Results: A total of 314 articles were included in the systematic review. Consensus among experts was reached after three rounds. A well-implemented ERAS protocol with good compliance is associated with a reduction in medical complications and length of hospital stay. The highest level of evidence was available for five items: avoiding hypothermia, use of wound catheters as an alternative to epidural analgesia, antimicrobial and thromboprophylaxis protocols and preoperative nutritional interventions for patients with severe weight loss (> 15%)., Conclusions: The current updated ERAS recommendations for PD are based on the best available evidence and processed by the Delphi method. Prospective studies of high quality are encouraged to confirm the benefit of current updated recommendations.

Objective: To estimate short and long-term morbidity after pancreatic surgery for multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs)., Background: Fifty percent of the MEN1 patients harbor multiple NF-pNETs. The decision to proceed to NF-pNET surgery is a balance between the risk of disease progression versus the risk of surgery-related morbidity. Currently, there are insufficient data on the surgical complications after MEN1 NF-pNET surgery., Methods: MEN1 patients diagnosed with a NF-pNET who underwent surgery were selected from the DutchMEN1 study group database, including >90% of the Dutch MEN1 population. Early postoperative complications, new-onset diabetes mellitus, and exocrine pancreatic insufficiency were captured., Results: Sixty-one patients underwent NF-pNET surgery at 1 of the 8 Dutch academic centers. Patients were young (median age 41 years) with low American Society of Anesthesiologists scores. Median NF-pNET size on imaging was 22 mm (3-157). Thirty-three percent (19/58) of the patients developed major early-Clavien-Dindo grade III to IV-complications mainly consisting International Study Group of Pancreatic Surgery grade B/C pancreatic fistulas. Twenty-three percent of the patients (14/61) developed endocrine or exocrine pancreas insufficiency. The development of major early postoperative complications was independent of the NF-pNET tumor size. Twenty-one percent of the patients (12/58) developed multiple major early complications., Conclusions: MEN1 NF-pNET surgery is associated with high rates of major short and long-term complications. Current findings should be taken into account in the shared decision-making process when MEN1 NF-pNET surgery is considered.

Background: An enhanced recovery after surgery (ERAS) program aims to reduce the stress response to surgery and thereby accelerate recovery. It is unclear whether these programs can be safely implemented for elderly patients, especially in highly complex surgery such as pancreaticoduodenectomy (PD). The objective of this study was to evaluate the feasibility of an ERAS program in elderly patients undergoing PD., Methods: Implementation of the ERAS protocol was studied prospectively in a consecutive series of patients undergoing PD between January 2009 and August 2013. Patients were divided into two groups: ≤ 65 years and ≥ 70 years. Endpoints were length of stay (LOS), readmissions, morbidity, mortality, and compliance with ERAS targets., Results: Of a total of 110 patients, 55 were ≤ 65 years (median 57) and 55 ≥ 70 years (median 77). Median LOS was 14 days in both groups. In patients without complications median LOS was 9 days. Both mortality and readmissions did not differ between groups (mortality n = 3 (5.5 %) in younger versus n = 6 (10.9 %) in older patients, p = 0.49, readmissions: n = 11 (20 %) versus n = 7 (12.7 %), p = 0.44). CT-drainage and relaparotomy-rates were not different between groups, nor was overall morbidity (n = 31 (56.3 %) in the older versus n = 35 (63.3 %) in the younger group, p = 0.44). There were no differences in compliance with elements of the ERAS protocol between groups., Conclusion: An ERAS program seems feasible and safe for patients ≥ 70 years of age undergoing PD.

Background: Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large number of patients needed to adequately power RCTs for relevant clinical single endpoints. A PD-specific composite endpoint (CEP) could solve this problem. The aim of the present study was to develop a PD-specific CEP, consisting of complications related to PD, allowing reduction in sample sizes and improving the ability to compare outcomes., Methods: PD-specific CEP components were selected after a systematic review of the literature and consensus between 25 international pancreatic surgeons. Ultimately, prospective cohorts of patients who underwent PD in two high-volume HPB centers (London, UK, and Maastricht, NL) were used to assess the event rate and effect of implementing a PD-specific CEP., Results: From a total of 18 single-component endpoints, intra-abdominal abscess, sepsis, post-PD hemorrhage, bile leakage, gastrojejunostomy leakage, leakage of the pancreatic anastomosis, delayed gastric emptying, and operative mortality within 90 days were selected to be included the PD-specific CEP. All eight components had consensus definitions and a Dindo-Clavien classification of 3 or more. The incidence of the PD-specific CEP was 24.7 % in the Maastricht cohort and 23.3 % in the London cohort. These incidence rates led to a twofold reduction in the theoretical calculated sample size for an adequately powered RCT on PD using this CEP as a primary endpoint., Conclusions: The proposed PD-specific CEP enables clinical investigators to adequately power RCTs on PD and increases the feasibility, comparability, and utility in meta-analysis.

Background: Pancreaticoduodenectomies (PDs) are complex surgical procedures that require high-standard perioperative care. The objective of this study was to evaluate the effects of implementing an Enhanced Recovery After Surgery (ERAS) program for PD on patient outcome., Methods: 230 patients undergoing PD in the Maastricht University Medical Centre between January 1995 and January 2012 were included. Group 1 (no ERAS; 1995-2005) received traditional care. From January 2006, several elements of an ERAS pathway for pancreatic surgery were implemented (group 2: 'ERAS-like'). From 2009 onwards the ERAS pathway was fully implemented (group 3: ERAS). Mortality, complications, readmissions and length of hospital stay (LOS) were evaluated in the subgroups and compared., Results: Median LOS was significantly reduced from 20 days in group 1 to 13 days in group 2 and 14 days in group 3 (p = 0.001). Median LOS of patients without complications was 16, 10 and 9 days in groups 1, 2 and 3, respectively (p < 0.0001). Over time, the average age of patients undergoing PD increased significantly. Complication rates as well as mortality and readmission rates did not change over time., Conclusion: Implementing an ERAS program contributed to a decrease of LOS without compromising other outcomes. Mortality, morbidity and readmission rates stayed unchanged and more complications were managed non-operatively., (© 2014 S. Karger AG, Basel.)

Background: Although mortality after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) has decreased, morbidity still remains high. The aim of this review article is to present, define, predict, prevent, and manage the main complications after pancreatic resection (PR)., Methods: A non-systematic literature search on morbidity and mortality after PR was undertaken using the PubMed/MEDLINE and Embase databases., Results: The main complications after PR are delayed gastric emptying (DGE), pancreatic fistula (PF), and bleeding, as defined by the International Study Group on Pancreatic Surgery. PF occurs in 10% to 15% of patients after PD and in 10% to 30% of patients after DP. The different techniques of pancreatic anastomosis and pancreatic remnant closure do not show significant advantages in the prevention of PF, nor does the perioperative use of somatostatin and its analogues. The trend is for conservative or interventional radiology therapy for PF (with enteral nutrition), which achieves a success rate of approximately 80%. DGE after PD occurs in 20% to 50% of patients. Prophylactic erythromycin may reduce the incidence of DGE. Gastric aspiration with erythromycin is usually effective in one to three weeks. Bleeding (gastrointestinal and intraabdominal) occurs in 4% to 16% of patients after PD and in 2% to 3% of patients after DP. Endovascular treatment can only be used for a haemodynamically stable patient. In cases of haemodynamic instability or associated septic complications, surgical treatment is necessary. In expert centres, the mortality rates can be less than 1% after DP and less than 3% after PD., Conclusion: There is a need for improved strategies to prevent and treat complications after PR., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background & Aims: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy., Methods: An international working group constructed within the Enhanced Recovery After Surgery (ERAS®) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak"., Results: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations., Conclusions: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Intestinal ischemia-reperfusion (IR) is a phenomenon related to physiological conditions (e.g. exercise, stress) and to pathophysiological events (e.g. acute mesenteric ischemia, aortic surgery). Although intestinal IR has been studied extensively in animals, results remain inconclusive and data on human intestinal IR are scarce. Therefore, an experimental harmless model for human intestinal IR was developed, enabling us to clarify the sequelae of human intestinal IR for the first time. Methods and Findings: In 30 patients undergoing pancreatico-duodenectomy we took advantage of the fact that in this procedure a variable length of jejunum is removed. Isolated jejunum (5 cm) was subjected to 30 minutes ischemia followed by reperfusion. Intestinal Fatty Acid Binding Protein (I-FABP) arteriovenous concentration differences across the bowel segment were measured before and after ischemia to assess epithelial cell damage. Tissue sections were collected after ischemia and at 25, 60 and 120 minutes reperfusion and stained with H&E, and for I-FABP and the apoptosis marker M30. Bonferroni's test was used to compare I-FABP differences. Mean (SEM) arteriovenous concentration gradients of I-FABP across the jejunum revealed rapidly developing epithelial cell damage. I-FABP release significantly increased from 290 (46) pg/ml before ischemia towards 3,997 (554) pg/ml immediately after ischemia (p<0.001) and declined gradually to 1,143 (237) pg/ml within 1 hour reperfusion (p<0.001). Directly after ischemia the intestinal epithelial lining was microscopically normal, while subepithelial spaces appeared at the villus tip. However, after 25 minutes reperfusion, enterocyte M30 immunostaining was observed at the villus tip accompanied by shedding of mature enterocytes into the lumen and loss of I-FABP staining. Interestingly, within 60 minutes reperfusion the epithelial barrier resealed, while debris of apoptotic, shedded epithelial cells was observed in the lumen. At the same time, M30 immunoreactivity was absent in intact epithelial lining. Conclusions: This is the first human study to clarify intestinal IR induced cell damage and repair and its direct consequences. It reveals a unique, endogenous clearing mechanism for injured enterocytes: rapid detachment of damaged apoptotic enterocytes into the lumen. This process is followed by repair of the epithelial continuity within an hour, resulting in a normal epithelial lining. [ABSTRACT FROM AUTHOR]