Search

Background: Ampullary adenocarcinoma (AAC) typically presents at an early stage due to biliary obstruction and therefore might be specifically suitable for minimally invasive pancreatoduodenectomy (MIPD). However, studies assessing MIPD specifically for AAC, including the robotic and laparoscopic approach, are limited. The aim of this study is to compare short- and long-term oncological resection and perioperative outcomes of robotic (RPD), laparoscopic (LPD) and open pancreatoduodenectomy (OPD) performed specifically for AAC., Methods: In this multicenter international cohort study, encompassing 35 centers from 11 countries, MIPD versus OPD and subgroup analyses of LPD versus RPD were undertaken. The primary outcomes regarded the oncological resection (R1 resection rate, lymph node yield) and 5-years overall survival. Secondary outcomes were perioperative outcomes (including intra-operative variables, surgical complications and hospital stay)., Results: In total, patients with AAC who underwent OPD (1721) or MIPD (141) were included. After propensity-score matching, 134 patients per cohort were included. The MIPD group consisted of 53 RPDs and 71 LPDs (50 per group after PSM). There was no difference in overall survival between MIPD and OPD (61.6 % vs 56.2 %, P = 0.215). In the MIPD group, operative time was longer (439 vs 360 min, P < 0.001). Between RPD and LPD, overall survival was not significantly different (75.8 % vs 47.4 %, P = 0.098) and lymph node yield was higher in RPD (21 vs 18, P = 0.014)., Conclusion: In conclusion, patients with AAC seem to have comparable oncological resection and perioperative outcomes from MIPD compared to the traditional OPD. Both RPD as LPD appear to be safe alternatives for patients with AAC, which warrants confirmation by future randomized studies., Competing Interests: Conflict of interest Mario Serradilla-Martín received research funding from Baxter S.L.. Patrick Pessaux is co-founder of Virtualisurg; Marc G. Besselink has received grants from Intuitive for the LEARNBOT European robot Whipple training program, the DIPLOMA-2 trial, and the E-MIPS quality registry, from Medtronic for the investigator-initiated DIPLOMA trial and from Ethicon for the PANDORA trial and the E-MIPS quality registry; Mohammed Abu Hilal received funding from Associazione Italiana per la Ricerca sul Cancro (AIRC). All remaining authors (BAU, AM, UB, MM, BGK, RDV, SK, LB, AM, ML, BKPG, MASM, BB, GK, BI, JK, PG, VKM, GKF, RS, AZ, KJR, AA, BAS, MV, DK, ZS, MG, SB, CMV, SWB, JDC) claim no conflicts of interests and no disclosures., (Copyright © 2024. Published by Elsevier Ltd.)

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use., Objective: To test external validity of the prognostic value of the hidden genome classifier of AA., Design, Setting, and Participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020., Exposures: The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin., Main Outcome and Measures: Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models., Results: Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability., Conclusions and Relevance: The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Objective: To evaluate whether drain fluid amylase levels on day-1 (DFA1) and day-3 (DFA3) can reliably estimate the risk of clinically relevant-postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) compared to either value alone or in combination with clinicopathologic variables., Background: CR-POPF is a major source of morbidity and mortality following PD. Current drain management algorithms are variable and are mostly dependent on DFA1, while the DFA3 is seldom utilized to guide clinical decision making., Methods: Between 2015-2020, patients who underwent PD at two high-volume pancreas centers and had intraoperative drain placement with measurement of DFA1 and DFA3 were retrospectively reviewed. Models to predict CR-POPF were constructed using DFA1, DFA3, fistula risk score (FRS) and other patient or treatment-related parameters. The fittest and more parsimonious model was used to construct a CR-POPF risk calculator., Results: Nine-hundred-twenty-three patients were included in the analysis. The FRS was high in 100(10.9%), intermediate in 524(57.3%), low in 211(23.1%) and negligible in 79(8.6%) patients. The overall rate of CR-POPF was 9.2%. Five logistic regression models were constructed using variables known to be implicated in CR-POPF. A model based solely on DFA1 and DFA3 with a cross-validated area under the curve of 0.846 was selected. A calculator using DFA1 and DFA3 was created based on this model to estimate the risk of CR-POPF., Conclusions: Risk of CR-POPF following pancreatoduodenectomy can be accurately estimated based on measurement of DFA1 and DFA3. Our CR-POPF kinetics calculator can facilitate postoperative risk stratification and guide drain management algorithms., Competing Interests: Disclosures: No conflict of interests to declare, financial or otherwise., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD)., Background: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience., Methods: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions., Results: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification., Conclusion: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To analyze the association of a surgeon's experience with postoperative outcomes of pancreatoduodenectomies (PDs) when stratified by Fistula Risk Score (FRS)., Background: Centralization is now well-established for pancreatic surgery. Nevertheless, the benefits of individual surgeon's experience in high-volume settings remain undefined., Methods: Pancreatoduodenectomies performed by 82 surgeons across 18 international specialty institutions (median: 140 PD/year) were analyzed. Surgeon cumulative PD volume was linked with postoperative outcomes through multivariable models, adjusted for patient/operative characteristics and the FRS. Then, surgeon experience was also stratified by the 10, previously defined, most clinically impactful scenarios for clinically relevant pancreatic fistula (CR-POPF) development., Results: Of 8189 PDs, 18.7% suffered severe complications (Accordion≥3), 4.8% were reoperated upon and 2.2% expired. Although the most experienced surgeons (top-quartile; >525 career PDs) more often operated on riskier cases, their experience was significantly associated with declines in CR-POPF ( P <0.001), severe complications ( P =0.008), reoperations ( P <0.001), and length of stay (LOS) ( P <0.001)-accentuated even more in the most impactful FRS scenarios (2830 patients). Risk-adjusted models indicate male sex, increasing age, ASA class, and FRS, but not surgeon experience, as being associated with severe complications, failure-to-rescue, and mortality. Instead, upper-echelon experience demonstrates significant reductions in CR-POPF (OR 0.66), reoperations (OR 0.64), and LOS (OR 0.65) in moderate-to-high fistula risk circumstances (FRS≥3, 68% of cases)., Conclusions: At specialty institutions, major morbidity, mortality, and failure-to-rescue are primarily associated with baseline patient characteristics, while cumulative surgical experience impacts pancreatic fistula occurrence and its attendant effects for most higher-risk pancreatoduodenectomies. These data also suggest an extended proficiency curve exists for this operation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS., Methods: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey., Results: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024)., Conclusion: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Recent studies support early drain removal after pancreaticoduodenectomy in patients with a drain fluid amylase on postoperative day 1 (DFA1) level of ≤5,000. The use of DFA1 to guide drain management is increasingly common among pancreatic surgeons; however, the benefit of checking additional drain fluid amylases beyond DFA1 is less known. We sought to determine whether a change in drain fluid amylase (ΔDFA) is a more reliable predictor of clinically relevant postoperative fistula than DFA1 alone., Methods: Using the American College of Surgeons National Surgical Quality Improvement Plan, pancreaticoduodenectomy patients with intraoperative drain placement, known DFA1, highest recorded drain fluid amylase value on postoperative day 2 to 5 (DFA2nd), day of drain removal, and clinically relevant postoperative fistula status were reviewed. Logistic models compared the predictive performance of DFA1 alone versus DFA1 + ΔDFA., Results: A total of 2,417 patients with an overall clinically relevant postoperative fistula rate of 12.6% were analyzed. On multivariable regression, clinical predictors for clinically relevant postoperative fistula included body mass index, steroid use, operative time, and gland texture. These variables were used to develop model 1 (DFA1 alone) and model 2 (DFA1 + ΔDFA). Model 2 outperformed model 1 in predicting the risk of clinically relevant postoperative fistula. According to model 2 predictions, the risk of clinically relevant postoperative fistula increased with any rise in drain fluid amylase, regardless of whether the DFA1 was above or below 5,000 U/L. The risk of clinically relevant postoperative fistula significantly decreased with any drop in drain fluid amylase, with an odds reduction of approximately 50% corresponding with a 70% decrease in drain fluid amylase (P < .001). A risk calculator was developed using DFA1 and a secondary DFA value in conjunction with other clinical predictors for clinically relevant postoperative fistula., Conclusion: Clinically relevant postoperative fistula after pancreaticoduodenectomy is more accurately predicted by DFA1 and ΔDFA versus DFA1 in isolation. We developed a novel risk calculator to provide an individualized approach to drain management after pancreaticoduodenectomy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance., Methods: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer., Results: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5)., Conclusions: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation strategies, respectively., Background: POPF remains the most common complication after DP. Despite several known risk factors, an adequate risk model has not been developed yet., Methods: Two prediction risk scores were designed using data of patients undergoing DP in 2 Italian centers (2014-2016) utilizing multivariable logistic regression. The preoperative score (calculated before surgery) aims to facilitate preventive strategies and the intraoperative score (calculated at the end of surgery) aims to facilitate mitigation strategies. Internal validation was achieved using bootstrapping. These data were pooled with data from 5 centers from the United States and the Netherlands (2007-2016) to assess discrimination and calibration in an internal-external validation procedure., Results: Overall, 1336 patients after DP were included, of whom 291 (22%) developed POPF. The preoperative distal fistula risk score (preoperative D-FRS) included 2 variables: pancreatic neck thickness [odds ratio: 1.14; 95% confidence interval (CI): 1.11-1.17 per mm increase] and pancreatic duct diameter (OR: 1.46; 95% CI: 1.32-1.65 per mm increase). The model performed well with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.78-0.88) and 0.73 (95% CI: 0.70-0.76) upon internal-external validation. Three risk groups were identified: low risk (<10%), intermediate risk (10%-25%), and high risk (>25%) for POPF with 238 (18%), 684 (51%), and 414 (31%) patients, respectively. The intraoperative risk score (intraoperative D-FRS) added body mass index, pancreatic texture, and operative time as variables with an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.74-0.85)., Conclusions: The preoperative and the intraoperative D-FRS are the first validated risk scores for POPF after DP and are readily available at: http://www.pancreascalculator.com . The 3 distinct risk groups allow for personalized treatment and benchmarking., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Summary Dr. Paul Greig is an icon of surgical education, transplantation, hepatobiliary surgery and Canadian surgery. Dr. Greig has trained experts in these fields all over the world and is regarded as one of the most important surgical educators in the past 25 years., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Objective: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD)., Summary Background Data: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking., Methods: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort., Results: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001)., Conclusion: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the role of intraoperative estimated blood loss (EBL) on development of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD)., Background: Minimizing EBL has been shown to decrease transfusions and provide better perioperative outcomes in PD. EBL is also felt to be influential on CR-POPF development., Methods: This study consists of 5534 PDs from a 17-institution collaborative (2003-2018). EBL was progressively categorized (≤150mL; 151-400mL; 401-1,000 mL; > 1,000 mL). Impact of additive EBL was assessed using 20 3- factor fistula risk score (FRS) scenarios reflective of endogenous CR-POPF risk., Results: CR-POPF developed in 13.6% of patients (N = 753) and median EBL was 400 mL (interquartile range 250-600 mL). CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs 400 mL, P = 0.002; 372 vs 500 mL, P < 0.001, respectively). Progressive EBL cohorts displayed incremental CR-POPF rates (8.5%, 13.4%, 15.2%, 16.9%; P < 0.001). EBL >400mL was associated with increased CR-POPF occurrence in 13/20 endogenous risk scenarios. Moreover, 8 of 10 scenarios predicated on a soft gland demonstrated increased CR-POPF incidence. Hypothetical projections demonstrate significant reductions in CR-POPF can be obtained with 1-, 2-, and 3-point decreases in FRS points attributed to EBL risk (12.2%, 17.4%, and 20.0%; P < 0.001). This is especially pronounced in high-risk (FRS7-10) patients, who demonstrate up to a 31% reduction (P < 0.001). Surgeons in the lowest-quartile of median EBL demonstrated CR-POPF rates less than half those in the upper-quartile (7.9% vs 18.8%; P < 0.001)., Conclusion: EBL independently contributes significant biological risk to CR-POPF. Substantial reductions in CR-POPF occurrence are projected and obtainable by minimizing EBL. Decreased individual surgeon EBL is associated with improvements in CR-POPF., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The American College of Surgeons National Surgical Quality Improvement Program was established to help participating hospitals track and report surgical complications with the goal of improving surgical care. We sought to determine whether this has led to improvements in surgical outcomes for pancreatic malignancies., Methods: Patients with pancreatic malignancies who underwent surgical resection were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2006-2019). Thirty-day postoperative major morbidity and mortality were analyzed by year. Major morbidity included organ and deep surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure., Results: Of the 28,888 patients identified, 51% were male, the median age was 68, 74.3% underwent a pancreaticoduodenectomy, and 25.7% underwent a distal pancreatectomy. Among patients who underwent a pancreaticoduodenectomy, there was a significant increase in major morbidity (annual percent change 0.77, P = .012) driven by increases in organ space surgical site infection (annual percent change 3.52, P < .001) and venous thromboembolism (annual percent change 4.72, P = .005). However, there was a decrease in postoperative mortality (annual percent change -4.58, P = .001). For distal pancreatectomy patients, there was no change in rates of overall major morbidity (annual percent change -1.35, P = .08) or mortality (annual percent change -3.21, P = .25)., Conclusion: Although major morbidity and mortality have not significantly changed for distal pancreatectomy patients, mortality has steadily decreased for patients undergoing pancreaticoduodenectomy, despite an increase in major morbidity. Whether this trend reflects a change in patient selection, an increase in detection of postoperative morbidities and/or an improvement in mitigation of these morbidities warrants further study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube)., Methods: A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules., Results: During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was "Understanding Clinical Trials" (n = 182,217), and the most common expert video viewed was "What are the different stages of pancreatic cancer?" (n = 15,357)., Conclusions: Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer., Competing Interests: The authors declare no conflict of interest. The Animated Pancreas Patient—An Animated Patient's Guide to Pancreatic Diseases is supported by unrestricted education grants from Abbvie Inc, Boston Scientific Corporation, Celgene Corporation, Ethicon US LLC, and Incyte Corporation. Mechanisms in Medicine, the developers of this resource, declare no conflict of interest in the development of the program., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4 + T-cell subsets from lean, overweight and obese AA patients., Methods: Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4 + T-cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese-related leptin dose on cytokine production and Treg cell function in AA-derived CD4 + T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese., Results: AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17-like cells rather than classic Th2-like cells. On the other hand, the frequencies of Th1-like, Br1 cells and regulatory CD4 + T-cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17-like cells positively correlated with leptin levels, the frequencies of regulatory CD4 + T-cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity-related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4 + T cell cultures from lean AA patients., Conclusion: In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17-like and Th2/Th17 cells and decreasing regulatory CD4 + T cell subsets, being adverse effects probably mediated by leptin overproduction., Competing Interests: All authors declare that there are no conflicts of interest., (© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%. We observe high concordance with whole-exome sequencing for evaluation of tumor mutational burden for 307 solid tumors (Pearson r = 0.95) and comparison of the elio tissue complete microsatellite instability detection approach with an independent PCR assay for 223 samples displays a positive percent agreement of 99%. Finally, evaluation of amplifications and translocations against DNA- and RNA-based approaches exhibits >98% negative percent agreement and positive percent agreement of 86% and 82%, respectively. These methods provide an approach for pan-solid tumor comprehensive genomic profiling with high analytical performance., (© 2022. The Author(s).)

Objective: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison., Background: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking., Methods: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021., Results: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications., Discussions: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF., Methods: The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach., Results: A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P < .001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone., Conclusion: In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: This study aims to present a full spectrum of individual patient presentations of pancreatic fistula risk, and to define the utility of mitigation strategies amongst some of the most prevalent, and vulnerable scenarios surgeons encounter., Background: The FRS has been utilized to identify technical strategies associated with reduced CR-POPF incidence across various risk strata. However, risk-stratification using the FRS has never been investigated with greater granularity. By deriving all possible combinations of FRS elements, individualized risk assessment could be utilized for precision medicine purposes., Methods: FRS profiles and outcomes of 5533 PDs were accrued from 17 international institutions (2003-2019). The FRS was used to derive 80 unique combinations of patient "scenarios." Risk-matched analyses were conducted using a Bonferroni adjustment to identify scenarios with increased vulnerability for CR-POPF occurrence. Subsequently, these scenarios were analyzed using multivariable regression to explore optimal mitigation approaches., Results: The overall CR-POPF rate was 13.6%. All 80 possible scenarios were encountered, with the most frequent being scenario #1 (8.1%) - the only negligible-risk scenario (CR-POPF rate = 0.7%). The moderate-risk zone had the most scenarios (50), patients (N = 3246), CR-POPFs (65.2%), and greatest non-zero discrepancy in CR-POPF rates between scenarios (18-fold). In the risk-matched analysis, 2 scenarios (#59 and 60) displayed increased vulnerability for CR-POPF relative to the moderate-risk zone (both P < 0.001). Multivariable analysis revealed factors associated with CR-POPF in these scenarios: pancreaticogastrostomy reconstruction [odds ratio (OR) 4.67], omission of drain placement (OR 5.51), and prophylactic octreotide (OR 3.09). When comparing the utilization of best practice strategies to patients who did not have these conjointly utilized, there was a significant decrease in CR-POPF (10.7% vs 35.5%, P < 0.001; OR 0.20, 95% confidence interval 0.12-0.33)., Conclusion: Through this data, a comprehensive fistula risk catalog has been created and the most clinically-impactful scenarios have been discerned. Focusing on individual scenarios provides a practical way to approach precision medicine, allowing for more directed and efficient management of CR-POPF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored., Methods: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with α = 0.05 and β = 0.2., Results: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.44; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P = .156)., Conclusion: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Despite abundant, high-level scientific evidence, there is no consensus regarding the prevention, mitigation, and management of clinically relevant pancreatic fistula after pancreatoduodenectomy. The aim of the present investigation is three-fold: (1) to analyze the multiple decision-making points for pancreatico-enteric anastomotic creation and fistula mitigation and management after pancreatoduodenectomy, (2) to reveal the practice of contemporary experts, and (3) to indicate avenues for future research to reduce the burden of clinically relevant pancreatic fistula., Methods: A 109-item questionnaire was sent to a panel of international pancreatic surgery experts, recognized for their clinical and scientific authority. Their practice habits and thought processes regarding clinically relevant pancreatic fistula risk assessment, anastomotic construction, application of technical adjuncts, and mitigation strategies, as well as postoperative management, was explored. Sixteen clinical vignettes were presented to reveal their certain approaches to unique situations-both common and uncommon., Results: Sixty experts, with a cumulative 48,860 pancreatoduodenectomies, completed the questionnaire. Their median pancreatectomy/pancreatoduodenectomy case volume was 1,200 and 705 procedures, respectively, with a median career duration of 22 years and 200 indexed publications. Although pancreatico-jejunostomy reconstruction with transperitoneal drainage is the standard operative approach for most authorities, uncertainty emerges regarding the employment of objective risk stratification and adaptation of practice to risk. Concrete suggestions are offered to inform decision-making in intimidating circumstances. Early drain removal is frequently embraced, while a step-up approach is unanimously invoked to treat severe clinically relevant pancreatic fistula., Conclusion: A comprehensive conceptual framework of 4 sequential phases of decision-making is proposed-risk assessment, anastomotic technique, mitigation strategy employment, and postoperative management. Basic science studies and outcome analyses are proposed for improvement., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The reported conversion rates for minimally invasive distal pancreatectomy (MIDP) range widely from 2 to 38%. The identification of risk factors for conversion may help surgeons during preoperative planning and patient counseling. Moreover, the impact of conversion on outcomes of MIDP is unknown., Methods: A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). The PubMed, Cochrane, and Embase databases were searched for studies concerning conversion to open surgery in MIDP., Results: Of the 828 studies screened, eight met the eligibility criteria, resulting in a combined dataset including 2592 patients after MIDP. The overall conversion rate was 17.1% (range 13.0-32.7%) with heterogeneity between studies associated with the definition of conversion adopted. Only one study divided conversion into elective and emergency conversion. The main indications for conversion were vascular involvement (23.7%), concern for oncological radicality (21.9%), and bleeding (18.9%). The reported risk factors for conversion included a malignancy as an indication for surgery, the proximity of the tumor to vascular structures in preoperative imaging, higher BMI or visceral fat, and multi-organ resection or extended resection. Contrasting results were seen in terms of blood loss and length of stay in comparing converted MIDP and completed MIDP patients., Conclusion: The identified risk factors for conversion from this study can be used for patient selection and counseling. Surgeon experience should be considered when contemplating MIDP for a complex patient. Future studies should divide conversion into elective and emergency conversion.

Objective: The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior., Background: The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series., Methods: Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence., Results: Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior., Conclusions: The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients., Competing Interests: This work was performed and written as part of a project of the 8th Pancreas 2000 program funded and organized by the European Pancreatic Club (EPC). None of the authors have any financial or any other kind of personal conflicts of interest in relation to this study The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood., Methods: The fistula risk score was applied to identify high-risk patients (fistula risk score 7-10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003-2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models., Results: Eight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (-49.7%) and career length (-41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35-0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22-0.74)., Conclusion: Surgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interests to disclose.

Pancreatic fistula has been the defining complication and challenge of pancreatic surgery. Better awareness and mitigation of postoperative pancreatic fistulas has led to significant improvements in morbidity and mortality of pancreatic surgery. The definition and management of pancreatic fistulas has sequentially progressed over the last three decades; the literature ranges from retrospective, observational studies to prospective multicenter randomized controlled trials. The landmark literature contributions driving the perioperative management of pancreatic fistulas are detailed in this article.

Background: Health care expenditure is increasing around the world and surgery is a major cause of financial hardship to patients and their families. Using pancreatoduodenectomy (PD), one of the most complex, morbid and costly operation as an example, this study aimed to identify the cost drivers of surgery, estimate relative contribution of these drivers, and derive and validate a cohort-specific cost forecasting tool., Methods: Data on the costs of 1406 patients undergoing PD in three tertiary hospitals in India, Italy and the United States were analysed. Cost drivers were identified and cost models developed using a 4-stage process., Results: There was a significant difference in overall cost of PD between the 3 cohorts. The cost drivers common to the 3 cohorts included duration of hospital stay and the outcome of death (Clavien-Dindo 5). Significant cohort-specific cost drivers included co-morbidities, operating theatre utilisation times and operative blood loss, development of pancreatectomy-specific complications (POPF, DGE, PPH), and need for interventional radiology to manage complications. Based on this, a cost forecasting tool was developed., Conclusions: Drivers of costs for a surgical procedure (e.g. PD) are different between hospitals. Developing cost models/nomograms to predict the expected cost of surgery and perioperative care will not be applicable between hospitals. However, the approach could be used to develop context-specific data that will provide patients (at the time of the informed financial consent) and funding agencies with a more realistic cost estimate for a given operation. The developed cost forecasting tool warrants future validation., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Major depressive disorder (MDD) can impact the severity of allergic rhinitis (AR) and asthma (AA). Here, we evaluated the cytokine production by T-cells from AR and AA patients with or without MDD. The effect of serotonin on the in vitro T-cell response was also evaluated., Methods: The cytokines produced by activated T-cells were measured by Luminex and flow cytometry. In some cell cultures, serotonin was added., Results: MDD not only enhanced the production of Th2- and Th17-related cytokines, but also, the levels of interleukin (IL)-5 and IL-17 were directly correlated with the severity of depression and anxiety symptoms. As compared with AR, the levels of IL-17 were higher and the release of IL-10 was lower in activated T-cell cultures from AA patients, mainly those with MDD. In AA/MDD patients, the severity of anxiety symptoms and lung disease was directly correlated with Th17-like and hybrid Th2/Th17 cells, but inversely correlated with IL-10-secreting CD4+ T-cells. Finally, the addition of serotonin reduced the production of Th2- and Th17-related cytokines, but elevated IL-10 secretion in cell cultures from both AR and AA patients., Conclusions: Our findings suggest that not only the occurrence of MDD but also the severity of anxiety symptoms, may adversely affect the outcome of allergic reactions by favoring the production of cytokines implicated in the pathogenesis of AR and AA, a phenomenon that was attenuated by serotonin., (© 2021 S. Karger AG, Basel.)