Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Estimating postoperative mortality in colorectal surgery- a systematic review of risk prediction models.

PURPOSE: Risk prediction models are frequently used to support decision-making in colorectal surgery but can be inaccurate. Machine learning (ML) is becoming increasingly popular, and its application may increase predictive accuracy. We compared conventional risk prediction models for postoperative mortality (based on regression analysis) with ML models to determine the benefit of the latter approach. METHODS: The study was registered in PROSPERO(CRD42022364753). Following the PRISMA guidelines, a systematic search of three databases (MEDLINE, EMBASE, WoS) was conducted (from 1/1/2000 to 29/09/2022). Studies were included if they reported the development of a risk model to estimate short-term postoperative mortality for patients undergoing colorectal surgery. Discrimination and calibration performance metrics were compared. Studies were evaluated against CHARMS and TRIPOD criteria. RESULTS: 3,052 articles were screened, and 45 studies were included. The total sample size was 1,356,058 patients. Six studies used ML techniques for model development. Most studies (n = 42) reported the area under the receiver operating characteristic curve (AUROC) as a measure of discrimination. There was no significant difference in the mean AUROC values between regression models (0.833 s.d. ± 0.52) and ML (0.846 s.d. ± 0.55), p = 0.539. Calibration statistics, which measure the agreement between predicted estimates and observed outcomes, were less consistent. Risk of bias assessment found most concerns in the data handling and analysis domains of eligible studies. CONCLUSIONS: Our study showed comparable predictive performance between regression and ML methods in colorectal surgery. Integration of ML in colorectal risk prediction is promising but further refinement of the models is required to support routine clinical adoption.

Rapid qualitative analysis in a mixed-methods evaluation of an infection prevention intervention in a UK hospital setting during the COVID-19 pandemic: A discussion of the CLEAN study methodology.

The COVID-19 pandemic created an urgent need for high-quality rapid research. One clinical challenge was how to minimise the risk of transmission in the hospital setting. The CLEAN study conducted a rapid evaluation of the potential utility of a spray-based disinfectant in a hospital setting. The study was undertaken between December 2020 and March 2021 and involved the implementation of the spray in 10 different clinical areas in one UK teaching hospital. A mixed-methods approach was adopted (including observations, surveys, and qualitative interviews) informed by the theories for understanding the implementation of new healthcare technologies. The evaluation found that while the spray had a number of perceived benefits when added to existing disinfection processes, other factors limited its potential utility. These findings informed a number of recommendations for future adoption within hospital settings. This paper describes and reflects on the rapid methodology that allowed us to undertake the study and deliver results in a short space of time. We experienced a number of pressures during set-up and fieldwork due to the challenging conditions caused by the pandemic, and the methodological approach had to evolve throughout the study because of the changing clinical context. The involvement of clinicians from the research setting as full members of the research team was key to the rapid delivery of the research. They provided an essential link to the implementation environment, and their experiential knowledge of the setting added an important perspective to the analysis. Balancing their involvement with their clinical roles was challenging, however, as was coordinating a large and diverse team of interviewers in such a short space of time. Overall, the study highlighted the value of rapid research to inform urgent healthcare decisions in a pandemic. Although our experience suggests that conducting such research requires some practical and methodological trade-offs, we found that there were also numerous benefits of using rapid methods and identified various opportunities to ensure their robustness.

Duplication and nonregistration of COVID-19 systematic reviews: Bibliometric review.

Objectives: This study examines the conduct of systematic reviews during the early stages of the COVID-19 pandemic, including compliance to protocol registration and duplication of reviews on similar topics. The methodological and reporting quality were also explored. Methods: A cross-sectional, bibliometric study was undertaken of all systematic review manuscripts on a COVID-19 intervention published between January 1st and June 30th, 2020. Protocol registration on a publicly accessible database was recorded. Duplication was determined by systematically recording the number of reviews published on each topic of analysis. Methodological quality and reporting quality were assessed using the AMSTAR-2 and PRISMA 2009 instruments, respectively. Results: Thirty-one eligible systematic reviews were identified during the inclusion period. The protocol of only four (12.9%) studies was registered on a publicly accessible database. Duplication was frequent, with 15 (48.4%) of the 31 included studies focusing on either hydroxychloroquine (and/or chloroquine) or corticosteroids. Only one study (3.2%) was of "high" methodological quality, four (12.9%) were "low" quality, and the remainder (n = 26, 83.9%) were of "critically low" quality. The median completeness of reporting was 20 out of 27 items (74.1%) with a range of 5-26 (interquartile range: 14-23). Conclusion: Systematic reviews during the early stages of the COVID-19 pandemic were uncommonly registered, frequently duplicated, and mostly of low methodological quality. In contrast, the reporting quality of manuscripts was generally good but varied substantially across published reports. There is a need for heightened stewardship of systematic review research, particularly during times of medical crisis where the generation of primary evidence may be rapid and unstable.

The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review.

AIM: Anastomotic leak is the most feared complication of gastrointestinal surgery. Mesenchymal stem cell technology is used clinically to promote wound healing; however, the safety and efficacy of this technology on anastomotic healing has yet to be defined. The aim of this study was to investigate whether mesenchymal stem cells confer any benefit when applied to animal models for gastrointestinal anastomotic leak, identify the methodology and how efficacy is assessed. METHODS: The MEDLINE, EMBASE, WebofScience and Cochrane Library databases were interrogated between 1 January1947 to 1 May 2020. All studies where mesenchymal stem cells were applied to laboratory animal leak models to demonstrate a healing effect were considered. All experimental and histological outcomes were examined. Compliance to ARRIVE and current International Consensus was assessed. RESULTS: A total of 1205 studies were screened. Twelve studies reported on 438 gastrointestinal anastomoses in four species using 11 models; seven in the colon. No studies utilised a model with a known leak rate. Significant variance was observed in histological outcomes with efficacy demonstrated in five out of 12 studies. One study demonstrated a benefit in leak rate. Colorectal studies had a greater median ARRIVE compliance, 60.8% (IQR 63.2-64.5) compared to noncolorectal 45.4% (IQR 43.8-49.0). CONCLUSIONS: Mesenchymal stem cell delivery to an animal anastomosis is safe and feasible. Use may confer benefit but findings are currently limited to surrogate histological outcomes. There is consistency in outcome measures reported but variance in how this is assessed. Poor compliance to ARRIVE but good compliance to current international consensus in leak models of the colon was observed.

Noninvasive vagus nerve stimulation to reduce ileus after major colorectal surgery: early development study.

AIM: Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of self-administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery. METHOD: A parallel-group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self-administered bilaterally over the cervical surface landmarks for 5 days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien-Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery. RESULTS: Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7 ± 0.9 days out of 5 days in the Sham group and 4.7 ± 1.1 in the Active group. Compliance with treatment after surgery was 4.1 ± 1.1 and 4.4 ± 1.5, respectively. Participants considered the intervention to be 'acceptable' according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35 ± 1.32 vs 1.65 ± 0.88) and tolerance of solid diet (2.18 ± 2.21 vs 1.75 ± 0.91) for Sham and Active groups, respectively. CONCLUSION: This study supports the safety, treatment compliance and usability of self-administered nVNS in patients undergoing major colorectal surgery.

Global academic response to COVID-19: Cross-sectional study.

This study explores the response to COVID-19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross-sectional bibliometric review of COVID-19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission-to-acceptance time and availability of original data. Publisher-responsiveness was assessed by measuring the acceptance-to-publication time and the provision of open access. Three hundred and ninety-eight of 2,835 COVID-19 and 55 of 1,513 MERS search results were eligible. Most COVID-19 studies were clinical reports (n = 242; 60.8%). The submission-to-acceptance [median: 5 days (IQR: 3-11) versus 71.5 days (38-106); P < .001] and acceptance-to-publication [median: 5 days (IQR: 2-8) versus 22.5 days (4-48·5-; P < .001] times were strikingly shorter for COVID-19. Almost all COVID-19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open-access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID-19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one-in-four were published alongside original data, which is a key target for improvement. Key points: COVID-19 publications show rapid response from investigators, specifically aiming to define the disease.Median time between submission and acceptance of COVID-19 articles is 5 days demonstrating rapid decision-making compared with the median of 71.5 days for MERS articles.Median time from acceptance to publication of COVID-19 articles is 5 days, confirming the ability to introduce rapid increases at times of crisis, such as during the SARS outbreak.The majority of both COVID-19 and MERS articles are available open-access.

Development and characterisation of a low-concentration sodium dodecyl sulphate decellularised porcine dermis.

The aim of this study was to adapt a proprietary decellularisation process for human dermis for use with porcine skin. Porcine skin was subject to: sodium chloride (1 M) to detach the epidermis, trypsin paste to remove hair follicles, peracetic acid (0.1% v/v) disinfection, washed in hypotonic buffer and 0.1% (w/v) sodium dodecyl sulphate in the presence of proteinase inhibitors followed by nuclease treatment. Cellular porcine skin, decellularised porcine and human dermis were compared using histology, immunohistochemistry, GSL-1 lectin (alpha-gal epitope) staining, biochemical assays, uniaxial tensile and in vitro cytotoxicity tests. There was no microscopic evidence of cells in decellularised porcine dermis. DNA content was reduced by 98.2% compared to cellular porcine skin. There were no significant differences in the biomechanical parameters studied or evidence of cytotoxicity. The decellularised porcine dermis retained residual alpha-gal epitope. Basement membrane collagen IV immunostaining was lost following decellularisation; however, laminin staining was retained.