Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort.

BACKGROUND AND AIM: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

Comparison of two-dimensional measurement with three-dimensional volume rendering for the assessment of loss of domain in incisional hernia patients.

PURPOSE: We aimed to compare simple two-dimensional (2D) measurement with comprehensive three-dimensional (3D) volume rendering to determine loss of domain (LOD), a clinically important decision-making feature for incisional hernia repair. METHODS: In this single-center retrospective study, we analyzed the CT scans of a consecutive cohort of adult patients with a midline incisional hernia. The hernia sac- and abdominal cavity volumes were obtained by two different methods. The 2D method estimated the volumes using the corresponding height, width, and depth. The 3D method comprised of a volume rendering tool. For both methods, LOD was calculated according to the Sabbagh ratio (hernia sac volume / (hernia sac volume + abdominal cavity volume)). Taking the 3D method as the reference standard, the performance of the 2D method was expressed as positive predictive value (PPV) and negative predictive value (NPV) for LOD of more than- and less than 20%. The agreement between both methods was expressed as Cohen's kappa coefficient (kappa). RESULTS: We analyzed 92 CT scans. Agreement between both methods was high (kappa = 0.854, p = 0.0001); all 67 measurements for which the 2D method assessed LOD to be less than 20% were correctly classified (NPV = 100%), and 20 of 25 measurements for which the 2D method assessed LOD to be more than 20% were correctly classified (PPV = 80%). CONCLUSIONS: The 2D method can exclude patients from perioperative actions needed for a more complex hernia. Since this method is easy to use and less time-consuming, it seems useful for the routine radiological assessment of LOD in clinical practice.

A computed tomography study investigating the effects of botulinum toxin injections prior to complex abdominal wall reconstruction.

OBJECTIVE: To explore how intramuscular injection of botulinum toxin A (BTA) affects the lateral abdominal wall (LAW) musculature, abdominal- and hernia dimensions, and muscle structure on computed tomography (CT) in patients scheduled for complex abdominal wall reconstruction (CAWR). METHODS: Retrospective analysis of prospectively registered patients who received bilateral intramuscular BTA injections into all three muscles of the LAW. Only patients for which a CT was available before and 3-6 weeks after BTA treatment prior to surgery were analyzed. RESULTS: Fifty-two patients were analyzed. Median hernia width in all patients decreased with 0.4 cm (IQR - 2.1;0.6) (p = 0.023). Median intra-abdominal transverse diameter increased with 0.9 cm (IQR - 0.2;3.3) (p = 0.001) and the intra-abdominal anterior-posterior diameter decreased with 0.5 cm (IQR - 1.3;0.5) (p = 0.017), making the abdomen more oval. Median LAW muscle length increased with 0.9 cm (IQR 0.0;2.4) per side (p < 0.001), muscle thickness decreased with 0.5 cm (IQR - 0.8;- 0.2) (- 25.0%) per side (p < 0.001), and muscle mass decreased with 3.9 cm2 (IQR - 6.4;-1.5) (- 15.8%) per side (p < 0.001). Median HU of the psoas muscles (density) increased with 4.8 HU (IQR 0.4;9.7) (10.3%) per side (p < 0.001). Effects of BTA were more pronounced in patients with a loss of domain (LoD) ≥ 20%. CONCLUSIONS: The main effect of BTA injections is elongation and thinning of the LAW muscles, more than a decrease in hernia width. Concomitantly, the abdomen becomes more oval. An increase of psoas muscles density is seen, associated with offloading of the LAW muscles. Patients with large LoD have a proportionally higher effect of BTA.

Yield of Adding chest CT to Abdominal CT to Detect COVID-19 in Patients Presenting With Acute Gastrointestinal Symptoms (SCOUT-3): Multicenter Study.

OBJECTIVE: To determine the incremental yield of standardized addition of chest CT to abdominal CT to detect COVID-19 in patients presenting with primarily acute gastrointestinal symptoms requiring abdominal imaging. Summary Background Data: Around 20% of patients with COVID-19 present with gastrointestinal symptoms. COVID-19 might be neglected in these patients, as the focus could be on finding abdominal pathology. During the COVID-19 pandemic, several centers have routinely added chest CT to abdominal CT to detect possible COVID-19 in patients presenting with gastrointestinal symptoms. However, the incremental yield of this strategy is unknown. METHODS: This multicenter study in 6 Dutch centers included consecutive adult patients presenting with acute nontraumatic gastrointestinal symptoms, who underwent standardized combined abdominal and chest CT between March 15, 2020 and April 30, 2020. All CT scans were read for signs of COVID-19 related pulmonary sequelae using the СО-RADS score. The primary outcome was the yield of high COVID-19 suspicion (СО-RADS 4-5) based on chest CT. RESULTS: A total of 392 patients were included. Radiologic suspicion for COVID-19 (СО-RADS 4-5) was present in 17 (4.3%) patients, eleven of which were diagnosed with COVID-19. Only 5 patients with СО-RADS 4-5 presented without any respiratory symptoms and were diagnosed with COVID-19. No relation with community prevalence could be detected. CONCLUSION: The yield of adding chest CT to abdominal CT to detect COVID-19 in patients presenting with acute gastrointestinal symptoms is extremely low with an additional detection rate of around 1%.

Spatioregional assessment of the gut microbiota in experimental necrotizing pancreatitis.

BACKGROUND: Infectious complications following experimental pancreatitis involve major disruptions in the gut microbiota. The aim of this study was to characterize this disruption by examining the spatioregional distribution in microbial community structure and function following experimental pancreatitis associated with pancreatic infection. METHODS: Mice were subjected to infusion of the pancreatic duct with either taurocholate to induce necrotizing pancreatitis or normal saline (control group). The spatial (lumen versus mucosa) and regional composition and function of the microbiota from the duodenum, ileum, caecum, colon, pancreas and blood were evaluated using 16S rRNA gene amplicon sequencing. RESULTS: Mice that developed necrotizing pancreatitis demonstrated a decrease in microbial richness and significantly altered microbiota in distal parts of the gastrointestinal tract, compared with controls. Among the most differentially increased taxa were the mucus-degrading Akkermansia muciniphila, and there was a decrease of butyrate-producing bacteria following pancreatitis. Application of the SourceTracker tool to the generated metadata indicated that the duodenum was the most probable source of bacteria that subsequently infected pancreatic tissue in this model. The functional prediction annotation using pathway analyses indicated a diminished capacity of the caecal microbiota to metabolize carbohydrate, and fatty and amino acids. DISCUSSION: The distal gut microbiota was significantly impacted in this model of experimental necrotizing pancreatitis. Data suggest that the duodenal microbiota might also play a role in bacterial translation and secondary infections.

A systematic review and meta-analysis of technical aspects and clinical outcomes of botulinum toxin prior to abdominal wall reconstruction.

PURPOSE: To systematically review technical aspects and treatment regimens of botulinum toxin A (BTA) injections in the lateral abdominal wall musculature. We also investigated the effect of BTA on abdominal muscle- and hernia dimensions, and clinical outcome. METHODS: PubMed, EMBASE, CENTRAL, and CINAHL were searched for studies that investigate the injection of BTA in the lateral abdominal wall muscles. Study characteristics, BTA treatment regimens, surgical procedures, and clinical outcomes are presented descriptively. The effect of BTA on muscle- and hernia dimensions is analyzed using random-effects meta-analyses, and exclusively for studies that investigate ventral incisional hernia patients. RESULTS: We identified 23 studies, comprising 995 patients. Generally, either 500 units of Dysport® or 200-300 units of Botox® are injected at 3-5 locations bilaterally in all three muscles of the lateral abdominal wall, about 4 weeks prior to surgery. No major procedural complications are reported. Meta-analyses show that BTA provides significant elongation of the lateral abdominal wall of 3.2 cm per side (95% CI 2.0-4.3, I2 = 0%, p < 0.001); 6.3 cm total elongation, and a significant but heterogeneous decrease in transverse hernia width (95% CI 0.2-6.8, I2 = 94%, p = 0.04). Furthermore, meta-analysis shows that BTA pretreatment in ventral hernia patients significantly increases the fascial closure rate [RR 1.08 (95% CI 1.02-1.16, I2 = 0%, p = 0.02)]. CONCLUSION: The injection technique and treatment regimens of botulinum toxin A as well as patient selection require standardization. Bilateral pretreatment in hernia patients significantly elongates the lateral abdominal wall muscles, making fascial closure during surgical hernia repair more likely. STUDY REGISTRATION: A review protocol for this meta-analysis was registered at PROSPERO (CRD42020198246).

Population preference for treatment of uncomplicated appendicitis.

BACKGROUND: Non-operative treatment of uncomplicated appendicitis is safe and increasing in popularity, but has other risks and benefits compared with appendicectomy. This study aimed to explore the preference of the general population regarding operative or antibiotic treatment of uncomplicated appendicitis. METHODS: In this prospective study, a clinical scenario and questionnaire were submitted to a panel comprising a sample of an average adult population. The survey was distributed by an independent, external research bureau, and included a comprehensive explanation of the risks and benefits of both treatment options. The primary outcome was the proportion of participants who would prefer antibiotics over surgery. Secondary outcomes were reasons for this preference and the accepted recurrence rate within 1 year when treated with antibiotics only. All outcomes were weighted for the average Dutch population. RESULTS: Of 254 participants, 49.2 per cent preferred antibiotic treatment for uncomplicated appendicitis, 44.5 per cent preferred surgery, and 6.3 per cent could not make a decision. About half of the participants preferring antibiotics would accept a recurrence risk of more than 50 per cent within 1 year. Avoiding surgery was their main reason. In participants preferring surgery, many tolerated a recurrence risk of no more than 10 per cent when treated with antibiotics. Removal of the cause of appendicitis was their main reason. CONCLUSION: Around half of the average population sample preferred antibiotics over surgical treatment of uncomplicated appendicitis and were willing to accept a high recurrence risk to avoid surgery initially. Participants who preferred surgery tolerated only a very low recurrence risk with antibiotic treatment.

Outcomes of mid-term and long-term degradable biosynthetic meshes in single-stage open complex abdominal wall reconstruction.

OBJECTIVE: To assess clinical outcomes in patients that underwent open single-stage complex abdominal wall reconstruction (CAWR) with biosynthetic mesh. METHODS: Retrospective observational study of two prospectively registered series of consecutive patients undergoing CAWR with either long-term degradable (LTD) Phasix™ or mid-term degradable (MTD) BIO-A® biosynthetic mesh in a single institution between June 2016 and December 2019. RESULTS: From 169 patients with CAWR, 70 consecutive patients were identified who underwent CAWR with either LTD or MTD biosynthetic mesh. More than 85% of patients had an incisional hernia that could be classified as moderately complex to major complex due to a previous wound infection (67%), one or more complicating comorbidities (87.1%), one or more complicating hernia characteristics (75.7%) or contaminated or dirty defects (37.1%). Concomitant component separation was performed in 43 of 70 patients (61.4%). Overall surgical site infection (SSI) rate in these CAWR patients was 45.7%. Seventeen of 70 patients (24.3%) had computed tomography (CT) - and culture-confirmed SSI in direct contact of mesh, suspicious of mesh infection. Mesh removal for persistent local infection occurred in 10% (7 of 70) after a median of 229 days since surgery. Salvage rate of mesh after direct contact with infection was 58.8%. All removed meshes were in the LTD group. Seven patients (10%) had a recurrence; four patients in the LTD group (10%) had a recurrence at a median follow-up of 35 months and three patients in the MTD group (10%) at a median follow-up of 11 months. Three of the seven recurrences occurred in patients with SSI in persistent and direct contact with mesh. CONCLUSIONS: Comorbid patients undergoing open complex abdominal wall reconstruction are at high risk of postoperative wound complications regardless of which type of biosynthetic mesh is used. When in persistent and direct contact with infection, long-term biodegradable biosynthetic meshes may need to be removed, whereas mid-term biodegradable biosynthetic meshes can be salvaged.

Diagnosis of Uncomplicated and Complicated Appendicitis in Adults.

BACKGROUND: Diagnostic work-up of acute appendicitis remains challenging. While some guidelines advise to use a risk stratification based on clinical parameters, others use standard imaging in all patients. As non-operative management of uncomplicated appendicitis has been identified as feasible and safe, differentiation between uncomplicated and complicated appendicitis is of paramount importance. We reviewed the literature to describe the optimal strategy for diagnosis of acute appendicitis. METHODS: A narrative review about the diagnosis of acute appendicitis in adult patients was conducted. Both diagnostic strategies and goals were analyzed. RESULTS: For diagnosing acute appendicitis, both ruling in and ruling out the disease are important. Clinical and laboratory findings individually do not suffice, but when combined in a diagnostic score, a better risk prediction can be made for having acute appendicitis. However, for accurate diagnosis imaging seems obligatory in patients suspected for acute appendicitis. Scoring systems combining clinical and imaging features may differentiate between uncomplicated and complicated appendicitis and may enable ruling out complicated appendicitis. Within conservatively treated patients with uncomplicated appendicitis, predictive factors for non-responsiveness to antibiotics and recurrence of appendicitis need to be defined in order to optimize treatment outcomes. CONCLUSION: Standard imaging increases the diagnostic power for both ruling in and ruling out acute appendicitis. Incorporating imaging features in clinical scoring models may provide better differentiation between uncomplicated and complicated appendicitis. Optimizing patient selection for antibiotic treatment of appendicitis may minimize recurrence rates, resulting in better treatment outcomes.

Enhanced PeriOperative Care and Health protection programme for the prevention of surgical site infections after elective abdominal surgery (EPO2CH): statistical analysis plan of a randomised controlled multicentre superiority trial.

BACKGROUND: Surgical site infections (SSI) are frequent complications after elective abdominal surgery. We designed the Enhanced PeriOperative Care and Health Protection programme (EPO2CH) care bundle, comprising of intraoperative high fractional inspired oxygen; intraoperative goal-directed fluid therapy; active preoperative, intraoperative and postoperative warming; glucose control and treatment of hyperglycaemia (> 10 mmol L- 1) in diabetics as well as non-diabetics; and wound irrigation before closure using an aqueous antiseptic. We hypothesise that EPO2CH added to standard care reduces the incidence of SSI compared to standard care alone for elective abdominal surgery. METHODS: This trial is designed as an open label, pragmatic randomised controlled parallel-group multicentre superiority trial. The primary endpoint is the incidence of SSI, defined by the Centers for Disease Control and prevention, within 30 days after surgery. The incidence of SSI is assessed using the Dutch national complication register and medical chart review. Secondary endpoints include the SSI incidence within 90 days, incidence of anastomotic leakage at 30 and 90 days, the incidence of incisional hernia within 1 year, mortality within 1 year and 5 years, quality of life, health and disability, and cost-effectiveness. Primarily, an intention-to-treat analysis will be performed to estimate the relative risk using a log binomial model. If not feasible, a logistic regression will be used to estimate the odds ratio. A per-protocol analysis will also be performed. Furthermore, the attributive effect of the distinct interventions will be explored. DISCUSSION: The results of the EPO2CH trial will determine if the EPO2CH bundle is effective to prevent SSI incidence for patients undergoing elective abdominal surgery. Details of the statistical analysis are described in this Statistical Analysis Plan (SAP). TRIAL REGISTRATION: Registration number: Dutch Trial Register Trial NL5572 . Registered on March 3, 2016. SAP version: V1.0, January 8, 2020. This SAP has been written based on study protocol V10.

Normal inflammatory markers and acute appendicitis: a national multicentre prospective cohort analysis.

PURPOSE: For the diagnosis of acute appendicitis, the combination of clinical and laboratory variables achieves high diagnostic accuracy. Nevertheless, appendicitis can present with normal laboratory tests of inflammation. The aim of this study was to investigate the incidence of normal inflammatory markers in patients operated for acute appendicitis. METHODS: This is an analysis of data from a prospective, multicentre SNAPSHOT cohort study of patients with suspected acute appendicitis. Only patients with histopathologically proven acute appendicitis were included. Adult patients with acute appendicitis and normal preoperative inflammatory markers were explored further in terms of abdominal complaints, preoperative imaging results and intraoperative assessment of the degree of inflammation and compared to those with elevated inflammatory markers. RESULTS: Between June and July 2014, 1303 adult patients with histopathologically proven acute appendicitis were included. In only 23 of 1303 patients (1.8%) with proven appendicitis, both preoperative white blood cell count and C-reactive protein levels were normal. Migration of pain was reported less frequently in patients with normal inflammatory markers compared to those with elevated inflammatory marker levels (17.4% versus 43.0%, p = 0.01). Characteristics like fever, duration of symptoms and localized peritonitis were comparable. Only 4 patients with normal inflammatory markers (0.3% overall) had complicated appendicitis at histopathological evaluation. CONCLUSION: Combined normal WBC and CRP levels are seen in about 2 per 100 patients with confirmed acute appendicitis and can, although rarely, be found in patients with complicated appendicitis.

Discriminating complicated from uncomplicated appendicitis by ultrasound imaging, computed tomography or magnetic resonance imaging: systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Discriminating complicated from uncomplicated appendicitis is crucial. Patients with suspected complicated appendicitis are best treated by emergency surgery, whereas those with uncomplicated appendicitis may be treated with antibiotics alone. This study aimed to obtain summary estimates of the accuracy of ultrasound imaging, CT and MRI in discriminating complicated from uncomplicated appendicitis. METHODS: A systematic literature review was conducted by an electronic search in PubMed, Embase and the Cochrane Library for studies describing the diagnostic accuracy of complicated versus uncomplicated appendicitis. Studies were included if the population comprised adults, and surgery or pathology was used as a reference standard. Risk of bias and applicability were assessed with QUADAS-2. Bivariable logitnormal random-effect models were used to estimate mean sensitivity and specificity. RESULTS: Two studies reporting on ultrasound imaging, 11 studies on CT, one on MRI, and one on ultrasonography with conditional CT were included. Summary estimates for sensitivity and specificity in detecting complicated appendicitis could be calculated only for CT, because of lack of data for the other imaging modalities. For CT, mean sensitivity was 78 (95 per cent c.i. 64 to 88) per cent, and mean specificity was 91 (85 to 99) per cent. At a median prevalence of 25 per cent, the positive predictive value of CT for complicated appendicitis would be 74 per cent and its negative predictive value 93 per cent. CONCLUSION: Ultrasound imaging, CT and MRI have limitations in discriminating between complicated and uncomplicated appendicitis. Although CT has far from perfect sensitivity, its negative predictive value for complicated appendicitis is high.

IMARI: multi-Interventional program for prevention and early Management of Anastomotic leakage after low anterior resection in Rectal cancer patIents: rationale and study protocol.

BACKGROUND: Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program. METHODS: IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power. DISCUSSION: The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL. TRIAL REGISTRATION: Trialregister.nl ( NL8261 ), January 2020.

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.

Alpha-1-antitrypsin deficiency (carrier) as possible risk factor for development of colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

AIM: Connective tissue changes due to ageing or diseases leading to changes in the colonic wall are one theory for the development of diverticula. Alpha-1-antitrypsin (A1AT), a protease inhibitor that protects connective tissue, possibly plays a role in the aetiology of diverticulosis. The aim of this study was to explore associations between the development of diverticula and A1AT deficiency. METHODS: This was a multicentre prospective case-control study. A total of 221 patients aged ≥ 60 years with acute abdominal pain undergoing abdominal CT were included and analysed. Patients with diverticula were defined as the research group, patients without diverticula as controls. Genotype analysis for A1AT deficiency was performed. RESULTS: Twenty-six of 221 (11.8%) patients were diagnosed with (being a carrier of) A1AT deficiency. A non-significant difference in prevalence between patients with and without diverticula was found, 20 (13.9%) of 144 vs 6 (7.8%) of 77, respectively, with a crude OR of 1.9 (95% CI 0.7-5.0; P = 0.186) and after adjustment for confounders an adjusted OR of 1.5 (95% CI 0.5-4.0; P = 0.466). A non-significant difference in 30-day mortality rate from acute diverticulitis between A1AT deficient patients (or carriers) and those without was observed: two (22.2%) of nine patients with A1AT deficiency vs 1 (1.8%) of 55 without. CONCLUSION: We found no convincing evidence that A1AT deficiency plays a role in the aetiology of diverticulitis, although deficient patients and carriers had a higher mortality when experiencing diverticulitis. Diverticulitis is a multifactorial disease and larger numbers may be needed to explore the role of A1AT deficiency among other contributing factors.

The development and validation of risk-stratification models for short-term outcomes following contaminated complex abdominal wall reconstruction.

BACKGROUND: Short-term outcomes for patients undergoing contaminated complex abdominal wall reconstruction (CCAWR), including risk stratification, have not been studied in sufficiently high numbers. This study aims to develop and validate risk-stratification models for Clavien-Dindo (CD) grade ≥ 3 complications in patients undergoing CCAWR. METHODS: A consecutive cohort of patients who underwent CCAWR in two European national intestinal failure centers, from January 2004 to December 2015, was identified. Data were collected retrospectively for short-term outcomes and used to develop risk models using logistic regression. A further cohort, from January 2016 to December 2017, was used to validate the models. RESULTS: The development cohort consisted of 272 procedures performed in 254 patients. The validation cohort consisted of 114 patients. The cohorts were comparable in baseline demographics (mean age 58.0 vs 58.1; sex 58.8% male vs 54.4%, respectively). A multi-variate model including the presence of intestinal failure (p < 0.01) and operative time (p < 0.01) demonstrated good discrimination and calibration on validation. Models for wound and intra-abdominal complications were also developed, including pre-operative immunosuppression (p = 0.05), intestinal failure (p = 0.02), increasing operative time (p = 0.04), increasing number of anastomoses (p = 0.01) and the number of previous abdominal operations (p = 0.02). While these models showed reasonable ability to discriminate patients on internal assessment, they were not found to be accurate on external validation. CONCLUSION: Acceptable short-term outcomes after CCAWR are demonstrated. A robust model for the prediction of CD ≥ grade 3 complications has been developed and validated. This model is available online at www.smbari.co.uk/smjconv2.

Meta-analysis and field synopsis of genetic variants associated with the risk and severity of acute pancreatitis.

BACKGROUND: Genetic risk factors can provide insight into susceptibility for acute pancreatitis (AP) and disease progression towards (infected) necrotizing pancreatitis and persistent organ failure. The aim of the study was to undertake a systematic review of the genetic evidence for AP. METHODS: Online databases (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) were searched to 8 February 2018. Studies that reported on genetic associations with AP susceptibility, severity and/or complications were eligible for inclusion. Meta-analyses were performed of variants that were reported by at least two data sources. Venice criteria and Bayesian false-discovery probability were applied to assess credibility. RESULTS: Ninety-six studies reporting on 181 variants in 79 genes were identified. In agreement with previous meta-analyses, credible associations were established for SPINK1 (odds ratio (OR) 2·87, 95 per cent c.i. 1·89 to 4·34), IL1B (OR 1·23, 1·06 to 1·42) and IL6 (OR 1·64, 1·15 to 2·32) and disease risk. In addition, two novel credible single-nucleotide polymorphisms were identified in Asian populations: ALDH2 (OR 0·48, 0·36 to 0·64) and IL18 (OR 1·47, 1·18 to 1·82). Associations of variants in TNF, GSTP1 and CXCL8 genes with disease severity were identified, but were of low credibility. CONCLUSION: Genetic risk factors in genes related to trypsin activation and innate immunity appear to be associated with susceptibility to and severity of AP.

ANTECEDENTES: Los factores de riesgo genético pueden contribuir a determinar la susceptibilidad para desarrollar una pancreatitis aguda (acute pancreatitis, AP) y de su progresión a pancreatitis necrotizante (infectada) e insuficiencia orgánica crónica. Nuestro objetivo fue revisar de forma sistemática la evidencia genética de la pancreatitis aguda. MÉTODOS: Se revisaron las bases de datos electrónicas (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) hasta febrero de 2018. Se incluyeron estudios que presentaban información de las asociaciones genéticas y la susceptibilidad de AP, gravedad y/o complicaciones. Se realizó un metaanálisis de las variantes genéticas descritas en al menos dos fuentes. Se aplicaron los criterios de Venecia y la probabilidad bayesiana de falsa alarma para la valoración de la credibilidad. RESULTADOS: Se identificaron 96 estudios que analizaron 181 variantes en 79 genes. De acuerdo con un metaanálisis previo, se establecieron asociaciones creibles con el riesgo de enfermedad para SPINK1 (razón de oportunidades, odds ratio, OR 2,87, i.c. del 95% 1,89-4,34), IL1B (OR 1,23, i.c. del 95% 1,06-1,42) e IL6 (OR 1,64, i.c. del 95% 1,15-2,32). Además, en poblaciones asiáticas, se identificaron dos nuevos polimorfismos de nucleótico único (SNP) creibles en ALDH2 (OR 0,48, i.c. del 95% 0,36-0,64) e IL18 (OR 1,47, i.c. del 95% 1,18-1,82). En cuanto a la gravedad de la enfermedad se identificaron variantes en los genes TNF, GSTP1 y CXCL8, pero de baja credibilidad en función de nuestra evaluación. CONCLUSIÓN: Los factores de riesgo genéticos en genes relacionados con la activación de la tripsina y la inmunidad innata parecen ser estar asociados con la susceptibilidad y gravedad de la pancreatitis aguda.

Long-term outcomes after contaminated complex abdominal wall reconstruction.

PURPOSE: Complex abdominal wall repair (CAWR) in a contaminated operative field is a challenge. Available literature regarding long-term outcomes of CAWR comprises studies that often have small numbers and heterogeneous patient populations. This study aims to assess long-term outcomes of modified-ventral hernia working group (VHWG) grade 3 repairs. Because the relevance of hernia recurrence (HR) as the primary outcome for this patient group is contentious, the need for further hernia surgery (FHS) was also assessed in relation to long-term survival. METHODS: A retrospective cohort study with a single prospective follow-up time-point nested in a consecutive series of patients undergoing CAWR in two European national intestinal failure centers. RESULTS: In long-term analysis, 266 modified VHWG grade 3 procedures were included. The overall HR rate was 32.3%. The HR rates for non-crosslinked biologic meshes and synthetic meshes when fascial closure was achieved were 20.3% and 30.6%, respectively. The rates of FHS were 7.2% and 16.7%, and occurred only within the first 3 years. Bridged repairs showed poorer results (fascial closure 22.9% hernia recurrence vs bridged 57.1% recurrence). Overall survival was relatively good with 80% en 70% of the patients still alive after 5 and 10 years, respectively. In total 86.6% of the patients remained free of FHS. CONCLUSIONS: In this study of contaminated CAWR, non-crosslinked biologic mesh shows better results than synthetic mesh. Bridging repairs with no posterior and/or anterior fascial closure have a higher recurrence rate. The overall survival was good and the majority of patients remained free of additional hernia surgery.

Observational versus antibiotic treatment for uncomplicated diverticulitis: an individual-patient data meta-analysis.

BACKGROUND: Two RCTs (AVOD and DIABOLO) demonstrated no difference in recovery or adverse outcomes when antibiotics for acute uncomplicated diverticulitis were omitted. Both trials showed non-significantly higher rates of complicated diverticulitis and surgery in the non-antibiotic groups. This meta-analysis of individual-patient data aimed to explore adverse outcomes and identify patients at risk who may benefit from antibiotic treatment. METHODS: Individual-patient data from those with uncomplicated diverticulitis from two RCTs were pooled. Risk factors for adverse outcomes and the effect of observational management were assessed using logistic regression analyses. P < 0·025 was considered statistically significant owing to multiple testing adjustment. RESULTS: In total, 545 patients in the observational group and 564 in the antibiotics group were included. No statistical differences were found in 1-year follow-up rates of ongoing diverticulitis (7·2 versus 5·0 per cent in observation versus antibiotics groups respectively; P = 0·062), recurrent diverticulitis (8·6 versus 9·6 per cent; P = 0·610), complicated diverticulitis (4·0 versus 2·1 per cent; P = 0·079) and sigmoid resection (5·0 versus 2·5 per cent; P = 0·214). An initial pain score greater than 7, white blood cell count exceeding 13·5 × 109 /l and previous diverticulitis at presentation were risk factors for adverse outcomes. Antibiotic treatment did not prevent adverse outcomes in patients at high risk of adverse events. CONCLUSION: Observational management of acute uncomplicated diverticulitis is safe. Some statistical uncertainty remains, depending on the thresholds of clinical relevance, owing to small differences, but no subgroup that would benefit from antibiotic treatment was apparent.

ANTECEDENTES: Dos ensayos clínicos aleatorizados y controlados (randomized controlled trials, RCTc) (AVOD y DIABOLO) no mostraron diferencias en la recuperación ni en los resultados adversos al tratar la diverticulitis aguda no complicada sin antibióticos. Ambos ensayos mostraron tasas más altas, estadísticamente no significativas, de diverticulitis complicada y cirugía en los grupos sin antibióticos. Este metaanálisis de datos individuales de pacientes tuvo como objetivo explorar resultados adversos e identificar pacientes en riesgo que pudieran beneficiarse del tratamiento con antibióticos. MÉTODOS: Se agruparon los datos individuales de pacientes con diverticulitis no complicada de dos RCT. Los factores de riesgo para los resultados adversos y el efecto del tratamiento observacional (sin antibióticos) se evaluaron mediante un análisis de regresión logística. Una P < 0,025 se consideró estadísticamente significativa debido al ajuste de múltiples comparaciones. RESULTADOS: En total, se incluyeron 545 pacientes en el grupo de observación y 564 pacientes en el grupo de tratamiento antibiótico. No se encontraron diferencias estadísticamente significativas (observación versus antibióticos, respectivamente) en el seguimiento a 1 año en los porcentajes de diverticulitis persistente (7,2% versus 5,0%; P = 0,062), diverticulitis recurrente (8,6% versus 9,6%; P = 0,610), diverticulitis complicada (4,0% versus 2,1%; P = 0,079) y resección sigmoidea (5,0% versus 2,5%; P = 0,214). Una puntuación de dolor inicial > 7, un recuento leucocitario > 13,5 x 109 /L y los antecedentes de diverticulitis fueron factores de riesgo para un resultado adverso. El tratamiento con antibióticos no previno los resultados adversos en pacientes con alto riesgo. CONCLUSIÓN: El tratamiento de la diverticulitis aguda no complicada basado en la observación es seguro. No obstante, persiste una cierta incertidumbre desde el punto de vista estadístico, dependiendo de los umbrales de relevancia clínica, debido a pequeñas diferencias, pero no fue evidente ningún subgrupo que se pudiera beneficiar del tratamiento con antibióticos.