Platelet-Rich stroma from Crohn's disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls.

BACKGROUND: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls. METHODS: Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis. RESULTS: Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*105 cells/mL versus non-IBD 12.20 ± 3.39*105). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples. CONCLUSIONS: The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products.

Efficacy and safety of autologous adipose-derived stromal vascular fraction enriched with platelet-rich plasma in flap repair of transsphincteric cryptoglandular fistulas.

BACKGROUND: Transanal advancement flap repair of transsphincteric fistulas is a sphincter-preserving procedure, which frequently fails, probably due to ongoing inflammation in the remaining fistula tract. Adipose-derived stromal vascular fraction (SVF) has immunomodulatory properties promoting wound healing and suppressing inflammation. Platelet-rich plasma (PRP) reinforces this biological effect. The aim of this study was to evaluate the efficacy and safety of autologous adipose-derived SVF enriched with PRP in flap repair of transsphincteric cryptoglandular fistulas. METHODS: A prospective cohort study was conducted including consecutive patients with transsphincteric cryptoglandular fistula in a tertiary referral center. During flap repair, SVF was obtained by lipoharvesting and mechanical fractionation of adipose tissue and combined with PRP was injected around the internal opening and into the fistulous wall. Endpoints were fistula healing at clinical examination and fistula closure on postoperative magnetic resonance imaging (MRI). Adverse events were documented. RESULTS: Forty-five patients with transsphincteric cryptoglandular fistula were included (29 males, median age 44 years [range 36-53 years]). In the total study population, primary fistula healing was observed in 38 patients (84%). Among the 42 patients with intestinal continuity at time of surgery, primary fistula healing was observed in 35 patients (84%). In one patient, the fistula recurred, resulting in a long-term healing rate of 82%. MRI, performed in 37 patients, revealed complete closure of the fistula tract in 33 (89.2%). In the other patients, the tract was almost completely obliterated by scar tissue. During follow-up, none of these patients showed clinical signs of recurrence. The postoperative course was uneventful, except for three cases; venous thromboembolism in one patient and bleeding under the flap, necessitating intervention in two patients. CONCLUSIONS: Addition of autologous SVF enriched with PRP during flap repair is feasible, safe and might improve outcomes in patients with a transsphincteric cryptoglandular fistula. TRIAL REGISTRATION: Dutch Trial Register, Trial Number: NL8416, https://www.trialregister.nl/.

Non-obstetric surgery in pregnancy (including bowel surgery and gallbladder surgery).

Non-obstetric surgery during pregnancy is required in 0.75-2% of pregnancies. Physiologic changes during pregnancy, both hormonal and anatomic, can have interactions with surgery and anesthesia. Indication, timing as well as risks of anesthesia and surgery should be considered in surgical decision making. The health status of the mother should always be put first. A preoperative multidisciplinary approach, also including an obstetrician and neonatologist, is mandatory. Delay in diagnosis and treatment carry risks of complications in all septic visceral indications. Considerations should be individualized.

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.

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.

Systematic review: pharmacotherapy for high-output enterostomies or enteral fistulas.

BACKGROUND: High-output enterocutaneous fistula or enterostomies can cause intestinal failure. There is a wide variety of options in medical management of patients with high output. AIM: To systematically review the literature on available pharmacotherapy to reduce output and to propose an algorithm for standard of care. METHODS: Relevant databases were systematically reviewed to identify studies on pharmacotherapy for reduction in (high-) output enterostomies or fistula. Randomised controlled trials and within subjects controlled prospective trials were included. An algorithm for standard of care was generated based on the outcomes of the systematic review. RESULTS: Two studies on proton pump inhibitors, six on anti-motility agents, three on histamine receptor antagonists, one on an α2- receptor agonist and eight on somatostatin (analogues) were included. One study examined a proton pump inhibitor and a histamine receptor antagonist within the same patients. Overall, we found evidence for the following medical therapies to be effective: omeprazole, loperamide and codeine, ranitidine and cimetidine. On the basis of these outcomes and clinical experience, we proposed an algorithm for standard of care which consists of high-dose proton pump inhibitors combined with high-dose loperamide as the first step followed by addition of codeine in case of insufficient output reduction. So far, there is insufficient evidence for the standard use of somatostatin (analogues). CONCLUSIONS: The available evidence on the efficacy of medication to reduce enterostomy or enterocutaneous fistula output is hampered by low quality studies. We propose an algorithm for standard of care output reduction in these patients.

Surgical treatment of secondary peritonitis : A continuing problem.

Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is challenging even in modern medicine. Surgical intervention for source control remains the cornerstone of treatment, beside adequate antimicrobial therapy and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery is the preferred treatment strategy, irrespective of the severity and extent of peritonitis. The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools, seems to hamper full implementation of ROD. The accuracy of the relap decision tool is reasonable for prediction of ongoing peritonitis and selection for computer tomography (CT). The value of CT in an early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT in cases of operated secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for intervention in a multidisciplinary setting.

[Surgical treatment of secondary peritonitis: A continuing problem. German version]. / Die chirurgische Therapie der sekundären Peritonitis : Ein weiter andauerndes Problem.

BACKGROUND: Secondary peritonitis remains associated with high mortality and morbidity rates. Treatment of secondary peritonitis is still challenging even in the era of modern medicine. Surgical intervention for source control remains the cornerstone of treatment besides adequate antimicrobial therapy and when necessary intensive medical care measures and resuscitation. A randomized clinical trial showed that relaparotomy on demand (ROD) after initial emergency surgery was the preferred treatment strategy, irrespective of the severity and extent of peritonitis. RESULTS AND DISCUSSION: The effective and safe use of ROD requires intensive monitoring of the patient in a setting where diagnostic tests and decision making about relaparotomy are guaranteed round the clock. The lack of knowledge on timely and adequate patient selection, together with the lack of use of easy but reliable monitoring tools seem to hamper full implementation of ROD. The accuracy of the relaparotomy decision tool is reasonable for prediction of the formation of peritonitis and necessary selection of patients for computed tomography (CT). The value of CT in the early postoperative phase is unclear. Future research and innovative technologies should focus on the additive value of CT after surgical treatment for secondary peritonitis and on the further optimization of bedside prediction tools to enhance adequate patient selection for interventions in a multidisciplinary setting.

Initial microbial spectrum in severe secondary peritonitis and relevance for treatment.

This study aims to determine whether abdominal microbial profiles in early severe secondary peritonitis are associated with ongoing infection or death. The study is performed within a randomized study comparing two surgical treatment strategies in patients with severe secondary peritonitis (n = 229). The microbial profiles of cultures retrieved from initial emergency laparotomy were tested with logistic regression analysis for association with 'ongoing infection needing relaparotomy' and in-hospital death. No microbial profile or the presence of yeast or Pseudomonas spp. was related to the risk of ongoing infection needing relaparotomy. Resistance to empiric therapy for gram positive cocci and coliforms was moderately associated with ongoing abdominal infection (OR 3.43 95%CI 0.95-12.38 and OR 7.61, 95%CI 0.75-76.94). Presence of only gram positive cocci, predominantly Enterococcus spp, was borderline independently associated with in-hospital death (OR 3.69, 95%CI 0.99-13.80). In secondary peritonitis microbial profiles do not predict ongoing abdominal infection after initial emergency laparotomy. However, the moderate association of ongoing infection with resistance to the empiric therapy compels to more attention for resistance when selecting empiric antibiotic coverage.

Identification of risk factors for an unfavorable laparoscopic cholecystectomy course after endoscopic retrograde cholangiography in the treatment of choledocholithiasis.

BACKGROUND: Laparoscopic cholecystectomy (LC) after an endoscopic retrograde cholangiography (ERC) has higher rates for complications and conversion caused by unpredictable adhesions. The risk factors for an adverse outcome of LC after an ERC were analyzed. METHODS: Variables from patients treated by LC after ERC for cholelithiasis in two clinics from 1996 to 2003 were retrospectively stored in a database. Complications and conversions were recorded. RESULTS: A total of 140 patients underwent LC after ERC (83 from clinic A and 57 from clinic B), 31% (44/140) of whom were men. Peri- or postoperative complications occurred for 28 patients (20%). For 19 patients (14%), a conversion was necessary. Significant variables associated with complications and conversions were an elevated level of C-reactive protein (CRP) at the time of LC (odds ratio [OR], 10.2; 95% confidence interval [CI], 1.1-91, P = 0.037 for both) and severe adhesions during laparoscopy (OR, 3.6; 95% CI, 1.5-8.6; P = 0.003 and OR, 5.2; 95% CI, 1.9-14.4; P = 0.002, respectively). Male gender (OR, 2.8; 95% CI, 1.1-7.6; P = 0.037) and serum bilirubin level at the time of ERC (OR, 3.7; 95% CI, 1.24-11; P = 0.014) were associated with conversion only. Time after ERC (LC within 1 week vs. >1 week or < or = 2 weeks vs. 2-6 weeks vs. >6 weeks or < or = 6 weeks vs. >6 weeks) was not associated with complications or conversion. Multivariate regression analysis showed a pre-LC CRP exceeding 6 to be predictive of complications (OR, 10.5; 95% CI, 1.1-95; P = 0.040) and conversion (OR, 10.6; 95% CI, 1.1-99; P = 0.034). CONCLUSION: Male gender, bilirubin levels during ERC, severe adhesions during LC, and pre-LC CRP levels were associated with an adverse outcome for an LC after endoscopic cholangiography. The time between LC and ERC failed to be a significant risk factor in this larger series.

Decision making for relaparotomy in secondary peritonitis.

BACKGROUND/AIMS: To provide a qualitative ranking of clinical variables by surgeons that influence their decision for reoperation and to evaluate whether these variables are related to positive findings at relaparotomy. METHODS: Importance in decision making for relaparotomy was evaluated for 21 factors using a 10-point visual analogue scale (VAS). Variables with median VAS scores >5.0 were labeled 'important'. Predictive value for positive findings was evaluated by multivariate analysis. RESULTS: The response rate was 64%. For each variable, a wide range of VAS scores was given. Of variables labeled 'important', a diffuse extent of abdominal contamination (odds ratio, OR 1.9; 95% CI 0.99-3.8; p = 0.052), localization of the infectious focus (upper gastrointestinal tract including small bowel: OR 2.6, 95% CI 0.98-7.0, p = 0.055; colon: OR 2.4, 95% CI 0.93-6.0, p = 0.071), and both low (<3 x 10(9)/l: OR 4.6, 95% CI 1.3-17, p = 0.021) and high (>20 x 10(9)/l: OR 2.2, 95% CI 1.0-4.9, p = 0.042) leukocyte counts independently predicted positive relaparotomy. As a set, these variables had only moderate predictive accuracy (c-statistic 0.69). CONCLUSIONS: There was no consensus among surgeons which variables were important in decision making for relaparotomy. Only three out of ten variables labeled as 'important' were indeed independently predictive, but even as a set had only moderate predictive accuracy.

[Relaparotomy in secondary peritonitis Planned relaparotomy or relaparotomy on demand?]. / Relaparotomie bei sekundärer Peritonitis. Programmierte Relaparotomie oder Relaparotomie "on demand"?

Secondary peritonitis is associated with serious morbidity and a persistent high mortality in recent decades, this despite improvement in antibiotic, intensive care and surgical treatment. The available literature regarding the surgical treatment of secondary peritonitis was searched through Pubmed (1966- January 2005) as well as a hand search of references of retrieved articles. Definitions, pathophysiology and classification of secondary peritonitis are discussed, as well as the scientific rationale for the surgical treatment in secondary peritonitis. The historical development and the scientific foundation of present-day relaparotomy strategies in secondary peritonitis are evaluated, with an emphasis on two frequently applied surgical treatment strategies: planned relaparotomy and relaparotomy on demand. Criteria for relaparotomy after the initial laparotomy and potential areas for further research to reduce both morbidity and mortality are discussed. Furthermore, the care of patients with secondary peritonitis is evolving from a surgical entity to a more multidisciplinary challenge uniting surgeons, intensivists, radiologists and microbiologists. Research needs to be expanded into novel fields to further decrease morbidity and mortality.

Survey among surgeons on surgical treatment strategies for secondary peritonitis.

BACKGROUND: There is controversy about performing either a planned relaparotomy (PR) or relaparotomy on demand (ROD) in patients with secondary peritonitis. Subjective factors influencing surgeons in decision making for either surgical treatment strategy have never been studied. METHODS: All 858 surgeons of the Association of Surgeons of The Netherlands were sent a survey with 16 case vignettes simulating peritonitis patients and evaluating the preference for PR or ROD. RESULTS: Sixty-two percent of surgeons responded to the survey. Of the returned surveys, 407 were eligible for evaluation. The responding surgeons had a slight overall preference for the ROD strategy, as shown by the mean overall preference score of 5.2 (range 3.54-6.52, with a maximal score of 7). Gastrointestinal surgeons and surgeons working in regional and smaller hospitals were significantly more in favour of a ROD strategy than their counterparts. Factors significantly influencing the preference towards PR were ischaemia as aetiology and performing a primary anastomosis; as for ROD, it was small bowel as focus, local extent of contamination and the question whether abdominal closure was possible. However, there was a considerable variability in treatment decisions by surgeons. CONCLUSION: The majority of responding surgeons would make a choice for a particular treatment strategy based on peritonitis and surgical treatment characteristics. There was a slight overall preference towards the ROD strategy despite the considerable variability per case vignette.