Activated HLA-DR+CD38+ Effector Th1/17 Cells Distinguish Crohn's Disease-associated Perianal Fistulas from Cryptoglandular Fistulas.

BACKGROUND: Perianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses. METHODS: We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets. RESULTS: Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts. CONCLUSIONS: Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas.

We applied high-dimensional analyses to profile the immune compartment in CD-associated and cryptoglandular perianal fistulas. Data analysis revealed activated HLA-DR+CD38+ effector Th1/17 cells as distinctly increased in CD-associated fistulas, suggesting a potential novel therapeutic target.

Laparoscopic repair of a traumatic diaphragmatic rupture.

INTRODUCTION AND IMPORTANCE: Traumatic diaphragmatic ruptures following blast injury or penetrating trauma rarely present themselves with chronic symptoms warranting elective surgery. CASE PRESENTATION: We present the case of a 49-year-old man who survived a grenade explosion and experienced chronic chest pain. Considering the previous trauma, computed tomography imaging was performed and showed a left-sided traumatic diaphragmatic rupture ventral to the spleen, resulting in herniation of the transverse colon and omentum in the thoracic cavity. Metal shrapnel was located between the stomach and spleen, the suspected cause of the diaphragmatic hernia. The patient was eligible for minimal invasive laparoscopic surgery. CLINICAL DISCUSSION: During surgery, a left diaphragmatic rupture and metal shrapnel on the right side of the rupture were found. The hernia was reduced and the metal shrapnel was removed, aiding in fully repositioning of the omentum and transversed colon. After which the left lower lung lobe was able to fully inflate. The rupture was closed using single V-lock sutures and strips of the Phasix mesh to reinforce the diaphragm repair with single ethibond sutures. No surgical or post-operative complications were observed and the patient did not experience any of his previous complaints. CONCLUSION: In this case, laparoscopic repair of diaphragmatic rupture after penetrating trauma can be considered as an effective surgical approach.

Hybrid operation technique for incisional hernia repair: a systematic review and meta-analysis of intra- and postoperative complications.

BACKGROUND: Incisional hernia (IH) occurs approximately in 15% of patients after midline surgery. Surgical treatment for IHs include a solely open or solely laparoscopic approach with mesh placement. Recently, hybrid (combined laparoscopic and open) approaches have been introduced. This systematic review evaluates perioperative complications of hybrid incisional hernia repair (HIHR). METHODS: EMBASE, Medline via OvidSP, Web of Science, Cochrane and Google Scholar databases were searched. Studies providing data on intra- and postoperative complications in patients who underwent HIHR were included. Data on intra- and postoperative complications were extracted and meta-analyses were performed. Study quality was assessed with the Newcastle Ottowa Scale, ROBINS-I tool, and Cochrane risk of bias. PROSPERO registration: CRD42020175053. RESULTS: Eleven studies (n = 1681 patients) were included. Five studies compared intra-operative complications between HIHR and laparoscopic incisional hernia repair (LIHR) with a pooled incidence of 1.8% in HIHR group and 2.8% in LIHR group (p = 0.13). Comparison of postoperative prevalence of surgical site occurrences (SSOs) (23% versus 26%, p = 0.02) and surgical site occurrences requiring interventions (SSOPIs) (1.5% versus 4.1%, p < 0.01) were in favour of the HIHR group. Overall postoperative complications seemed to occur less frequent in the HIHR group, though no hard statements could be made due to the vast heterogeneity in reporting between studies. CONCLUSION: Although the majority of studies were retrospective and included a small number of patients, HIHR seemingly led to less SSOs and SSOPIs. This systematic review forms a strong invitation for more randomized controlled trials to confirm the benefits of this approach.

A new three-step hybrid approach is a safe procedure for incisional hernia: early experiences with a single centre retrospective cohort.

PURPOSE: In this study, a three-step novel surgical technique was developed for incisional hernia, in which a laparoscopic procedure with a mini-laparotomy is combined: so-called 'three-step incisional hybrid repair'. The aim of this study was to reduce the risk of intestinal lacerations during adhesiolysis and recurrence rate by better symmetrical overlap placement of the mesh. OBJECTIVES: To evaluate first perioperative outcomes with this technique. METHODS: From 2016 to 2020, 70 patients (65.7% females) with an incisional hernia of > 2 and ≤ 10 cm underwent a elective three-step incisional hybrid repair in two non-academic hospitals performed by two surgeons specialised in abdominal wall surgery. Intra- and postoperative complications, operation time, hospitalisation time and hernia recurrence were assessed. RESULTS: Mean operation time was 100 min. Mean hernia size was 4.8 cm; 45 patients (64.3%) had a hernia of 1-5 cm, 25 patients (35.7%) of 6-10 cm. Eight patients had a grade 1 complication (11.4%), five patients a grade 2 (7.1%), two patients (2.8%) a grade 4 complication and one patient (1.4%) a grade 5 complication. Five patients had an intraoperative complication (7.0%), two enterotomies, one serosa injury, one omentum bleeding and one laceration of an epigastric vessel. Mean length of stay was 3.3 days. Four patients (5.6%) developed a hernia recurrence during a mean follow-up of 19.5 weeks. CONCLUSION: A three-step hybrid incisional hernia repair is a safe alternative for incisional hernia repair. Intraoperative complications rate was low.

Laparoscopic Repair with Mesh Reinforcement is a Feasible Alternative for Epigastric Hernia: A Retrospective Study Comparing Laparoscopic with Open Repair.

BACKGROUND: Epigastric hernias may lead to discomfort and pain. The mainstay of treatment is surgical repair with mesh reinforcement. The primary aim of this study was to compare the recurrence rates of laparoscopic epigastric hernia repair (LEHR) and conventional open epigastric hernia repair (OEHR) with mesh reinforcement. Secondary aims were to evaluate perioperative outcomes and quality of life. METHODS: Ninety-nine patients (58% female) from two non-academic hospitals were retrospectively reviewed. The Short-Form 36 Health Survey questionnaire and Carolina Comfort Scale were used to assess quality of life and complaints related to mesh implantation. RESULTS: Forty-two (42%) patients underwent LEHR and 57 (58%) underwent OEHR. The mean follow-up at the outpatient clinic was 7.1 months in the LEHR group and 8.1 months in the OEHR group. The mean follow-up by telephone contact was 67.8 months in the OEHR group and 58.1 months in the LEHR group. The risk of recurrence appeared to be slightly lower for LEHR (2%) compared to OEHR (7%), but this difference was not significant (p=0.298). The median surgical duration was 54 minutes in the LEHR group and 28 minutes in the OEHR group (p<0.001). The median hospitalization time was 1 day in the LEHR group and 0.5 days in the OEHR group (p<0.001). CONCLUSION: Laparoscopic hernia repair tended to be associated with a lower risk of recurrence, but this difference was not statistically significant. Although the surgical duration was longer for the LEHR group, the postoperative outcomes were similar between groups, making laparoscopic repair a feasible alternative to the open approach for epigastric hernias.

The ileo neo rectal anastomosis: long-term results of surgical innovation in patients after ulcerative colitis and familial adenomatous polyposis.

PURPOSE: Restorative proctocolectomy with ileo neo rectal anastomosis (INRA) combines cure of ulcerative colitis (UC) or familial adenomatous polyposis (FAP) with restoration of intestinal continuity. Evaluation of long-term results was needed to determine if there is a place for INRA in the armamentarium of a surgeon besides the ileal pouch anal anastomosis (IPAA). METHODS: All patients with INRA were included in the analysis. Patient demographics and clinical and follow-up data (morbidity, dietary problems, defecation frequency, fecal continence, anal and neorectal physiology, and neorectal mucosa assessment) were registered prospectively. RESULTS: Seventy-nine patients were enrolled, and in 58 patients (50 UC, 8 FAP), INRA was successful. In 21 patients, intraoperative conversion to IPAA was needed. In 49 patients with INRA, a functional reservoir was achieved. No pelvic sepsis or bladder or sexual dysfunction occurred. Thirteen patients experienced episodes of reservoir inflammation. Median bowel movements of six (5, 8) with a nocturnal defecation frequency of one were recorded with fecal continence or minor incontinence. Anal manometry and neorectal physiology showed a decrease in resting pressure and an increase in squeeze pressure and maximum tolerated volume. The median follow-up was 8.1 years (6.7, 10.1). CONCLUSIONS: This is an example of a surgical innovation with a theoretical potential to be superior to the current technique. This potential was not confirmed in short- and long-term evaluations. Hence, IPAA is currently the best available alternative to a conventional ileostomy.

Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies.

OBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.

Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients.

OBJECTIVE: To analyze the literature of ileal pouch anal anastomosis (IPAA) regarding complications and functional outcome, to provide audit data for individual surgeons and units to assess their own performance against and also to serve as reference standard for the assessment of novel alternatives. BACKGROUND: IPAA is the standard restorative procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). This operation is, however, associated with distinct rates of failure, complications and fecal incontinence. METHODS: A meta-analysis on pooled incidences of complications of IPAA was conducted. Medline search and cross-reference search identified studies on IPAA (n > or = 50). Two authors independently performed the data extraction on study characteristics, diagnosis, type of operation, pouch-related complications, pouch failure and functional results. In case of disagreement consensus was reached by joint review of the study. Estimates of pouch-related complications, pouch failure and functional results are described as pooled percentages with 95% confidence interval. RESULTS: The initial search based on 1,206 abstracts yielded 43 studies eligible for further analysis. Indications for IPAA were UC in 87.5%, FAP in 8.9% and other diagnoses in 3.6%. The median follow-up was 36.7 months. Pouch failure was 6.8%, increasing to 8.5% in case of follow-up of more than 60 months. Pelvic sepsis occurred in 9.5%. Severe, mild and urge fecal incontinence were reported in 3.7, 17, and 7.3%, respectively. No effect of experience, duration of follow-up and type of surgical technique on the incidence of pouch failure and pelvic sepsis was demonstrable. CONCLUSIONS: Current techniques for restorative surgery after proctocolectomy are associated with non-negligible complication rates and leave room for improvement and continuation of development of alternative procedures.