Dendritic Cells Require TMEM176A/B Ion Channels for Optimal MHC Class II Antigen Presentation to Naive CD4+ T Cells.

Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. In this study, we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in retinoic acid-related orphan receptor γt+ cells and conventional dendritic cells (DCs) using germline and conditional double knockout mice. Although Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells in the intestinal mucosa, we found that they were required in conventional DCs for optimal Ag processing and presentation to CD4+ T cells. Using a real-time imaging method, we show that TMEM176A/B accumulate in dynamic post-Golgi vesicles preferentially linked to the late endolysosomal system and strongly colocalize with HLA-DM. Taken together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC class II compartment of DCs for the fine regulation of Ag presentation and naive CD4+ T cell priming.

Clinical and functional outcome of surgery for posttraumatic cloacal deformity.

AIM: Cloacal deformity is a disabling condition that severely affects a patient's quality of life. Surgery to repair cloacal deformity remains the mainstay of treatment. The aim of this study is to assess the clinical and functional outcome of patients treated for traumatic cloacal deformity by three different techniques. METHOD: A retrospective multicentre study was carried out using data from women operated on for cloacal deformity between 2015 and 2019. Demographic characteristics, the presence of urinary and/or faecal incontinence and manometric findings were collected. The main outcome measures were represented by St Mark's and Rockwood faecal incontinence quality of life scores. RESULTS: Thirty eight women with a median age of 34 years [interquartile range (IQR) 31-39 years] were enrolled. Perineoplasty was performed in 23 patients by direct suture of the rectovaginal septum, in five using the X-flap and in 10 by the Singapore flap. Median resting and squeezing pressures increased significantly from 28.15 (IQR 23-32.7) cmH2 O to 45 (IQR 31-60.7) cmH2 O (p = 0.0001) and from 47 (IQR 41.2-54.7) cmH2 O to 97.2 (IQR 80-118) cmH2 O (p = 0.0001), respectively. Maximum tolerable volume improved from 120 (IQR 90-137.5) ml to 137.5 (IQR 120-150) ml (p = 0.002). The St Mark's score decreased from 18 (IQR 14-20) to 4.5 (IQR 2-8) after 20 months (p = 0001). Sexual activity was confirmed by 16 patients preoperatively and by 27 postoperatively. A diverting stoma was performed in three patients after X-flap perineoplasty and in 14 treated by direct closure. No significant differences were found pre- and postoperatively between the three groups. CONCLUSION: Regardless of the technique used, surgical repair significantly improves both clinical and functional outcomes irrespective of the presence of a covering stoma.

Implant of Self-Expandable Artificial Anal Sphincter in Patients With Fecal Incontinence Improves External Anal Sphincter Contractility.

BACKGROUND: External anal sphincter contractility significantly contributes to control the passage of stool. An artificial anal sphincter placed into the intersphincteric space is a safe and effective procedure to treat fecal incontinence, even if its mechanism of action has not been fully elucidated. OBJECTIVE: The aim of this study was to evaluate external anal sphincter contractility changes after a self-expandable hyexpan prostheses was implanted into the intersphincteric space of the anal canal and clinical outcomes compared. DESIGN: This was a prospective clinical study. SETTINGS: The study was conducted at a university teaching hospital. PATIENTS: Consecutive patients affected by fecal incontinence for at least 6 months after failure of conservative treatment were included. INTERVENTIONS: All of the patients underwent 10-prostheses implantation and were examined preoperatively and postoperatively by endoanal ultrasound and anorectal manometry. MAIN OUTCOME MEASURES: Fecal incontinence symptoms were assessed by severity scores. The external anal sphincter muscle tension was calculated using a specific equation. RESULTS: Thirty-nine patients (34 women; median age = 68 y) were included in the study; no morbidity was registered. After a median follow-up period of 14 months, both the median maximum voluntary squeeze pressure and the median inner radius of the external anal sphincter significantly increased. A statistically significant increase of external anal sphincter muscle tension was detected. A decrease of any fecal incontinence symptom and an improvement in severity scores were observed at the last follow-up examination. The external anal sphincter contractility was significantly higher in patients reducing incontinence episodes to solid stool by >50% and improving their ability to defer defecation for >15 minutes. LIMITATIONS: This was a single-center experience with a relatively small and heterogeneous sample size, patients with a potentially more severe disease because our institution is a referral center, and an absence of quality-of-life evaluation. CONCLUSIONS: Artificial anal sphincter implantation improved the external anal sphincter muscle tension; there was a positive correlation between its increase and the clinical outcome. See Video Abstract at http://links.lww.com/DCR/B468. IMPLANTE DE ESFNTER ANAL ARTIFICIAL AUTOEXPANDIBLE EN PACIENTES CON INCONTINENCIA FECAL MEJORA LA CONTRACTILIDAD DEL ESFNTER ANAL EXTERNO: ANTECEDENTES:La contractilidad del esfínter anal externo contribuye significativamente al control del paso de las heces. Un esfínter anal artificial colocado en el espacio interesfinteriano es un procedimiento seguro y eficaz para tratar la incontinencia fecal, incluso si su mecanismo de acción no se ha definido por completo.OBJETIVO:El objetivo de este estudio fue evaluar los cambios en la contractilidad del esfínter anal externo después de la implantación de una prótesis de hyexpan autoexpandible en el espacio interesfinteriano del canal anal y comparar los resultados clínicos.DISEÑO:Estudio clínico prospectivo.ENTORNO CLINICO:El estudio se realizó en un hospital universitario.PACIENTES:Pacientes consecutivos afectados por incontinencia fecal durante al menos 6 meses, tras fracaso de tratamiento conservador.INTERVENCIONES:Todos los pacientes fueron sometidos a la implantación de 10 prótesis, y fueron examinados pre y postoperatoriamente mediante ecografía endoanal y manometría anorrectal.PRINCIPALES MEDIDAS DE VALORACION:Los síntomas de incontinencia fecal se evaluaron mediante puntuaciones de gravedad. La tensión del músculo del esfínter anal externo se calculó mediante una formula específica.RESULTADOS:Treinta y nueve pacientes (34 mujeres; mediana de edad 68 años) fueron incluidos en el estudio; no se registró morbilidad. Después de un período de seguimiento medio de 14 meses, tanto la presión de compresión voluntaria máxima media como el radio interior medio del esfínter anal externo aumentaron significativamente. Se detectó un aumento estadísticamente significativo de la tensión del músculo del esfínter anal externo. En el último examen de seguimiento se observó una disminución de cualquier síntoma de incontinencia fecal y una mejora en las puntuaciones de gravedad. La contractilidad del esfínter anal externo fue significativamente mayor en los pacientes que redujeron los episodios de incontinencia a heces sólidas en más del 50% y mejoraron la capacidad para diferir la defecación durante más de 15 minutos.LIMITACIONES:Experiencia de un solo centro; tamaño de muestra relativamente pequeño y heterogéneo; pacientes con una enfermedad potencialmente más grave porque nuestra institución es un centro de referencia; ausencia de evaluación de la calidad de vida.CONCLUSIONES:La implantación del esfínter anal artificial mejoró la tensión muscular del esfínter anal externo; hubo una correlación positiva entre su aumento y el resultado clínico. Consulte Video Resumen en http://links.lww.com/DCR/B468.

A worldwide survey on proctological practice during COVID-19 lockdown (ProctoLock 2020): a cross-sectional analysis.

AIM: Proctology is one of the surgical specialties that has suffered the most during COVID-19 pandemic. Using a cross-sectional non-incentivised World Wide Web survey, we aimed to snapshot the current status of proctological practice in six world regions. METHOD: Surgeons affiliated to renowned scientific societies with an interest in coloproctology were invited to join the survey. Members of the ProctoLock Working Group enhanced recruitment by direct invitation. The predictive power of respondents' and hospitals' demographics on the change of status of surgical and outpatient activities was calculated. RESULTS: Respondents (n = 1050) were mostly men (79%), with a mean age of 46.9 years, at consultant level (79%), practising in academic hospitals (53%) offering a dedicated proctology service (68%). A total of 119 (11%) tested positive for SARS-CoV-2. The majority (54%) came from Europe. Participants from Asia reported a higher proportion of unaltered practice (17%), while those from Europe had the highest proportion of fully stopped practice (20%). The likelihood of ongoing surgical practice was higher in men (OR 1.54, 95% CI 1.13-2.09; P = 0.006), in those reporting readily availability of personal protective equipment (PPE) (OR 1.40, 1.08-1.42; P = 0.012) and in centres that were partially or not at all involved in COVID-19 care (OR 2.95, 2.14-4.09; P < 0.001). This chance decreased by 2% per year of respondent's age (P = 0.001). CONCLUSION: Several factors including different screening policies and resource capacity affected the current status of proctological practice. This information may help health authorities to formulate effective preventive strategies to limit curtailment of care of these patients during the pandemic.

Gatekeeper Improves Voluntary Contractility in Patients With Fecal Incontinence.

BACKGROUND: Gatekeeper (GK) has shown to be safe and effective in patients with fecal incontinence (FI). We aimed to understand its mechanism of action by comparing pre- and post-implant change in the external anal sphincter (EAS) contractility. METHODS: Study of EAS contractility was conducted in 16 FI females (median age = 69 years) before and after implant of 6 GK prostheses. Muscle tension ( Tm), expressed in millinewtons per centimeter squared, mN(cm2)-1, was calculated using the equation Tm = P(ri)(tm)-1, where P is the average maximum squeeze pressure and ri and tm the inner radius and thickness of the EAS, respectively. The effect of a predefined set of covariates on Tm was tested by restricted maximum likelihood models. RESULTS: Compared with baseline, despite unchanged tm (2.7 [2.5-2.8] vs 2.5 [2.2-2.8] mm; P = .31 mm), a significant increase in P (median = 45.8 [26.5-75.8] vs 60.4 [43.1-88.1] mm Hg; P = .017), and ri (12.4 [11.5-13.4] vs 18.7 [17.3-19.6] mm; P < .001) resulted in an increase in Tm (233.2 [123.8-303.2] vs 490.8 [286.9-562.4] mN(cm2)-1; P < .001) at 12 months after GK implant. Twelve-month follow-up improvements were also observed on Cleveland Clinic FI score (8-point median decrease; P = .0001), St Marks FI score (10-point median decrease; P < .0001), and American Medical Systems score (39-point median decrease; P < .0001). Restricted maximum likelihood models showed that years of onset of FI was negatively associated with change in Tm ( P = .048). CONCLUSIONS: GK-related EAS compression positively influences muscle contractility by increasing ri, with consequent increase in Tm (length-tension relationship). Further studies are needed to confirm the long-term effectiveness of GK.

Transanal Total Mesorectal Excision vs Laparoscopic Total Mesorectal Excision in the Treatment of Low and Middle Rectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND: Transanal total mesorectal excision is a novel and promising technique in the treatment of low and middle rectal cancer. OBJECTIVE: This study aimed to compare the safety and feasibility of transanal total mesorectal excision versus laparoscopic total mesorectal excision. DESIGN: This was a retrospective study using propensity score matching analysis. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: Patients with low and middle rectal cancer who underwent total mesorectal excision with curative intent between 2007 and 2017 were recruited. INTERVENTIONS: Laparoscopic total mesorectal excision and transanal total mesorectal excision had been performed. MAIN OUTCOME MEASURES: Intraoperative, pathological, and 30-day postoperative outcomes were compared between the transanal and laparoscopic groups. RESULTS: Overall, 105 patients were selected from the whole sample of 316 patients with rectal cancer. After propensity score matching analysis, 46 patients for each group were compared. Laparoscopic total mesorectal excision was associated with a higher conversion rate to open surgery (19.6% vs 0%, p = 0.002). Transanal total mesorectal excision showed a longer distal resection margin (15 mm vs 25 mm; p < 0.001), and similar results regarding the completeness of mesorectal excision and circumferential resection margin involvement, compared to laparoscopy. There were no statistically significant differences between the 2 groups in terms of postoperative complications. LIMITATIONS: The study was limited by its retrospective design and the small size of the sample. CONCLUSIONS: Transanal total mesorectal excision is a safe and feasible technique that results in a high-quality rectal cancer resection specimen and favorable 30-day postoperative outcomes.

High Smad7 sustains inflammatory cytokine response in refractory coeliac disease.

Refractory coeliac disease (RCD) is a form of coeliac disease (CD) resistant to gluten-free diet and associated with elevated risk of complications. Many effector cytokines over-produced in the gut of patients with RCD are supposed to amplify the tissue-destructive immune response, but it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms. The aim of the present study was to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor-ß1 (TGF-ß1 ) activity. Smad7 was evaluated in duodenal biopsy samples of patients with RCD, patients with active CD, patients with inactive CD and healthy controls by Western blotting, immunohistochemistry and real-time PCR. In the same samples, TGF-ß1 and phosphorylated (p)-Smad2/3 were evaluated by ELISA and immunohistochemistry, respectively. Pro-inflammatory cytokine expression was evaluated in RCD samples cultured with Smad7 sense or antisense oligonucleotide. Smad7 protein, but not RNA, expression was increased in RCD compared with active and inactive CD patients and healthy controls and this was associated with defective TGF-ß1 signalling, as marked by diminished p-Smad2/3 expression. TGF-ß1 protein content did not differ among groups. Knockdown of Smad7 in RCD biopsy samples reduced interleukin-6 and tumour necrosis factor-α expression. In conclusion, in RCD, high Smad7 associates with defective TGF-ß1 signalling and sustains inflammatory cytokine production. These results indicate a novel mechanism by which the mucosal cytokine response is amplified in RCD and suggest that targeting Smad7 can be therapeutically useful in RCD.

High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer.

HMGA2 is a small, non-histone, chromatin-associated protein with a key role in tumorigenesis and adipogenesis. Indeed, HMGA2 overexpression has been frequently detected in several malignant neoplasms and inhibition of its expression prevents thyroid cell transformation. Moreover, HMGA2 null mice show a pigmy phenotype with a great reduction in fat tissue. To investigate whether HMGA2 expression correlates with clinico-pathological parameters and patient outcome, immunohistochemical analysis of HMGA2 expression was performed in ovarian cancer specimens from 117 patients. HMGA2 overexpression was found in 39% of the cases and, interestingly, positively correlated with the body mass index (BMI). Moreover, high BMI (≥ 25 kg/m(2) ) and high HMGA2 expression/BMI combined evaluation predicted shorter disease-free survival. High BMI (≥ 25 kg/m(2) ), high expression of HMGA2 and high HMGA2 expression/BMI combined evaluation predicted shorter overall survival. In multivariate analysis, the concomitant high expression of HMGA2 and high BMI (≥ 25 kg/m(2) ) was an independent prognostic factor. Finally, the BMI (≥ 25 kg/m(2) ) negatively correlated with the patient response to chemotherapy (P=0.039). Therefore, the data reported herein suggest that the combined evaluation of HMGA2 expression and obesity assessed through BMI can be considered a marker of poor prognosis in patients affected by ovarian carcinoma.

Timing and Modality of Hemorrhoidal Prolapse Impact on Patients' Quality of Life.

Background: The aim of this study was to assess whether the frequency and presentation modality of hemorrhoidal prolapse may have an impact on patients' quality of life, leading to a different categorization of patients. Methods: A consecutive series of patients affected by primary hemorrhoidal disease were administered specific questionnaires to assess the severity of symptoms and their quality of life. The frequency/modality of prolapse was also assessed, and the classification of the patients into five categories was hypothesized. The severity of disease was assessed using a validated patient-reported score, while the health-related quality of life was evaluated with the Short Health Scale for hemorrhoidal disease. Results: A total of 122 patients were enrolled. The evaluation of the prolapse modality led to the following classification: type I, 5 patients (4.1%); type II, 9 (7.4%), type IIIa, 48 (39.3%); type IIIb, 52 (42.6%); and type IV, 8 (6.6%). The mean total hemorrhoidal disease score was 9.8 ± 3.3, while the mean total Short Health Scale score was 18.6 ± 5.2. Both scores progressively increased in the five types of prolapse identified, thus showing a worsening of symptoms and quality of life related to the increase in the frequency and modality of prolapse. The assessment of the quality of life showed that all four domains of the Short Health Scale score and the total score were significantly worse in group IIIb compared to IIIa. Conclusions: The frequency and modality of hemorrhoidal prolapse has an impact on the quality of life and allows the identification of new types of patients.

Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibro-stenosis in Crohn's disease.

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibro-stenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate to the mechanisms underlying fibro-stenosis in CD, we analysed the transcriptome of cells isolated from the transmural ileum of CD patients, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from non-CD patients. Our computational analysis revealed that pro-fibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibro-stenosis in CD.

IL-1R signaling drives enteric glia-macrophage interactions in colorectal cancer.

Enteric glia have been recently recognized as key components of the colonic tumor microenvironment indicating their potential role in colorectal cancer pathogenesis. Although enteric glia modulate immune responses in other intestinal diseases, their interaction with the colorectal cancer immune cell compartment remains unclear. Through a combination of single-cell and bulk RNA-sequencing, both in murine models and patients, here we find that enteric glia acquire an immunomodulatory phenotype by bi-directional communication with tumor-infiltrating monocytes. The latter direct a reactive enteric glial cell phenotypic and functional switch via glial IL-1R signaling. In turn, tumor glia promote monocyte differentiation towards pro-tumorigenic SPP1+ tumor-associated macrophages by IL-6 release. Enteric glia cell abundancy correlates with worse disease outcomes in preclinical models and colorectal cancer patients. Thereby, our study reveals a neuroimmune interaction between enteric glia and tumor-associated macrophages in the colorectal tumor microenvironment, providing insights into colorectal cancer pathogenesis.

Fistulotomy with end-to-end primary sphincteroplasty for anal fistula: results from a prospective study.

BACKGROUND: Fistulotomy plus primary sphincteroplasty for complex anal fistulas is regarded with scepticism, mainly because of the risk of postoperative incontinence. OBJECTIVES: The aim of this study was to evaluate safety and effectiveness of this technique in medium-term follow up and to identify potential predictive factors of success and postoperative continence impairment. DESIGN AND SETTING: This was a prospective observational study conducted at a tertiary care university hospital in Italy. PATIENTS: A total of 72 patients with complex anal fistula of cryptoglandular origin underwent fistulotomy and end-to-end primary sphincteroplasty; patients were followed up at 1 week, 1 and 3 months, 1 year, and were invited to participate in a recent follow-up session. MAIN OUTCOME MEASURES: Success regarding healing of the fistula was assessed with 3-dimensional endoanal ultrasound and clinical evaluation. Continence status was evaluated using the Cleveland Clinic fecal incontinence score and by patient report of post-defecation soiling. RESULTS: Of the 72 patients, 12 (16.7%) had recurrent fistulas and 29 patients (40.3%) had undergone seton drainage before definitive surgery. At a mean follow-up of 29.4 (SD, 23.7; range, 6-91 months, the success rate of treatment was 95.8% (69 patients). Fistula recurrence was observed in 3 patients at a mean of 17.3 (SD, 10.3; range, 6-26) months of follow-up. Cleveland Clinic fecal incontinence score did not change significantly (p = 0.16). Eight patients (11.6% of those with no baseline incontinence) reported de novo postdefecation soiling. None of the investigated factors was a significant predictor of success. Patients with recurrent fistula after previous fistula surgery had a 5-fold increased probability of having impaired continence (relative risk = 5.00, 95% CI, 1.45-17.27, p = 0.02). LIMITATIONS: The study was limited by potential single-institution bias, lack of anorectal manometry, and lack of quality of life assessment. CONCLUSIONS: Fistulotomy with end-to-end primary sphincteroplasty can be considered to be an effective therapeutic option for the treatment of complex anal fistulas, with low morbidity, a high rate of success even at long-term follow-up, and a very low rate of postoperative major fecal incontinence, although minor impairment of continence (postdefecation soiling) may occur. Caution should be used in selecting patients with a history of recurrent fistula and fecal incontinence.

Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer.

Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. Although conclusive evidence is still lacking, epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has chemopreventive properties against CRC. Similarly, regular consumption of mesalazine, a drug structurally related to NSAIDs, seems to reduce the risk of CRC in patients with ulcerative colitis. These observations are supported by a large body of experimental data showing the ability of such drugs to inhibit multiple pathways that sustain colon carcinogenesis. This review summarizes the current information on the molecular mechanisms by which NSAIDs and mesalazine could interfere with CRC cell growth and survival.

The dual role of Smad7 in the control of cancer growth and metastasis.

Smad7 was initially identified as an inhibitor of Transforming growth factor (TGF)-ß due mainly to its ability to bind TGF-ß receptor type I and prevent TGF-ß-associated Smad signaling. More recently, it has been demonstrated that Smad7 can interact with other intracellular proteins and regulate also TGF-ß-independent signaling pathways thus making a valid contribution to the neoplastic processes in various organs. In particular, data emerging from experimental studies indicate that Smad7 may differently modulate the course of various tumors depending on the context analyzed. These observations, together with the demonstration that Smad7 expression is deregulated in many cancers, suggest that therapeutic interventions around Smad7 can help interfere with the development/progression of human cancers. In this article we review and discuss the available data supporting the role of Smad7 in the modulation of cancer growth and progression.

Would Surgeons Like to Be Submitted to Anal Fistulotomy? An International Web-Based Survey.

Traditional fistulotomy is the most performed surgical procedure in anal fistula surgery. We conducted an international online survey to explore colorectal surgeons' opinions and preferences on fistulotomy. Considering the healing and continence impairment rates reported in the literature, surgeons were invited to answer as a hypothetic patient susceptible to being submitted to fistulotomy for low and high anal fistula. A total of 767 surgeons completed the survey from 72 countries. The majority of respondents were consultants, having treated more than 20 anal fistulas in the last year. Most of them declared that anal fistula would be able to negatively affect quality of life and would be worried/anxious about it. Taking into account all aspects, 87.5% and 37.8% of respondents would agree to be treated with a fistulotomy in case of a low and high fistula, respectively, with an acceptance rate that varied worldwide. At multivariate analysis, factors correlated to the acceptance of anal fistulotomy were male gender (p = 0.003), practice of less than 20 fistula operations during last year (p = 0.020), and low fistula (p < 0.001). Surgeons recognized the extreme complexity of this approach. This study highlighted the necessity of an accurate patients' selection and the adoption of alternative strategy to reduce the risk of anal continence impairment.

Cytological, molecular, cytogenetic, and physiological characterization of a novel immortalized human enteric glial cell line.

Enteric glial cells (EGCs), the major components of the enteric nervous system (ENS), are implicated in the maintenance of gut homeostasis, thereby leading to severe pathological conditions when impaired. However, due to technical difficulties associated with EGCs isolation and cell culture maintenance that results in a lack of valuable in vitro models, their roles in physiological and pathological contexts have been poorly investigated so far. To this aim, we developed for the first time, a human immortalized EGC line (referred as ClK clone) through a validated lentiviral transgene protocol. As a result, ClK phenotypic glial features were confirmed by morphological and molecular evaluations, also providing the consensus karyotype and finely mapping the chromosomal rearrangements as well as HLA-related genotypes. Lastly, we investigated the ATP- and acetylcholine, serotonin and glutamate neurotransmitters mediated intracellular Ca2+ signaling activation and the response of EGCs markers (GFAP, SOX10, S100ß, PLP1, and CCL2) upon inflammatory stimuli, further confirming the glial nature of the analyzed cells. Overall, this contribution provided a novel potential in vitro tool to finely characterize the EGCs behavior under physiological and pathological conditions in humans.

Tunneling of Mesh during Ventral Rectopexy: Technical Aspects and Long-Term Functional Results.

Avoiding the extensive damage of pelvic structures during ventral rectopexy could minimize secondary disfunctions. The objective of our observational study is to assess the safety and functional efficacy of a modified ventral rectopexy. In the modified ventral rectopexy, a retroperitoneal tunnel was created along the right side of rectum, connecting two peritoneal mini-incisions at the Douglas pouch and sacral promontory. The proximal edge of a polypropylene mesh, sutured over the ventral rectum, was pulled up through the retroperitoneal tunnel and fixed to the sacral promontory. In all patients, radiopaque clips were placed on the mesh, making it radiographically "visible". Before surgery and at follow up visits, Altomare, Longo, CCSS, PAC-SYM, and CCFI scores were collected. From March 2010 to September 2021, 117 patients underwent VR. Modified ventral rectopexy was performed in 65 patients, while the standard ventral rectopexy was performed in 52 patients. The open approach was used in 97 cases (55 and 42 patients in modified and standard VR, respectively), while MI surgery was used in 20 cases (10 and 10 patients in modified and standard VR, respectively). A slightly shorter operative time and hospital stay were observed following modified ventral rectopexy (though this was not statistically significant). Similar overall complication rates were registered in the modified vs. standard ventral rectopexies (4.6% vs. 5.8%, p = 0.779). At follow-up, the Longo score (14.0 ± 8.6 vs. 11.0 ± 8.2, p = 0.042) and "delta" values of Altomare (9.2 ± 6.1 vs. 5.9 ± 6.3, p = 0.008) and CCSS (8.4 ± 6.3 vs. 6.1 ± 6.1, p = 0.037) scores were significantly improved in the modified ventral rectopexy group. A similar occurrence of symptoms recurrence was diagnosed in the two groups. Radiopaque clips helped to accurately diagnose mesh detachment/dislocation. The proposed modified VR seems to be feasible and safe. Marking the mesh intraoperatively seems useful.