Long-term results following sacral nerve stimulation for chronic constipation.

AIM: The long-term outcome of sacral nerve stimulation (SNS) for chronic functional constipation was assessed. METHOD: Patients who received a definitive SNS implant for chronic functional constipation only (according to the Rome III criteria) and were followed up for at least 3 years were included in this study. Slow transit constipation (STC) was distinguished from obstructed defaecation (OD) and mixed/undetermined constipation (MU). Constipation features, Cleveland Clinic Constipation score (CCCS) and SF-36 questionnaire data were collected; physiological tests were performed. RESULTS: Forty-two out of 61 patients suitable for SNS received a definitive implant (14 for STC, 15 for OD, 13 for MU). Following SNS device implantation (mean follow-up 51 ± 15 months), the baseline CCCS (17 ± 6) dropped to 9 ± 6 (P < 0.001) and 47% of patients had an improvement in the CCCS of more than 50%. Such improvement was more significant in patients with OD. Anal pressures did not change, while threshold and urgency rectal sensation significantly decreased, in particular in patients with OD. All aspects of patients' health status (SF-36) improved significantly following SNS; this was more marked in patients with OD. CONCLUSION: Data from this study suggest that the clinical efficacy of SNS can be prolonged in constipated patients, but in both the preliminary diagnostic assessment and pathophysiological interpretation every effort should be made to select patients for SNS. Although SNS showed efficacy in a low percentage of patients with STC, patients with OD were more responsive.

Sacral neuromodulation for bowel dysfunction: a consensus statement from the Italian group.

BACKGROUND: Representatives from the Italian centers experienced in sacral neuromodulation (SNM) for the treatment of bowel dysfunction met in order to define the current clinical practice in Italy and to produce a consensus statement regarding indications for this therapy and patient management. METHODS: Fifty Italian colonproctologists were asked to complete a questionnaire concerning their clinical practice in SNM (290 questions, grouped within 4 broad areas). Physicians expressed their opinion by completing the questionnaire, assigning to each statement their level of agreement according to the 5-point Likert scale; the data were analyzed by attributing to each expert's answers a weight proportional to the degree of experience. During a meeting held 2 months later, the critical aspects of the therapy were re-examined and discussions held with the goal of reaching an agreement on controversial topics. The available literature was reviewed. RESULTS: Patient selection criteria, etiology, diagnostic investigations, test procedures and implantation, follow-up and evaluation of results have been reviewed. The aim was to achieve an algorithm for patient management, showing the place of SNM in the treatment of bowel dysfunction. The approach in case of treatment failure was also discussed. CONCLUSIONS: Analysis of the data collected reveals substantial consensus at the national level concerning all the main points with regard to the therapy. The recommendations expressed in this article can be considered as national guidelines and taken into account by the principal international implantation centers.

Transperineal repair with bulbocavernosus muscle interposition for recto-urethral fistula.

AIM: The results of repair of recto-urethral fistulae (RUF) are presented using a bulbocavernosus muscle graft. METHOD: Prospectively collected data were reviewed on 11 patients with RUF operated on between 2003 and 2011. Of these, six were treated by a bulbocavernosus flap. Two RUF had occurred after prostatectomy, three after prostatectomy and radiotherapy and one after perineal trauma; all had a urinary diversion. RESULTS: Closure of the fistula was achieved in all patients and was maintained for the duration of the period of follow up (mean ± SD = 43.5 ± 24.7 months; range, 8-80 months) There were no complications. CONCLUSION: This new technique for the repair of RUF is safe and effective, especially in patients with complex postradiation RUF.

Internal Delorme's procedure for rectal outlet obstruction.

AIM: The outcome of the internal Delorme's procedure (IDP) for obstructed defaecation was assessed. METHOD: From October 2001 to March 2009, 167 patients with obstructed defaecation associated with rectal intussusception were operated on. Patients were selected on the basis of validated constipation and continence scores, clinical examination and defaecography. Seventy-six patients were treated by the IDP alone and 91 patients were treated by the IDP with a levatorplasty. Before surgery and after a mean ± SD follow up of 3.0 ± 1.5 years, patients were assessed using the Cleveland Clinic Incontinence and Constipation Score (CCIS and CCCS), the Obstructed Defecation Score (ODS), faecal urgency and the Patient Assessment of Constipation Quality of Life (PAC-QoL) questionnaire. RESULTS: Seventeen (10.2%) patients developed a postoperative complication including fissure-in-ano (4.2%), proctalgia (3.0%), suture-line dehiscence with stenosis (1.8%) and Clostridium difficile colitis (1.2%). Faecal urgency changed from 22% to 17.6% (P = 0.754). Tenesmus fell from 53.9% to 17.1% (P < 0.001). The CCCS and the ODS fell by 50% or more in 82.6% and 73.7% of the patients, respectively. The CCIS did not worsen significantly in patients who remained incontinent, and 45.7% of the previously incontinent patients regained normal continence. The CCCS decreased from 11 to 3 (P < 0.001) in the patients treated by the IDP and from 12 to 3 (P < 0.001) in the patients treated by the IDP with levatorplasty. The overall recurrence rate was 5.4%. The PAC-QoL showed a reduction of anxiety/depression and of physical and psychological discomfort (P < 0.001). CONCLUSION: The IDP is an effective and safe option for rectal outlet obstruction caused by rectal intussusception with excellent function and patient satisfaction.

Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry.

Exposure to microgravity (µG) during space flights produces a state of immunosuppression, leading to increased viral shedding, which could interfere with long term missions. However, the cellular mechanisms that underlie the immunosuppressive effects of µG are ill-defined. A deep understanding of human immune adaptations to µG is a necessary first step to design data-driven interventions aimed at preserving astronauts' immune defense during short- and long-term spaceflights. We employed a high-dimensional mass cytometry approach to characterize over 250 cell-specific functional responses in 18 innate and adaptive immune cell subsets exposed to 1G or simulated (s)µG using the Rotating Wall Vessel. A statistically stringent elastic net method produced a multivariate model that accurately stratified immune responses observed in 1G and sµG (p value 2E-4, cross-validation). Aspects of our analysis resonated with prior knowledge of human immune adaptations to µG, including the dampening of Natural Killer, CD4+ and CD8+ T cell responses. Remarkably, we found that sµG enhanced STAT5 signaling responses of immunosuppressive Tregs. Our results suggest µG exerts a dual effect on the human immune system, simultaneously dampening cytotoxic responses while enhancing Treg function. Our study provides a single-cell readout of sµG-induced immune dysfunctions and an analytical framework for future studies of human immune adaptations to human long-term spaceflights.

Right colectomy: consecutive 100 patients treated with laparoscopic and robotic technique for malignancy. Cumulative experience in a single centre.

Robotic-assisted resections prove beneficial in overcoming potential limitation of laparoscopy, but clear evidences on patient's benefits are still lacking. We report our experience on 100 consecutive patients who underwent right colectomy with either robotic or laparoscopic approaches. Data were prospectively collected on a dedicated database (ASA score, age, operative time, conversion rate, re-operation rate, early complications, length of stay, and pathological results). Median total operative time was 160 min in LS group (IQR = 140-180) and 204 min for RS group (IQR = 180-230). Median time to first flatus was 2.5 days for LS group (IQR = 2 - 3) and 2 days for RS group (IQR = 1-2). Length of stay (median) was 8 days in LS group (IQR = 6-10) and 5 days in RS group (IQR = 5-7). No statistically significant difference was found between the 2 groups when the number of harvested nodes, the anastomotic leakage and the postoperative bleeding were analyzed. The 30-day mortality was 0% in LS and RS groups. Conversion rate for LS group was 14% (7/50 pts) and for RS group was 0% (0/50). Minimally invasive surgery is a feasible and safe technique. The RS may overcome some technical limitations of laparoscopic surgery and it achieves the same oncological results compared to LS but with higher costs. The lower conversion rate allows to expect better clinical outcomes and lower complication rate.

Systemic Immunologic Consequences of Chronic Periodontitis.

Chronic periodontitis (ChP) is a prevalent inflammatory disease affecting 46% of the US population. ChP produces a profound local inflammatory response to dysbiotic oral microbiota that leads to destruction of alveolar bone and tooth loss. ChP is also associated with systemic illnesses, including cardiovascular diseases, malignancies, and adverse pregnancy outcomes. However, the mechanisms underlying these adverse health outcomes are poorly understood. In this prospective cohort study, we used a highly multiplex mass cytometry immunoassay to perform an in-depth analysis of the systemic consequences of ChP in patients before (n = 28) and after (n = 16) periodontal treatment. A high-dimensional analysis of intracellular signaling networks revealed immune system-wide dysfunctions differentiating patients with ChP from healthy controls. Notably, we observed exaggerated proinflammatory responses to Porphyromonas gingivalis-derived lipopolysaccharide in circulating neutrophils and monocytes from patients with ChP. Simultaneously, natural killer cell responses to inflammatory cytokines were attenuated. Importantly, the immune alterations associated with ChP were no longer detectable 3 wk after periodontal treatment. Our findings demarcate systemic and cell-specific immune dysfunctions in patients with ChP, which can be temporarily reversed by the local treatment of ChP. Future studies in larger cohorts are needed to test the boundaries of generalizability of our results.

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study.

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

[Peritonitis in elderly patients. Diagnostic and therapeutic considerations]. / La peritonite nel paziente anziano. Considerazioni diagnostiche e terapeutiche.

Abdominal surgical emergencies in the aged patients are considered on the basis of personal experience. Peritonitis from acute infections, is for many reasons, a higher challenge in the elderly.

[Evaluation of the prognostic value of certain biological indices in acute pancreatitis]. / Valutazione del valore predittivo di alcuni indici biologici nella pancreatite acuta.

After a review of the aetiological, clinical and diagnostic aspects of acute pancreatitis, personal experience is reported of the prognostic indications supplied by the analysis of certain simple haematic parameters. The reliability of the results is confirmed. This technique will be used in a personal diagnostic and therapeutic protocol as a means of early identification of patients at the greatest risk.