Obstructed defecation syndrome associated with paradoxical puborectalis contraction: osteopathic treatment versus anal biofeedback. Results of a pilot study.

BACKGROUND: Biofeedback is the most widespread rehabilitative therapy for the treatment of anismus after failed conservative treatment. Osteopathy represents an alternative therapy for constipation. The aim of this study was to evaluate short- and long-term results of osteopathic treatment as compared to biofeedback in patients with dyssynergic defecation. METHODS: This was a prospective cohort pilot study on 30 patients with dyssynergic defecation enrolled at the Colorectal Clinic of the University Hospital of Ferrara, Italy, from May 2015 to May 2016 and followed until May 2020. Dyssynergic defecation was defined as the inappropriate contraction of the pelvic floor or less than 20% relaxation of basal resting sphincter pressure (on anal manometry) with adequate propulsive forces during attempted defecation. Dyssynergic patients were divide into 2 treatment groups: 15 patients had osteopathy and 15 patients had biofeedback. Before and 3 months after rehabilitation treatment, all patients had anorectal manometry, defecography, and ultrasound, and were evaluated with the Cleveland Clinic Florida (CCF) constipation score, obstructed defecation syndrome (ODS) score, Colo-rectal-anal Distress Inventory (CRADI-8), Colo-rectal-anal Impact Questionnaire (CRAIQ-7), and the Brusciano Score (BS). To evaluate the efficacy of osteopathy and biofeedback in the long-term, all patients completed the above-mentioned questionnaires 5 years later via a telephone interview. RESULTS: The two treatments were similarly effective in the short term with reduction in questionnaires scores, and increase in the percentage of anal sphincter release at straining at anorectal manometry in both groups. The ODS score was significantly reduced in biofeedback group (p = 0.021). The 3-month post-treatment BS was lower in the osteopathy group, but this just failed to reach statistical significance (p = 0.050). Periodic rehabilitation reinforcements were provided. The CCF constipation score decreased significantly in the osteopathy group (p = 0.023) after 5 years. CONCLUSIONS: Osteopathy is a promising treatment for dyssynergic defecation, and it can be associated with biofeedback.

Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): ulcerative colitis.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position Statement of Italian colorectal surgeons to address the surgical aspects of ulcerative colitis management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of ulcerative colitis. The committee was able to identify some points of major disagreement and suggested strategies to improve the quality of available data and acceptance of guidelines.

Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): Crohn's disease.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a position statement of Italian colorectal surgeons to address the surgical aspects of Crohn's disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of Crohn's disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Correction to: Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): ulcerative colitis.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication.

Correction to: Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication. The complete correct affiliation should read as follows.

Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position Statement of Italian colorectal surgeons to address the surgical aspects of inflammatory bowel disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the general principles of surgical treatment of inflammatory bowel disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Correction to: Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): Crohn's disease.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication.

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

IOIBD technical review on endoscopic indices for Crohn's disease clinical trials.

BACKGROUND: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. METHODS: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. RESULTS: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease.

The altered expression of micro-RNA (miRNA) has been associated with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to establish specific miRNA expression patterns in the serum and mucosa of inflammatory bowel disease (IBD) patients (UC and CD with colonic involvement) at different stages of the disease. Serum and biopsies from nine active CD (aCD), nine inactive CD (iCD), nine active UC (aUC) and nine inactive UC (iUC) and serum from 33 healthy subjects were collected. Up to 700 miRNAs were evaluated by the TaqMan human miRNA array. The ΔCt values were obtained using the mean expression values of all expressed miRNAs in a given sample as a normalization factor for miRNA real-time quantitative polymerase chain reaction data. The levels of serum miRNAs in CD and UC patients were different to healthy subjects. Thirteen serum miRNAs were expressed commonly in CD and UC patients. Two miRNAs were higher and four miRNAs were lower in the serum of aCD than iCD. No serum miRNA was regulated exclusively in aUC compared with iUC patients. Four miRNAs were higher and three miRNAs were lower in the mucosa of aCD than iCD. Two miRNAs were higher and three miRNAs were lower in the mucosa of aUC than iUC. No serum miRNAs coincided with tissue miRNAs in aCD and aUC patients. Our results suggest the existence of specific miRNA expression patterns associated with IBD and their different stages and support the utility of miRNA as possible biomarkers. This pilot study needs to be validated in a large prospective cohort.

Folate in gastrointestinal health and disease.

OBJECTIVE: Folate has heterogeneous functions and is involved in several activities in both animal and human body. It is an important constituent of our organism, and its bioavailability is mainly dependent from the correct function of our gastrointestinal tract. Our aim is to describe what happens to folate homeostasis in gastrointestinal health and disease, analyzing the alterations of folate metabolism in some specific conditions of intestinal and liver impairment. DISCUSSION: Folate absorption and metabolization involve the small intestine and the liver; in conditions of gastrointestinal tract disease (i.e. celiac disease, liver disease) folate function may be compromised with important consequences on the whole organism. Moreover, folate deficiency may produce gastrointestinal alterations too. For this reason, the gastrointestinal tract could be the responsible but also the victim of folate deficiency. CONCLUSIONS: The presence of folate deficiency should always be assessed in patients with a gastrointestinal disease. Further studies are needed to assess the role of folates in gastrointestinal tract diseases and in other gynecologic, neurologic, psychiatric, cardiovascular, ophthalmic and neoplastic diseases. Folates supplementation could be considered, in the future, as an effective complimentary therapy in several pathologic conditions.

Symptom burden, management and treatment goals of people with MS spasticity: Results from SEEN-MSS, a large-scale, self-reported survey.

BACKGROUND: Spasticity occurs frequently in people with multiple sclerosis (PwMS) and may affect non-physical aspects of life. However, there is a paucity of data assessing the full impact of spasticity in PwMS. OBJECTIVE: This survey of PwMS and spasticity (PwMSS) was undertaken to understand the impact of spasticity in physical, functional, emotional, and social domains. METHODS: SEEN-MSS (Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity), an online survey, was developed in collaboration with three US-based MS organizations (conducted February-April 2021). RESULTS: Survey was completed by 1,177 PwMSS, 78% female, mean age 56.8yrs, 16.8yrs from MS diagnosis, 11.5yrs with spasticity. Considering day-to-day goals of treatment, respondents reported that managing symptoms(46%) was nearly as important as slowing disease progression(54%). Most reported spasticity was a constant reminder of their MS. Participants reported that spasticity limited daily activities (92%), caused pain (92%), impaired sleep (89%) and negatively impacted emotional well-being (87%). Spasticity fostered a sense of dependence (61%), isolation (40%), decline in self-confidence (75%), self-image (70%), and social connection (62%). CONCLUSIONS: Spasticity has wide-reaching negative impacts on multiple aspects of life, causing substantial burden for PwMSS. Results emphasize the need to fully understand the burden of spasticity and addressing individual needs of PwMSS.

ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology.

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.

Endoscopic flexible treatment of Zenker's diverticulum: a modification of the needle-knife technique.

BACKGROUND AND STUDY AIM: Endoscopic treatment of Zenker's diverticulum has been successfully reported over the last 10 years using different approaches. The hook-knife is a new device originally developed for endoscopic submucosal dissection procedures. This study aimed to investigate the safety and efficacy of endoscopic myotomy performed with the hook-knife. PATIENTS AND METHOD: From July 2005, 32 consecutive patients (23-male, mean age 74.8 years) with dysphagia secondary to the presence of Zenker's diverticulum were prospectively enrolled. Myotomy was performed using a straight-end transparent hood to the tip of the scope and the hook-knife for the incision of the bridge between the Zenker's diverticulum and the esophagus. Clinical outcome was evaluated assigning a dysphagia symptom score from 0 (symptoms absent) to 4 (inability to swallow saliva). RESULTS: General anesthesia was used in 4 patients, deep sedation with propofol in 23 patients, while midazolam was used in 5 patients. The mean procedural time was 28 minutes. Complications occurred in 2 patients (6.25 %). At 1 month follow-up, the mean dysphagia score was significantly improved from 2.9 to 0.6 ( P < 0.001) with 87.5 % of patients free of symptoms and 4 patients with dysphagia that was persistent but milder than before the treatment. Three of these 4 patients underwent a successful second endoscopic treatment with complete relief of dysphagia; one was not re-treated because of advanced age (92 years). During the follow-up period (23.87 +/- 9.6 months), 2 patients developed dysphagia recurrence. The overall success rate was 90.6 %. CONCLUSIONS: Diverticulectomy with a flexible scope and the hook-knife may represent a safe and effective alternative treatment for patients with Zenker's diverticulum.

Inflammatory Bowel Disease Management During the COVID-19 Outbreak: The Ten Do's and Don'ts from the ECCO-COVID Taskforce.

Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease [IBD]. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: [i] in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated [with a particular focus on corticosteroids] always with the purpose of treating active disease and maintaining remission; [ii] non-urgent surgeries and endoscopic procedures should be postponed for all patients; [iii] online consultancy should be implemented; and [iv] hospitalization and surgery should be limited to life-threatening situations.

Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients.

BACKGROUND AND AIMS: The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. METHODS: All UC patients undergoing SC were included. Postoperative complications according to ClavienDindo's classification, long term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. RESULTS: A TOTAL OF: 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], 'diverticulitis' [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median followup of 40 months, 24/69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. CONCLUSIONS: After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.