Description and management of patients with anal fissure: insights on Italian primary care setting coming from real-world data.

To describe patients with anal fissure (AF) and their management in primary care. Retrospective study using the Italian Longitudinal Patient Database on 18 + years old subjects with AF records during 'July 2016-June 2021' (selection period). Index Date (ID) was the first AF record during selection period. Sub-cohorts were defined by presence/absence of prescriptions on ID of the combination of topical nifedipine 0.3% and lidocaine 1.5% (NIF/LID). Patients' information on the 12-month period before (baseline) and after (follow-up) ID was analyzed. Subjects with AF were 8632: 14.0% had NIF/LID on ID. Mean age was 52 (± 17.2) years, there were more women in ' < 50 years' group, and more men in '50-70' one. Prevalences of pregnancy and immunodepression were around 5%; most common comorbidities were hypertension (29.6%) and heart disease (13.1%), while constipation and diarrhea were < 5%. Healthcare resources utilization (HRUs) increased during follow-up, but still few patients were prescribed NIF/LID (2.8%), other treatments for AF (10.3%), or proctological visits (7.7%). NIF/LID patients were younger (< 40 years people: 30.7% versus 23.9%; p value < 0.0001), and more likely to have constipation (4.3% versus 2.5%; p value < 0.001); patients without NIF/LID showed slightly higher prevalences of hypertension (30.0% versus 27.1%; p value: 0.039) and depression (4.0% versus**2.5%; p value: 0.009), and a little higher overall HRUs. Results show that general practitioners are used to manage AF. However, there is still a gap between guidelines' recommendations and actual management. Educational campaigns on common anal problems in primary care might help further improving AF management and optimizing HRUs.

Sacral Neuromodulation for defecation disorders after non oncologic pelvic surgery.

PURPOSE: Defecation disorders (DD) can sometimes affect the outcomes of pelvic or colorectal surgery. The aim of the present study is to evaluate the role of sacral neuromodulation for the treatment of constipation and other evacuation disorders after surgery. METHODS: A retrospective analysis in all the consecutive patients that underwent sacral nerve modulation (SNM) for DD arisen or worsened after pelvic or colorectal surgery was performed from January 2010 to December 2020. DD were defined starting from Rome IV Criteria, and according to manometric results, all patients were further divided into the two subgroups: inadequate defecatory propulsion and dyssynergic defecation. Cleveland Clinic Constipations Score (CCCS) and SF-36 have been evaluated in the time. RESULTS: Thirty-seven patients have been included in the study. Twenty-seven out of thirty-seven (73.3%) patients had experienced sufficient benefits to implant the definitive device, and 22 patients (59.4% of tested and 81.5% of permanently implanted) still had the device functioning after a mean follow-up of 6.3 years. The most represented manometric pattern was inadequate propulsive function (59% of patients). CCCS at preoperative assessment for all patients was 17.5 with a reduction to 10.4 at the first year of follow-up (p < 0.001). CONCLUSION: SNM appears to be a feasible, safe, and well-tolerated procedure with durable benefit in the long-term treatment of defecatory dysfunction after pelvic or colorectal surgery for benign diseases.

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Sclerotherapy with 3% polidocanol foam to treat second-degree haemorrhoidal disease: Three-year follow-up of a multicentre, single arm, IDEAL phase 2b trial.

BACKGROUND: Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD. METHODS: This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score. RESULTS: The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months. CONCLUSIONS: Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate.

Anoplasty for anatomical anal stenosis: systematic review of complications and recurrences.

AIM: The optimal surgical treatment for anatomical anal stenosis (AS) remains to be determined. The aim of this study was to determine the rates of complications and recurrence after anoplasty for anatomical AS and, wherever feasible, compare the outcomes for the various techniques. METHOD: A PROSPERO-registered systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medline, PubMed, Embase, Cochrane Library of Systematic Review, Scopus and Web of Science were searched for articles published up to May 2021. Studies that assessed the outcomes of anoplasty in adult patients with anatomical AS were selected. The primary outcomes were complications and recurrence. The methodological quality of studies was appraised using the Joanna Briggs Institute critical appraisal tools. RESULTS: From the total of 2705 unique screened records, 151 were assessed for eligibility. Only 29 studies (two prospective) met the inclusion criteria, reporting data on 556 patients [mean age 53 (18-83) years, 46% female]. Previous history of surgery for haemorrhoidal disease accounted for three quarters of cases. A total of 14 types of anoplasty were found, with the Y-V flap being the most performed technique [27% of cases (n = 149)]. Complications frequently occurred, with a pooled prevalence of 10.2% (95% CI 3.9%-24.1%) after Y-V flap and 11.5% (5.3%-23.0%) after rhomboid/diamond flap. Patients undergoing house flap achieved better results in terms of clinical improvement, satisfaction and quality of life compared with Y-V flap and rhomboid/diamond flap. When considering only studies with at least 12 months of follow-up, the pooled prevalence of recurrence was 4.7% (2.2%-9.8%), with significantly higher rates observed in the prospective versus retrospective series [pooled prevalence 18.9% (11.5%-29.5%) vs. 3.6% (1.7-7.8%), respectively; p < 0.001]. CONCLUSION: Both complications and recurrence were significantly lower after house flap compared with rhomboid/diamond and Y-V flap. Better designed multicentre studies with longer follow-up are needed to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42021239493.

Preliminary Results of the First 50 Patients Undergoing Sclerotherapy for II-Degree Hemorrhoidal Disease Using an Automated Device.

Background: Sclerotherapy is defined as the injection of sclerosant agents causing fibrosis and scarring of the surrounding tissue. It is currently employed for the treatment of I-III degree hemorrhoidal disease (HD). The aim of this study is to investigate the use of a new automated device for the injection of 3% polidocanol foam. Methods: This is an observational study including 50 patients who underwent a sclerotherapy procedure with 3% polidocanol foam for II-degree HD according to Goligher classification. Patients were evaluated through validated scores [Giamundo score, Hemorrhoidal Disease Symptom Score (HDSS), Short Health Scale (SHS-HD) and Vaizey score]. Follow-up was conducted until 3 months from the procedure. Results: Complete resolution of bleeding was achieved in 72% and 78% of patients, respectively, at 1 week and after 3 months from the procedure. Forty eight percent of patients were symptom free after the last follow-up visit (HDSS = 0). No major surgical complications were reported. Three patients out of 36 successfully treated, recurred, and needed a second sclerotherapy injection, which was successful in 2 of them. Conclusion: These preliminary results of 3% polidocanol foam injection on 50 patients suggest the efficacy and reproducibility of the technique with this new device in the short-term follow-up.

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.

Anatomo-functional outcomes of the laparoscopic Frykman-Goldberg procedure for rectal prolapse in a tertiary referral centre.

Rectal prolapse is a common disorder that represents a burden for patients due to the associated symptoms that may include both incontinence and constipation. Currently, a huge variation in techniques exist. The aim of this study was to evaluate the anatomo-functional results of the laparoscopic Frykman-Goldberg procedure (LFGP) for the treatment of both internal (IRP) and complete rectal prolapse (CRP). Between July 2004 and October 2019, 45 patients with IRP and CRP underwent a LFGP. The Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Syndrome Score (ODSS) and Vaizey Score (VS) were assessed preoperatively, 3 months before the procedure, 12 months after the procedures and at the final follow-up visit. The patients' mean age was 51.4 ± 17.9 (15-93) years, and the mean follow-up was 9.24 ± 4.57 (1.6-16.3) years. The VS, CCCS and ODSS significantly improved (p = 0.008; p < 0.001; p < 0.001) from median preoperative values of 3, 20 and 18 to 2, 6 and 5, respectively. Furthermore, the improvements in scores during follow-up remained constant and significant over time when considering the two groups separately (time effect for ODSS p < 0.001, for VS p = 0.026, for CCCS p < 0.001) and when the patients were divided by age (< 40, 41-60 and > 60; p < 0.001). The overall complication rate was 8.9% (4/45), and no intraoperative complications or anastomotic leakage occurred. Conversion to the open approach was not necessary in any case. The overall success rate was 97.7%, and only one recurrence in the IRP group occurred after 14 months. LRGP can be considered a safe, effective and long-lasting procedure in young patients with IRP or CRP, a history of ODS and a redundant sigmoid colon.

Excisional Haemorrhoidectomy: Where Are We?

Haemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most frequent and ancient anorectal conditions. Bleeding, during or after defecation, is the most common symptom. The color of the blood is typically bright red covering the outer surface of the stools. The severity of HD is based on the degree of the prolapse. There are several excisional surgery treatments. In this review, we describe the most common techniques such as Milligan and Morgan, Parks, Ferguson and Whitehead technique. Despite significant improvements in conservative treatments, excisional haemorrhoidectomy techniques are the most effective treatment for III- and IV degree.

Short-Term Results of Sclerotherapy with 3% Polidocanol Foam for Symptomatic Second- and Third-Degree Hemorrhoidal Disease.

BACKGROUND: Hemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most common proctological diseases. Sclerotherapy (ST) with 3% polidocanol foam induces an inflammatory reaction with sclerosis of the submucosal tissue and consequent suspension of the hemorrhoidal tissue. The aim of this study was to evaluate the short-term effectiveness and safety of ST with 3% polidocanol foam for the treatment of symptomatic second- and third-degree HD. METHODS: A total of 66 patients with symptomatic second- and third-degree HD underwent a single ST session between March 2017 and July 2018. A visual analog scale score was used to assess post-operative pain and patient satisfaction. The symptoms severity and anal continence were investigated through the Hemorrhoid Severity Score (HSS) and Vaizey score, respectively, at baseline, at 4 weeks and after 1 year. RESULTS: Fifty-seven out of 66 patients were male (86.3%), and the mean age was 52 (29-75; SD ± 12) years. The mean operative time was 4.5 (2-6; SD ± 1.23) minutes. No intraoperative complications and no drug-related side effects occurred. The overall success rate was 78.8% (52/66 patients) after a single ST session and 86% after two ST sessions (57/66 patients). The mean treatment effect, obtained comparing preoperative and 12 months symptom scores in each patient, showed a median change of 8 (p < 0.001). All patients resumed their normal daily activities the day after the procedures. CONCLUSIONS: ST with 3% polidocanol foam is a safe, cost-effective and repeatable conservative treatment.

Conservative Treatment of Hemorrhoidal Disease.

BACKGROUND: Hemorrhoids are vascular cushions underlying the distal rectal mucosa and contributing to approximately 15-20% of the resting anal pressure with a complete closure of the anal canal. They can become pathological (hemorrhoidal disease, HD) being the most common cause of painless rectal bleeding during defecation with or without prolapsing anal tissue. The treatment of HD must be tailored to both the severity of disease and patient's expectation. METHODS: A narrative review of all the most relevant papers present on the three major databases (PUBMED, EMBASE and WEB OF SCIENCE) regarding conservative treatment was conducted. RESULTS: Conservative treatment is effective in managing the majority of patients complaining of early stages of the disease. Dietary and lifestyle modifications are the first therapeutic step necessary to achieve a regular defecation with soft stool whereas oral phlebotonic drugs can help to control symptoms. The use of topical medications, particularly during the acute phase or in the post-operative period can also be beneficial for all patients complaining of HD. CONCLUSION: Despite a large number of available products in the market and the high incidence of HD, very few randomized controlled trials have been carried out and most of the studies are uncontrolled case series. Larger and better designed studies are necessary to establish the real benefit of all types of drugs for the treatment of early stages of HD.

Short-Term Outcomes of Polycarbophil and Propionibacterium acnes Lysate Gel after Open Hemorrhoidectomy: A Prospective Cohort Study.

BACKGROUND: Pain is the most common complication after open excisional hemorrhoidectomy (OEH). We assessed the effectiveness of polycarbophil and Propionibacterium acnes lysate gel (Emorsan®Gel) on pain control after OEH. RESEARCH DESIGN AND METHODS: Fifty consecutive patients undergoing OEH were included. All patients received stool softeners and oral analgesia in the post-operative period. Emorsan®Gel was also used topically by the last 25 patients (Emorsan®Gel group (EG)) until Post-Operative Day 20 (POD 20). The primary outcome was the effectiveness of Emorsan®Gel on pain relief using an 11-point visual analogue scale (VAS). Morbidity, wound healing (WH), and time to work were documented at POD 1, POD 10, POD 20, and POD 40. RESULTS: Of the 50 patients enrolled, twenty-eight (56%) were males; median age, 49 (range, 28-73) years. The VAS score decreased over time in all patients, with significantly lower scores at POD 20 in the EG (1.44 (SD, 1.16) vs. 2.12 (0.93) in the control group (CG); p = 0.045). All patients in the EG achieved complete WH at last follow-up, compared to only 17 (68%) in the CG (p = 0.004). The likelihood of WH was 66% higher in the EG (OR, 1.66 [95%CI, 0.80-3.44; p = 0.172). CONCLUSIONS: Emorsan®Gel is safe and effective at reducing pain after EOH, promoting earlier WH compared to standard care treatment.

Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine.

Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called "ideal biomarkers", for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.