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.

The 8q24 region hosts miRNAs altered in biospecimens of colorectal and bladder cancer patients.

BACKGROUND: The 8q24 locus is enriched in cancer-associated polymorphisms and, despite containing relatively few protein-coding genes, it hosts the MYC oncogene and other genetic elements connected to tumorigenesis, including microRNAs (miRNAs). Research on miRNAs may provide insights into the transcriptomic regulation of this multiple cancer-associated region. MATERIAL AND METHODS: We profiled all miRNAs located in the 8q24 region in 120 colorectal cancer (CRC) patients and 80 controls. miRNA profiling was performed on cancer/non-malignant adjacent mucosa, stool, and plasma extracellular vesicles (EVs), and the results validated with The Cancer Genome Atlas (TCGA) data. To verify if the 8q24-annotated miRNAs altered in CRC were dysregulated in other cancers and biofluids, we evaluated their levels in bladder cancer (BC) cases from the TCGA dataset and in urine and plasma EVs from a set of BC cases and healthy controls. RESULTS: Among the detected mature miRNAs in the region, 12 were altered between CRC and adjacent mucosa (adj. p < 0.05). Five and four miRNAs were confirmed as dysregulated in the CRC and BC TCGA dataset, respectively. A co-expression analysis of tumor/adjacent tissue data from the CRC group revealed a correlation between the dysregulated miRNAs and CRC-related genes (PVT1 and MYC) annotated in 8q24 region. miR-30d-5p and miR-151a-3p, altered in CRC tissue, were also dysregulated in stool of CRC patients and urine of BC cases, respectively. Functional enrichment of dysregulated miRNA target genes highlighted terms related to TP53-mediated cell cycle control. CONCLUSIONS: Altered expression of 8q24-annotated miRNAs may be relevant for the initiation and/or progression of cancer.

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.

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.

Altered Fecal Small RNA Profiles in Colorectal Cancer Reflect Gut Microbiome Composition in Stool Samples.

Dysbiotic configurations of the human gut microbiota have been linked to colorectal cancer (CRC). Human small noncoding RNAs are also implicated in CRC, and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis, but their role has been less extensively explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens from patients with CRC or with adenomas and from healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We observed considerable overlap and a correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. We identified a combined predictive signature composed of 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC samples separately from healthy and adenoma samples (area under the curve [AUC] = 0.87). In the present study, we report evidence that host-microbiome dysbiosis in CRC can also be observed by examination of altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more-accurate tools for diagnostic purposes.IMPORTANCE The characteristics of microbial small RNA transcription are largely unknown, while it is of primary importance for a better identification of molecules with functional activities in the gut niche under both healthy and disease conditions. By performing combined analyses of metagenomic and small RNA sequencing (sRNA-Seq) data, we characterized both the human and microbial small RNA contents of stool samples from healthy individuals and from patients with colorectal carcinoma or adenoma. With the integrative analyses of metagenomic and sRNA-Seq data, we identified a human and microbial small RNA signature which can be used to improve diagnosis of the disease. Our analysis of human and gut microbiome small RNA expression is relevant to generation of the first hypotheses about the potential molecular interactions occurring in the gut of CRC patients, and it can be the basis for further mechanistic studies and clinical tests.

Altemeier's procedure for complete rectal prolapse; outcome and function in 43 consecutive female patients.

BACKGROUND: The aim of this retrospective study was to evaluate morbidity, mortality, postoperative function and recurrences in patients treated by Altemeier's rectosigmoidectomy for complete rectal prolapse in a referral center for pelvic floor functional disorders. METHODS: Peri-operative data on 43 consecutive female patients were reviewed. At follow-up any change in pelvic floor function and recurrences were determined. Thirty four patients were assessed at a median interval of 49 (2-135) months, six being deceased for reason not related to the prolapse and three lost to follow-up. RESULTS: Post-operative complications at 30 days occurred in 18 patients (38%). Major complication occurred in only one patient that was pneumonia with lung failure. Major complications were not related to the ASA score, BMI or age [average age 76.4]. There was no post-operative mortality at 30 days. At long-term follow-up functional results demonstrate a statistically significant decrease in the Obstructive Defecation Syndrome (ODS) score, but no statistically significant changes in the Vaizey score, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) score and the urinary retention score. ODS score decreased with respect to levatorplasty and the change was statistically significant instead of Vaizey score in which were not. At the same follow-up there were 12 (35%) cases of recurrence with an estimated risk at 48 months of 40%. There were no statistically significant differences between patients with and without recurrence regarding age (p = 0.188), BMI (p = 0.864), ASA score (p = 0.433), previously repaired prolapse (p = 0.398), previous hysterectomy (p = 0.705), length of resected bowel (p = 0.126), and levatorplasty (p = 0.304). Patient satisfaction showed a mean of 8.8 and 6.4 respectively in patients without and with recurrences (p = 0.012). CONCLUSIONS: Altemeier's procedure had in our series low complications rate and no mortality. It offered improved evacuation in constipated patients while didn't improve fecal and urinary continence. Recurrence of prolapse was 40% at four years.

Efficacy of Mesoglycan in Pain Control after Excisional Hemorrhoidectomy: A Pilot Comparative Prospective Multicenter Study.

INTRODUCTION: Various pain management strategies for patients undergoing open excisional hemorrhoidectomy have been proposed, yet postoperative pain remains a frequent complaint. OBJECTIVE: To determine whether mesoglycan (30 mg two vials i.m. once/day for the first 5 days postoperative, followed by 50 mg 1 oral tablet twice/day for 30 days) would reduce the edema of the mucocutaneous bridges and thus improve postoperative pain symptoms. PATIENTS AND METHODS: For this prospective observational multicenter study, 101 patients undergoing excisional diathermy hemorrhoidectomy for III-IV degree hemorrhoidal disease were enrolled at 5 colorectal referral centers. Patients were assigned to receive either mesoglycan (study group SG) or a recommended oral dose of ketorolac tromethamine of 10 mg every 4-6 hours, not exceeding 40 mg per day and not exceeding 5 postoperative days according to the indications for short-term management of moderate/severe acute postoperative pain, plus stool softeners (control group CG). RESULTS: Postoperative thrombosis (SG 1/48 versus CG 5/45) (p < 0.001) and pain after rectal examination (p < 0.001) were significantly reduced at 7-10 days after surgery in the mesoglycan-treated group, permitting a faster return to work (p < 0.001); however, in the same group, the incidence of postoperative bleeding, considered relevant when needing a readmission or an unexpected outpatient visit, was higher, possibly owing to the drug's antithrombotic properties. CONCLUSIONS: The administration of mesoglycan after an open diathermy excisional hemorrhoidectomy can reduce postoperative thrombosis and pain at 7-10 days after surgery, permitting a faster return to normal activities.

Martius' flap for recurrent perineal and rectovaginal fistulae in a patient with Crohn's disease, endometriosis and a mullerian anomaly.

BACKGROUND: Rectovaginal fistulas represent 5% of all anorectal fistulae and are a disastrous manifestation of Crohn's disease that negatively affects patients' social and sexual quality of life. Treatment remains challenging for colorectal surgeons, and the recurrence rate remains high despite the numerous available options. CASE PRESENTATION: We describe a 31-year-old female patient with a Crohn's disease-related recurrent perineo-vaginal and recto-vaginal fistulae and a concomitant mullerian anomaly. She complained of severe dyspareunia associated with penetration difficulties. The patient's medical history was also significant for a previous abdominal laparoscopic surgery for endometriosis for the removal of macroscopic nodules and a septate uterus with cervical duplication and a longitudinal vaginal septum. The patient was successfully treated using a Martius' flap. The postoperative outcome was uneventful, and no recurrence of the fistula occurred at the last follow-up, eight months from the closure of the ileostomy. CONCLUSION: Martius' flap was first described in 1928, and it is considered a good option in cases of rectovaginal fistulas in patients with Crohn's disease. The patient should be referred to a colorectal centre with expertise in this disease to increase the surgical success rate.