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.

Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients.

The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially­and still unknown­more aggressive tumoral phenotype in EOCRC.

Negative-pressure wound therapy after stoma reversal in colorectal surgery: a randomized controlled trial.

BACKGROUND: Stoma-reversal surgery is associated with high postoperative morbidity, including wound complications and surgical-site infections (SSIs). This study aims to assess whether the application of negative-pressure wound therapy (NPWT) can improve wound healing compared with conventional wound dressing. METHODS: This was a single-centre, superiority, open-label, parallel, individually randomized controlled trial. Patients undergoing stoma reversal were randomized (1 : 1) to receive NPWT or conventional wound dressing. The primary endpoint of the study was the rate of wound complications and SSIs after stoma closure. The secondary endpoints were postoperative wound pain, rate of wound healing after 30 days from stoma closure, and wound aesthetic satisfaction. RESULTS: Between June 2019 and January 2021, 50 patients were allocated to the NPWT group (all received NPWT, 49 were analysed); 50 patients were allocated to the conventional wound dressing group (48 received the treatment, 45 were analysed). No significant difference was found in wound-complication rate (10 per cent NPWT versus 16 per cent controls; odds ratio 0.61 (95 per cent c.i. 0.18 to 2.10), P = 0.542) and incisional SSI rate (8 per cent NPWT versus 7 per cent controls; odds ratio 1.24 (95 per cent c.i. 0.26 to 5.99), P = 1.000). The NPWT group showed less pain, higher aesthetic satisfaction (P < 0.0001), and a higher proportion of wound healing (92 versus 78 per cent; P = 0.081) compared with the control group. CONCLUSION: NPWT does not reduce the incidence of SSI after stoma-reversal surgery compared with conventional wound dressing. However, NPWT improved the healing of uninfected wounds, reduced wound pain and led to better aesthetic outcomes.Registration number: NCT037812016 (clinicaltrials.gov).

Transanal Transection and Single-Stapled Anastomosis (TTSS): A comparison of anastomotic leak rates with the double-stapled technique and with transanal total mesorectal excision (TaTME) for rectal cancer.

BACKGROUND: in the literature on rectal cancer (RC) surgery many studies have focused on the quality of total mesorectal excision (TME) dissection, while there is a scarcity of comparative data on transection and anastomosis. No anastomosis has so far proved to be superior to any other. The aim of this study was to compare anastomotic leak (AL) rates between conventional laparoscopic double-stapled (DS), transanal total mesorectal excision (TaTME) and Transanal Transection and Single-Stapled anastomosis (TTSS) techniques. METHODS: consecutive mid-low RC patients undergoing elective laparoscopic TME with stapled anastomosis and protective stoma, by either DS, TaTME or TTSS techniques were retrieved from a prospectively collected database. RESULTS: 127 DS; 100 TaTME and 50 TTSS were included. Demographics, distance of the tumor from anal verge and neoadjuvant therapy were comparable. Operative time was longer in TaTME over DS and TTSS (p < 0.0001). More 90-days complications occurred in DS group vs TTSS (p = 0.029). The AL rate was 17.5% in DS, 6% in TaTME and 2% in TTSS group (p = 0.005). AL grade was: one B (2%) in TTSS; 2 grade B (2%) and 4 grade C (4%) in TaTME; 6 grade A (4.7%), 7 grade B (5.5%) and 9 grade C (7.1%) in DS group. Reintervention rate after AL was higher in DS group over TTSS (12.6% vs 2%; p = 0.003). The rate of stoma closure, pathology data and margin positivity did not differ. CONCLUSIONS: TTSS strategy is feasible, safe and leads to very low AL rates after TME for RC.

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.

Noninvasive Biomarkers of Colorectal Cancer: Role in Diagnosis and Personalised Treatment Perspectives.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. It has been estimated that more than one-third of patients are diagnosed when CRC has already spread to the lymph nodes. One out of five patients is diagnosed with metastatic CRC. The stage of diagnosis influences treatment outcome and survival. Notwithstanding the recent advances in multidisciplinary management and treatment of CRC, patients are still reluctant to undergo screening tests because of the associated invasiveness and discomfort (e.g., colonoscopy with biopsies). Moreover, the serological markers currently used for diagnosis are not reliable and, even if they were useful to detect disease recurrence after treatment, they are not always detected in patients with CRC (e.g., CEA). Recently, translational research in CRC has produced a wide spectrum of potential biomarkers that could be useful for diagnosis, treatment, and follow-up of these patients. The aim of this review is to provide an overview of the newer noninvasive or minimally invasive biomarkers of CRC. Here, we discuss imaging and biomolecular diagnostics ranging from their potential usefulness to obtain early and less-invasive diagnosis to their potential implementation in the development of a bespoke treatment of CRC.

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.

Rectal perforation during defecography: extraluminal barium impaction removed by TEM (Transanal Endoscopic Microsurgery).

AIM: Defecography is the standard diagnostic technique for the diagnosis of functional disorders of the posterior pelvic compartment. However it has some limits as radiation exposure, low-contrast resolution, some degrees of embarrassment and discomfort for the patients. Furthermore it often fails to directly visualize the changes that affect the pararectal space. Here we present a never described case of rectal perforation after defecography with barium impaction removed by TEM (Transanal Endoscopic Microsurgery). CASE REPORT: We present a case of a 50 years old woman with extraluminal barium impaction due to perforation occurred during defecography. Both pelvic MR and endoanal ultrasound confirmed the presence of the extramural rectal mass below rectal mucosa. It was completely and safely removed using transanal endoscopic microsurgery (TEM). RESULTS: The barium impaction has been radically removed using transanal endoscopic microsurgery. The post-operative period was uneventful and the patient was discharged 3 days after the operation. She is asymptomatic after 6 months from surgery. CONCLUSION: Defecography is not completely safe and its use must be indicated only in selected cases. When a patient has complications during or after this investigation he must be referred to a specialistic centre where a tailored treatment can be performed. It is mandatory that the indication for defecography and other diagnostic functional investigations is given by a colorectal specialist KEY WORD: Barium Impaction, Defecography, Rectal Perforation, TEM (Transanal Endoscopic Microsurgery).

Polypoid anal melanoma. A case report and review of the literature.

INTRODUCTION: Ano-rectal melanoma is an uncommon finding in patients complaining of rectal bleeding and/or anal mass often misinterpreted as a haemorroidal pile. CASE REPORT: A 55-years-old woman, complaining of rectal bleeding, frequent anal pain and anal mass suspected for haemorroidal thrombosis was referred for evaluation and possible treatment. A brown polypoid mass arising from the anal canal/lower rectum with a maximum diameter of 6 cm was diagnosed. The hystological examination of the neoplasm, transanally removed, revealed the presence of a polypoid melanoma partially involving the resection margin. Nor metastases nor limph-node involvement were found at the total-body CT scan and at a CT-PET. C-KIT examination was negative. Multidisciplinary evaluation recommended an abdominoperineal resection followed by an adjuvant chemotherapy as the only possible salvage treatment. To date the patient has refused it. DISCUSSION: The delay in the diagnosis of an anal melanoma is well-known, bringing frequently to treat advanced stages of the disease that to date has no clear guidelines for the treatment. KEY WORDS: Ano-rectal melanoma, Mucosal melanoma, Rectal bleeding.

Delayed Coloanal Anastomosis for rectovaginal fistula after colorectal resection for deep endometriosis.

AIM: The deep infiltrating endometriosis, defined as a subperitoneal infiltration of endometrial implants of ≥ 5 mm involving not only the colorectal tract but also rectovaginal septum, vagina and bladder often requires a challenging surgery. Endometriosis nodes of the rectovaginal septum, if symptomatic, need a resection of the involved colorectal tract with colorectal or coloanal anastomosis. Unfortunately in these cases is not uncommon the possibility of a postoperative rectovaginal fistula (RVF), caused by the weakness of the septum that must be skeletonized to completely remove the endometriosis nodes. Here we present a case of anastomotic leakage with high RVF after colorectal resection and low colorectal anastomosis for deep endometriosis in which, for a chronic pelvic sepsis and a high risk of failure of a new immediate coloanal anastomosis, a Turnbull-Cutait pull-through with delayed coloanal anastomosis (DCAA) has been performed. CASE REPORT: A now 34 years old woman was admitted to our Clinic because of a RVF due to recto-sigmoid resection with colorectal anastomosis for endometriosis. An evaluation in anesthesia confirmed the RVF. In this case we avoided an immediate new colorectal anastomosis for the high risk of a recurrent anastomotic leakage and performed a DCAA. RESULTS: The outcome of the two-steps operation has been satisfactory both for the healing of the RVF and for the functional results bringing the young patient to a completely restored social, sexual and working life. CONCLUSIONS: In our opinion Turnbull-Cutait pull-through with delayed coloanal anastomosis is a good choice in patients with RVF in which a new colorectal or coloanal anastomosis can bring to a recurrent leakage. KEY WORDS: Delayed coloanal anastomosis, Deep endometriosis, Rectovaginal fistula.

The effect of sacral nerve modulation on cerebral evoked potential latency in fecal incontinence and constipation.

OBJECTIVE: Influence of sacral nerve modulation (SNM) on cerebral somatosensory evoked potentials (SEP) was determined in patients with incontinence and constipation. BACKGROUND: Selection of patients with incontinence and constipation for SNM could be improved. METHODS: The latency (ms) of SEP induced by pudendal nerve stimulation was compared before (T0) and at 1 month during peripheral nerve evaluation (PNE) of SNM at frequencies of 21 Hz (T1) and 40 Hz (T2). The results were correlated with clinical outcome at 6 months. RESULTS: In 16 of 23 incontinent patients with clinical "success" from SNM (Wexner incontinence score ≤7), there was a significant difference between P40 latency at T0 and T2 (38.81 vs. 37.49 ms, P = 0.049). In the 7 with "failure," there was no change between T0 and T2. In 12 of 19 constipated patients with "success" (Wexner constipation score ≤15), there was no difference between T0 and T2 P40 latency (39.28 vs. 38.25 ms, P = 0.374). In the 7 with "failure," there was a significant fall in P40 latency (41.20 vs. 39.30 ms, P = 0.047) but not to the normal range. The T0 P40 latency in incontinent patients having "success" was significantly higher than in the normal range (P = 0.044). In constipated patients it was significantly higher than in the normal range in both those with "success" (P = 0.001) and "failure" (P = 0.022). CONCLUSIONS: Measurement of P40 latency of SEP at baseline and at 1 month of SNM at a frequency of 40 Hz may help to predict the outcome of SNM and thus influence the decision for permanent implantation for patients with incontinence and constipation.

Recurrent caecal volvulus in mesenterium commune. A case report.

We report a case of recurrent abdominal pain due to intermittent caecal volvulus arising in a patient with mesenterium commune. Colonic enema, abdominal CT scan and virtual colonography with three-dimensional colonic reconstruction were useful for detecting this rare abnormal intestinal fixation. Although right hemicolectomy was indicated, we performed a wide colonic resection from the terminal ileum to the distal sigmoid because the patient's short mesentery made it impossible to perform an ileum-transverse anastomosis. At six months follow-up, the patient was in good health and free of abdominal symptoms.