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.

Fecal miRNA profiles in colorectal cancers with mucinous morphology.

Diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study (Pardini et al., Gastroenterology 2023) behave in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n=172), including 27 CRC with mucinous morphology (mucinous cancers with >50% mucinous morphology and those with mucinous component >5% but <50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n=98). Most of the differentially expressed (DE) stool miRNAs (n=324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.

Global International Society of University Colon and Rectal Surgeons in collaboration with European Society of Coloproctology audit on office-based and surgical treatment of haemorrhoidal disease: Study protocol.

AIM: Haemorrhoidal disease (HD) is one of the most common anal disorders in the adult population. Despite that, treatment options differ among different countries and specialists, even for the same grade of HD. The aim of this study is to evaluate the differences in patient demographics, surgeon preference for the treatment option, outcomes as well as patient satisfaction rate for the procedure using an office-based or surgical approach for the treatment of HD among International Society of University Colon and Rectal Surgeons (ISUCRS) and European Society of Coloproctology (ECSP) fellows. METHOD: A panel of the ISUCRS and ECSP members will answer questions that are included in a questionnaire about the treatment of HD. The questionnaire will be distributed electronically to ISUCRS and ECSP fellows included in our database and will remain open from 1 April 2024 to 31 May 2024. CONCLUSION: This multicentre, global prospective audit will be delivered by consultant colorectal and general surgeons as well as trainees. The data obtained will lead to a better understanding of the incidence of HD, treatment and diagnostic possibilities. This snapshot audit will be hypothesis generating and inform areas the need future prospective study.

European Society of Coloproctology: Guidelines for diagnosis and treatment of cryptoglandular anal fistula.

AIM: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. METHODS: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. RESULTS: In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. CONCLUSION: This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.

Evaluating the Diagnostic Potential of Combined Salivary and Skin Biomarkers in Parkinson's Disease.

Oligomeric alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin have emerged as promising diagnostic biomarkers for Parkinson's disease (PD). This study aimed to assess and compare the diagnostic value of these biomarkers in discriminating between 38 PD patients and 24 healthy subjects (HSs) using easily accessible biological samples. Additionally, the study sought to determine the diagnostic potential of combining these biomarkers and to explore their correlations with clinical features. Salivary oligomeric α-syn levels were quantified using competitive ELISA, while skin biopsies were analyzed through immunofluorescence to detect phosphorylated α-syn at Ser129 (p-S129). Both biomarkers individually were accurate in discriminating PD patients from HSs, with a modest agreement between them. The combined positivity of salivary α-syn oligomers and skin p-S129 aggregates differentiated PD patients from HSs with an excellent discriminative ability with an AUC of 0.9095. The modest agreement observed between salivary and skin biomarkers individually suggests that they may reflect different aspects of PD pathology, thus providing complementary information when combined. This study's results highlight the potential of utilizing a multimodal biomarker approach to enhance diagnostic accuracy in PD.

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey.

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

An international survey exploring the management of pilonidal disease.

AIM: Pilonidal disease (PD) is a common debilitating condition frequently seen in surgical practice. Several available treatments carry different benefit/risk balances. The aim of this study was to snapshot the current management of PD across European countries. METHOD: Members affiliated to the European Society of Coloproctology were invited to join the survey. An invitation was extended to others via social media. The predictive power of respondents' and hospitals' demographics on the change of therapeutic approach was explored. RESULTS: Respondents (n = 452) were mostly men (77%), aged 26-60 years, practising in both academic and public hospitals and with fair distribution between colorectal (51%) and general (48%) surgeons. A total of 331 (73%) respondents recommended surgery at first presentation of the disease. Up to 80% of them recommended antibiotic therapy and 95% did not use any classification of PD. A primary closure technique was the preferred procedure (29%), followed by open technique (22%), flap creation (7%), sinusectomy (7%) and marsupialization (7%). Approximately 27% of subjects would choose the same surgical technique even after a failure. Almost half (46%) perform surgery as office based. A conservative approach was negatively associated with acutely presenting PD (p < 0.001). Respondents who were not considering tailored surgery based on patient presentation tended to change their approach in the case of a failed procedure. CONCLUSION: With the caveat of a heterogeneous number of respondents across countries, the results of our snapshot survey may inform the development of future guidelines.

Long term results of video-assisted anal fistula treatment for complex anal fistula: another shattered dream?

AIM: Complex anal fistula represents a burden for patients, and its management is a challenge for surgeons. Video-assisted anal fistula treatment (VAAFT) is one sphincter-sparing technique. However, data on its long-term effectiveness are scant. We aimed to explore the outcomes of VAAFT in a retrospective cohort of patients referred to a tertiary centre. METHOD: Consecutive adult patients with a minimum of 2 years' follow-up after VAAFT were reviewed. Patients were followed up to 5 years postoperatively. Failure was defined as incomplete healing of the external orifice(s) during the first 6 months. Recurrence was defined as new radiologically and/or clinically confirmed onset of the fistula after primary healing. A generalized linear model was fitted to evaluate the association between failure and sociodemographic characteristics. Predictors of recurrence were determined in a subgroup analysis of patients found to be free from disease at 6 months postoperatively. RESULTS: Overall, 106 patients (70% male; mean age 41 years) were reviewed. Of these 86% had a previous seton placement. Fistulas were either high trans-sphincteric (74%), suprasphincteric (12%) or extrasphincteric (13%). Eight (7%) patients experienced postoperative complications, none of which required reintervention. Mean follow-up was 53 ± 13.2 months. VAAFT failed in 14 (13%) patients. The overall recurrence rate ranged from 29% at 1 year to 63% at 5 years. Multiple external orifices, suprasphincteric fistula, younger age, previous surgery and higher complexity of the fistulous tract were independent risk factors for recurrence. CONCLUSION: VAAFT is a safe sphincter-sparing technique. The initially high success rate decreases over time and relates to a higher degree of complexity.

Endoscopic sinusectomy: 'a rose by any other name'. A systematic review of different endoscopic procedures to treat pilonidal disease.

AIM: Pilonidal sinus or Pilonidal Disease (PD) is a relatively common, benign but challenging condition. Although commonly encountered in practice, its ideal treatment is controversial. One of the most validated treatments is video-assisted surgery. In this context, very similar endoscopic techniques have been published under different names. The aim of this systematic review is to assess the differences among these proposed techniques and their outcomes. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during all stages of this systematic review. A systematic search of the English literature was performed on multiple databases from 1 January 2014 to 3 April 2022. The primary outcome measure was the IDEAL framework stage of innovation. The key secondary outcome measures were the adherence to the IDEAL reporting guidelines, the Blencowe framework and the core outcome set (COS) for studies evaluating the introduction and evaluation of novel surgical techniques, the qualitative assessment using appropriate tools, the procedural variations and outcomes of each technique. RESULTS: A total of 38 articles were included reporting a very similar technique under eight different acronyms. The number of patients varied from 9 to 250. Mean follow-up ranged from 1 to 60 months. There was only one published study of IDEAL 3. The majority (58%) were IDEAL 2a studies. Reporting of domains in the IDEAL reporting guidelines and Blencowe framework was poor, with most studies not reporting the component steps of procedures or efforts to standardize them. Half of COS domains were markedly underreported. The quality of the evidence was categorized as having a risk of bias from moderate to critical level in all nine comparative non-randomized series. Postoperative complications occurred in 0%-6% of cases, including surgical site infection, poor or failed wound healing bleeding, granuloma, haematoma, and pain requiring intervention. The recurrence rate varied from 0% to 22%. CONCLUSION: The study demonstrates that reporting on technical aspects of interventions for PD is poor, thus warranting a better-quality control of surgical techniques. It is advisable to group all endoscopic procedures under the umbrella term of 'endoscopic sinusectomy', thus embracing the two main principles of this technique, that is, video assistance and PD ablation.

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.

An international assessment of surgeon practices in abdominal wound closure and surgical site infection prevention by the European Society for Coloproctology.

AIM: The burden of abdominal wound failure can be profound. Recent clinical guidelines have highlighted the heterogeneity of laparotomy closure techniques. The aim of this study was to investigate current midline closure techniques and practices for prevention of surgical site infection (SSI). METHOD: An online survey was distributed in 2021 among the membership of the European Society of Coloproctology and its partner societies. Surgeons were asked to provide information on how they would close the abdominal wall in three specific clinical scenarios and on SSI prevention practices. RESULTS: A total of 561 consultants and trainee surgeons participated in the survey, mainly from Europe (n = 375, 66.8%). Of these, 60.6% identified themselves as colorectal surgeons and 39.4% as general surgeons. The majority used polydioxanone for fascial closure, with small bite techniques predominating in clean-contaminated cases (74.5%, n = 418). No significant differences were found between consultants and trainee surgeons. For SSI prevention, more surgeons preferred the use of mechanical bowel preparation (MBP) alone over MBP and oral antibiotics combined. Most surgeons preferred 2% alcoholic chlorhexidine (68.4%) or aqueous povidone-iodine (61.1%) for skin preparation. The majority did not use triclosan-coated sutures (73.3%) or preoperative warming of the wound site (78.5%), irrespective of level of training or European/non-European practice. CONCLUSION: Abdominal wound closure technique and SSI prevention strategies vary widely between surgeons. There is little evidence of a risk-stratified approach to wound closure materials or techniques, with most surgeons using the same strategy for all patient scenarios. Harmonization of practice and the limitation of outlying techniques might result in better outcomes for patients and provide a stable platform for the introduction and evaluation of further potential improvements.

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.

Fissurectomy versus lateral internal sphincterotomy in the treatment of chronic anal fissures: no advantages in terms of post-operative incontinence.

PURPOSE: The standard treatment for chronic anal fissures that have failed non-operative management is lateral internal sphincterotomy. Surgery can cause de novo incontinence. Fissurectomy has been proposed as a sphincter/saving procedure, especially in the presence of a deep posterior pouch with or without a crypt infection. This study investigated whether fissurectomy offers a benefit in terms of de novo post-operative incontinence. METHODS: Patients surgically managed with fissurectomy or lateral internal sphincterotomy for chronic anal fissures from 2013 to 2019 have been included. Healing rate, changes in continence and patient satisfaction were investigated at long-term follow-up. RESULTS: One hundred twenty patients (55 females, 65 males) were analysed: 29 patients underwent fissurectomy and 91 lateral internal sphincterotomy. Mean follow-up was 55 months [confidence interval (CI) 5-116 months]. Both techniques showed some rate of de novo post-operative incontinence (> +3 Vaizey score points): 8.9% lateral internal sphincterotomy, 17.8% fissurectomy (p = 0.338). The mean Vaizey score in these patients was 10.37 [standard deviation (sd) 6.3] after lateral internal sphincterotomy (LIS) and 5.4 (sd 2.3) after fissurectomy Healing rate was 97.8% in the lateral internal sphincterotomy group and 75.8% in the fissurectomy group (p = 0.001). In the lateral internal sphincterotomy group, patients with de novo post-op incontinence showed a statistically significant lower satisfaction rate (9.2 ± 1.57 versus 6.13 ± 3; p = 0.023) while no differences were present in the fissurectomy group (8.87 ± 1.69 versus 7.4 ± 1.14; p = 0.077). CONCLUSIONS: Lateral internal sphincterotomy is confirmed as the preferred technique in term of healing rate. Fissurectomy did not offer a lower rate of de novo post-operative incontinence, but resulted in lower Vaizey scores in patients in whom this occurred. Satisfaction was lower in patients suffering a de novo post-operative incontinence after lateral internal sphincterotomy.

Basosquamous Cell Carcinoma of the Nipple-Areola Complex-Report of a Case.

Basosquamous cell carcinoma (BSCC) is a rare malignancy usually arising on sun-exposed areas of the skin. BSCC is described as a rare variant of Basal cell carcinoma (BCC) which shows clinical and microscopic features of both BCC and of Squamous cell carcinoma (SCC). We report the case of a 70-year-old male with a cutaneous lesion of the nipple-areola complex (NAC); to the best of our knowledge, this is the first ever reported patient with BSCC in this area. The lesion had a fast growth, but, due to the COVID19 crisis, the patient only came to our observation one year after onset of this condition. Physical examination showed a bleeding red ulcerated lesion that involved the NAC, measuring 27 mm × 20 mm. Biopsy showed a BSCC. Pre-operative breast ultrasound scan, mammogram and MRI were all performed before surgery, which consisted of simple mastectomy and sentinel lymph-node biopsy. The patient was discharged home on the 4th post-operative day, and at 18-month follow-up there are no signs or clinical evidence of local recurrence or metastases. Diagnosis of BSCC of the nipple-areola complex requires high index of suspicion and a thorough differential diagnosis, management, and suitable radical treatment due to well described high rates of recurrence and of metastases. Differential diagnosis with similar lesions (e.g., Paget's disease, Bowen's disease, BCC, and SCC) should also be taken into account.

Laparoscopic versus open colectomy for locally advanced T4 colonic cancer: meta-analysis of clinical and oncological outcomes.

BACKGROUND: The aim of this study was to review the early postoperative and oncological outcomes after laparoscopic colectomy for T4 cancer compared with open surgery. METHOD: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for any relevant clinical study comparing laparoscopic and open colectomy as treatment for T4 colonic cancer. The risk ratio (RR) with 95 per cent c.i. was calculated for dichotomous variables, and the mean difference (m.d.) with 95 per cent confidence interval for continuous variables. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was implemented for assessing quality of evidence (QoE). RESULTS: Twenty-four observational studies (21 retrospective and 3 prospective cohort studies) were included, analysing a total of 18 123 patients: 9024 received laparoscopic colectomy and 9099 underwent open surgery. Laparoscopic colectomy was associated with lower rates of mortality (RR 0.48, 95 per cent c.i. 0.41 to 0.56; P < 0.001; I2 = 0 per cent, fixed-effect model; QoE moderate) and complications (RR 0.61, 0.49 to 0.76; P < 0.001; I2 = 20 per cent, random-effects model; QoE very low) compared with an open procedure. No differences in R0 resection rate (RR 1.01, 1.00 to 1.03; P = 0.12; I2 = 37 per cent, random-effects model; QoE very low) and recurrence rate (RR 0.98, 0.84 to 1.14; P = 0.81; I2 = 0 per cent, fixed-effect model; QoE very low) were found. CONCLUSION: Laparoscopic colectomy for T4 colonic cancer is safe, and is associated with better clinical outcomes than open surgery and similar oncological outcomes.

Colonic cancer is a common condition, and in 10-20 per cent of patients the tumour has grown beyond the bowel wall or invaded other organs at diagnosis (called locally advanced colonic cancer). This study reviews the use of laparoscopic (minimally invasive surgery or keyhole surgery) to treat these locally advanced tumours. Medical databases were searched for research publications on the subject. In total, 24 studies (including data on 18 123 patients) comparing laparoscopic with traditional open surgery were identified. Analysing the data of the studies together found that laparoscopic surgery was associated with lower rates of mortality and surgical complications. No difference in survival or cancer recurrence was found.

The impact of experience on recurrence rates after biopsy punch excision for pilonidal disease.

AIM: We present the outcomes and the recurrences of 848 patients with pilonidal disease (PD) treated by biopsy punch excision (BPE) and we weigh our results against progressively obtained operative experience. BPE is a modified 'merged' version of both the Bascom 'pit picking' procedure and the Gips procedure. It employs biopsy punches of different calibre, depending on whether treatment is in the natal cleft (calibre as small as possible) or lateral (larger calibre punches or even small incision). Sometimes this procedure is referred to as the Bascom-Gips procedure. METHODS: In all, 848 consecutive patients with PD were treated from January 2011 until December 2016 (sex 622 [73.4%] men and 226 [26.6%] women; median age 26.2 years, mean age 24.6 ± 28.99 [range 14-55] years, men 25.1 years, women 24.8 years). Of these 848 patients, 287 were operated in 2011-2012, 301 in 2013-2014 and 260 in 2015-2016. The recurrence rates were recorded 12, 24 and 60 months after surgery both cumulatively and by examining the outcomes of the three biennia individually (years of treatment 2011-2012 or group A, 2013-2014 or group B, 2015-2016 or group C). RESULTS: The mean operating time was 34 ± 24.45 min. Postoperative complications included early (<24 h; n = 22 or 2.6%) and delayed (>24 h; n = 26 or 3.1%) postoperative bleeding. Postoperative fluid collections (<2 weeks) occurred in 83/848 patients (9.8%) and included haematoma (n = 25) and seroma (n = 58). Full recovery was obtained after a mean of 21 ± 12.72 days and work/school/university activities were resumed after a mean of 4 ± 12.02 days. Twelve-, 24- and 60-month follow-ups were possible in 725 (85.5%), 682 (80.4%) and 595 (70.2%) patients out of 848. An overall significant (ꭓ2  = 16.87, P = 0.0002) difference was found in the recurrence rates: 59 recurrences/725 patients (or 8.1%) after 1 year, 89 recurrences/682 patients (or 13.0%) after 2 years and 98 recurrences/595 (or 16.4%) after 5 years. However, when subgrouping patients in three 24-month subsets, the recurrence rates showed a steady and progressive decrease in the three biennia 2011-2012 (group A), 2013-2014 (group B) and 2015-2016 (group C) at 12-, 48- and 60-month follow-ups. Recurrences after 12 months were 29/225 (12.9%), 19/285 (6.7%) and 11/215 (5.1%) (ꭓ2  = 8.53, P = 0.014) in groups A, B and C respectively; after 24 months, 36/226 (15.9%), 31/242 (12.8%) and 22/214 (10.2%) (ꭓ2  = 2.38, P = 0.30 N.S.) in groups A, B and C respectively; after 60 months, 38/194 (19.5%), 36/215 (16.7%) and 24/186 (12.9%) (ꭓ2  = 2.23, P = 0.32) in groups A, B and C respectively. CONCLUSIONS: BPE is an effective, disease-targeted, minimally invasive and inexpensive way to treat PD. Its results are influenced by the experience of the team involved, especially regarding early recurrences/failure of surgery. At least 5-year follow-ups are needed to ascertain the outcome of surgery for PD.

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.

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.

Low-pressure versus standard-pressure pneumoperitoneum in laparoscopic cholecystectomy: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: It has been previously demonstrated that the rise of intra-abdominal pressures and prolonged exposure to such pressures can produce changes in the cardiovascular and pulmonary dynamic which, though potentially well tolerated in the majority of healthy patients with adequate cardiopulmonary reserve, may be less well tolerated when cardiopulmonary reserve is poor. Nevertheless, theoretically lowering intra-abdominal pressure could reduce the impact of pneumoperitoneum on the blood circulation of intra-abdominal organs as well as cardiopulmonary function. However, the evidence remains weak, and as such, the debate remains unresolved. The aim of this systematic review and meta-analysis was to demonstrate the current knowledge around the effect of pneumoperitoneum at different pressures levels during laparoscopic cholecystectomy. MATERIALS AND METHODS: This systematic review and meta-analysis were reported according to the recommendations of the 2020 updated Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, and the Cochrane handbook for systematic reviews of interventions. RESULTS: This systematic review and meta-analysis included 44 randomized controlled trials that compared different pressures of pneumoperitoneum in the setting of elective laparoscopic cholecystectomy. Length of hospital, conversion rate, and complications rate were not significantly different, whereas statistically significant differences were observed in post-operative pain and analgesic consumption. According to the GRADE criteria, overall quality of evidence was high for intra-operative bile spillage (critical outcome), overall complications (critical outcome), shoulder pain (critical outcome), and overall post-operative pain (critical outcome). Overall quality of evidence was moderate for conversion to open surgery (critical outcome), post-operative pain at 1 day (critical outcome), post-operative pain at 3 days (important outcome), and bleeding (critical outcome). Overall quality of evidence was low for operative time (important outcome), length of hospital stay (important outcome), post-operative pain at 12 h (critical outcome), and was very low for post-operative pain at 1 h (critical outcome), post-operative pain at 4 h (critical outcome), post-operative pain at 8 h (critical outcome), and post-operative pain at 2 days (critical outcome). CONCLUSIONS: This review allowed us to draw conclusive results from the use of low-pressure pneumoperitoneum with an adequate quality of evidence.

Essential tremor and cognitive impairment: who, how, and why.

BACKGROUND AND AIMS: Recent years have witnessed the switch from considering essential tremor (ET) a monosymptomatic disorder to consider it as part of a spectrum, including other neurological signs, such as mild cognitive impairment and dementia, thus defining it as "ET plus." There are few data on cognitive impairment in ET patients. The aim of this review is to analyze the clinical characteristics of ET patients developing cognitive impairment, their neuropsychological profile, the underpinning mechanisms, and the possible biomarkers. METHODS: The authors performed a narrative review on cognitive decline in essential tremor, including articles written in English since the year 2000. DISCUSSION: The most recent pathogenetic theories of cognitive impairment in ET rely on the cerebellar dysfunction, being part of the Cerebellar Cognitive Affective Syndrome spectrum. Cognitive impairment in ET patients could be assessed through many tests that demonstrate the involvement of different domains, such as attention, executive functions, and language. There are some clinical characteristics of ET that may indicate a greater risk of developing cognitive impairment, namely, cerebellar symptoms, falls, age at onset, and family history. However, there are no established clinical, neurophysiological, neuropathological, and fluid biomarkers of cognitive impairment in ET. CONCLUSIONS: Increasing data are showing in ET the presence of cerebellar symptoms and cognitive impairment. Further studies are needed to better understand cognition in ET patients, and to define the boundary between ET and ET plus, since deeper phenotyping might have important clinical and therapeutic implications.