Functional Outcomes After Transanal Total Mesorectal Excision (taTME) for Rectal Cancer: Results from the Phase II North American Multicenter Prospective Observational Trial.

OBJECTIVE: To investigate fecal incontinence and defecatory, urinary, and sexual functional outcomes after taTME. SUMMARY BACKGROUND DATA: Proctectomy for rectal cancer may result in alterations in defecatory, urinary, and sexual function that persist beyond 12 months. The recent multicenter Phase II taTME trial demonstrated the safety of taTME in patients with stage I-III tumors. METHODS: Prospectively registered self-reported questionnaires were collected from 100 taTME patients. Fecal continence (FIQL, Wexner), defecatory function (COREFO), urinary function (IPSS), and sexual function (FSFI-female, IIEF-male) were assessed preoperatively (PQ), 3-4 months post-ileostomy closure (FQ1), and 12-18 months post-taTME (FQ2). RESULTS: Among 83 patients who responded at all three time points, FIQL, Wexner, and COREFO significantly worsened post-ileostomy closure. Between FQ1 and FQ2, FIQL lifestyle and coping, Wexner, and COREFO incontinence, social impact, frequency, and need for medication significantly improved, while FIQL depression and embarrassment did not change. IPSS did not change relative to preoperative scores. For females, FSFI declined for desire, orgasm, and satisfaction between PQ and FQ1, and did not improve between FQ1 and FQ2. In males, IIEF declined with no change between FQ1 and FQ2. CONCLUSIONS: Although taTME resulted in initial decline in defecatory function and fecal continence, most functional domains improved by 12 months after ileostomy closure, without returning to preoperative status. Urinary function was preserved while sexual function declined without improvement by 18 months post-taTME. Our results address patient expectations and inform shared decision-making regarding taTME.

SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.

AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection. METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected. DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy. TRIAL REGISTRATION: NCT05010850.

Multicenter phase II trial of transanal total mesorectal excision for rectal cancer: preliminary results.

BACKGROUND: Transanal TME (taTME) combines abdominal and transanal dissection to facilitate sphincter preservation in patients with low rectal tumors. Few phase II/III trials report long-term oncologic and functional results. We report early results from a North American prospective multicenter phase II trial of taTME (NCT03144765). METHODS: 100 patients with stage I-III rectal adenocarcinoma located ≤ 10 cm from the anal verge (AV) were enrolled across 11 centers. Primary and secondary endpoints were TME quality, pathologic outcomes, 30-day and 90-day outcomes, and stoma closure rate. Univariable regression analysis was performed to assess risk factors for incomplete TME and anastomotic complications. RESULTS: Between September 2017 and April 2022, 70 males and 30 females with median age of 58 (IQR 49-62) years and BMI 27.8 (IQR 23.9-31.8) kg/m2 underwent 2-team taTME for tumors located a median 5.8 (IQR 4.5-7.0) cm from the AV. Neoadjuvant radiotherapy was completed in 69%. Intersphincteric resection was performed in 36% and all patients were diverted. Intraoperative complications occurred in 8% including 3 organ injuries, 2 abdominal and 1 transanal conversion. The 30-day and 90-day morbidity rates were 49% (Clavien-Dindo (CD) ≥ 3 in 28.6%) and 56% (CD ≥ 3 in 30.4% including 1 mortality), respectively. Anastomotic complications were reported in 18% including 10% diagnosed within 30 days. Higher anastomotic risk was noted among males (p = 0.05). At a median follow-up of 5 (IQR 3.1-7.4) months, 98% of stomas were closed. TME grade was complete or near complete in 90%, with positive margins in 2 cases (3%). Risk factors for incomplete TME were ASA ≥ 3 (p = 0.01), increased time between NRT and surgery (p = 0.03), and higher operative blood loss (p = 0.003). CONCLUSION: When performed at expert centers, 2-team taTME in patients with low rectal tumors is safe with low conversion rates and high stoma closure rate. Mid-term results will further evaluate oncologic and functional outcomes.

Discordance in Total Mesorectal Excision Specimen Grading in a Prospective Phase 2 Multicenter Rectal Cancer Trial: Are We Overestimating the Quality of Our Resections?

OBJECTIVES: To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase 2 trial of transanal TME. BACKGROUND: Grading of TME specimens is based on the macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described. METHODS: A phase 2 prospective transanal TME trial was conducted from 2017 to 2022 across 11 North American centers with TME quality as the primary study endpoint. QC measures included (1) training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance before trial reporting. Cohen Kappa statistic was used to assess agreement in grading. RESULTS: Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ = 0.35; 95% CI: 0.10-0.61; P < 0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases, respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre versus postreconciliation rates of complete or NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC-NC; N = 1) or major downgrade (NC/C-IC, N = 4) in 5 cases overall (5%). CONCLUSIONS: A 14% rate of major discordance was observed in TME grading between the site and central reviewers. The resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through a central review of TME photographs and reconciliation of major discordances is strongly recommended.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

AIM: Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. METHODS: A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. RESULTS: Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. CONCLUSIONS: Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

The long-term impact of an interprofessional humanistic faculty development programme: A qualitative investigation.

RATIONALE, AIMS, AND OBJECTIVES: While it has long been supported that faculty development programmes serve as a means to improving practical knowledge, professional skills, and identity formation for faculty, significantly less research is focused on how learning that occurs in faculty development programmes is actually employed in the workplace and ingrained in day-to-day activities. The present study qualitatively explored the long-term impact of the Mentoring and Professionalism in Training (MAP-IT) programme, a longitudinal, interprofessional faculty development curriculum designed to enhance clinicians' humanistic mentoring skills, specifically nurses and physicians. METHOD: Participants included 21 former high-potential mentors and facilitator leaders who had graduated from the MAP-IT programme from 2014 to 2016. Semi-structured focus groups and interviews were conducted between August and September of 2017 to collect participant experiences of the impact of MAP-IT skills on their professional roles (with colleagues and patients) in their clinical environments. Qualitative data were analysed using content analysis methodology. RESULTS: Qualitative analyses using an editing analysis style resulted in nine major themes, including incorporation into clinical practice, self-care, team building and conflict resolution, mindfulness, mentorship, professionalism, interprofessional collaboration, humanism, and appreciative inquiry. CONCLUSION: The personal and professional development instilled through the MAP-IT programme was found to remain important over time, years after participation in the programme had concluded, supporting its "durability." Implications are also discussed.

Infliximab-induced Depression and Suicidal Behavior in Adolescent with Crohn's Disease: Case Report and Review of Literature.

Infliximab, an anti-inflammatory agent, is used to treat various autoimmune disorders. There are at least 3 reports of severe psychiatric adverse effects of the drug, including suicidal behaviors in adults and psychosis in adult and adolescent patients. We report a case of an adolescent who developed depression and suicidal behaviors shortly after beginning infliximab. Although there have been reports of adolescents developing acute psychosis shortly after starting infliximab, this is, to our knowledge, the first report of adolescent suicidal behavior in the setting of infliximab treatment. METHODS: We describe a patient's presentation and clinical course, as well as existing reports of adverse psychiatric effects of infliximab. RESULTS: A 16-year-old male with a 2-year history of disabling symptoms and complications of Crohn's disease was initiated on a trial of infliximab. Within days of the first infliximab infusion, he experienced symptoms of depression, which intensified over weeks and resulted in a serious suicide attempt. The patient was treated with fluoxetine, melatonin, and psychotherapy, which effectively managed his infliximab-induced depressive disorder with suicidal thoughts and behaviors. Posttreatment, he tolerated additional infliximab infusions without the recurrence of psychiatric symptoms. CONCLUSIONS: Treatment with infliximab may rarely and suddenly cause severe and potentially life-threatening psychiatric symptoms. Therefore, youth with chronic illnesses considered for infliximab treatment should be screened for preexisting, as well as for a family history of, psychiatric disorders and suicidal behavior.

A Mixed-Methods Approach to Humanistic Interprofessional Faculty Development.

INTRODUCTION: This study evaluated the effectiveness of the Mentoring and Professionalism in Training (MAP-IT) program, a longitudinal, interprofessional faculty development curriculum designed to enhance clinicians' humanistic mentoring skills, specifically nurses and physicians. METHODS: During 2014 to 2016, two consecutive cohorts of nurses and physicians completed the MAP-IT program. Participants included 169 high potential mentors (HPMs) and 61 facilitator leaders. Each 10-month program consisted of small group work, experiential learning, and critical reflection aimed at enhancing humanistic mentoring skills. Throughout the program, facilitator leaders served as mentors for the HPMs. Both quantitative and qualitative data were collected to measure changes in skill levels specific to humanistic teaching practices, as well as overall evaluation of the program's curriculum and logistics. Quantitative data were analyzed using the Wilcoxon signed-rank test, descriptive statistics, and Fisher exact test, as appropriate. Qualitative data assessing the overall impact and applicability of the program to the clinical setting were analyzed using content analysis methodology. RESULTS: Across cohorts, HPMs demonstrated significant increases in perceptions of humanistic teaching skills. During objective structured teaching simulations, significant increases were also found in HPMs' self-reported mentoring skills and their skills as rated by a standardized RN/MD. Qualitative analyses revealed themes of the program to be skill development and application, mentorship, humanism, mindfulness, self-care, and acknowledgment of overlapping interprofessional roles. DISCUSSION: Utilizing an interprofessional education approach, the MAP-IT program was determined to be a feasible strategy to positively impact the personal and professional development of nurses and physicians.