Shogan, Benjamin D.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a “watch-and-wait” nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

BACKGROUND: Revisional and reconstructive surgery for IPAA is rare given the high success of pouch surgery for chronic ulcerative colitis. Limited data exist on both surgical and functional outcomes in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction. OBJECTIVE: This study aimed to determine the surgical and functional outcome in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction. DESIGN: A prospectively collected surgical database was accessed for this study. SETTING: This study was conducted at an IBD referral center. PATIENTS: Patients with chronic ulcerative colitis who underwent IPAA revision or reconstruction were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were 30-day postoperative outcomes and long-term pouch function. RESULTS: Eighty-one patients were identified. Original IPAA was performed for chronic ulcerative colitis (n = 71; 88%) and indeterminate colitis (n = 11; 12.%), and the most common configuration was a J-pouch (n = 69; 86%) with handsewn anastomosis (n = 41;68%). No independent predictors of 30-day postoperative complications following reconstructive/revisional surgery were identified. Pelvic abscesses and Crohn’s disease of the pouch were independently associated with ultimate pouch excision. Median follow-up following revision/reconstruction was 40 months (range, 1–292 months) during which 15 patients (23%) had pouch failure. The 5- and 10-year pouch survival rates following revision were 85 ± 5% and 65 ± 9% by Kaplan-Meier estimation; age <30 years was significantly associated with pouch survival. Long-term function (n = 30; 35%) compared with a matched control cohort of primary IPAA was characterized by significantly increased daytime bowel incontinence (p = 0.0119), liquid stool (p = 0.0062), and medication to thicken stools (p = 0.0452). LIMITATIONS: This was a single-center series, and response rate for functional data was 35%. CONCLUSIONS: In properly selected patients with a failing pouch, originally made for chronic ulcerative colitis or indeterminate colitis, revisional and reconstructive surgery is associated with low complication rates, high pouch salvage, and acceptable long-term pouch function. See Video Abstract at http://links.lww.com/DCR/A640.

Objective: Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice. Summary: Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion. Methods: Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models. Results: One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 – 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5– 0.9; P = 01). Conclusions: Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.

Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis (UC) patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self-emptying (SEL) ileal loops using wild-type (WT), IL-10 knockout (KO) (IL-10), TLR4 KO (T4), and IL-10/T4 double KO mice. After 5 wk, loop histology, host gene/protein expression, and bacterial 16s rRNA profiles were examined. SFL exhibit fecal stasis due to directional motility oriented toward the loop end, whereas SEL remain empty. In WT mice, SFL, but not SEL, develop pouchlike microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. The inflammation associated with IL-10 required TLR4, as animals lacking both pathways displayed little disease. Furthermore, germ-free IL-10 mice conventionalized with SFL, but not SEL, microbiota populations develop severe colitis. These data support essential roles of stasis-induced, colon-like microbiota, TLR4-mediated colonic metaplasia, and genetic susceptibility in the development of pouchitis and possibly UC. However, these factors by themselves are not sufficient. Similarities between this model and human UC/pouchitis provide opportunities for gaining insights into the mechanistic basis of IBD and for identification of targets for novel preventative and therapeutic interventions.