Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

Circulating Hybrid Cells: A Novel Liquid Biomarker of Treatment Response in Gastrointestinal Cancers.

BACKGROUND: Real-time monitoring of treatment response with a liquid biomarker has potential to inform treatment decisions for patients with rectal adenocarcinoma (RAC), esophageal adenocarcinoma (EAC), and colorectal liver metastasis (CRLM). Circulating hybrid cells (CHCs), which have both immune and tumor cell phenotypes, are detectable in the peripheral blood of patients with gastrointestinal cancers, but their potential as an indicator of treatment response is unexplored. METHODS: Peripheral blood specimens were collected from RAC and EAC patients after neoadjuvant therapy (NAT) or longitudinally during therapy and evaluated for CHC levels by immunostaining. Receiver operating characteristics (ROCs) and the Kaplan-Meier method were used to analyze the CHC level as a predictor of pathologic response to NAT and disease-specific survival (DSS), respectively. RESULTS: Patients with RAC (n = 23) and EAC (n = 34) were sampled on the day of resection, and 11 patients (32%) demonstrated a pathologic complete response (pCR) to NAT. On ROC analysis, CHC levels successfully discriminated pCR from non-pCR with an area under the curve of 0.82 (95% confidence interval [CI], 0.71-0.92; P < 0.001). Additionally, CHC levels in the EAC patients correlated with residual nodal involvement (P = 0.026) and 1-year DSS (P = 0.029). The patients with RAC who were followed longitudinally during NAT (n = 2) and hepatic arterial infusion therapy for CRLM (n = 2) had CHC levels that decreased with therapy response and increased before clinical evidence of disease progression. CONCLUSION: Circulating hybrid cells are a novel blood-based biomarker with potential for monitoring treatment response and disease progression to help guide decisions for further systemic therapy, definitive resection, and post-therapy surveillance. Additional validation studies of CHCs are warranted.

Assessing the Value of Endoscopy Simulator Modules Designed to Prepare Residents for the Fundamentals of Endoscopic Surgery Examination.

BACKGROUND: The Fundamentals of Endoscopic Surgery examination is required for all general surgery residents. The test modules are not available for practice before the examination; however, similar modules are commercially available. OBJECTIVE: This study aims to determine which modules are most valuable for resident training and preparation for the examination by evaluating which correlates best with experience level. DESIGN: This was a single-institution study. SETTING: A virtual reality endoscopy simulator was utilized. PARTICIPANTS: General surgery residents and faculty endoscopists performed endoscopy simulator modules (Endobasket 2, Endobubble 1 and 2, Mucosal Evaluation 2, and Basic Navigation) designed to prepare residents for the Fundamentals of Endoscopic Surgery examination. Residents were assigned into junior and senior groups based on the completion of a dedicated endoscopy rotation. MAIN OUTCOME MEASURES: The primary outcomes measured were the mean time to completion, mean number of balloons popped, and mean number of wall hits for the 3 groups. RESULTS: A total of 21 junior residents, 11 senior residents, and 3 faculty participated. There were significant differences among groups in the mean time to completion for the Endobasket, Endobubble, and Mucosal Evaluation modules. The modules that correlated best with experience level were Endobubble 2 and Mucosal Evaluation 2. For Endobubble 2, juniors were slower than seniors, who were in turn slower than faculty (junior 118.8 ± 20.55 seconds, senior 100.3 ± 11.78 seconds, faculty 87.67 ± 2.848 seconds; p < 0.01). Juniors popped fewer balloons than seniors, who popped fewer balloons than faculty (junior 9.441 ± 3.838, senior 15.62 ± 4.133, faculty 28.78 ± 1.712; p < 0.001). For Mucosal Evaluation 2, juniors were slower than seniors, who were in turn slower than faculty (junior 468.8 ± 123.5 seconds, senior 368.6 ± 63.42 seconds, faculty 233.1 ± 70.45 seconds; p < 0.01). LIMITATIONS: Study residents have not completed the Fundamentals of Endoscopic Surgery examinations, so correlation with examination performance is not yet possible. CONCLUSIONS: Performance on Endobasket, Endobubble, and Mucosal Evaluation correlated well with experience level, providing benchmarks for each level to attain in preparation for the Fundamentals of Endoscopic Surgery examination. See Video Abstract at http://links.lww.com/DCR/A823.

Who Undergoes Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Appendiceal Cancer? An Analysis of the National Cancer Database.

BACKGROUND: We sought to identify patterns of care for patients with appendiceal cancer and identify clinical factors associated with patient selection for multimodality treatment, including cytoreductive surgery and perioperative intraperitoneal chemotherapy (CRS/PIC). MATERIALS AND METHODS: National Cancer Database (NCDB) data from 2004 to 2014 of all diagnoses of appendiceal cancers were examined. We examined treatment modalities, as well as demographic, tumor-specific, and survival data. A multivariate logistic regression analysis was performed to determine the patient cohort most likely to receive CRS/PIC. Kaplan-Meier was used to estimate survival for all treatment groups. Significance was evaluated at P ≤ 0.05. RESULTS: We analyzed data on 18,055 patients. Nine thousand nine hundred ninety-two (55.3%) were treated with surgery only, 5848 (32.4%) received surgery and systemic chemotherapy, 1393 (7.71%) received CRS/PIC, 520 (2.88%) received chemotherapy alone, and 302 (1.67%) received neither surgery nor chemotherapy. Significant predictors of receiving CRS/PIC included male sex (OR 1.33, 95% CI: 1.11-1.59), white race (OR 2.00, 95% CI 1.40-2.86), non-Hispanic ethnicity (OR 1.92, 95% CI 1.21-3.05), private insurance (OR 1.52, 95% CI 1.26-1.84), and well-differentiated tumors (OR 4.25, CI: 3.39-5.32) (P < 0.05). Treatment with CRS/PIC was associated with a higher 5-year survival for mucinous malignancies, when compared to surgery alone (65.6% versus 62.4%, P < 0.01). Treatment with CRS/PIC was also associated with higher 5-year survival for well-differentiated malignancies, when compared to all other treatment modalities (74.9% versus 65.4%, P < 0.01). CONCLUSIONS: Patients were more likely to undergo CRS/PIC if they were male, white, privately insured, and with well-differentiated tumors. CRS/PIC was associated with improved survival in patients with mucinous and low-grade tumors.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

Travel distance influences readmissions in colorectal cancer patients-what the primary operative team needs to know.

BACKGROUND: Many colorectal cancer patients receive complex surgical care remotely. We hypothesized that their readmission rates would be adversely affected after accounting for differences in travel distance from primary/index hospital and correlate with mortality. MATERIALS AND METHODS: We identified 48,481 colorectal cancer patients in the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Travel distance was calculated, using Google Maps, and SAS. Multivariate negative binomial regression was used to identify factors associated with readmission rates. Overall survival was analyzed, using Kaplan-Meier and Cox proportional hazard. RESULTS AND CONCLUSIONS: Thirty-day readmissions occurred in 14.9% of the cohort, 27.5% of which were to a nonindex hospital. In the colon and rectal cancer cohorts, readmissions were 14.5% and 16.5%, respectively. Rectal cancer patients had an increase in readmission by 13% (incidence rate ratios [IRR] 1.13; 95% confidence interval [CI] 1.05-1.21). Factors associated with readmission were male gender, advanced disease, length of stay (LOS), discharge disposition, hospital volume, Charlson score, and poverty level (P < 0.05). Greater distance traveled increased the likelihood of readmission but did not affect mortality. Travel distance influences readmission rates but not mortality. Discharge readiness to decrease readmissions is essential for colorectal cancer patients discharged from index hospitals.

Variation in the Use of Chemoradiotherapy for Stage II and III Anal Cancer: Analysis of the National Cancer Data Base.

BACKGROUND: Treatment for anal canal cancer has evolved from radical operations to definitive chemoradiotherapy (CRT), which allows for sphincter preservation in most patients. OBJECTIVE: The aim of this study was to examine the use of CRT for patients with stage II and III anal cancer, among different patient demographics, geographic regions, and facility types. METHODS: Utilizing the National Cancer Data Base, we examined patients with stage II and III anal canal squamous cell carcinoma from 2003 to 2010. Via univariate analysis, we examined patterns of treatment by patient demographics, tumor characteristics, geographic region, and facility type (academic vs. community). A multivariable logistic regression model was built to evaluate differences in treatment patterns when adjusting by age, sex, race, comorbidities, and stage. RESULTS: A total of 12,801 patients were analyzed, of which 11,312 (88 %) received CRT. After adjusting for confounders, CRT was less likely to be administered to males [odds ratio (OR) 0.61, 95 % confidence interval (CI) 0.54-0.69], Black patients (OR 0.70, 95 % CI 0.59-0.83), and those with multiple comorbidities (OR 0.60, 95 % CI 0.51-0.72). CRT was not as widely utilized in the West (OR 0.74, 95 % CI 0.59-0.93), and patients treated in academic-based centers were less likely to receive CRT (OR 0.81, 95 % CI 0.72-0.92). Improved median overall survival was observed when CRT was utilized (p = 0.008). CONCLUSION: When controlling for age, sex, race, comorbidities, and stage, discrepancies in the use of CRT for anal cancer treatment exist between demographic subtypes, geographical regions, and facility types.

Nomogram for Predicting Overall Survival and Salvage Abdominoperineal Resection for Patients with Anal Cancer.

BACKGROUND: Anal cancer treatment has evolved from abdominoperineal resection to chemoradiotherapy, which allows for sphincter preservation. OBJECTIVE: The aim of this study was to develop an accurate model and nomogram to predict overall survival and the probability of salvage abdominoperineal resection for anal cancer patients. DESIGN: This is a retrospective cohort study. SETTINGS: Data were gathered from National Cancer Database entries from 1998 to 2010. PATIENTS: Patients with de novo anal cancer were selected from the National Cancer Database in the years 1998 through 2010; 1778 patients were included, and their data were analyzed. MAIN OUTCOME MEASURES: Variables included time to death, censoring indicator, age, race, sex, tumor size, year of diagnosis, surgery status, nodal status, TNM stage, and chemoradiation therapy. A stratified Cox proportional hazards model for overall survival and a logistic regression model for salvage abdominoperineal resection were developed. Our final models were internally validated for discrimination and validation. RESULTS: Statistically significant variables in the salvage surgery model were tumor size and nodal status (p ≤ 0.001). For overall survival model, statistically significant variables (all with p ≤ 0.005), fitted across the strata of TNM clinical stage included age, sex, tumor size, nodal status, chemoradiotherapy treatment, and combination salvage surgery and chemoradiotherapy. Nomograms that predict events are based on our final models. LIMITATIONS: Limitations included clerical database errors and nonmeasured variables, such as HIV status. CONCLUSIONS: A nomogram can predict overall survival and salvage surgery for an individual with anal cancer. Such tools may be used as decision support aids to guide therapy and predict whether or not patients may need salvage surgery.

Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.

BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. FUNDING: National Institutes of Health National Cancer Institute.

Psychiatric Illness is a Disparity in the Surgical Management of Rectal Cancer.

BACKGROUND: Psychiatric disorders are common in the US and represent a major health disparity but little is known about their impact on surgical management and outcomes in cancer. OBJECTIVE: The aim of this study was to determine whether rectal cancer patients with psychiatric diagnoses have fewer sphincter-preserving procedures and higher postoperative complications. METHODS: Overall, 23,914 patients from the Nationwide Inpatient Sample (NIS) who underwent surgery for rectal cancer from 2004 to 2011 were identified. Patients with comorbid common psychiatric diagnoses were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes. Main outcomes were measured by operation performed, length of stay (LOS), postoperative complications, and discharge disposition. RESULTS: Twenty percent of patients had a psychiatric diagnosis, with substance use being the most common psychiatric disorder (63 %). Patients with psychiatric diagnoses were more likely to be younger, White, have lower income, and have Medicaid insurance (p < 0.001) than those without. In a logistic regression model, patients with any psychiatric diagnosis were less likely to have sphincter-sparing surgery, controlling for patient sociodemographics, Charlson score, hospital procedure volume, and year (odds ratio 0.77; 95 % CI 0.72-0.83). LOS and postoperative complications were similar among the cohorts. Patients with psychiatric disorders were more likely to have home health care at discharge (p < 0.001). CONCLUSIONS: Fewer sphincter-sparing procedures were performed on rectal cancer patients with psychiatric diagnoses. However, no significant differences in postoperative complications were observed.

Molecular markers for colon diagnosis, prognosis and targeted therapy.

Colorectal adenocarcinoma (CRC), the second leading cancer-related death in the United States, remains a global public health issue. Sporadic CRC is considered the result of sequential mucosal changes from normal colonic mucosa to adenocarcinoma. Efforts in understanding the molecular pathways leading to CRC tumorigenesis may lead to identifying novel, individually tailored therapeutic targets for patients. In this review, we focus on well-published prognostic and predictive markers in CRC and examine their role in clinical practice.

Addressing the appropriateness of elective colon resection for diverticulitis: a report from the SCOAP CERTAIN collaborative.

OBJECTIVE: To assess the reported indications for elective colon resection for diverticulitis and concordance with professional guidelines. BACKGROUND: Despite modern professional guidelines recommending delay in elective colon resection beyond 2 episodes of uncomplicated diverticulitis, the incidence of elective colectomy has increased dramatically in the last 2 decades. Whether surgeons have changed their threshold for recommending a surgical intervention is unknown. In 2010, Washington State's Surgical Care and Outcomes Assessment Program initiated a benchmarking and education initiative related to the indications for colon resection. METHODS: Prospective cohort study evaluating indications from chronic complications (fistula, stricture, bleeding) or the number of previously treated diverticulitis episodes for patients undergoing elective colectomy at 1 of 49 participating hospitals (2010-2013). RESULTS: Among 2724 patients (58.7 ± 13 years; 46% men), 29.4% had a chronic complication indication (15.6% fistula, 7.4% stricture, 3.0% bleeding, 5.8% other). For the 70.5% with an episode-based indication, 39.4% had 2 or fewer episodes, 56.5% had 3 to 10 episodes, and 4.1% had more than 10 episodes. Thirty-one percent of patients failed to meet indications for either a chronic complication or 3 or more episodes. Over the 4 years, the proportion of patients with an indication of 3 or more episodes increased from 36.6% to 52.7% (P < 0.001) whereas the proportion of those who failed to meet either clinical or episode-based indications decreased from 38.4% to 26.4% (P < 0.001). The annual rate of emergency resections did not increase significantly, varying from 5.6 to 5.9 per year (P = 0.81). CONCLUSIONS: Adherence to a guideline based on 3 or more episodes for elective colectomy increased concurrently with a benchmarking and peer-to-peer messaging initiative. Improving adherence to professional guidelines related to appropriate care is critical and can be facilitated by quality improvement collaboratives.

Chemoradiotherapy with a radiation boost for anal cancer decreases the risk for salvage abdominoperineal resection: analysis from the national cancer data base.

BACKGROUND: Chemoradiotherapy (CRT), the primary treatment for anal cancer, achieves complete tumor regression in most patients. Abdominoperineal resection (APR) is reserved for persistent or recurrent disease. An additional boost dose of radiation after CRT often is used to improve the response rate for advanced local disease (T3, 4, and N+). This study examines the need for salvage APR after radiation boost. METHODS: Patients with de novo anal cancer in the National Cancer Data Base from the years 2004-2010 were analyzed. Patients with missing data points or who did not receive standard CRT were excluded. Variables included age, gender, race, primary tumor size, clinical nodal status, TNM stage, radiation boost, and APR. A logistic regression model assessing the relationship between boost radiation and APR was developed. RESULTS: Of 1,025 patients meeting inclusion criteria, 450 patients received CRT without a radiation boost and 575 patients received CRT with a radiation boost. The two groups were similar in age, gender, race, tumor size, nodal status, and TNM stage (p values all >0.05). Significant multivariate predictors of salvage APR were tumor size, negative nodal status, and boost RT (all p < 0.05), whereas gender, age, race, and TNM stage were not significant (all p > 0.05). When controlling for age, tumor size, and nodal status, salvage APR is less likely to occur after boost RT (odds ratio 0.63; 95 % confidence interval 0.47, 0.85; p = 0.003). CONCLUSIONS: When controlling for age, tumor size, and nodal status, those who received boost radiation for anal cancer were less likely to require salvage APR.

Initial surgical management of ulcerative colitis in the biologic era.

BACKGROUND: The initial minimum operation for ulcerative colitis is a total abdominal colectomy. Healthy patients may undergo proctectomy at the same time; however, for ill patients, proctectomy is delayed. Since the introduction of biologic medications in 2005, ulcerative colitis medical management has changed dramatically. OBJECTIVE: We examined how operative management for ulcerative colitis has changed from the prebiologic to biologic eras. DESIGN: We conducted a retrospective review of data on patients with ulcerative colitis who were included in the Nationwide Inpatient Sample database. SETTINGS: This study was conducted at a single university. PATIENTS: A total of 1,547,852 patients with ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were included in the study. MAIN OUTCOME MEASURES: We examined patients whose initial operation consisted of total abdominal colectomy without proctectomy versus a total proctocolectomy with or without a pouch. We also examined which operation was done at the time of the construction of an ileoanal pouch. Patients who underwent colectomy and pouch construction in the same hospitalization were compared with those who received pouch formation at a subsequent hospitalization. RESULTS: Ulcerative colitis-related admissions rose by 170% during the years examined, and the number of patients who required total abdominal colectomy increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total proctocolectomy (p < 0.001). Pouch construction at a subsequent operation increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed total proctocolectomy as the most common initial surgical intervention for ulcerative colitis. LIMITATIONS: The Nationwide Inpatient Sample is a retrospective database, and we were limited to examining the variables within it. CONCLUSIONS: Total abdominal colectomy is currently the most common initial operation for patients with ulcerative colitis, and an ileoanal pouch is more frequently constructed at a subsequent hospitalization. These trends coincide with the initiation of biologic treatments and may imply that patients are acutely ill at the time of initial operation. Alternately, there may be surgeon-perceived bias of increased surgical risk or a shift in care to specialized surgeons for pouch construction.

A virtual reality endoscopic simulator augments general surgery resident cancer education as measured by performance improvement.

Colorectal cancer is the second most common cause of death in the USA. The need for screening colonoscopies, and thus adequately trained endoscopists, particularly in rural areas, is on the rise. Recent increases in required endoscopic cases for surgical resident graduation by the Surgery Residency Review Committee (RRC) further emphasize the need for more effective endoscopic training during residency to determine if a virtual reality colonoscopy simulator enhances surgical resident endoscopic education by detecting improvement in colonoscopy skills before and after 6 weeks of formal clinical endoscopic training. We conducted a retrospective review of prospectively collected surgery resident data on an endoscopy simulator. Residents performed four different clinical scenarios on the endoscopic simulator before and after a 6-week endoscopic training course. Data were collected over a 5-year period from 94 different residents performing a total of 795 colonoscopic simulation scenarios. Main outcome measures included time to cecal intubation, "red out" time, and severity of simulated patient discomfort (mild, moderate, severe, extreme) during colonoscopy scenarios. Average time to intubation of the cecum was 6.8 min for those residents who had not undergone endoscopic training versus 4.4 min for those who had undergone endoscopic training (p < 0.001). Residents who could be compared against themselves (pre vs. post-training), cecal intubation times decreased from 7.1 to 4.3 min (p < 0.001). Post-endoscopy rotation residents caused less severe discomfort during simulated colonoscopy than pre-endoscopy rotation residents (4 vs. 10%; p = 0.004). Virtual reality endoscopic simulation is an effective tool for both augmenting surgical resident endoscopy cancer education and measuring improvement in resident performance after formal clinical endoscopic training.

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial.

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.