Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Urethral Injury and Other Urologic Injuries During Transanal Total Mesorectal Excision: An International Collaborative Study.

OBJECTIVE: To identify risk factors for urethral and urologic injuries during transanal total mesorectal excision (taTME) and evaluate outcomes. BACKGROUND: Urethral injury is a rare complication of abdominoperineal resection (APR) that has not been reported during abdominal proctectomy. The Low Rectal Cancer Development Program international taTME registry recently reported a 0.8% incidence, but actual incidence and mechanisms of injury remain largely unknown. METHODS: A retrospective analysis of taTME cases complicated by urologic injury was conducted. Patient demographics, tumor characteristics, intraoperative details, and outcomes were analyzed, along with surgeons' experience and training in taTME. Surgeons' opinion of contributing factors and best approaches to avoid injuries were evaluated. RESULTS: Thirty-four urethral, 2 ureteral, and 3 bladder injuries were reported during taTME operations performed over 7 years by 32 surgical teams. Twenty injuries occurred during the teams' first 8 taTME cases ("early experience"), whereas the remainder occurred between the 12th to 101st case. Injuries resulted in a 22% conversion rate and 8% rate of unplanned APR or Hartmann procedure. At median follow-up of 27.6 months (range, 3-85), the urethral repair complication rate was 26% with a 9% rate of failed urethral repair requiring permanent urinary diversion. In patients with successful repair, 18% reported persistent urinary dysfunction. CONCLUSIONS: Urologic injuries result in substantial morbidity. Our survey indicated that those occurring in surgeons' early experience might best be reduced by implementation of structured taTME training and proctoring, whereas those occurring later relate to case complexity and may be avoided by more stringent case selection.

Anatomical Considerations and Procedure-Specific Aspects Important in Preventing Operative Morbidity during Transanal Total Mesorectal Excision.

As transanal total mesorectal excision (taTME) becomes increasingly utilized, its technical challenges and potential pitfalls have become more clearly appreciated. This chapter explores the differences in how anatomy presents itself from the taTME vantage point as compared with traditional approaches to taTME, and how special problems unique to taTME pose a new set of operative challenges. Morbidity related, specifically, to the technique of taTME is also delineated with particular focus on male urethral injury.

A Multicenter Matched Comparison of Transanal and Robotic Total Mesorectal Excision for Mid and Low-rectal Adenocarcinoma.

OBJECTIVE: To compare the quality of surgical resection of transanal total mesorectal excision (TA-TME) and robotic total mesorectal excision (R-TME). BACKGROUND: Both TA-TME and R-TME have been advocated to improve the quality of surgery for rectal cancer below 10 cm from the anal verge, but there are little data comparing TA-TME and R-TME. METHODS: Data of patients undergoing TA-TME or R-TME for rectal cancer below 10 cm from the anal verge and a sphincter-saving procedure from 5 high-volume rectal cancer referral centers between 2011 and 2017 were obtained. Coarsened exact matching was used to create balanced cohorts of TA-TME and R-TME. The main outcome was the incidence of poor-quality surgical resection, defined as a composite measure including incomplete quality of TME, or positive circumferential resection margin (CRM) or distal resection margin (DRM). RESULTS: Out of a total of 730 patients (277 TA-TME, 453 R-TME), matched groups of 226 TA-TME and 370 R-TME patients were created. These groups were well-balanced. The mean tumor height from the anal verge was 5.6 cm (SD 2.5), and 70% received preoperative radiotherapy. The incidence of poor-quality resection was similar in both groups (TA-TME 6.9% vs R-TME 6.8%; P = 0.954). There were no differences in TME specimen quality (complete or near-complete TA-TME 99.1% vs R-TME 99.2%; P = 0.923) and CRM (5.6% vs 6.0%; P = 0.839). DRM involvement may be higher after TA-TME (1.8% vs 0.3%; P = 0.051). CONCLUSIONS: High-quality TME for patients with rectal adenocarcinoma of the mid and low rectum can be equally achieved by transanal or robotic approaches in skilled hands, but attention should be paid to the distal margin.

Radiologic Evaluation of Clinically Benign Rectal Neoplasms May Not Be Necessary Before Local Excision.

BACKGROUND: Local excision may be curative for benign and malignant rectal neoplasms. Because many early rectal cancers are discovered incidentally after local excision of clinically benign lesions, it is unclear whether preoperative imaging with transrectal ultrasound or MRI affects management. OBJECTIVE: The purpose of this study was to determine the diagnostic characteristics and effect of preoperative imaging on the incidence of malignancy in benign rectal lesions undergoing local excision. DESIGN: Prospective data from 2 institutions were included. Coarsened exact matching created a balanced cohort comparing imaging and no-imaging groups. SETTING: The study was conducted at high-volume specialist referral hospitals. PATIENTS: Adult patients undergoing local excision via transanal endoscopic surgery between 1997 and 2016 for clinically benign rectal neoplasms were included. INTERVENTION: The study intervention included preoperative imaging with transrectal ultrasound and/or MRI. MAIN OUTCOME MEASURES: We measured the incidence of malignancy and diagnostic accuracy of preoperative imaging. RESULTS: A total of 620 patients were included (272 with preoperative imaging and 348 without). There were 250 patients undergoing transrectal ultrasound, and 24 patients undergoing MRI (2 patients underwent both). Transrectal ultrasound and MRI correctly identified malignant polyps in 50% (11/22) and 44% (8/18). Overall agreement for benign versus malignant polyps between preoperative imaging and final pathology was κ = 0.30 (95% CI, 0.18-0.41) for transrectal ultrasound and 0.29 (95% CI, 0.01-0.57) for MRI. In both the overall and unmatched cohorts, the incidence of malignancy, margin involvement, and proportion of patients requiring salvage surgery was similar. LIMITATIONS: Data were obtained from 2 institutions with different equipment over a long time period. CONCLUSIONS: Preoperative imaging did not accurately identify malignancy in clinically benign rectal lesions and did not affect the incidence of malignancy, margin involvement, or proportion of patients requiring salvage surgery. Therefore, preoperative imaging may not be necessary for clinically benign lesions undergoing local excision. See Video Abstract at http://links.lww.com/DCR/A695.

Impact of colorectal surgeon case volume on outcomes and applications to quality improvement.

PURPOSE: To evaluate the impact of surgeon case volumes on procedural, financial, and clinical outcomes in colorectal surgery and apply findings to improve hospital care quality. METHODS: A retrospective review was performed using 2013-2014 administrative data from a large hospital system in Southeast U.S. region; univariate and multivariable regression analyses were used to explore the impact of surgeon case volume on outcomes. RESULTS: One thousand one hundred ninety patients were included in this 2-year study. When compared with low-volume surgeons (LVS) (< 14 cases in 2 years), the high-volume surgeons (HVS) (> 34 cases) were estimated per case to have shorter cut-to-close time in the operation room by 79 min, ([95% CI 58 to 99]), lower total hospitalization cost by $4314, ([95% CI $2261 to $6367]), and shorter post-surgery and overall length of stay by 0.92 days, ([95% CI 0.50 to 1.35]) and 1.27 days ([95% CI 0.56 to 1.98]), respectively. The HVS also showed a higher tendency to choose a laparoscopic approach over an open approach, with an odds ratio of 3.16 ([95% CI 1.23 to 8.07]). When compared with medium-volume surgeons (MVS) (14-34 cases), the HVS were estimated per case to have shorter cut-to-close time in the operation room by 62 min ([95% CI 37 to 87]). Surgeon case volumes had no statistically significant impact on outcomes including in-hospital mortality, 30-day readmission, blood utilization, and surgical site infection (SSI). CONCLUSIONS: Surgeon case volume had positive impacts on procedural, financial, and clinical outcomes and this finding may be used to improve hospital's quality of care.

Outcomes of Closed Versus Open Defects After Local Excision of Rectal Neoplasms: A Multi-institutional Matched Analysis.

BACKGROUND: The management of the rectal wall defect after local excision of rectal neoplasms remains controversial, and the existing data are equivocal. OBJECTIVE: This study aimed to determine the effect of open versus closed defects on postoperative outcomes after local excision of rectal neoplasms. DESIGN: Data from 3 institutions were analyzed. Propensity score matching was performed in one-to-one fashion to create a balanced cohort comparing open and closed defects. SETTINGS: This study was conducted at high-volume specialist referral hospitals. PATIENTS: Adult patients undergoing local excision via transanal endoscopic surgery from 2004 to 2016 were included. Patients were assigned to open- and closed-defect groups, and further stratified by full- or partial-thickness excision. INTERVENTION: Closure of the rectal wall defect was performed at the surgeon's discretion. MAIN OUTCOME MEASURES: The primary outcome measured was the incidence of 30-day complications. RESULTS: A total of 991 patients were eligible (593 full-thickness excision with 114 open and 479 closed, and 398 partial-thickness excision with 263 open and 135 closed). After matching, balanced cohorts consisting of 220 patients with full-thickness excision and 210 patients with partial-thickness excision were created. Operative time was similar for open and closed defects for both full-and partial-thickness excision. The incidence of 30-day complications was similar for open and closed defects after full- (15% vs. 12%, p = 0.432) and partial-thickness excision (7% vs 5%, p = 0.552). The total number of complications was also similar after full- or partial-thickness excision. Patients undergoing full-thickness excision with open defects had a higher incidence of clinically significant bleeding complications (9% vs 3%, p = 0.045). LIMITATIONS: Data were obtained from 3 institutions with different equipment and perioperative management over a long time period. CONCLUSIONS: There was no difference in overall complications between open and closed defects for patients undergoing local excision of rectal neoplasms, but there may be more bleeding complications in open defects after full-thickness excision. A selective approach to defect closure may be appropriate. See Video Abstract at http://links.lww.com/DCR/A470.

Establishing the learning curve of transanal minimally invasive surgery for local excision of rectal neoplasms.

INTRODUCTION: Transanal minimally invasive surgery (TAMIS) is an endoscopic operating platform for local excision of rectal neoplasms. However, it may be technically demanding, and its learning curve has yet to be adequately defined. The objective of this study was to determine the number of TAMIS procedures for the local excision of rectal neoplasm required to reach proficiency. METHODS AND PROCEDURES: All TAMIS cases performed from 07/2009 to 12/2016 at a single high-volume tertiary care institution for local excision of benign and malignant rectal neoplasia were identified from a prospective database. A cumulative summation (CUSUM) analysis was performed to determine the number of cases required to reach proficiency. The main proficiency outcome was rate of margin positivity (R1 resection). The acceptable and unacceptable R1 rates were defined as the R1 rate of transanal endoscopic microsurgery (TEM-10%) and traditional transanal excision (TAE-26%), which was obtained from previously published meta-analyses. Comparisons of patient, tumor, and operative characteristics before and after TAMIS proficiency were performed. RESULTS: A total of 254 TAMIS procedures were included in this study. The overall R1 resection rate was 7%. The indication for TAMIS was malignancy in 57%. CUSUM analysis reported that TAMIS reached an acceptable R1 rate between 14 and 24 cases. Moving average plots also showed that the mean operative times stabilized by proficiency gain. The mean lesion size was larger after proficiency gain (3.0 cm (SD 1.5) vs. 2.3 cm (SD 1.3), p = 0.008). All other patient, tumor, and operative characteristics were similar before and after proficiency gain. CONCLUSIONS: TAMIS for local excision of rectal neoplasms is a complex procedure that requires a minimum of 14-24 cases to reach an acceptable R1 resection rate and lower operative duration.

Transanal Minimally Invasive Surgery for Local Excision of Benign and Malignant Rectal Neoplasia: Outcomes From 200 Consecutive Cases With Midterm Follow Up.

OBJECTIVE: This study describes the outcomes for 200 consecutive transanal minimally invasive surgery (TAMIS) local excision (LE) for rectal neoplasia. BACKGROUND: TAMIS is an advanced transanal platform that can result in high quality LE of rectal neoplasia. METHODS: Consecutive patients from July 1, 2009 to December 31, 2015 from a prospective institutional registry were analyzed. Indication for TAMIS LE was endoscopically unresectable benign lesions or histologically favorable early rectal cancers. The primary endpoints were resection quality, neoplasia recurrence, and oncologic outcomes. Kaplan-Meier survival analyses were used to describe disease-free survival (DFS) for patients with rectal adenocarcinoma that did not receive immediate salvage radical surgery. RESULTS: There were 200 elective TAMIS LE procedures performed in 196 patients for 90 benign and 110 malignant lesions. Overall, a 7% margin positivity and 5% fragmentation rate was observed. The mean operative time for TAMIS was 69.5 minutes (SD 37.9). Postoperative morbidity was recorded in 11% of patients, with hemorrhage (9%), urinary retention (4%), and scrotal or subcutaneous emphysema (3%) being the most common. The mean follow up was 14.4 months (SD 17.4). Local recurrence occurred in 6%, and distant organ metastasis was noted in 2%. Mean time to local recurrence for malignancy was 16.9 months (SD 13.2). Cumulative DFS for patients with rectal adenocarcinoma was 96%, 93%, and 84% at 1-, 2-, and 3-years. CONCLUSIONS: For carefully selected patients, TAMIS for local excision of rectal neoplasia is a valid option with low morbidity that maintains the advantages of organ preservation.

Uptake of Transanal Total Mesorectal Excision in North America: Initial Assessment of a Structured Training Program and the Experience of Delegate Surgeons.

BACKGROUND: Transanal total mesorectal excision is a new approach to curative-intent rectal cancer surgery. Training and surgeon experience with this approach has not been assessed previously in America. OBJECTIVE: The purpose of this study was to characterize a structured training program and to determine the experience of delegate surgeons. DESIGN: Data were assimilated from an anonymous, online survey delivered to attendees on course completion. Data on surgeon performance during hands-on cadaveric dissection were collected prospectively. SETTINGS: This study was conducted at a single tertiary colorectal surgery referral center, and cadaveric hands-on training was conducted at a specialized surgeon education center. MAIN OUTCOME MEASURES: The main outcome measurement was the use of the course and surgeon experience posttraining. RESULTS: During a 12-month period, eight 2-day transanal total mesorectal excision courses were conducted. Eighty-one colorectal surgeons successfully completed the course. During cadaveric dissection, 71% achieved a complete (Quirke 3) specimen; 26% were near complete (Quirke 2), and 3% were incomplete (Quirke 1). A total of 9.1% demonstrated dissection in the incorrect plane, whereas 4.5% created major injury to the rectum or surrounding structures, excluding the prostate. Thirty eight (46.9%) of 81 surgeon delegates responded to an online survey. Of survey respondents, 94.6% believed training should be required before performing transanal total mesorectal excision. Posttraining, 94.3% of surgeon delegates planned to use transanal total mesorectal excision for distal-third rectal cancers, 74.3% for middle-third cancers, and 8.6% for proximal-third cancers. The most significant complication reported was urethral injury; 5 were reported by the subset of survey respondents who had performed this operation postcourse. LIMITATIONS: The study was limited by inherent reporting bias, including observer and recall biases. CONCLUSIONS: Although this structured training program for transanal total mesorectal excision was found to be useful by the majority of respondents, the risk of iatrogenic injury after training remains high, suggesting that this training pedagogy alone is insufficient. See Video Abstract at http://links.lww.com/DCR/A335.

Quality of Local Excision for Rectal Neoplasms Using Transanal Endoscopic Microsurgery Versus Transanal Minimally Invasive Surgery: A Multi-institutional Matched Analysis.

BACKGROUND: There are no data comparing the quality of local excision of rectal neoplasms using transanal endoscopic microsurgery and transanal minimally invasive surgery. OBJECTIVE: The purpose of this study was to compare the incidence of tumor fragmentation and positive margins for patients undergoing local excision of benign and malignant rectal neoplasms using transanal endoscopic microsurgery versus transanal minimally invasive surgery. DESIGN: This was a multi-institutional cohort study using coarsened exact matching. SETTINGS: The study was conducted at high-volume tertiary institutions with specialist colorectal surgeons. PATIENTS: Patients undergoing full-thickness local excision for benign and malignant rectal neoplasms were included. INTERVENTIONS: Transanal endoscopic microsurgery and transanal minimally invasive surgery were the included interventions. MAIN OUTCOME MEASURES: The incidence of poor quality excision (composite measure including tumor fragmentation and/or positive resection margin) was measured. RESULTS: The matched cohort consisted of 428 patients (247 with transanal endoscopic microsurgery and 181 with transanal minimally invasive surgery). Transanal minimally invasive surgery was associated with shorter operative time and length of stay. Poor quality excision was similar (8% vs 11%; p = 0.233). There were also no differences in peritoneal violation (3% vs 3%; p = 0.965) and postoperative complications (11% vs 9%; p = 0.477). Cumulative 5-year disease-free survival for patients undergoing transanal endoscopic microsurgery was 80% compared with 78% for patients undergoing transanal minimally invasive surgery (log rank p = 0.824). The incidence of local recurrence for patients with malignancy who did not undergo immediate salvage surgery was 7% (8/117) for transanal endoscopic microsurgery and 7% (7/94) for transanal minimally invasive surgery (p = 0.864). LIMITATIONS: All of the procedures were also performed at high-volume referral centers by specialist colorectal surgeons with slightly differing perioperative practices and different time periods. CONCLUSIONS: High-quality local excision for benign and rectal neoplasms can be equally achieved using transanal endoscopic microsurgery or transanal minimally invasive surgery. The choice of operating platform for local excisions of rectal neoplasms should be based on surgeon preference, availability, and cost. See Video Abstract at http://links.lww.com/DCR/A382.

Chemoradiation and Local Excision for T2N0 Rectal Cancer Offers Equivalent Overall Survival Compared to Standard Resection: a National Cancer Database Analysis.

BACKGROUND: Local excision (LE) alone is associated with worse survival compared to radical surgery (RS) for T2 rectal cancer, but LE with additional chemoradiation (CRT) may improve outcomes. The objective of this study was to compare combined CRT and LE versus RS for T2 rectal cancer. METHODS: The 2004-2014 National Cancer Database was queried for patients with T2N0M0 rectal cancer undergoing LE with neoadjuvant(NA-CRT + LE) or adjuvant(LE + Adj-CRT) CRT, or RS. The main outcome was 5-year overall survival (OS). Cox proportional hazards was used to determine the independent effect of treatment on OS. RESULTS: A total of 4822 patients were included (4367 RS, 242 CRT + LE, 213 LE + Adj-CRT). Mean follow-up was 48.6 (SD28.5) months. There were no differences in patient characteristics, but more high-risk features in the LE + Adj-CRT group. There were no differences in 90-day mortality. Five-year OS was similar (RS 77.4% vs. CRT + LE 76.1% vs. LE + Adj-CRT 79.7%, p = 0.786). Older age, male gender, and higher Charlson score were independently associated with worse OS, whereas treatment type was not. If 90-day mortality was excluded, LE + Adj-CRT was independently associated with worse OS compared to RS. CONCLUSIONS: CRT with LE for T2N0M0 rectal cancer was not associated with worse OS compared to RS, and may be a viable treatment modality.

Stereotactic navigation for TAMIS-TME.

Stereotactic navigation allows for real-time, image-guided surgery, thus providing an augmented working environment for the operator. This technique can be applied to complex minimally invasive surgery for fixed anatomic targets. Transanal minimally invasive surgery represents a new approach to rectal cancer surgery that is technically demanding and introduces the potential for procedure-specific morbidity. Feasibility of stereotactic navigation for TAMIS-TME has been demonstrated, and this could theoretically translate into improved resection quality by improving the surgeon's spatial awareness. The future of minimally invasive surgery as it relates to augmented reality and image-guided surgery is discussed.