The role of endoscopic evaluation for radiation proctitis in patients receiving intermediate-dose postoperative radiotherapy for rectal cancer.

OBJECTIVES: High-dose pelvic radiotherapy (RT) is known to be associated with chronic radiation proctitis (RP). However, the effects of intermediate radiation doses are unknown. We assessed the incidence of late clinical RP among patients with rectal cancer receiving intermediate-dose postoperative RT, as well as the role of early endoscopic abnormalities in predicting RP development. METHODS: We retrospectively reviewed 153 patients with rectal cancer who received postoperative RT at a median dose of 54 Gy between 2005 and 2009 and who underwent endoscopic examination within 12 months thereafter. Endoscopic RP was assessed using the Vienna rectoscopy score (VRS). Late clinical RP toxicity was evaluated, as was its correlation with endoscopic RP. RESULTS: All patients underwent an endoscopic examination at a median of 9 months after postoperative pelvic RT. Endoscopic RP was detected in 45 patients (29.4%); the predominant patterns were telangiectasia and congested mucosa. During the median 88-month follow-up period, 29 patients (19.0%) experienced late clinical RP; only 3 (2.0%) had Grade 3 or above. The VRS predicted the development of late clinical RP as well as its cumulative incidence (P < 0.001). Endoscopic evidence of telangiectasia was significantly associated with the development of late clinical RP (P < 0.001). CONCLUSIONS: Early endoscopic findings using VRS are useful for predicting the possibility of late clinical RP, although the incidences of severe cases were low. Patients with endoscopic abnormalities should be followed closely owing to their susceptibility to clinical RP.

The magnetic resonance imaging-based approach for identification of high-risk patients with upper rectal cancer.

OBJECTIVE: To assess the efficacy of preoperative magnetic resonance imaging (MRI) in identifying upper rectal cancer patients who are at high risk for local recurrence. METHODS: 110 upper rectal cancer patients with locally advanced (pT3-4N0 or pTanyN+) tumors treated with tumor-specific mesorectal excision and no adjuvant radiotherapy were identified from an institutional database at a large academic medical center in Korea. Information on the extent of mesorectal invasion, sacral-side involvement was collected from preoperative MRI. RESULTS: At a median follow-up of 47 months, 5 patients (4.5%) experienced local recurrence (LR). LR rates for patients with intermediate risk (T1-2/N1, T3N0), moderately high risk (T1-2/N2, T3N1, T4N0), and high risk (T3N2, T4/N1-2) were 3%, 4.8%, and 8.7%, respectively. Patients who did not have sacral-side involvement or mesorectal invasion of 5 mm or less did not experience LR. The patients with sacral-side involvement and intermediate risk, moderately high risk, and high risk had an LR rate of 4.2%, 5.6%, and 10%, respectively, or 11.1%, 33.3%, and 18.2%, respectively, when combined with those with mesorectal invasion of greater than 5 mm. Multivariate analyses demonstrated the presence of both sacral-side location and mesorectal invasion of greater than 5 mm was significantly associated with adverse disease-free and overall survival (P < 0.05). CONCLUSIONS: Patients with mesorectal invasion of greater than 5 mm and sacral-side involvement identified on MRI were at an increased risk of local recurrence. The detection of these features on MRI provides prognostic information that is not available in conventional risk classification systems. Improved identification of a high-risk subset of upper rectal cancer patients may guide indications for preoperative chemoradiotherapy in this subset.

Preoperative chemoradiotherapy effects on anastomotic leakage after rectal cancer resection: a propensity score matching analysis.

OBJECTIVE: To assess the effects of preoperative chemoradiotherapy (CRT) on anastomotic leakage (AL) after rectal cancer resection, using propensity score matching. BACKGROUND: Conflicting data have emerged over the last decade regarding the effect of preoperative CRT on AL. METHODS: We reviewed 1437 consecutive patients with rectal cancer who underwent low anterior resection (LAR) at our institution between 2005 and 2012. AL evaluated as grade C was the primary endpoint, as proposed by the International Study Group of Rectal Cancer in 2010. The patients were treated with (n = 360) or without (n = 1077) preoperative CRT. The total radiation dose was 50.4 Gy in 28 fractions. Multivariate and propensity score matching analyses were used to compensate for the differences in some baseline characteristics. RESULTS: The preoperative CRT group contained more patients with the following characteristics, older age, male sex, smoker, advanced stage tumor, lower/mid rectal tumor location, ultra-LAR, and diverting stoma, than the non-preoperative CRT group (all Ps < 0.05). Postoperative AL occurred in 91 patients (6.3%). Before propensity score matching, the incidence of AL in patients with or without preoperative CRT was 7.5% and 5.9%, respectively (P = 0.293). After propensity score matching, the 2 groups were nearly balanced except for the initial stage and the length of the surgeon's career, and the incidence of AL in patients with or without preoperative CRT was 7.5% and 8.1%, respectively (P = 0.781). CONCLUSIONS: We did not observe that preoperative CRT increased the risk of postoperative AL after LAR in patients with rectal cancer, using propensity score matching analysis.

The role of primary colectomy after successful endoscopic stenting in patients with obstructive metastatic colorectal cancer.

BACKGROUND: Although the initial clinical efficacy of self-expandable metal stents is acceptable, doubt still remains about long-term clinical outcomes and complications. OBJECTIVE: The aim of this study was to evaluate the stoma formation rate and risk factors for complications after successful stenting in patients with obstructive metastatic colorectal cancer. DESIGN: This was a tertiary-care center retrospective study. PATIENTS: From January 2000 to December 2010, 130 patients with unresectable obstructive colorectal cancer received successful self-expandable metal stent placement. Among them, 14 patients received primary colectomy after successful stenting. INTERVENTIONS: Self-expandable metal stent placement and primary colectomy were performed. MAIN OUTCOME MEASURES: The stoma formation rate and complications were measured. RESULTS: In patients with successful stenting, stoma formation rates at 1 and 2 years were 15.6% (95% CI, 8.74-22.4) and 24.4% (95% CI, 13.8-35.0), and the median patency duration was 157 days (range, 2-1590 days). However, long-term complications occurred in 58 patients (44.6%), including reobstruction (32.6%), stent migration (10.3%), and perforation (7.8%), and a large number of reinterventions (45.7%) and hospitalizations (37/9%) were needed to manage complications. In multivariate analysis, primary colectomy after successful endoscopic stenting was a negative predictive factor for reobstruction (OR, 0.12; 95% CI, 0.02-0.99; p = 0.04). LIMITATIONS: This was a retrospective, single-center study. CONCLUSIONS: To reduce stent-related late complications, primary colectomy after successful endoscopic stenting could be a therapeutic option in patients who have unresectable colorectal cancer with obstruction, especially in those who expect long-term survival.

Oncologic outcomes and perioperative clinicopathologic results after robot-assisted tumor-specific mesorectal excision for rectal cancer.

BACKGROUND: Robot-assisted surgery is a new and emerging surgical procedure for rectal cancer patients. However, there is a lack of information regarding oncologic outcomes for this procedure. We aimed to evaluate oncologic and perioperative clinicopathologic outcomes of surgical resection using robotic instruments for rectal cancer. METHODS: Data from rectal cancer patients (n = 370) diagnosed with stage I-IV disease sited below 15 cm from the anal verge who underwent robot-assisted tumor-specific mesorectal excision consecutively from June 2006 to December 2010 were evaluated. Clinicopathologic and follow-up data were recorded prospectively and analyzed retrospectively. Perioperative clinicopathologic outcomes, postoperative complications, 3-year overall survival rate, and 3-year disease-free survival rate were analyzed. RESULTS: All patients underwent robot-assisted tumor-specific mesorectal excision. Of all postoperative pathologic stages, 15 (4.1 %) were stage 0 (pathologic complete remission), 126 (34.1 %) stage I, 95 (25.7 %) stage II, 118 (31.9 %) stage III, and 16 (4.3 %) stage IV. The 3-year overall survival rate was 93.1 % (pathologic complete remission = 100 %, stage I = 99.2 %, stage II = 97.1 %, stage III = 90.1 %, and stage IV = 48.4 %). The 3-year disease-free survival rate was 79.2 % (pathologic complete remission = 100 %, stage I = 93.7 %, stage II = 79.8 %, stage III = 69.6 %, and stage IV = 0.0 %). The 3-year cumulative local recurrence rate was 3.6 % (n = 10). The circumferential resection margin positive rate was 5.7 % (n = 21). Local recurrence developed in one patient and systemic recurrence developed in five patients. The total number of patients with postoperative complications was 86 (23.2 %). CONCLUSIONS: These data show the feasibility and safety of robot-assisted tumor-specific mesorectal excision for rectal cancer in terms of oncologic outcomes.

Prognostic value of mucinous histology depends on microsatellite instability status in patients with stage III colon cancer treated with adjuvant FOLFOX chemotherapy: a retrospective cohort study.

BACKGROUND: The close association between mucinous histology and microsatellite instability (MSI) may have hindered the evaluation of prognostic significance of mucinous histology. The aim of this retrospective study was to investigate whether mucinous histology was associated with a worse prognosis, independent of MSI status, compared to nonmucinous histology in patients with stage III colon cancer. METHODS: This study enrolled 394 consecutive patients with stage III colorectal cancer treated with adjuvant FOLFOX after curative resection (R0). Clinicopathological information was retrospectively reviewed. Tumors were analyzed for MSI by polymerase chain reaction to determine MSI status. Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models were used. RESULTS: The estimated rate of 3-year disease-free survival (DFS) in patients with nonmucinous adenocarcinoma (NMA 79.2 %) was significantly greater than that in patients with mucinous adenocarcinoma (MA) and adenocarcinoma with mucinous component (MC) (56.9 %; log-rank, P = 0.002). In univariate analysis, histology (NMA vs. MA/MC), American Joint Committee on Cancer stage (IIIA, IIIB, and IIIC), and lymphovascular invasion (present vs. absent) were significantly associated with DFS. In multivariate analysis, mucinous histology (MA/MC) was associated with decreased DFS in all patients (hazard ratio 1.82, 95 % confidence interval 1.03-3.23, P = 0.0403). In patients with MA/MC, no difference in DFS was observed between MSI and microsatellite stability (log-rank, P = 0.732). CONCLUSIONS: Mucinous histology is an independent poor prognostic factor for DFS in patients with stage III colon cancer after adjuvant FOLFOX chemotherapy.

Long-term outcome of palliative therapy for malignant colorectal obstruction in patients with unresectable metastatic colorectal cancers: endoscopic stenting versus surgery.

BACKGROUND: Self-expandable metal stents (SEMSs) provide a promising alternative for initial palliation of malignant bowel obstruction. However, data on the long-term outcomes of SEMSs are limited. OBJECTIVE: The aim of this study was to compare the long-term outcomes of endoscopic stenting with those of surgery for palliation in patients with incurable obstructive colorectal cancer. DESIGNS AND SETTING: A retrospective study. PATIENTS: From January 2000 to December 2008, patients with incurable obstructive colorectal cancer who were treated with SEMSs (n = 71) or palliative surgery (n = 73) were reviewed. INTERVENTIONS: SEMS placement by using through-the-endoscope methods or surgery. MAIN OUTCOME MEASUREMENTS: Success rates and complication rates. RESULTS: Early success rates in the SEMS group and those in the surgery group were not different (95.8% vs 100%, P = .12), and the SEMS group had fewer early complications than the surgery group (15.5% vs 32.9%, P = .015). Although the patency duration of the first stent in the SEMS group was shorter than that in the surgery group (P < .001), the median patency duration after a second stenting was comparable to that of the surgery group (P = .239). There were more late complications in the SEMS group than in the surgery group (P = .028), but the rates of major complications did not differ between the 2 groups (P = .074). LIMITATIONS: Retrospective and single-center study. CONCLUSIONS: SEMSs were not only an effective and acceptable therapy for initial palliation of malignant colorectal obstruction, but they also showed long-term efficacy comparable to that with surgery.

Mapping of lateral pelvic lymph node recurrences in rectal cancer: a radiation oncologist's perspective.

PURPOSE: Patterns of locoregional rectal cancer recurrences following total mesorectal excision (TME) were analyzed to define the irradiation volume, especially the lateral pelvic lymph node (LPLN). MATERIALS AND METHODS: Of 1243 patients who underwent TME without pelvic radiotherapy between 2005 and 2012, the data of 826 patients with rectal adenocarcinoma without distant metastases were analyzed for relapse patterns, categorized as distant and locoregional (anastomosis, mesorectum, presacral area, and LPLNs) failure. RESULTS: The median follow-up was 61.8 months. The 5-year local recurrence-free, distant metastasis-free, overall survival rates were 88, 82, and 89%, respectively. Relapse occurred in 108 (13%) patients: 90 (11%) had distant and 28 (3%) had locoregional failure. Eight patients had LPLN recurrence: the 2 recurrences from upper rectal cancers occurred near the bifurcation of the common iliac artery into the external and internal iliac vessels; the 6 mid-lower rectal cancers had 16 recurrences near the internal iliac and obturator arteries-five occurred anterior to the obturator artery and posterior to the external iliac artery, superior to the femoral head. LPLN recurrence was associated with pN2 stage, perinodal extension, and lymphovascular invasion. CONCLUSION: The LPLN component of pre- or postoperative irradiation volumes could potentially be optimized based on our mapping data. However, since patients in our institution at high risk for relapse received either preoperative or postoperative chemoradiation, further analyses are needed to confirm our findings.

Reduced pelvic field sparing anastomosis for postoperative radiotherapy in selected patients with mid-upper rectal cancer.

The aim of this study was to report the clinical results of reduced pelvic field radiotherapy (RT), excluding the anastomotic site, after total mesorectal excision in selected patients with rectal cancer. Between 2011 and 2014, 99 patients underwent upfront surgery for clinically less-advanced tumors but were finally diagnosed as pT3/N+. Among them, 50 patients with mid-upper rectal cancer who received postoperative RT with a reduced pelvic field were included in this retrospective review. This group was composed of patients with high seated tumors, complete resection with a clear circumferential resection margin, and no complication during surgery. We investigated treatment outcomes, toxicity and the effect of RT-field reduction on organs-at risk in 5 randomly selected patients. During the median follow-up period of 42 months (range: 15-59 months), tumors recurred in 9 patients (18%). The 3-year overall and disease-free survival were 98% and 81%, respectively. Distant metastasis was the dominant failure pattern (n = 8, 16%), while no recurrences occurred at or near anastomotic sites. No anastomotic complications were found on pelvic examination, images and/or colonoscopy. Reported acute and late RT-related toxicities were mostly mild to moderate, with only small numbers of Grade 3 toxicities. None of the patients developed Grade 4-5 acute or late toxicity. With a caudally reduced field, 64% reduction in absolute anastomotic exposure at the maximum dose was achieved compared with the traditional whole-pelvic field (P = 0.008). The reduced pelvic field RT was able to minimize late anastomotic complication without increasing its recurrence in selected patients with mid-upper rectal cancer in the postoperative setting.

Long-term oncologic outcomes of laparoscopic right hemicolectomy during the learning curve period: comparative study with cases after the learning curve period.

BACKGROUND: This study aimed to assess the learning curve in laparoscopic right hemicolectomy and compare the long-term oncologic outcomes of the learning curve period. MATERIALS AND METHODS: We retrospectively reviewed 97 patients who underwent a laparoscopic right hemicolectomy by a single surgeon between July 2006 and January 2009. Among them, 87 patients, excluding patients with stage IV (n=10) disease, were evaluated for long-term oncologic outcomes. They were divided into 2 phases: phase 1 (the learning curve period) and phase 2 (the expert period). The cumulative sum method was used for estimating the learning curve. RESULTS: The learning curve was determined at the 42nd case. Patient characteristics and postoperative clinicopathologic outcomes were similar in both groups except for the operation time (212.5±65.0 min vs. 146.4±37.1 min; P<0.001) and length of stay (10.7±5.4 d vs. 8.4±2.9 d; P=0.015). The 5-year overall survival rates were similar in both groups throughout all stages. The 5-year disease-free survival rate of stage III disease in phase 2 (85%) was better than that of phase 1 (53.3%; P=0.046). CONCLUSIONS: Laparoscopic right hemicolectomy during the learning curve period showed acceptable clinicopathologic outcomes. However, the 5-year disease-free survival rate was compromised in patients with stage III disease in phase I.

The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. METHODS: PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. RESULTS: Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). CONCLUSION: These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours.