Clinical outcomes of endoscopic submucosal dissection for colorectal tumors: a large multicenter retrospective study from the Hiroshima GI Endoscopy Research Group.

BACKGROUND AND AIMS: Although advanced high-volume centers have reported good outcomes of colorectal endoscopic submucosal dissection (ESD), a limited number of highly skilled experts in specialized institutions performed these procedures. We undertook a retrospective multicenter survey, which included nonspecialized hospitals, to investigate the clinical outcomes of colorectal ESD. METHODS: We recruited 1233 consecutive patients with 1259 colorectal tumors resected by ESD at 12 institutions. We evaluated the en bloc resection rate, histologic complete resection rate, curative (R0) resection rate, adverse events, and the long-term prognoses, including local recurrence, metachronous tumor development, and survival rate. RESULTS: The en bloc, histologic complete, and R0 resection rates were 92.6%, 87.4%, and 83.7%, respectively. The delayed bleeding, intraoperative perforation, and delayed perforation rates were 3.7%, 3.4%, and .4%, respectively. The long-term outcomes analysis included 1091 patients (88.4%). Local recurrences occurred in 1.7%, and metachronous tumors (>5 mm) developed in 11.0% of the patients. The 3- and 5-year overall survival rates were 95.1% and 92.3%, respectively. The number of colonic tumors, severe submucosal fibrosis, and en bloc resection rates were significantly higher in the high-volume centers (Group H) than those in the low-volume centers (Group L). The average tumor size in Group H was significantly larger than that in Group L. CONCLUSIONS: Colorectal ESDs are feasible, have acceptable adverse event risks, and favorable long-term prognoses. (Clinical trial registration number: UMIN000016197.).

Predictors of incomplete resection and perforation associated with endoscopic submucosal dissection for colorectal tumors.

BACKGROUND AND OBJECTIVE: Colorectal endoscopic submucosal dissection (ESD) is technically challenging. Our aim was to identify predictors of incomplete resection and perforation in colorectal ESD. DESIGN: Retrospective study. SETTING: Academic Japanese endoscopy unit. PATIENTS AND MAIN OUTCOME MEASUREMENTS: A total of 267 consecutive cases of colorectal tumors treated by ESD from May 2010 to February 2013 were analyzed. Predictors of incomplete resection and perforation, including lesion size, growth type, pathological diagnosis, use of hemostatic forceps, degree of fibrosis, history of biopsy, history of local endoscopic treatment, and endoscopic operability. RESULTS: The incomplete resection rate was 4.1%. The perforation rate was 5.6%. Univariate analysis identified severe fibrosis (P = .032), submucosal (SM) deep (>1000 µm) invasion (P = .033) and poor endoscopic operability (P = .030) as predictors of incomplete resection, and severe fibrosis (P = .038), postendoscopic treatment (P = .016), and poor endoscopic operability (P = .012) as predictors of perforation. Multivariate analysis identified poor endoscopic operability and SM deep invasion as independent predictors of incomplete resection, and poor endoscopic operability and severe fibrosis as independent predictors of perforation. There was no adjustment of P values for multiple testing. LIMITATION: A single-center study by a single colonoscopist. All statistical results should be taken as descriptive only. CONCLUSIONS: Poor endoscopic operability and SM deep invasion were significant independent predictors of incomplete resections. Poor endoscopic operability and severe fibrosis were significant independent predictors of perforation. These features may provide helpful information when planning colorectal ESD.

Risk factors for delayed bleeding after endoscopic submucosal dissection for colorectal neoplasms.

PURPOSE: Although delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) for colorectal neoplasms, few reports have assessed the risk factors for delayed bleeding after colorectal ESD. METHODS: This study included 363 consecutive patients in whom 377 colorectal neoplasms were resected using ESD between April 2006 and August 2012. We classified patients and lesions into two groups on the basis of presence or absence of delayed bleeding and retrospectively compared the clinicopathological characteristics and clinical outcomes of ESD between the two groups. RESULTS: Delayed bleeding occurred in 25 (6.6 %) of 377 lesions, and all cases of delayed bleeding were successfully controlled by endoscopic procedures. With respect to patient-related factors, there was no significant difference between the groups in mean age, sex ratio, and current use of antithrombotic agents. With respect to lesion-related factors, there was no significant difference between the groups in mean lesion size, growth pattern, and mean procedure time (p = 0.6). Lesions located in the rectum (vs colon, p = 0.0005) and lesions with severe submucosal fibrosis (vs no or mild fibrosis, p = 0.022) were significantly related to delayed bleeding. Upon multivariate analysis, lesions located in the rectum (vs colon, odds ratio 4.19; p = 0.0009) were significantly related to delayed bleeding after colorectal ESD. CONCLUSIONS: This study demonstrated that location of lesions in the rectum was a significant independent risk factor for delayed bleeding after ESD for colorectal neoplasms.

Condition of muscularis mucosae is a risk factor for lymph node metastasis in T1 colorectal carcinoma.

BACKGROUND: The Japanese Society for Cancer of the Colon and Rectum Guidelines for the Treatment of Colorectal Cancer 2010 state that curable T1 colorectal carcinoma (CRC) after endoscopic resection shows favorable histologic grade, absence of vessel involvement, submucosal invasion depth of <1,000 µm, and low-grade tumor budding. METHODS: We evaluated 322 consecutive T1 CRCs with LN dissection between January 1993 and March 2012. According to the muscularis mucosae condition, CRCs were classified into three groups: type A, clearly identified; type B, incompletely disrupted with deformity; or type C, completely disrupted. We examined the relationship between the muscularis mucosae condition, clinicopathological findings, and lymph node (LN) metastasis. RESULTS: The overall incidence of LN metastasis was 11.8 % (38/322): 0 % (0/46) for the type A group, 7.2 % (7/97) for the type B group, and 17.3 % (31/179) for the type C group. In univariate analysis of type B and C groups, unfavorable histologic grade, submucosal invasion of ≥1,000 µm, positive lymphatic invasion, high-grade tumor budding, and the type C group were associated with a significantly higher incidence of LN metastasis. In multivariate analysis, high-grade tumor budding (P < 0.001, odds ratio [OR] = 4.86), unfavorable histologic grade (P = 0.026, OR = 4.83), positive lymphatic invasion (P < 0.001, OR = 4.17), and the type C group (P = 0.012, OR = 3.38) were significantly associated with LN metastasis. The type C group showed a high incidence of moderate/severe lymphatic invasion. CONCLUSIONS: The condition of the muscularis mucosae was an indicator of LN metastasis in T1 CRC.

Risk factors for vertical incomplete resection in endoscopic submucosal dissection as total excisional biopsy for submucosal invasive colorectal carcinoma.

PURPOSE: Endoscopic submucosal dissection (ESD) for colorectal tumor is a minimally invasive treatment. Histologic information obtained from the entire ESD specimen is important for therapy selection in submucosal invasive colorectal carcinoma (SMca). This study aimed to identify risk factors for vertical incomplete resection (vertical margin-positive [VM+]) when ESD was performed as total excisional biopsy for SMca. METHODS: From June 2003 through December 2011, 78 SMca cases were resected by ESD at Hiroshima University Hospital. Patient and tumor characteristics, intraoperative variables, and histopathology were compared between the VM+ group and the vertical complete resection (vertical margin-negative) group. The ability of magnifying endoscopy (ME) and endoscopic ultrasonography (EUS) to predict VM+ was assessed. RESULTS: ESD resulted in VM+ in eight cases (10.3 %), with a greater percentage invading to a depth of ≥2,000 vs. <2,000 µm (P = 0.047). Severe submucosal fibrosis was found in five of the eight cases (62.5 %, P = 0.017). Poor differentiation was seen at the deepest invasive portion in six cases (75.0 %), and two of six cases had an invasion depth <2,000 µm. Of 39 EUS cases, 36 not showing deep invasion close to the muscularis propria were completely resected by ESD. CONCLUSIONS: Submucosal fibrosis and poor differentiation at the deepest invasive portion may be risk factors for VM+ in colorectal ESD for tumors with submucosal deep invasion. ME plus EUS is more likely to help determine whether ESD is indicated as complete total excisional biopsy for SMca.

Characteristic magnifying narrow-band imaging features of colorectal tumors in each growth type.

PURPOSE: We investigated the surface characteristics and vascular patterns of colorectal tumors according to growth type by means of magnifying narrow-band imaging (NBI). METHODS: Four hundred ninety-seven colorectal tumors larger than 10 mm (204 tubular adenomas [TAs], 199 frankly invasive intramucosal carcinomas to shallow invasive submucosal [M/SM-s] carcinomas, and 94 deeply invasive submucosal [SM-d] carcinomas) were analyzed. These colorectal tumors were classified according to growth type as follows: polypoid type, n = 224; laterally spreading tumor-granular (LST-G) type, n = 133; and LST-non-granular (LST-NG) type, n = 140. Surface and vascular patterns were evaluated in relation to histology and growth type. RESULTS: The absent and irregular surface patterns were observed in approximately 40 % of the SM-d carcinomas of the polypoid and LST-G type. The unclear surface pattern was more frequent in tumors of the LST-NG type than in those of other growth types, regardless of histology. Among TAs and M/SM-s carcinomas, the dense vascular pattern was most frequent in polypoid type, the dense and corkscrew vascular patterns were most frequent in the LST-G type, and the honeycomb and avascular and/or fragmentary patterns were most frequent in the LST-NG type. The avascular and/or fragmentary vessel pattern was more frequent in SM-d carcinomas than in TA and M/SM-s carcinomas, regardless of growth type. CONCLUSIONS: A part of LST-NG was difficult to identify the NBI magnifying surface pattern. Although NBI magnifying findings were almost same in each type lesion in SM-d lesion, those of LST-NG were different from those of LST-G and polypoid type in M/SM-s lesion.

Warning for unprincipled colorectal endoscopic submucosal dissection: accurate diagnosis and reasonable treatment strategy.

Piecemeal endoscopic mucosal resection (EMR) is generally indicated for laterally spreading tumors (LST) >2 cm in diameter. However, the segmentation of adenomatous parts does not affect the histopathological diagnosis and completeness of cure. Thus, possible indications for piecemeal EMR are both adenomatous homogenous-type granular-type LST (LST-G) and LST-G as carcinoma in adenoma without segmentalizing the carcinomatous part. Diagnosis of the pit pattern using magnifying endoscopy is essential for determining the correct treatment and setting segmentation borders. In contrast, endoscopic submucosal dissection (ESD) is indicated for lesions requiring endoscopic en bloc excision, as it is difficult to use the snare technique for en bloc excisions such as in non-granular-type LST (LST-NG), especially for the pseudodepressed type, tumors with a type VI pit pattern, shallow invasive submucosal carcinoma, largedepressed tumors and large elevated lesions, which are often malignant (e.g. nodular mixed-type LST-G). Other lesions, such as intramucosal tumor accompanied by submucosal fibrosis, induced by biopsy or peristalsis of the lesion; sporadic localized tumors that occur due to chronic inflammation, including ulcerative colitis; and local residual early carcinoma after endoscopic treatment, are also indications for ESD. In clinical practice, an efficient endoscopic treatment with segregation of ESD from piecemeal EMR should be carried out after a comprehensive evaluation of the completeness of cure, safety, clinical simplicity, and cost-benefit, based on an accurate preoperative diagnosis.

Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm.

BACKGROUND AND AIMS: Colorectal laterally spreading tumors (LST) > 20 mm are usually treated by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Endoscopic piecemeal mucosal resection (EPMR) is sometimes required. The aim of our study was to compare the outcomes of ESD and EMR, including EPMR, for such LST. METHODS: A total of 269 consecutive patients with a colorectal LST > 20 mm were treated endoscopically at our hospital from April 2006 to December 2009. We retrospectively evaluated the complications and local recurrence rates associated with ESD, hybrid ESD (ESD with EMR), EMR, and EPMR. RESULTS: ESD and EMR were performed successfully for 89 and 178 LST, respectively: 61 by ESD; 28 by hybrid ESD; 70 by EMR; and 108 by EPMR. Between-group differences in perforation rates were not significant. Local recurrence rates in cases with curative resection were as follows: 0% (0/56) in ESD; 0% (0/27) in hybrid ESD; 1.4% (1/69) in EMR; and 12.1% (13/107) in EPMR; that is, significantly higher in EPMR. No metastasis was seen at follow up. The recurrence rate for EPMR yielding ≥ three pieces was significantly high (P < 0.001). All 14 local recurrent lesions were adenomas that were cured endoscopically. CONCLUSIONS: As for safety, ESD/hybrid ESD is equivalent to EMR/EPMR. ESD/hybrid ESD is a feasible technique for en bloc resection and showed no local recurrence. Although local recurrences associated with EMR/EPMR were seen, which were conducted based on our indication criteria, all local recurrences could obtain complete cure by additional endoscopic treatment.

Management of T1 colorectal carcinoma with special reference to criteria for curative endoscopic resection.

BACKGROUND AND AIM: In guidelines 2010 for the treatment of colorectal cancer from the Japanese Society for Cancer of the Colon and Rectum (JSCCR), the criteria for identifying curable T1 colorectal carcinoma after endoscopic resection were well/moderately differentiated or papillary histologic grade, no vascular invasion, submucosal invasion depth less than 1000 µm and budding grade 1 (low grade). We aimed to expand these criteria. METHODS: A total of 499 T1 colorectal carcinomas, resected endoscopically or surgically, were analyzed. Relationships between clinicopathologic findings and lymph node metastasis were evaluated. RESULTS: Lymph node metastasis was found in 41 (8.22%) of the 499 cases. The incidence of lymph node metastasis was significantly higher in lesions featuring poorly differentiated/mucinous adenocarcinoma, submucosal invasion ≥ 1800 µm, vascular invasion, and high-grade tumor budding than in other lesions. Multivariate logistic regression analysis showed all of these variables to be independent risk factors for lymph node metastasis. When cases that met three of the JSCCR 2010 criteria (i.e. all but invasion < 1000 µm) were considered together, the incidence of lymph node metastasis was only 1.2% (3/249, 95% confidence interval: 0.25-3.48%), and there were no cases of lymph node metastasis without submucosal invasion to a depth of ≥ 1800 µm. CONCLUSIONS: Even in cases of colorectal carcinoma with deep submucosal invasion, the risk of lymph node metastasis is minimal under certain conditions. Thus, even for such cases, endoscopic incisional biopsy can be suitable if complete en bloc resection is achieved.

Current status and future perspectives of endoscopic submucosal dissection for colorectal tumors.

Endoscopic submucosal dissection (ESD) allows for en bloc tumor resection irrespective of the size of the lesion. In Japan, ESD has been established as a standard method for endoscopic ablation of malignant tumors in the upper gastrointestinal tract. Although the use of colorectal ESD has been gradually spreading with the development of numerous devices, ESD has not yet been fully established as a standard therapeutic method for colorectal lesions. Currently, colorectal ESD is performed as an 'advanced medical treatment' without national health insurance coverage. With the recent accumulation of numerous cases, the safety and simplicity of colorectal ESD have improved remarkably. Currently in Japan, a prospective multicenter cohort study organized by the Japan Gastroenterological Endoscopy Society is ongoing to clarify the safety and efficacy of colorectal ESD to obtain remuneration from national health insurance. In this report, we showed the outcome regarding safety and efficacy of colorectal ESD through a review of the published work. Of 2719 cases with colorectal ESD at 13 institutions, the complete en bloc resection and perforation rates were 82.8% (61-98.2%, 2082/2516) and 4.7% (1.4-8.2%, 127/2719), respectively. Additional surgery for perforation was very rare because perforations were tiny enough to be closed endoscopically by clips in most of the cases and treated conservatively. In the near future, colorectal ESD will be a common therapeutic method for early colorectal carcinoma.