Endoscopic submucosal dissection for tumors involving the ileocecal valve with extension into the terminal ileum: a multicenter study from the Hiroshima GI Endoscopy Research Group.

BACKGROUND: The efficacy and safety of endoscopic submucosal dissection (ESD) for tumors extending into the terminal ileum remain obscure. We aimed to evaluate the outcomes of ESD for tumors involving the ileocecal valve (ICV) with extension into the terminal ileum. METHODS: Sixty-eight patients (40 men; mean age, 67 years) with 68 tumors involving the ICV that were resected by ESD between December 2013 and December 2018 were included and classified into Group A (21 tumors with extension into the terminal ileum) and Group B (47 tumors without extension). ESD outcomes were compared between groups. RESULTS: The clinical features of the patients and tumors were not significantly different between the groups. There were no significant differences in en bloc resection rate (95% and 94%, respectively; p = 0.79), R0 resection rate (90% and 89%, respectively; p = 0.89), procedure time (95 ± 54 min and 94 ± 69 min, respectively; p = 0.64), postoperative bleeding rate (5% and 3%, respectively; p = 0.79), intraoperative perforation rate (0% and 4%, respectively; p = 0.34), delayed perforation rate (0% and 0%, respectively), or postoperative symptomatic stenosis rate (0% and 0%, respectively) between Groups A and B. No specific factors related to the outcomes of ESD were found by subgroup analysis according to the dominance and degree of circumference of the ICV. Local recurrence was observed in 1 patient in Group A who was retreated using ESD. CONCLUSIONS: ESD for tumors involving the ICV with extension into the terminal ileum is safe and effective.

Efficacy and safety comparison of scissor-type knives with needle-type knives for colorectal endoscopic submucosal dissection: a post-hoc propensity score-matched analysis (with videos).

BACKGROUND AND AIMS: Many knives have been developed to improve the efficacy and safety of endoscopic submucosal dissection (ESD). We aimed to evaluate the efficacy and safety of scissor-type knives for colorectal ESD compared with needle-type knives. METHODS: We performed a post-hoc propensity score-matched analysis in an 11-facility study between August 2013 and December 2018. A total of 2330 patients (2498 lesions) who underwent colorectal ESD were divided into needle-type (1923 patients, 2067 lesions) and scissor-type (407 patients, 431 lesions) knife groups. Short-term outcomes were compared between the 2 groups. RESULTS: Two-to-one propensity score-matched analysis identified 814 (709 patients) and 407 (386 patients) lesions in the needle- and scissor-type knife groups, respectively. The median resection speed was significantly faster in the needle-type group (18.3 mm2/min) than in the scissor-type group (13.2 mm2/min, P < .0001), whereas en-bloc and histologic complete resection rates were not significantly different between the needle- and scissor-type groups (96.8% [788/814] vs 98.3% [400/407], P = .1888 and 95.1% [774/814] vs 95.6% [389/407], P = .7763, respectively). The rate of lesions resected using a single knife was significantly higher in the scissor-type group (98.5% [401/407]) than in the needle-type group (43.9% [357/814], P < .0001). Rates of intraoperative perforation and delayed bleeding were significantly lower in the scissor-type group than in the needle-type group (.7% [3/407] vs 2.5% [20/814], P = .0431 for each). CONCLUSIONS: Scissor-type knives are safer for colorectal ESD. However, they are associated with slower resection speeds compared with needle-type knives. (Clinical trial registration number: UMIN000016197.).

Factors for conversion risk of colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become a widely accepted treatment method for colorectal tumors; however, there are some persistent problems. This multi-center study aimed to characterize the risk factors for incomplete resection and perforation in standardized colorectal ESD procedures. METHODS: This study included 2423 consecutive patients who underwent ESD for 2592 colorectal tumors between August 2013 and December 2018 at 11 institutions (1 academic hospital and 10 affiliated hospitals) from the Hiroshima GI Endoscopy Research Group. We evaluated the risk factors for interruption, piecemeal resection, and perforation of standardized colorectal ESD in relation to clinicopathologic and endoscopic characteristics. RESULTS: The incidences of interruption, piecemeal resection, and perforation were 0.7%, 2.9%, and 3.0%, respectively. Multivariate analysis identified the following risk factors for interruption: perforation during the procedure, deep submucosal invasion (> 1000 µm), poor scope operability, and severe submucosal fibrosis. The risk factors for piecemeal resection included poor scope operability, severe submucosal fibrosis, and procedure time (≥ 85 min). The risk factors for perforation during the procedure were severe submucosal fibrosis, poor scope operability, procedure time (≥ 85 min), and tumor size (≥ 40 mm). Independent risk factors for severe submucosal fibrosis included a history of biopsy and lesions located on the fold or flexure. CONCLUSIONS: Severe submucosal fibrosis and poor scope operability are the common risk factors for interruption, piecemeal resection, and perforation in standardized colorectal ESD.

Real-world learning curve analysis of colorectal endoscopic submucosal dissection: a large multicenter study.

BACKGROUND: The current status of colorectal endoscopic submucosal dissection (ESD) performed by endoscopists without colorectal ESD experience is unknown. This study evaluated the quality of colorectal ESD performed by endoscopists without colorectal ESD experience. METHODS: We retrospectively examined the outcomes of 420 consecutive patients with 427 superficial colorectal tumors (male/female, 251/169; mean age, 69 years) who underwent ESD. The procedures were performed by 31 endoscopists without colorectal ESD experience using needle knife-type devices at 13 hospitals from October 2008 to June 2017. Cases were divided into the first and second phases according to the experience of the endoscopist: the first phase included the first 20 cases and the second phase included case 21 and beyond. We also identified factors associated with en bloc resection failure. RESULTS: Rates of colonic tumors, laterally spreading tumors of the non-granular type, poor scope operability, and severe submucosal fibrosis for the first phase were significantly lower than those for the second phase. The en bloc resection rates for the first and second phases were 93% and 96%, respectively. The factors associated with en bloc resection failure were poor scope operability (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.0-6.5), severe submucosal fibrosis (OR 6.5; 95% CI 2.6-15.9), and the first 20 cases (OR 3.4; 95% CI 1.2-10.1). CONCLUSION: Inexperienced endoscopists should initially perform colorectal ESD for tumors without severe submucosal fibrosis under good scope operability for at least 20 cases.

Long-term prognosis after treatment for T1 carcinoma of laterally spreading tumors: a multicenter retrospective study.

PURPOSE: Long-term prognosis of T1 laterally spreading tumors (LSTs) after treatment have not been clarified. This study compared clinicopathological characteristics and long-term prognosis of T1 LSTs. METHODS: We retrospectively assessed 169 patients with 169 T1 LSTs between January 1992 and December 2008 by ten hospitals. Patients who did not meet the Japanese Society for Cancer of the Colon and Rectum (JSCCR) 2016 guidelines for the treatment of colorectal carcinoma (CRC) criteria were defined as non-endoscopically curable. The number of non-endoscopically curable patients with LST-granular/ nodular mixed (LST-G-M) was 61, that with LST-non-granular/ flat elevated (LST-NG-FE) was 23, and that with LST-non-granular/ pseudo depressed (LST-NG-PD) was 23. Clinicopathological variables and long-term prognosis were analyzed. RESULTS: For overall patients, tumor size, number of non-endoscopically curable cases, and rate of submucosal invasion depth ≥ 1000 µm for the LST-G-M group were significantly higher than those in the other groups. For non-endoscopically curable patients, the tumor size for those with LST-G-M was significantly larger than those in the other groups. The rate of submucosal invasion width ≥ 4000 µm and type B/C muscularis mucosae with LST-G-M was higher than that with LST-NG-FE. All recurrences occurred in non-endoscopically curable patients with LST-G-M. Five-year overall and disease-free survivals for non-endoscopically curable patients with LST-G-M were significantly shorter than those for patients with non-endoscopically curable LST-NG-FE and PD. CONCLUSIONS: Our data supported adequacy of the JSCCR guidelines for the treatment of CRC criteria for endoscopically curable patients after T1 LSTs treatment. Patients with T1 LST-G-M should be followed up more carefully.

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.).

Endoscopic submucosal dissection for anorectal tumor with hemorrhoids close to the dentate line: a multicenter study of Hiroshima GI Endoscopy Study Group.

BACKGROUND: The lower rectum close to the dentate line has distinct characteristics, making endoscopic submucosal dissection (ESD) of tumors challenging. We assessed clinical outcomes of ESD for such patients with hemorrhoids. METHODS: Sixty-four patients (mean age, 68 years) underwent ESD for anorectal tumors close to the dentate line. We divided patients into those with (Group A, 45 patients) and without hemorrhoids (Group B, 19 patients). We examined en bloc and histological en bloc resection rates, procedure time, complication rates, and postoperative prognosis after ESD. RESULTS: The mean tumor size was 43 mm. Histologic diagnoses were adenoma (42 %, 27/64), carcinoma in situ (44 %, 28/64), and T1 carcinoma (14 %, 9/64). There was no significant difference in en bloc resection (93 %, 42/45 vs. 95 %, 18/19) or postoperative bleeding rates (16 %, 7/45 vs. 11 %, 2/19) between Groups A and B, respectively. The mean procedural durations were 120 and 124 min, respectively, in Groups A and B. No perforations occurred. There was no significant difference in postoperative anal pain rate between Groups A (18 %, 8/45) and B (16 %, 3/19), and it resolved within a few days in all cases. There was one case of stricture in Group B. Two patients with T1 carcinoma underwent additional surgery, one underwent chemotherapy, and five had no additional treatment. No recurrence occurred during the follow-up period of 38 months. CONCLUSIONS: ESD is safe and effective for anorectal tumors close to the dentate line in patients with hemorrhoids.

Overlooked muscle cramps in patients with chronic liver disease: in relation to the prevalence of muscle cramps.

INTRODUCTION: Muscle cramps are common comorbidities in chronic liver disease (CLD). Although the prevalence of these has been reported in patients with liver cirrhosis (LC), that of CLD is unknown. In this study, we aimed to clarify the prevalence and characteristics of muscle cramps in individual CLD. PATIENTS AND METHODS: A total of 432 patients with CLD who visited our hospital were enrolled. The existence of muscle cramps, frequency, time zone, duration, and the degree of pain were investigated using a medical interview questionnaire. RESULTS: The median age of the patients was 65 years and 48.6% of the patients were women. The prevalence of muscle cramps was 25.9%. Age, female sex, lower BMI, existence of comorbid diseases, and liver fibrosis were associated significantly with muscle cramps. In LC, muscle cramps were significantly frequent, and the severity and duration of these were significantly stronger and longer compared with chronic hepatitis. Female sex [odds ratio (OR): 2.26; P=0.014], diabetes (OR: 29.4; P<0.001), chronic kidney disease (OR: 8.33; P=0.004), and lower BMI (OR: 0.853; P<0.001) were independent factors associated with muscle cramps in CLD. Muscle mass indices were significantly lower among nonalcoholic fatty liver disease patients with muscle cramps, female patients, elderly patients, and patients with advanced fibrosis. CONCLUSION: The prevalence of muscle cramps was relatively high in CLD. Female sex, comorbid diabetes, and chronic kidney disease are associated with muscle cramps in CLD. Furthermore, reduced muscle mass is related to muscle cramps in nonalcoholic fatty liver disease.

Preceding endoscopic submucosal dissection for T1 colorectal carcinoma does not affect the prognosis of patients who underwent additional surgery: a large multicenter propensity score-matched analysis.

BACKGROUND: We analyzed the influence of preceding endoscopic submucosal dissection (ESD) on the prognosis of patients with T1 colorectal carcinoma (CRC) after additional surgery using propensity-score matching. METHODS: 1638 consecutive patients with T1 CRC were retrospectively identified between January 1998 and December 2016 at the Hiroshima GI Endoscopy Research Group. We assessed 602 patients with 602 T1 CRC who underwent additional surgery after ESD (n = 216) or surgery alone (n = 386). The enrolled patients were treated according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016, and were defined as non-endoscopically curable (non-e-curable) when they did not satisfy its curative criteria. We analyzed the pathological characteristics and the prognosis of non-e-curable patients using propensity-score matching between the additional surgery after ESD and surgery alone groups. RESULTS: There were no cases of recurrence and lymph node metastasis among the e-curable patients. The rate of lymph node metastasis and recurrences in the non-e-curable patients were 10.8% and 2.6%, respectively. After propensity-score matching, there were no significant differences in the 5-year overall survival rates (96.9% vs. 92.0%), 5-year disease-free survival rates (96.7% vs. 96.7%) and 5-year disease-specific survival rates (100% vs. 98.6%) after treatment of T1 CRCs between the 2 groups in non-e-curable patients. CONCLUSIONS: Preceding ESD with histological en bloc resection for patients with T1 CRC did not affect their oncologic behavior adversely after additional surgery.

Long-term outcomes after treatment for T1 colorectal carcinoma: a multicenter retrospective cohort study of Hiroshima GI Endoscopy Research Group.

BACKGROUND: We aimed to clarify the long-term outcomes of patients with T1 colorectal carcinoma (CRC) after endoscopic resection (ER) and surgical resection. METHODS: We examined T1 CRC patients treated during 1992-2008 and who had ≥5 years of follow-up. Patients who did not meet the curative criteria after ER according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines were defined as "non-endoscopically curable" and classified into three groups: ER alone (Group A: 121 patients), additional surgery after ER (Group B: 238 patients), and surgical resection alone (Group C: 342 patients). Long-term outcomes and predictors of recurrence were analyzed. RESULTS: Of the 882 patients with T1 CRC, 701 were non-endoscopically curable. Among these patients, recurrence and 5-year overall survival (OS) rates were 0.6 and 91.1%, respectively. In Groups A, B, and C, recurrence rates were 5.0, 5.5, and 3.8%, OS rates were 79.3, 92.4, and 91.5% (p < 0.01), and 5-year disease-free survival (DFS) rates were 98.1, 97.9, and 98.5%, respectively. Thirty-two patients experienced local recurrence or distant/lymph node metastasis (Group A: 6; Group B: 13; Group C: 13) and 14 patients died of primary CRC (Group A: 3; Group B: 7; Group C: 4). Age ≥65 years, protruded gross type, positive lymphatic invasion, and high budding grade were significant predictors of recurrence in non-endoscopically curable patients. CONCLUSIONS: Our findings supported the JSCCR criteria for endoscopically curable T1 CRC. ER for T1 CRC did not worsen the clinical outcomes of patients who required additional surgical resection.

Long-term outcomes after treatment for pedunculated-type T1 colorectal carcinoma: a multicenter retrospective cohort study.

BACKGROUND: The risk for lymph node metastasis and the prognostic significance of pedunculated-type T1 colorectal carcinomas (CRCs) require further study. We aimed to assess the validity of the 2014 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines based on long-term outcomes of pedunculated-type T1 CRCs. METHODS: In this multicenter retrospective cohort study, we examined 176 patients who underwent resection endoscopically or surgically at 14 institutions between January 1990 and December 2010. Patients meeting the JSCCR curative criteria were defined as "endoscopically curable (e-curable)" and those who did not were "non-e-curable". We evaluated the prognosis of 116 patients (58 e-curable, 58 non-e-curable) who were observed for >5 years after treatment. RESULTS: Overall incidence of lymph node metastasis was 5 % (4/81; 95 % confidence interval 1.4-12 %: three cases of submucosal invasion depth ≥1000 µm [stalk invasion] and lymphatic invasion, one case of head invasion and budding grade 2/3). There was no local or metastatic recurrence in the e-curable patients, but six of them died of another cause (observation period, 80 months). There was no local recurrence in the non-e-curable patients; however, distant metastasis was observed in one patient. Death due to the primary disease was not observed in non-e-curable patients, but six of them died of another cause (observation period, 72 months). CONCLUSIONS: Our data support the validity of the JSCCR curative criteria for pedunculated-type T1 CRCs. Endoscopic resection cannot be considered curative for pedunculated-type T1 CRC with head invasion alone.

Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma.

AIM: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vascular system. The aim of this study was to elucidate the clinical significance of VEGF-C expression and microvessel density (MVD) at the deepest invasive site in advanced colorectal carcinoma (CRC). METHODS: 152 patients who had undergone surgical resection for advanced CRC entered this study. VEGF-C expression was examined immunohistochemically with anti-VEGF-C polyclonal antibody C-20. Tumor MVD was determined immunohistochemically with anti-CD34 antibody. VEGF-C expression was defined as positive if distinct staining of the cytoplasm was observed in at least 10% of tumor cells at the deepest invasive site, central portion and superficial part of the tumor. MVD was estimated by averaging the count of three x400 fields in the most vascular area at the deepest invasive site. RESULTS: VEGF-C expression was detected in 71 of 152 lesions (46.7%) at the deepest invasive site. VEGF-C expression correlated significantly with poorer histologic grade, depth of invasion, lymphatic invasion, lymph node metastasis, venous invasion, liver metastasis and Duke's stage. At the central portion and superficial part, there were no significant differences between VEGF-C expression and clinicopathological findings. VEGF-C expression at the deepest invasive site also correlated significantly with MVD. In cases with curative surgery, patients with VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without VEGF-C expression. Furthermore, prognosis for patients with both VEGF-C expression and high MVD at the deepest invasive site was significantly poorer than that of patients without VEGF-C expression and with low MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF-C expression were significant risk factors. CONCLUSION: VEGF-C expression at the deepest site of tumor invasion can be a useful predictor of poor prognosis in advanced CRC and show a close relation to angiogenesis.