Risk factors for non-curative resection of early gastric neoplasms with endoscopic submucosal dissection: Analysis of 1,123 lesions.

Although the frequency of residual disease and recurrence following endoscopic submucosal dissection (ESD) has markedly decreased, a few cases of residual disease and recurrence following ESD are still observed. The aims of the present study were to clarify the causes of non-curative resection and to investigate the risk factors. A total of 1,123 early gastric neoplasm lesions treated by ESD were investigated. Non-curative resection was defined as histological positivity of the resected margins, vascular invasion or failure of en bloc resection. Cases of non-curative resection were classified as being caused by one of three reasons: Inadequate technique, pre-procedural misdiagnosis or problems in the histological diagnosis. Following classification, the cases of non-curative and curative resection were compared based on a range of patient characteristics: Procedure time, and size, type and location of the lesions. The frequency of non-curative resection was 16% (182 lesions). Non-curative resection occurred due to inadequate technique in 59 cases, pre-procedural misdiagnosis in 88 cases and problems in the histological diagnosis in 35 cases. Multivariate analysis revealed that a large lesion size, long procedure time and inexperienced endoscopist were associated with a significantly higher risk of non-curative resection due to an inadequate technique. Furthermore, it was found that lesions located in the upper area of the stomach and cancer with submucosal invasion were associated with a significantly higher risk of non-curative resection due to pre-procedural misdiagnosis. In conclusion, the present study has shown that the major reasons for non-curative resection are an inadequate technique and pre-procedural misdiagnosis. The risk factors for these problems have been clarified.

Risk factors for perforation and delayed bleeding associated with endoscopic submucosal dissection for early gastric neoplasms: analysis of 1123 lesions.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is a useful procedure for the treatment of early gastric neoplasms; however, this advanced technique has also resulted in an increase in serious complications such as perforation and delayed bleeding. This study aimed to elucidate the risk factors for these complications. METHODS: A total of 1123 lesions diagnosed with early gastric neoplasms and treated by ESD at three institutions were investigated. Retrospectively, patients with or without these complications were compared on the basis of the patient characteristics and treatment results. RESULTS: Perforation occurred in 27 lesions (2.4%) and delayed bleeding in 56 lesions (5.0%). Multivariate analysis indicated that lesions located in the upper area of the stomach (odds ratio [OR]: 4.88, 95% confidence interval [CI]: 2.21-10.75) was associated with a significantly higher risk of perforation, and that age ≥ 80 years (OR: 2.15, 95% CI: 1.18-3.90) and a long procedure time (OR: 1.01, 95% CI: 1.001-1.007) were associated with a significantly higher risk of delayed bleeding after ESD. The en bloc resection rate (74% vs 94%) and curative resection rate (48% vs 85%) of lesions with perforation were significantly lower than those without perforation. The rate of residual disease or recurrence after ESD was significantly higher in lesions with delayed bleeding than that without delayed bleeding (5.4% vs 0.84%). CONCLUSIONS: This study demonstrated risk factors for perforation and delayed bleeding associated with ESD. Furthermore, it was clarified that perforation and delayed bleeding influenced post-procedure results and prognosis after ESD.

Serum folate and homocysteine levels are associated with colon tumorigenesis in end-stage renal disease patients.

The aim of this study was to evaluate the effect of folate and homocysteine on colon tumorigenesis by performing colonoscopy and examining serum folate and homocysteine levels in end-stage renal disease (ESRD) patients. We performed colonoscopy in 72 ESRD patients who were undergoing hemodialysis and also measured their serum folate and homocysteine levels. Serum folate and homocysteine concentrations of the 72 ESRD patients were 6.0±3.9 µg/l and 37.3±25.5 µmol/l, respectively. Colorectal neoplasia was detected in 47 (65%) of the patients. Compared to a control group, ESRD patients had significantly more and larger neoplasia (P=0.002 and 0.001, respectively). Multivariate analysis revealed that ESRD patients with lower levels of serum homocysteine had significantly more and larger neoplasia than those with higher levels (P=0.02 and 0.03, respectively). In addition, patients with a shorter duration of hemodialysis were likely to have larger neoplasia. ESRD patients had higher than normal serum homocysteine levels. Interestingly, patients with lower homocysteine levels were likely to carry more and larger colorectal neoplasia. These results suggest that suppression of folate metabolism and an elevated serum homocysteine concentration are inversely associated with colon tumorigenesis in ESRD patients.

Clinical outcomes of ESD for early gastric neoplasms in elderly patients.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard treatment in Japan for early gastric neoplasms. With an increase in elderly population, the number of elderly patients in whom ESD performed has also steadily increased. AIMS AND METHODS: The aim of study was to evaluate the effectiveness of and problems associated with ESD for early gastric neoplasms in elderly patients. Subjects were 514 patients (586 lesions) with early gastric neoplasms performed ESD at two institutions. The patients were classified into an elderly group (age ≥ 75 years) and a nonelderly group (age < 75 years). We compared the characteristics of patients and lesions, treatment results, ESD-related complications and prognosis between the two groups. RESULTS: The elderly group included 200 patients (229 lesions), and the nonelderly group included 314 patients (357 lesions). The incidences of underlying disease, such as hypertension and heart disease, and the rate of antiplatelet agents use were significantly higher in the elderly group. En bloc and curative resection rates were high in both groups. The bleeding rate was significantly higher in the elderly group. Residual disease or recurrence rates were very low in both groups. The death rate due to other diseases was significantly higher in the elderly group. CONCLUSIONS: This study demonstrates the efficacy of ESD in both elderly and nonelderly patients. However, we must be attentive to ESD-related bleeding, death caused by other diseases, and underlying diseases when we perform ESD in elderly patients.

The presence of large serrated polyps increases risk for colorectal cancer.

BACKGROUND & AIMS: There is evidence that serrated polyps (serrated adenomas and hyperplastic polyps) have different malignant potential than traditional adenomas. We used a colonoscopy database to determine the association between the presence of serrated colorectal polyps and colorectal neoplasia. METHODS: We performed a multicenter observational study of 10,199 subjects who underwent first-time colonoscopies. Data collected on study subjects included age and sex and the location, size, and histology of polyps or tumors found at colonoscopy. Serrated polyps were defined as those diagnosed by the pathologists in the participating hospitals as a serrated lesion (a lesion given the term of "classical hyperplastic polyp," "traditional serrated adenoma," "sessile serrated adenoma," or "mixed serrated polyp"). Large serrated polyps (LSPs) were defined as those ≥ 10 mm. RESULTS: There were 1573 patients (15.4%) with advanced neoplasia, 708 patients (6.9%) with colorectal cancer (CRC), and 140 patients (1.4%) with LSPs in our cohort. Multivariate analysis associated the presence of LSPs with advanced neoplasia (odds ratio [OR], 4.01; 95% confidence interval [CI], 2.83-5.69) and CRC (OR, 3.34; 95% CI, 2.16-5.03). The presence of LSPs was the greatest risk factor for CRC, particularly for proximal CRC (OR, 4.79; 95% CI, 2.54-8.42). Proximal and protruded LSPs were the highest risk factors for proximal CRC (OR, 5.36; 95% CI, 2.40-10.8 and OR, 9.00; 95% CI, 2.75-19.2, respectively). CONCLUSIONS: The presence of LSPs is a risk factor for CRC, particularly CRC of the proximal colon.

Combination of sigmoidoscopy and a fecal immunochemical test to detect proximal colon neoplasia.

BACKGROUND & AIMS: The combination of sigmoidoscopy and a sensitive fecal occult blood test was recommended as one strategy for colorectal cancer screening by the US Preventive Services Task Force in 2008. However, there have been no studies to evaluate the sensitivity of a one-time screen that uses both flexible sigmoidoscopy and a fecal immunochemical test (FIT) to detect advanced colorectal neoplasia. METHODS: We analyzed data from 21,794 asymptomatic persons who had undergone colonoscopy and a FIT. Analyses were performed with the following assumptions: colonoscopy would be performed for any positive FIT result; colonoscopy would be performed if the FIT result was negative and if advanced neoplasia was detected in the rectosigmoid (or plus descending) colon. The sensitivities and specificities of the combination of sigmoidoscopy and the FIT in detecting advanced neoplasia in the proximal colon were determined. RESULTS: When colonoscopy was performed for a positive FIT result alone, for a positive sigmoidoscopy finding, and for a positive FIT result or sigmoidoscopy finding, the sensitivities in detection of advanced proximal neoplasia were 22.3%, 16.3%, and 31.7%, respectively. The sensitivities for detection of proximal invasive cancer were 58.3%, 8.3%, and 62.5%, respectively. CONCLUSIONS: The combination of sigmoidoscopy and FIT can detect advanced proximal neoplasia better than either test alone. The incremental yield of advanced neoplasm detection by a screening program that uses both a FIT and sigmoidoscopy is approximately 10%. The FIT adds the most in terms of finding proximal cancers in a screening program that uses both tests. The combination of sigmoidoscopy and FIT is a viable and useful screening option.

Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas.

BACKGROUND: Although the immunochemical fecal occult blood test (FOBT) is reportedly more sensitive to large adenomas or colorectal cancer (CRC) than the guaiac-based FOBT, the sensitivity of the immunochemical FOBT to small adenomas has scarcely been reported. Previous reports have indicated that the guaiac-based FOBT can detect small adenomas only by serendipity. OBJECTIVES: To investigate the sensitivity of immunochemical FOBT to small adenomas using a large-scale cohort. METHODS: We analyzed 21,805 consecutively enrolled asymptomatic persons who underwent colonoscopy and immunochemical FOBT. RESULTS: The sensitivity to adenomas 60 yr 11.3%). On the other hand, the sensitivity in women was not significantly different from the false-positive rate in any generation (5.1%vs 4.7% for all eligible women, P= 0.72). CONCLUSIONS: Immunochemical FOBT detected a small percentage of small adenomas in men at a rate that is significantly higher than the false-positive rate. Studies comparing the guaiac and immunochemical FOBTs using the end point of CRC-related death are expected.

Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations.

BACKGROUND & AIMS: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. METHODS: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. RESULTS: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P = .002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P < .0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%). CONCLUSIONS: High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.

A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population.

BACKGROUND & AIMS: The fecal occult blood test (FOBT) is recommended as a screening test for colorectal cancer, but there are few reliable studies on the accuracy of immunochemical FOBT. The aim of this study was to analyze the sensitivity of immunochemical FOBT and to compare the results with the findings from complete colonoscopy. METHODS: Asymptomatic adults underwent 1-time immunochemical FOBT and total colonoscopy simultaneously. The prevalence and location of colorectal neoplasia were determined by colonoscopy. The results of immunochemical FOBT and the colonoscopic findings were compared. RESULTS: Of 21,805 patients, immunochemical FOBT was positive in 1231 cases (5.6%). The sensitivity of 1-time immunochemical FOBT for detecting advanced neoplasia and invasive cancer was 27.1% and 65.8%, respectively. In addition, the sensitivity for invasive cancer according to Dukes' stage showed 50.0% for Dukes' stage A, 70.0% for Dukes' stage B, and 78.3% for Dukes' stages C or D. The sensitivity for detecting advanced neoplasia at the proximal colon was significantly lower than that detected in the distal colon (16.3% vs 30.7%, P = .00007). CONCLUSIONS: Although the screening of asymptomatic patients with immunochemical FOBT can identify patients with colorectal neoplasia to a certain extent, the sensitivity is relatively low and different according to the tumor location. Therefore, programmatic and repeated screening by immunochemical FOBT may be necessary to increase sensitivity for colorectal cancer detection.