宮倉 安幸

Purpose: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. Methods: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. Results: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. Conclusion: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.

Background and aim: Patients with stage T3 or T4 rectal cancer are candidates for neoadjuvant chemoradiation therapy. The aim of this study is to clarify the usefulness of circumferential tumor extent determined by computed tomography (CT) colonography in differentiating T3 or T4 from T1 or T2 rectal cancer. Methods: Seventy consecutive rectal cancer patients who underwent curative-intent surgery were enrolled in this study. All patients underwent colonoscopy and CT colonography on the same day. The circumferential tumor extent was estimated in 10% increments. The pathological T stage was used as the reference. Results: The median circumferential tumor extent evaluated by colonoscopy for T1 (n = 6), T2 (n = 21), and T3/T4 (n = 43) were 10%, 30%, and 80%, respectively (T1/T2 vs. T3/T4, p < 0.0001). The median circumferential tumor extent evaluated by CT colonography for T1, T2, and T3/T4 is 10%, 30%, and 70%, respectively (T1/T2 vs. T3/T4, p < 0.0001). The correlation coefficient between colonoscopy and CT colonography was very high (0.94). By defining a circumferential tumor extent >= 50% by CT colonography as the criterion for stage T3 or T4, the sensitivity, specificity, positive predictive value and accuracy were 72%, 88%, 91%, and 79%, respectively. Conclusion: Circumferential tumor extent >= 50% determined by CT colonography is a simple and potentially useful marker to identify candidates for neoadjuvant chemoradiation therapy. Copyright (C) 2015, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.

Although size criteria have been proposed to identify lymph node metastases in patients with rectal cancer, size may not be an accurate predictor. Specimens from consecutive rectal cancer patients who underwent curative-intent radical surgery were examined. The long and short axes of lymph nodes were measured on the glass slides using micrometer calipers. The pathologic diagnosis was used as the reference. The diagnostic accuracy of metastatic status according to lymph node size was evaluated. Overall, 1283 lymph nodes from 78 patients were reviewed. The metastatic rate correlates with the length of both the long and short axes. However, metastases were present even in 1-mm lymph nodes, and the metastatic rate exceeds 5 per cent in lymph nodes measuring 3 mm along both axes. Cutoff values of >= 4 mm and >= 3 mm for the long and short axes result in a sensitivity of 76 per cent and 79 per cent, and a specificity of 36 per cent and 33 per cent, respectively, for each axis. Size criteria alone do not accurately predict the N-stage of rectal cancer. Diminutive lymph nodes, which are not seen on imaging studies, can contain metastatic disease.

Background: Methylation of the MLH1 promoter region has been suggested to be a major mechanism of gene inactivation in sporadic microsatellite instability-positive (MSI-H) colorectal cancers (CRCs). Recently, single-nucleotide polymorphism (SNP) in the MLH1 promoter region (MLH1-93G/A rs1800734) has been proposed to be associated with MLH1 promoter methylation, loss of MLH1 protein expression and MSI-H tumors. We examined the association of MLH1-93G/A and six other SNPs surrounding MLH1-93G/A with the methylation status in 210 consecutive sporadic CRCs in Japanese patients. Methods: Methylation of the MLH1 promoter region was evaluated by Na-bisulfite polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. The genotype frequencies of SNPs located in the 54-kb region surrounding the MLH1-93G/A SNP were examined by SSCP analysis. Results: Methylation of the MLH1 promoter region was observed in 28.6% (60/210) of sporadic CRCs. The proportions of MLH1-93G/A genotypes A/A, A/G and G/G were 26% (n = 54), 51% (n = 108) and 23% (n = 48), respectively, and they were significantly associated with the methylation status (p = 0.01). There were no significant associations between genotype frequency of the six other SNPs and methylation status. The A-allele of MLH1-93G/A was more common in cases with methylation than the G-allele (p = 0.0094), especially in females (p = 0.0067). In logistic regression, the A/A genotype of the MLH1-93G/A SNP was shown to be the most significant risk factor for methylation of the MLH1 promoter region (odds ratio 2.82, p = 0.003). Furthermore, a haplotype of the A-allele of rs2276807 located -47 kb upstream from the MLH1-93G/A SNP and the A-allele of MLH1-93G/A SNP was significantly associated with MLH1 promoter methylation. Conclusions: These results indicate that individuals, and particularly females, carrying the A-allele at the MLH1-93G/A SNP, especially in association with the A-allele of rs2276807, may harbor an increased risk of methylation of the MLH1 promoter region.