MUTYH-associated colorectal cancer and adenomatous polyposis.

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

Limits of diagnosis and molecular markers for early detection of ulcerative colitis-associated colorectal neoplasia.

The incidence of colorectal neoplasia has been increasing among patients with long-standing and extensive ulcerative colitis (UC), and therefore surveillance colonoscopy has been widely recommended. However, because UC-associated neoplasia is often difficult to detect endoscopically and to discriminate from inflammatory regenerative epithelium histologically, the efficacy of current surveillance remains unsatisfactory. In order to overcome these difficulties, adjunctive modalities for diagnosing UC-associated neoplasia, chromo- and magnifying endoscopy for endoscopic diagnosis and analysis of p53 alteration for histological diagnosis have been introduced. Furthermore, if it were possible to differentiate UC patients with long-standing and extensive colitis into subgroups with a high and a low risk of neoplasia, it would enable physicians to conduct more intensive surveillance with these modalities for patients at higher risk. Several molecular alterations of nonneoplastic epithelium in UC patients with neoplasia may be promising as markers for identifying individuals with UC at increased risk of neoplasia. We evaluated estrogen receptor (ER) methylation of nonneoplastic colorectal epithelium to clarify whether this epigenetic alteration can contribute to the prediction of increased neoplasia risk in UC patients and demonstrated that the ER methylation level in nonneoplastic epithelium was higher throughout the colorectum in patients with neoplasia than in those without. These results suggest that analysis of ER gene methylation may be potentially useful for identifying individuals at increased risk of neoplasia among patients with long-standing and extensive UC.

[A case of effective treatment of oral TS-1 and intravenous MMC administration for multiple metastases of gastric cancer].

A 49-year old man underwent distal gastrectomy (D3) for circumferential type 3 cancer at the gastric antrum and cholecystectomy in September 2002. During the surgery, multiple metastases were observed predominantly in the left lobe of the liver, and lateral segmentectomy was performed as non-curative (curability-C) resection leaving the small metastases in the right lobe of the liver. Based on the results of chemo-sensitivity tests (5-FU 15.0%, CDDP 34.0%, MMC 35.3%, TXT 0.0%), we started to administer TS-1 (100 mg/day for 4 weeks followed by a 2-week rest interval) and MMC (10 mg/body on day 1). Due to leukocytopenia, the regimen was changed to TS-1 (100 mg/day for 4 weeks followed by a 2-week rest interval) and MMC (4 mg/body every other week [day 1, 14]) from the second course. Levels of tumor markers dropped and liver metastatic lesions remarkably decreased in size by CT after the third course. In conclusion, a combination of TS-1/MMC may be regarded as one option for postoperative adjuvant chemotherapy for outpatients.

PET/CT supports breast cancer diagnosis and treatment.

The application of positron emission tomography with (18)F fluoro-2-deoxy-D-glucose (FDG-PET) has remarkably improved the management of cancer patients. However, some caution is necessary in the interpretation of FDG-PET images. Because of its low spatial resolution, it is difficult to identify the anatomical location of radiotracer uptake and to distinguish between normal physiological accumulation and pathological uptake. A novel combined PET/CT system has been developed that improves the capacity to correctly localize and interpret FDG uptake. Although only a few studies have been conducted on the potential role of PET/CT in the management of breast cancer patients, the advantage of this modality compared with PET alone should be relevant for application in the field of breast cancer. In this review, we describe the clinical impact of PET/CT on breast cancer diagnosis compared with PET alone with respect to disease restaging, treatment monitoring, preoperative staging and primary diagnosis. In addition, the possible role of PET/CT with iodine contrast is noted for evaluation of intra-ductal spreading.

Depth of tumor invasion in locally advanced rectal cancer correlates with patients' prognosis: the usefulness of elastic stain for its measurement.

PURPOSE: The relationship between the prognosis and the extent of colorectal carcinoma (CRC) is still unclear. As a simple parameter of the local invasion of CRC, we assessed the extent of tumor invasion beyond the outer border of the muscularis propria (MP). METHODS: We examined 147 cases of CRC using a slight modification of the procedure established by the Japanese Society for Cancer of the Colon and Rectum. For the statistical analysis, the patients were divided into two groups, namely, a "shallow" group and a "deep" group, using a specific cut-off value (COV). A multivariate analysis to identify independent prognostic factors was performed. RESULTS: Significant differences in the 5-year survival rate were observed between the "shallow" and "deep" groups in 39 cases of rectal carcinoma (COV 4 mm; 72.4% vs. 30.0%, hazard ratio = 3.204), but not observed in 147 cases of CRC. In addition, the outcome for patients with "deep" cancer in the lower rectum was markedly worse than that for patients with "shallow" cancer (COV 4 mm; 81.8% vs. 12.5%, hazard ratio = 5.371). CONCLUSIONS: The depth of tumor invasion beyond the MP is thus considered to be an important prognostic factor for patients with T3/T4 rectal carcinoma, especially in the lower rectum. A careful follow-up is required for the patients with rectal carcinoma that has invaded more than 4 mm beyond the MP.