Koji Sekikawa

BRAF mutations in papillary carcinomas of the thyroid.

BRAF is a serine/threonine kinase that receives a mitogenic signal from RAS and transmits it to the MAP kinase pathway. Recent studies have reported that mutations of the BRAF gene were detected with varying frequencies in several cancers, notably more than 60% in melanoma. We analysed mutations of BRAF and RAS genes in 100 cases of thyroid carcinoma to investigate genetic aberrations in the RAS/RAF/MEK/MAP kinase pathway. BRAF mutations were detected exclusively in papillary carcinomas (40 in 76 cases: 53%), and were exclusively V599E, a mutation frequently observed in other carcinomas. NRAS mutation was observed in six cases (6%), all in histological types other than papillary carcinoma, and was exclusively Q61R. No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid.

Flow cytometric DNA analysis of thyroid carcinoma

Abnormal DNA content has been considered as an additional criterion for determining the biological behavior of a tumor. Flowcytometric DNA analysis was done on 121 patients with thyroid carcinoma encountered during the period between 1975 and 1987. Tumor tissues were sampled from paraffin-embedded blocks and the histology of thyroid carcinoma found to consist of 91 papillary, 23 follicular, 2 medullary, 1 squamous cell and 4 anaplastic carcinomas. The incidence of aneuploidy in thyroid carcinoma was 7.4 per cent (9 patients) while that of diploidy was 92.6 per cent (112 patients). The aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 anaplastic carcinomas and, of 4 anaplastic carcinoma patients with subsequent death within 6 months, only 1 was aneuploid. As an indicator of proliferative potential, S-phase fraction (SPF) was also determined by flow cytometry, but this could not be used as an independent prognostic factor. The aneuploid patients showed a significantly decreased survival rate (p<0.01). Thus, although DNA measurement proved useful for predicting the survival of aneuploid patients, there is some discrepancy between DNA content and the biological behavior of the tumor.

Combined laparoscopic abdomino-endoscopic perineal total mesorectal excision for anorectal malignant melanoma: A case report

Highlights • This is the first report of combined laparoscopic abdomino-endoscopic perineal total mesorectal excision for anorectal malignant melanoma.• This procedure provides not only better exposure of the extralevator surgical field, but also safety resection margins compared with the conventional abdominoperineal resection.• Our experience showed safety and feasible option for anorectal malignant diseases.

A case of perianal mucinous adenocarcinoma arising from an anorectal fistula successfully resected after preoperative radiotherapy.

A case of mucinous adenocarcinoma arising on a long-standing anorectal fistula is described. A 60-year-old man with a long history of mucinous discharge, pain and perianal induration underwent a biopsy of the external opening of the fistula that showed a mucinous infiltrating adenocarcinoma. Due to the large size of the tumor and the fact that it had extended into the surrounding tissue, preoperative radiotherapy was performed. Radiotherapy was given with 40 Gy in 25 fractions for 5 weeks through posterior and bilateral portals. After radiotherapy the tumor was markedly shrunk and the serum level of carcinoembryonic antigen was also improved. Abdominoperineal resection was performed 8 weeks after the termination of radiotherapy. Histological examination of the resected specimen revealed that the invasion of the tumor remained within the sphincter muscle and that no cancer cells were present on the surgical margin. The histological effect of radiotherapy was judged as grade 1b. This treatment can result in downstaging and R0 resection, which also has a possibility to prevent local recurrence. This case suggests that preoperative radiotherapy may play an important role in the definitive treatment of locally advanced perianal mucinous adenocarcinoma.

Recent indications and methods of surgery for inflammatory bowel disease.

Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can require surgical intervention. Surgery represents only one of the treatment options, but prediction of whether UC and CD are likely to progress to serious conditions and determination of when to undertake surgery is essential. Various surgical procedures have been developed over time, and the postoperative results are now generally good. Regarding laparoscopic surgeries, relatively few cases have been accumulated, and addressing the indications and limitations is premature at this point. However, this procedure is likely to fulfill a central role in surgical treatment strategies and represent a major benefit to patients. This paper discusses surgical treatment indications and methods for UC and CD, and explains the practical aspects of laparoscopic surgery, which has made remarkable progress in recent years, for such cases.