Incidence of and risk factors for dysplasia in mucosectomy area in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND AND AIMS: We evaluated the incidence of dysplasia in the mucosectomy area using resected specimens to determine preoperative risk factors for the occurrence of dysplasia in this area. PATIENTS AND METHODS: We prospectively studied a consecutive series of 137 patients, each of whom underwent a restorative proctocolectomy with a mucosectomy and hand-sewn ileal J-pouch anal anastomosis between January 2003 and December 2004. Sections from the anal transitional zone mucosa were taken from the dentate line to 2.5 cm above the resected line and stained with hematoxylin and eosin then characterized as indefinite for dysplasia, low-grade dysplasia, and high-grade dysplasia based on the criteria of an international working group for rectal mucosal atypia. RESULTS: Dysplasia of the mucosectomy area was present in six (4.4%) of the patients, including one with low-grade and five with high-grade dysplasia. A multivariate analysis showed relations between age at time of surgery (>or=40 years) and duration of disease (>or=10 years) with a risk for development of mucosectomy area dysplasia. CONCLUSION: The incidence of dysplasia of the mucosectomy area was 4.4%, and preoperative risk factors were shown to be duration of disease and age at time of surgery.

Mechanism of carcinogenesis in familial tumors.

It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G1 or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudson's two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.

Poorly controlled ulcerative colitis treated by colectomy during remission induced by extracorporeal leukocyte removal therapy.

Both monocyte-granulocytapheresis (M-GCAP) and leukocytapheresis (LCAP) are categorized as extracorporeal leukocyte removal therapies (ECCTs). These therapies have been recognized as efficient adjuncts for patients of steroid-resistant ulcerative colitis (UC). This study aimed to consider the adaptation and the limitation of these new therapies from the clinical standpoint based on a case of UC showing strong resistance to high-dose continuous steroid injection therapy. The patient successfully underwent a scheduled colectomy while maintaining remission after applying M-GCAP and LCAP independently. Surgical therapy was chosen because of a deep ulcer in the patient's sigmoid colon, which was assumed to constitute a future risk for perforation. This case suggests that combining ECCT with steroid therapy can maintain such poorly controlled and high-risk UC patients safely for the scheduled colectomy while improving the prognosis by reducing the dosage of steroid efficiently prior to operation.