Barrett's esophageal cancer is defined as carcinoma developing in Barrett's esophagus. The esophagogastric junction is located at the distal end of a network of fine longitudinal vessels, and the columnar epithelium existing above it is Barrett's mucosa. Barrett's mucosa, especially specialized columnar epithelium is considered as precancerous lesion, and malignant potential is examined in various ways. For the surveillance of malignant lesions from Barrett's esophagus, periodic endoscopic examination is necessary with chromoendoscopy or magnifying endoscopy. Treatment strategies are EMR and other endoscopic treatment for mucosal cancer, and surgical treatment for submucosal and advanced cancer. Several surgical modalities are employed depending on the stage of cancerous progression, the location of the cancer in Barrett's esophagus, and the length of Barrett's esophagus. There remain many unexplained problems in Barrett's esophagus and Barrett's cancer.

Constitutively activating mutations in the TSH receptor gene have been found in various disorders. Somatic mutations were identified in autonomously functioning thyroid nodules(AFTNs) and toxic multinodular goiters(TMNGs). Germline mutations were identified in autosomal dominantly inherited non-autoimmune hyperthyroidism and sporadic congenital hyperthyroidism. Most of activating TSH receptor mutations were identified in western countries. Only one Japanese family has been reported to have an activating TSH receptor mutation. Previous very poor and insensitive study identified no somatic TSH receptor activating mutations in 45 AFTNs and TMNGs developed in Japanese. Our recent study completely reversed their observation; about half of AFTNs in Japanese had activating mutations.

A 56-year-old woman with Ph1--Positive acute Lymphoblastic Leukemia was admitted to our hospital for induction chemotherapy in June 1999. The patient was presented with a central scotoma of left eye during treatment course and was given diagnosis of endophthalmitis. Thereafter she also developed skin induration and suffered from serious pneumonia. Amphotericin B administration was started because of high titer of beta-D-glucan, but soon discontinued due to its adverse effect. Blood cultures yielded colonies of fungus and it was identified Fusarium solani. Her general condition deteriorated with progression of pneumonia, and she died of respiratory insufficiency. Autopsy was performed, and its specimen revealed the disseminated infection of Fusarium solani (lung, eye, heart, kidney and skin). We should pay special attention to the fusariosis in Japan also.

Transurethral removal of the ureter in nephroureterectomy has been reported by several centers as being a useful procedure. We also have employed this procedure in selective cases, but we had several problems in this procedure. So we tried the modified pluck nephroureterectomy technique (En bloc removal of kidney and ureter) to improve the procedure.

The clinical usefulness of tumor markers for malignant lymphoma is thought to be in monitoring the therapeutic effect and as a prognostic factor before treatment. The former include specific biological marker such as soluble interleukin-2 receptor measured by ELISA. The latter are cellular prognostic markers detected by immunohistological and flow cytometric analysis. The cyclin D1 over-expression of mantle cell lymphoma in diffuse large B-cell lymphoma, which should be recommended for myeloablative therapy, is a significantly poor prognostic risk factor.

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by Philadelphia chromosome and resultant production of the constitutively activated BCR-ABL tyrosine kinase. Imatinib (STI571), selective inhibitor of the ABL-tyrosine kinase, inhibits the activity of BCR-ABL tyrosine kinase. A phase I and II study of STI571 showed remarkable cytogenetic effect in patients with interferon-refractory CML, offering new hope for therapy for CML. It will, however, require long-term follow-up data from phase II and III clinical studies to validate the effect of STI571 on survival. As therapy for CML improves, monitoring minimal residual disease will be important.

Developing the technological innovation for genomic and molecular biology rapidly, the strategy of molecular target chemotherapy for cancer is recognized in the medical circles to be defined on the basic science and the ethical society. The novel strategy of the individuated anticancer chemotherapy is growing of geno-projects to be determined of more effective and harmless therapeutic methods for every cancer patients by the individual difference of pharmacogenetics and molecular biology. The new strategy is dependent on the general analysis for the personal life science from pharmacokinetics, pharmacodynamics, and oncogenomics. We summarized the problems and the possibility of the translational research for these strategies from the position of medical oncology.

To assess whether a satellite lesion in the primary-tumor lobe is intrapulmonary metastasis from primary cancer (pm 1) or they are double primary lung cancers, we examined the postoperative prognosis of patients with pm 1 and the p 53 genetic differentiation between a satellite lesion and a primary lesion. Of 772 consecutive patients with N0-2M0 non-small cell lung cancer who underwent surgical resections between 1979 and 2000, 31 patients had a satellite lesion in the primary-tumor lobe. The 5-year survival rate was 26.3% in the pm 1 (+) T 4 group (n = 37), 14.7% in the pm 1 (-) T 4 group (n = 43), and 32.5% in the T 3 group (n = 132), suggesting that pm 1 cases should be classified as T 3. We examined 16 of 37 patients with pm 1 for mutations of the p 53 gene occurring exons 5 through 8 by the fluorescence-based polymerase chain reaction single-strand conformation polymorphism. Seven of the 16 patients analyzed had at least one p 53 mutations in their tumors. The mutational status of the p 53 gene was discordant in 5 patients, suggesting they were double primary lung cancers. The mutational status including DNA sequencing of the p 53 gene was concordant in 2 patients, suggesting they were intrapulmonary metastases. It remains arguable in the TNM staging system whether a satellite lesion in the primary-tumor lobe is intrapulmonary metastasis from primary cancer or they are double primary lung cancers.

Molecular-based diagnosis of thyroid carcinomas can be more easily established by utilizing specific mRNAs that are expressed only in cancer tissues. In a previous study, we introduced a new method of preoperatively diagnosing thyroid carcinomas. This technique, aspiration biopsy-RT-PCR(ABRP), facilitated simultaneous cytological and molecular-based diagnoses by extracting RNA from cells remaining within the needle used for fine needle aspiration biopsies(FNABs). ABRP provides both RNA information and a cytological diagnosis without further invasion to the patient. We proved that by ABRP detection of oncofetal fibronectin(onfFN) mRNA in FNABs, papillary and anaplastic carcinomas are accurately diagnosed preoperatively. Further, by real-time monitoring RT-PCR measuring onfFN mRNA, a fully automated system was established. It is not clarified, however, why cancer-specific mRNAs, especially those overexpressed in fetal tissues, can clearly distinguish benign tissues from carcinomas, while genomic alternation such as mutations in RAS or P53 gene cannot. Further, a widely accepted hypothesis, multi-step carcinogenesis, does not explain some of the clinical and experimental evidence from thyroid carcinomas. Considering these facts, we propose a new concept of thyroid carcinogenesis called "germ-cell carcinogenesis", in which cancer cells are derived from the remnant of fetal thyroid germ cells(thyroblasts) instead of normal thyroid follicular cells.

Death-associated protein-kinase(DAP-Kinase) is a pro-apoptotic serine/threonine kinase with a death domain, which is involved in apoptosis induced by interferon-gamma, tumor necrosis factor-alpha, and Fas ligand. Epigenetic down-regulation of DAP-Kinase gene expression by hypermethylation of its promoter region was reported in certain kinds of malignancies. Previous patho-epidemiological studies indicated that thyroid lymphoma(TL) evolves among active lymphoid cells in chronic lymphocytic thyroiditis(CLTH). With the use of methylation specific polymerase chain reaction, methylation status of DAP-Kinase CpG island was examined in thyroid lesions of 19 cases with TL and 9 with CLTH. Frequency of methylation was higher in TL cases(16 of 19, 84.2%) than in CLTH cases(2 of 9, 22.2%) (p < 0.01). DNA extracted from peripheral blood leukocytes from TL and CLTH cases never showed methylation, indicating that the methylation occurred somatically in lesional lymphocytes in the thyroid. We also examined the methylation status of DAP-kinase gene in 16 cases of T-cell malignancies including eight adult T-cell leukemia/lymphoma and 24 NK/T-cell, 34 B-cell, and two immunophenotypically undetermined lymphomas. Frequency of methylation was higher in B-cell(27 of 34, 79.4%) than in T-cell malignancies(eight of 16, 50%) (p < 0.05). Fifteen of 24(62.5%) NK/T-cell lymphomas showed DNA methylation. Hematopoietic cell lines with a methylated gene were resistant to apoptosis. Treatment of the cells with a demethylating agent restored apoptotic cell death in one B-cell lymphoma cell line with DNA methylation. Our results suggested that suppression of DAP-Kinase expression by DNA methylation might play a role in the development of B-cell malignancies.

Recently, PCR techniques have been introduced for genetic diagnosis of colorectal cancer. The clinical significance of the genetic diagnosis of cancers includes preclinical diagnosis of hereditary cancers and viral tumors, prediction of malignancy and chemosensitivity focusing on expression profiling of related genes, and detection of micrometastasis in lymph node or bone marrow as well as of circulating tumor cells in peripheral blood targeting tumor-specific mRNA expression such as cytokeratin 19, 20 and CEA. In this report, molecular biological techniques for genetic diagnosis of colorectal cancer are discussed.

At present histopathological examination based on clinical findings is the most important and definitive method of diagnosing gastrointestinal tumors. In this field, gene analysis is sometimes used as a supplemental diagnosis. However, fruitful analyses of gene abnormalities in gastrointestinal tumors have facilitated thoughtful morphological diagnosis. Gene diagnosis is expected to play an important role in the grading of malignancy, examining sensitivity for chemotherapy and discovering micrometastases, in cases of cancers definitively diagnosed by histopathology.

Environmental factors act in concert with individual susceptibility to cause most human cancers. The modulation of these environmental factors by host susceptibility has rarely been evaluated. Recently, the molecular epidemiology of human cancer has been extended to a study clarifying individual variation and gene-environmental interactions by integrating molecular biology, in vitro and in vivo laboratory models, biochemistry and epidemiology to infer individual cancer risk. This article briefly reviews genetic polymorphisms frequently used in molecular epidemiological studies and shows, as an example, a possible association between the genetic polymorphisms of CYP17 genes and prostate cancer risk.

Carcinoma is a genetic disease. The malignant phenotype is acquired only after several mutations lead to derangement in a variety of gene products. Traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. In recent years, new technology, called DNA microarray, has attracted interest. This technology promises to monitor the whole genome on a single chip so that researchers can have a better picture of the interactions among thousands of genes simultaneously. In cancers, the detection of minimal residual disease may have prognostic and therapeutic implications. Molecular tools are being used more frequently to enhance the detection of minimal residual disease in many types of cancer. Reverse-transcription polymerase chain reaction (RT-PCR) amplification of genes expressed by the tumor in a tissue-specific manner is the method with the highest diagnostic sensitivity. Quantification of tumor mRNA markers expressed by occult circulating tumor cells may be of prognostic value in a variety of neoplasms and disease stages. Medical professionals need to understand the basic concepts and principles of genetics; the role of genetics in diagnosing and managing different cancers; the ethical, legal and social issues surrounding genetic predisposition testing; and how to manage long-term care of patients at high risk for cancer.