Dermatology Division

Introduction
Most of the patients seen by the Dermatology Division are treated for skin cancer. We also conduct basic research on skin cancer. The division has the largest pool off patients with skin cancer in the country, as patients are referred from all over the country. Surgery is the main treatment modality for skin cancer, and multidisciplinary treatments, consisting of chemotherapy, immunotherapy, and radiotherapy, are also routinely carried out in this division. In addition, the division takes the lead in advanced medical treatment for skin cancer all over the country, and plays the most active part in multicenter trials.

Routine Activities
Thereare two staff dermatologists and three residents in the division. In the outpatient clinic, new patients and follow-up patients are seen every day except Tuesday, which is reserved for surgery.
Operations including wide local resection, finger- and toe-amputation, free skin graft, local skin flap plasty, and selective and radical lymph node dissection are mainly performed in the division. Rounds are made and case presen-tations are held every morning. A division conference is held every Monday to discuss the therapeutic principles for outpatients and inpatients. A clinicopathological conference focusing on surgically removed skin specimens is held with pathologists once a month.

Research Activities
1. Malignant melanoma
The Dermatology Division cooperates with the Japanese Society for Skin Cancer in gathering data for the epidemiological and statistical survey of Japanese melanoma patients. Ishihara et al described the Society s nation-wide survey obtained from 24 main medical institutions in Japan in the period of 1987 to 1996. The survey revealed that the number of patients with malignant melanoma was increasing. The data was analyzed base on sex, primary sites, disease subtype, disease stage, Clark s level of invasion and Breslow s tumor thickness. The prognosis of advanced melanoma is poor, as it is highly resistant to chemotherapy. Thus, early detection is mandatory in order to improve the prognosis.
Elective lymph node dissection has been the usual treatment in cases where the tumor thickness at the primary focus is >3 mm in Japan. This division has assessed sentinel node technology using 1% patent blue. Sentinel nodes could be detected at a high rate in the inguinal region, but detection was difficult in the axillary and cervical regions. Thus combination method using radioisotope and 1% patent blue is planned recently.
5-S-cysteinyldopa (5-S-CD) has been used as a biological marker of melanoma progression. Wakamatsu et al measured serum levels of 5-S-CD in 2,648 samples taken from 218 patients in order to evaluate the usefulness of this parameter to follow melanoma progression and prognosis. The sensitivity of elevated serum 5- S-CD levels in detecting distant metastasis was 73% while the specificity was 98% and the positive predictable value was 94%. And the other results prove that the level of 5-S-CD in the serum is a sensitive and specific marker to predict distant metastasis.
Serological identification of tumor antigens by cDNA expression cloning is a technique used to isolate cDNAs encoding tumor antigens that are recognized by IgG antibodies in sera from cancer patients. It is also useful for the isolation of tumor antigens recognized by T cells. Kiniwa et al applied this method to identify melanoma antigens recognized from the serum of a patient with a good prognosis who had T-cell-infiltrated melanoma and vitiligo.
1. Sweat gland carcinoma
Eccrine spiradenoma is a well-differentiated benign tumor of the sweat glands. Malignant change arising within eccrine spiradenoma is rare. Ishikawa et al described a patient with malignant eccrine spiradenoma exhibiting both cartinomatous and sarcomatous differentiation who died from systemic metastasis 7 months after
diagnosis

Clinical Trials
(1) Sentinel node technology is being assessed using 1% patent blue in melanoma patients and combination
method with radioisotope and 1% patent blue is planned recently.
(2) Combination chemotherapy consisting of dimethyl-triazeno-imidazol carboxamide, nimustine hydrochloride, cis-diaminedichloro-platinum, and tamoxifen is being assessed for advanced malignant melanoma.
(3) Serum 5-S-cysteinyldopa levels as tumor maker of malignant melanoma are periodically measured. We are studying their correlation with the patho-physiological conditions of patients.
(4) A new allogeneic immunotherapy with a non-myeloablative transplantation regimen is being assessed for the treatment of metastatic melanoma in a phase I clinical trial. We have conducted clinical studies for two patients, and intend to investigate more cases.
(5) A new immunotherapy using melanoma-associated antigen is being assessed for treatment of metastatic melanoma in a phase I clinical trial. This is a procedure of taking samples from peripheral blood of patients, pulsing the cultivated dendritic cells with melanoma-specific antigen peptides, and subcutaneously administering the dendritic cells to the patients in the vicinity of the superficial lymph nodes.

A. YAMAMOTO

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