Tohru Nagano

Docetaxel: a therapeutic option in the treatment of cutaneous angiosarcoma: report of 9 patients.

Effective treatment options are limited for patients with cutaneous angiosarcoma (AS). Docetaxel, a member of the taxane family of drugs, reportedly has been effective in the treatment of lung, head and neck, and breast cancers. Another taxane drug, paclitaxel, reportedly had unique activity in the treatment of AS of the scalp and neck and acquired immunodeficiency syndrome‐related Kaposi sarcoma. Therefore, the authors hypothesized that docetaxel may be of value in the treatment of cutaneous AS that is resistant to conventional therapy. However, there were only 3 case reports of the successful treatment of AS in elderly patients using docetaxel in combination with surgery and radiotherapy.

Cyclin D and retinoblastoma gene product expression in actinic keratosis and cutaneous squamous cell carcinoma in relation to p53 expression

Masato Ueda, Abnormality of the molecules regulating the cell cycle has been shown to lead cells to transformation. Recently, overexpression of cyclin D protein, one of the G1 cyclins, and the abnormality of the retinoblastoma gene have been found in various human cancers. We analyzed the expression of cyclin D, retinoblastoma gene product (pRB) and p53 in actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) by immunohistochemistry to elucidate the role of these molecules in keratinocyte carcinogenesis. In the normal epidermis, a few cyclin D positive cells were seen mainly at die basal layer. In 11 seborrheic keratoses, no overexpression of cyclin D was observed. Twelve of 26 AKs (4.5%) and 27 of 45 SCCs (60%) showed cyclin D overexpression. A few pRB positive cells were seen in the basal layer and in the supra‐basal spinous layer of the normal epidermis. An abnormality of pRB, loss of expression, was seen in 2 of 26 AKs (8%) and 7 of 45 SCCs (16%). p53 protein was positive in 12 of 26 AKs (46%) and 24 of 45 SCCs (53%). Forty‐five SCCs examined were divided into 22 ultraviolet (UV)‐related SCCs and 23 UV‐unrelated SCCs. Though UV‐related SCCs showed a significantly higher incidence of p53 positivity, as previously reported by us, no significant difference in cyclin D overexpression and loss of the pRB expression was observed between UV‐related and UV‐unrelated SCCs. These results suggest that cyclin D overexpression is frequently involved in keratinocyte carcinogenesis and that this is an early event, as well as p53 abnormality. In addition, abnormality of the retinoblastoma gene is also related to epidermal cell carcinogenesis, though die frequency is relatively low.

Reduction of ultraviolet-induced skin cancer in mice by topical application of DNA excision repair enzymes

Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6–4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV‐induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 ± 1.3 tumors per mouse, and control mice had 6.3 ± 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome‐treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV‐induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal‐looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome‐treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.

Trends in Nonmelanoma Skin Cancer in Japan

We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976-1980 with those who attended between 1986-1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986-1990 were higher than those from 1976-1980. In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100,000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III. The present study indicates that the prevalences of NMSC and SK in Japanese have increased during the last three decades and that skin type I may be a risk factor for NMSC in Japanese.

Rapid Desensitization with Autologous Sweat in Cholinergic Urticaria

BACKGROUND The majority of patients with cholinergic urticaria presents with strong hypersensitivity to autologous sweat. Patients with severe cholinergic urticaria are frequently resistant to H(1) antagonists which are used in conventional therapies for various types of urticaria. It has been reported that desensitization using partially purified sweat antigen was effective in a patient with cholinergic urticaria. METHODS The aim of this study is to determine the usefulness of rapid desensitization with autologous sweat in severe cholinergic urticaria, because rapid desensitization has proven to be a quick and effective immunotherapy for allergies to various allergens. Six patients with severe cholinergic urticaria who are resistant to H(1) antagonists and have sweat hypersensitivity were enrolled in a rapid desensitization protocol. RESULTS In all six patients, the responses for skin tests with autologous sweat were attenuated after rapid desensitization with autologous sweat. Two of the three cholinergic urticaria patients showed reduced histamine release with autologous sweat after the rapid desensitization with autologous sweat. Further, the rapid desensitization and subsequent maintenance treatment reduced the symptoms in five of the six patients. CONCLUSIONS This study provides evidence that rapid desensitization with autologous sweat is beneficial for treating cholinergic urticaria patients resistant to conventional therapy who have sweat hypersensitivity.

Incidence of actinic keratosis of Japanese in Kasai City, Hyogo

We determined the incidence of actinic keratosis (AK) among Japanese by screening for skin cancer in Kasai City, Hyogo, Japan, between 1993 and 1995. The incidence per 100,000 Japanese residents was 223.6 in 1993 and 171.2 in 1994. The prevalence of AK was 291.2 per 100,000 residents in 1993, 203.7 in 1994, and 86.8 in 1995. The prevalence in people who had more than six seborrheic keratoses on sun-exposed body sites and in people who had experienced severe sunburns with blister formation during childhood were significantly higher. These results indicate that more than six seborrheic keratoses and several episodes of blister formation in childhood may be risk factors for AK in the Japanese.

Prevalence of actinic keratosis in Japan

Most of the epidemiological studies on skin cancer that have been conducted to date have addressed the incidence in light-skinned Caucasians. To determine the prevalence rate of skin cancer and actinic keratosis (AK) on sun-exposed body sites of Japanese in Japan, we examined the skin of 4736 people during health examinations. The study was undertaken in Kasai City, Japan, which had a population of 52,837 in 1992, where participants in a regional health examination were seen by dermatologists. The final diagnosis was made histopathologically. Participants were also interviewed by means of a questionnaire. A total of 36 cases of AK and two of basal cell carcinoma were identified, to give a prevalence of 413.4 per 100,000 for AK. The prevalence among outdoor workers was significantly higher than that of indoor workers. Furthermore, when the participants were classified into three Japanese skin types, the prevalence of AK among people of skin Type I, who are sensitive to UV irradiation, was significantly higher than that among people of skin Types II and III, who are less sensitive.

Successful treatment of Rosai–Dorfman disease with low‐dose oral corticosteroid

We present herein a Japanese case of Rosai–Dorfman disease (RDD) in which cutaneous manifestations completely remitted after treatment with low‐dose oral corticosteroid. A 69‐year‐old Japanese man presented with a 1‐year history of enlarged submandibular lymph nodes and subsequent nasal and pharyngeal bleeding. RDD was diagnosed based on biopsy results from a lymph node in the left parotid region. The patient had also noted several skin eruptions that repeatedly appeared and disappeared on the face and arms. Biopsies were taken from skin eruptions on the face and cuboidal fossa. Both biopsy specimens showed dense, well‐demarcated infiltration of histiocytes, lymphocytes and multinucleated giant cells from just under the epidermis to the subcutaneous tissue. These histiocytes were positive for CD68 and S‐100, but negative for CD1a, and some displayed emperipolesis. Given the histopathological findings and the fact that the patient was suffering from RDD, skin lesions were diagnosed as cutaneous manifestations of RDD. Cutaneous lesions gradually began to persist concomitant with enlargement of extranodal lymphadenopathy in the nasopharyngeal area. Increasing respiratory obstruction prompted a trial with oral prednisolone commencing at 0.4 mg/kg per day. Both the lymphadenopathy and skin lesions responded quickly. Within 3 months, all his skin lesions disappeared completely with almost complete resolution of lymphadenopathy. Twelve months after the beginning of oral prednisolone therapy, slight recurrence of mucosal and cutaneous lesions appeared, but disappeared quickly with an increase in prednisolone to 0.3 mg/kg per day. Low‐dose prednisolone appeared very effective in the case of RDD.

Expression of p53 protein in melanoma progression

p53, A tumor suppressor gene, has been documented as the most frequently mutated gene in human cancers including non-melanoma skin tumors. It has been controversial whether the p53 gene mutation plays a major role for melanoma genesis. To examine the role of p53 in human malignant melanoma carcinogenesis, we performed immunohistochemical analysis using anti-p53 antibodies (CM-1 and DO-7) in microwaved paraffin sections. When cases having more than 1% reactive cells were regarded as positive, immunohistochemical analysis revealed that in primary melanomas 14 of 51 (27%) were positive with CM-1 or 15 of 51 (29%) were positive with DO-7. Tumor thickness of primary melanomas in p53 positive cases was significantly thicker than that in p53 negative cases. In metastatic melanomas, 35 of 41 (85%) lymph node metastases were positive with either antibody and in skin metastases 16 of 28 (57%) lesions with CM-1 or 18 of 28 (64%) lesions with DO-7 were positive. The mean percentages of reactive cells were 2.3% in primary lesions and 4.9% in metastases. The incidence of positivity was significantly higher in metastases than primary lesions. In 10 cases examined, with both primary and metastatic melanoma, 3 cases were negative in both lesions and 1 case was positive in both lesions, while 6 cases were negative in the primary lesions and positive only in metastatic lesions. Four Spitz nevi, 6 dysplastic nevi and 11 common nevi were all negative. These data suggest that the expression of p53 protein may be a late event in melanoma progression.

Cutaneous infection caused by Curvularia species in an immunocompetent patient.

increases by hours, and makes most fungal elements become visible even they are embedded in thick specimens such as in nail scrapings. Most nonfungal objects are not stained or only slightly stained in a pale purple colour. Stained preparations were well preserved if drying up is avoided. Alkaline Trypan Blue has merits in staining speed and specificity compared with Direct Blue 1 or Parker ink. We propose Alkaline Trypan Blue as a new potent stain for fungi in keratinous tissue.