Malignant melanoma of the vulva. Report of 89 patients.

BACKGROUND: Rates of melanoma have increased worldwide over the last few decades. Currently, this rate of increase is greater for melanoma than for any other cancer in the U.S. Approximately 3% of all melanomas diagnosed in women are located within the genital tract, predominantly affecting the vulva. Overall, melanomas of the vulva account for 2-10% of all malignancies of the female external genitalia. Due to the rarity of this disease, treatment recommendations do not exist. METHODS: This retrospective study was designed to evaluate the significance of clinical and pathologic features for survival among 89 patients examined for malignant melanoma at 5 hospitals in Germany from 1978 to 1991. A complete workup based on age, initial symptoms, tumor localization, presence of ulceration, postoperative stage, surgical procedure, and survival, was performed. RESULTS: The overall 5-year survival rate of 36.7% confirms the poor prognosis of this disease. Definitive treatment concepts require a standardized treatment of patients with malignant melanoma of the vulva; however, because of the rarity of vulvar melanomas, prospective studies are difficult to perform. CONCLUSIONS: Parameters such as age, Breslow's thickness of invasion, Clark's level of invasion, lymph node involvement, anatomic site, and postoperative stage are prognostic factors for survival. Surgery should be performed in accordance with the accepted standards for cutaneous melanoma.

[HPV-Dna hybridization allows differentiation of cervix lesions in PAP III cytologic findings]. / Die HPV-DNA-Hybridisierung ermöglicht eine Differenzierung zervikaler Läsionen bei PAP III Zytobefunden.

A repeat Pap smear as well as a smear for human papillomavirus (HPV)-DNA detection with the Hybrid Capture assay (Digene diagnostics/Murex, Burgwedel) were collected from 30 women with Pap smears recurrently classified as "Pap III". All patients underwent colposcopy and histological assessment. The repeat Pap smear distinguished correctly in 15, colposcopy in 19 and the Hybrid Capture assay in 27 cases between neoplastic and inflammatory lesions. All invasive neoplasms were positive for HPV-DNA. HPV typing seems to be a suitable non-invasive method for early selection of cervical lesions that need histological assessment in women with smears classified as "Pap III".

[Electrosurgical loop excision of the transformation zone in treatment of cervix neoplasia]. / Die elektrochirurgische Schlingen-exzision der transformationszone (LEEP) zur Behandlung zervikaler Neoplasien.

100 patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were treated with the loop electrosurgical excisional procedure (LEEP). Compared with 60 women who underwent cold-knife conization, the number of lesions classified as CIN-3 or more did not differ between the two groups (53% vs 53.3%). Severe haemorrhage and cervical stenosis were only observed after conization. Involvement of resection margins was found in 18% of all LEEP and in 16.7% of all cone biopsies. 3-12 months after LEEP the rate of cytologically and biopsy proven neoplasia was 2.2%. LEEP is a safe and effective procedure and should be used as the treatment of choice for distinct cervical lesions.

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Pattern of carboplatin-induced emesis. The German Ondansetron Study Group.

In contrast to the broad experience concerning the therapeutic use of carboplatin, only limited data are available regarding the patterns of carboplatin-induced emesis, one of its most distressing side effects. This study reports frequency, severity and time course of carboplatin-induced vomiting and nausea refractory to 5-HT3 antagonism. A total of 216 patients receiving single-day carboplatin-based chemotherapy regimen were enrolled into an open multicenter study focusing on the safety and efficacy of ondansetron 8 mg t.d.s. Emesis on day 1 occurred in 22% and nausea in 75% of the patients; 44% of patients reported some degree of vomiting within the 5 days observation period. The risk for emesis and nausea over 2-5 days was increased in patients suffering from emesis on day 1 (relative risk 2.25 for vomiting and 2.84 for nausea, respectively). The median cumulative number of emetic episodes was 0 for all patients and 4 for the patients who did vomit at least on 1 day. Vomiting began on average 1.77 days following chemotherapy administration. The mean duration of vomiting was 2 days and 3.1 days for nausea. Carboplatin showed a monophasic prolonged pattern of emesis. The combination with cyclophosphamide led to an earlier onset and a higher frequency of vomiting. The analysis of the pattern of emesis refractory to 5-HT3 receptor blockade should help to describe the course of emesis, which is probably triggered through a 5-HT3 receptor-independent mechanisms.

Cyclophosphamide, methotrexate, 5-fluorouracil, and folinic acid (CMFF) as first line chemotherapy for treatment of advanced breast cancer. A pilot study.

In order to evaluate the maximum tolerable dose of a combination chemotherapy consisting of cyclophosphamide, methotrexate, 5-fluorouracil, and folinate (CMFF), 30 female patients with histopathologically confirmed, previously untreated advanced breast cancer were entered into this pilot study. Chemotherapy consisted of fixed doses for methotrexate (40 mg/m2 i.v. on day 1), 5-fluorouracil (500 mg/m2 i.v. on day 2 to 4) and folinic acid (2 x 200 mg/m2 i.v., 0 + 2 h on day 2 to 4). The dose of cyclophosphamide was escalated stepwise, starting with 200 mg/m2 i.v. on day 2 to 4, to 240 mg/m2, 290 mg/m2, 360 mg/m2 and 400 mg/m2, respectively, for each subsequent five patients. Treatment was repeated every four weeks. A total of 92 treatment cycles was given. Myelosuppression was the dose-limiting toxicity: leukopenia WHO grade III or IV was observed after a total of 28 cycles and anemia of equal intensity after 1 cycle. No thrombocytopenia WHO grade III or IV was recorded. Myelotoxicity increased with higher doses of cyclophosphamide. Among non-hematologic toxicities, alopecia was reported in two-thirds of the patients. Nausea and vomiting was noted in 25% of treatment cycles, but in one cycle only WHO grade III was recorded. No other toxicities exceeding WHO grade II occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

[Uterine metastases of malignant melanoma]. / Uterine Metastasen maligner Melanome.

Uterine metastases of extragenital malignomas are rarely presented in literature. Malignant melanoma as primary tumour is described more often than can be expected with regard to its relative incidence in comparison to other malignomas. If the uterus is involved in melanoma disease, mostly cervix and myometrium are affected, endometrial metastases are considered to be very rare. If the primary tumour is known, bleeding abnormalities frequently lead to the diagnosis of uterine metastases, but occasionally abnormal bleeding appears to be the first symptom of melanoma disease. In the following another such case is described and an additional case of endometrial metastases of malignant melanoma is presented.

[Malignant melanoma in gynecology]. / Das maligne Melanom in der Gynäkologie.

The malignant melanoma mostly is situated on the skin, the vulva being more often affected then expected in relation to its share in the total body surface. The peak of incidence lies in the fifth and sixth life decade. Five types of the tumor are known: lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, acrolentiginous melanoma and non-classifiable melanoma. For estimation of prognosis and choice of adequate mode of therapy histopathological examinations with regard to the level of invasion according to Clark and Chung, histomorphometric evaluation of the depth of invasion suggested by Breslow and the pronostic index of Schmoeckel and Braun-Falco are useful. The operative therapy of choice is the extensive tumor excision. In case of extended local invasion radical vulvectomy is indicated, in certain cases combined with inguinal, sometimes even pelvic lymphonodectomy. In inoperable cases radiotherapy may be tried, but success seems to be poor. Polychemotherapy may induce remissions, but hardly a prolongation of survival. New therapy trials are dealing with immunmodulation, mostly using different substances of biological response modifiers. The prognosis of malignant melanoma of the vulva must be considered to be poorer than that of melanomas in other sites of the body, local recurrence is frequent, the five year survival rate being 30-35%. Whether pregnancy does have an effect on melanoma growth is still unknown. Early stages of melanoma disease may be treated without interrupting pregnancy, whereas advanced stages require termination of pregnancy, followed by specific tumor therapy.

Inhomogenous capillary flow and its prevention by verapamil and hydralazine in the cardiomyopathic Syrian hamster.

There is clinical evidence that human dilated cardiomyopathy is related to microcirculatory disorders. We used an experimental preparation of the disease that consisted of a study of the microcirculation of 45 cardiomyopathic Syrian and 18 control hamsters with timed plasma staining. To investigate dynamic vascular disorders a double injection technique was used that permitted demonstration of all permanently and temporarily perfused capillaries in the same animal. The results showed a total capillary density of 3423 +/- 470 capillaries/mm2 in the cardiomyopathic hamster during the premyocytolic phase (30 days of age) and that of 3289 +/- 506 capillaries/mm2 during the myocytolytic phase (44 days). These values were not significantly different from those in the control group (3349 +/- 473 capillaries/mm2 at 30 days and 3383 +/- 556 capillaries/mm2 at 44 days). However, tissue areas with extended coronary transit times were detected only in the cardiomyopathic hamsters. These areas were of the same individual and cumulative size at 30 days (diameter approximately 200 micron, 4% of the tissue) as the myocytolytic zones at 44 days. In cardiomyopathic hamsters verapamil and hydralazine prevented both hypoperfusion and myocytolysis. The results favor the view that microcirculatory disorders generate tissue damage in the cardiomyopathic hamster and that these disorders can be prevented through treatment with the calcium antagonist verapamil or with the vasodilator hydralazine.