Large cell neuroendocrine carcinoma of the lung: an aggressive disease potentially treatable with surgery

BACKGROUND: Assessment of clinical and pathologic features of large cell neuroendocrine carcinoma to confirm its specificity in the setting of high grade neuroendocrine pulmonary tumors. METHODS: From 1989 to 2001, 123 patients with a neuroendocrine carcinoma were surgically treated in a curative intent at a single institution. According to the 1999 World Health Organization classification, 20 patients were reviewed as having a large cell neuroendocrine carcinoma. Clinical data as well as detailed pathologic analysis and survival were collected. RESULTS: There were 18 men and 2 women. The median age was 62 years. Four patients had a preoperative diagnosis of large cell neuroendocrine carcinoma. The resections consisted of 14 lobectomies and 6 pneumonectomies. There was no operative death. Complications occurred in 7 patients (35%). Four patients had a stage I of the disease, 4 had stage II, 9 had stage III, and 3 had stage IV. At follow-up (median, 46 months), 13 patients died from general recurrence and 7 patients were still alive. Median time to progression was 9 months (range, 1 to 54 months). The 5-year survival rate was 36% (median, 49 months) and it seemed to be negatively influenced by the disease stage (54% for stage I-II vs 25% for stage III-IV; p = 0.07), the presence of metastatic lymph node (45% for N0/N1 vs 17% for N2; p = 0.12), or vessel invasion (66 vs 25%; p = 0.18). CONCLUSIONS: Large cell neuroendocrine carcinoma predominantly occurred in men. An accurate tissue diagnosis was rarely obtained preoperatively. Although overall survival after resection was substantial, large cell neuroendocrine carcinoma frequently showed pathologic features of occult metastatic disease, such as lymph node or vessel invasion, or both.     

Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases

The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57 weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1-2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and soft-tissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.     

The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors

Nonmelanoma skin cancer is the most commonly diagnosed malignant disease in Caucasians. Known risk factors include fair skin, sun exposure, male gender, advancing age, and the presence of solar keratosis. No viral risk factors have been established thus far. To examine the association between nonmelanoma skin cancer and infection with human papilloma virus (HPV) types, we performed a retrospective study in which skin biopsies were collected from 496 nonimmunosuppressed patients attending dermatologic clinics during a defined period and for whom a biopsy or resection of a tumor was indicated for medical reasons. A total of 390 patients with histologically confirmed diagnosis of warts (n = 209), solar keratosis or Bowen's disease (n = 91), squamous cell carcinoma (n = 72), or basal cell carcinoma (n = 18), as well as 106 control patients with normal skin was analyzed for infection with HPV and, if positive, HPV typed by sequencing. Logistic regression was performed to separately investigate association of certain HPV types with the occurrence of warts, precancerous lesions, and skin cancer compared with normal skin. For all three histological groups, both crude risk and risk adjusted for age, sex, and sun exposure were calculated. HPV DNA was detected in only 4.7% of controls, in 90.9% of benign warts, in 60.4% of precancerous lesions, in 59.7% of squamous cell carcinoma, and in 27.8% of basal cell carcinoma, which demonstrates that viral infection is specifically linked to skin disorders. The distribution of viral types found is distinctly different between warts and precancers or cancers, supporting an etiologic role of specific HPV types. This is supported by statistical analysis, where after adjusting for age, gender, and sun exposure, the odds ratio for nonmelanoma skin cancer in patients who were DNA positive for the high-risk mucosal HPV types, 16, 31, 35, and 51 was 59 (95% confidence interval, 5.4-645) with normal skin as controls. These findings suggest that persistent infections of the skin with high risk genital HPV types recently identified as significant risk factors for cervical cancer may also represent a risk factor for nonmelanoma skin cancer in a nonimmunosuppressed population.     

Epidemiology of cutaneous melanoma in Germany and worldwide

Rising incidence rates of cutaneous melanoma have been observed during the last three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per 100,000 inhabitants and year were reported by the Saarland Cancer Registry in Germany. Other incidence studies from Germany in the 1990s even reported 10-12 cases per 100,000 inhabitants and year, which is more likely to be the representative melanoma incidence in Western Germany. In a worldwide comparison this is a medium incidence rate as compared to clearly higher incidence rates in the United States (10-20 cases per 100,000 inhabitants and year) and in Australia (40-60 cases per 100,000 inhabitants and year). In Europe the highest incidence rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants and year) and the lowest from the Mediterranean countries (about 5-7 cases per 100,000 inhabitants and year). Mortality rates likewise increased in Germany between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to 2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many other countries a leveling off of mortality rates was observed. 48,928 melanoma patients have been recorded by the Central Malignant Melanoma Registry from the German-speaking countries in the time period from 1983 to September 2000, and clinico-epidemiological analysis of cutaneous melanoma is based on this data material. While 2/3 of all melanoma patients in Germany were females in the 1970s, there is now a more balanced gender distribution with more than 45% of patients being males. Age distribution does not significantly change during the last three decades. Most melanomas are diagnosed in the age group between 50 and 60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear decrease of Breslow's tumor thickness was found from the beginning of the 1980s to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower Breslow's tumor thickness at first diagnosis of cutaneous melanoma has only been reported from Australia. This development indicates improved early recognition of cutaneous melanoma which is presently the main factor for a more favorable prognosis.     

German Cohort Study of Women's Health--benefits of oral contraceptives. Study protocol

This publication is about the study protocol of the German Cohort Study on Women's Health. The main objective is to investigate medical benefits of a long-term oral contraceptive use. The design is an analytical cohort study based on inquiries. Additional cases will be recruited to analyse rare events in separate case-control studies. Voluntary participants who signed to participate in a long-term study are included. An annual drop-out rate of 15% is expected. Study variables encompass personal characteristics, lifetime history of diseases, but also disturbances of the state of health, and quality of life. It is anticipated to achieve 400,000 women-years of observation by 2001 (historic and concurrent follow-up). The study started April 1, 1998 and the current financial phase finishes December 31, 2001. 6000 participants were recruited until December 1998 equivalent to about 190,000 observation-years. Until the end of 1999, an additional 70,000 women-years should be included. There have been many suggestions from participants' to include additional issues of women's health into the study.     

High prevalence of seborrhoeic dermatitis on the face and scalp in mountain guides

BACKGROUND: High incidence rates of seborrhoeic dermatitis (SD) have been reported in HIV-infected individuals, indicating immunosuppression to be involved in the pathogenesis. OBJECTIVE: To establish the prevalence of SD in mountain guides who have a high occupational exposure to solar UV radiation. PATIENTS AND METHODS: In November 1999, 283 mountain guides were physically examined on the face and scalp for symptoms of SD in Austria (n = 75), Switzerland (n = 123) and Germany (n = 85); they were 21.3-93.1 years of age (median age 41.4 years). RESULTS: Forty-six of 283 (16. 3%) mountain guides when examined clinically were found to have SD. The median age of mountain guides with SD was 41.2 years. There were similar incidence rates in all three countries. CONCLUSION: SD affects mountain guides in a clearly higher percentage as the general population. We suggest UV-induced immunosuppression due to occupational sun exposure as a pathogenetic factor.     

Epidemiologie, Prävention und Nachsorge maligner Melanome

Das maligne Melanom der Haut geh?rt zu den Tumoren, bei denen ein schneller Anstieg der Inzidenz und ebenfalls ein deutlicher Anstieg der Mortalit?t zu verzeichnen ist. W?hrend die Inzidenzrate bei etwa 3 F?llen/100.000 Einwohner/Jahr zu Beginn der 70er Jahre lag, wird die gegenw?rtige Inzidenz auf 12 F?lle/100.000 Einwohner/Jahr gesch?tzt. Auf der anderen Seite findet sich beim Melanom eine deutliche Verbesserung der Früherkennung. W?hrend die mediane Tumordicke Anfang der 80er Jahre bei ca. 1,3 mm lag, lag sie in der 2. H?lfte der 90er Jahre bei 0,8 mm. Damit hat sich die Prognose maligner Melanome verbessert und eine Heilung wird bei ca. 70% aller Patienten durch die prim?re Exzision erzielt. Die vertikale Tumordicke nach Breslow ist der wichtigste prognostische Faktor prim?rer kutaner Melanome, gefolgt vom Invasionslevel nach Clark, histologisch gesicherter Ulzeration sowie Geschlecht des Patienten und Lokalisation des Tumors. Die Verbesserung der Früherkennung ist v. a. auf gro?e Aufkl?rungskampagnen zurückzuführen, die insbesondere von den dermatologischen Gesellschaften durchgeführt wurden. Auf der anderen Seite wurden mit Einführung der Auflichtmikroskopie auch die diagnostischen M?glichkeiten der Dermatologen zur Erkennung des Melanoms verbessert. Eine weitere Verbesserung der Früherkennung ist allerdings notwendig, noch immer kommt etwa die H?lfte der Patienten mit Tumoren zur ersten Diagnose, bei denen ein erh?htes Metastasierungsrisiko besteht. In der Versorgung der Melanompatienten spielt die Nachsorge eine wichtige Rolle. Mehr als 80% aller Rezidive werden in geordneten Nachsorgeuntersuchungen erkannt. Die Früherkennung von Rezidiven (inbesondere lokoregion?ren Rezidiven) ist von wichtiger prognostischer Bedeutung für die Patienten. In den letzten Jahren hat sich die Lymphknotensonographie als wesentliche Untersuchungstechnik zur Früherkennung lokoregion?rer Metastasierungen etabliert. Das von der Deutschen Dermatologischen Gesellschaft vorgeschlagene Nachsorgeschema wird zurzeit kritisch geprüft, bei dünnen Tumoren kann wahrscheinlich auf technische Untersuchungen verzichtet werden. Die Verbesserung der Früherkennung und die Optimierung der Nachsorgeuntersuchungen sind wichtige Zielsetzungen in der künftigen Versorgung von Patienten mit kutanen malignen Melanomen.     

Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women.

BACKGROUND: The risk of cardiovascular disease associated with progestogen-only pills has rarely been studied so far. METHODS: In the Transnational case-control study we were looking for a potential cardiovascular disease risk with oral progestogen-only pills in women aged 16-44 years. A total of 1058 cases of myocardial infarction, thromboembolic cerebrovascular accident or venous thromboembolism, and 3808 controls unaffected by these diseases, were enrolled. The group of women who had either used oral progestogen-only pills or no oral contraceptives included 394 cardiovascular disease cases (123 cases of myocardial infarction, 90 cases of thromboembolic cerebrovascular accident and 181 cases of venous thromboembolism) and 2366 controls. RESULTS: The adjusted (matched) odds ratio (OR) for all cardiovascular diseases combined for women using progestogen-only pills compared with non-users of oral contraceptives was 0.84 (95% confidence interval (CI), 0.45-1.58). The adjusted ORs for myocardial infarction, thromboembolic cerebrovascular accidents and venous thromboembolism for users of progestogen-only pills were 0.94 (95% CI, 0.31-2.91), 1.60 (95% CI, 0.24-0.72) and 0.68 (95% CI, 0.28-1.66), respectively. Hence, there was no significant increase in cardiovascular disease risk associated with progestogen-only pill use. The association between cardiovascular disease and established risk factors (smoking and hypertension) was confirmed. CONCLUSION: Although limited by the small number of exposed cases, our data suggest that there is no convincing evidence for an increased risk of cardiovascular disease associated with progestogen-only pill use.