Testicular germ cell tumours in Iceland: a nationwide clinicopathological study.

The purpose of this study was to examine the pathology of all germ cell tumours of the testis diagnosed in Iceland 1955-2002. A total of 214 patients were included in the study. The current age-standardized incidence was found to be 6.1 per 100,000 and had increased almost fourfold during the study period. Seminoma was diagnosed in 55% of cases. Non-seminomas were diagnosed in 45%, and these were further classified as mixed germ cell tumours (33%), embryonal carcinoma (8%), teratoma (3%), and yolk sac tumour (n=1). The mean age at diagnosis was significantly higher for the seminomas than the non-seminomas (38 years versus 29 years) (p<0.001) and the non-seminomas were diagnosed at a significantly higher stage than the seminomas (p<0.001). Thus, in seminoma patients the tumour was localized to the testis (stage I) in 81% of cases, in 17% of patients the tumour had spread to the lymph nodes (stage II or III), and only 2% had extranodal metastasis at diagnosis (stage IV). In contrast, in the non-seminoma patients, the tumours were found to be stage I in 56%, stage II or III in 24%, and stage IV in 20% of cases. No significant difference in staging was found between non-seminoma subtypes. Identification of necrosis or vascular invasion was significantly associated with metastatic disease at diagnosis (p=0.002). During the study period a significant increase in stage I tumours was found as well as a decrease in the size of the tumours.

A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers.

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.

Dynamics of group formation in collective motion of organisms.

A mathematical description of the collective motion of organisms using a density-velocity model is presented. This model consists of a system of nonlinear parabolic equations, a forced Burgers equation for velocity and a diffusion-convection equation for density. The motion is mainly due to forces resulting from the differences between local density levels and a prescribed density level. The existence of a global attractor for a 1D density-velocity model is proved by asymptotic analysis to demonstrate different patterns in the attractors for density. The theoretical results are supplemented with numerical results. These patterns correspond to movements of collective organized groups of organisms such as fish schools and bird flocks.

A population-based analysis of increased incidence and improved survival of testicular cancer patients in Iceland.

OBJECTIVE: For unknown reasons the incidence of testicular cancer has risen dramatically in many industrialized countries. At the same time, the prognosis for these patients has improved even more significantly. This has mostly been explained by the introduction of an effective cisplatin-based multidrug chemotherapy regimen for patients with metastatic or recurrent disease, but better diagnostic tools and surveillance may also play a role. In this population-based study the clinical behaviour of testicular cancer cases (n = 198) in Iceland between 1955 and 1999 was investigated, with a special emphasis on changes in incidence, staging and survival. MATERIAL AND METHODS: The tumours were staged and pathologically classified and the crude probability of survival evaluated. The incidence was calculated for the whole period and further clinical evaluation was done for all the patients diagnosed after 1970 (n = 172). RESULTS: Of 198 patients, 111 (58%) were diagnosed with seminomas and 82 with non-seminomas (42%). Age-adjusted incidence increased from 2.2 per 100,000 men between 1955 and 1959 to 5.3 per 100,000 men between 1995 and 1999 (p < 0.01). More patients were diagnosed with localized disease (stage I) in the second compared to the first time period of the study: 71% vs 52% respectively (p < 0.01). After the introduction of cisplatin-based multidrug chemotherapy in Iceland in 1978, 5-year survival has increased from 67% in the period 1955-77 to 96% in the period 1978-99. CONCLUSIONS: During the study period the incidence of testicular cancer in Iceland increased almost threefold. After multidrug chemotherapy was introduced in 1978 only two patients have died from the disease. Since 1987, patients with stage I disease have been followed with surveillance after orchiectomy, without any deaths. Our population-based findings of increased incidence, lower staging and improved survival of patients with testicular cancer in Iceland are important for planning future treatment strategies. The availability of effective treatment, even for patients with advanced disease, stresses the importance of reducing treatment-related morbidity (infertility and secondary malignancies).

Spontaneous regression of pleural metastases after nephrectomy for renal cell carcinoma--a histologically verified case with nine-year follow-up.

Spontaneous regression of metastatic renal cell carcinoma is a rare but well documented event, most often involving pulmonary metastases. A case of spontaneous regression of histologically verified pleural metastases after nephrectomy is reported.

A population-based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas.

The etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2-3 for first-degree relatives and 1.6 for third-degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC.

[Two cases of spontaneous regression of metastasis secondary to renal cell carcinoma.].

Spontaneous regression of metastatic renal cell carcinoma is a rare but well documented event, most often involving pulmonary metastasis. Two cases involving brain and pleural metastasis are presented. In both cases nephrectomy was the only treatment.