Familial testicular cancer in Norway and southern Sweden.

Information about occurrence of testicular cancer (TC) in relatives of TC patients has been collected using questionnaires from 797 out of 922 consecutive Norwegian and 178 out of 237 Swedish patients with TC seen at the Norwegian Radium Hospital and the University Hospital Lund in Sweden during 1981-91. Fifty-one Norwegian and five Swedish patients had a relative with confirmed TC. Thus, 51/922 (5.5%) of the Norwegian and 5/237 (2.1%) of the Swedish patients treated during the time interval investigated were considered to have familial TC. Thirty-two of the patients had an affected first-degree relative. Expected numbers of cancers in the relatives were computed from data in the Norwegian and Swedish Cancer Registries. Standardised incidence ratios (SIRs) were taken as observed numbers of TC/expected numbers of TC in the relatives. The SIR for brothers was 10.2 (95% confidence interval 6.22-15.77). SIR for fathers was 4.3 (1.6-9.3) and for sons 5.7 (0.7-23.2). The point estimate for the risk to brothers in the Norwegian part of the sample to develop TC by the age of 60 was 4.1% (95% CI 1.7-6.6%). This study indicates that genetic factors may be of greater importance in TC than previously assumed. Patients with familial testicular cancer had bilateral tumours more often than sporadic cases (9.8% bilaterality in familial vs 2.8% in sporadic cases, P=0.02). For patients with seminoma age of onset was lower in familial than in sporadic cases (32.9 vs 37.6 years, P=0.06). In father-son pairs, there was a statistically significant earlier age of diagnosis in the generation of sons (28.8 years vs 44.9 years, P=0.04). The prevalence of undescended testis (UDT) did not seem to be higher in familial than in sporadic TC (8.2% in familial TC and 13.3% in sporadic cases). This may indicate that different factors are of importance for the development of familial TC and UDT

Risk of cancer in relatives of testicular cancer patients.

The incidence of cancer at sites other than the testis has been investigated in the families of 797 Norwegian and 178 Swedish patients diagnosed with testicular cancer during 1981-91. In the families of the Norwegian patients, the total number of cancers in the relatives was significantly lower than the expected number derived from national incidence rates [observed number of cancers 250, expected number of cancers 281.92, standardised incidence ratio (SIR) 0.89, 95% confidence interval (CI) 0.78-1.00]. This finding can be accounted for almost entirely by the finding of fewer than expected prostate and gastrointestinal cancers in the parents of cases. The other common cancers were found at slightly lower than or near the expected levels in the relatives. In the Swedish cohort, which accounts for less than 20% of cases, the observed number of cancers was very close to the expected number. Fourteen fathers of cases had prostate cancer compared with 27.57 prostate cancers expected, giving a SIR of 0.51 (P=0.006). Mothers had more lung cancers (ten cases observed, SIR=2.11, P=0.04) and cancers of the endometrium than expected (13 cases observed, SIR=1.73, P=0.09). These findings may be interpreted as support for theories proposing hormonal dysfunction as causing testicular cancer. Fifty-four gastrointestinal cancers were observed in the parents compared with 68.48 expected (SIR=0.78, P=0.082). Furthermore, testicular cancer was not found to be associated with the known dominantly inherited cancer syndromes [Familial breast (-ovarian) cancer, hereditary no-polyposis colon cancer]. However, one patient belonged to a Li-Fraumeni family, raising the possibility that testicular cancer may be an infrequent component of this rare cancer syndrome. This study supports the hypothesis that families of testicular cancer patients are not prone to cancer

Familial risk in testicular cancer as a clue to a heritable and environmental aetiology

We used the nation-wide Swedish Family-Cancer Database to examine the risk for testicular cancer in offspring through parental and sibling probands. Among 0-68-year-old offspring, 4082 patients had testicular cancer in years 1961-2000, among whom 68 (1.67%) had an affected father/brother. Standardized incidence ratios (SIRs) for familial risk were four-fold when a father and nine-fold when a brother had testicular cancer. Histology-specific risks (for the testicular cancer) were similar for sons of affected fathers, but were higher among brothers for teratoma and seminoma than for mixed histologies. Standardized incidence ratios for either histology depended on the age difference between the brothers: 10.81 when the age difference was less than 5 years compared to 6.69 for a larger age difference. Parental colorectal, pancreatic, lung and breast cancer and non-Hodgkin's lymphoma and Hodgkin's disease were associated with seminoma among sons. Seminoma risk was also increased when a sibling had melanoma. Teratoma was associated with parental lung cancer and melanoma. The high familial risk may be the product of shared childhood environment and heritable causes. Familial cases of fraternal pairs with an early-onset teratoma represent a challenge for gene identification

Strain and strain rate parametric imaging. A new method for post processing to 3-/4-dimensional images from three standard apical planes. Preliminary data on feasibility, artefact and regional dyssynergy visualisation

BACKGROUND: We describe a method for 3-/4D reconstruction of tissue Doppler data from three standard apical planes, post processing to derived data of strain rate / strain and parametric colour imaging of the data. The data can be displayed as M-mode arrays from all six walls, Bull's eye projection and a 3D surface figure that can be scrolled and rotated. Numerical data and waveforms can be re-extracted. METHODS: Feasibility was tested by Strain Rate Imaging in 6 normal subjects and 6 patients with acute myocardial infarction. Reverberation artefacts and dyssynergy was identified by colour images. End systolic strain, peak systolic and mid systolic strain rate were measured. RESULTS: Infarcts were visualised in all patients by colour imaging of mid systolic strain rate, end systolic strain and post systolic shortening by strain rate. Reverberation artefacts were visible in 3 of 6 normals, and 2 of 6 patients, and were identified both on bull's eye and M-mode display, but influenced quantitative measurement. Peak systolic strain rate was in controls minimum -1.11, maximum -0.89 and in patients minimum -1.66, maximum 0.02 (p = 0.04). Mid systolic strain rate and end systolic strain did not separate the groups significantly. CONCLUSION: 3-/4D reconstruction and colour display is feasible, allowing quick visual identification of infarcts and artefacts, as well as extension of area of post systolic shortening. Strain rate is better suited to colour parametric display than strain

Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment

The current follow-up study concerning the supraglottic type of exercise-induced laryngeal obstruction (EILO) was performed to reveal the natural history of supraglottic EILO and compare the symptoms, as well as the laryngeal function in conservatively versus surgically treated patients. A questionnaire-based survey was conducted 2–5 years after EILO was diagnosed by a continuous laryngoscopy exercise (CLE) test in 94 patients with a predominantly supraglottic obstruction. Seventy-one patients had been treated conservatively and 23 with laser supraglottoplasty. The questionnaire response rate was 70 and 100% in conservatively treated (CT) and surgically treated (ST) patients, respectively. A second CLE test was performed in 14 CT and 19 ST patients. A visual analogue scale on symptom severity indicated improvements in both the groups, i.e. mean values (± standard deviations) declined from 73 (20) to 53 (26) (P < 0.001) in the CT group and from 87 (26) to 25 (27) (P < 0.001) in the ST group. At follow-up, ST patients reported lower scores regarding current level of complaints, and higher ability to perform exercise, as well as to push themselves physically, all compared to CT patients (P < 0.001). CLE scores were normalized in 3 of 14 (21%) CT and 16 of 19 (84%) ST patients (Z = −3.6; P < 0.001). In conclusion, symptoms of EILO diagnosed in adolescents generally decreased during 2–5 years follow-up period but even more after the surgical treatment. Patients with supraglottic EILO may benefit from supraglottoplasty both as to laryngeal function and symptom relief

Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa.

Autosomal recessive cutis laxa type I (ARCL type I) is characterized by generalized cutis laxa with pulmonary emphysema and/or vascular complications. Rarely, mutations can be identified in FBLN4 or FBLN5. Recently, LTBP4 mutations have been implicated in a similar phenotype. Studying FBLN4, FBLN5, and LTBP4 in 12 families with ARCL type I, we found bi-allelic FBLN5 mutations in two probands, whereas nine probands harbored biallelic mutations in LTBP4. FBLN5 and LTBP4 mutations cause a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seems to be more severe in patients with LTBP4 mutations. Functional studies showed that most premature termination mutations in LTBP4 result in severely reduced mRNA and protein levels. This correlated with increased transforming growth factor-beta (TGFβ) activity. However, one mutation, c.4127dupC, escaped nonsense-mediated decay. The corresponding mutant protein (p.Arg1377Alafs(*) 27) showed reduced colocalization with fibronectin, leading to an abnormal morphology of microfibrils in fibroblast cultures, while retaining normal TGFβ activity. We conclude that LTBP4 mutations cause disease through both loss of function and gain of function mechanisms

Guidelines for follow-up of women at high risk for inherited breast cancer: Consensus statement from the Biomed 2 Demonstration Programme on Inherited Breast Cancer

Protocols for activity aiming at early diagnosis and treatment of inherited breast or breast-ovarian cancer have been reported. Available reports on outcome of such programmes are considered here. It is concluded that the ongoing activities should continue with minor modifications. Direct evidence of a survival benefit from breast and ovarian screening is not yet available. On the basis of expert opinion and preliminary results from intervention programmes indicating good detection rates for early breast cancers and 5-year survival concordant with early diagnosis, we propose that women at high risk for inherited breast cancer be offered genetic counselling, education in ‘breast awareness’ and annual mammography and clinical expert examination from around 30 years of age. Mammography every second year may be sufficient from 60 years on. BRCA1 mutation carriers may benefit from more frequent examinations and cancer risk may be reduced by oophorectomy before 40–50 years of age. We strongly advocate that all activities should be organized as multicentre studies subjected to continuous evaluation to measure the effects of the interventions on long-term mortality, to match management options more precisely to individual risks and to prepare the ground for studies on chemoprevention