Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project.

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD). METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day. RESULTS: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services. INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Using e-cigarettes for smoking cessation: evaluation of a pilot project in the North West of England.

AIMS: E-cigarettes have been advocated as an effective smoking cessation intervention, with evidence indicating that they are substantially less harmful than conventional cigarettes. As a result, a pilot to encourage people to swap from conventional cigarettes to e-cigarettes was conducted in 2018 in a socially deprived area in the North West of England. This evaluation highlights the key findings from the pilot. METHODS: An analysis of secondary data at 4 weeks (n = 1022) was undertaken to predict those who used solely used e-cigarettes (i.e. had quit tobacco, as confirmed by a carbon monoxide test, CO < 10 ppm) from baseline characteristics, using chi-square tests and logistic regression. Baseline data were demographics, smoking levels and service provider type. RESULTS: Of the 1022 participants who engaged with the pilot 614 were still engaged at 4 weeks, of whom 62% had quit; quitting was more likely in younger participants (aged 18-24) and less likely in those who were sick and disabled. Of those who still smoked tobacco at week 4 (n = 226), smoking had reduced from a baseline of 19.1 cigarettes/day to 8.7. Overall, 37% (381) of those initially enrolled were confirmed to be using an e-cigarette on its own at follow-up. Successful quit was associated with occupation (unemployed, 33% vs intermediate, 47%, p = .023) and residing in the less deprived quintiles of deprivation (50% vs 34% in the most deprived quintile, p = .016). CONCLUSIONS: Making the conservative assumption that all those not in contact at 4 weeks were still smoking tobacco, for every five people entering the scheme, three people stayed on the programme and reduced their cigarette smoking and one person cut out tobacco altogether. E-cigarettes appear to be an effective nicotine replacement therapy; however, further research is required to determine whether e-cigarette users are more likely to reduce their overall nicotine consumption in the longer term.

Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.

Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories.

Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these services.

A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial.

This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m(-2) day 1, followed on days 1-5 by ifosfamide 1 g m(-2) intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR(-ve)); favourable response rate (FRR = CR + PR(-ve)) 60%, 95% CI (44-75%); survival at 1 year was 70% (56-84%) and failure-free survival 36% (22-50%). In the group of 26 patients meeting the 'good-risk' criteria described by the Memorial Hospital, the FRR was 73% (52-88%) compared with 41% (18-67%) for the 17 'poor-risk' patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.

A comparative study on methods of measuring mesiodistal tooth diameters for interceptive orthodontic space analysis.

AIM: This study was designed to find the most reliable method of measurement of mesiodistal tooth diameter. METHODS: Measurements were made of all erupted permanent teeth of 14 orthodontic study casts. These measurements were made directly by using A) a digital calliper, B) measuring photocopies of casts with a calliper, C) a Magiscan Image Analysis using a photocopy of the casts. Measurements derived from the two methods were compared by statistical analysis. RESULTS: These showed that the electronic digital calliper was the most reliable method of measuring mesiodistal tooth diameter using dental study casts. The measurement of photocopies was unreliable and the image analysis method had a too high error factor.

Adjuvant bleomycin, vincristine and cisplatin (BOP) for high-risk stage I non-seminomatous germ cell tumours: a prospective trial (MRC TE17).

Adjuvant BEP (bleomycin, etoposide, cisplatin) is effective treatment for high-risk clinical stage I (HRCS1) non-seminomatous germ cell tumours (NSGCT), but the known toxicities of etoposide, and the expansion of the HR group to any patient with vascular invasion (50% of patients), led the Medical Research Council to pilot the BOP regimen. Patients received two courses of BOP 14 days apart: cisplatin 50 mg m(-2) days 1 and 2, vincristine 1.4 mg m(-2) (max. 2 mg) days 2 and 8, bleomycin 30,000 IU days 2 and 8. Primary outcome was relapse rate; quality of life, fertility, hearing and lung function were assessed pre- and post-treatment. In all, 100 patients were required. A total of 115 eligible patients were registered, all received two courses of chemotherapy. Median follow-up is 70 months; two relapses have occurred and the 5-year relapse-free rate is 98.3% (95% confidence interval (CI) 95.5%, 99.9%). As assessed by clinicians during treatment, complete (reversible) alopecia was present in 20% of patients; World Health Organization (WHO) grade 1/2 neurotoxicity was present in 41%/5% of patients during treatment and 22%/1% at 6 months. However, 12% of patients reported 'quite a bit' or 'very much' pain/numbness/tingling in hands/feet 2 years after chemotherapy. Mature follow-up confirms high efficacy for two courses of cisplatin-based adjuvant chemotherapy in HRCS1 NSGCT. Substituting vincristine for etoposide decreases alopecia, but gives a low incidence of significant neuropathy. There are no clearcut advantages to 2 x BOP over 2 x BEP, except for patients who wish to maximise the chance of avoiding significant alopecia.

An automated approach to connectivity-based partitioning of brain structures.

We present an automated approach to the problem of connectivity-based partitioning of brain structures using diffusion imaging. White-matter fibres connect different areas of the brain, allowing them to interact with each other. Diffusion-tensor MRI measures the orientation of white-matter fibres in vivo, allowing us to perform connectivity-based partitioning non-invasively. Our new approach leverages atlas-based segmentation to automate anatomical labeling of the cortex. White-matter connectivities are inferred using a probabilistic tractography algorithm that models crossing pathways explicitly. The method is demonstrated with the partitioning of the corpus callosum of eight healthy subjects.

Why do primary school children smoke? A longitudinal analysis of predictors of smoking uptake during pre-adolescence.

The objectives of this longitudinal study were to determine the prevalence of smoking among primary school children in Liverpool, and to identify the predictors of experimentation with cigarettes during pre-adolescence. A cohort of children (n = 270) completed questionnaires that elicited patterns of child smoking behaviour and children's experiences of smoking in their families and communities each year between the ages of 9 and 11 years. Parents also completed questionnaires. Children's first trials with cigarettes and repeated smoking were reported. The independent variables measured were socio-economic status, familial and peer smoking, and intentions to smoke. By age 11, 27% of children had tried smoking, 12% had smoked repeatedly and 3% were smoking regularly. Variables measured at age 9 predicting experimentation with cigarettes by age 11 were male gender 9P = 0.041) paternal smoking (P = 0.001) fraternal smoking (P = 0.017) a best friend who smoked (P = 0.026) and knowing someone with a smoking-related disease (P = 0.006) Intentions to smoke at age 9 did not predict smoking at age 11 (P < 0.001). In univariate analyses, child smoking was also associated with maternal smoking (P = 0.002 at age 11), living in a low-income household (P < 0.001 at age 10) and living in a deprived area ( P = 0.025 at age 11). Early smoking presents a considerable challenge to health promoters, not least because it is socially patterned. The interventions required must tackle the structural and social pressures that shape smoking behaviour during childhood.

Relationship between the use of hospital services and deprivation score of place of residence among HIV-positive individuals in the north west of England.

We used routine surveillance data to investigate whether deprivation relates to hospital admission in a HIV-positive population. HIV-positive individuals living in the poorest areas were more likely to have spent one or more nights in hospital for HIV-related care (adjusted odds ratio = 1.6, p = 0.009, after controlling for infection route, disease stage and demographic variables). This implies that healthcare networks in poorer areas may incur disproportionately greater costs.

Knowing the risk: relationships between risk behaviour and health knowledge.

Communicating risk is a key public health strategy. The implicit assumptions are that the public interprets risk information in a logical fashion and adopts behavioural changes to reduce risk. We assessed risk behaviour, and knowledge and perception of voluntary and involuntary risks using an anonymous questionnaire completed by 472 students. Risk-taking behaviour was measured as the number of different risk behaviours undertaken in the previous 12 months. Knowledge and perception were measured by the extent to which subjects agreed with statements of risk-related information. These varied in complexity from simple statements linking a behaviour with a health risk to numerical statements describing the strength of such relationships. Risk-taking behaviour was highest amongst younger people, males, people whose parents were in non-manual occupations, and people who believed in God (risk-taking behaviour was not related to voting preference or birth order). Overall, knowledge was not significantly related to risk-taking behaviour (P=0.889). However, risk-taking was positively related to more accurate responses to numerical risk questions (P<0.001) and risk-takers were also more likely to perceive both voluntary and involuntary risks as less risky (P<0.05). At least in this cohort, more information about risk is not related to lower risk behaviour. In fact, those individuals with a better understanding of the precise risk associated with certain behaviours were more likely to be higher risk-takers while those who consistently over-estimated risks were low risk-takers. Overall, knowledge and perception of risk explained relatively little of the variance in behaviour. Although these findings need further examination within the general population, public health measures should not assume that information campaigns will necessarily lead to a reduction in risk behaviour.

Digital neurorrhaphy after the age of 60 years.

Fifteen patients over the age of 60 years (average age: 65 years), with 19 digital nerve lacerations, were evaluated more than 1 year after injury. Two-point discrimination, Semmes-Weinstein evaluation, and subjective return of sensibility were examined by a certified hand therapist before and after local anesthetic block of the uninjured digital nerve. Sixty-three percent of the patients regained moving two-point discrimination less than 15 mm; 100 percent regained Semmes-Weinstein values of less than 4.56; and 84 percent of the patients subjectively noted greater than half of their normal sensation. Crossover innervation was a factor in four of 14 repairs. Based on the data, useful sensation can be regained by repairing a digital nerve in the majority of patients older than 60 years of age.

Re-emerging syphilis in the UK: a behavioural analysis of infected individuals.

In-depth interviews with 27 individuals infected with syphilis in a recent UK outbreak (out of a total of 58 diagnosed between May 1999 and August 2000 in three city hospitals) were carried out to examine behaviour and attitudes. Most (23/27) participants were homosexual men, seven of whom were HIV positive. Between them, the 23 gay men had 1,494 different contacts in the twelve months prior to their awareness of having syphilis, but only 10% of these contacts could be named. While oral sex (usually unprotected) was the most prevalent behaviour (median = 30 partners per year), only 39% perceived unprotected oral sex as a syphilis risk (c.f. 70% for anal sex). Many gay men (61%) used gamma hydroxybutyrate (GHB) during sex as an aphrodisiac. This syphilis-infected subset of the population had high levels of unprotected and anonymous sex, which brings into question the usefulness of contact tracing to control syphilis outbreaks. The majority of partners were casual oral sex partners. More awareness is urgently needed around syphilis symptoms and risks, and risks of using drugs to reduce sexual inhibitions.

Predictors of hepatitis B and C infection in injecting drug users both in and out of drug treatment.

AIMS: To assess prevalence of, and behavioural risk factors for, hepatitis B and C in drug users both in and out of contact with drugs services. DESIGN: Cross-sectional survey of hepatitis B and C prevalence using blood samples and self-completed risk factor questionnaires. PARTICIPANTS: Three hundred and sixty injecting drug users (IDUs) in treatment for their drug use, attending syringe exchange schemes (SES), and not in contact with any services in Wirral and Manchester between 1997 and 1999, for whom test results were available for 334 (hepatitis B) and 341 (hepatitis C). FINDINGS: Hepatitis B prevalence differed between groups, from 19% of those not in contact to 41% of those presenting to request a test (p = 0.040). Prevalence of hepatitis C ranged from 48% (SES) to 62% among those presenting for a test (p = 0.233). After multivariate adjustment, hepatitis B was predicted by prison stays (p = 0.030) and injecting for longer (p = 0.003). For hepatitis C, length of injecting career (p = 0.036), having been to prison (p = 0.034), having injected more than one drug type (p < 0.001) and being female (p = 0.037) predicted infection. Overall, 38% had shared some form of injecting equipment in the previous 4 weeks. People recently starting injecting were more likely to share, and sharing was more likely to occur when injecting with only one other user rather than in larger groups. Those who had previously presented for a hepatitis C test, regardless of the result, were less likely to have recently shared injecting equipment. CONCLUSIONS: Behaviours associated with transmission of hepatitis B and C are common among IDUs. In particular, sharing of injecting equipment was more likely in small groups and in those recently beginning injecting. More broadly, chaotic drug use and time in prison were also risk factors for hepatitis infections. When assessing prevalence of hepatitis B and C, our results suggest that figures cannot be extrapolated from those in service contact to those in the wider drug-using population.

The effect of early static loading on the in vitro shear/peel bond strength of a 'no-mix' orthodontic adhesive.

This study addressed the question of whether shear and tensile loads applied 15 minutes after bonding metal brackets to enamel affected the shear/peel bond strength of the adhesive. Ninety standard 0.022-inch stainless steel edgewise premolar mesh-backed brackets were bonded using a no-mix chemical-cured adhesive to 90 teeth, which had been prepared in a standardized manner. After 15 minutes three groups of 30 teeth were subjected to the following regimes: no applied load, tensile static load of 0.77 N (78 g), and shear static load of 0.77 N. After 14 days storage in 100 per cent relative humidity at 37 degrees C, the shear/peel strength of the adhesive bond was measured using a purpose built jig mounted on a universal testing machine. Shear/peel bond strengths were analysed using Weibull statistics. The Weibull moduli of the three groups indicated that the adhesive performed consistently despite early static loading. Characteristic strengths were 9.22, 9.27, and 9.05 MPa for the control, tensile, and shear groups, respectively. The findings indicate that static loads (such as tying in of archwires) can be placed on brackets 15 minutes after cementation, without a clinically significant reduction in bond strength of the tested adhesive.

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

Prosthodontic considerations in complicated restorative and esthetic dental problems.

An axiom of prosthetic dentistry has always been that the restoration of esthetics, speech and function requires the successful arrangement of teeth in space. The road to this success often requires the restorative dentist be a visionary who can coordinate multidisciplined planning in the presence of such obstacles as deficient alveolar bone and gingival tissues, poor occlusal plane, and jaw malrelations. Dr. Cook would like to thank the many Albuquerque generalists and specialists whose experienced hands contributed to the successful treatment of these patients.

Postchemotherapy residual masses in germ cell tumor patients: content, clinical features, and prognosis. Medical Research Council Testicular Tumour Working Party.

BACKGROUND: In a retrospective study that included a detailed histopathologic review, the clinicopathologic features of patients with germ cell tumors (GCT) and resectable residual masses after chemotherapy were assessed. METHODS: Histologic material from 153 patients was available for review. Recorded details included primary histologic diagnosis, location, size and number of metastases, marker levels before and after chemotherapy, and completeness of surgical excision. A median of seven histologic sections per resection were reviewed by two pathologists independently (and together when disagreement occurred). In each case, details were recorded regarding fibrosis, necrosis, hemorrhage, embryonal carcinoma (undifferentiated teratoma), yolk sac tumor, choriocarcinoma (trophoblastic tumor), differentiated teratoma (mature and immature), dysplasia in somatic tissues, and non- germ cell tumor (GCT) malignancies. The percentage of the sample that each of these components comprised was also estimated. RESULTS: The median postchemotherapy follow-up time was 7 years, and 38 of 153 patients (25%) experienced disease progression. In a multivariate analysis, incomplete resection of all residual masses (in 38 patients) and the presence of malignant elements (in 23 patients) were independent risk factors for progression. In the subset of patients in whom all masses were completely resected, the presence of embryonal carcinoma (undifferentiated teratoma) was the single most significant risk factor for progression. Seven percent of patients had this factor, which was associated with a 2-year progression free survival rate of 12.5%, compared with 88.0% where this component was absent. CONCLUSIONS: Progression free survival can be predicted well by the completeness of excision of residual masses and the presence of malignant germ cell elements. The latter confers a relatively poor prognosis even if all of these elements are completely resected.

Intratubular germ cell neoplasia of the contralateral testis in testicular cancer: defining a high risk group.

PURPOSE: We define a group of testis cancer patients who are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. MATERIALS AND METHODS: The histology was reviewed in 186 testis cancer patients who underwent contralateral testicular biopsy either because of a history of testicular maldescent or an atrophic contralateral testis (defined as a volume of 12 ml. or less). Testicular volume, semen analysis, serum gonadotropin levels, serum testosterone and estradiol levels were assessed in the majority of patients. RESULTS: Univariate analyses identified contralateral testicular atrophy, low sperm density, young age at presentation and low Johnsen score as factors associated with increased risk of a positive biopsy. A history of maldescent in the absence of atrophy was associated with carcinoma in situ prevalence of only 4%. Multivariate analysis identified only testicular atrophy and age at presentation as independent determinants of a positive biopsy. Testis cancer patients with a small contralateral testis had a 20% and those presenting at age 30 years or younger had a 34% prevalence, respectively, of carcinoma in situ on contralateral testis biopsy (95% confidence interval 20 and 46%, respectively). CONCLUSIONS: Testis cancer patients with an atrophic contralateral testis who present before the age of 31 years are at high risk for carcinoma in situ of the contralateral testis and, therefore, a second germ cell tumor. It is estimated that this group comprises 6% of all testis cancer patients. We predict that a policy of performing contralateral testicular biopsy will produce positive results for carcinoma in situ in a third of these patients and will detect contralateral carcinoma in situ in approximately 40% of all testis cancer patients.