Online acceptance and commitment therapy (iACT) for adults with persistent physical symptoms - 3-month follow-up study of a randomized controlled trial.

OBJECTIVE: Persistent physical symptoms (PPS) represent a major health problem affecting daily functioning. This RCT aimed to examine whether a guided Internet-based treatment based on acceptance and commitment therapy (ACT) provided additional benefits compared to Treatment as Usual (TAU) in reducing somatic complaints and psychological distress in adults with PPS. METHODS: A total of 103 adults with PPS related to indoor environments, chronic fatigue or both conditions were assigned to receive either either a 14-week intervention (video-based case conceptualization + Internet-based ACT) combined with TAU (iACT + TAU; n = 50) or TAU alone (n = 53). Somatic symptoms, depression, anxiety, insomnia, and psychological flexibility were assessed from pre-intervention to a 3-month follow-up. Additionally, the association between changes in psychological flexibility from pre- to post-intervention and changes in symptoms from pre to 3-month follow-up was explored. Analyses were conducted using a multigroup method with full information maximum likelihood estimator. RESULTS: The results revealed a significant interaction effect, indicating reductions in somatic symptoms and symptoms of depression and anxiety with moderate to large between-group effects (d = 0.71-1.09). No significant interaction effect was observed in insomnia and measures of psychological flexibility. CONCLUSION: Internet-based ACT, when combined with Treatment as Usual, demonstrated efficacy for individuals with PPS associated with indoor environments and chronic fatigue. These findings are pertinent for primary healthcare providers, suggesting that the current treatment model could serve as a low-threshold first-line treatment option. THE CLINICAL TRIAL REGISTRATION NUMBER: NCT04532827.

Prognosis of patients with post-Covid-19 condition: Prospective cohort cluster analysis at one year.

OBJECTIVE: We aimed to identify clinically relevant clusters among patients with post-Covid-19 condition (PCC) and assess prognosis overall and within clusters. METHODS: Prospective cohort study of patients with PCC attending a rehabilitation clinic. We monitored patient reported outcome measures (PROMs): EuroHIS quality of life and symptoms. Unsupervised hierarchical cluster analyses were performed to identify clusters of patients with different quantity of symptoms, and symptoms presenting together. Preliminary findings on symptom prevalence and quality of life at 12 months are reported. RESULTS: Among 409 patients, 70.4% were women, with an average baseline of 20.3 (SD 6.8) symptoms. Three clusters emerged based on symptom quantity, labelled by the average number of symptoms at baseline: Cluster-11 (17% of all patients), Cluster-17 (35%), and Cluster-25 (48%). Multinomial logistic regression showed female sex, multiple comorbidities predicting more symptoms. Four symptom-based clusters were defined: fatigue and cognitive complaints; pain, trouble sleeping, palpitations and other symptoms; gastrointestinal symptoms; and emotion-related symptoms. Linear regression models showed that female sex, multiple comorbidities, anxiety, use of antidepressants, BMI and smoking were among the determinants of symptom clusters. In 12-month follow-up, symptom count decreased, and quality of life improved across all clusters, with 9% having good quality of life at baseline and 33% at 12 months. CONCLUSION: Four patient clusters based on symptoms were identified in the PCC cohort. Prognosis was favorable across all clusters, with symptom reduction and improved quality of life observed. Female sex, comorbidities, BMI, and mental-health related variables predicted higher symptom burden, suggesting multifactorial origins of PCC.

Parkinson's disease and occupational exposure to organic solvents in Finland: a nationwide case-control study.

OBJECTIVE: This study aimed to investigate the association between Parkinson's disease (PD) and occupational exposure to organic solvents generally and chlorinated hydrocarbons (CHC) in particular. METHODS: We assembled a Finland-wide case-control study for birth years 1930-1950 by identifying incident PD cases from the register of Reimbursement of Medical Costs and drawing two controls per case using incidence density sampling from the Population Information System, matched on sex, birth year, and residency in Finland in 1980-2014. Occupation and socioeconomic status (SES) were identified from national censuses. We assessed cumulative occupational exposures via FINJEM job-exposure matrix. Smoking was based on occupation-specific prevalence by sex from national surveys. We estimated confounder-adjusted PD incidence rate ratios (IRR) via logistic regression and evaluated their sensitivity to errors in FINJEM through probabilistic bias analysis (PBA). RESULTS: Among ever-employed, we identified 17 187 cases (16.0% potentially exposed to CHC) and 35 738 matched controls. Cases were more likely to not smoke and belong to higher SES. Cumulative exposure (CE) to CHC (per 100 ppm-years, 5-year lag) was associated with adjusted IRR 1.235 (95% confidence interval 0.986-1.547), with stronger associations among women and among persons who had more census records. Sensitivity analyses did not reveal notable associations, but stronger effects were seen in the younger birth cohort (1940-1950). PBA produced notably weaker associations, yielding a median IRR 1.097 (95% simulation interval 0.920-1.291) for CHC. CONCLUSION: Our findings imply that PD is unlikely to be related to typical occupational solvent exposure in Finland, but excess risk cannot be ruled out in some highly exposed occupations.

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Solvent exposed occupations and risk of Parkinson disease in Finland.

INTRODUCTION: Epidemiologic and toxicology studies suggest that exposure to various solvents, especially chlorinated hydrocarbon solvents, might increase Parkinson disease (PD) risk. METHODS: In a population-based case-control study in Finland, we examined whether occupations with potential for solvent exposures were associated with PD. We identified newly diagnosed cases age 45-84 from a nationwide medication reimbursement register in 1995-2014. From the population register, we randomly selected non-PD controls matched on sex, along with birth and diagnosis years (age). We included 11,757 cases and 23,236 controls with an occupation in the 1990 census, corresponding to age 40-60. We focused on 28 occupations with ≥ 5% probability of solvent exposure according to the Finnish Job Exposure Matrix. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression modeling, adjusting for age, sex, socioeconomic status, and smoking probability. RESULTS: Similar proportions of cases (5.5%) and controls (5.6%) had an occupation with potential exposure to any solvents. However, all occupations with a point estimate above one, and all significantly or marginally significantly associated with PD (electronic/telecommunications worker [OR = 1.63, 95% CI 1.05-2.50], laboratory assistant [OR = 1.40, 95% CI 0.98-1.99], and machine/engine mechanic [OR = 1.23, 95% CI 0.99-1.52]) entailed potential for exposure to chlorinated hydrocarbon solvents, specifically. Secondary analyses indicated exposure to polycyclic aromatic hydrocarbons and some metals might contribute to the association for mechanics. CONCLUSION: PD risk might be slightly increased in occupations with potential exposure to chlorinated hydrocarbon solvents. Confirmation is required in additional studies that adjust for other occupational exposures and smoking.

Limitations of periodical health examinations in detecting occupational chronic solvent encephalopathy.

OBJECTIVES: Occupational diseases (ODs) are globally underdetected, and chronic solvent encephalopathy (CSE) is no exception. The aim was to study how the recommended policies and protocols were followed in occupational health services (OHS) periodical health examinations where symptomatic CSE cases have remained undetected. METHODS: We retrospectively studied the medical records of occupational CSE cases (n=18) found in a screening project, which had not been detected in preceding OHS health examinations. We collected data from three sources: OHS units, the screening project and the Finnish Institute of Occupational Health. We analysed the health examinations conducted between symptom onset and the detection of CSE: regularity, content, use of recommended screening tools, exposure estimation and whether a physician was involved in the examinations, as recommended. RESULTS: The mean duration of symptoms before OD identification was 7.3 years (range 3-13), and 36 health examinations had been conducted. Fifteen workers had attended these (1-9 times each) while suffering from CSE symptoms, and two before symptoms. Only one had not had access to OHS. The recommended symptom screening questionnaire, Euroquest, was used in five (14%) examinations, and previous solvent exposure inquired once. A physician was involved in 24 (67%) examinations, whereas the rest were carried out by a nurse. CONCLUSIONS: Although health examinations are conducted, guidelines are not followed. This may be due to a lack of awareness concerning CSE, and may apply to other ODs. In addition to legislation and policies, OH professionals must be continuously educated to improve awareness, prevention and detection of ODs.

Cost of detecting a chronic solvent encephalopathy case by screening.

BACKGROUND: Stepwise screening of chronic solvent encephalopathy (CSE), using a postal survey followed by clinical examinations, has been shown to detect symptomatic exposed workers with an occupational disease even in industrialized countries with long-term, but relatively low dose exposure. Previous studies have suggested under-detection and late recognition of CSE, when work ability is already markedly reduced. AIMS: The aim was to estimate the cost of detecting one new CSE case by screening and diagnostics, to estimate the career extension needed to cover the cost of screening, and to study the work ability of the CSE cases. METHODS: A financial analysis of stepwise postal CSE screening followed by clinical examinations (SPC screening) was carried out, and the results were compared to those of the group of CSE cases referred to the Finnish Institute of Occupational Health (FIOH) by the existing national practice of occupational health services (OHS screening). The work ability of the SPC screened CSE cases was studied in relation to the retirement rate and the Work Ability Index (WAI). RESULTS: An analysis of the costs of detecting a new verified CSE case revealed them to be approximately 16,500 USD. Using the mean monthly wages in the fields concerned, we showed that if a worker is able to continue working for four months longer, the screening covers these costs. The cost for detecting a CSE case was twenty times higher with the existing OHS routine, when actualized according to the national guidelines. A CSE case detected at an early stage enables occupational rehabilitation or measures to decrease solvent exposure. The retirement rate of the SPC screened CSE cases was significantly lower than that of the OHS screened cases (6.7% vs. 74%). The results suggest that SPC screening detects patients at an earlier stage of the disease, when they are still capable of working. Their WAI sores were nevertheless lower than those of the general population, implying a greater risk of becoming excluded from the labor market. CONCLUSION: Stepwise screening of CSE using a postal survey followed by clinical examinations detected new CSE cases at lower costs than existing OHS screening routines. Detecting CSE at an early stage prevents early retirement.

Detecting chronic solvent encephalopathy in occupations at risk.

Chronic solvent encephalopathy (CSE) is under-reported worldwide due to difficulties in recognition and differences in national legislation. Although its occurrence in developed countries has declined, new cases continue to be detected. Our aim was to determine whether CSE can be detected in risk trades, using a stepwise screening procedure. Another aim was to evaluate if this method detects more cases than present occupational health service (OHS) practices do in Finland, a country with decreasing exposures, high OHS coverage and an annual rate of around forty cases of suspected CSE and seven cases of occupational CSE. The studied fields, based on the national occurrence of CSE, were industrial and construction painting, floor layering, the printing press industry, boat construction, reinforced plastic laminating and the metal industry. We obtained contact information from trade union registers and municipal OHS. A postal survey including the Euroquest (EQ) neurotoxic symptom questionnaire, Beck's Depression Inventory (BDI) and the Alcohol Use Disorders Identification Test-Consumption (Audit-C), and questions on exposure and medical conditions, was sent to 3,640 workers in the age range of 30-65 years in two Finnish provinces. The survey resulted in 1,730 responses (48%). This was followed by a clinical examination, with methods applicable to OHS, of subjects fulfilling the criteria: three or more EQ memory and concentration symptoms and sufficient exposure, a BDI score≤18, an AUDIT-C score≤8, and no evident medical condition explaining their symptoms. Of 338 respondents with memory and concentration symptoms, 129 subjects fulfilled all the criteria, of which 83 participated in clinical examinations. We found 38 CSE compatible cases. The study shows that more CSE compatible cases can be detected when the screening is directed towards the occupational fields at greatest risk. This stepwise method is more effective for finding CSE compatible cases than regular OHS activity. The number of cases was similar to the total annual occurrence, of new CSE-suspected cases, although the sample represented approximately 18% of the abundantly exposed workforce in Finland. Combining of exposure and medical differential diagnostics to neurotoxic symptom questionnaire, decreases the amount of cases needing clinical examinations. This two-step procedure can be carried out with methods suitable for OHS and other primary health care, both in industrialized and developed countries.

Occupational chronic solvent encephalopathy in Finland 1995-2007: incidence and exposure.

PURPOSE: The aim of the study was to define the incidence of chronic solvent encephalopathy (CSE) in Finland during 1995-2007, evaluate the duration and nature of exposure, and identify the work tasks where CSE is encountered. METHODS: Data were from the register and patient records at the Finnish Institute of Occupational Health. The Finnish Job-Exposure Matrix (FINJEM) and National Statistics were used to estimate the incidence of CSE in exposed workforce. RESULTS: CSE cases during 1995-2007 numbered 129. The annual incidence has decreased from 8.6 to 1.2/million employed, i.e. from 18 to 3 patients per year. The number of suspected patients has, however, remained constant (mean 38.6/year). The mean age at diagnosis was 52.8, the mean duration of exposure 28.4 years, and the mean occupational exposure limit years (OELY) 10.5. During 1995-2007, the mean age increased annually by 0.6 and years of exposure by 0.8, but OELY remained constant. In comparison to FINJEM, the highest incidence was in workers exposed to aromatic hydrocarbons. Relative to workforce in occupations with solvent exposure, CSE was most frequent in wooden surface finishers and in industrial, metal, or car painters followed by floor layers and lacquerers. CONCLUSIONS: The incidence of CSE has declined due to legislative, technical, and hygienic actions. CSE is most probable in spray painting tasks with main exposure to aromatic hydrocarbons, when occupational solvent exposure exceeds 20 years, and the age of the worker is above 45. Our results indicate slower CSE development at lower exposure levels.

Frequent loss of heterozygosity at 6q in pheochromocytoma.

Multiple genetic alterations have been associated with pheochromocytoma (PCC). Most PCCs are sporadic, but they also occur in inherited tumor syndromes, including von Hippel-Lindau disease. Although the etiology of most inherited PCCs is well documented, little is known about the etiology of sporadic tumors. Mutations of those genes that harbor germ-line mutations in familial cases cover only 10% to 15% of somatic mutations in sporadic PCCs. A previous cytogenetic analysis indicated frequent loss of 6q in sporadic PCCs. We therefore investigated in detail 18 PCCs using 22 microsatellite markers spanning 6q to search for the presence of allele deletions and identify specific regions likely to contain tumor suppressor genes involved in PCC. Moreover, we sought to compare PCC with capillary hemangioblastoma, another von Hippel-Lindau disease-associated tumor that we previously found to harbor frequent loss of heterozygosity (LOH) at 6q. Our study revealed a high frequency (13/18; 72%) of overall 6q LOH in PCCs. Loss of heterozygosity at 6q was observed in 6 benign (6/9; 67%) and 7 borderline (7/9; 78%) tumors. We identified 2 regions where LOH or allelic imbalance was common (ie, 6q14 [9/18; 50%] and 6q23-24 [6/18; 33%]). We further focused the search using markers specific for the ZAC1 gene region located at 6q24-25. Altogether, for all 6q23-25 markers, including the ZAC1-specific ones, LOH or allelic imbalance was observed in 50% (9/18) of the PCCs. Similar to our findings for capillary hemangioblastomas, our data for the first time suggest that one or several tumor suppressor genes located at 6q, particularly at 6q23-24, may play a role in the tumorigenesis of PCCs.

Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type 2.

Schwannomatosis is characterized by multiple peripheral and cranial nerve schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas. The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2), which is a related but distinct disorder. The genetic factors underlying the differences between schwannomatosis and NF2 are poorly understood, although available evidence implicates chromosome 22 as the primary location of the gene(s) of interest. To investigate this, we comprehensively profiled the DNA copy number in samples from sporadic and familial schwannomatosis, NF2, and a large cohort of normal controls. Using a tiling-path chromosome 22 genomic array, we identified two candidate regions of copy number variation, which were further characterized by a PCR-based array with higher resolution. The latter approach allows the detection of minute alterations in total genomic DNA, with as little as 1.5 kb per measurement point of nonredundant sequence on the array. In DNA derived from peripheral blood from a schwannomatosis patient and a sporadic schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL) locus, which is unlikely to be due to a B-cell specific somatic recombination of IGL. Analysis of normal controls indicated that these IGL rearrangements were restricted to schwannomatosis/schwannoma samples. In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders.

Anosmia in association with occupational use of a waterproof coating chemical.

A case of acute permanent anosmia is described in a renovation worker during exposure to a waterproof coating chemical. The chemical consisted of several substances of which four (acetone, acrylates, butyl acetate and carbon disulfide) has been previously reported to induce hyposmia or anosmia in workers. Other aetiologies were clinically excluded but a large arachnoidea cyst in the frontal part of the left temporobasal fossa with possible compression of the left entorhinal cortex. The toxic aetiology of anosmia is supported by the acute onset and the temporal relationship with occupational exposure. The silent cyst as the cause of anosmia is improbable, but it may have had some contributory role. Our case illustrates both the challenges when clinically examining patients with work-related olfactory impairment and the importance of multi-disciplinary approach to such patients.

Effects of long-term occupational solvent exposure on contrast sensitivity and performance in visual search.

Sensitive and easily applicable screening tests are greatly needed for the early detection of nervous system dysfunction in people working with neurotoxic substances. Previous studies have shown that long-term solvent exposure may cause deficits in visual perception. We, therefore, studied the effects of long-term occupational solvent exposure and chronic encephalopathy on performance in three vision tests novel in the present context. Two visual search tasks were used: the letter search test measured the speed of finding a letter in an array of numerals, and the pop-out search test required the observer to detect the presence or absence of a tilted line segment in an array of vertical line segments. With the letter contrast sensitivity test we measured the contrast threshold for the identification of band-pass filtered letters. Before testing, comprehensive eye examination was carried out to reveal any structural or functional abnormality and to ensure correct refraction. The patients had healthy eyes, 2 out of 14 had reduced contrast sensitivity (Vistech) and 5 out of 14 had deficits in colour vision (FM 100). In both visual search tasks, the patients were statistically highly significantly (p<0.001) slower than the age-matched control observers. Instead, in the contrast sensitivity test, the difference between the patient and the control group was small relative to normal variability although still statistically significant (p<0.05). The results suggest that visual search tests can be useful in evaluating and characterising the effects of long-term solvent exposure on visual perception. Because our patients' letter contrast sensitivity was only moderately deteriorated, it seems that the observed defect of visual search cannot be explained by deteriorated letter identification alone, although it can be a contributory factor. Rather, the finding suggests that the speed by which visual information is transmitted and/or processed in the central visual system has become considerably slower.

Loss of heterozygosity at 6q is frequent and concurrent with 3p loss in sporadic and familial capillary hemangioblastomas.

Capillary hemangioblastoma is a benign tumor, occurring sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Inactivation of the VHL gene at 3p25-26 has been demonstrated in all VHL-associated hemangioblastomas. However, the VHL gene has been found to be inactivated in only 20% to 50% of sporadic tumors. So far, no other gene has been reported to be involved in the development of hemangioblastomas. DNA losses at 6q are frequent alterations in hemangioblastomas, as shown by comparative genomic hybridization. We therefore analyzed 15 hemangioblastomas for loss of heterozygosity (LOH) on chromosome 3p and 6q to reveal the frequency of allelic losses and to determine minimal deleted areas. We detected LOH at 6q for one or more markers in 11 (73%) out of 15 cases (in 9 of 11 sporadic and in 2 of 4 VHL-associated tumors). The analyses revealed a minimal 3-megabase (Mb) deleted region at 6q23-24, where 9 of 11 (82%) informative cases showed LOH. LOH at 3p was seen in 14 out of 15 tumors. LOH occurred concurrently at 6q and 3p in 67% of cases. Our data strongly suggests that a tumor suppressor gene located at 6q23-24 is involved in tumorigenesis of hemangioblastomas, in addition to the VHL gene.

Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. A characteristic genetic alteration in GISTs is constitutive activation of the c-kit proto-oncogene, but alterations in chromosomes 14 and 22 may also play a role in the molecular pathogenesis. In this study, 42 GISTs were analyzed for loss of heterozygosity (LOH) on the long arm of chromosome 22 (22q). Overall, 69% of the tumors studied showed LOH with at least 1 of the 22q markers. Allele losses were compared with tumor mitotic activity, the most commonly used prognostic marker for this tumor. Interestingly, allele deletion at 22q was significantly more frequent in tumors with high mitotic activity (>/= l2 mitoses/10 high-power fields [HPF]) than in tumors with low mitotic activity (< 2 mitoses/HPF)-88% versus 56% (P < 0.01). A total of 26% (11 of 42) of all tumors demonstrated loss of all 22q sites analyzed, consistent with the loss of 1 copy of the entire long arm. Such tumors carried a 4.6-fold (95% confidence interval, 0.5 to 49.8) risk for recurrence compared with tumors with no LOH. LOH was frequently detected at the neurofibromatosis 2 (NF2) tumor-suppressor gene locus at 22q12. Sequencing of the NF2 gene from 5 GISTs did not reveal mutations, however. Furthermore, 16 of 19 tumors (84%) analyzed by immunohistochemistry were positive for the NF2 gene product, merlin. The findings suggest that allelic losses at 22q are associated with high mitotic activity and recurring disease, and that alterations in the NF2 gene are unlikely to participate in the pathogenesis of GIST.

Concurrent LOH at multiple loci in human malignant mesothelioma with preferential loss of NF2 gene region.

Human malignant mesothelioma (MM) is a highly aggressive neoplasm related to occupational asbestos exposure and characterised by a long latency period between the exposure and onset of disease. Previous studies indicate that losses at different genomic regions are present in MM. We examined allele loss at three known tumour suppressor gene regions (22q/NF2 gene, 9p/p16 gene, and 3p/FHIT gene) and at two other frequently deleted areas (14q and 6q) in MM. Loss of heterozygosity (LOH) was investigated in cell cultures and primary tumours with several highly polymorphic markers for each site. To study if LOH of the NF2 gene is a consistent feature in MM, we performed a more detailed analysis of chromosome 22q that included a NF2 marker (NF2CA3). We observed a high frequency of LOH occurring simultaneously at multiple loci. In particular, 100% of the cultured MM cells exhibited LOH at the NF2 gene region. From the other chromosomal sites analysed, recurrent allele loss was detected at 9p (5/7; 71%), 3p (4/7; 57%), 14q (3/7; 43%), and 6q (3/7; 43%). Of the 32 tumours, even those trimmed to exclude normal tissue, few showed LOH, suggesting consielment by normal cells within MM tumours, whereas tumour cells in primary cultures showed LOH already in passages 1-2. In conclusion, our present LOH data indicate that MM cells exhibit allele losses at multiple tumour suppressor gene sites concurrently, involving NF2 gene preferentially. This supports the view that the accumulation of multiple genetic hits is characteristic to malignant transformation of MM cells.

Recurrent DNA sequence copy losses on chromosomal arm 6q in capillary hemangioblastoma.

Capillary hemangioblastomas (CHB) of the central nervous system, the most common tumor in von Hippel-Lindau (VHL) disease, usually show mutations in the VHL tumor suppressor gene on chromosome 3p25-p26. Because little is known concerning the cytogenetic changes in these tumors, we studied 22 cases through comparative genomic hybridization to screen for DNA copy number changes in both sporadic and VHL-associated CHB. Our analysis revealed that 6 of 22 samples (27%) contained DNA copy number losses, whereas no gains were observed. The most recurrent finding was loss of chromosomal arm 6q, seen in five cases. In two of these cases also loss of chromosome 3 was noted. The third aberration observed was loss of chromosome 8, seen in one case. No differences were noted between VHL-associated and sporadic tumors, nor did the cytogenetic aberrations correlate with the clinical outcome. The loss of 6q, seen in this study and previously in other VHL-associated tumors (renal cell carcinomas and pheochromocytomas) and other tumors, suggest that this chromosome area may contain tumor suppressor genes involved in the early steps of tumorigenesis.