The Stockholm Spinal Cord Uro Study: 2. Urinary tract infections in a regional prevalence group: frequency, symptoms and treatment strategies.

Objective: To examine symptomatic urinary tract infections (UTI) in a regional prevalence group of patients with traumatic spinal cord injury (SCI), to assess risk factors for recurring infections and to identify a high-risk sub-population for frequently recurring and severe febrile UTIs.Materials and Methods: Four hundred and twelve patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies and a questionnaire regarding complications during the preceding year. Descriptive statistics and regression analysis were used to estimate risk factors.Results: Nearly half of all patients reported ≥1 UTI during the preceding year with a mean number of 3.6. Persons who use normal voiding had the lowest frequency, while those with catheter-assisted voiding reported the highest numbers. A sub-group of patients had more frequent and severe UTIs. They were characterized by a cervical or thoracic neurological level lesion and a more severe injury and the presence of SCI-related complications such as spasticity, neuropathic pain and autonomic dysreflexia. The most common signs and symptoms of UTI were smelly and cloudy urine, feelings of malaise and increased spasticity.Conclusions: Risk profiles for recurring and severe UTIs were catheter-assisted voiding, cervical or thoracic levels and more complete neurological lesions and the co-existence of other SCI-related complications. There is a need for an increased understanding of the special symptoms of UTI in this patient group and a strategy to avoid unspecific antibiotic treatment.

The Stockholm Spinal Cord Uro Study: 1. Basic characteristics and problem inventory.

Objective: To assess urinary tract function and complications in a regional prevalence group of patients with traumatic spinal cord injury (SCI), and to estimate risk factors for recurring complications.Materials and methods: A total of 412 patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional follow-up programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies, and a questionnaire regarding complications during the preceding year. Descriptive statistics and logistic regression were used to estimate risk factors.Results: All patients completed blood tests and the questionnaire. A urine culture was completed by 96%, ultrasound by 88%, residual urine by 75%, urodynamics by 51%, and all parts of the study by 47%. One quarter of patients displayed pathological findings regarding kidney function. Urodynamics verified neurogenic overactive bladder in a majority, and a high proportion with intravesical filling pressures above 40 cm H2O, a commonly used cut-off level for kidney safety. Subjectively, 47% of patients reported complications during the past year with urinary tract infection (UTI) as the most common one. Other complications were rare.Conclusions: With the aid of a regular follow-up programme, SCI patients can achieve a relatively stable situation regarding urinary tract function. UTI is the most common complication. Indicators of renal complications are frequent but not clearly related to the number of UTIs, nor to intravesical filling pressures. Main risk factors for complications are cervical levels and more complete neurological lesions.

Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment.

OBJECTIVE: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations. MATERIALS AND METHODS: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients' life. RESULTS: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being. CONCLUSION: Patients with bladder cancer T1G2-G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient's well-being. It is important to record the patients' baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder.

OBJECTIVE: The aim of this study was to compare the long-term efficacy of BCG monotherapy to alternating therapy of mitomycin C (MMC) and BCG in patients with carcinoma in situ (CIS). MATERIALS AND METHODS: Between 1992 and 1997, 321 patients with CIS were randomized from Finland, Norway and Sweden in a prospective multicenter trial into two treatment groups. The alternating therapy comprised six weekly instillations of MMC 40 mg followed by 10 instillations of BCG (Connaught 120 mg) or MMC alternating monthly for 1 year. BCG monotherapy followed the same 6 + 10 schedule. Stratification was done by nationality and CIS category. Primary endpoints were time to first recurrence and time to progression. Secondary endpoints were disease-specific mortality and overall survival. The main statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model with the cumulative incidence and Kaplan-Meier analyses. RESULTS: The median follow-up time was 9.9 years (maximum 19.9 years) in the BCG group and 8.9 years (maximum 20.3 years) in the alternating group. The risk of recurrence was significantly lower in the BCG group than in the alternating group (49 vs 59% at 15 years, respectively; hazard ratio 0.74, 95% confidence interval 0.54-1.00, p = 0.048). There were no significant differences in the other endpoints. Patients who progressed after 2 years were particularly prone to dying from bladder carcinoma. Younger patients performed worse than older ones. CONCLUSIONS: BCG monotherapy including monthly maintenance was effective and better than the alternating therapy. The risk of dying from bladder carcinoma after progression was high.

Impact of hospital volume on local recurrence and distant metastasis in bladder cancer patients treated with radical cystectomy in Sweden.

OBJECTIVE: This study evaluated the impact of hospital volume on local recurrence and distant metastasis in a population-based series of radical cystectomy patients in Sweden. MATERIAL AND METHODS: All patients who underwent cystectomy for bladder cancer in 1997-2002 in Sweden and were reported to the National Bladder Cancer Registry were included. A high-volume hospital (HVH) was defined as one with ≥10 cystectomies/year and a low-volume hospital (LVH) as one with <10 cystectomies/year. Information on preoperative tumour, node, metastasis (TNM) classification, operative procedure, postoperative course and follow-up was obtained from medical records. RESULTS: Of the 1126 patients, 827 (74%) were males. The mean age was 66 years and median follow-up 47 months. Of the 610 (54%) HVH patients, 68 (11%) were pT0, 123 (20%) < pT2, 177 (29%) pT2, 242 (40%) > pT2 and 69 (11%) were microscopic non-radical. Corresponding figures for the 516 (46%) LVH patients were 35 (7%), 68 (13%), 191 (37%), 222 (43%) and 96 (19%). Local recurrence was observed in 245 patients (22%): 113 (19%) at HVHs and 132 (26%) at LVHs. Distant metastasis was found in 363 (32%): 203 (33%) at HVHs and 160 (31%) at LVHs. Perioperative chemotherapy was given to 193 (17%). Multivariate Cox proportional hazards analysis showed that local recurrence was associated with LVHs and non-organ-confined disease, whereas distant metastasis was correlated with non-organ-confined disease and lymph-node metastases. CONCLUSIONS: In this retrospective analysis, local tumour recurrence after cystectomy was common, particularly in patients with non-organ-confined disease. Furthermore, local recurrence was more frequent at LVHs than HVHs, and overall survival was better at HVHs. These findings suggest that concentrating cystectomies in HVHs may improve outcomes such as local recurrence and overall survival.

Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: a Swedish population-based survey.

OBJECTIVE: To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material. MATERIAL AND METHODS: Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003. RESULTS: During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p < 0.015). CONCLUSIONS: Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.

Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: a report from the Swedish-Norwegian Testicular Cancer Group.

PURPOSE: From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. METHODS: Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for ß-human chorionic gonadotropin (ß-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. RESULTS: Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. CONCLUSION: With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.

Defecation disturbances after cystectomy for urinary bladder cancer.

OBJECTIVE: • To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: • During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. • During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. • Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: • The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: • Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.

Sleep disturbances decrease self-assessed quality of life in individuals who have undergone cystectomy.

PURPOSE: The best possible urinary diversion after cystectomy, if any, is yet to be defined to our knowledge. Therefore, we investigated nocturnal urinary disturbances and quality of life in individuals who have undergone cystectomy with urinary diversion for bladder cancer. MATERIALS AND METHODS: All patients 30 to 80 years old who had undergone cystectomy with urinary diversion at 7 urological centers in Sweden were included in the study. Sleep disturbances, nocturnal urinary leakage and urine evacuation frequency, as well as their effect on self-assessed quality of life variables were measured with a study specific questionnaire. We received the questionnaire from 452 (92%) of 491 identified individuals. Outcome variables were dichotomized and the results are presented as relative risks. RESULTS: Those individuals with an orthotopic neobladder had an increased risk of nocturnal urinary leakage and/or urine evacuation frequency compared to those with a noncontinent urostomy or cutaneous continent reservoir. Of the patients with an orthotopic neobladder 37% reported negative effects on nocturnal sleep compared to 22% and 14% of those with a noncontinent or continent urostomy, respectively. Of those patients reporting that the urinary diversion had a negative effect on nocturnal sleep 88% had a decreased quality of life vs 65% of those who stated that the urinary diversion had no or little influence on nocturnal sleep. CONCLUSIONS: Nocturnal urinary problems are of great concern for individuals with urinary diversion, especially those with an orthotopic neobladder. Regular disruption of sleep decreases quality of life.

Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients.

OBJECTIVE: To assess whether diagnostic random bladder biopsies and the detection of concomitant carcinoma in situ (CIS) have an impact on the frequency of intravesical bacille Calmette-Guérin (BCG) instillations or radical cystectomy; and whether this affects the cancer-specific survival in patients with pTaG3 or pT1G1-G3 transitional cell carcinoma of the urinary bladder. MATERIAL AND METHODS: A population-based cohort of 538 patients with newly diagnosed bladder cancer was prospectively registered in the Stockholm County during 1995 and 1996 and followed for more than 5 years. RESULTS: Random biopsies were recommended in all patients but the decision to take biopsies was made by the treating urologist and hence performed in 326 out of 538 patients (61%), which revealed concomitant CIS in 47 patients(14%). Sixty out of 103 (58%) patients with pTaG3 or pT1G1-G3 tumours, in whom random biopsies were performed, received intravesical BCG compared with five out of 22 patients (23%) where random biopsies were not taken (p = 0.004). Moreover, 23 out of 103 patients (22%) with pTaG3 or pT1G1-G3 tumours in whom random biopsies were performed underwent radical cystectomy compared with none out of 22 patients (0%) without random biopsies (p = 0.013). The Cox proportional hazard ratio for death due to bladder cancer in patients with pTaG3 or pT1G1-G3 tumours among patients not having versus having undergone random biopsies was 2.5 (95% confidence interval 1.1-5.6). CONCLUSION: Patients diagnosed in Stockholm in 1995 or 1996 with pTaG3 or pT1G1-G3 bladder tumours having undergone random bladder biopsies more frequently underwent BCG treatment and radical cystectomy and had higher cancer-specific survival than patients who did not undergo random biopsies.

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer.

OBJECTIVES: To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer. PATIENTS AND METHODS: We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval. RESULTS: We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI. CONCLUSIONS: We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.

Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: the SWENOTECA management program.

PURPOSE: To offer minimized risk-adapted adjuvant treatment on a nationwide basis for patients with clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT). The aim was to reduce the risk of relapse and thereby reducing the need of later salvage chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From 1998 to 2005, 745 Norwegian and Swedish patients were included into a prospective, community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) management program. Treatment strategy depended on the presence or absence of vascular tumor invasion (VASC). VASC-positive patients were recommended brief adjuvant chemotherapy (ACT) with bleomycin, etoposide, and cisplatin (BEP), whereas VASC-negative patients could choose between ACT and surveillance. RESULTS: At a median follow-up of 4.7 years, there have been 51 relapses. On surveillance, 41.7% of VASC+ patients relapsed, compared with 13.2% of VASC- patients. After one course of BEP, 3.2% of VASC+ and 1.3% of VASC- patients relapsed. The toxicity of adjuvant BEP was low. Eight patients have died, none died from progressive disease. CONCLUSION: One course of adjuvant BEP reduces the risk of relapse by approximately 90% in both VASC+ and VASC- CS1 NSGCT, and may be a new option as initial treatment for all CS1 NSGCT. One course of adjuvant BEP for VASC+ CS1 reduces the total burden of chemotherapy compared with surveillance or two courses of BEP. SWENOTECA currently recommends one course of BEP as standard treatment of VASC+ CS1 NSGCT, whereas both surveillance and one course of BEP are options for VASC- CS1 NSGCT.

Clinical outcome following prostatic capsule- and seminal-sparing cystectomy for bladder cancer in 25 men.

OBJECTIVE: To improve the functional outcome after cystectomy for bladder cancer, cystectomy was performed with a prostatic capsule- and seminal-sparing approach. This report describes the clinical outcome of the first 25 patients. MATERIAL AND METHODS: A total of 25 male patients underwent cystectomy with preservation of the seminal vesicles, posterior prostate and neurovascular bundles. Orthotopic neobladders were used to divert the urine. At the time of last follow-up, patients were interviewed in a standard fashion to evaluate urinary, bowel and sexually related symptoms. RESULTS: During the follow-up period (mean 72 months, range 33-129) five patients developed metastases and died of bladder cancer. Four men were diagnosed with concomitant prostate cancer. Complete day-time continence was reported in 17/20 (85%) patients. Complete nocturnal continence was seen in 10/20 (50%) men. A total of 20/21 (95%) were sexually active following prostate-sparing cystectomy. CONCLUSION: Prostatic capsule- and seminal-sparing cystectomy appears to combine acceptable oncological outcome with satisfactory function of the lower urinary tract; however, standard radical cystectomy still represents the gold standard.

Patient-assessed outcomes in Swedish and Egyptian men undergoing radical cystectomy and orthotopic bladder substitution--a prospective comparative study.

OBJECTIVES: To compare two patient populations with assumed cultural differences undergoing radical cystectomy and orthotopic bladder substitution to determine whether these translate into differences in the answers to self-report instruments. METHODS: The questionnaires Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-BL), consisting of a general version (FACT-G) and a bladder cancer specific module, and Hospital Anxiety and Depression Scale (HADS) were used preoperatively and 3 and 12 months postoperatively to assess patient well-being, urologic symptoms, depression, and anxiety in 29 and 32 Swedish and Egyptian male patients, respectively. RESULTS: Significant differences were found between the two groups. Higher FACT-G scores (ie, better outcomes) were obtained in the Swedish patients, both preoperatively and 3 months postoperatively, but not after 12 months. Differences were also seen in the urogenital assessment provided by the FACT-BL module. HADS revealed more depression among the Egyptian patients throughout the study period. Also, anxiety was more common preoperatively and 3 months postoperatively in the Egyptian patients, but not after 12 months. CONCLUSIONS: Swedish men scored better than Egyptian men on the FACT-BL and HADS, although the latter improved with time after surgery. These results show that patient-assessed outcomes differ in patients from different sociocultural backgrounds. This should be recognized when analyzing results from comparative studies. Also, the use of culture-fair instruments is important when assessing patients with different sociocultural backgrounds.

Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer.

OBJECTIVE: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. PATIENTS AND METHODS: Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1-G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. RESULTS: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes. CONCLUSION: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival.

Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer.

OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.

Concentrations of polychlorinated biphenyls in blood and the risk for testicular cancer.

An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.

Polymorphisms in DNA repair and metabolic genes in bladder cancer.

We investigated the association of urinary bladder cancer with genetic polymorphisms in the xeroderma pigmentosum complementation group C (XPC), group D (XPD) and group G (XPG), X-ray repair cross-complementing group 1 (XRCC1) and group 3 (XRCC3), Nijmegen breakage syndrome 1 (NBS1), cyclin D1, methylene-tetrahydrofolate reductase (MTHFR), NAD(P)H dehydrogenase quinone 1 (NQO1), H-ras and glutathione S-transferase theta 1 (GSTT1) genes. Bladder cancer patients from the different hospitals in Stockholm County Council area and matching controls were genotyped for different polymorphisms. The frequency of the variant allele for A/C polymorphism in exon 15 of the XPC gene was significantly higher in the bladder cancer cases than in the controls (OR 1.49, 95% CI 1.16-1.92, P = 0.001). The variant allele homozygote genotype for the T/C polymorphism in exon 1 of the H-ras gene was associated with a decreased risk for bladder cancer (OR 0.12, 95% CI 0.02-0.67, P = 0.006). The variant allele genotypes for the single nucleotide polymorphisms (SNPs) in DNA repair genes, XPG and NBS1, showed a marginal association with the occurrence of bladder cancer (OR 0.38, 95% CI 0.15-0.94, P = 0.03 and OR 1.64, 95% CI 0.92-2.90, P = 0.09, respectively). We also report a positive correlation between the null homozygote of GSTT1 with the risk of bladder cancer (OR 2.54, 95% CI 1.32-4.98, P = 0.003). For other polymorphisms included in this study, NBS1 Glu185Gln, XPD Lys751Gln, XPG Asp1104His, XRCC1 Arg399Gln, XRCC3 Thr241Met, cyclin D1 Pro242Pro, MTHFR Ala222Val and Glu429Ala, NQO1 Arg139Trp and Pro187Ser, no significant differences for genotype distributions and allele frequencies between the bladder cancer cases and the controls were observed in the present study.

Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer.

An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or nonseminoma testicular cancer.

Bladder neoplasms--regions at chromosome 9 with putative tumour suppressor genes.

OBJECTIVES: To investigate the prevalence of loss of heterozygosity (LOH) at 12 different loci on chromosome 9 in patients with bladder neoplasms using a newly developed fluorescent multiplex polymerase chain reaction. PATIENTS AND METHODS: In a population-based study, freshly frozen tissue was collected from all cases of newly detected bladder neoplasms in the Stockholm region during 1995 and 1996 (n = 538) and 156 representative cases were subsequently studied in the present series. RESULTS: In total, at one or more loci of chromosome 9, 89% (139/156) of the tumours showed LOH. Loss of heterozygosity in informative cases was in the range from 33.1% (41/124) at the 9p21 locus to 67% (77/115) at the 9q31.3-32 loci. When minor LOH was studied, representing a single LOH with retention of heterozygosity at both adjacent markers, relatively frequent losses were detected at 9q22.3 harbouring the PTCH gene (7.7%), at 9q32-33.1 (6.6%) and at 9q33.2 harbouring the DBCCR1 gene (7.5%). In relation to clinical information, LOH at 9p22.1 was statistically significantly correlated with tumour grade (p = 0.01), but not with tumour stage. Replication errors were observed in 14 of 156 (9%) tumours. CONCLUSIONS: Our observation of relatively frequent minor LOH at 9p22.1, 9q22.3 and 9q32-33.1 identifies regions within which putative tumour suppressor genes, including the PTCH and the DBCCR1 genes, may reside.