Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. PATIENTS AND METHODS: Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. RESULTS: Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. CONCLUSION: We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. CLINICAL TRIAL NUMBER: NCT00672282.

Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP.

OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). CONCLUSIONS: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear. METHODS: A population-based cohort of 36,959 Swedish men aged 45-79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases). RESULTS: From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m(-2) when compared with 22 kg m(-2) was 0.69 (95% CI 0.52-0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88-1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51-1.01)). CONCLUSION: Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa--a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.

Incidence and mortality of incidental prostate cancer: a Swedish register-based study.

In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

A prospective study of lifetime physical activity and prostate cancer incidence and mortality.

BACKGROUND: The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear. METHODS: A prospective cohort of 45,887 men aged 45-79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer. RESULTS: We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2-27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7-31%). The rate ratio linearly decreased by 7% (95% CI=1-12%) for total, 8% (95% CI=0-16%) for localised and 12% (95% CI=2-20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day. CONCLUSIONS: Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort.

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high ets-related [corrected] gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors.

BACKGROUND: The incidence of prostate cancer has increased during the past 30 years but has been paralleled by increases in survival rates from this disease, despite the absence of documented major improvement in curative treatment. Since a high prevalence of microscopic prostate cancer has been observed in autopsied men and because many prostate cancers may never surface clinically, increased diagnostic activities might have led to increased detection of less aggressive tumors. PURPOSE: This study was conducted to elucidate whether the trends in prostate cancer incidence and patient survival may be due to increasing diagnoses of nonlethal tumors. METHODS: We analyzed a population-based cohort comprising all cases of prostate cancer (n = 80,901) detected in Sweden during the period of 1960 through 1988. Five hundred eighteen patients (0.64% of the total number) who could not be followed because of emigration or an incomplete national registration number were excluded. Observed and relative survival rates were calculated for the entire cohort of 80,383 assessable patients per 5-year age group in 5-year periods of diagnosis and according to diagnostic method and were compared between geographic areas with differences in incidence rates. To estimate the independent effects of these determinants, multivariate analyses were performed. RESULTS: For the 80,383 patients with complete follow-up, the 10- and 20-year observed survival rates were 17.5% (95% confidence interval [CI] = 17.2%-17.9%) and 3.5% (95% CI = 3.2%-3.7%), and the relative survival rates were 41.1% (95% CI = 40.3%-41.9%) and 28.6% (95% CI = 26.5%-30.1%), respectively. Relative survival rates improved markedly over time; 10-year relative survival rates increased from 29% (95% CI = 27%-31%) among case patients diagnosed in 1960 through 1964 to 45% (95% CI = 43%-46%) among those diagnosed in 1975 through 1979. Relative survival rates leveled off after about 18 years at 18% (95% CI = 15%-20%) among patients diagnosed in 1960 through 1964 and at 31% (95% CI = 28%-34%) among those diagnosed in 1970 through 1974. An even more favorable outlook was observed in those case patients diagnosed later. In areas with a high or low incidence of prostate cancer, the 10-year relative survival rates were 45% (95% CI = 44%-47%) and 36% (95% CI = 34%-38%), respectively. In the early 1960s, the calculated loss of life expectancy after diagnosis varied from about 68% (95% CI = 61%-75%) of the expected length of life in the youngest age group to about 48% (95% CI = 46%-50%) in the oldest age group. From 1960 through 1964 to 1985 through 1988, the loss of life expectancy decreased by more than 50% in all age groups. The differences in relative survival rates between age groups were small, with a gradual decrease in age groups more than 60-64 years of age. CONCLUSIONS: Most of the great temporal improvement and geographic variation in survival rates are quantitatively consistent, with likely increases in the rate of detection of nonlethal tumors. IMPLICATIONS: The increase in relative survival rates must be taken into consideration when evaluating the outcome of treatment of prostate cancer, since nonrandomized comparisons may be confounded by time trends. Diagnosis of nonlethal tumors raises concerns because the individual would suffer from the psychologic burden of a cancer diagnosis without any therapeutic benefit.

Graft-versus-host Disease After Intestinal or Multivisceral Transplantation: A Scandinavian Single-center Experience.

BACKGROUND: Graft-versus-host disease (GVHD) that develops after intestinal or multivisceral transplantation is difficult to diagnose and is associated with high morbidity and mortality. MATERIAL AND METHODS: The objectives of this study were to investigate the incidence, clinical picture, risk factors, and outcome of GVHD in a Scandinavian cohort of patients who underwent intestinal or multivisceral transplantation during a period of 16 years (1998-2014). All transplanted patients (n = 26) were retrospectively analyzed with respect to donor- and recipient-derived risk factors. The diagnosis of GVHD was based on clinical signs, chimerism analyses of leukocytes, and histopathologic findings in biopsy specimens. RESULTS: Five of 26 patients (19%) were diagnosed with GVHD, of which three had skin GVHD, one had skin and bone marrow GVHD, and one had passenger leukocyte syndrome. Only multivisceral-transplanted patients developed GVHD. Risk factors for development of GVHD were an underlying tumor diagnosis and neoadjuvant chemo- or brachytherapy administered before intestinal transplantation. All patients were given high-dose corticosteroids as first line treatment for their GVHD, and all survived their episodes of GVHD. CONCLUSIONS: The risk of GVHD appears to be increased in recipients of multivisceral transplantations who received chemotherapy due to an underlying malignancy. The reasons may be the large amount of lymphoid tissue in these types of grafts, and the cytotoxic effects of the malignancy and chemotherapy on healthy recipient tissues. These patients should be monitored closely for the development of GVHD.

Prostate cancer associated with CYP17 genotype.

Androgens play an important role in the development of prostate cancer. Androgen regulating genes that show allelic variation may be susceptibility factors for the disease. One of these genes, CYP17, encodes the cytochrome P450c17alpha enzyme. It catalyses steroid 17alpha-hydroxylase/17,20 lyase activities at key points in testosterone biosynthesis. We investigated the association between a polymorphism in the CYP17 gene and prostate cancer in a population-based case-control study. All individuals studied were Caucasians born in Sweden, 178 were consecutive clinical prostate cancer patients, and 160 were age-matched control individuals randomly selected from the same catchment area. DNA was extracted from blood samples. A CYP17 gene fragment was amplified by polymerase chain reaction. The MspA1I restriction enzyme, which recognizes the base pair substitution, was used to identify the allelic variants CYP17A1 and CYP17A2. Significantly more men homozygous for the CYP17A1 allele were found among prostate cancer patients compared with control individuals; odds ratio 1.61 (95% confidence interval 1.02; 2.53), P = 0.04. According to a preliminary report, the CYP17A1/A1 genotype leads to higher circulating androgen levels, possibly by encoding for a more active androgen synthesizing CYP17 enzyme. Consequently, the CYP17A1/A1 genotype, which was found in a higher frequency among prostate cancer patients, may prove to be one of the important susceptibility factors for prostate cancer. If verified, this genotype is likely to convey a larger risk on a population basis, than the rare hereditary prostate cancer genes do.

Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer.

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.

Gastro-intestinal toxicity related to bone marrow transplantation: disruption of the intestinal barrier precedes clinical findings.

The intensive cytotoxic treatment given in connection with bone marrow transplantations induces severe injury to the gut consistent with an increase in intestinal permeability. Currently, extent of the gut injury is assessed by inspecting the mouth and recording symptoms deriving from the gastro-intestinal tract. The aims of this study were to evaluate whether changes in permeability correlate with clinical assessment of gut toxicity, according to the WHO criteria, and also to examine the duration of intestinal permeability after high-dose chemotherapy. In 18 consecutive patients undergoing bone marrow transplantation, gastrointestinal permeability was assessed by a 51Cr-EDTA absorption test before the start of cytotoxic treatment, and 4, 7, 10 and 14 days after stem-cell infusion. In another seven patients, permeability was assessed 2 days after the start of cytotoxic treatment, and 1, 7 and 14 days after stem cell infusion. During the same period, oral- and non-oral clinical toxicity according to the WHO criteria were recorded. Permeability increased significantly 2 days after the start of cytotoxic treatment (P < 0.05), on day 1 (P < 0.05), on day 4 (P < 0.0005), on day 7 (P < 0.0005) and on day 10 (P < 0.005) after stem cell infusion, compared with pre-treatment permeability. Despite significant barrier dysfunction, clinical toxicity was very moderate in the early transplantation course. Gastro-intestinal, but not oral clinical toxicity requiring therapy, was consistent with a significant increase in permeability compared with no clinical toxicity or toxicity not requiring therapy. Similarly, cumulative gastro-intestinal, but not oral toxicity correlated positively with the increase in permeability. The permeability test was unable to predict the severity of the clinical gastro-intestinal toxicity.

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study.

Intensive cytotoxic therapy with bone-marrow transplantation (BMT) allows a potential cure for haematological malignancies. Protective strategies to minimise haematological toxicities have been successful and currently toxicity to the gastro-intestinal tract is the major cause of treatment-related morbidity and the dose-limiting factor that prevents further dose escalation. In a randomised, placebo-controlled trial we investigated whether an oral immunoglobulin preparation (IgA-IgG) can diminish intestinal toxicity with autologous BMT. IgA-IgG (n = 6) and placebo (n = 7) were orally administered from 1 day prior to the start until 1 week after the termination of the cytotoxic treatment (a total of 14 days). Intestinal toxicity was assessed by a 51Cr-EDTA absorption test for intestinal permeability and by the clinical criteria laid down by the WHO for the period before the start of the cytotoxic treatment, 1 day prior to stem-cell infusion and 4, 7, 10 and 14 days after stem-cell infusion. In the placebo group there was a significant increase in intestinal permeability on day 4 (P < 0.005) and on day 7 (P < 0.05) after stem-cell infusion, compared with the baseline, which was not seen for IgA-IgG. In addition, patients receiving IgA-IgG had significantly less intestinal permeability on day 4 (P < 0.05) and on day 7 (P < 0.05), compared with the placebo group. No significant, positive effect as regards clinical toxicity was observed. Oral administration of IgA-IgG to patients undergoing intensive cytotoxic therapy prior to BMT seems to have a protective effect on the gut mucosa barrier which is normally disrupted by this therapy.

The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning.

The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD.

Gastric emptying after autologous haemopoietic stem-cell transplantation: a prospective trial.

Gastroparesis may be involved in the pathophysiology of prolonged nausea and vomiting after haemopoietic stem-cell transplantation (HSCT), but this has not been prospectively investigated. Gastric emptying (GE) was investigated in 20 patients before and 2 months after autologous HSCT. Gastrointestinal symptoms were graded prospectively and oral energy intake was recorded in parallel. Before transplant, all patients were asymptomatic and GE was within the reference range. Post transplant GE was delayed in three patients and three patients reported nausea and/or vomiting. Neither gastrointestinal symptoms nor oral energy intake post transplant discriminated between patients with or without delayed GE. Oral energy intake before transplant was lower (P=0.05), and there was a greater need for total parenteral nutrition (TPN) among patients who developed gastroparesis post transplant (P<0.05). Delayed GE after HSCT was found to be less common than had been believed from retrospective studies. Gastroparesis may be involved in some cases of prolonged nausea and vomiting after autologous HSCT but alternative explanations should be considered. Symptoms consistent with gastroparesis did not correlate with GE. Patients at risk of developing gastroparesis may be found among those with nutritional difficulties before and during the transplant course.

Results of window operation for primary hydrocele.

The window operation for hydrocele repair has been reported to be a safe out-patient procedure, with few complications and relapses. In this pilot study the procedure could be safely done on an out-patient basis and the rate of complications (8%) was comparable to that of other procedures. However, 21/23 evaluated hydroceles relapsed and retreatment with a second window operation led to further relapses within a short time. Eight patients with 11 hydroceles required another procedure. We have therefore abandoned the window operation for hydrocele repair.

Hemorrhagic infarctions of testis due to intimal fibroplasia of spermatic artery.

Two cases of hemorrhagic infarctions of the testis are presented. The infarctions were due to intimal fibroplasia of the branches of the spermatic artery; to our knowledge, a condition described only in the kidney. The differences between intimal fibroplasia and the lesions of polyarteritis nodosa and thromboangiitis obliterans are discussed.

Benign prostatic hyperplasia in Sweden 1987 to 1994: changing patterns of treatment, changing patterns of costs.

OBJECTIVES: To assess health care use and costs for benign prostatic hyperplasia (BPH) in Sweden from 1987 to 1994 when minimal invasive procedures, including transurethral microwave therapy (TUMT) and drugs, were introduced, in addition to conventional surgery. METHODS: Cross-sectional annual data on health care utilization based on national information systems and surveys were used for calculation of direct 1994 cost. RESULTS: The total number of men in the age group at risk for BPH was virtually constant, and the total direct health care costs for BPH treatment increased from 1987 to 1992. A slight decrease was evident for the years 1993 and 1994, notwithstanding the introduction of new ambulatory procedures in 1991 and of new drugs in 1992. The number of physician office visits changed little during the study period, although this estimate may be low. TUMT procedures were introduced rapidly but decreased; nevertheless, their share was never more than 3% of total costs. Drug sales were 15-fold those in 1992 and accounted for 12% of the total costs in 1994. Conventional transurethral resection of the prostate (TURP) operations decreased markedly after the introduction of the new treatments. CONCLUSIONS: The new treatments were adopted differently. TUMT procedures decreased as rapidly as they were introduced. Three years after the introduction of the new drugs, drug sales indicated that the number of men receiving drug treatment was greater than the annual number of men receiving TURP operations and TUMT procedures combined. Yet the total costs showed a slight decrease, mainly due to the decreasing numbers of TURP operations.

Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate.

The efficacy and side effects of flutamide were compared with estramustine in patients with advanced prostatic carcinoma. Thirty patients with metastatic cancers but with no serious cardiovascular (CV) conditions were randomly assigned to receive treatment either with flutamide (250 mg X 3) or with estramustine (280 mg X 2). Clinical examination, bone scan, laboratory measurements, including coagulation studies were performed prior to randomization, every three months during year one, and at six-month intervals thereafter. The two groups were comparable with respect to age and tumor characteristics. However, more patients presented with skeletal pain among those later treated with flutamide. During an observation period of between one and two and one-half years, flutamide was discontinued in 1 case (7%) because of icterus, and estramustine in 3 cases (20%) because of CV complications. Of the remaining 14 flutamide-treated patients, 13 responded initially. Eleven of them relapsed, and 5 died of cancer. In the corresponding group of 12 estramustine-treated patients, there were 11 primary responders. Of these, only 2 relapsed and died as did the only nonresponder. The difference between the two groups with regard to relapse is significant (P less than 0.01), but not with regard to mortality. All estramustine-treated patients lost their libido, whereas only 20 per cent of the patients treated with flutamide did so. In the present limited material there was an initial favorable response to flutamide without signs of CV complications and with maintained libido in most cases. However, due to significantly increased risk for relapse compared with estramustine, flutamide cannot be recommended as single therapy except in cases where estrogens are contraindicated or when interference with libido and potency is unacceptable.