A higher prediagnostic insulin level is a prospective risk factor for incident prostate cancer.

A higher insulin level has been linked to the risk of prostate cancer promotion. However, several reports claim that there is no association between a higher insulin level and the risk of incident prostate cancer. In the present report, the insulin hypothesis was tested once more prospectively in men with a benign prostatic disorder. Three hundred and eighty-nine consecutive patients referred with lower urinary tract symptoms without clinical prostate cancer were included during 1994-2002. Follow-up was performed in 2006. Data were obtained from the Swedish National Cancer Register and the Regional Cancer Register, Oncological Centre, Göteborg, Sweden. At this follow-up, 44 of the patients included had developed prostate cancer. Men with prostate cancer diagnosis had a higher systolic (P<0.001) and diastolic blood pressure (P<0.000), were more obese as measured by BMI (P=0.010), waist (P=0.007) and hip measurements (P=0.041) than men who did not have prostate cancer diagnosis at follow-up. These men also had a higher uric acid level (P=0.040), and a higher fasting serum insulin level (P=0.023) than men who did not have prostate cancer diagnosis at follow-up. Following exclusion of T1a/b prostate cancer cases, the difference of the fasting serum insulin level between the groups was still significant (P=0.038). Our data support the hypothesis that a higher insulin level is a promoter of prostate cancer. Moreover, our data suggest that the insulin level could be used as a marker of the risk of developing prostate cancer. The present findings also seem to confirm that prostate cancer is a component of the metabolic syndrome. Finally, our data generate the hypothesis that the metabolic syndrome conceals early prostate cancer.

Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia.

The aetiology of benign prostatic hyperplasia (BPH) remains unclear. The objective of the present study was to test the insulin, oestradiol and metabolic syndrome hypotheses as promoters of BPH. The design was a risk factor analysis of BPH in which the total prostate gland volume was related to endocrine and anthropometric factors. The participants studied were 184 representative men, aged 72-76 years, residing in Göteborg, Sweden. Using a multivariate analysis, BPH as measured by the total prostate gland volume correlated statistically significantly with fasting serum insulin (beta=0.200, P=0.028), free oestradiol (beta=0.233, P=0.008) and lean body mass (beta=0.257, P=0.034). Insulin and free oestradiol appear to be independent risk factors for BPH, confirming both the insulin and the oestradiol hypotheses. Our findings also seem to confirm the metabolic syndrome hypothesis. The metabolic syndrome and its major endocrine aberration, hyperinsulinaemia, are possible primary events in BPH.

Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia.

OBJECTIVE: To determine the validity coefficient of the total prostate gland volume as an expression of the transition zone (TZ) volume. To test the hypothesis of hyperinsulinaemia as a causal factor for the development of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Three hundred and seven consecutive patients with lower urinary tract symptoms were studied. A subgroup of 114 patients were tested with regard to the validity coefficient between the total prostate gland volume and the TZ volume. In the total material of 307 men, a BPH risk factor analysis was performed in which groups of men with the following conditions were related to the annual BPH growth rate: men without or with metabolic disease; men with different components of the metabolic syndrome, and men with low or high fasting plasma insulin values. The prostate gland volume and the TZ volume were determined using ultrasound. The presence of non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension was obtained from the patients' medical records. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index and waist/hip ratio were calculated. Blood samples were drawn from fasting patients to determine the insulin and HDL-cholesterol values. RESULTS: In the subgroup of men subjected to measurement of both the total prostate gland volume and the TZ volume, the correlation coefficient between total prostate gland volume and the TZ volume was r.s. = 0.97 (p < 0.0001) which, thus, constituted the validity coefficient. The median annual BPH growth rate in the total group was 1.03 ml/year. The median annual BPH growth rate was faster in men with metabolic disease (p < 0.0001), NIDDM (p < 0.0001), treated hypertension (p < 0.0001), obesity (p < 0.0001) and dyslipidaemia (p < 0.0001) than in men without metabolic disease. Moreover, the annual BPH growth rate correlated positively with the diastolic blood pressure (r.s. = 0.27; p < 0.001), the BMI (r.s. = 0.22; p < 0.001) and four other expressions of obesity, and negatively with the HDL-cholesterol level (r.s. = -0.15; p < 0.001). The median annual BPH growth rate was faster in men with a high than in men with a low fasting plasma insulin level (p = 0.019). When the patients were divided into quartiles, the median annual BPH growth rate increased statistically significantly with increasing fasting plasma insulin levels. The fasting plasma insulin values correlated with the annual BPH growth rates (p = 0.009). When performing a multivariate analysis using the total prostate gland volume as dependent variable, fasting plasma insulin (p = 0.001) and age (p < 0.001) became statistically significant. CONCLUSION: The results of the present report suggest that the total prostate gland volume constitutes a valid expression of BPH. The findings support the hypothesis that hyperinsulinaemia is causally related to the development of BPH and generate the hypothesis of an increased sympathetic nerve activity in men with BPH.

Clinical, anthropometric, metabolic and insulin profile of men with fast annual growth rates of benign prostatic hyperplasia.

The purpose of this study was to test the hypothesis of a causal relationship between high insulin levels and the development of benign prostatic hyperplasia (BPH) and to determine the clinical, anthropometric, metabolic and insulin profile in men with fast-growing BPH compared with men with slow-growing BPH. The present study was designed as a risk factor analysis of BPH in which the estimated annual BPH growth rate was related to components of the metabolic syndrome. Two hundred and fifty patients referred to the Urological Section, Department of Surgery, Central Hospital, Varberg, Sweden, with lower urinary tract symptoms with or without manifestations of the metabolic syndrome were consecutively included. The prevalences of atherosclerotic disease manifestations, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, total cholesterol, triglycerides, HDL and LDL cholesterol, uric acid, alanine aminotransferase (ALAT) and prostate-specific antigen (PSA). The prostate gland volume was determined using ultrasound. The median annual BPH growth rate was 1.04 ml/year. Men with fast-growing BPH had a higher prevalence of NIDDM (p = 0.023) and treated hypertension (p = 0.049). These patients were also taller (p=0.004) and more obese as measured by body weight (p<0.001), BMI (p=0.026), waist measurement (p <0.001), hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they had elevated fasting plasma insulin levels (p = 0.018) and lower HDL cholesterol levels (p = 0.021) than men with slow-growing BPH. The annual BPH growth rate correlated positively with diastolic blood pressure (rs = 0.14; p = 0.009), BMI (rs = 0.24; p < 0.001) and four other expressions of obesity and fasting plasma insulin level (rs = 0.18; p = 0.008), and negatively with the HDL cholesterol level (rs = -0.22; p = 0.001). In conclusion, the data suggest that NIDDM, hypertension, tallness, obesity, high insulin and low HDL cholesterol levels constitute risk factors for the development of BPH. The results also suggest that BPH is a component of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinaemia, as patients with the metabolic syndrome. The findings support the hypothesis of a causal relationship between high insulin levels and the development of BPH, and give rise to a hypothesis of increased sympathetic nerve activity in men with BPH.

S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.

A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.

Components of the metabolic syndrome-risk factors for the development of benign prostatic hyperplasia.

The purpose of the present study was to perform a BPH risk factor analysis in men, relating the prostate gland volume to components of the metabolic syndrome and to identify clues to the etiology of BPH. Our material comprised a consecutive series of 158 patients with lower urinary tract symptoms with or without manifestations of the metabolic syndrome. In this group, the measured volume of the prostate was related consecutively to potential risk factors. The diagnoses atherosclerosis, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained from the patient's medical history. Data on blood pressure, waist and hip measure, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, cholesterol, triglycerides, HDL and LDL-cholesterol, uric acid and ALAT. The prostate gland volume was determined using ultrasound. Our results show that there was a larger prostate gland in men with NIDDM (P=0.0058), treated hypertension (P=0.0317), obesity (P<0.0001), low HDL-cholesterol levels (P=0.0132) and high insulin levels (P<0.0001) than in men without these conditions. The prostate gland volume correlated positively with the systolic blood pressure (r(s)=0.17; P=0.03), obesity (r(s)=0.34; P<0.0001) and fasting insulin (r(s)=0.38; P<0.0001) and negatively with HDL-cholesterol (r(s)=-0.22; P=0.009). On the basis of our findings, we concluded that NIDDM, treated hypertension, obesity, low HDL-cholesterol levels and high insulin levels constitute risk factors for the development of BPH. The results suggest that BPH is a facet of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinemia as patients with the metabolic syndrome. The findings generate a hypothesis of a causal relationship between high insulin levels and the development of BPH. In a clinical setting, the findings of the present report suggest that, in any patient presenting with BPH, the possible presence of NIDDM, hypertension, obesity, high insulin and low HDL-cholesterol levels should be considered. Conversely, in patients suffering from these conditions, the possibility of a clinically important BPH should be kept in mind.

[Saphenous vein-saving surgery--an alternative to stripping]. / Vena saphena magna-sparande kirurgi--ett alternativ till stripping.

Over the past 12 years, long saphenous vein-saving surgery has been explored as an alternative to standard stripping at the Dept. of Surgery, Varberg Hospital, Varberg, Sweden. Four-year follow-up has shown vein-saving surgery, based on pre-operative phlebographic mapping of incompetent perforators and their occlusion at surgery, to yield clinical and plethysmographic outcome comparable to that obtained after standard stripping. The long saphenous vein (LSV) was thus preserved, and the patients reported postoperative discomfort to be milder than that following standard stripping. The findings suggest perforator incompetence to be an early event in the formation of primary varicose veins, and the improved haemodynamic function following vein-saving surgery to be due to the occlusion of incompetent perforators and the restoration of LSV function. This procedure might be worth considering in cases of patients at great risk of needing future arterial reconstruction, or who for any other reason wish to avoid LSV ablation.

Does transurethral resection of a clinically benign prostate gland increase the risk of developing clinical prostate cancer? A 10-year follow-up study.

BACKGROUND: Theoretical considerations have raised the suspicion that transurethral resection of the prostate (TURP) may increase the risk of developing prostate cancer in clinically benign prostate glands. Previous studies have not shown an increased risk among men who had undergone TURP for benign prostatic hyperplasia compared with the risk in age-matched control subjects. However, in all of these studies, all men with stage T1 prostate cancer in the TURP-group were excluded, possibly creating a bias, because no similar exclusion could be made for the controls. METHODS: The incidence and mortality of clinical prostate cancer were studied in 198 patients who had TURP and in 203 age-matched male control subjects. In both groups, all patients with known prostate cancer and patients with suspected cancer by digital rectal examination were excluded from the study. However, patients with stage T1 cancer found by the TURP were included in the comparison between the groups. RESULTS: The mean age in the two groups was 67 +/- 6 years. The patients were followed for an average of 10.2 +/- 1.2 years and 10.4 +/- 1.8 years in the TURP group and the control group, respectively. Clinical prostate cancer developed in six patients who had TURP and subsequently in five control (odds ratio, 0.8 [0.2-3.1]; P < 0.97). Before follow-up, three men in each group died because of prostate cancer (odds ratio, 1.3 (0.24-7.45); P < 0.97). CONCLUSIONS: The results of this study suggest that neither benign prostatic hyperplasia nor TURP increased the risk of developing clinical prostate cancer over the next 10 years in patients with a benign prostate gland determined by rectal examination before TURP.

Tuberculosis in a Tulsa high school.

Following the discovery of a high school student with communicable tuberculosis, the Tulsa City-County Health Department skin tested 1,005 persons in the family, community, and school. Of the 931 persons tested at the school, 10 were reactors in March and 33 more were reactors in May. All 5 family members and 4 community contacts were tuberculin reactive. In all, 52 new tuberculin reactors were identified, evaluated, and considered for treatment or prophylaxis. This situation illustrates the conundrum that tuberculosis remains an important public health issue because of the possibility of transmission from small pockets of diseased persons to the larger community, especially in institutions of all kinds. Physicians and public health agencies must be vigilant and identify new cases for treatment and begin contact tracing to minimize the spread of tuberculosis.

Norfloxacin as prophylaxis against urethral strictures following transurethral resection of the prostate: an open, prospective, randomized study.

An open, prospective, randomized study was performed to investigate the effect of norfloxacin prophylaxis on stricture formation and operative outcome after transurethral resection of the prostate. After resection, the 359 patients studied were randomly divided into 2 groups: 1) those given norfloxacin as prophylaxis for 15 days following removal of the catheter (norfloxacin group) and 2) those given no antimicrobial prophylaxis during the same period (control group). Of the patients 94 were excluded. At followup 6 to 12 months postoperatively, the number of strictures in the anterior urethra was 2 of 135 in the norfloxacin group and 22 of 130 in the control group (p < 0.01). Strictures in the bladder neck developed in 3 of 135 and 4 of 130 patients, respectively (not significant). As a consequence of a lower structure incidence in the anterior urethra in the norfloxacin group, fewer patients in that group were dissatisfied with the operative outcome. The results suggest that norfloxacin provides effective prophylaxis against stricture formation after transurethral resection of the prostate.

Suprapubic catheter following transurethral resection of the prostate: a way to decrease the number of urethral strictures and improve the outcome of operations.

A prospective, randomized study was done to investigate the role of transurethral catheters in stricture formation after transurethral resection of the prostate. The operative outcome after using transurethral catheters made of 2 different materials compared with suprapubic catheters was also investigated. We studied 344 patients who underwent transurethral resection of the prostate. After resection the patients were randomly divided into 3 groups: 1) those drained by a transurethral polytetrafluoroethylene (Teflon)-coated latex catheter, 2) those drained by a transurethral polyvinylchloride catheter and 3) those drained by a suprapubic polyvinylchloride catheter. At 6 to 24 months the numbers of strictures in the anterior urethra were 10 of 102 and 11 of 102 in the transurethral drainage groups, respectively. The corresponding number of strictures in the suprapubic drainage group was 1 of 94 (p less than 0.01). Strictures in the bladder neck had developed in 5 of 102, 3 of 103 and 3 of 94 patients, respectively (not significant). As a consequence of a lower incidence of strictures in the anterior urethra in the suprapubic drainage group, more patients in that group were satisfied with the results of the operation.

Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study.

The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied.

Long saphenous vein saving surgery for varicose veins. A long-term follow-up.

The autologous saphenous vein is widely recognised as the graft material of choice in infra-inguinal arterial reconstructions. This study was undertaken to evaluate the long-term results of long saphenous vein saving surgery compared with standard stripping. Forty-two patients with varicose veins were randomly allocated to treatment, either with standard stripping of the long saphenous vein or high ligation. In both groups, local varicosities were avulsed and insufficient perforators ligated, on the basis of physical examination and phlebography. Follow-up was performed 52 +/- 5 months postoperatively. The recurrence rate was 12 and 11% in the stripping and the high ligation group respectively. At follow-up, the venous return time was increased significantly in both groups (P greater than 0.001). Vein mapping by means of high-resolution, real-time ultrasound at follow-up showed that 78% of the preserved saphenous veins were suitable for use as arterial conduits. These results suggest that removal of the long saphenous vein per se is of no therapeutic value if insufficient perforators have been ligated. It is possible to perform elective vein surgery for varicose veins with good results and preserve the long saphenous vein, which in turn can be used for future arterial reconstruction in most cases.

Arterial embolism and atrial arrhythmias.

In a retrospective study, the frequency of atrial arrhythmias of types known to cause systemic embolisation and the effect of anticoagulant treatment were studied in 106 patients with arterial embolism. Such embolising arrhythimas were found in 84 patients (79%). Permanent atrial fibrillation was documented in 53 patients (50%) and episodic atrial arrhythmia was encountered in 28 patients (26%). In 21 of 28 patients with sinus rhythm on admission, an embolising arrhythmia could be identified in previous ECG recordings. Patients with atrial arrhythmias had a significantly higher rate of prior embolic episodes and embolic events during follow-up (53 events in 84 patients) compared to the patients without arrhythmia (6 events in 22 patients) (P less than 0.05). In patients with atrial arrhythmias postoperative treatment with peroral anticoagulation was associated with a lower mortality (P less than 0.003) and a lower rate of reembolisation and stroke (P less than 0.0005). It is concluded that every fourth patient presenting with arterial embolism had an atrial arrhythmia of episodic nature. Most of these patients had normal sinus rhythm on admission but could be identified in previous ECG recordings. This study suggests that patients with arterial embolism and atrial arrhythmia have a higher risk of further embolisation with an ensuing risk of morbidity and death, compared to patients without arrhythmia. A positive effect of anticoagulation seemed to be present in patients with atrial arrhythmia whereas such a positive effect could not be identified in patients without arrhythmia.

Urethral strictures following transurethral resection of the prostate. The role of the catheter.

Urethral stricture is the most common late complication of transurethral prostatectomy (TURP). The cause is unknown. A prospective, randomised study was undertaken to investigate the role of the transurethral catheter in stricture formation. A total of 205 patients subjected to TURP were studied. Following resection, they were randomly divided into 2 groups: those drained by a transurethral siliconised latex catheter and those drained by a suprapubic siliconised latex catheter. At follow-up, 6 to 24 months later, 17% of the patients in the transurethral group had developed urethral stricture; the corresponding figure in the suprapubic group was 4%. As a consequence of the higher incidence of stricture in the transurethrally drained group, more patients in that group were dissatisfied with the results of the operation. It was concluded that the post-operative transurethral catheter was an important factor in stricture formation following TURP and that transurethral drainage with a siliconised latex catheter resulted in a higher incidence of stricture. This led to a greater number of patients being dissatisfied with the results of the operation, but the catheter did not affect the results in any other way.

Disopyramide-associated liver dysfunction.

A case of disopyramide-associated cholestatic jaundice is presented, and all reported cases of disopyramide-associated liver dysfunction are reviewed. Manifestations of liver dysfunction usually appear during the first week of treatment. Discontinuing administration of the drug often results in prompt clinical resolution, although in rare instances, laboratory abnormalities persist up to 18 months. Physicians should be aware of this rare but serious complication of disopyramide therapy.

The use of clonidine for management of opiate abstinence in a chronic pain patient.

The use of clonidine in the management of opiate abstinence is presented in a patient dependent upon levorphanol tartrate given for chronic pain. Use of levorphanol was abruptly discontinued, and the patient was monitored for signs and symptoms of opiate withdrawal. He manifested a significant increase in pulse and blood pressure and had perspiration, agitation, and opiate-seeking behavior. Clonidine effectively abolished these signs and symptoms. The mechanism by which clonidine prevents the opiate abstinence syndrome is discussed. Clonidine is a safe and inexpensive means of achieving rapid opiate withdrawal.