Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Sweden.

OBJECTIVE: To report the initial results from Sweden of a large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven. METHODS: From the population registry men aged 50-66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus f/tPSA assay (Perkin-Elmer, Turku, Finland). Men with a tPSA of < 3.0 ng/mL were not further investigated, while those with a tPSA of > or = 3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies. RESULTS: Of those invited, 60% accepted PSA testing and 11.3% had a tPSA of > or = 3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3-4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2-4, 71% 5-6, 19% 7 and 2% Gleason score 8-10. A threshold tPSA of > or = 4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of > or = 3.0 ng/mL combined with a f/tPSA threshold of < or = 18%. CONCLUSIONS: PSA screening detects early-stage low-grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of < 4 ng/mL.

Selective urological evaluation in men with febrile urinary tract infection.

OBJECTIVE: To investigate the prevalence and clinical importance of urological abnormalities in men with community-acquired febrile urinary tract infection (UTI). PATIENTS AND METHODS: In this prospective study, 85 men (median age 63 years, range 18--86) were followed for 1 year after an episode of febrile UTI. They were investigated by excretory urography, cysto-urethroscopy, uroflowmetry, digital rectal examination and measurement of postvoid residual urine volume by abdominal ultrasonography. RESULTS: The radiological examination of the upper urinary tract in 83 patients revealed 22 abnormal findings in 19 men. Relevant clinical abnormalities leading to surgical intervention were found in only one patient who had renal calyceal stones. The lower urinary tract investigation disclosed 46 findings in 35 men. In all, surgically correctable disorders were found in 20 patients, of whom 15 had previously unrecognized abnormalities. All patients who required surgery were identified either by a history of voiding difficulties, acute urinary retention at the time of infection, the presence of microscopic haematuria at follow-up after one month, or early recurrent symptomatic UTI. CONCLUSION: Routine imaging studies of the upper urinary tract seem dispensable in men with febrile UTI. To reveal abnormalities of clinical importance, any urological evaluation should primarily be focused on the lower urinary tract.

Outcome of laterally directed sextant biopsies of the prostate in screened males aged 50--66 years. Implications for sampling order.

OBJECTIVE: Prostate cancer has its most frequent location in the posterior-lateral part of the gland. The aim of this study was to evaluate the cancer detection rate of six systemic prostate biopsies with mid lobar biopsies taken far laterally in the prostate. PATIENTS AND METHODS: A total of 692 patients (aged 50--66 years) enrolled in a screening study underwent prostate biopsies because of an elevated serum prostate-specific antigen (PSA; > or =3 ng/ml) level. The outcome of the biopsies was related to findings at digital rectal examination (DRE) and transrectal ultrasound (TRUS) and to the location within the prostate. RESULTS: Prostate cancer was detected in 164 patients. DRE and TRUS were suspicious of malignancy in 66 cases (40%) and 84 cases (51%), respectively. The two biopsies taken far laterally midlobar in the prostate detected as many as 83% of the cancers and when combined with two apical biopsies, 96% of all cancers were detected. CONCLUSION: At PSA screening in this age-group, only 57% of the prostate cancers detectable by sextant biopsies were palpable or visible at TRUS. Most of the cancers (96%) were detectable by only four systematic, carefully directed biopsies. In men with normal DRE, the two lateral midlobar biopsies should be taken first during the biopsy procedure.

Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography.

OBJECTIVE: To determine the frequency of prostatic involvement in men with community-acquired febrile urinary tract infection. PATIENTS AND METHODS: This prospective study included 70 men (18-85 years old) who had a fever of >/=38.0 degrees C, symptoms or signs of urinary tract infection and a positive urine culture. Serum prostate-specific antigen (PSA) was measured and transrectal ultrasonography of the prostate and seminal vesicles performed during the acute phase of the disease and during a 1-year follow-up. RESULTS: Although only six patients had a tender prostate on digital rectal examination, the initial serum PSA level was elevated in 58 (83%) patients (median 14 ng/mL, range 0.54-140). There was no correlation between PSA levels, patient age, inflammatory response to infection or presence of positive blood cultures. Despite a rapid decline in PSA level after one month, there was a protracted decrease in some patients. After 3 months the median prostate volume was reduced by 31% (range 11-54; P<0.001) in 46 of 55 patients examined, and the width of the right and left seminal vesicle was reduced by 14% and 22%, respectively. The reductions in PSA and prostate volume were significantly correlated (r=0.36, 95% confidence interval 0.09-0.58; P=0.01). CONCLUSION: These results show that the prostate and seminal vesicles are frequently involved in men with febrile urinary tract infection and that PSA may be a useful marker of prostatic infection. The slow decline of PSA levels in some patients after appropriate antibiotic treatment indicates a protracted healing process and should be considered when PSA is used to detect prostate cancer.

Transrectal ultrasound with separate measurement of the transition zone volume predicts the short-term outcome after transurethral resection of the prostate.

OBJECTIVES: To determine whether the volume of prostatic adenomas as assessed by transrectal ultrasound (TRUS) influenced the outcome after transurethral resection of the prostate (TURP). METHODS: TRUS with total prostate and transition zone (TZ) volume determinations was performed preoperatively in 298 consecutive patients undergoing TURP for benign prostatic hyperplasia without prior urodynamic evaluation. Postoperatively, the outcome of surgery was stated as excellent (no or minor remaining symptoms), improved (but with some remaining symptoms), or failure (the same or aggravated symptoms) according to a patient-administered questionnaire. Six possible risk factors were evaluated: TZ volume 20 cc or less, neurologic disorders, previous TURP/transurethral incision of the prostate (TUIP), diabetes, indwelling catheter, and age older than 80 years. RESULTS: Thirty patients (10.1%) had treatment failure, 45 (15.1%) improvement, and 223 (74.8%) had excellent outcome. After subdivision into preoperative TZ volume of 20 cc or less and greater than 20 cc, it was found that the outcomes of 20.9% (n = 19) were failures if the TZ volume was 20 cc or less but only 5.3% (n = 11) if the TZ volume was greater than 20 cc. Additional independent risk factors for failure were neurologic disorders and previous TURP/TUIP. When all patients with risk factors were excluded (TZ volume 20 cc or less, neurologic disorders, previous transurethral surgery, and diabetes), the risk of failure was 3.3%. CONCLUSIONS: Patients with a preoperative TZ volume greater than 20 cc and no history of neurologic disorders, previous TURP/TUIP, or diabetes had a very high chance of favorable outcome after TURP, even though no pressure/flow evaluation had been performed preoperatively.

Pronounced anti-HIV-1 activity of foscarnet in patients without cytomegalovirus infection.

Combined therapy using reverse transcriptase (RT) and protease inhibitors is the current established treatment for HIV-1 infection. Foscarnet is an RT inhibitor that is a product analogue, in contrast to the widely used nucleoside analogues. In this study, the anti-HIV-1 effect of foscarnet, 50 mg three times per day administered intravenously for 4 weeks, was evaluated in 10 patients with minor or no symptoms. Serious adverse events developed in 2 patients, although most patients experienced some side effects. The levels of HIV-1 RNA decreased from a median value of 4.7 to 2.6 10log copies/ml. The effect was sustained through 4 weeks. One week after cessation of treatment, HIV-1 RNA levels increased to baseline. In contrast, no increase in the number of CD4+ cells was observed. The anti-HIV-1 effect was considered to be a direct effect on HIV-1 replication because no patient had concomitant cytomegalovirus (CMV) infection.

Lower urinary tract symptoms. A comparison of micturition symptoms in patients scheduled for transurethral prostatic resection and outpatients of both sexes referred for non-urological complaints.

The presence of ten different micturition symptoms was investigated by means of a patient-administered questionnaire in 355 males and females over 50 years of age referred for non-urological complaints, and compared to those of 131 patients selected for transurethral prostatic resection (TURP) due to symptomatic benign prostatic hypertrophy. Each symptom was evaluated further by a subsequent "bother" question and the questionnaire also contained a global "bother" question. Each of the symptoms was significantly more frequent and pronounced in the TURP group than in the control group. Moderate or severe symptoms were found in 25% of males and 18% of females in the control group as compared to 92% in the TURP group. In the control group most symptoms increased with age regardless of sex, and this was most pronounced for weak stream and hesitancy. Males in the control group had a significantly higher total symptom score than females (5.3 vs 4.3; p < 0.05). This difference was, however, mainly due to higher scores in weak stream, hesitancy and post-micturition dribbling in males. Females tended to have more urgency. The symptom scores and the associated "bother" scores were highly correlated, indicating that each symptom carried the same potential to bother the patient. The single global "bother" question gave an adequate reflection of the combined "bother" scores, and seems sufficient in the evaluation of the individual patient's concern.

Characteristics of screening detected prostate cancer in men 50 to 66 years old with 3 to 4 ng./ml. Prostate specific antigen.

PURPOSE: We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization. MATERIALS AND METHODS: Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy. RESULTS: Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to data detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6. CONCLUSIONS: By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these mean as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.

Stone formation in the prostatic urethra after cryotherapy for prostate cancer.

We report on 3 cases of stone formation in the prostatic urethra after cryosurgical ablation of the prostate. This complication occurred late in the course, many months after the normal postoperative healing process apparently was finished and patients enjoyed normal voiding. Transrectal ultrasound proved to be useful in making the diagnosis. Treatment included lithotripsy and cold resection of residual dead tissue.

Effects of intravesical instillation of 5-fluorouracil and interferon in patients with recurrent superficial urinary bladder carcinoma. A clinical and pharmacodynamic study.

Eleven patients with recurrent superficial bladder tumours were treated with 6 weekly instillations of 10 million IU Introna and 1000 mg 5-fluorouracil for 1 h. Before and immediately after the first treatment biopsies were taken from normal urothelium and tumour for analysis of thymidylate synthase (TS). One papillary tumour was left as a marker. Tumour tissue had 9 times higher TS concentrations than normal urothelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large variation in TS concentration in the tumours between different patients (range 0.02-2.24 pmol/g), after instillation the TS concentration decreased significantly in all but one patient. Six patients had complete and 2 had partial tumour regression after treatment. The effect was inversely correlated to the initial TS value. A low TS value seemed to predict a good response. The data suggest that weekly administrations are not sufficient in those with high TS concentrations. New treatment schedules may be beneficial in those with highly proliferating bladder tumours.

Mechanical small-bowel obstruction after conventional appendectomy in children.

During the period May 1988 to August 1990, 871 children aged between 0 and 15 years were appendectomized by laparotomy because of suspected appendicitis at the department of pediatric surgery, St. Göran's Children's Hospital. The children were followed 4-6 years after appendectomy. 1.3 % (10/791) developed clinical symptoms consistent with mechanical small bowel obstruction (SBO) resulting in relaparotomy and confirmation of the diagnosis. The patients were divided into subgroups according to the degree of appendicitis. In the group with normal appendix 1.8% (3/170) developed mechanical SBO, simple appendicitis 0% (0/209), gangrenous appendicitis 0.4 % (1/236) and perforated appendicitis 3.4% (6/176). There was no mortality due to postoperative complications. Two patients died due to unrelated causes during the follow-up period.

Infection after transrectal core biopsies of the prostate--risk factors and antibiotic prophylaxis.

OBJECTIVE: To compare the infection rate between different durations of antibiotic prophylaxis after transrectal core biopsy and to evaluate the impact of possible risk factors. PATIENTS AND METHODS: The study comprised 491 patients who underwent transrectal core biopsies of the prostate and who were randomized to receive 400 mg of norfloxacin twice daily for one day or one week. RESULTS: Patients receiving prophylaxis for one week had a significantly lower rate of infection (4.9%) compared to patients who received only two tablets (11%; P < 0.05). The most pronounced effect was seen in those patients with risk factors (e.g. an indwelling catheter, a former history of urinary tract infection, diabetes or prostatitis) in whom the infection rate was reduced from 17.9% to 3.3% (P < 0.02), and febrile infections from 9.5% to 1.1% (P < 0.02). CONCLUSIONS: Some factors have a clear impact on the risk of developing an infection after transrectal core biopsy. Prophylaxis for one week with norfloxacin is an effective way to minimize these infections.

Reference range of prostate-specific antigen after transurethral resection of the prostate.

OBJECTIVES: The aim of the present study was to investigate how transurethral resection of the prostate (TURP) affected the serum levels of prostate-specific antigen (PSA) and to establish reference ranges of PSA in patients who have undergone TURP. METHODS: PSA was determined preoperatively and 3 months postoperatively in 190 patients who underwent TURP because of benign prostatic hyperplasia (BPH). RESULTS: Mean PSA levels were reduced by 70%, from 6.0 to 1.9 ng/mL. Prostate volume was reduced by 58% from 63.3 to 26.5 cc, which is close to the reported normal volume in men without BPH. Ninety percent of the patients had a postoperative PSA value of less than 4 ng/mL and 98% less than 10 ng/mL. CONCLUSIONS: After a complete TURP with a benign histopathologic specimen, PSA should be expected to be within the normal reference range, that is, less than 4 ng/mL.

Changes in permeability of sheep's lungs by oleic acid are dose dependent.

OBJECTIVE: To evaluate a two-isotope technique to detect graded changes in pulmonary microvascular permeability. DESIGN: Open experimental study. SETTING: University hospital, Sweden. MATERIAL: Fifty-seven sheep. INTERVENTIONS: Catherisation of one carotid artery, pulmonary artery and central vein. Control group 1 (n = 10), control group 2 (n = 12) had an additional pulmonary artery balloon catheter inserted, experimental group 3 (n = 9) was given oleic acid 0.005 mg kg-1 BW, experimental group 4 (n = 12) received oleic acid 0.02 mg kg-1 BW and experimental group 5 (n = 11) 0.05 mg kg-1 BW. Groups 3-5 had all PA catheters. All animals were intubated and ventilated artificially. Duration of experiments was 6 hours. OUTCOME MEASURES: Transferrin was labelled in vivo with 113mIn chloride and erythrocytes with 99mTc following injection of stannous chloride. External gamma counting was corrected for background, decay and scatter. Blood activity was used as reference. Normalised slope index (NSI) and transferrin leak index (TLI) were calculated as measures of pulmonary microvascular permeability. RESULTS: A graded response in both NSI and TLI was found. Insertion of the PA catheter (group 2) significantly increased NSI from (group 1) (1.4 (0.1)) 10(-4) min-1 to (11 (2)) 10(-4) min-1 (p < 0.05). TLI increased significantly from (9 (2)) 10(-4) min-1 to (72 (13)) 10(-4) min-1. Oleic acid increased NSI significantly to (13 (1)) 10(-4) min-1, (32 (2)) 10(-4) min-1 and (61 (5)) 10(-4) min-1 in groups 3-5, respectively. Corresponding values for TLI were (95 (13)) 10(-4) min-1, (162 (6)) 10(-4) min-1 and (228 (26)) 10-4 min-1, respectively. CONCLUSION: The double-isotope technique of external monitoring of permeability changes to protein in the lungs was sensitive to pick up graded increments in leakage, related in a dose-dependent way to lung injury.

Prostate cancer mortality in patients surviving more than 10 years after diagnosis.

PURPOSE: We investigated the long-term outcome of prostate cancer. MATERIALS AND METHODS: Causes of death were examined in 490 patients diagnosed with prostate cancer in Göteborg between 1960 and 1979 who survived for longer than 10 years. RESULTS: Of the patients 75 were alive and 415 died, including 62% as a direct or indirect consequence of prostate cancer. CONCLUSIONS: Early prostate cancer is a slow growing but progressive malignant disease that will, if the patient survives long enough, kill the host.

Prophylactic antibiotics in uncomplicated appendicitis during childhood--a prospective randomised study.

544 children operated upon for uncomplicated appendicitis were randomised into three groups. Group I received no antibiotics, patients in Group II were administered one single pre-operative dose of metronidazole (10 mg/kg) and patients in Group III received both both metronidazole (20 mg/kg) and cefuroxime (50 mg/kg) in a single preoperative dose. The rate of infectious complications in Group I was 6.3% but only 2.1 and 2.3 in Groups II and III, respectively. Among patients with a normal appendix or patients with simple appendicitis there was no difference in the rate of post-operative infections between the three different groups. However, in patients with gangrenous appendicitis the rate of postoperative infections was significantly lower in the two groups who received preoperative antibiotics (1.8% and 3.0% respectively) than in the group receiving no prophylactic antibiotics (infection rate 14%). It is concluded that a single preoperative dose of metronidazole significantly decreases the rate of postoperative infectious complications in children with appendicitis. No further improvement could be demonstrated if cefuroxime against aerobic organisms was added.

Influence of benign prostatic hyperplasia, testosterone and age on serum levels of prostate specific antigen.

Prostate specific antigen (PSA) and PSA-density (PSAd) were studied in 120 symptomatic patients with benign prostatic hyperplasia at digital rectal examination. PSA and PSAd were measured before and 3 months after transurethral resection. Comparisons were made between patients in whom histologic examination showed benign hyperplasia and those with histologically demonstrated prostatic cancer. The influence of age and of serum testosterone on PSA and PSAd was determined. PSAd in benign prostatic hyperplasia was the same in the transition zone (the adenomas) and the peripheral zone (mean 0.065), indicating no increased synthesis or leakage of PSA. PSAd with cut-off value 0.10 ng x ml-1 x cc-1 showed higher sensitivity and positive predictive value (75% vs 50% and 0.33 vs 0.15, respectively) in nonpalpable prostatic cancer than did PSA with cut-off at 4 ng x ml-1. No statistically significant influence of testosterone and/or age on serum-PSA or PSAd was found.

Volume determinations of the whole prostate and of adenomas by transrectal ultrasound in patients with clinically benign prostatic hyperplasia: correlation of resected weight, blood loss and duration of operation.

OBJECTIVE: To study whether transrectal ultrasound (TRUS) volume determinations of the whole prostate and of the adenomas alone correlate to resected weight, operation time and blood loss in patients operated upon with transurethral resection of the prostate because of presumed benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The whole prostate and the transition zone, which corresponds to the adenomas, were measured separately in 159 patients with presumed BPH, pre-operatively and 4 months post-operatively. RESULTS: The transition zone volume correlated well with the resected weight (r = 0.91; P < 0.0001), the blood loss (r = 0.67; P < 0.0001) and the operation time (r = 0.67; P < 0.0001). Four months post-operatively a reduction of the total prostate volume was recorded which corresponded well with the resected weight (r = 0.91; P < 0.0001). CONCLUSION: TRUS with high resolution 7 MHz probes successfully estimated the size of the whole prostate and that of the adenomas alone. The transition zone volume predicted the expected resection weight of adenomas and to some extent the duration of the operation and the blood loss. These calculations may be used for more accurate pre-operative planning. Together with its superior detection rate for prostate cancer, TRUS seems to be a powerful tool in the pre-operative morphological assessment of patients with prostatism.

Outpatient transurethral incision of the prostate under local anesthesia: operative results, patient security and cost effectiveness.

Thirty patients with small and medium-sized obstructive prostates were operated by transurethral incision of the prostate (TUIP) under local anesthesia as an outpatient procedure. All patients except one tolerated this manoeuvre without any complications or discomfort. The obstructive symptoms were relieved in all patients; however, 6 patients had lasting irritative symptoms, 2 of whom were cured after TURP. The costs of TUIP was calculated to be one sixth of that of TURP. During one year follow-up 5 patients were found to have prostate cancer despite careful rectal examination and PSA measurement preoperatively. In conclusion, TUIP may be carried out as safely and cost-effectively as an outpatient procedure and is beneficial in patients with predominantly obstructive symptoms. However, careful investigations concerning possible prostate cancer must be undertaken in this group of patients with small but symptomatic prostates.