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Biomedical subjects

T Tammela

Publications and source records attributed to T Tammela.

At least 19 recordsLinked to original sources
PubMed1998

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Aged↗
PubMed1997

Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer.

Progression of prostate cancer during endocrine therapy is a major clinical problem, the molecular mechanisms of which remain poorly understood. Amplification of the androgen receptor (AR) gene was recently described in recurrent prostate carcinomas from patients who had failed androgen deprivation therapy. To evaluate the hypothesis that amplification of the AR gene is a cause for the failure of androgen deprivation therapy in prostate cancer, we studied whether AR amplification leads to gene overexpression, whether the amplified AR gene is structurally intact, and whether tumors with AR amplification have distinct biological and clinical characteristics. Tumor specimens were collected from 54 prostate cancer patients at the time of a local recurrence following therapy failure. In 26 cases, paired primary tumor specimens from the same patients prior to therapy were also available. Fifteen (28%) of the recurrent therapy-resistant tumors, but none of the untreated primary tumors, contained AR gene amplification as determined by fluorescence in situ hybridization. According to single-stranded conformation polymorphism analysis, the AR gene was wild type in all but one of the 13 AR amplified cases studied. In one tumor, a presumed mutation in the hormone-binding domain at codon 674 leading to a Gly --> Ala substitution was found, but functional studies indicated that this mutation did not change the transactivational properties of the receptor. AR amplification was associated with a substantially increased level of mRNA expression of the gene by in situ hybridization. Clinicopathological correlations indicated that AR amplification was most likely to occur in tumors that had initially responded well to endocrine therapy and whose response duration was more than 12 months. Tumors that recurred earlier or those that showed no initial therapy response did not contain AR amplification. The median survival time after recurrence was two times longer for patients with AR amplification in comparison to those with no amplification (P = 0.03, Willcoxon-Breslow test). In conclusion, failure of conventional androgen deprivation therapy in prostate cancer may be caused by a clonal expansion of tumor cells that are able to continue androgen-dependent growth despite of the low concentrations of serum androgens. Amplification and the increased expression of a wild-type AR gene may play a key role in this process.

Aged↗
PubMed1997

Immunodetection of androgen receptor in human urinary bladder cancer.

We investigated the expression of androgen receptor (AR) protein in transitional cell carcinoma of human urinary bladder in paraffin-embedded sections of tumours obtained from nine patients with urinary bladder cancer treated by radical cystectomy. In addition, immunoblotting of AR was also performed on selected samples. Nuclear immunoreactivity of AR was found in seven of the nine urinary bladder cancers studied. AR showed variable staining intensity within a tumour. In the immunoblots, a 110 kDa AR signal was seen with anti-AR antibody, and faint bands of 90 and 60 kDa were also observed. Immunohistochemistry of p53 and c-erbB-2 was also carried out and compared with the distribution of AR. The high frequency of AR expression suggests a role for androgens in transitional cell carcinoma of human urinary bladder.

Adenocarcinoma↗
PubMed1997

Bioabsorbable and biodegradable stents in urology.

Since the early 1970s, bioabsorbable polymers have been used increasingly as suture and device materials. Bioabsorbable materials are high-molecular-weight polymers of polylactide (PLA; poly[lactic acid]) or polyglycolide (PGA; poly[glycolic acid]). The mechanical properties of self-reinforced (SR) devices (SR-PGA, SR-PLLA, and SR-PLA96 spiral stents) are acquired by special processing methods from polymer materials. As a result, the spiral stent has an expansion property of up to 70% of its original outer diameter, 50% of which may occur in 30 minutes. The stent may also have variable degradation properties in different parts of the device. The use of bioabsorbable devices in urology is novel. Today, SR-PGA spirals (Biofix) to be used for the prostatic urethra are commercially available but with restrictions. Their indications are the prevention of urinary retention after thermal therapy of prostatic hyperplasia, temporary treatment of urinary retention in patients waiting for surgery, and the early-phase resolution of bladder outlet obstruction in patients waiting for the effect of medical therapy. Stents can be also used to observe the effects of prostatic surgery on bladder function. The SR-PLLA and SR-PLA96 spiral stents are still under development for use in the anterior urethra, prostatic urethra, and ureters. Further experimental and controlled clinical studies are needed to find out the suitability of bioabsorbable devices in urology. Many efforts have been made to discover the best possible materials, models, coating materials, and additives of bioabsorbable stents in urology.

Absorption↗
PubMed1997

Androgen receptor gene amplification in a recurrent prostate cancer after monotherapy with the nonsteroidal potent antiandrogen Casodex (bicalutamide) with a subsequent favorable response to maximal androgen blockade.

OBJECTIVE: We recently found amplification of the androgen receptor (AR) gene in approximately 30% of locally recurrent prostate carcinomas from patients treated by conventional androgen deprivation (castration) therapy, whereas none of the untreated primary prostate tumors showed this amplification. This suggests that AR gene amplification was selected during androgen deprivation therapy. The present case study represents our initial approach to evaluate the role that AR amplification may play in therapy resistance after other forms of endocrine therapy. MATERIAL AND METHODS: Specimens from both a primary and a subsequent locally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antiandrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Ltd). RESULTS AND CONCLUSIONS: High-level amplification of the AR gene was found in the recurrent tumor, whereas no evidence of amplification was found in the primary tumor. After recurrence, the patient first received chemotherapy (ifosfamide) for 15 weeks with no response, followed by maximal androgen blockade (MAB). The latter therapy resulted in a favorable short-term response. This case study has the following implications which warrant further research: (1) AR amplification may be selected not only by castration but also by therapy with a competitive peripheral androgen-receptor-blocking agent, and (2) recurrent tumors with AR amplification may be particularly likely to benefit from MAB as a second-line therapy.

Adenocarcinoma↗
PubMed1997

Benign prostatic hyperplasia. Practical treatment guidelines.

Symptomatic benign prostatic hyperplasia (BPH) is a common condition in older men and has a significant impact on their daily lives. Transurethral resection of the prostate (TURP) or open prostatectomy are currently the most effective therapies for BPH. TURP is, however, associated with clinically significant adverse events in 20% of patients. Therefore, patients who need treatment for BPH based on the presence of symptoms should also be offered other therapy options. Transurethral incision of the prostate is an effective therapy with minimal adverse effects in patients with a prostate not larger than 30 g. Minimally invasive procedures, such as electrovaporisation, laser prostatectomy, transurethral needle ablation, high intensity focused ultrasound, transurethral microwave therapy and insertion of prostatic stents, can be performed instead of the standard surgical procedures. They are either performed as outpatient procedures or are associated with shorter durations of hospitalisation than TURP; in addition, they can also be performed in high risk patients. The efficacy of these procedures lies between that of TURP and medical therapy. Medical therapy is becoming increasingly important in the treatment of patients with moderate symptoms of BPH. Both androgen-suppressing therapy and alpha-adrenoceptor blockade are well tolerated and effective modalities. Compared with placebo, both types of therapy produce improvements in maximum urinary flat rate and reductions in symptom scores of 15 to 20%. Finasteride, a potent 5 alpha-reductase inhibitor, must be given for 6 months before it effectiveness in a given patient can be assessed, and for at least 12 months to achieve maximum prostate shrinkage and the full extent of its other beneficial effects. This may be perceived as a disadvantage when compared with the rapid relief afforded by surgery or alpha-blockade. The efficacy of finasteride is also dependent on prostate size; it should not be tried in patients with a prostate volume of < 40 ml. On the other hand, finasteride may reverse the progression of the disease process. Of the alpha 1-adrenoceptor antagonists, terazosin, doxazosin and tamsulosin can be administered once daily. In contrast, prazosin, alfuzosin and indoramin must be administered twice daily, which may have a negative impact on patient compliance. Because of its specificity for alpha 1A-receptors, no dosage titration is needed when tamsulosin is used; in addition, in contrast with the other alpha-blockers used in BPH, tamsulosin lacks significant effects on blood pressure. On the other hand, nonselective alpha-blockers are preferable in hypertensive patients with BPH. The final decision about the best treatment for a particular patient must take into account the patient's preference after he has been informed of the different options.

Adrenergic alpha-Antagonists↗
PubMed1997

A randomized study to compare biodegradable self-reinforced polyglycolic acid spiral stents to suprapubic and indwelling catheters after visual laser ablation of the prostate.

PURPOSE: A randomized controlled study was done to evaluate the efficacy of the self-reinforced polyglycolic acid spiral stent compared to a suprapubic catheter, and combined suprapubic and indwelling catheters in the prevention of urinary retention after visual laser ablation of the prostate. MATERIALS AND METHODS: We studied 72 men with benign prostatic hyperplasia who underwent placement of a suprapubic catheter and visual laser ablation of the prostate. In 27 men in group 1 the self-reinforced polyglycolic acid spiral stent was inserted into the prostatic urethra after visual laser ablation of the prostate, while 23 in group 2 received no other devices. In 22 men in group 3 an indwelling catheter was left in situ for an average of 6.5 days. RESULTS: Voiding began 1 or 2 days postoperatively in 20 of 27 patients (median 1 day) in group 1, and 8 of 23 (median 6 days) in group 2. In 16 of 22 men in group 3 voiding began 1 or 2 days (median 6) after removal of the indwelling catheter. Improvements in patient weighted symptom score, mean peak urinary flow rate and post-void residual volume were significant (p < 0.001) at 6 months of followup in all groups. The overall infection rate was 30%. CONCLUSIONS: The self-reinforced polyglycolic acid spiral stent is superior to the suprapubic catheter alone, and to combined indwelling and suprapubic catheters for the treatment of postoperative urinary retention after laser therapy, offering possibilities for shorter catheterization time.

Aged↗
PubMed1997

Antibiotic prophylaxis in patients with urinary retention undergoing transurethral prostatectomy.

BACKGROUND AND AIMS: The risk of severe infection and complications in connection with transurethral resection of the prostate (TURP) has clearly increased in patients with urinary retention and an indwelling catheter. The aim of this study was to determine whether the antibiotics ciprofloxacin and ceftazidime are equally efficient in preventing infective complications in these patients. MATERIAL AND METHODS: An open randomized prospective study was carried out on 72 patients with urinary retention undergoing TURP, to compare of 500 mg of ciprofloxacin (CF) orally twice daily and 1 g of ceftazidime (CT) intravenously twice daily. RESULTS: The incidence of early complications was 26% in the CF group and 17% in the CT group. All the complications were minor. On removal of the indwelling catheter, a positive urinary culture was detected in 6% of the patients in the CF group and in 3% in the CT group. One month after TURP, a positive urinary culture was detected in 14% of the patients in the CF group and in 18% of the CT group. CONCLUSIONS: It is concluded that both of the antibiotics used in this trial were equally effective in the prevention of early urinary and other infections and also late complications, in patients with urinary retention undergoing TURP.

Adult↗
PubMed1996

Screening for prostate cancer using serum prostate-specific antigen: a randomised, population-based pilot study in Finland.

The possibility of screening the general population for prostate cancer using serum prostate-specific antigen (PSA) level (alone or in combination with other tests) as screening test has recently been discussed. A number of studies are on the way, but the published reports have almost exclusively been based on men volunteering for screening. We assessed the feasibility of a screening study based on men identified from a central population registry. A random sample of 600 men in the age groups 55, 60 and 65 years was identified from the Finnish Population Registry as the study population. Half of them were randomised to the intervention group and an invitation to participate was sent to them. The participation rate was 77% (230 out of 300). Twenty-five men had a serum PSA concentration of 4.0 micrograms l-1 or above and were invited for further examination including digital rectal examination, transrectal ultrasound and transrectal Tru-cut biopsies (directed and/or random). Six cases of cancer were detected among the 230 participating men, which corresponds to a detection rate of 2.6% and a positive predictive value of 24%. The number of cases detected is equivalent to the expected number of prostate cancer cases during a 10 year follow-up in this population. The ratio of free to total PSA was also measured and a cut-off level of 0.20 was chosen. Its use as an additional criterion of the screening test would have decreased the prevalence of false-positive screening tests from 8% (19 of 230) to 3% (7 of 230) at a cost of missing one of the six cancers compared with serum total PSA concentration alone. Of the six cancers, five were clinically regarded as localised and locally confined disease was confirmed pathologically in four of them. In conclusion, a population-based study in Finland seems feasible and the properties of the PSA test can be regarded as suitable for a randomised screening study. Thus, all prerequisites for a multicentre study, which is planned, seem to exist.

Age Factors↗
PubMed1996

Prospective randomized open study between ciprofloxacin and a combination of sulfadiazine and trimethoprim in antibiotic prophylaxis in connection with transurethral prostatectomy.

A randomized open prospective study with antibodies was conducted on 398 cases of TURP to compare the efficacy of either 250 mg of ciprofloxacin twice daily (CF) or 500 mg/160mg of sulfadiazine-trimethroprim twice daily (ST) in the prevention of urinary and other infection complications. The medication was started on the evening preceding the operation and continued up to the day following the removal of an indwelling catheter. The preoperative risk factors were similar in both groups. The groups did not differ in terms of the duration of the operation, the volume of irrigation fluid or the weight of the resected chips. The incidence of immediate complications was 26% in the CF group and 20% in the ST group. All the complications were minor. There were three serious late complications, one intertervertebral discitis and one coxitis in the CF group and one endocarditis in the ST group. The patient with endocarditis died. One the removal of the indwelling catheter on the third postoperative day, bacteriuria was detected in 3% of the patients in the CF group and in 9% in the ST group. The difference was statistically significant (p < 0.05). One month after TURP, bacteriuria was detected in 7% in both study groups. It is concluded that ciprofloxacin may be more effective to preventing immediate urinary tract infections after TURP than a combination of sulfadiazine and trimethoprim. There were three serious late complications. As late as one month after TURP, bacteriuria was still diagnosed in about 7% of all patients, which is post-TURP monitoring of urinary values is important.

Aged↗
PubMed1995

Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization.

Genetic changes leading to the development of prostate cancer and factors that underlie the clinical progression of the disease are poorly characterized. Here, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes along all chromosomes in 31 primary and 9 recurrent uncultured prostate carcinomas. The aim of the study was to identify those chromosome regions that contain genes important for the development of prostate cancer and to identify genetic markers of tumor progression. CGH analysis indicated that 74% of primary prostate carcinoma showed DNA sequence copy number changes. Losses were 5 times more common than gains and most often involved 8p (32%), 13q (32%), 6q (22%), 16q (19%), 18q (19%), and 9p (16%). Allelic loss studies with 5 polymorphic microsatellite markers for 4 different chromosomes were done from 13 samples and showed a 76% concordance with CGH results. In local recurrences that developed during endocrine therapy, there were significantly more gains (P < 0.001) and losses (P < 0.05) of DNA sequences than in primary tumors, with gains of 8q (found in 89% of recurrences versus 6% of primary tumors), X (56% versus 0%), and 7 (56% versus 10%), as well as loss of 8p (78% versus 32%), being particularly often involved. In conclusion, our CGH results indicate that losses of several chromosomal regions are common genetic changes in primary tumors, suggesting that deletional inactivation of putative tumor suppressor genes in these chromosomal sites is likely to underlie development of prostate cancer. Furthermore, the pattern of genetic changes seen in recurrent tumors with the frequent gains of 7, 8q, and X suggests that the progression of prostate cancer and development of hormone-independent growth may have a distinct genetic basis. These chromosome aberrations may have diagnostic utility as markers of prostate cancer progression.

Chromosome Deletion↗
PubMed1995

In vivo amplification of the androgen receptor gene and progression of human prostate cancer.

Overexpression of amplified genes is often associated with the acquisition of resistance to cancer therapeutic agents in vitro. We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene. Comparative genomic hybridization shows that amplification of the Xq11-q13 region (the location), is common in tumours recurring during androgen deprivation therapy. We found high-level AR amplification in seven of 23 (30%) recurrent tumours, but in none of the specimens taken from the same patients prior to therapy. Our results suggest that AR amplification emerges during androgen deprivation therapy by facilitating tumour cell growth in low androgen concentrations.

Aged↗
PubMed1995

Aetiology of priapism in 207 patients.

Two hundred and seven patients were treated for priapism in Finnish hospitals in 1973-1990. In order to analyse the aetiology of priapism, the original data on these and on 163 age- and time-matched controls, who underwent appendicectomy, were collected from the hospitals. The information was completed by collecting extra data from other hospitals and health centres or by personal contacts. In 43 of the 207 cases (21%), the cause of priapism was an intracavernous injection of a vaso-active drug. These patients were excluded from the logistic regression analysis used to evaluate the most essential factors associated with priapism. They were found to abuse alcohol (p < 0.001), use psychopharmaceuticals (p < 0.001), antihypertensive drugs (p = 0.003), anticoagulants (p = 0.005), as well as to have lumbar disc pain (p = 0.002) and chronic prostatitis (p = 0.01). Smoking was also significantly more common in the patients affected by priapism (56%) than in the controls (33%), being significantly associated with heavy alcohol drinking and use of psychopharmaceuticals. A disease or trauma was a possible causative factor in one third of the patients. The present study confirms the suggestion of a multifactorial aetiology for the initiation of priapism.

Adolescent↗
PubMed1995

Analysis of genetic changes underlying local recurrence of prostate carcinoma during androgen deprivation therapy.

The molecular mechanisms and genetic changes that lead to the progression of prostate cancer during endocrine therapy are poorly characterized. Here, paired specimens from both untreated primary tumors and from local recurrences were collected from 10 prostate cancer patients treated by conventional androgen deprivation therapy. The genetic progression of the tumors was studied by using interphase fluorescence in situ hybridization and chromosome-specific probes. Six primary tumors (60%) and all ten recurrent tumors were aneuploid by fluorescence in situ hybridization. The recurrent tumors also showed a high degree of chromosome copy number variability from one cell to another. Increased copy number of chromosome X was particularly common in the recurrent tumors. In addition, specific high level amplification of the androgen receptor (AR) gene (Xq12) was detected in three highly aneuploid recurrent tumors. Our findings suggest that hormone-refractory prostate cancers are genetically very complex and show intratumor genetic heterogeneity. Increased copy number of chromosome X and the amplification of the androgen receptor (AR) gene may confer proliferative advantage during androgen deprivation and thus contribute to the development of recurrence.

Androgen Antagonists↗
PubMed1995

Biodegradable self-reinforced polyglycolic acid spiral stent in prevention of postoperative urinary retention after visual laser ablation of the prostate-laser prostatectomy.

PURPOSE: The efficacy and safety of a new biodegradable (self-reinforced polyglycolic acid) spiral stent in securing free voiding despite edema after visual laser ablation of the prostate were studied. MATERIALS AND METHODS: A biodegradable spiral stent was inserted into the prostatic urethra in 22 patients immediately after visual laser ablation of the prostate. Uroflowmetry, measurement of residual urine volume, urine culture, cystoscopy and assessment of symptomatic improvement were done before, and 1, 3 and 6 months after visual laser ablation of the prostate. RESULTS: All 22 patients voided freely on day 1 or 2 after visual laser ablation of the prostate. However, 4 patients later had urinary retention due to a short spiral or too rapid spiral degradation. Half of the patients experienced a transient decrease in flow with some obstructive symptoms at 3 weeks that lasted 1 to 2 weeks. At 4 weeks all spirals were degraded and 3 patients had a positive urine culture. The maximum flow rate increased and the residual urine volume decreased significantly concomitantly with significant symptomatic improvement. CONCLUSIONS: The self-reinforced polyglycolic acid spiral stent can effectively and safely prevent postoperative urinary retention after visual laser ablation of the prostate.

Aged↗
PubMed1995

Postoperative urinary retention--why the patient cannot void.

The etiology of postoperative urinary retention involves a combination of many factors, including sedation, type of anesthesia, increased sympathetic stimulation, overdistension of the bladder by large quantities of fluids given intravenously, pain and anxiety.

Anesthesia, Spinal↗