Toxicity in patients receiving adjuvant docetaxel + hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer: a preplanned safety report of the SPCG-13 trial.

BACKGROUND: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men >18 and ≤75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mgm(-2) d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

Initiators in processes leading to hearing loss identification in Finnish children.

The objective was to examine processes leading to the diagnosis of hearing loss in children. The subjects were 328 children (hearing loss >30 dB HL) fitted with hearing aids in Helsinki University Central Hospital. The risk factor initiated hearing loss detection in 31%, whereas parental suspicion accounted for 26% and hearing screening at the well-baby clinics for 20% of the subjects. Parents were foremost to suspect hearing loss at the age spoken language normally emerges (1.5-3.4 years). Screening was equally effective irrespective of the severity of hearing loss. Parents with misgivings of hearing impairment in their child should have compliant access to audiological units.

Role of transtympanic endoscopy of the middle ear in the diagnosis of perilymphatic fistula in patients with sensorineural hearing loss or vertigo.

BACKGROUND: The diagnosis of perilymphatic fistula (PLF) is often difficult, and therefore the condition can be overlooked. Tympanoscopy presents an alternative procedure for visualising the middle ear anatomy, and it may help to diagnose PLF. AIM: The aim of this study was to evaluate the use of middle ear endoscopy in establishing the diagnosis of PLF and in defining its incidence in patients with sensorineural hearing loss and/or vertigo and tinnitus. SUBJECTS AND METHODS: Two hundred and sixty-five patients (22-80 years of age, mean 48 years) were prospectively and consecutively referred for middle ear examination with tympanoscopy. Tympanoscopy was performed using endoscopes with visual angles of 5 and 25 degrees and an outer diameter of 1.7 mm. The round window niche (with its secondary membrane), the oval window with a stapes superstructure, a part of the facial recess and the area in the fissula ante fenestram were examined and video-recorded. RESULTS: For 1 patient, tympanoscopy revealed fistula in the round window membrane that was covered with a fibrinous layer. In 4 cases abnormal mucosal shining appeared in the round window, but no PLF was present. In 7 cases the tympanic cavity could not be visualised because of the adhesive tympanic membrane, abnormal anatomy or the prominent exostoses of the external ear canal. In 6 cases a postendoscopic middle ear infection was found. No permanent tympanic membrane perforation occurred in any of the patients in this study. CONCLUSIONS: Tympanoscopy is a rapid examination tool with which to verify certain areas of the middle ear anatomy, but it is of limited value for ruling out the presence of PLF.

Effect of intravesical instillations on the human complement factor H related protein (BTA stat) test.

OBJECTIVES: The BTA stat is a rapid, non-invasive, qualitative urine test that detects bladder tumor-associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test. METHODS: 501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty-seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations. RESULTS: The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended. CONCLUSION: The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.

Cochlear blood flow measurement in patients with Ménière's disease and other inner ear disorders.

To identify an eventual vascular aetiology in different diseases with sensorineural hearing loss (SNHL), the cochlear blood flow (CoBF) was measured using laser Doppler flowmetry (LDF) in 69 patients with Ménière's disease (MD), 38 patients with progressive SNHL and 8 patients with sudden deafness. The mean CoBF amplitude at rest was 0.70 mV (SD 0.25) for patients with MD, 0.66 mV (SD 0.21) for patients with SNHL and 0.69 mV (SD 0.23) for those with sudden deafness. No statistically significant difference was observed between the groups with respect to the CoBF amplitudes at rest or during the Valsalva manoeuvre. There was a statistically significant correlation (r = -0.4, p < 0.05) between the hearing level and CoBF amplitude in the SNHL group only. It is concluded that the reduction in vascular flow may not be the main aetiological factor in Ménière's disease or sudden deafness. In SNHL the correlation of hearing level with the level of the LDF amplitude can be secondary to the progression of hearing loss.

Auditory pathway function after vestibular schwannoma surgery.

We studied seven patients before and after vestibular schwannoma surgery. Four patients became unilaterally profoundly deaf and three patients preserved their hearing. Cortical responses were recorded with a 122-channel whole-scalp SQUID neuromagnetometer using tone-burst stimuli to the healthy ear. Brainstem auditory evoked potentials (BAEPs) were measured using alternating clicks. Ten healthy volunteers served as a control group. In patients, preoperative cortical response latencies and strengths did not differ significantly from those of controls. However, 6 months after the operation the latency was, on average, 7 ms longer than preoperatively over both hemispheres. BAEPs were in the normal range both before and after the operation. These results suggest that unilateral lesion in peripheral auditory pathways also affects cortical reactivity to stimuli presented to the non-affected ear, possibly reflecting altered binaural interaction in the auditory pathways.

Human complement factor H related protein test for monitoring bladder cancer.

PURPOSE: The BTA stat test is a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine. We compared BTA stat test to voided urine cytology in patients monitored for bladder cancer in a prospective trial, and determined whether this test is effective in detection of recurrence not seen by regular cystoscopy. MATERIALS AND METHODS: A total of 445 consecutive patients with bladder cancer were studied. A voided urine sample was obtained before cystoscopy and divided for culture, cytology and BTA stat testing. In cases of a positive BTA stat test but negative cystoscopy, excretory urography or renal ultrasound, random biopsies and collected ureteral urine samples for ureteral cytology were obtained. The overall sensitivity and specificity as well as positive and negative predictive values for BTA stat test, cytology and their combination were calculated. RESULTS: Of the 445 patients 118 (26.5%) had bladder cancer recurrence on cystoscopy, which was detected by BTA stat test and cytology in 63 (53.4%) and 21 (17.8%), respectively. Of the remaining 327 patients not having recurrent tumor on cystoscopy 81 (24.8%) had a positive BTA stat test. Excretory urography or renal ultrasound and random biopsies in 48 (59.3%) of these patients revealed 7 recurrences, making the total number of recurrent tumors 125 of 412 (30.3%). The overall sensitivities and specificities for the BTA stat test, cytology and their combination were 56.0%, 19.2%, 60.0% and 85.7%, 98.3% and 85.0%, respectively. CONCLUSIONS: The sensitivity for detection of recurrent tumor on BTA stat test is superior to that of voided urine cytology in all bladder cancer categories, whereas the specificity of voided urine cytology is higher than that for BTA stat test. However, a sixth of the patients with apparent false-positive BTA stat test results chosen for further investigation had recurrent tumors that were not found on routine cystoscopy. Although the sensitivity and specificity were highest when both tests were used, the differences were not significant overall. Therefore, the BTA stat test could potentially replace urine cytology for followup of superficial bladder cancer.

Sensitivity of human complement factor H related protein (BTA stat) test and voided urine cytology in the diagnosis of bladder cancer.

PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

Prostatic expression of human 5alpha-reductase type 2 during finasteride therapy: a randomized, double-blind, placebo-controlled study.

This study was aimed at exploring the effect of finasteride, a non-steroidal competitive inhibitor of the enzyme 5alpha-reductase, on 5alpha-reductase type 2 at the mRNA level in human prostate, using an in situ hybridization technique. After randomization, 10 men with benign prostatic hyperplasia (BPH) received oral finasteride (5 mg daily) and five men with BPH received placebo daily. Careful clinical examination was carried out and 2 biopsy samples were taken transrectally before the treatment and after 3, 6, and 12 months of treatment. In situ hybridization was carried out and expression of 5alpha-reductase type 2 mRNA was measured. The results showed that finasteride treatment had no permanent effect on expression of 5alpha-reductase type 2 in prostatic epithelium, compared with placebo treatment. Expression varied during treatment, but there was no clear tendency in this expression. The signal was localized in the epithelial cells. We conclude that finasteride treatment had no clear effect on human 5alpha-reductase type 2 expression in the prostate.

Effects of finasteride in patients with inflammatory chronic pelvic pain syndrome: a double-blind, placebo-controlled, pilot study.

OBJECTIVES: To investigate whether treatment of inflammatory chronic pelvic pain syndrome (ICPPS) with finasteride has any influence on symptoms associated with ICPPS. METHODS: Forty-one patients with ICPPS were randomized (1:3) to treatment with either placebo (25%, n = 10) or finasteride 5 mg daily (75%, n = 31 ) for 1 2 months. Efficacy was evaluated by analysis of symptomatic improvement through responses to symptom questionnaires, pain evaluation on an analytical visual scale, analgesic use as reported in patient diaries, urine flow and residual volume, and prostate volume. RESULTS: Prostatitis Symptom Severity Index and prostatism scores dropped significantly in patients in the finasteride group (P < 0.001 and P < 0.05, respectively). There were no statistically significant differences in pain between the groups. There were significant differences in the changes of prostate volume and in serum prostate-specific antigen concentrations between the finasteride and placebo groups (P < 0.03 and P < 0.02, respectively). The groups did not differ with regard to side effects. CONCLUSIONS: Our results indicate that finasteride has an effect in ICPPS. The mechanisms by which finasteride works in these patients are unclear and could not be solved in this pilot study, which had relatively few patients. A further trial with larger numbers is required to confirm these results.

Behavioural observation audiometry in testing young hearing-impaired children.

The aim was to examine the accuracy of unconditioned behavioural observation audiometry (BOA) in predicting hearing acuity in children and the validity of test results at various frequencies. The study was designed to longitudinally compare each child's best BOA response level (at the age >12 months) with the conclusive pure-tone threshold of the better ear. The subjects were 119 children derived from a material of 353 children fitted with a hearing aid at Helsinki University Central Hospital. BOA was carried out on 119 children, 19 of whom did not respond to frequency-specific stimuli. The predictive power of BOA depended on the severity of hearing loss. At the hearing level of 30-39 dB, BOA registered 10-15 dB poorer levels than the pure-tone audiometry. The pure-tone averages (0.5, 1, 2 kHz) of 50-69 dB agreed best with the BOA responses. In severe impairments (more than 70 dB HL), the BOA registered too good hearing. Correlation of the results from the two modes to measure hearing level was highly significant (r = 0.71, p = 0.000), and the pure-tone hearing level agreed with that of BOA at the frequencies 0.5 to 4 kHz. Our results show that BOA averages < or =30 dB rarely indicate hearing loss demanding fitting of a hearing aid.

Hearing loss after continuous or single-shot spinal anesthesia.

BACKGROUND AND OBJECTIVES: Hearing loss after spinal anesthesia is probably caused by cerebrospinal fluid (CSF) leakage. Spinal catheters may mechanically plug the hole in the dura and cause inflammatory swelling which should prevent cerebrospinal fluid leakage and hearing loss. An audiometric evaluation was therefore performed in patients who had spinal anesthesia by single-shot or catheter. METHODS: Twenty-one patients received single-shot spinal anesthesia and 19 patients continuous spinal anesthesia for orthopedic surgery of the lower limbs. Spinal catheters were removed 24 hours after the start of anesthesia. Audiometry was performed on the day before the operation and on the first, second, and third postoperative day and repeated on the fifth postoperative day, if necessary. RESULTS: The frequency of hearing impairment (threshold change > 10 dB) was 43% in the single-shot and 37% in the continuous spinal group. The deterioration lasted longer in the continuous spinal group (3 days vs. 1.4 days; P < .01). CONCLUSION: Although inflammatory swelling of the dura mater around the spinal catheter had been observed, use of such a catheter for 24 hours did not prevent hearing loss after its removal.

Hearing disability assessment in evaluating hearing aid benefit.

The aim was to study the applicability of an eight-item questionnaire in evaluating the benefit derived from hearing-aid use. Since 1977, 3402 hard-of-hearing patients have been fitted with a hearing aid for the first time and followed up for 3 months in the Helsinki University Central Hospital. The questionnaire included eight situation-specific items in hearing: speech face-to-face, speech in a small and large group, loud speech, in telephone and radio/TV, doorbell, telephone signal. The scoring ranged from 0 to 16. After a 3 months' use of amplification, the questionnaire was completed again. The median (interquartile range) and arithmetic mean (standard deviation) of the prefitting scores were 5.0 (4.0-6.0) and 5.3 (2.33). The postfitting scores were 1.0 (0.0-2.0) and 1.1 (1.17), respectively. The difference was highly significant. An eight-item questionnaire in the evaluation of hearing problems provided a reliable numerical score of disability. Follow-up is important to secure satisfactory results in rehabilitation, especially in old age.

Identification of childhood hearing impairment in Uusimaa County, Finland.

The purpose was to report the identification age of the hard-of-hearing children born between 1 January 1973 and 31 December 1990. The subjects comprised all children (353) fitted with hearing aid in an age-matched target population of 270 726 persons in Uusimaa County including Helsinki. The age of identification was studied in three groups; pure tone average (0.5, 1 and 2 kHz) > or = 30 dB, > or = 35 dB and > or = 50 dB HL enabling comparison with the identification ages reported in the literature. In the first group the median identification age was 3.6 years (mean 4.2), in the second 2.9 years (mean 3.8) and in the third 2.1 years (mean 2.8). The first group was identified significantly later than the third one (P = 0.004). The second group differed from the third significantly in detection age as well (P = 0.004). The severity of hearing impairment correlated highly with the detection age (r = -0.69. P < 0.0001). The data clustered at the ages of 1-2.5 years (hearing level 90-120 dB) and at 4-8 years (30-60 dB).

Prevalence of childhood hearing impairment in southern Finland.

The Department of Audiology in Helsinki University Central Hospital provides paedoaudiological services for the Province of Uusimaa, including Helsinki. Our purpose was to study the prevalences of hearing threshold loss in children born in the period 1973 to 1990. The material consisted of 353 hearing-disabled children. The pure-tone average (0.5, 1 and 2 kHz) of the better ear was the parameter for hearing threshold. In 36 subjects the hearing acuity was determined with the behavioural observation test or the brainstem electric response measurement. The number of hearing-impaired per birth year (hearing level > or = 35 dB) ranged from 6 to 30 and the prevalence rate from 0.3 to 1.9 in 1000, totalling 1.1. After matching the hearing-impairment criteria with those of the previous reports from northern Sweden, Denmark and the European Community, we were able to compare the prevalences.

Auditory disturbance associated with interscalene brachial plexus block.

We performed an audiometric study in 20 patients who underwent surgery of the shoulder region under an interscalene brachial plexus block (IBPB). Bupivacaine 0.75% with adrenaline was given followed by a 24-hr continuous infusion of 0.25% bupivacaine. Three audiometric threshold measurements (0.25-18 kHz) were made: the first before IBPB, the second 2-6 h after surgery and the third on the first day after operation. In four patients hearing impairment on the side of the block was demonstrated after operation, in three measurements on the day of surgery and in one on the following day. The frequencies at which the impairment occurred varied between patients; in one only low frequencies (0.25-0.5 kHz) were involved. The maximum change in threshold was 35 dB at 6 kHz measured at the end of the continuous infusion of bupivacaine. This patient had hearing threshold changes (15-20 dB) at 6-10 kHz on the opposite side also. IBPB may cause transient auditory dysfunction in the ipsilateral ear, possibly via an effect on sympathetic innervation.

Binding of beta-adrenergic antagonists 3H-DHA and 3H-CGP 12177 to intact rainbow trout (Salmo gairdneri) and carp (Cyprinus carpio) red blood cells.

beta-Adrenergic ligand binding to trout (Salmo gairdneri) and carp (Cyprinus carpio) red cells using a hydrophobic (3H-DHA) and a hydrophilic (3H-CGP) ligand was studied. Conditions which lead to the appearance (in vivo and in vitro hypoxia in carp cells) or disappearance ("winter" acclimation history in trout red cells) of beta-adrenergic responses were associated with either an appearance or marked increase of isoproterenol-displaceable binding (carp), or a disappearance of isoproterenol-displaceable binding (trout), respectively. The apparent number of binding sites was markedly greater for the hydrophobic than for the hydrophilic ligand, suggesting that binding of the hydrophobic ligand to internalized receptors and to nonreceptor sites may affect the results obtained with intact cells.

Comparison of pure tones and noise stimuli in sonotubometry.

Sonometric data on the Eustachian tube opening response to swallowing and to pressing the mandible down were evaluated in 51 normal ears and 62 ears with chronic disease. Testing with a narrow-band noise which was centered on 7 and 8 kHz gave the best results. The limit for a positive response was set at 3 dB, and of the normal ears, 80% showed a positive response in a short routine test. The data correlated reasonably well with surgical results. If test results point to tubal insufficiency, measures should be taken to prevent the formation of retraction pockets.

Comparison of pure tones and noise stimuli in sonotubometry.

Sonometric data on the Eustachian tube opening response to swallowing and to pressing the mandible down were evaluated in 51 normal ears and 62 ears with chronic disease. Testing with a narrow-band noise which was centered on 7 and 8 kHz gave the best results. The limit for a positive response was set at 3 dB, and of the normal ears, 80% showed a positive response in a short routine test. The data correlated reasonably well with surgical results. If test results point to tubal insufficiency, measures should be taken to prevent the formation of retraction pockets.