Innovative treatment for clinically localized adenocarcinoma of the prostate: the future role of molecular imaging.
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Adenocarcinoma↗
Biomedical subjects
F Debruyne
Publications and source records attributed to F Debruyne.
Molecular genetics and epidemiology of prostate carcinoma.
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Animals↗
Daily follow-up of serum parathyroid hormone and calcium after surgery for primary hyperparathyroidism.
OBJECTIVE: To describe the course of parathyroid hormone (PTH) and serum calcium after surgery for primary hyperparathyroidism and to evaluate the usefulness of daily measurement of these parameters. DESIGN: Prospective clinical study. SETTING: University hospital K. U. Leuven. METHOD: Daily monitoring of PTH and serum calcium (preoperatively, the first to the 5th postoperative day, and around the 10th day) in 30 patients where a parathyroid adenoma was removed and in 1 patient with a negative neck exploration. RESULTS: In the adenoma cases, PTH and serum calcium showed a sharp drop of PTH to a very low level already on the first postoperative day, whereafter a rapid recovery of the PTH was seen. Serum calcium decreased more slowly: on average, the lowest calcium level was measured on the third day, when a majority of the patients were temporarily hypocalcemic; after 2 weeks, only four patients remained slightly hypocalcemic and no one showed recurrence of the hypercalcemia. In contrast, after unsuccessful surgery (biopsy of four normal glands), the PTH decrease on the first day was far less pronounced and the hypercalcemia disappeared only for a short time. CONCLUSIONS: After removal of a parathyroid adenoma, an abrupt fall of PTH precedes the decrease of serum calcium. The first day's PTH level is a reliable indicator of the success of the intervention, and it should be a major point in the postoperative biochemical follow-up. Repeated measurements of serum calcium are useful, but the daily dosage of PTH might be omitted for economic reasons.
Adenoma↗
Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression.
OBJECTIVES: To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression. METHODS: We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models. RESULTS: pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P=0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS. CONCLUSIONS: These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.
Adjuvants, Immunologic↗
Early clinical experience with liarozole (Liazal) in patients with progressive prostate cancer.
Liarozole (Liazal) is the first retinoic acid (RA) metabolism blocking agent (RAMBA) in clinical practice. RAMBA therapy promotes differentiation and inhibits proliferation by increasing endogenous RA in tumours. Liarozole was investigated in two open-label pilot studies of 100 patients with progressive prostate cancer in relapse despite previous androgen ablation. Liarozole (150-300 mg twice daily, for > or = 1 month) produced > or = 50% reduction in prostate specific antigen (PSA) serum levels in 15 of 30 evaluable patients in study 1 (50%) and 10 of 55 patients in study 2 (18%). PSA responders had more marked reductions in prostatic acid phosphatase, alkaline phosphatase and symptom scores for bone pain and urological symptoms, and improved general well being. Plasma levels of adrenal androgens did not alter during chronic treatment with liarozole nor at adrenocorticotrophic hormone (ACTH) stimulation test. Liarozole did not alter plasma levels of adrenal androgens or cortisol. Cortisol response to ACTH stimulation was slightly blunted. Liarozole was generally well tolerated. Dermatological adverse events were probably related to increased intracellular RA. Liarozole appears to be a promising treatment option in prostate cancer.
Aged↗
Serum parathyroid hormone and calcium during the first days after resection of a parathyroid adenoma.
Serum parathyroid hormone, calcium and phosphate were daily monitored in 12, 30 and 30 patients respectively during the early postoperative period after removal of a solitary parathyroid adenoma. In all patients PTH concentration dropped to very low values on the first postoperative day, whereafter a rapid recovery began. So the first day is the best time to evaluate the results of the intervention. Hypocalcemia was most frequent on the third day. After ten days 26 patients showed a normal calcemia, while 4 patients still had a mild hypocalcemia (8-8.8 mg/dl). These data may guide management of patients after parathyroid surgery.
Adenoma↗
Heterogeneous expression of E-cadherin and p53 in prostate cancer: clinical implications. BIOMED-II Markers for Prostate Cancer Study Group.
Histologic grade and tumor volume are markers of malignant phenotype. More objective markers, however, have been sought for needle biopsy specimens. The aim of this study was to evaluate how immunohistochemical expression of the potential prognostic markers E-cadherin and p53 in biopsy specimens relates to the expression of these markers in prostatectomy specimens. Therefore, we analyzed 47 prostatectomy specimens and their preoperative biopsy specimens. Fixation of surgical specimens and the immunohistochemical assay for both E-cadherin and p53 expression was optimized. All paraffin blocks containing areas of carcinoma were submitted for immunohistochemical analysis. The prevalence of abnormal p53 immunoreactivity was only 11%. In addition, abnormal p53 expression was virtually restricted to cases that were already identified as having a poor prognosis on the basis of the large volume and the high grade of their carcinomas. In 28% of the cases, we found abnormal immunoreactivity for E-cadherin. These cases revealed considerable heterogeneity in topographic distribution of abnormal expression. The level of sensitivity to the detection of abnormal E-cadherin expression or abnormal p53 in the prostatectomy specimen was 15% and 60%, respectively. In view of the inherent heterogeneity of E-cadherin expression and the low prevalence of abnormal p53 expression, we question the use of these markers for prognostic purposes in needle biopsy specimens. Unless representative sampling by needle biopsy can be assured, the use of E-cadherin expression will be of most value in prostatectomy specimens.
Biopsy↗
Cell kinetics of prostate exocrine and neuroendocrine epithelium and their differential interrelationship: new perspectives.
The prostate gland consists of a complex ductal system lined with exocrine basal and luminal cells, and neuroendocrine epithelial cells. This paper reviews the histologic and molecular cell biologic characteristics of these cells, in normal adult tissue, during prostate morphogenesis, and in the development of benign and malignant neoplastic conditions. Expression of differentiation markers, as well as proliferation and apoptosis markers, growth factors and associated receptors, and abnormalities in genes and chromosomes are reviewed. Accumulating data indicate that (1) pluripotent immortal stem cells are located in the basal cell compartment of the prostate; (2) there is a subpopulation of epithelial cells in the prostate gland (intermediate cells) that have both structural and functional characteristics common to basal and luminal cells, which may be identified in various conditions; and prostate NE cells may have the same common origin as other exocrine cells, and share the same differentiation pathway. A stem cell model is proposed in which both exocrine and endocrine cells are derived from a subpopulation of basal cells (stem cell) that give rise to luminal cells through intermediate cells (pluripotent amplifying cells). These cells are also probably highly implicated in the early development of prostate benign and malignant neoplasia.
Adult↗
Interdependency between intensity and pitch in the normal speaking voice.
Intensity and pitch of the normal speaking voice are to some degree connected to each other. From a physiological point of view this interdependency can be explained by the fact that, to a certain extent, the same laryngeal and respiratory forces are involved in the regulation of both parameters. Measurements in 250 normal speakers show, on the average, a spontaneous pitch rise of about 9 semitones when the vocal intensity increases with 30 dB. The rise is non-linear and most pronounced on the highest intensities. A too high pitch, e.g., really more than 9 semitones for a vocal intensity increase of 30 dB, could represent a voice misuse.
Adult↗
Adjuvant chemotherapy for superficial transitional cell bladder carcinoma: long-term results of a European Organization for Research and Treatment of Cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone.
PURPOSE: We compared the efficacy of transurethral resection alone or transurethral resection followed by bladder instillations of doxorubicin or ethoglucid for 1 year in patients with superficial bladder carcinoma, and followed them long term for the incidence of progression to muscle invasion. MATERIALS AND METHODS: A total of 443 patients with superficial transitional cell carcinoma of the bladder was randomized. After randomization of 206 patients the control arm was closed to patient entry based on the results of an interim analysis showing a significant difference in favor of those receiving adjuvant chemotherapy. RESULTS: Final analysis of treatment results for recurrence included 432 patients at a median followup of 3.4 years for time to first recurrence, 5 years for analysis of time to invasion (Category T2 disease or worse) and 10.7 years for duration of survival. Time to first recurrence was significantly prolonged by both drugs compared to transurethral resection alone (doxorubicin versus transurethral resection alone p < 0.001 and ethoglucid versus control p < 0.001). Recurrence rate per year was 0.30 for both adjuvant treatment arms and 0.68 for the resection only group. Progression to muscle invasion was rare (15.1% of cases) and not apparently different in the 3 treatment arms. Of the 423 patients death from any cause in 199 and from malignant disease in 59 was not correlated with treatment. However, there was a strong correlation between death from malignant disease, and T category and tumor grade. CONCLUSIONS: In regard to time to first recurrence and recurrence rate per year this study indicates that adjuvant chemotherapy with doxorubicin and ethoglucid using the indicated schedule is superior to transurethral resection alone. However, progression in stage or survival was not influenced by the treatment regimen.
Aged↗
Evaluation and follow-up of patients with N1-3 M0 or NXM1 prostate cancer in phase III trials.
OBJECTIVES: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer. METHODS: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting. RESULTS: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group. CONCLUSIONS: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.
Clinical Trials, Phase III as Topic↗
Acoustic analysis of the speaking voice after thyroidectomy.
Voices of 47 female patients were analyzed before and after thyroidectomy, with preservation of the recurrent and superior laryngeal nerves and normal vocal fold motility during the observation period. A mean decrease of the speaking fundamental frequency (SFF) of 12 Hz was found on day 4; in 8 patients the postoperative vocal pitch was more than 2 semitones lower. The distance between the highest and lowest F0 during speaking was diminished (speech was more monotone) and the vocal jitter was elevated. In the frequency spectrum, there was a diminished prominence of the harmonics. The other spectral parameters (as the slope of the spectrum and the H1/H2 ratio) were unchanged. All changes had disappeared the fifteenth day, except for a lower SFF (> 2 semitones) in 2 cases. It is concluded that after normal dissection of the laryngeal nerves, and in the absence of vocal fold paresis, other reasons for voice changes immediately after thyroidectomy remain: alterations in the neck muscles, in the laryngeal mucosa, and in the patient's general condition. Although the effects seem limited and of short duration, knowledge of them is helpful when informing the patient before thyroid surgery.
Female↗
Distribution of the solitary adenoma over the parathyroid glands.
One hundred and ten patients with primary hyperparathyroidism were studied, in which a normal parathyroid gland was found on the same side as an adenoma (both confirmed by histological examination), and the upper or lower location could clearly be defined during surgery. The distribution of the adenomas over the upper and lower glands was unequal: 61.8 per cent in the superior versus 38.2 per cent in the inferior position. Statistical analysis revealed that this is not a random distribution (p = 0.013). The explanation of this relative predilection is unknown. The finding should not influence the surgical procedure for primary hyperparathyroidism.
Adenoma↗
Changes in spectral measures and voice-onset time with age: a cross-sectional and a longitudinal study.
In this study, we searched for changes in spectral features (during the sustained vowels [a] and [i]) and the voice onset time (VOT, of [pa] and [ka]) of the ageing voice. A longitudinal study (on 20 participants) and a cross-sectional study (on 265 participants) were conducted. The spectral parameters under consideration were: the difference in amplitude between the first and the second harmonic, the energy difference between the frequency band below 1 kHz and 2-4 kHz, and the energy difference between < 1 kHz and 4-5 kHz. The VOT was also measured. Comparing five age bands of men and women, the cross-sectional study revealed a stronger H2 relative to H1 for women above 60 years pronouncing both vowels [a] and [i]. A relatively stronger spectral level was found between 4 and 5 kHz in elderly men and women (60+) for [i] compared to young men and women (20-29 years). Significant differences in the longitudinal study were not identical to those of the cross-sectional study. After a time interval of 30 years, 20 men produced a relatively weaker 2- to 4-kHz part of the spectrum and the VOT became much longer. It was impossible to attribute the changes purely to the process of ageing. Situations and emotions also play an important role and contribute to the different findings of the two groups of participants under consideration.
Adult↗
The ageing voice: changes in fundamental frequency, waveform stability and spectrum.
In the present study we searched for age dependent acoustic changes in the voice of 205 men and women divided in four age groups from 60 to 99 years old. Sixty young men and women served as a comparison group. The findings cover three domains of acoustic features. Firstly, the voice pitch of males and females congruate one to another, while range and variability both increase. The values of jitter, shimmer and harmonics-to-noise ratio (measures of microstability of frequency, amplitude and waveform resp.) reflect a growing voice instability. From all spectral characteristics, only the difference between the first and the second harmonic differs significantly when comparing young to old women.
Acoustics↗
Labyrinthine fistulae: a retrospective analysis.
A retrospective analysis has been conducted of 57 labyrinthine fistulae found in 375 cholesteatoma cases, primarily treated by removal of the matrix of the cholesteatoma and covering the fistula with a mixture of bone paste and fibrin glue. CT-scan with slices of 1 mm demonstrated the fistula in almost 90% of the cases. Eighteen percent of the ears were pre-operatively totally deaf. Large fistulae are riskier than smaller ones for post-operative perceptive losses, but even in very large and multiple fistulae the hearing may be preserved in most cases.
Bone Cements↗
Temporary voice changes after uncomplicated thyroidectomy.
Voice characteristics were studied before and after thyroidectomy in patients with intact vocal fold motility. The speaking voice was acoustically analysed in 47 patients and phonetograms were made in 17 patients. Eight parameters were measured and the pre- and postoperative values compared. The results show that the most affected parameter was the pitch of the speaking voice. The fourth postoperative day there was, on average, a lower SFo and a smaller Fo range during speaking. Postoperatively a progressive normalisation took place. After three months there were no more statistical differences and, looking at the individual measures, the SF0 of all patients fell within 2 semitones from their preoperative level. Vocal quality was also altered in the first postoperative examination, as shown by the higher jitter and smaller harmonics. These measures normalised after two weeks. In the same way, the evaluation of the limits of the voice by means of the phonetogram, showed that the maximal performances in the intensity and pitch domain were decreased in the earliest postoperative period. Information about temporary voice change is useful in patients undergoing thyroidectomy.
Female↗
Prostatic neuroendocrine cells have a unique keratin expression pattern and do not express Bcl-2: cell kinetic features of neuroendocrine cells in the human prostate.
We investigated the keratin phenotype and bcl-2 immunoreactivity of neuroendocrine cells in the human prostate to determine whether the postmitotic status of these cells is associated with protection from apoptosis by bcl-2 protein expression and to elucidate the possible cell kinetic relationship between neuroendocrine cells and the other epithelial components of the prostate. Tissue specimens were selected from prostates of 19 patients harboring normal secretory glands (n = 15) and glandular benign prostatic hyperplasia (n = 10). Using a novel sequentially selective destaining immunoenzymatic cytochemical technique we were able to demonstrate the distribution of neuroendocrine cells, keratin markers identifying either basal, luminal, or intermediate cells, and the bcl-2 protein in single sections. Basal cell keratins were expressed in the minority of the neuroendocrine cells. In most of the cells, intermediate and luminal cell keratins were found and bcl-2 was constantly negative. Our findings indicate that neuroendocrine cells and other epithelial cells in the human prostate share a common keratin phenotype and probably originate from a common epithelial precursor. From the absence of bcl-2 we infer that the neuroendocrine cells have no progenitor cell characteristics.
Aged↗