Do clinically insignificant tumors of the prostate exist?

BACKGROUND: The discrepancy between minimal disease on biopsy and disease found in the subsequent prostatectomy specimen, in terms of the size and grade of tumor, extracapsular extension or positive margins, led several authors to dispute the existence of clinically insignificant impalpable tumors of the prostate. However, considering that prostate-specific antigen (PSA) is an indicator of prostate malignancy and since many impalpable prostatic carcinomas (PCs) are detected by a combination of PSA, transurethral ultrasound and needle biopsy (T1c), in the era of PSA screening, it is expected that most of the impalpable tumors found incidentally at transurethral resection of the prostate (stage T1a/b), could be clinically insignificant. AIM: The aim of this study was to identify the characteristics of latent, impalpable PCs and to analyze the incidence of clinically insignificant PCs among hypothetical stage T1 prostate cancers in tumors found incidentally at postmortem examination. METHODS: We examined 40 cases of impalpable PCs found in 212 prostate autopsy specimens of men between 30 and 98 years of age who died of diseases other than carcinoma of the prostate and related conditions. RESULTS: Most of T1 histological PCs (57.5%) had a Gleason score between 2 and 4, while 30% had Gleason score between 5 and 6. Only 5 (12.5%) had a Gleason score above 7. Twenty-nine of 40 stage T1 histological cancers (67.5%) had volume of <1 cm(3). The highest volume tumors were those of intermediate and high grade (Gleason sums 5-8). Among tumors with volumes of <1 cm(3), 96.55% were confined within the prostatic capsule. CONCLUSIONS: The majority of impalpable PCs were low-volume, well-differentiated tumors corresponding to clinically insignificant neoplasms. Similar characteristics could be attributed to most of the impalpable carcinomas detected after prostatectomy in clinical practice.

Evidence-based medicine and radiology.

In the early 1990's, a group of physician-epidemiologists developed ways of efficiently tracking down and appraising literature and wrote them up in order to help other doctors, with no or with minimal formal epidemiological training. Today Evidence-Based Medicine (EBM) integrates clinical experience and patient values with the best available research information in order to expand research evidence and to provide sensible answers to medical questions in clinical decision making. Although EBM does not provide the answer to every clinical question, it provides us valuable additional evidence helpful in decision making. EBM process includes five steps: answerable questions asking; accessing for the best information; information appraisal for validity and relevance; data application to patient care and finally evaluation of the performance. The purpose of this paper is to help radiologists who have no postgraduate specialist training in research to become familiar with EBM and to find solutions that are based on best current evidence for problems arising in their practice.

Study on the efficacy of cefaclor for the treatment of asymptomatic bacteriuria and lower urinary tract infections in pregnant women with a history of hypersensitivity to penicillin.

PURPOSE: The purpose of this study was to compare the efficacy and safety profile of twice daily versus the conventional three daily intake of cefaclor administrated orally for five to seven days in the treatment of asymptomatic bacteriuria or acute cystitis in pregnant women with a history of hypersensitivity to penicillin. METHODS: Between August 2003 and August 2004, 63 pregnant women with a positive urine culture and a history of suspicion of hypersensitivity to penicillin were randomly divided into two groups. The women in the first group received 500 mg of cefaclor while those in the second group received 750 mg of cefaclor for five to seven days. Laboratory and clinical results were assessed a week and a month after complettion of the therapy. RESULTS: Final therapy (bacteriologic eradication) succeeded in 93.7% (30/32) of the first group and in 90.3% (28/31) of the second group. CONCLUSION: Dosage of cefaclor at 750 mg is as effective as conventional cefaclor at 500 mg and better tolerated.

Tricyclic antidepressant-induced acute urine retention in a young woman with postpartum depression--case report.

A rare case of acute urinary retention in a young woman due to simultaneous use of a tricyclic antidepressant and anticholinergic drugs is presented along with the data from the current literature, including the pharmacological action of these drugs, mainly focused on urological patients.

Endometriosis of ureter-induced recurrent urinary tract infections in a premenopausal woman--case report.

Endometriosis of the urinary tract is infrequent. The ureters and kidneys are the least usual place of localization. Endometriosis of the ureter often leads to silent loss of renal function due to delayed diagnosis. We report a case of a premenopausal female with endometriosis of the left distal ureter, presenting an infection of the urinary tract and having reported previous incidents of menorrhagia and left flank renal pain with automatic recession. Pharmacological treatment was applied with a satisfactory outcome. A short review of the literature is presented.

Incidence of impalpable carcinoma of the prostate and of non-malignant and precarcinomatous lesions in Greek male population: an autopsy study.

OBJECTIVE: The present study investigates the incidence of impalpable carcinoma of the prostate and the pathological findings of impalpable prostate carcinoma (PC) detected in autopsy material. The frequency of pre-carcinomatous and non-carcinomatous lesions as well as their relationship to the impalpable PC, were also examined. MATERIALS AND METHODS: Data were obtained from 212 autopsy specimens of the prostate gland, of men aged above 30 and under 98 years of age, born and living in Greece, who died (between 8/2002 and 8/2004), of causes other than carcinoma of the prostate. RESULTS: The age-independent frequency of histological PC in our study's population is 18.8% (ranging from 0% to 56.2% according to different age groups), whereas the age-independent frequency of histological benign prostate hyperplasia is 65.5% (ranging from 27.7% to 90.6%), of atypical adenomatous hyperplasia 15.5% (ranging from 5.5% to 25%), of prostatic intraepithelial neoplasia (PIN) 26.4% (ranging from 5.5% to 47.2%) and of prostate atrophy (PA) 10.3% (ranging from 0% to 43.7%). There was a statistically significant correlation between PIN and PC volume. Most impalpable carcinomas found within necropsy material were characterized by small volume, favorable histological type, and relatively low aggressiveness. The prevalence of PC and pre-carcinomatous lesions in our study population appears to be lower than that of most autopsy studies. CONCLUSIONS: The frequency of clinical PC in a certain population could be related to the frequency and prevalent model of impalpable carcinoma as well as to the frequency of pre-carcinomatous lesions.

Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: an autopsy study.

A series of 212 prostate specimens of men dead between August 2002-August 2004, have been sectioned in consecutive autopsies and subjected to whole mount analysis in purpose to determine the epidemiology of impalpable prostate cancer in Greece. Impalpable prostate carcinomas were found in 40 cases (18.8%) most in the peripheral region. In all, 29 of 40 impalpable cancers (70.7%) had volume less than 1 cm3. Most of impalpable carcinomas were of favorable (Gleason score 2-4) or intermediate (Gleason score 5 and 6) histological type (55 and 27.7%, respectively) while only five (12.5%) were undifferentiated (Gleason score 7 and 8). In all, 24 (60%) of the 40 impalpable carcinomas were multifocal and consisted of two or more foci, most of small size (<0.5 cm3). Most of the impalpable cancers found in this autopsy study were potentially insignificant tumors (relatively low volume, favorable or intermediate histological pattern and absence of invasiveness). Prostate intraepithelial neoplasia (PIN) coexisted with impalpable carcinomas, in almost half of the cancer-positive specimens. There was a positive correlation between PIN foci and coexistent cancer foci in most of the cases. Frequency rate and pathological features of both entities show significant variations in medical literature. Since the incidence of clinical prostate cancer in Greece is relatively low, and according to our autopsy findings, it is plausible that the frequency of clinical prostate cancer in a certain population could be related to the prevalent model of impalpable cancer as well as to the frequency and extend of the precancerous lesions.

Physical activity and stroke risk.

Stroke represents a leading cause of morbidity and mortality especially among the elderly people, and therefore the need for effective preventive strategies is imperative. The value of physical activity for stroke prevention is not as well established as for other cardiovascular diseases. Despite some conflicting results, the majority of published studies have demonstrated a negative association between physical activity and stroke risk. In this article, we provide a concise overview of the epidemiological studies that investigate this association as well as a comprehensive analysis of the most relevant underlying pathophysiological mechanisms.

Control of the cardiovascular system of Aplysia by identified neurons.

The neural network that controls the cardiovascular system of Aplysia adapts cardiovascular function to a variety of different physiological and behavioral situations. It (1) coordinates the cardiovascular system with the renal and respiratory systems; (2) modifies both systemic and regional blood flow during food-elicited arousal and feeding; and (3) changes the tension of longitudinal vascular muscle to adapt the arterial tree to changes in body shape. Indirect evidence suggests that the cardiovascular control circuit may also play a role in maintaining homeostasis during egg laying. Several putative neurotransmitters, including acetylcholine, serotonin, R15 alpha 1 and R15 alpha 2 peptides, have been localized to identified neurons in this circuit.

Distribution of buccalin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californica.

The neuropeptide buccalin A was originally purified and sequenced from a nerve-muscle system used in feeding-related behaviors of Aplysia californica in which it has been proposed that it acts as a modulatory cotransmitter. The distribution of buccalin-like immunoreactivity in the central ganglia and in peripheral tissues of Aplysia californica was examined by whole mount immunohistochemical techniques. Immunoreactive material was located in specific cell bodies and clusters of neurons in each of the ganglia. Immunoreactive fibers were present in each of the connectives between ganglia, in tracts coursing through the ganglia, and in the majority of the peripheral nerves. Most fibers were smooth in contour, but some had regularly spaced swellings. Varicosities containing immunoreactive material were located on specific neuronal somata and on certain tissues associated with the feeding, circulatory, digestive, and reproductive systems. The specific and widespread distribution of buccalin-like immunoreactivity supports the hypothesis that members of the buccalin peptide family act as neuromodulators or neurotransmitters in a variety of central and peripheral circuits in Aplysia.

Localization of myomodulin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californica.

The distribution of myomodulin-like peptides in the nervous system of Aplysia californica was examined by using immunocytochemical techniques. Neurons and cell clusters containing immunoreactive material were located in each of the major central ganglia. Myomodulin-like immunoreactivity was also present in fibers in each of the connectives between the ganglia and in peripheral nerves. Varicosities containing immunoreactive material were located on specific regions of peripheral tissues associated with the feeding, digestive, cardiovascular, and reproductive systems. Double-labeling experiments were used to demonstrate myomodulin-like immunoreactivity in two identified neurons, the motor neuron B16 in the buccal ganglion and the widely acting interneuron L10 in the abdominal ganglion. Structures in the eye and cerebral ganglion that may correspond to the optic circadian pacemaker system were also stained. The central and peripheral distribution of myomodulin-like immunoreactivity indicates that this family of neuropeptides is present in specific efferent, afferent, and interneuronal elements that participate in a diversity of neural circuits in Aplysia.

Structure, bioactivity, and cellular localization of myomodulin B: a novel Aplysia peptide.

Important insights into mechanisms by which neuromuscular activity can be modulated have been gained by the study of experimentally advantageous preparations such as the ARC neuromuscular system of Aplysia. Previous studies have indicated that one source of modulatory input to the ARC muscle is its own two motor neurons, B15 and B16. Both of these neurons synthesize multiple peptide cotransmitters in addition to their primary neurotransmitter acetylcholine (ACh). Peptides present in the ARC motor neurons include SCPA, SCPB, buccalin A and B, and myomodulin A. We have now purified a novel neuropeptide, myomodulin B, which is structurally similar to myomodulin A. Myomodulin B is present in two identified Aplysia neurons that contain myomodulin A; the ARC motor neuron B16 and the abdominal neuron L10. Ratios of myomodulin A to myomodulin B are approximately 6:1 in both cells. Like myomodulin A, myomodulin B potentiates ARC neuromuscular activity; it acts postsynaptically, and increases the size and relaxation rate of muscle contractions elicited either by motor neuron stimulation or by direct application of ACh to the ARC. When myomodulin A is applied to the ARC in high doses (e.g., at about 10(-7) M), it decreases the size of motor neuron-elicited muscle contractions. This inhibitory effect is never seen with myomodulin B. Thus, despite the structural similarity between the two myomodulins, there exists what may be an important difference in their bioactivity.

R15 alpha 1 and R 15 alpha 2 peptides from Aplysia: comparison of bioactivity, distribution, and function of two peptides generated by alternative splicing.

The mRNA precursor encoded by the R15 gene is alternatively spliced in different neurons to form two related variants, R15-1 and R15-2 mRNA. One of the peptides encoded by the R15-2 mRNA, the R15 alpha 1 peptide, is expressed in the endogenously bursting neuron R15 and mediates some of its central and peripheral synaptic actions. In this study we found that the R15 alpha 2 peptide, which is encoded by the R15-1 mRNA, is synthesized in other neurons in the abdominal ganglion and is also bioactive. The R15 alpha 1 and R15 alpha 2 peptides were found to exert many similar actions on the cardiovascular, digestive, respiratory, and reproductive systems. However, the differences between many of the pharmacological effects of the R15 alpha 1 and R15 alpha 2 peptides indicate that alternative splicing in this system results in two functionally different peptides. Widespread immunoreactivity was found for an antibody directed against the R15 alpha 2 peptide, both in the central nervous system and the periphery. But because of the shared sequence with the R15 alpha 1 peptide, the antibody cross-reacts with the R15 alpha 1 peptide. To distinguish immunocytochemically between the two peptides, we also raised a second antibody that recognizes only the R15 alpha 1 peptide. This antibody labeled the cell body of only one neuron in the central nervous system, R15, although widespread immunoreactivity was found in axons and varicosities in the periphery.

Synaptic actions of identified peptidergic neuron R15 in Aplysia. I. Activation of respiratory pumping.

The purpose of the study described in this and the following two companion papers was to determine the synaptic actions of neuron R15, an endogenously bursting neurosecretory cell in Aplysia, as a step toward determining its physiological function. The results described in this paper demonstrate that activity in R15 increases the frequency of bursting in the R25/L25 network that triggers respiratory pumping. This excitatory modulatory effect appears to be mediated by R15 alpha 1 peptide. R15 activates both strong and weak modes of respiratory pumping. In contrast, the two R20 cells, which are thought to use the neuropeptides SCPA and SCPB as transmitters, elicit only strong episodes of respiratory pumping. The synaptic actions of R15 also differ from those of the R20 cells in being longer lasting and in exhibiting profound desensitization. Chronic recording of R15 activity in vivo indicates that it does not burst spontaneously in the intact animal, so the synaptic actions of R15 are not chronically desensitized. The neuroendocrine bag cells, which initiate egg laying, had been shown by others to excite R15 and the R25/L25 network that triggers respiratory pumping. Our data indicate that the excitatory effects of the bag cells on the R25/L25 cells are mediated in part by R15.

Synaptic actions of identified peptidergic neuron R15 in Aplysia. III. Activation of the large hermaphroditic duct.

The purpose of the study described in this and the preceding two companion papers was to determine the synaptic actions of neuron R15, an endogenously bursting neurosecretory cell in Aplysia, as a step toward determining its physiological function. The results described in this paper demonstrate that activity in R15 activates anterograde peristaltic movements in the segment of the large hermaphroditic duct through which eggs move during egg-laying behavior. This action is mimicked by R15 alpha 1 peptide, a putative transmitter of R15. The neuroendocrine bag cells, which initiate egg laying when they fire in a population burst, have been shown by others to excite R15. Our data suggest that R15 mediates excitatory effects of the bag cells on the large hermaphroditic duct. Taken with the results of the two companion papers, these data support the hypothesis that R15 integrates various aspects of egg-laying behavior. The desensitization of R15's postsynaptic actions may complement the long-lasting refractoriness of the bag cells described by others, with both effects contributing to the episodic nature of egg laying.

Synaptic actions of identified peptidergic neuron R15 in Aplysia. II. Contraction of pleuroabdominal connectives mediated by motoneuron L7.

The purpose of this study was to determine the synaptic actions of the bursting peptidergic neuron R15 in Aplysia. R15 is known to be excited by the neuroendocrine bag cells, which trigger egg laying. In the two companion papers, we show that R15 mediates some of the effects of the bag cells on respiratory and reproductive organs. In this paper, we demonstrate that R15 excites L7, a multimodal motoneuron located in the abdominal ganglion. Although L7 excites several types of muscle fibers as well as neurons, the excitation of L7 by R15 is probably strong enough to cause contraction only of the sheath muscle of the pleuroabdominal connectives, which has an exceptionally low threshold for activation. The excitatory actions of R15 on L7, which desensitize profoundly, appear to be mediated by R15 alpha 1 peptide. The synaptic action of R15 on L7 and on the respiratory pumping system (Alevizos et al., 1991a) can be fully expressed only if R15 is first silenced for 2 hr by injection of hyperpolarizing current. A similar protocol for eliminating desensitization may prove to be generally useful for revealing the synaptic actions of other spontaneously active neurons that have rapidly desensitizing postsynaptic actions.