Natural Cures For Prostate Cancer

Prevent And Heal Prostate Problems

The Extensive Guide To Prevent And Heal Prostate Problems Including Prostate Cancer, Bph Enlarged Prostate And Prostatitis. This New Book Explains How To Cure Your Prostate Problem Naturally Without The Devastating Side Effects Of Medical Treatments. With Healthy Prostate at your fingertips, you'll quickly identify the best treatment option for whatever prostate condition you have. You'll gain a thorough understanding of the prostate, how it works, the disease conditions that can affect it and which one you have or how to prevent problems in the first place. You'll learn about toxins and other environmental factors in the food we eat, the air we breathe, even the water we drink that can have devastating effects on your prostate health and what you can do to combat them. Including: 12 warning signs that you may have benign prostatic hyperplasia. Which nation has the highest incidence of prostate cancer? The 11 healthiest foods you can eat and 10 foods you should avoid at all costs. How prostate illness increases your chance of urinary tract and kidney infection. 8 ways to treat prostatitis without prescription medications or surgery. 5 reasons why you should want to keep your prostate as healthy as possible. Why drinking milk may cause your prostate to become inflamed.

Prevent And Heal Prostate Problems Summary

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Laparoscopic Radical Prostatectomy

As mentioned above, Schuessler and coworkers were the first to perform laparoscopic lymphadenectomy for prostate cancer prior to open radical prostatectomy 10 . The same group described removal of the seminal vesicles during laparoscopic lymphadenec-tomy 5 . In 1992 this group was the first to perform transperitoneal laparoscopic radical prostatectomies, and they published their initial series of 9 patients in 1997 9 . They were not enthusiastic about the technique and concluded that laparoscopy is not an efficacious surgical alternative to open prostatectomy for malignancy This team was not able to define a clear advantage of laparoscopic surgery over the traditional open radical retropubic prostatectomy regarding hospital stay, continence and reconvalescence. It is noteworthy that these first operations lasted almost 9 h on average, which was considered a major drawback for the further development of the technique. Raboy et al. described the first extraperitoneal radical...

Neuroanatomical Basics of Radical Prostatectomy

During radical prostatectomy the surgeon encounters nerve fibres that run dorsally and laterally to the prostate, also known as neurovascular bundles (NVB). This term does not have an exact anatomical correlate as it describes a topographically related cluster of nerves and blood vessels. In the literature the description of the NVB differs widely and in regard to its existence and exact position is subject to inter-individual variations 9-12 . These autonomic nerve fibres originate in the pelvic plexus (synonyms pelvic ganglion, inferior hypogastric plexus), which unites sympathetic and parasympathetic nerves. In contrast to the NVB the pelvic plexus is an anatomical structure subjected to only minute inter-individual variability. It is rhombic in shape, situated at the lateral pelvic wall and represents a concentration of ganglion cells. The pelvic plexus is the central neural plexus that provides autonomic innervation to male urogenital organs. Particular attention is paid to the...

And Epidemiology Of Prostate Cancer

The vast majority of malignant tumors of the prostate are epithelial and termed adenocarcinomas. The prostate normally has several types of epithelial cells. Basal cells are located between the luminal cells and the basement membrane and form a continuous layer in the non-neoplastic gland. This cell layer may also contain a stem cell compartment that differentiates into luminal cells. Neuroendocrine cells are androgen-independent cells dispersed throughout the basal layer and are believed to provide paracrine signals that support the growth and function of luminal cells. The luminal cells are androgen-dependent and produce prostatic secretory proteins. Prostate adenocarcinomas have features of both basal and luminal cells, raising controversy as to the cell of origin (4). A likely possibility is that most cancers are derived from the ill-defined stem cell compartment. The prostate develops through budding of epithelium from the urogenital sinus into the surrounding mesenchyme....

Experimental Biology Of Prostate Cancer

Several excellent reviews of the molecular biology of prostate cancer are available, and only a few of the more common molecular alterations and their potential significance are highlighted here (4,12). The analysis of chromosomal alterations in cancer has identified many changes reflecting loss or gain of function of particular genes. Consistent allelic loss is expected to reflect the location of putative tumor suppressor genes. Loss of heterozygosity at chromosome arms 8p, 10q, 13q, and 17p are frequent events in prostate cancer, and losses at 6q, 7q, 16q, and 18q also occur. Gains of genetic material are expected to reflect the location of oncogenes. In prostate cancer, gains at 8q and 7 are fairly common. Individual genes at these loci have not been definitely assigned a role in prostate cancer, but several reasonable candidate genes have been proposed based on their location and functional properties. One of the more common events in early prostate cancer development is loss of...

Results Of Gene Expression Analysis Of Prostate Cancer

The Prostate Transcriptome The subset of genes expressed in normal and neoplastic prostate tissue has been estimated based on theoretical and practical considerations. These studies are beginning to define the prostate cancer transcriptome and a possible role for some genes in critical processes. The Cancer Genome Anatomy Project (CGAP) of the National Cancer Institute was designed to identify genes responsible for cancer by sequencing of cDNA clones representing RNA from normal, precancerous, and malignant cells (http cgap.nci.nih.gov ). Currently, there are 17,040 genes identified in the 139,041 ESTs from prostate libraries listed in CGAP. These resources have been combined with independent data to identify 15,953 prostate-specific EST clusters in the prostate expression database (http www.pedb.org ) (37). This is believed to represent about 50-75 of the prostate transcriptome. An additional estimate, based on combining publicly available SAGE data, predicted 37,000 genes in the...

Cpg Island Hypermethylation Changes During Prostate Cancer Progression And Metastasis

Abstract Recent studies have implicated the dysregulation or maladaptation of epigenetic mechanisms to be a central feature of prostate carcinogenesis. Hypermethylation of CpG islands (CGI), clusters of CpG dinucleotides frequently found at gene regulatory regions, has been demonstrated to be one of the most frequent somatic genome alterations associated with prostate carcinogenesis. A few recent studies have explored the role of CGI hypermethylation during prostate cancer progression from the early precursor lesions to distant metastases. This chapter will focus on the time course of CGI hypermethylation changes that occur at each step during the development and progression of prostate cancer in an effort to understand how these epigenetic changes contribute to the formation of prostate cancer metastases. We will begin by giving an overview of the epidemiology, natural progression, and pathogenesis of prostate cancer, then detail the CGI hypermethylation changes that occur at each...

Proliferative Inflammatory Atrophy of the Prostate

Another, more attractive, hypothesis maintains that widespread chronic inflammation, atrophy, and regeneration in the prostate might provide the fertile ground of stress and genome damage that lead to the development of multiple prostate cancer lesions that are heterogeneous in their age and aggressiveness. The identification of highly prevalent PIA lesions lends much support to this hypothesis, and offers direct evidence for a link between prostate inflammation and carcinogenesis. As mentioned previously, the blunted, dysfunctional luminal epithelia in these PIA glands generally express high levels of stress response and caretaker genes such as GSTP1, GSTA1 and COX2 (5, 7, 8). The induction of these genes may be a response to electrophile and oxidative stress. However, a minority of epithelial cells within PIA lesions lose GSTP1 expression (5, 61). This observation led to the hypothesis that a subset of PIA cells may have already begun to repress GSTP1 expression by hypermethylation...

Prostate Cancer Angiogenesis

Tumour hypoxia is thought to be the likely explanation for the induction of angiogenesis in prostate cancer (Izawa and Dinney 2001). Hypoxia induces vascular endothelial growth factor (VEGF) transcription via hypoxia-inducible factor-1 (Zhong et al. 1999). VEGF is a recognised stimulus of neoan-giogenesis in tumours, and is also a potent tissue permeability factor (Dvorak et al. 1995). Androgens seem to regulate VEGF expression in prostate cancer cells and prostatic fibroblasts (Joseph et al. 1997 Levine et al. 1998). It has been shown that VEGF is produced in abundance by the secretory epithe lium of normal, hyperplastic, and tumorous prostate glands (Jackson et al. 1997 Ferrer et al. 1998). The physiological role(s) of VEGF in the prostate is poorly understood and target cells may include cells other than the vascular endothelium. With respect to the vasculature, it is clear that VEGF is required for vascular homeostasis in the prostate gland and maintains the high fraction of...

Metastatic Prostate Cancer

Very few studies have described CGI hypermethylation patterns in metastatic prostate cancers, due to the difficulty in obtaining metastatic cancer tissue. Surgical resection of metastatic deposits of prostate cancer does not enhance survival from the disease significantly. Therefore, most patients with refractory, metastatic prostate cancer are not candidates for further surgical intervention. Therefore, the few studies that have examined CGI hypermethylation patterns in metastases obtained these specimens from autopsy cases of patients who died from refractory prostate cancer or from the small group of patients undergoing surgical resection of bone metastases to alleviate symptoms or monitor for response to novel therapies. Over a 7 year period, we systematically collected metastatic prostate cancer specimens at autopsy from 28 men who died of refractory prostate cancer. One to six anatomically distinct metastases from a wide array of sites, including bone, lymph node, liver, adrenal...

Weighted Dcemri of the Prostate

After intravenous contrast medium administration, T1-weighted images can demonstrate prostatic zonal anatomy but in general, unenhanced T2-weighted spin-echo images are better in this regard. On MRI, after the administration of intravenous contrast medium, the normal central gland enhances more than the peripheral prostate both enhancing homogeneously. In the presence of benign prostatic hyperplasia (BPH), enhancement of the central gland becomes heterogeneous (Mirowitz et al. 1993 Brown et al. 1995). Prostate cancer also enhances following contrast medium administration (Brown et al. 1995 Jager et al. 1997). The role of contrast enhancement for evaluating patients with prostate cancer has not been completely defined. Early studies suggested no additional role of contrast enhancement compared to conventional T2-weighted imaging (Mirowitz et al. 1993 Quinn et al. 1994). However, Brown et al. (1995) showed improved depiction of the tumour when MR images are obtained early after contrast...

Molecular Mechanisms In The Generation And Propagation Of Aberrant Dna Methylation Patterns In Prostate Cancer

In our discussions thus far, we have been continually alluding to a fundamental paradox concerning CGI hypermethylation in prostate cancer initiation and propagation DNA methylation processes appear to be dysregulated enough to cause hypermethylation of CGIs at multiple genes yet, the same DNA methylation processes have high enough fidelity that they can maintain the acquired changes in CGI hypermethylation through every step of prostate cancer initiation and progression. This observed paradox would suggest that the CGI hypermethylation changes in prostate cancer are not due to a total dysregulation of the DNA methylation machinery, with subsequent loss of discrimination and fidelity in which CGI sequences are stochastically hypermethylated. Rather, it appears that certain CGI sequences are targeted for hypermethylation resulting in silencing of the corresponding genes. One possibility is that targeting these genes for CGI hypermethylation provides a growth advantage for these cells...

Prior Transurethral Resection of the Prostate

Prior transurethral resection of the prostate (TURP) can make the case more challenging. Clinical experience has proven that there is a wide variation in TURP technique and in the amount of tissue resected. In addition, the bladder neck is resected more aggressively by some surgeons than others. When the bladder neck has been extensively resected, the extent of scar formation can make it extremely challenging to define the border between bladder neck and prostate and to identify the ureteral orifices. Preoperative cystoscopic clarification of the shape of the prostate and the ureteral orifices is suggested. Furthermore, we recommend double-pigtail insertion during the preopera-tive cystoscopic evaluation. This provides a more secure bladder neck dissection in these patients. The double-pigtail stents can be extracted either after completion of the posterior part of the urethrovesical anastomosis or after the urethral catheter has been extracted (5th postoperative day). Fig. 4.3. a...

Urinary Retention After Prostatectomy

Prostate cancer treatment with curative intent can also predispose to urinary retention. Although the true incidence of bladder neck contracture following radical prostatectomy is not known, 1.3 -27 of patients will develop symptomatic BNC requiring treatment (Anger et al. 2005). Surgical technique remains a critical determinant of BNC development however, risk factors for microvascular disease such as smoking, hypertension, and diabetes mellitus also appear to play a role (Borboroglu et al. 2000). Simple dilation appears to be effective however, some authors question the long-term patency rates with such treatment. Transurethral incision of the contracture using cold knife, electrocautery, or the holmium YAG laser is the most commonly recommended treatment for severe BNC and those cases involving urinaryretention (Anger et al. 2005 Salant et al. 1990). Great care must be taken when performing transurethral incision since deep incision may cause sphincteric damage and, in turn, stress...

Surgical Transurethral Prostatectomy with CC

Prostate cancer is the most common type of cancer in men and the second leading cause of death among men in the United States. The American Cancer Society estimated that, in 2005, there would be 232,090 new cases and 30,350 men would die from prostate cancer. Overall, 1 in 6 men are diagnosed with prostate cancer and 1 in 33 die from this disease. The 5-year survival rate is 99 . Prostate cancer may begin with a condition called prostatic intraepithelial neoplasia (PIN), which can develop in men in their 20s. In this condition, there are microscopic changes in the size and shape of the prostate gland cells. The more abnormal the cells look, the more likely that cancer is present. It has been noted that 50 of men have PIN by the time they are 50 years old. Adenocarcinomas compose 99 of the prostate cancers. They most frequently begin in the outer portion of the posterior lobe in the glandular cells of the prostate gland. Local spread occurs to the seminal vesicles, bladder, and...

Reproductive System DRG Category 336 Mean LOS 40 days Description Surgical Transurethral Prostatectomy with CC

Prostatitis, an inflammation of the prostate gland, is classified in four categories. Acute bacterial prostatitis is an acute, usually gram-negative, bacterial infection of the prostate gland, generally in conjunction with acute bacterial cystitis. Chronic bacterial prostatitis is a subclinical chronic infection of the prostate by bacteria that can be localized in prostatic secretions and is the most common recurrent urinary tract infection in men. Nonbacterial prostatitis is a chronic prostatitis for which there is no identifiable organism. Prostatodynia is a condition in which the patient experiences irritation and pelvic pain on voiding the symptoms suggest an acute inflammatory process, but there is no evidence of inflammatory cells in the prostatic secretions. The most common complication of prostatitis is a urinary tract infection. If it is left untreated, a urinary tract infection can progress to prostatic edema, urinary retention, pyelonephritis, epi-didymitis, and prostatic...

Atypical Size and Shape of Prostate Large Prostate Large Middle Lobe Asymmetric Prostate

It is known that very small (< 30 g) as well as very large prostates represent a challenge for open as well as laparoscopic endoscopic prostatectomy. Based on our personal experience we would suggest that prostates with a size of 100-150 g should not be selected during the learning curve of a surgeon. Prostates larger than 150 g (or even over 200 g see Fig. 4.3) should be managed only by experienced surgeons. Especially the posterior apical dissection can be very demanding because of the size of the specimen. This has to be performed in a mixture of a descending and ascending The size of the middle lobe of the prostate varies from very small to very large (Fig. 4.4). A cystoscopic evaluation before the procedure is suggested to determine the dimensions of the middle lobe. For beginners we would suggest the insertion of double-pigtail catheters to ascertain the integrity of the ureteral orifices during posterior bladder neck dissection. If difficulties are encountered during bladder...

Models For The Development Of Prostate Cancer Metastases

The mechanisms underlying the dissemination of primary prostate cancer and establishment of metastatic deposits is a topic of great interest since these lesions are ultimately responsible for the vast majority of prostate cancer deaths. It is clear from clinical observations that prostate cancers have a predilection to metastasize to a distinct set of anatomical organ systems, such as lymph node, bone and liver. The first formal hypothesis suggesting an explanation for the non-random distribution of sites to which primary cancers metastasize was proposed by Stephen Paget in 1889 (111, 112). His seed and soil hypothesis suggested that factors in the target site environment promoted the growth of cancer cells there, much like fertile soil would promote the growth of seeds. A modern view of this hypothesis would suggest two possibilities i) that the target site microenvironment would either promote cancer cells to change and adapt when they reach the target site and then establish a...

Cpg Island Hypermethylation Changes During Prostate Cancer Initiation And Progression

Prostate Examine

In 1994, Lee et al. demonstrated that hypermethylation of CGI sequences within the regulatory region of GSTP1, which encodes the pi-class glutathione S-transferase (GST) enzyme, is an extremely frequent feature of human prostate cancer (49, 50). Since that initial study, numerous groups have independently corroborated these findings using a wide array of techniques applied to numerous prostate cancer DNA sources, including prostatectomy specimens, prostate autopsy specimens, prostate biopsy specimens, prostate secretions, and various bodily fluids from prostate cancer patients. Furthermore, GSTP1 CGI hypermethylation appears to be an extremely specific finding for prostate cancer as it is not characteristic of normal prostates or benign prostatic hyperplasia. The GST enzymes catalyze the detoxification of carcinogens and reactive chemical species via the conjugation of glutathione. It has been hypothesized that loss of this detoxification agent in prostate cells might make them...

And Radical Prostatectomy

Sphincter Muscle Radical Prostatectomy

A further point of controversy is the craniocaudal extension of the external sphincter over the prostate and bladder. Dorschner's groups and others advocate that the urethral sphincter is ventrally more strongly developed. Furthermore, the apex of the prostate is ventrally overlapped by the striated muscle fibres of the external urethral sphincter. In contrast, Oelrich et al. and Myers et al. described a vertically orientated sphincter muscle system, from the base of the bladder to the bulb of the penis 18, 19 . Interestingly, Dorschner et al. found two vertically orientated muscles in the urethral muscular sheet, the ventrolateral longitudinal muscle and the dorsal longitudinal muscle ( 2.3.4) 20-22 . The interpretation of the various longitudinally orientated muscular structures remains unclear. During radical prostatectomy we are able to identify and preserve three muscular structures. The ring-shaped vesical (internal) sphincter can be preserved during bladder neck-sparing radical...

Salvage Prostatectomy After Brachytherapy External Beam Radiation and HIFU

During the past few decades, various minimally invasive alternative therapies have been developed with the aim of being as efficient as surgical therapy while minimizing side effects and complications. Some of the recently developed therapies are cryosurgical ablation of the prostate, HIFU and radiofrequency interstitial tumor ablation (RITA). These approaches are categorized in the European Association of Urology guidelines as experimental local treatments of prostate cancer 1 . Fig. 4.6. a, b Postprostatectomy cystogram in a patient with previous machine gun injury before prostatectomy. c Postpros Fig. 4.6. a, b Postprostatectomy cystogram in a patient with previous machine gun injury before prostatectomy. c Postpros Most recurrent or persistent prostate cancers after failed HIFU or radiotherapy are discovered at an early stage due to the wide use of prostatic-specific antigen (PSA) as a marker for monitoring treatment response. For patients in good general condition with a life...

Prostate Cancer

Prostate cancer is the second leading urological cancer after renal cell carcinoma associated with paraneoplas-tic syndromes. Paraneoplastic syndromes in association with prostate cancer are uncommon and include Cushing's syndrome, the inappropriate antidiuretic hormone syndrome, hypercalcemia, and hypophosphatemia (Table 14.3). Table 14.3. Most common paraneoplastic syndromes associated with prostate cancer

Extraperitoneal Access The Term EERPE

The first laparoscopic prostatectomies described were performed using transperitoneal access. Despite the fact that the extraperitoneal route was almost simultaneously reported 8 , the French team at the Mont-souris center chose to develop the transperitoneal approach 4 . However, general skepticism persisted due to the fact that an extraperitoneal organ, the prostate, was being accessed by a transperitoneal route with possible intraperitoneal complications bowel injuries, in-traperitoneal bleeding, ileus, intraperitoneal leakage of urine, and acute infection of the peritoneal cavity are considered the main short-term or intraoperative complications, while intraperitoneal adhesion formation and subsequent chronic bowel obstruction with recurrent ileus are the principal long-term complications. The perspective of an extraperitoneal approach to the prostate was developed after the initial report by Raboy and coworkers. The first series of 42 patients to undergo extraperitoneal radical...

Parasympathetic System

The sacral component of the parasympathetic system originates from spinal segments S2-4. Sacral fibres run in the spinal nerves of the pudendal plexus but emerge shortly after exit from the sacral foramina as pelvic splanchnic nerves (Fig. 2.1.2). Their further presynaptic course follows the rectum and the dorso-lateral boundaries of the prostate. The relay station for sympathetic and parasympathetic fibres, which emerge as the important pelvic plexus, is also situated here. The pelvic plexus also receives the sympathetic hypogastric nerves, which form after division of the superior hypogastric plexus. This mesh of parasym-pathetic and sympathetic fibres gives rise caudally to the cavernosal nerves of the penis, which eventually innervate the cavernosal bodies. Figures 2.1.3 and 2.1.4 show that the cavernosal nerves of the penis traverse the apex of the prostate at a distance of only a few millimetres from the prostatic capsule at the 5 and 7 o'clock positions. Together with the deep...

Pelvic Plexus Inferior Hypogastric Plexus Pelvic Ganglion

In the male the plexus is situated laterally to the rectum, seminal vesicle, prostate and posterior part of the bladder (Fig. 2.1.2). These structures may be injured during radical cystectomy, rectal resection, ure Sympathetic fibres of the superior hypogastric plexus, the sacral sympathetic chain ganglia and parasympathetic fibres of the pelvic splanchnic nerves, as well as somatic afferents, feed into the pelvic plexus. This is the main coordinating centre for pelvic autonomic innervation. The main efferent branches are the vesical plexus with fibres for the urinary bladder and the seminal vesicles the prostatic plexus with fibres for the prostate, seminal vesicle, bulbourethral glands and ejaculatory ducts as well as cavernosal nerves for the cavernosal bodies the deferential plexus for the vas deferens the ureteric plexus for the pelvic ureter and the medial and inferior rectal plexus with fibres for the colon and external anal sphincter muscle. The nerve-sparing radical...

Preoperative Preparation

A cystoscopy can be performed before the initiation of the procedure. It is always useful, especially for beginners, to evaluate the presence of a median lobe and to locate the ureteral orifices. When previous transurethral resection of the prostate has been performed the insertion of double-pigtail catheters is advisable.

Prior Abdominal Surgery

Little is known about the effect of previous surgery on the results of laparoscopy. Seifman et al. reported that previous abdominal surgery increased the overall risk of transperitoneal laparoscopic renal and adrenal surgery 11 . In contrast, Parsons et al. described no adverse effect of previous abdominal surgery on the subsequent performance of predominantly laparoscopic renal surgery 12 . While extensive transabdominal surgery or previous pelvic surgery has been regarded as a contraindication for laparoscopic prostatectomy by some authors 13 , previous major abdominal surgery or pelvic surgery is not seen as a contraindication per se by others 14 . Nevertheless, in a detailed analysis of perioperative complications by the latter group, the effect of previous intra-abdominal surgery and urological surgery was not clearly stated 15 . In a recent study from our center we analyzed the impact of previous surgery on EERPE. 500 patients who underwent EERPE for clinically localized...

Role of Carbon Dioxide

An additional CO2 pressure effect on the cerebral circulation is caused in patients in Trendelenburg position for prostate and bladder surgery. A rise in CO2 blood tension increases cerebral blood flow, whereas intra-abdominal pressure and central haemodynamic effects reduce cerebral blood flow. In addition to an osmotic diuresis towards the end of the procedure, the routine for the prolonged head-down position included restricted fluid loads and maintenance while so positioned. Increases in ventilation rates adjust the rises in end-tidal CO2.

Prostatic Intraepithelial Neoplasia

While PIA lesions usually express high levels of stress response proteins such as GSTP1 and COX2, PIN lesions are most often characterized by an absence of GSTP1 and COX2 expression. Despite this stark contrast, PIA lesions can be considered as precursors to PIN lesions for the following reasons first, like PIN and primary prostate cancer lesions, PIA is most often found within the peripheral zone of the prostate second, the secretory cells in PIA are highly dysfunctional, like PIN and prostate cancer epithelia finally, and perhaps most compellingly, PIA regions can often be observed to merge directly into regions of PIN, often within the same secretory gland (5, 6). One possible explanation for these paradoxical observations is that PIN lesions may develop from PIA epithelia that repress or lose expression of genes such as GSTP1 and COX2. Consistent with this possible explanation, PIN lesions exhibit a much higher frequency of hypermethylation at CGI sequences at the regulatory...

Sympathetic System

The sympathetic innervation is responsible for the secretory functions of the prostate and seminal vesicles as well as ejaculation (contraction of the vas deferens and synchronous activation of the internal urethral sphincter). Hence, injury to the pelvic sympathetic fibres during extended lymphadenecto-

Nervesparing EERPE

Clinically organ-confined prostate cancer. 3. No palpable induration at the apex or posterolateral margins of the prostate. In selected cases intraoperative frozen section may be helpful to decide whether or not a nerve-sparing technique should be performed. Contraindications for the performance of a nervesparing technique are the following 1. Prostate cancer with a Gleason score of 8-10. In the case of unilateral Gleason 8 disease, then a nerve-sparing procedure can be performed con-tralaterally by an experienced surgeon. 4. Induration at the apex or posterolateral borders of the prostate.

Obesity

Obesity is an increasing health issue and a burden for the public health system. Recent studies reported an age-adjusted prevalence of approximately 20-25 in the German population 4 . Almost 2 of people are is morbidly obese, i.e. have a BMI of at least 40 kg m2 4 . Among the best-known obesity-linked diseases are diabetes mellitus, hypertension and cancer, especially breast cancer. In the latter, obesity is a well-known risk factor linked with poorer prognosis. However, the relationship between obesity and prostate cancer is not completely clear. A growing number of studies suggest that the risk of developing prostate cancer as well as the probability of higher-grade disease and disease progression after radical prostatectomy increases with increased BMI. In contrast, an equal number of studies propose a weak association or none at all 5, 6 . Only few reports are available on radical prostatectomy in obese patients 7-10 .

Postoperative Pain

In a recent study by Hoznek et al., the mean dose of morphine and the mean duration of its administration was 53.1 and 44.4 lower, respectively, after extraperitoneal than after transperitoneal radical prostatectomy. Although the difference was not statistically significant, the authors considered it clinically relevant. In addition, abdominal tenderness and shoulder pain, commonly observed among LRPE patients, were not reported in their extraperitoneal series 11 . Our initial experience with minimally invasive treatment of prostate cancer includes 70 cases performed transperitoneally in 2000 and 2001. Due to the lack of experience at that time we postoperatively transferred all patients to the intensive care unit. Administration of analgesia was started intraoperatively, with a peripherally acting analgesic (metamizole 1-2 g) and continued postoperatively using a patient-controlled analgesia (PCA) pump (with piritramide). Later, the PCA pumps were omitted due to the fact that...

Oncolytic Adenoviruses

Type II CRAds are adenoviruses where the expression of genes essential for adenoviral replication are under the control of a tumor-specific promoter. When this promoter is active, expression of this gene will result in replication of the virus. These promoters should mainly be active in tumor cells to ensure that replication predominantly occurs inside the malignant tissue. An example of a tissue-specific promoter is the prostate-specific antigen (PSA) promoter which is highly active in PSA-producing prostate cells and shows limited activity in other tissues. Placing a gene essential for replication directly under the control of the PSA promoter directs adenoviral replication primarily to prostate cells that express PSA. 6 Thus this adenovirus will replicate inside prostate (tumor) tissue while sparing the other tissues. At the moment, phase I and II trials are being conducted. Another example of a tumor-specific promoter is the telomerase promoter, which is active in more than 80 of...

Physical Examination 231

The reduced interrater reliability (Close et al. 2001) or accuracy (Weatherall and Harwood 2002) of some physical tests should not lead to a dismissal of the physical examination as a whole. For example, blood at the urethral meatus is only 50 predictive of posterior urethral distraction injury, and a high-riding prostate is only 33 predictive, but they are nonetheless useful features of the assessment. It remains the task of uni

Surgical Considerations

Denonvilliers' fascia is intimately adherent to the anterior mesorectal fat but only loosely adherent to the seminal vesicles. During anterior rectal dissection, the deep parasympathetic nerves situated in the narrow space between the rectum and the prostate and seminal vesicles may be damaged, leading to impotence 72 . For benign disease, most surgeons will tend to stay posterior to Denonvilliers' fascia in an attempt to protect the pelvic nerves. For malignant disease, the choice is less straightforward, because dissection behind rather than in front of the fascia may, in theory, be associated with incomplete resection and or local recurrence.

Deep Vein Thrombosis and Pulmonary Embolism 321

Perioperative thromboembolic disease and pulmonary embolism contribute to morbidity and mortality in urological patients. Venous thromboembolism is a multifactorial disease involving clinical risk factors as well as genetic and environmental interactions. It is uncommon in the young, but after 40 years of age the incidence doubles with each decade of life. Hereditary risk factors include factor V Leiden mutation, G20210A prothrombin gene mutation, and deficiencies in protein C, protein S, and antithrombin. Hereditary and or acquired risk factors are hyperhomocysteinemia and elevated levels of factor I, VIII, and IX. Acquired risk factors include malignancy, hospitalization immobili-ty, surgery, venous trauma, estrogen therapy, pregnancy, and the presence of antiphospholipid antibodies. Especially operations at the prostate activate the coagulation cascade. These patients are therefore prone to develop deep veins thrombosis and thrombosis in the pelvic vein bearing an increased risk of...

Estrogen Is Required For Breast Development And Tumorigenesis

Like the other steroids, E2 is lipophilic and enters cells and their nuclei primarily by diffusing through plasma and nuclear membranes. Once in the nucleus, E2 encounters proteins known as ERs, because they bind E2 with high affinity and specificity. Until relatively recently, only one ER gene (now called the ERa) was thought to be present in either humans or rodents. However, in 1996, a second species, or ERp, was isolated and cloned from rat prostate and ovary, closely followed by the human homolog in the same year (10,11). Both ERa and ERp are members of the steroid thyroid hormone nuclear receptor superfamily, and may be described as ligand-dependent nuclear transcription factors. Both proteins have the modular structure that typifies the nuclear receptor superfamily comprising six functional domains designated A-F, which include regions involved in steroid binding and interaction with DNA. The ERp gene shows a high degree of sequence homology with the ERa in its hormone-binding...

Age of Cancer Incidence

The sixth section examines the different patterns of incidence between the two sexes. Males have slightly more cancers early in life. From approximately age 20 to 60, females have more cancers, mainly because breast cancer rises in incidence earlier than the other major adulthood cancers. After age 60, during the period of greatest cancer incidence, males have more cancers than females, male incidence rising to about twice female incidence. The excess of male cancers late in life occurs mainly because of sharp rises in male incidence for prostate, lung, and colon cancers. Male cancers accelerate more rapidly with age than do female cancers for lung, colon, bladder, melanoma, leukemia, and thyroid. Female cancers accelerate more rapidly for the pancreas, esophagus, and liver, but the results for those tissues are mixed among samples taken from different countries.

Genes implicated in breast cancer predisposition

Collaborative studies by the Breast Cancer Linkage Consortium (BCLC) have examined multiple families with germline mutations in BRCA1 and BRCA2 to establish the penetrance of mutations in these genes and the risks of other cancers (Ford et al., 1994 Ford et al., 1998 Puget et al., 1999a) (Figure 2.1). These studies suggest that carriers of mutations in BRCA1 have an associated cumulative breast cancer risk of 80-85 by age 80 years. Once affected with a first breast cancer, such gene carriers have a subsequent risk of contralateral breast cancer estimated to be up to 48 by age 50 years and 64 by age 70 years. Similarly, the risk of ovarian cancer in carrier women is 60 by age 80 years as compared with a population risk of around 1 . Colon cancer risk is increased to 6 by the age of 70 years and prostate cancer may occur three times more often than expected in male BRCA1 mutation carriers, with an absolute risk of 6 by age 74 years (Ford et al., 1998). Germline mutations in BRCA1...

Tumour Characterisation

The ability of DCE-MRI to quantify a range of characteristics of the tumour microvasculature has encouraged many investigators to use this technique as a basis for in-vivo staging of tumours. Correlation of DCE-MRI-based features of the tumour microv-asculature with pathology, therapeutic response and prognosis remains the main goal for future work with these techniques. Even early studies were able to demonstrate a clear relationship between rapid and large increases in signal enhancement and high grade malignant behaviour in a range of tumours. Several studies however have also shown significant overlapping of contrast enhancement patterns between benign and malignant tumours (Fig. 1.0). This has been described in breast cancer and fibroadenoma (Kvistad et al. 2000) and prostate cancer and benign prostatic hyperplasia (Barentsz et al. 1999) (Figs. 1.11, 1.12). It is hoped that increased specificity and accuracy in the identification of microvas-cular characterisation parameters will...

Using Oligonucleotide Microarrays

It is also important to assess RNA integrity once the samples have been collected. Stamey et al., for example, collected samples of prostatic tissue within 15 min of interruption of blood flow to the prostate and froze the tissue immediately, thereby providing excellent conditions for preserving RNA (8). Yet even under these conditions, 5 out of 22 samples showed signs of considerable degradation. After inspecting the RNA by agarose gel electrophoresis and spectrophotometry, the authors used a test microarray, the GeneChip Test3 array, to determine the ratio of 3' to 5' transcript levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and overall transcript levels for 24 housekeeping genes (55). Only 17 of the 22 samples were selected for subse In identifying expression patterns associated with disease progression, for example, it is useful to first distinguish tumors based on pre-established markers. Stamey et al. showed that the most robust histologic predictor of progression in...

Detection And Purification Of Biochemical Compounds

Immunoassay uses antibodies to form a precipitate with specific compounds. Antibodies are special proteins produced by the body to bind with foreign substances so that they can be made harmless. Each antibody is highly specific, binding only to a single substance and binding extremely tightly in what is called a lock-and-key relationship. Molecular biology techniques have enabled the production of large quantities of antibodies of a specific type, called monoclonal antibodies. They are used for research purposes as well as to detect specific hormones in pregnancy tests and tests for prostate cancer. Immunoassay is a highly sensitive and selective detection method. Its use has been extended to organic pollutants and even to heavy metals.

Gender Ethnicracial And Life Span Considerations

By the age of 50, 50 of men have some degree of prostate enlargement. Many of these men do not manifest any clinical symptoms in the early stages of hypertrophic changes. As men become older, the incidence of symptoms increases to more than 75 for those over 80 years of age. Of Benign Prostatic Hyperplasia (Hypertrophy) 123

Primary Nursing Diagnosis

Those patients with the most severe cases, in which there is total urinary obstruction, chronic urinary retention, and recurrent urinary tract infection, usually require surgery. Transurethral resection of the prostate (TURP) is the most common surgical intervention. The procedure is performed by inserting a resectoscope through the urethra. Hypertrophic tissue is cut away, thereby relieving pressure on the urethra. Prostatectomy can be performed, in which the portion of the prostate gland causing the obstruction is removed. The relatively newer surgical procedure called TUIP involves making an incision in the portion of the prostate attached to the bladder. The gland is split, reducing pressure on the Benign Prostatic Hyperplasia (Hypertrophy) 125 urethra. TUIP is more helpful in men with smaller prostate glands that cause obstruction. Other minimally invasive treatments for BPH rely on heat to cause destruction of the prostate gland. The heat is delivered in a controlled...

Discharge And Home Healthcare Guidelines

Provide instructions about all medications used to relax the smooth muscles of the bladder or to shrink the prostate gland. Provide instructions on the correct dosage, route, action, side effects, and potential drug interactions and when to notify these to the physician. Cancer of the urinary bladder is the second most common genitourinary (GU) cancer after prostate cancer. It accounts for approximately 4 of all cancers and 2 of deaths from cancer in the United States. The American Cancer Society estimates that, in 2005, there will be over 63,000 new cases of bladder cancer diagnosed, and over 13,000 deaths in the United States. The majority of bladder tumors (> 90 ) are urothelial or transitional cell carcinomas arising in the epithelial layer of the bladder, although squamous cell (4 ), adenocarcinoma (1 to 2 ), and small cell (1 ) may occur. Urothelial tumors are classified as invasive or noninvasive, and according to their shape, papillary or flat. Noninvasive...

Characterizing Individual Tumor Biology

MMCM-enhanced MRI can also non-invasively assay tumor angiogenesis, the process by which cancers recruit new vessels growing in from the nontumor host tissue. Although there is no single gold standard assay for angiogenesis, the counting of immunohistochemically stained endothelial cell clusters within a given area of the tumor to yield the microvascular density (MVD) has been used widely as a surrogate marker of the angiogenesis process (Weidner 1995). Clinical series have shown that MVD correlates with the presence of metastases at time of diagnosis and with decreased patient survival in numerous types of malignancies including breast, lung, prostate, bladder, ovary, and head and neck carcinomas. Of note, the status of tumor cell differentiation, for example, the SBR score, and that of concomitant tumor angiogenesis do not necessarily correlate. In fact, tumor grade and angiogenesis are considered independent biological characteristics. In a similar experiment, yet another tyrosine...

Internal Male Reproductive Organs

The internal male reproductive organs consist of the epididymis, vas deferens, seminal vesicles, prostate gland, ejaculatory ducts, and urethra. (See Figure 3.1.) The vas deferentia consist of two tubes that serve as sperm ducts. The vas deferentia actually look a lot like strands of spaghetti, but they serve as the pipes and plumbing works for sperm. They transport the mature sperm from the epididymis and into the pelvic cavity. Once inside the pelvic cavity, the vas deferentia pass over the bladder and eventually connects with the seminal vesicles to form the ejaculatory ducts. Just prior to ejaculation, the sperm are mixed with the seminal fluid. The seminal fluid is composed of secretions from the seminal vesicles and the prostate gland. Prostate Gland The prostate gland is a walnut-sized gland located below the bladder. It contributes the majority of the secretions to the seminal fluid. The prostate's secretions are opaque white and give the semen its characteristic milky white...

Sage Uses In Human Genome Mining And Annotation

In recent studies, comparison of SAGE libraries from pancreatic adenocarcinomas was performed with that of normal tissues, and thus, additional markers were identified, and these included lipocalin, trefoil factor 2, and prostate stem cell antigen (PSCA). PSCA was confirmed overexpressed in 60 of primary pancreatic adenocarcinomas (20). Ovarian, Breast, and Prostate Cancer SAGE studies were also performed with prostate cancer samples some specific transcripts were observed up-regulated in tumor epithelial cells, while others were found increased in tumor stroma (36). In other studies, the transcript for PMEPA1, a gene mapping to chromosome 20q13, was detected by SAGE to be up-regulated by androgen treatment in the LNCaP prostate cancer cells and appears to be a direct target for transcriptional regulation by the synthetic androgen R1881 (37).

Take Home Messages

L-PLND may once again be commonly employed in that many patients are now electing minimally invasive treatments such as brachytherapy as a treatment for localized prostate cancer. L-PLND has a useful role in the performance of a complete evaluation of these patients as candidates for such localized therapy. Furthermore, with the advent of laparoscopic radical prostatectomy, a laparoscopic approach to the lymph nodes will be required. 4. L-PLND as a staging modality may also be applied to evaluation of urologic malignancies other than prostate cancer. However, extended L-PLND for the evaluation of such entities requires more laparoscopic experience and operative time. Again, postoperative benefits of this procedure compared with open surgery are significant.

Comparative Genomic Hybridization In Cancer Cytogenetics

Tumors, including prostate cancer, testicular germ cell tumors, breast cancer, uveal melanomas, small-cell lung carcinoma, gliomas, sarcomas, head, neck, and pancreatic carcinomas, and uterine leiomyomata. The chromosomal aberrations detected by CGH have also provided prognostic information in a number of neoplasms including renal cell carcinomas, bladder cancer, cervical carcinomas, node-negative breast cancer, uveal melanoma, cutaneous melanoma, and prostate cancer. Various international CGH databases have been established including Tokyo Medical and Dental University CGH database (http the database of Humboldt-University of Berlin (http amba.charite.de ksch cghdatabase index.htm), the Progenetix cytogenetic online database (http www.progenetix.net), and the National Cancer Institute and National Center for Biotechnology Information Spectral Karyotyping SKY and Comparative Genomic Hybridization CGH Database (2001), (http www.ncbi.nlm.nih.gov sky). These databases provide a wealth of...

Background Information

Although cell yield and viability can vary, mechanical disaggregation has been demonstrated to be superior to enzymatic digestion for aneuploid cell recovery in breast (McDivitt et al., 1994), colon (Crissman et al., 1988), prostate (K nig et al., 1993), and ovarian tumors (Costa et al., 1987). Neoplasms of squamous origin or differentiation, however, require enzymatic digestion for their complete dissociation. Cell yield and viability and aneuploid cell recovery are all increased when compared to mechanical methods for these tumors (Bijman et al., 1985 Ensley et al., 1988). There is no universal disaggregation method, so any technique should be optimized to obtain maximum recovery of target cell populations comprising a solid tumor and individualized for tumor type. neoplastic and benign tissue in some lesions as well as admixture of preinvasive and invasive tissue in other lesions. In general, sampling is optimized if tissue is obtained from the areas of the invasion front...

Etiology of Fecal Incontinence

Other causes of anatomical disruption include iatrogenic factors such as anorectal surgery for hemorrhoids, fistulae, or fissures and proctitis after radiotherapy for prostate cancer. Postoperative fecal incontinence may affect up to 45 of patients after lateral internal sphincterotomy 6 , 8 , and 1 reported incontinence to flatus, minor fecal soiling, and loss of solid stool, respectively, 5 years later 23 . Incontinence following lateral internal sphincteroto-my does not appear to recover in the long term and appears to be an independent cause of fecal incontinence 24 . Similarly, the risk of fecal incontinence after fistulotomy ranges from 18 to 52 25 . The internal anal sphincter is occasionally and inadvertently damaged during hemorrhoidectomy 26 . The risk of developing fecal incontinence is about 28.3 in patients receiving closed hemorrhoidectomy by Ferguson technique 27 , which is now considered a gold standard for hemorrhoidectomy. Pelvic radiotherapy results in chronic...

Familial ovarian cancer

Families with a history of ovarian cancer are classified into three main groups (1) families with a history of ovarian cancer only (site specific), (2) families that develop either ovarian and or breast carcinoma, and (3) families with a history of non-polyposis colorectal neoplasms and endometrial, prostate and lung cancers (Lynch II syndrome) (Lynch et al., 1997). It is estimated that 5-10 of ovarian cancers result from a hereditary predisposition and that these are caused, in the vast majority of cases (90 ), by germline mutations in tumour suppressor genes, BRCA1 and BRCA2 (Miki et al., 1994 Wooster et al., 1995). The remaining 10 of familial cases are likely to be accounted for by the Lynch II syndrome.

Reproduction And Development

Each ejaculation releases 2 to 5 mL of semen, the fluid containing the sperm. Semen normally contains between 20 and 100 million sperm per milliliter. The sperm consists of a 5-p.m head containing the nucleus, a midpiece containing mitochondria, and a 55-p.m-long flagellum, or tail, which can propel the sperm at a speed of 1 to 4 mm min. The seminal vesicles and the prostate gland produce much of the liquid that makes up semen, which includes fructose to provide energy for the sperm, and alkalinity to counter the acidity of the vagina. When the male becomes sexually excited, nerves of the autonomic nervous system produce dilation of arterioles in the penis, causing blood to enter that organ faster than it can leave. This causes the erectile tissue to become engorged, causing an erection. The male then inserts the penis into the female's vagina in the act of copulation, injecting the semen by rhythmic contractions called ejaculations.

Complement activation and expression of complement regulatory proteins by malignant cells

Deposit complement fragments on the cell surface14'27-30. Numerous investigations have shown that various mechanisms for complement protection are upregulated in malignant cells and cell lines. These include, for example, an increased expression of the complement-regulatory proteins CD35, CD46, CD55, or CD59 in prostate cancer14'30-32. It has been observed that loss of one complement-inhibitory protein may be compensated for by increased expression of another. We and others have demonstrated that some malignant cells express ectokinases (cell bound extracellular protein kinases, PKs) with specificity for complement proteins, and we postulate that extracellular phosphorylation may be one mechanism by which malignant cells can attenuate or disarm the complement system. We have shown that the myeloid leukaemia cell line U937 releases a CK2-like PK that phosphorylates C3 and increases its cleavage by elastase into C3 fragments33. Similar results have been reported by Paas and coworkers34,...

Molecular Diagnosis Of Cancers

The molecular diagnosis of cancers relies on biomarker molecules that are produced in higher than normal levels either directly by tumor cells or by the response of the human body to the presence of cancers. Detection of the biomarkers in a patient's body fluids can serve as the first step in cancer diagnosis and provide critical information to doctors as to whether or not a biopsy is needed. Tumor markers can be proteins or hormones. Some classic tumor markers include a-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA). They are usually not very specific to a particular cancer as the level of one tumor marker can be elevated by more than one type of cancers. Another problem is that the presence of cancer does not necessarily cause a detectable level of tumor markers, especially in the early stages. Extra caution is thus needed in some cases to avoid false negatives.

C3 And Other Substrates For Prostasomal

Fibrinogen, which plays a role in tumor angiogenesis and metastasis, has also been found to be phosphorylated in the a-chain by PKA, PKC, and CK2 from all the prostasome preparations tested25. This observation is intriguing since fibrinogen has been implicated in playing a role in tumor angiogenesis and metastasis49, and it has been reported that several of its functions are affected by phosphorylation with various PKs46. In addition, vitronectin, which is involved in cell adhesion and cancer proliferation, is phosphorylated to a high degree by PKA and CK2 (Babiker et al., manuscript in preparation). As in the case when C3 is used as substrate, the phosphorylation of vitronectin was at least 10-fold greater with prostasomes derived from malignant cells than with seminal prostasomes. Suppression of fibrinolysis is important for metastatic prostate cancer, and phosphorylation of vitronectin has previously been reported to suppress fibrinolysis50.

Which symptoms are most relevant

The reliance on functional measures to evaluate disease severity can be misleading. In patients with benign prostatic hyperplasia, urodynamic studies help to quantify the degree of urinary obstruction, which causes a weak stream and hesitancy but this correlates poorly with the severity of urgency and nocturia, which are the more troublesome symptoms for the patient. Thus, urodynamic measures have limited value in assessing the symptomatic actions of an intervention.

Introduction And Clinical Issues

Carcinoma of the prostate is the most common noncutaneous cancer of men in the U.S. and is expected to affect approx 198,000 individuals in 2001 (1). It is estimated that more than 1 million men, over the age of 50 yr alive today, will die of this disease. The incidence of prostate cancer has increased sharply in the last decade, as serum prostate-specific antigen (PSA) testing has become widely available. This is primarily due to detection of clinically inapparent and early stage disease. Many early stage prostate cancers are relatively indolent, such that older men with disease often die of other causes. For example, the estimated lifetime risk of a man developing prostate cancer is 16 , however the risk of dying from the disease is about 3.4 (2). In early stages, most prostate cancers are curable with local therapy, either surgery or radiation. On the other hand, more extensively invasive tumors and metastatic disease are much more aggressive and in many cases lethal. A critical...

Which Tests in Which Condition

In Table 2, a proposed schema of an integrated diagnostic workup is presented. From a general point of view, ARM and rectal sensation assessment should be considered mandatory in almost every clinical condition, being widely performed in coloproctolog-ical laboratories, moderately time consuming, and allowing considerable useful information. However, even if ARM could show a pressure pattern of sphincter asymmetry, it is not enough to diagnose a sphincter lesion therefore, integration with other diagnostic tests is mandatory. Rectal sensation assessment should be useful to eventually identify alterations due to central or peripheral neuropathy, metabolic diseases (i.e., diabetes), or radiotherapy given for pelvic neoplasms (situated at the anus, rectum, prostate, bladder, or gynecological organs).

Gene Expression Analysis

Given the limitations in our present understanding of the basic biology of prostate cancer, many investigators have turned to the use of high-throughput gene expression studies to provide a more complete characterization of this disease. Most commonly, these efforts have been designed to identify genes that participate in the process of prostate cancer development, progression, and androgen independence, or to identify genes that may serve as clinically useful markers for diagnosis or prognosis. These studies have many inherent technical and analytical challenges, however initial efforts are providing reason for optimism that these challenges can be met. Fig. 1. Manual microdissection of prostate cancer to enrich for tumor cells. Photomicrographs depicting the complex histologic heterogeneity of prostate cancers and steps to manually dissect and enrich for tumor cells in samples for gene expression analysis. CaP designates prostate cancer. Fig. 1. Manual microdissection of prostate...

Initial Diagnosis And Evaluation

Genitourinary lesions are seen in 6 to 16 of pelvic and acetabular fractures (3,24,25). These lesions can be detected by a thorough genital and rectal examination as well as routine urinalysis. Urethral injury is indicated by perineal ecchymosis and edema, a high-riding or ballotable prostate on rectal examination, or difficulty passing a urinary catheter. There should be a low threshold for obtaining a retrograde urethro-gram or CT cystogram. An anuric patient must also be aggressively investigated. Though likely caused by insufficient hemodynamic resuscitation, there have been reports of a pelvic compartment syndrome causing anuria in some patients (26). This phenomenon is analogous to the abdominal compartment syndrome and causes postre-nal failure from compression of the ureters. These cases have been seen in patients with concomitant acetabular and severe pelvic injuries.

Biofilm and Medical Devices

Biofilm, as a matter of fact, is involved in acute and chronic infectious diseases and has been described in human and experimental pathology such as native valve endocarditis, otitis media, bacterial chronic rhinosinusitis, COPD, chronic urinary infections, bacterial prostatitis, osteomyelitis, dental caries, biliary tract infections, Legionnaire's disease and amyloidosis.

Functions of CEHC Metabolites

It has been appreciated for some time that y-tocopherol inhibits prostate cancer cell proliferation via down regulation of cyclin-related signalling. Recently, Galli and colleagues 43 demonstrated that y-CEHC exerts an inhibitory effect on cyclin DI expression, which closely reflects the decrease in cell growth. Importantly, the anti-proliferative effect on prostate cancer cells was achieved at concentrations of y-CEHC of between -0.1 and 1.0 M, levels that can easily be achieved with y-tocopherol supplementation 18,31 . Given the negative influence that a-tocopherol supplementation has on y-tocopherol concentrations, Galli and colleagues have highlighted that intervention studies with high dose a-tocopherol may have poor outcomes.

Results From Expression Profiling Studies Of Lung Carcinomas Reveals Distinct Adenocarcinoma Subclasses

And MCM6, was highest in SCLC, which is known to be the most rapidly dividing lung tumor followed by squamous cell carcinomas (Fig. 1D). The overexpression of PCNA and other proliferative markers, although not reported, were noted in the data of Garber et al. (30). However, unlike the other major lung tumor classes shown in our studies, lung adenocarcinomas were not defined by a unique set of marker genes in all three studies (29-31). Even in global tumor classification studies, the lung adenocarcinomas have few marker genes that accurately distinguish lung adenocarcinomas from other anatomically distinct primary epithelial tumors, such as prostate cancers (3,32).

Genetic Testing And Counseling In Hereditary Breast And Ovarian Cancer Syndrome

Breast, ovarian, colon, and prostate cancer Breast, ovarian, prostate, pancreatic, bile duct and gall bladder, stomach cancer, and malignant melanoma Soft-tissue sarcomas, breast cancer, brain tumors, acute leukemia, and other epithelial and mesenchymal tumors Breast cancer, thyroid cancer, and colonic neoplasms

Molecular And Structural Characteristics

PepTl is expressed primarily in small intestinal epithelial cells, the S1 (pars convoluta) segment of renal proximal tubules, hepatic bile duct epithelial cells, and the pancreas.13'35-38 Localization studies have also demonstrated that PepTl is expressed to a lesser extent in the kidney, placenta, and prostate, while in the small intestine, expression is maximal in the duodenum.35 Ogihara et al. further demonstrated PepTl localization to the apical plasma membrane of enterocytes in rats.39 Interestingly, PepTl expression decreases along the descending small intestinal segments, with ileal expression appearing to be lower than jejunal.35 Recently, Terada et al. demonstrated that PepTl is also relatively highly expressed in the stomach of cancer patients, although interindividual differences were apparent.40 Interestingly, histological results suggest that gastric PepTl may originate from intestinal metaplasia, which is characterized by the transdifferentiation of gastric epithelial...

Tumortargeted Anticancer Prodrugs And Their Biochemical Basis

One of the challenges in anticancer prodrug design is the identification of cancer-associated biochemical processes that can be utilized to release anticancer drugs from prodrugs. The obvious advantage of this approach is its high selectivity. Ideally, the cancer-associated biochemical processes do not or barely occur in normal cells. Two cancer-related features that have been extensively used for anticancer prodrug design are hypoxia and metastasis. Anticancer prodrugs based on the biochemical processes associated with hypoxia and metastasis have demonstrated high selectivity in killing cancer cells.3-5 In addition, enzymes with elevated activities in cancer cells, such as p-glucuronidase, prostate specific antigen, and cytochrome P450, have also been exploited for anticancer prodrug design. Further, the enzyme selected to activate an anticancer prodrug can be enhanced or delivered to tumor sites through gene expression gene-directed enzyme prodrug therapy (GDEPT) 6-8 or...

Why was aTocopherol Selected in Higher Organisms

In fact, in HMC-1 mast cells, the four tocopherols inhibited cell proliferation with different potency (8 > a y > P), and 8-tocopherol even led to apoptosis at higher concentrations 57 . Similar to that, induction of apoptosis by y- and 8-tocopherol, but not by a-tocopherol was recently shown with prostate cancer cells 58 , with mouse activated macrophages 59 and with mammary epithelial cells 60 . In prostate cancer cells it was suggested that the inhibition of dihydroceramide desaturase is involved in the induction of apoptosis 58 . A nascent body of epidemiological data suggests that y-tocopherol is a better negative risk factor for certain types of cancer and myocardial infarction than is a-tocop-herol 10 . This can be explained by activities of the tocopherols and their metabolites that do not map directly to their chemical antioxidant behaviour, but rather reflect anti-inflammatory, antineoplastic, and natriuretic functions possibly mediated through specific binding...

Epidemiology and Diagnosis

Have clinically enlarged prostate glands but no histological confirmation of BPH. Hence the term benign prostatic enlargement (BPE) is more appropriate in those in whom tissue diagnosis is not confirmed. BPH is one of the most prevalent conditions affecting men aged 40 and above. Histological studies have shown features of BPH to be present in the prostate of approximately 60 of men aged 60, and closer to 100 of men aged 80 and above. The only clear risk factors for the development of BPH are increasing age and the presence of circulating androgens. Clearly there are specific genetic patterns since histological BPH has been shown to be more prevalent in Afro-Caribbean than Caucasian populations. Asians tend to have a lower incidence still, but this is not maintained in migratory populations, also implying environmental factors in the development of BPH. Clinical BPH seems to run in families, although the genes responsible are yet to be identified. Diagnosis is based on clinical...

Lower Urinary Tract Symptoms

Clearly these symptoms are not disease-specific and a wide range of other disease states can cause LUTS. These include neurological conditions such as those mentioned above, malignancy (including prostate cancer and urothelial tumors), inflammatory conditions (including UTI, bladder stones, interstitial cystitis), polyuria (diabetes, congestive cardiac failure), and other causes of BOO, including bladder neck or external sphincter dyssynergia, urethral stricture (see Sect. 11.2.4) and severe phimosis. Some symptoms such as a poor urine stream are also found in conditions such as detrusor underactivity or detrusor failure, which do not necessarily have an obstructive component. The role of inflammation within the prostate has also been investigated recently, with several series showing that in tissue samples from prostates of patients in AUR, there is more inflammation than in prostates with BPH BOO, which in turn have more inflammation than normal prostates (Anjum et al. 1998...

An Intriguing Patent Problem

Infectious organism is often compartmentalized in particular tissues such as the tonsils and the prostate gland. An antibiotic that can penetrate and sustain therapeutic levels in those diseased tissues would actually be more useful than one that was largely in the blood serum. This concept is also true of cancer chemotherapy agents, which need to accumulate in the tumor cells rather than in the bloodstream or healthy tissue. Scientists at Sour Pliva in Zagreb, in what was then Yugoslavia,14 and at Pfizer in Groton, Connecticut,15 were able, almost simultaneously and concurrently to solve the tissue penetration problems and acid instability issues by cleverly adding an additional basic nitrogen atom in a Beckman rearrangement process followed by reduction. Almost simultaneously and the resulting blockbuster drug, azithromycin (VIII), is the subject of two U.S. composition of matter patents Although Pliva filed their patent more than a year earlier, Pfizer's patent was issued seven...

Suppression of Abnormally Activated Proinflammatory Signaling Pathways

The generation of ROS, tissue injury, or infection can create a state of inflammation, which is causally linked to tumorigenesis. Accumulating evidence suggests that chronic inflammation acts as a predispoding factor for cancers of different organs and tissues including stomach, colon, breast, skin, prostate, and pancreas 36-39 . Examples of inflammation-associated malignancies are the development of carcinomas of stomach, liver, gallbladder, prostate, and pancreas from Helicobacter pylori-induced gastric inflammation, chronic hepatitis, cholecystitis, inflammatory atrophy of the prostate, and chronic pancreatitis, respectively 40,41 . Proinflammatory mediators, such as cytokines, chemokines, prostaglandins (PGs), nitric oxide (NO), and leukotrienes, promote neoplastic transformation of cells by altering normal cellular signaling cascades 42 . For example, IL-6 and TNF-a, two proinflammatory cytokines, have been implicated in tumor promotion 43 . Moreover, the incidence and the...

What are the Effects on Gene Expression by Different Tocopherols

4) Tocopherols may be metabolized to bioactive compounds, which can bind to transcription factors and enzymes and modulate their activity. The metabolite of y-tocopherol, y-CEHC has natriuretic activity, inhibits cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis in activated macrophages and epithelial cells, two events that could change the cellular behavior and affect gene expression 76,77 . Recently, a metabolite of vitamin E, 2,2,5,7,8-pentamethyl-6-chromanol (PMCol), has been found to inhibit growth of androgen-sensitive prostate carcinoma cells, which is due to the potent anti-androgenic activity of this compound 163 .

Some Microbial Pathogens and Parasites Subvert the Role of Galectins as PRRs

A recent study identified galectin-1 as the receptor for the protozoan parasite T. vaginalis (Okumura et al. 2008) the causative agent of the most prevalent non-viral sexually transmitted human infection in both women and men. As an obligate extracellular parasite, establishment and persistence of T. vaginalis infection requires adherence to the host epithelial cell surface. Like Leishmania spp, T. vaginalis displays a surface LPG rich in galactose and N-acetyl glucosamine, which is recognized in a carbohydrate-dependent manner by galectin-1 expressed by the epithelial cells in the cervical linings, as well as placenta, prostate, endometrial, and decidual tissue, also colonized by the parasite (Okumura et al. 2008).

Ordered Categorical Data

In clinical trials it is not uncommon to have more discrete efficacy and safety endpoints with more than two categories. For example, although an adverse event can be classified into dichotomous groups, such as serious or nonserious adverse event, as a binary response, the intensity of an adverse event is evaluated according to the categories mild, moderate, or severe. Similar examples are seen in laboratory safety assessments. For example, we can assess the safety of a drug based on a particular laboratory parameter such as aspartate transaminase (AST) or alanine transaminase (ALT). Using the observed value of this particular parameter, subjects are usually classified into three categories below, within, and above the referenced laboratory normal range. For another example, each individual symptom score in the composite AUA symptom index for benign prostatic hyperplasia (BPH) presented in Table 9.1.3 consists of six categories. These six categories evaluate individual symptoms in an...

Urinary Tract Infection

Urinary tract infections are relatively rare in male patients, but they do represent a proportion of men attending with AUR. Many of these patients will have a degree of BOO and or LUTS, and some will be known to have incomplete bladder emptying. They are also commonly seen in BOO caused by stricture disease. The patient will typically give a history of LUTS, but associated with a short-term history of dysuria, offensive-smelling or dark cloudy urine, and suprapubic pain. Some patients may describe passing debris and others may have frank hematuria. They may have perineal pain if the prostate is infected, with associated pain on defecation. In some cases, one or both epididy-mides and testes may be affected also. The patient will usually volunteer this information, although it tends to be obvious on examination. On examination, the patient will typically complain of suprapubic discomfort on palpation, and in cases with prostatic involvement, the prostate will be exquisitely tender on...

Urothelial Malignancy

Bladder neoplasms themselves are rare causes of AUR. Large pedunculated tumors can act in a similar fashion to ball-valves, causing mechanical obstruction of the bladder neck, but this is very unusual. More commonly, a bladder tumor may invade the base of the bladder or the prostate, causing progressive stenosis of either the bladder neck or the prostatic urethra in the same way as prostatic malignancy can lead to BOO.

Comparison between Genotypes in Laboratory Populations

Lab studies rarely analyze the quantitative patterns of cancer onset in the way that I did in the previous sections. Instead, the analysis typically emphasizes the qualitative pattern of whether certain combinations of mutations cause earlier or later cancer onset than do other combinations. For example, Figure 8.6 compares the survival of two mouse strains (Kwabi-Addo et al. 2001). One strain has the TRAMP genotype that predisposes mice to develop prostate cancer. The other strain carries the same genes that predispose to prostate cancer, but also is heterozygous at the Pten locus, with one allele knocked out. Pten mutations are common in many cancers, including cancers of the prostate. The figure shows that the Pten heterozygotes progress more rapidly to cancer.

Decreased Radiation Survival of Ras Transformed Cells After FTI277 Treatment

Radiosensitization of murine prostate tumor cells by FTI-277 treatment was also observed. Survival after 2 Gy irradiation of H-Ras plus v-myc transformed mouse prostate tumor cells was reduced from 0.85 to 0.36 when cells were treated with 5 y'M FTI-277 prior to irradiation. This demonstrates that radiosensitization can be obtained not only in

Anatomy Of The Anorectum

Fig. 2. (A) Normal rectal endoscope ultrasound (RUS) imaging of seminal vesicles and bladder in a male patient. (B) Normal RUS imaging of prostate. (C) Normal RUS imaging of IAS EAS. Fig. 2. (A) Normal rectal endoscope ultrasound (RUS) imaging of seminal vesicles and bladder in a male patient. (B) Normal RUS imaging of prostate. (C) Normal RUS imaging of IAS EAS. Because RUS has been useful in evaluating for cancer invasion into the surrounding regional organs, it is important, in males, to examine the bladder, seminal vesicles, prostate, and IAS and EAS (Fig. 2A-C) and in females, to examine the bladder, uterus, vagina, and IAS and EAS.

Real World Applications Research and Clinical

The same principles applied to a separate study in which a novel xenotropic gamma retrovirus was detected in prostate tumor biopsies of men with a mutant variant of the RNASEL gene. Integration sites and full-length genomes were subsequently cloned and the virus was demonstrated to be replication competent, thus validating the microarray result. Again, the broad-spectrum nature of the DNA microarray was critical to the success of the project, since there were no preconceptions that such a virus might be a candidate, given that no xenotropic gamma retrovirus had been previously observed in a human subject.

Criterion 3 Response To Hormone Ablation Prl Synthesis by Mammary Cells

In human BC, the lack of correlation between clinical data and in vitro responses to PRL may be explained, in part, by the observation that BC cells themselves synthesize and secrete this hormone. Although hPRL was first characterized as a 22-25-kDa pituitary (pit) hormone, in recent years, synthesis of PRL and PRL-like molecules by a variety of tissues other than the pit has been reported (98). In humans, circulating levels of all pit hormones, except for PRL, become undetectable following surgical removal of the pituitary. Circulating levels of PRL remained at 30-80 of the presurgical levels for as long as 10 mo in BC patients who received a total hypophysectomy (99). Patients given bromocriptine plus somatostatin persistently maintained low levels of circulating bio-active PRL (83). These data could result from other PRL-like molecules circulating in the blood, but it was also possible that PRL itself was produced by peripheral tissues. Both normal tissue and tumors appear to...

Clinical Experience

A limited number of studies have reported in abstract form on the feasibility of using susceptibility weighted DCE-MRI to examine the prostate gland (Noseworthy et al. 1999 Gibbs et al. 2001). Their observations show that it is possible to demonstrate first pass, signal lowering effects using echo-planar T2*-weighted sequences and that limited tissue characterisation is possible. That is, significant differences have been noted between peripheral gland and tumour with respect to signal intensity change (Gibbs et al. 2001). However, no systematic differences between central gland and tumour enhancement values have been observed. We too have performed a limited number of T2* weighted DCE-MRI studies and have found that prostate cancer has relatively low blood volume levels compared to pericapsular and neurovascular bundle vessels and other tumours such as breast and rectal cancers. Occasionally, strong susceptibility effects can be recorded from prostatic tumours (Fig. 12.1). No studies...

Perspectives and conclusion

A randomized, controlled chemoprevention trial of selenium in familial prostate cancer rationale, recruitment, and design issues. Urology 57 (Suppl. 1) S182-4. GreenwaldP (2001). Clinical trials of breast and prostate cancer prevention. JNutr 131 (Suppl.), S176-8. Nabhan C and Bergan R (2001). Chemoprevention in prostate cancer. Cancer Treat Res 106 103-36. Neal DE, Leung HY, Powell PH, Hamdy FC and Donovan JL (2000). Unanswered questions in screening for prostate cancer. Eur J Cancer 36 1316-21. Stephan C, Jung K, Lein M, Sinha P, Schnorr D and Loening SA (2000). Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer. Cancer Epidemiol Biomarkers Prev 9 1133-47. Wolk A, Andersson SO, Mantzoros CS, Trichopoulos D and Adami HO (2000). Can measurements of IGF-1 and IGFBP-3 improve the sensitivity of prostate-cancer screening Lancet 356 1902-3.

Clinical manifestation

Papules or pustules evolve into purulent, verrucous, or ulcerative nodules or plaques, characterized by sharp and heaped-up borders with centrally located granulation tissue and exudate pulmonary findings signs of acute pneumonia, including fever, night sweats, wheezing and dyspnea signs and symptoms of chronic pneumonia last for 26 months, including weight loss, night sweats, fever, cough, and chest pain osteo-lytic bone lesions prostatitis or epididymi-tis

Hypercalcemia of Malignancy

Hypercalcemia is the most common paraneoplastic syndrome of malignancy (Fojo 2005). Among genitourinary malignancies, it is most frequently identified in association with RCC (3 -25 ) (Zekri et al. 2001 Walther et al. 1997 Papac and Poo-Hwu 1999 Skinner et al. 1971). In comparison, hypercalcemia is an uncommon manifestation of prostate cancer and transitional cell carcinoma (Coleman 1997). The incidence of hypercalcemia in RCC correlates with the stage of the primary tumor as well as with the presence or absence of bone metastases (Fahn et al. 1991). Hypercalcemia typically occurs late in the course of disease and has demonstrated independent significance as a poor prognostic factor in patients with advanced RCC (Motzer et al. 1999).

Tumour Volume and Staging

Tumour volume is a recognised prognostic indictor in prostate cancer. A disparity between tumour volume on conventional T2-weighted MRI and pathology is well recognised tumour volume is often underestimated (Bezzi et al. 1988 Kahn et al. 1989 McSherry et al. 1991 Quint et al. 1991 Schnall et al. 1991 Sommer et al. 1993 Brawer et al. 1994 Lencioni et al. 1997). This occurs because microscopic tumour in the peripheral zone is not always visible on T2-weighted images (Carter et al. 1991 Outwater et al. 1992 Lencioni et al. 1997) and poorly differentiated prostate cancer can grow by infiltration, thus causing little architectural distortion or alteration in signal intensity (Schiebler et al. 1989). Limited literature data is available comparing DCE-MRI with T2-weighted MRI to depict tumour volume (Jager et al. 1996), which suggests that subtraction DCE-MR images may be marginally better than T2-weighted MRI at depicting the full intraprostatic extent of tumours (Fig. 12.9). There is also...

Radiotherapy Planning

The choice of appropriate treatment for patients with prostate cancer remains controversial. The most commonly offered treatments include observation only, radical prostatectomy, radiotherapy, hormone ablation treatment, or a combination. Treatment selection is guided by patient age and general condition, tumour stage and histological grade, serum PSA, and patient and physician preferences. External beam radiotherapy treatment failure is often attributed to the need to limit radiation dose because of the sensitivity of surrounding neighbouring structures including the bladder, bowel and hips. Escalation of dose is one of the major strategies currently being explored to improve local control and overall survival in prostate cancer. Using intensity-modulated radiotherapy (IMRT), a complex 3D dose distribution can be produced to match areas of disease selectively avoiding normal tissue (Nutting et al. 2000 LeibeL et al. 2002). IMRT may be used to escalate dose in excess of 80 Gy to the...

Monitoring Response to Treatment

Hormone ablation is the preferred treatment choice for patients with advanced disease, but is also used in patients before radiation therapy or prostatectomy. The response of patients to treatment can be assessed by digital rectal examination, by changes in serum PSA levels, TRUS and MRI (Pinault et al. 1992 SheareR et al. 1992 Chen et al. 1996 Nakashima et al. 1997 Padhani et al. 2001). Clinical evaluations and imaging studies all show significant reductions in both glandular size and tumour volume. Reductions of 10 -52 in prostate glandular volume and 20 -97 in tumour volume have been reported (Pinault et al. 1992 Shearer et al. 1992 Chen et al. 1996 Nakashima et al. 1997 Padhani et al. 2001). On MRI, the central gland decreased in signal and became more homogenous with treatment and seminal vesicle atrophy has also been noted (Secaf et al. 1991 Chen et al. 1996 Nakashima et al. 1997 Padhani et al. 2001). As a result, hormonal ablation also reduced the number of MR detectable...

Tissues Procurement And Processing

The OSE, from which ovarian carcinomas arise, represents a minute fraction of cells in the ovary (for e.g., see Fig. 2 in ref. 4). This contrasts with carcinomas that arise in other organs, such as the prostate, where normal epithelial cells constitute a greater fraction of the tissue. The small amount of OSE poses special challenges for comparing the transcription of genes in the normal state, where there is a limited amount of RNA available, vs transcription in carcinomas, where cancerous epithelial cells tends to be more plentiful, particularly in late stage disease. Many studies have not taken these features of ovarian biology into account and have simply used whole ovarian tissue as a normal control to compare transcriptional profiles in ovarian carcinomas. Clearly, the results of these studies must be interpreted cautiously. A more biologically relevant approach has been to isolate OSE brushings from the surface of freshly procured ovaries. Samples are literally brushed, or...

Malignant Spinal Cord Compression

Spinal cord compression is a debilitating complication of metastatic cancer identified in 5 -14 of cancer patients (Patchell et al. 2005). Among urologic malignancies, it is most commonly seen with prostate cancer (PCa), which accounts for 9 -24 of cases overall (van der Linden et al. 2005 Flynn and Shipley 1991). In fact, PCa is the second most common cause of malig Prostate cancer is the most commonly diagnosed noncutaneous malignancy in American men today and the second most common cause of cancer death (Jemal et al. 2005). Screening through the use of serum prostate-specific antigen (PSA) has led to both stage and risk migration such that the proportion of patients presenting with metastatic disease has fallen from 14.1 in 1988 to 3.3 in 1998 (Paquette et al. 2002). While distant metastatic disease is now uncommon at presentation, an additional 70 of patients with locally advanced PCa can be expected to develop metastases in follow-up (Coleman 1997). Skeletal metastases are the...

Class Discovery And Correlates Of Disease Histology

Molecular signatures of carcinomas from diverse anatomic sites. To identify tumor class-specific classifiers, we sought genes whose expression was uniformly high among carcinomas of a specific anatomic site, and uniformly low among carcinomas of all other anatomic sites or histologies (i.e., one-vs-all depicted in panel A). This was achieved using the Wilcoxon rank sum test, which tests the null hypothesis that gene expression in one tumor class is no different from gene expression in any other tumor class. The genes in each class that had significant p scores represent those that dispute the null hypothesis and define those that are most different among tumor classes. One hundred of the Wilcoxon-selected genes from each tumor class, depicted in panel B, were subjected to a prediction accuracy test, in which each of the genes was tested for its ability to discriminate one tumor class from all other tumor classes, using a support vector machine (SVM)-learning algorithm....

Identifying Which Genes Are Differentially Expressed Between Classes

Example 7.4 (Genes showing differential expression in prostate cancer versus. BPH in the Luo Prostate Cancer dataset Bonferroni adjustment). The data are from cDNA microarrays performed on 16 prostate cancer specimens and 9 BPH specimens see Appendix B for details. In Example 7.1, we considered differential expressions for clone 139331, and obtained a p-value of 0.038 from a t-test. This is one of 6500 clones on the microarray. If we restrict attention to clones for which there were data from at least 3 prostate cancer specimens and 3 BPH specimens, this reduces the number of analyzed clones to 5854. The Bonferroni-adjusted p-value for clone 139331 is p 0.038 x 5854 > 1, so with control for the multiple comparisons there is no evidence that this gene is differentially expressed. Forty-seven genes have unadjusted p-values < .05 5854 8.54 x 10 6, so their Bonferroni-adjusted p-values are < 0.05.

Major Molecular Targets of Selected Dietary Chemopreventive Phytochemicals to Induce Apoptosis

Prostate cancer cells PC-3 cells Gastric cancer cells HL-60 cells HL-60 cells One of the key transcription factors that regulate expression of hypoxia-responsive genes is the transcription factor hypoxia inducible factor (HIF), which acts as a master regulator of cellular oxygen homeostasis 83 . The HIF is induced at early stages of carcinogenesis and often correlated with increased angiogene-sis in progressing tumors 80 . The HIF family of transcription factors includes four members HIF-1a, HIF-1 , HIF-2a, and HIF-3a. While HIF-1a and HIF-2a are overexpressed in many human cancers, a splice variant of HIF-3a acts as an inhibitor of HIF-1a 79,81 . An increase in HIF-1a protein has been recorded in cancers of breast, prostate, lungs, and pancreas 81 . The induction of HIF-1a has also been observed in spontaneously generated epidermal squamous cell

Bladder Outlet Obstruction

Tients placed on watchful waiting will eventually require transurethral prostatectomy (TURP) for symptomatic progression or urinary retention (Whitmore et al. 1991). Likewise, surgical and nonsurgical therapies directed toward prostate cancer may predispose to urinary retention. Bladder neck contracture (BNC) is reported in 1.3 -27 of patients after radical prostatectomy and 1.5 -22 of patients will develop urinary retention following prostatic brachytherapy (Anger et al. 2005 Stone and Stock 2002).

Sexual Differentiation

Prostate prostate The urogenital sinus and genital tubercle are the primitive structures that give rise to the external genitalia in both sexes. Masculinization of these structures to form the penis, scrotum, and prostate gland depends on secretion of testosterone by the fetal testis. Unless stimulated by androgen, these structures develop into female external genitalia. When there is insufficient

Stem Cells Tissue Renewal

The second section describes the shape of cell lineages in renewing tissues. Many tissues that renew frequently have a clear hierarchy of cell division and differentiation. Rare stem cells divide occasionally, each division giving rise on average to one replacement stem cell for future renewal and to one transit cell. The transit cell undergoes multiple rounds of division to produce the various short-lived, differentiated cells. New stem cell divisions continually replace the lost transit cells. I review the stem-transit architecture of cell lineages in blood formation (hematopoiesis), in gastrointestinal and epidermal renewal, and in sex-specific tissues such as the sperm, breast, and prostate.

Urinary Retention After Brachytherapy

Urinary retention affects 1.5 -22 of men within a median of 2 months following prostatic brachytherapy (Stone and Stock 2002 Flam et al. 2004). Identified preimplant risk factors include an International Prostate Symptom Score above 20 and a prostate volume larger than 35 cm3 (Terk et al. 1998 Gelblum et al. 1999). Attempts to reduce the risk of urinary retention with prophylactic a-adrenergic blockade (Flomax) have thus far been unsuccessful (Elshaikh et al. 2005). The majority of cases respond to conservative measures such as catheter drainage plus or minus a-block-ade, those that do not require TURP. According to a recent meta-analysis, up to 8.7 of brachytherapy patients undergo TURP after implantation however, large contemporary series report a lower rate of 1.1 2 (Stone and Stock 2002 Allen et al. 2005 Kollmeier et al. 2005). Urinary incontinence, while uncommon after TURP performed for BPH (1 -5 ), is reported in up to 70 of brachytherapy patients who undergo TURP (Foote et al....

The general population

The main difference between hypothetical and retrospective studies is that the 'general population' can be offered a 'gene test for breast cancer', as opposed to a test for a faulty family gene. This expression was used by Ulrich et al. (1998), who also offered men 'a gene test for prostate cancer', in a random telephone poll in Washington State, USA, in 1995-96. They found that 76 of women and 83 of men said that they would definitely or probably take this test, for which no fee was mentioned. The sample included 6.9 of participants who had a personal history of (non-specific) cancer, and no assessment was made of the family history reported by 5 of men and 9 of women. It was noted that the very-well-educated women showed less interest in this hypothetical test than those who were less educated.