Natural Cures For Prostate Cancer

The 21 Day Prostate Fix

21 Day Prostate Fix written by Radu Belasco is a healthier alternative to drugs and invasive medical procedures. Radu Belasco is an early prostate problem sufferer, with a family history of prostate pain, problems and cancer. Using a unique system of natural remedies, he fixed his prostate problems and wrote them in his smash hit eBook The 21 Day Prostate Fix. It is about miraculous herbs and fruits from all over the world. These unique foods have the power to cure your prostates inflammation in record time and shrink it to a healthier size. Also, you will learn how to concoct the miracle elixir that will not just cleanse your prostate, but also burn body fat. Aside from these, youll get topnotch information on nutrition, so you can keep your prostate healthy and your sex drive at its peak. Plus, youll learn other health conditions that might be contributing to your prostate issues, so you can also remedy them and get your body in its best shape ever.

The 21 Day Prostate Fix 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...

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...

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...

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...

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

Salvage External Beam Radiation

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...

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...

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....

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...

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...

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...

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...

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...

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

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...

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...

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.

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...

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...

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.

Discharge And Home Healthcare Guidelines

Pregnancy, pelvic inflammatory disease, and infertility. Untreated infections in men can result in nongonococcal urethritis (NGU), epididymitis, or prostatitis. Infections in either gender can result in proctitis, lymphogranuloma venereum (LGV), and, potentially, infertility and sterility.

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...

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,...

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...

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.

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).

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...

Epidemiology and Diagnosis

The population incidence of prostate cancer has dramatically increased since the advent of PSA testing. It now represents the most common cancer in males, although this includes many cancers not requiring intervention other than monitoring, and is among the leading causes of cancer death in men. This does not mean that the true incidence of prostate cancer is higher, but that more cases are being diagnosed than previously. Most men presenting acutely with symptoms of UR of any cause will most likely have BPH, but several large population studies have shown that a significant proportion of these will have clinically undetectable foci of prostate cancer. This proportion increases dramatically with age (Johansson et al. 2004 Kessler and Albertsen 2003). The patient may present in exactly the same manner as the patient with BPH, i.e., in AUR or less commonly CUR. On initial assessment, it maybe evident that they are under investigation for, or being treated for, prostate cancer. DRE may...

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).

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...

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...

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).

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.

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.

Effect Of hCg On Pcd Gene Expression

The mammary glands of hCG- and DMBA + hCG groups of animals showed elevated expression of testosterone repressed prostate message 2 (TRPM2) and interleukin-1 -converting enzyme (ICE) transcripts as early as 5 d after initiation of treatment (70-d-old groups) Their values remained elevated at all subsequent time-points tested, and up to 20 d posttreatment (125-d-old groups) (43). The hormonal treatment induced an increase of 2.5-5-fold and 1.5-5-fold in the expression of TRPM2 and ICE transcripts, respectively. Maximal induction was observed in the animals sacrificed at the ages of 85 and 105 d. DMBA treatment alone, on the other hand, did not modify, or even slightly reduce, the expression of TRPM2 and ICE transcripts, since the values found were similar to those of the respective control groups. The product of the proto-oncogene, bcl2 and one of its family members, bcl-XL, are known to play a role in promoting cell survival and inhibiting apoptosis, and expression of bcl-XS is...

Preoperative Assessment

During a surgeon's initial experience with the LRP, patients may be selected with low-grade, low-stage cancers that do not require laparoscopic pelvic lymph node dissection. This helps limit the operating time, which is likely to be prolonged during the early patients. The first 25 patients we selected had prostate-specific antigen (PSA) less than 10 and a Gleason of 6 or below. Factors that can adversely affect the prostatic dissection include obesity a large ( 80 g) or small prostate (

Screening versus Diagnostic Tests

Examples of routine population screening currently used in the health care field include Pap smears for women to predict their risk for cervical cancer, mammograms for women to predict their risk for breast cancer, the PPD skin test to predict exposure to tuberculosis mycobacterium (TB) in health care workers, and the prostatic antigen screening (PSA) test for men to predict their risk for prostate cancer.

Is There a Relationship between Cancer Associated DNA Hypomethylation and DNA Hypermethylation

Hypomethylation of some DNA sequences and hypermethylation of other sequences has been found in rat hepatocarcinomas and human breast, colon, and prostate adenocarcinomas.45,76 72 Given the prevalence of both of these types of changes in cancers when they have been studied individually, they probably coexist in the vast majority of cancers but simply have not yet been documented to be simultaneously present. Hypermethylation of the GST P promoter and hypomethylation of LINE-1 repeats were found in some of the same prostate adenocarcinomas but no significant association was observed between these two types of epigenetic changes in this kind of cancer.41 Recently, in collaboration with Peter Laird and Emerich Fiala, we have shown that global DNA hypomethylation, satellite DNA hypomethylation, hypomethylation of a promoter, and hypermethylation of CpG island-promoters are present concurrently in many Wilms tumors.75 Global hypomethylation was significantly associated with Sat2...

Human Chorionic Gonadotropin

The association of secretion of human chorionic gonadotropin with prostate cancer has been reported in one case. Broder et al. have analyzed prospectively 16 patients with stage D adenocarcinoma for the presence of human placental lactogen (hPL), placental alkaline phosphatase (PAP), and human chorionic gonadotropin (hCG). Ectopic production of hCG was found in one of the 16 cases. Serial serum hCG levels in that patient mirrored his course more reliably than concomitant acid phosphatase levels. Serum estradiol, testosterone, the hCG-alpha subunit, hPL, and PAP were not elevated. There was a minimal elevation of serum follicle-stimulating hormone (FSH). There were no elevations of the other placental proteins in ten evaluable cases. A retrospective evaluation of serum bank specimens from 47 patients with prostatic carcinoma revealed no elevation of the placental proteins hPL, hCG-beta, and hCG-alpha. In this peculiar case, the ectopic origin of the hormone secretion was not documented...

Neuromuscular and Cutaneous Syndromes

Vere dermatomyositis associated with a low-grade, low-stage prostate cancer was reportedly cured by radical perineal prostatectomy (Tallai et al. 2006). Only a few cases of prostate cancer associated with dermatomyositis have been reported, all of which had advanced disease (Subramonian 2000 Joseph et al. 2002). In one case, the diagnosis was made at autopsy and in the two other cases presented with bladder outflow obstruction and skin lesions.

Is DNA Hypomethylation Like DNA Hypermethylation Sometimes Associated with Tumor Progression

In a prostate cancer study, LINE-1 hypomethylation had a highly significant relationship with lymph node involvement for prostate adenocarcinomas.41 Recently, we have shown that hypomethylation of both Sata centromeric and Sat2 juxtacentromeric repeats is significantly associated with tumor grade and decreased survival in primary ovarian carcinomas (M. Ehrlich and M. Widschwendter, unpub. results). In collaboration with Louis Dubeau, we also demonstrated that there is a significant association of malignant potential and hypomethylation of Sat2 DNA in the juxtacentromeric heterochromatin of chromosomes 1 and 16 in a comparison of benign ovarian cystadenomas, low malignant potential tumors, and carcinomas.46 Moreover, there was also a significant association of Sat2 hypomethylation with global hypomethylation of the genome in these neoplasms, as determined by Southern blot analysis for satellite hypomethylation and high-performance liquid chromatography of DNA digested to...

Dissection Of Endopelvic Fascia

The endopelvic fascia is incised on the right and the lateral aspect of the prostate exposed. Fig. 7. The endopelvic fascia is incised on the right and the lateral aspect of the prostate exposed. dissection with a laparoscopic Kittner, to eliminate overlying fat. The superficial dorsal venous complex is coagulated and divided before the puboprostatic ligaments are exposed (Fig. 6). The endopelvic fascia is incised with endoshears just lateral to the prostatic surface along the lateral pelvic wall (Fig. 7). Precise bipolar electrocoagulation assures hemostasis. The lateral surface of the prostate is separated from the levator muscle with a laparoscopic Kittner dissector. The puboprostatic ligaments are divided close to their attachment to the pubic bone. The apex of the prostate is visualized before the dorsal venous complex is ligated.

Ligation Of The Dorsal Venous Complex

The urethral catheter is replaced with a 24-French curved metal bougie. Angulating the tip of the bougie posteriorly, places the dorsal venous complex on stretch. The dorsal venous complex is ligated (Fig. 8) with a figure-of-eight stitch with 0 or 2 0 polyglactin on a 36-mm CT-1 needle (Ethicon Inc., Somerville, NJ). The curve of the needle is made parallel to the curve of the pubic arch and the needle is passed posterior to the dorsal venous complex with the right-handed needle holder. A second back-bleeding stitch can be applied on the anterior surface of the prostate to identify the base of the prostate to help with bladder neck dissection. The author does not typically use the second stitch because the vessels can be controlled during the bladder neck dissection. The dorsal venous complex is not divided until later in the operation.

Bladder Neck Dissection

With experience, the demarcation between the base of prostate and the bladder neck can be accurately determined. The margin of the perivesical fatty tissue helps identify the plane of dissection (Fig. 9). The difference between the floppy bladder wall and the solid prostatic surface can be visualized. Movement of a urethral bougie or a Foley catheter within the bladder can also help. The prostatic base is separated from the bladder neck with blunt and sharp dissection. We use the Harmonic scalpel during this dissection. The dissection is continued posteriorly on either side of the prostatic urethra (Fig. 10). The anterior bladder neck is incised in the midline with endoshears, exposing the metal bougie. Coagulation is not used during this maneuver for the potential for coagulating the urethra in the presence of the urethral metal bougie. After the anterior bladder neck is divided, the metal bougie is brought out through this opening, and the base of prostate is rotated anteriorly....

Control Of Prostatic Pedicles

The prostatic pedicles are exposed by holding the seminal vesicle and vas anteriorly (Fig. 12). We use the Harmonic scalpel for division of the prostatic pedicle, because it has less lateral thermal damage and may be less likely to damage the neurovascular bundles. The periprostatic fascia on the lateral aspect of the prostate is carefully incised and the neurovascular bundle dissected off the prostatic capsule. Completion of the division of the prostatic pedicles is accomplished without injury to the neurovascular bundles by maintaining the dissection close to the prostate. The nerve-sparing transection of the prostatic pedicle on the opposite side is similarly performed before the base of the prostate is free. Remnants of the Denonvilliers fascia are divided to free to posterior aspect of the prostate. Fig. 12. The seminal vesicles are held up to place the prostatic pedicles (Arrow) on stretch. The pedicles are controlled close to the prostate with bipolar coagulation or Harmonic...

Division Of The Dorsal Venous Complex

The deep dorsal venous complex that was previously ligated is divided using endoshears or the Harmonic scalpel. Manipulation of the urethral bougie helps displace the prostate posteriorly and place the dorsal venous complex on stretch. The previously placed stitch may become dislodged during the division of the dorsal venous complex. Bleeding from the complex is controlled with a combination of increasing the intraabdominal pressure and precise bipolar coagulation of the bleeding vessels. Occasionally a figure-of-eight hemostatic stitch is applied with 2-0 polyglactin on a 36-mm CT-1 needle or 26-mm SH needle (Ethicon Inc., Somerville, NJ).

Division Of The Urethra

The prostatic apical dissection is completed to maximize the length of the urethral stump, without violation of the apical tissue. The anterior wall of the urethra is divided with the endoshears or a laparoscopic knife, and the metal bougie within the urethra exposed. The metal bougie is then delivered through this opening, and the posterior urethral wall divided. The rectourethralis muscle is divided, without damage to the neurovascular bundles. The same procedure is repeated on the opposite side. The prostate along with the seminal vesicles is then entirely freed, provided the posterior dissection was previously completed. Occasionally, remnants of the Denonvillier's fascia will need to be divided. Care should be taken during this dissection to avoid injury to the rectum. The prostate is placed in a 10-mm Endocatch bag (Fig. 13), which Fig. 13. The prostate is placed in the 10-mm Endocatch bag. Fig. 13. The prostate is placed in the 10-mm Endocatch bag.

Drain Insertion Port Site Closure And Specimen Extraction

A 10-French Blake drain is inserted through a right lateral 5-mm port site and placed in the region of the urethrovesical anastomosis. A 0 polyglactin suture is inserted across each 10- 12-mm port site for closure, with a Carter-Thomason suture passer and Pilot 10- 12-mm suturing guide (Inlet Medical). After closure of the 10- 12-mm port sites and removal of the 5-mm trocars under vision, the prostate that was previously placed in an Endocatch bag (U.S. Surgical Corp. Fig. 15) is extracted through the umbilical Early Results Following Laparoscopic Radical Prostatectomy Early Results Following Laparoscopic Radical Prostatectomy

Improving Gene Expression

Replacement of repressive viral sequences with similar sequences from heterologous retroviruses and the minimization of CpG dinucleotides within viral promoters has lessened, but not eliminated, silencing of transgene expression. 12 Silencing of viral promoters has sparked an interest in the use of gene-specific regulatory sequences to direct transgene expression. Logg et al. have reported prostate-specific gene expression which persists over time by incorporation of the prostate-specific probasin promoter into RCR vectors, demonstrating the benefits of improved gene expression and tissue-specificity achieved with an authentic human promoter. 13 Incorporation of gene-specific locus control regions (LCR) into retroviral vectors confers integration site-independent and tissue-specific vector gene expression. 14 Additionally, the use of authentic genomic elements such as scaffold or matrix attachment regions and insulator elements has been reported to improve transgene expression when...

DNA Methylation in Urological Cancers

Urological cancers are a diverse group with different alterations of DNA methylation. In all urological cancers, DNA hypermethylation of specific genes has been described. In contrast, methylation of repetitive sequences is often diminished, resulting in decreased overall methylation levels ( global hypomethylation ). Altered imprinting is also found. Tes-ticular tumors are derived from more or less immature germ cells whose methylation patterns they often reflect. Subtypes can be distinguished by the extents of global hypomethylation and hypermethylation. Renal cell carcinomas typically display hypermethylation restricted to specific genes important for tumor development and progression. By comparison, methylation patterns are more severely disturbed in prostate and bladder cancers in which hypermethylation of multiple genes coexists with genome-wide hypomethylation. Causes of altered methylation may also differ. Hypermethylation could be incidental in renal cancers, but is more...

An Overview of Urological Cancers

The more common urological malignancies befall older people. This is most evident for prostate carcinoma which is now the most prevalent lethal cancer of older men in industrialized countries. This adenocarcinoma is derived from the secretory epithelium of the gland. Organ-confined cases can be cured by surgical removal of the prostate (prostatectomy) or by radiotherapy. Since testosterone is essential for the proliferation of normal and many transformed prostate cells, many locally advanced and metastatic tumors respond to androgen deprivation, although this treatment is not curative. Because of the difficulty to clinically distinguish organ-confined from nonorgan confined disease, curative treatment fails in up to 40 of the patients. Therefore goals of prostate cancer research are not only to detect prostate carcinoma early, but also to identify those patients who will definitively benefit from curative treatment options. cystectomy. Thus, as for prostate carcinoma, the challenge is...

Fecal Incontinence Associated with Radiotherapy for other Cancers

Several studies have shown that radical radiotherapy for both prostate cancer and bladder cancer is associated with an increased risk of fecal incontinence 21-24 . After 2 years, bowel frequency, fecal urgency, and fecal incontinence were increased in 50 , 47 , and 26 of patients, respectively 24 . These functional deficits were associated with a reduction in resting anal pressures, squeeze pressure, and rectal compliance 24 .

Planning of Definitive Treatment

Patients with suspected bladder or urethral injuries (patients with pelvic fractures, high riding prostate on rectal examination, patients with blood at the urethral meatus and who are unable to void) need to undergo an evaluation of the lower urinary tract, but these injures are not considered life-threatening in themselves. Retrograde urethrocy-stography is generally recommended by trauma management algorithms, but in scenarios of mass casualties it should be postponed. In these cases the minimal acceptable treatment will be one gentle trial of bladder catheterization or up-front insertion of a suprapubic cystostomy followed by transfer of the patient to the surgical ward and deferred radiological evaluation. Bladder injuries, both following blunt or penetrating trauma, are usually associated with other severe injuries (McAninch and Santucci 2002) and thus deserve a prioritizing surgical approach. The patients are usually unstable, as blunt bladder injuries are often encountered...

Applications in Biology and Medicine

Gazi et al. (46) have imaged freeze-dried prostate cancer (PC-3) cell cultures, demonstrating chemical differences in the phospholipid composition of fractured and nonfractured cells. A TOF-SIMS study of different cell lines revealed that multivariate analysis can distinguish nonmalignant and malignant prostate cell lines derived from different metastatic sites, providing valuable information on the biochemical basis of metastasis (E. Gazi et al., unpublished data, 2005). Fartmann et al. (47) have imaged freeze-fractured, freeze-dried osteoblasts and MeWo cancer cell cultures using TOF-SIMS and, to aid quantification of elemental ions, laser postionization of sputtered neutrals.

Global View of DNA Methylation Alterations in Urological Cancers

So far, the data from these more comprehensive methylation analysis techniques largely confirm that urological cancers differ considerably in the extent of methylation changes, as suggested by analyses of individual genes. Analysis of DNA methylation in germ cell tumors by RLGS has confirmed the fundamental difference between seminomas and nonseminomas, i.e., global hypomethylation in seminomas vs. hypermethylation of multiple CpG-islands with less extensive hypomethylation in nonseminomas.10 A comparison of different urological malignancies by a bisulfite-modification based chip technique showed the smallest difference between tumor and normal tissue in the kidney,94 as expected. Conversely, wide-spread and progressive deterioration of methylation patterns was confirmed by different methods in prostate and bladder carcinoma. DNA hypermethylation in bladder cancer may affect up to 7000 CpG-islands96 in spite of almost all classes of CpG-containing repetitive sequences being...

Causes of Altered DNA Methylation in Urological Cancers

The causes of altered methylation may be distinct in different cancers (Fig. 2). In some cancers, apparently aberrant methylation may in fact largely reflect the methylation pattern of the affected stem cell. Thus, different germ cell tumors display methylation patterns at imprinted genes corresponding to distinct stages of germ cell development.8,10,14 Conversely, failure to set up proper methylation patterns of mature cells may underlie blocked differentiation. Clear-cell renal carcinomas may exemplify a group of cancers displaying a limited number of methylation changes. Some of these could be caused by incidental errors for which there is strong selection during tumor development because they lead to inactivation of crucial tumor suppressor genes such as VHL. Others such as CA9 hypomethylation62 may be secondary to alterations in transcriptional activators. In contrast, advanced prostate and bladder cancers are typically characterized by severely disturbed DNA methylation patterns...

Plots of Cancer Incidence at Different Times and Places

The following plots show cancer incidence and acceleration patterns at different time periods and in different countries. In some cases, the acceleration plots fluctuate between countries because of the nature of the data, which may have small numbers of cases at early or late ages. Thus, it is best to focus only on the broad trends in the acceleration plots, particularly those patterns that recur in different years and in different locations. For example, prostate cancer shows a remarkably strong and linear decline in acceleration beginning in midlife (Figure A.2). Some cancers show midlife peaks in acceleration, for example, colon and bladder cancer (Figure A.4). All Breast Prostate Lung Figure A.2 Age-specific acceleration for different time periods and geographic locations. Male cases shown by solid lines female cases shown by dashed lines. Data description as in Figure A.1. The prostate acceleration is shown on a different scale, to accomodate the very high acceleration that...

Screening and Diagnosis

Of the zone of provisional cartilaginous calcification (94). DXA scan shows decreased BMD however, the condition is indistinguishable from osteoporosis. Case reports and small studies have reported that bone scans and technetium scintigraphy show increased uptake at sites of fractures and pseudofractures (117,118). This finding, however, can be confusing, especially in prostate cancer patients who develop osteomalacia. Bone scans often show hot spots, which are interpreted as bone metastasis. If these findings occur with concurrent hypophosphatemia, phosphaturia, decreased 1,25(OH)2D, and normal PTH, thay are more likely to represent osteomalacia than bone metastasis.

Metastases Involving Colon

Transverse colon and splenic flexure. Cancer of the prostate may directly invade the lower rectum via Denonvillier's fascia. More frequently, prostate cancer invades the seminal vesicles then the rectosigmoid junction (60). Cancer of the cervix may directly invade the anterior wall of the rectosigmoid junction. On barium enema examination extrinsic mass effect (Fig. 25) cannot be distinguished from direct invasion if only a smooth-surfaced mass effect on the colonic wall is seen. However, spiculation of the colonic contour and tethering of mucosal folds (61) implies direct invasion of the colonic wall

Extended Lymph Node Dissection

Though obturator lymph node dissection is satisfactory for evaluation of prostate cancer, an extended lymph node dissection is usually required in cases of bladder, ure-thral, and penile cancer. An extended pelvic lymph node dissection may sometimes be carried out in patients with prostate cancer and negative obturator nodes that are highly suspected of having metastatic local disease (such as in cases of clinical T3 disease and or markedly elevated PSA 60 (11). For extended pelvic lymphadenectomy the fan or inverted U array as previous described is preferred because it allows for more assistance with retraction.

Synthetic LHRH Analogue in Solution

Analogue Chemical

The pivotal role that LHRH and its analogues play in the modulation of reproductive functions have attracted considerable scientific interest because of their usefulness in the treatment of endocrine-based diseases such as prostate cancer, breast cancer, endometriosis and precocious puberty. Several LHRH agonists, represented by Leuprolide ( DLeu6, desGly' -LHRH-ethylamide), are currently used in the treatment of the above conditions. The goal of this research is the synthesis and conformational analysis of a LHRH analogue, such as Aib6, desGly10 -LHRH-ethylamide in order to gain valuable insights on bioactive conformation and use these for the design of further analogues. This LHRH analogue was synthesized by the solid phase methology on a AM resin via Fmoc tBu methology. ID and 2D NMR experiments were carried out in 2-2.5mM solution of Aib6, desGly' -LHRH ethylamide in DMSO-d . The average structure of LHRH analogue was calculated from the family of the 20 models and refined using...

Male factor infertility

Painful ejaculation, dysuria, haematospermia, tenderness of the epididymis and prostate. Confirmation is by semen culture, urethral swabs and the presence of more than 1 million polymorphonuclear leucocytes per ml of semen. Theroleof subclinical infection in thegenesis of maleinfer-tility is unclear and there is little consensus on appropriate criteria for diagnosis. Retrograde Transurethral prostatectomy

Are There Tumor Specific DNA Hypomethylation Profiles Like the Tumor Specific DNA Hypermethylation Profiles

In contrast to increased DNA methylation in cancer, cancer-associated hypomethylation of DNA frequently involves repeated DNA elements. The most well-documented interspersed repeat displaying hypomethylation in various cancers are the LINE-1 sequences.38-41 Most of these human retrotransposon- derived repeats are probably incapable of retrotransposition.42 They are up to 6 kb in length and comprise about 15 of the human genome. In a study of 73 urothelial carcinomas, about 54 of tumors were hypomethylated in 10 of the LINE-1 repeats compared to normal bladder.43 Hypomethylation of a much lower copy-number retrotransposon, HERV-K proviruses, significantly paralleled that of LINE-1 repeats.43 In another study by the same group, 53 of 32 examined prostate adenocarcinomas were found to have LINE-1 hypomethylation.41 However, no LINE-1 hypomethylation was detected in 34 renal cell carcinomas compared to normal bladder.43 Therefore, LINE-1 hypomethylation appears to vary in frequency...

Treatment of Additional Pelvic Injuries

Arcuate Lines

From a lower abdominal midline incision, the dome of the bladder is opened and the lesion repaired intravesically with 3 0 absorbable sutures. To avoid secondary complications such as urinary incontinence or erectile dysfunction (ED), injuries of the bladder neck, the proximal urethra, the prostate, or the vagina must be excluded. These injuries should be carefully reconstructed intravesically via the bladder dome incision. If the vagina is affected, a formal repair from a transvaginal approach is necessary.

Hypothesis of Pathophysiology

Pelvic radiotherapy can play an important role in the pathogenesis of functional disturbances of continence 40-42 . In patients treated with pelvic radiotherapy for prostate, gynecological, bladder, anal, or rectal cancer, the incidence of FI is 3-53 43 . This is despite progress in irradiation procedure. The patient's age and presence of anal symptoms are described as risk factors. In their review article, Putta and Andreyev 43 assessed that rectal cancer seems to present the highest incontinence rate, probably due to the additive effects of surgery to those of radiotherapy. In this work, only 8-56 of incontinent patients were found affected in their quality of life. The authors interpreted this finding because patients do not feel or seem ill, will not report symptoms, as they believe they are inevitable consequences of radiotherapy treatment, of being old, or that there is nothing that can be done . With the aim of investigating bowel dysfunctions, Peeters et al. 44 sent a...