Prostate Gland Protection and Natural Prostate Health

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.

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Indications and Contraindications for Permanent Prostate Implantation

This group includes those with prostate-specific antigen (PSA) levels < 10ng ml and with Gleason scores < 7. Although not essential for staging, pre-treatment magnetic resonance imaging (MRI) of the prostate with endorectal coil may be helpful in the assessment of the integrity of the prostatic capsule as well as the geometry of the gland. Such information may be invaluable in the planning aspects of transperineal implantation (TPI), as well as determining whether a patient is a candidate for the procedure. The prostate gland size should preferably be less than 60 cm3. With larger gland sizes, the pubic arch may interfere with needle placement to the anterolateral portions of the gland, resulting in inadequate coverage of the target volume. In addition, larger glands require more seeds and activity to achieve coverage of the gland with the prescription dose, resulting in a concomitant increase in the central urethral doses and potentially increasing the risk of urinary...

Cpg Island Hypermethylation Changes During Prostate Cancer Initiation And Progression

Prostate Cancer Disease Progression

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...

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...

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...

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...

Future Directions in Prostate Brachytherapy Integrating Biologic Based Imaging Information into Treatment Planning

Reports from investigators at the University of California San Francisco have indicated that magnetic resonance spectroscopy (MRS) may provide reliable information regarding the ability to more precisely localize malignant zones within the prostate gland 40 . MRS takes advantage of the significantly higher choline levels and significantly lower citrate levels in regions of cancer compared to regions of benign prostatic hypertrophy and normal prostatic epithelium. Detection was especially enhanced when magnetic resonance imaging was combined with MRS, with specificity and sensitivity of detection of abnormal zones within the prostate as high as 91 and 95 , respectively. While it is well recognized that prostate cancers are often multifocal, MRS may provide valuable information to highlight regions in the prostate that contain the most densely populated zones of biologically active disease. This information could then be used to design more optimal radiotherapy treatment plans and...

High Intensity Focused Ultrasound HIFU for the Treatment of Localized Prostate Cancer

We evaluated 85 patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU) for biochemical disease-free rate, safety, morbidity, and predictors of biochemical outcome. A total of 85 patients underwent HIFU with the use of Sonablate and with at least 12 months of follow-up. The median age was 70 years (range, 54 to 86 years), and the median preoperative prostate-specific antigen (PSA) level was 10.9ng ml (range, 3.39 to 89.6). The median length of follow-up was 20 months (range, 6 to 56). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Biochemical failure developed in 27 (23 85) of the patients. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10ng ml, 10.01 to 20.0ng ml, 20.01 to 30.0ng ml,and more than 30.0ng ml were 97 ,75 , 33 , and 0 , respectively. Final follow-up sextant biopsies...

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...

Bladder and prostate gland

Inflammation of the prostate causes a variety of urinary symptoms, which can include perineal and penile pain, as well as and a dull suprapubic or ill-defined rectal discomfort. These symptoms form part of the chronic pelvic pain syndrome. This syndrome can also affect women. In a minority of cases a diagnosis of interstitial cystitis can be made (see below).

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...

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...

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....

Cryoablation as a Primary Treatment for Localized Prostate Cancer

Prostate cancer presents a spectrum of disease ranging from relatively nonaggressive, low-risk disease to very aggressive, high-risk disease. Therefore, assessment of treatment outcome is best done by stratifying patients into those with low-, intermediate-, and high-risk disease, as done by d'Amico et al. 13 . Low risk is defined as T1-2a, Gleason score of 6 or less, and PSA less than 10ng ml. Intermediate risk is defined as one of the following stage higher than T2a, Gleason score greater than 6, or PSA greater than 10ng ml. High risk is defined as two or more of the following stage higher than T2a, Gleason score greater than 6, and PSA greater than 10ng ml. Figure 3 (reprinted with permission from Katz and Rewcastle 44 ) shows a range of outcomes for the three risk groups from published papers with a minimum 5-year follow-up. These results show excellent outcomes, particularly for patients with higher-risk disease, which is notoriously difficult to treat successfully. Figures 4 and...

Prostate Surgical Procedures

Prostate surgery is usually performed for either benign prostatic hyperplasia (BPH) or prostate cancer. Common surgical techniques employed include transurethral resection of prostate (IURP), transurethral incision of prostate (IUIP), transurethral laser vaporization, and transurethral microwave thermotherapy. Surgical procedures of the prostate typically involve direct manipulation of the urinary outflow tract. Iherefore, common complications include hematuria, clots with subsequent urinary retention, urethral strictures, and urinary tract infections. Some patients experience obstructive or irritative voiding symptoms that may include incontinence, hesitancy, dribbling, urgency, and frequency. I2.,3and 4

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...

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...

Prostate Cryoablation

The incidence of prostate cancer in Japan has risen dramatically in the past four decades. This increase, along with the advent of prostate-specific antigen (PSA) screening, has meant that an increasing number of patients are diagnosed at an early stage of the disease, when cure is possible. Currently, radical surgery and external-beam radiation are considered the standards of care for curative treatment of localized disease. Although many patients are helped by these treatment approaches, both are associated with potentially serious complications. Cryoablation is another option in the treatment of localized prostate cancer. The current technique utilizes real-time transrectal ultrasound (TRUS) for guidance and monitoring, multiple cryoprobes, a urethral warming device, multiple thermocouples, and two freeze-thaw cycles. Seven-year outcomes are now available for cryosurgical treatment of primary disease, and they indicate an efficacy similar to that of radical surgery and...

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

Robotic Surgery Assisted by the ZEUS System

Aesop Robotic Surgical System

Urology has continuously embraced novel technologies, such as shockwave lithotripsy, lasers, and laparoscopy, that reduce patient morbidity yet maintain an excellent standard of care. To potentially increase the clinical applicability of laparoscopy, robots that enhance operative performance have recently been introduced for a variety of laparoscopic procedures, such as laparoscopic radical prostatectomy, pyeloplasty, and nephrectomy. Although the introduction of robotics has generated excitement, its benefits in large series of patients remain largely unknown. In this review, we mainly focus on one of the available robotic systems, the ZEUS system, and describe its features, including its advantages and limitations. We also review the emerging clinical applications of the ZEUS robotic system, including our recent cases of laparoscopic radical prostatectomy assisted by ZEUS, and the future potential of robotics in urology. Keywords. Robotic surgery, ZEUS, Laparoscopy,...

Complications Safety and Oncological Efficacy

Because ultrasound energy is not completely transferred to thermal and mechanical energy (cavitation effects), there is a possibility that cells will mobilize, causing cancer cells to enter the circulation and promote metastasis. In various studies, no evidence of metastases has been reported. Chapelon and associates 47 determined the impact of HIFU on the development of metastases of experimental prostate cancer. In the control population, 28 of the animals developed distant metastases, whereas in the HIFU-treated animals, this percentage dropped to 16 . Similar findings were reported by Oosterhof and colleagues 48 using a T-6 Dunning R3327 rat prostate cancer subline. Metastases were seen in 23 of the HIFU-treated animals, as compared with 25 of the sham-treated animals (difference not statistically significant). From these data, it can be concluded that HIFU applied to cancer tissue does not accelerate the development of distant metastases.

Robot Assisted Da Vinci Urologic Surgery An Emerging Frontier

Robotic urologic surgery is an interesting and new development in the field of urology that has tremendous possibilities for progress in the future. Reports from various centers worldwide of complex urologic procedures in humans performed with robotic assistance have documented their safety, efficacy, efficiency, and feasibility. This review attempts to define the incorporation of robotics into laparoscopic urologic surgery and also reflects on our experience with over 900 cases of robotic surgery. Most of the recent reports pertaining to robotic surgery have been in the domain of localized cancer of the prostate (radical prostatectomy), bladder cancer (radical cystectomy and urinary diversion for muscle-invasive bladder cancer), kidney surgery (nephrectomy, donor nephrectomy, and pyeloplasty), and adrenal surgery. There are also reports in other areas of urology such as male infertility. Keywords. Robotics, Urology, Prostate, Bladder, Kidney, Adrenal Introduction ment to...

Merging of Endourology and Oncology Endourooncology

There is a growing need to bring together endourological approaches and sound oncological principles to achieve minimally invasive cancer control in urologic malignancies. Reduced treatment morbidity and quality-of-life issues are becoming more valued by both patients and physicians. In this chapter, we present an overview of the most recent advances in endoscopic, laparoscopic, and energy-based ablation techniques for the treatment of upper-tract transitional-cell carcinoma, renal-cell carcinoma, prostate cancer, adrenal tumors, and germ-cell testicular tumors. The merge between endourology and urologic oncology will undeniably revolutionize our approach to urologic malignancies. Keywords. Renal cell carcinoma, Transitional cell carcinoma, Prostate cancer, Testicular cancer, Laparoscopy (T1-T2) renal neoplasia in many institutions around the world. Other energy-based technologies, including cryosurgery, radiofrequency ablation, and high-intensity focused ultrasound (HIFU),...

Materials and Methods HIFU Equipment

For this study, we used a modified second- and third-generation device called the Sonablate 200 and 500 (Focus Surgery, Indianapolis, IN, USA) in 35 and 50 patients, respectively. A treatment module includes the ultrasound power generator, multiple transrectal probes of different focal depths, the probe positioning system, and a cooling system (Fig. 1). The transrectal HIFU probes use proprietary transducer technology with low-energy ultrasound (4 MHz) for imaging of the prostate and for the delivery of high-energy ablative pulses (site intensity, 1300-2200W cm2). The single piezoelectric crystal alternates between high-energy ablative (1-4sec) and low-energy (6-12 sec) ultrasound for a total cycle of 7-16sec. Before the start of treatment, the operator uses longitudinal and transverse sonograms by imaging of the prostate and selects the prostate tissue volume to be ablated by a set of cursors on these images. The probe houses a computer-controlled positioning system that directs each...

Acute Urinary Retention

Acute urinary retention (AUR) is a known risk that can occur immediately after prostate brachytherapy. Locke et al. 20 reported the experience from Seattle in 62 consecutive patients followed after prostate brachytherapy. In that prospective study, all patients were evaluated with baseline AUA scores, urodynamic assessments, and prostate-volume assessments. The patients were contacted at monthly intervals to obtain accurate follow-up information. Catheterization was required in 42 (26 of 62) of the patients. The incidence of urinary retention was 34 at one week, 29 at one month, and 18 at three months from completion of the procedure. Among many variables analyzed, a prostate volume > 33 cm3 was an independent predictor of AUR. Other reports in the literature have indicated much lower incidences of AUR after prostate brachytherapy. Crook et al. 21 studied 150 patients treated with prostate brachytherapy between 1999 and 2001. In this group, 13 (n 20) developed AUR. Of these 20...

Sequelae of LDR Brachytherapy Acute and Late Toxicity

Transient urinary morbidity related to radiation-induced urethritis or prostatitis represents the most common side effect after prostate brachytherapy. The symptoms include urinary frequency, urinary urgency, and dysuria. Because of the varying definitions of toxicity reported in the literature, it is difficult to quantify the true risks of treatment-related toxicities after seed implantation. Many reports have not described toxicity outcomes using actuarial methods, and in some studies only severe toxicity is reported while more moderate complications (grade 2) are not reported. In addition, various implantation techniques, seed activity, and source distribution patterns used by different centers have contributed to the wide range of side-effect profiles reported after prostate brachytherapy.

History of Modern Cryoablation

Transurethral freezing and an open perineal approach that exposed the apex of the prostate. This approach allowed for separation of the anterior rectal wall from the prostate, thereby significantly reducing the risk of rectal injury 7 . Although the rectum was protected, this approach resulted in significant urinary dysfunction and the development of urethrocutaneous urinary fistulas. However, it did provide sufficient cancer control to prompt further development. A transperineal percutaneous approach was reported in 1974 by Megalli et al. 8 . These authors used a single 6.3-mm sharp-tipped liquid-nitrogen cryoprobe. This cryoprobe was introduced through a small skin incision in the perineum and was guided into the prostate by digital palpation. Freezing, however, continued to be monitored primarily by digital transrectal palpation. Despite the ability of cryoablation to effectively ablate tumor tissue, surgeons remained unable to accurately place the cryoprobes and control the extent...

Brachytherapy Treatment Planning Standard Techniques and New Developments

The standard technique used for prostate brachytherapy planning is a preplanning method. With this approach, transrectal ultrasound imaging is obtained several days to weeks before the planned procedure to measure the prostate volume. A computerized plan is generated from the transverse ultrasound images, which will in turn demonstrate the optimal location of seeds within the gland to deliver the prescription dose to the prostate. Several days to weeks later, the implantation procedure is performed, and needles are placed through a per-ineal template according to the coordinates calculated by the preplan. Needle placement is performed under ultrasound guidance, and the radioactive seeds are individually deposited within the needle with the aid of an applicator or with preloaded seeds on a semirigid strand containing the preplanned number of seeds. Although a preplanning implantation technique has been associated with excellent clinical outcomes, there are some limitations to this...

HIFU High Intensity Focused Ultrasound and Gene Delivery

HIFU also has the potential to assist in the noninvasive spatial regulation of gene transfer into the targeted tissue 31 . In contrast with low-pressure ultrasound, HIFU waves can be focused on different anatomical locations in the human body, including the prostate, kidney, and bladder, without significant adverse effects. Huber et al. showed that HIFU can significantly enhance the transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 in vitro and in vivo after direct plasmid injection without marked side effects (Fig. 4) 32 . This enhancement could be demonstrated by means of histological analysis, as well as by quantitation of gene expression using ELISA assay. It was also indicated that ultrasound interaction mechanisms other than heat are probably responsible for transfection enhancement. Nevertheless, focused ultrasound-induced gene transfection could be favorably combined with the thermal effects of focused ultrasound occurring at increasing intensities,...

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...

Robotic Surgery in Urology

Robots designed for surgery have three potential advantages over humans three-dimensional spatial accuracy, reliability, and the capability of achieving much greater precision. Surgical robots were initially used in neurosurgery and orthopedics. Surgical robots were used for stereotactic framing in neurosurgery 15 , and a robot was used to cut and ream bones with great precision for the fitting of joint prostheses or for replacing ligaments 16 . In urology, robotic systems have been developed to assist with intraoperative percutaneous renal access 58 , transperineal prostate biopsy 59 , radioactive seed delivery into the prostate 60 , and transurethral resection of the prostate 61 . Kavoussi and coworkers compared the control of the endoscope by AESOP with control by the assistant, and they reported the usefulness of this robotic camera control system 62 .

Technique

The technique in salvage treatment is similar to that in primary treatment. Generally speaking, the prostate gland is somewhat smaller and the blood flow to the gland is not as good as in the primary cases. As a result of this, the freezing process tends to proceed more rapidly, and the operator must bear this in mind. Also, because the anterior rectal wall has frequently been adversely affected by the radiation therapy, particular care has to be taken to ensure that the anterior rectal wall is not frozen during treatment. There is definitely a higher risk of developing urethrorectal fistulas after salvage cryoablation than after primary cryoablation 39, 45, 46 . In some patients, it may not be possible to bring the thermocouples to -40 C before the iceball begins to invade the anterior rectal wall. In these case, the preservation of the anterior rectal wall must be the primary consideration. The use of a thermocouple placed in the external sphincter has been shown to significantly...

HIFU Procedure

Radical Prostatectomy

All patients were anesthetized by epidural or spinal anesthesia and were placed in the lithotomy position. A condom was placed over the probe, degassed water was used to inflate the condom, which was covered with ultrasound gel for close coupling of the ultrasound probe to the rectal wall, and the probe was inserted manually into the rectum. The probe was fixed in position by an articulating arm attached to the operating table. After selection of the treatment region of the prostate from the verumontanum to the bladder neck, the treatment was started. Transrectal probes with focal lengths of 2.5, 3.0, 3.5, 4.0, and 4.5 cm were used according to the size of the prostate, as determined by transrectal ultrasound (TRUS), with larger glands requiring longer focal lengths. The treatment continued layer by layer (10-mm thicknesses) from the apex to the base (Fig. 3). Usually, three successive target areas (anterior, mid-part, and base) were defined to treat the whole prostate (Fig. 4). After...

Results

Seventy-one patients were treated in one HIFU session, 13 patients in two sessions, and 1 patient in three sessions, for a total of 100 procedures in 85 patients (1.2 sessions per patient). The reasons for repeat HIFU treatments were as follows six patients were retreated because of short on (2sec) or long off (8 to 12 sec) intervals four patients were retreated for residual tumor two patients were hemilaterally treated on the right or left lobe of the prostate two patients needed a repeat session to treat the whole prostate because of larger prostate size (37.9 and 50.6 ml) and one patient was retreated because of machine trouble. The median operating time and hospitalization was 150 min (range 30 to 356 min) and 4.0 days (range 3 to 20). A gradual reduction in prostate volume occurred in all patients. The gland size decreased from an initial volume of 25.6 mL (range 9.3-68.8 mL) to a final median volume of 12.5 mL (range 2.7 to 55.2) (p < 0.0001) in average 6.5 months (range,...

Urinary Tolerance

In general, almost all patients after prostate brachytherapy develop acute urinary symptoms such as urinary frequency, urinary urgency, and occasional urge incontinence. Depending upon the isotope used, these symptoms often peak at one to three months after the procedure and subsequently gradually decline over the ensuing three to six months. Most patients significantly benefit from the use of an alpha-blocker, which ameliorates such symptoms in 60 to 70 of patients. Brown et al. 27 reported on 87 patients who underwent prostate brachyther-apy and whose urinary symptoms were carefully assessed after the procedure. Urinary effects such as frequency, nocturia, and dysuria generally developed two to three weeks postimplantation and peaked three to four months after the procedure. A gradual decline in the severity of symptoms was noted in approximately 75 of the patients during the first 12 months. In this series, 41 of the patients experienced acute grade 2 or 3 urinary morbidity, with 6...

Erectile Function

Although reports have noted relatively low rates of impotence after prostate implantation 33 , this endpoint was only evaluated at two years after implantation. There is a paucity of long-term data critically examining this issue. Stock et al. 33 also reported gradually declining erectile function with continued follow-up after brachytherapy in 89 patients. However, the median follow-up in that report was only 15 months. It appears that impotence rates after TPI are probably underestimated in the literature. With longer follow-up observations, Zelefsky et al. 3 reported that whereas the incidence of impotence two years after implantation was 21 , the rate increased to 42 five years after the procedure. Although the development of erectile dysfunction after prostate brachyther-apy is likely to be a multifactorial phenomenon, the influence of the dose of radiation to the penile bulb may be an important variable. Merrick et al. reported a 61 six-year actuarial rate of erectile...

Conclusion

For many reasons, transrectal HIFU appears highly attractive as a minimally invasive treatment for localized prostate cancer. HIFU treatment requires no incision or puncture, it is bloodless, it can be performed on an outpatient basis, and repeatable added even though patients with local recurrence have already been treated with radiation therapy. In addition, the option of HIFU may be more attractive to the patient who wants to avoid postoperative incontinence and erectile dysfunction for his quality of life. The small number of patients and the relatively short follow-up period in our series limit our ability to draw any definitive conclusions. We believe that the data we present here suggest that HIFU may be a useful treatment option for patients with localized prostate cancer. Our goal to be able to treat patients with localized prostate cancer by HIFU within one hour in an outpatient clinic under local anesthesia.

Morbidity

With any cancer therapy, there is a fine balance between aggressive disease eradication and increased treatment-induced morbidity, with a corresponding negative impact on QOL. This balance applies to any of the treatment modalities available for localized prostate cancer. As the technique of prostate cryoablation is evolving, and as experience with this modality is increasing, the morbidity reported has steadily declined. Sexual dysfunction and bladder and bowel changes have the greatest negative impact on the lives of prostate cancer patients following treatment for their disease. Historically, urorectal fistula formation was a major concern with prostate cryoablation. Advances in technology and technique have virtually eliminated this concern with cryoablation. Among four recent publications 14,24-26 , only one found rectal complications 14 , with a fistula rate of less than 0.1 . Incontinence in these series ranged from 1.3 to 5.4 , and postoperative impotence ranged from 82.4 to...

Statistical Analysis

All statistical analyses were performed using commercially available software (StatView 5.0, Abacus Concepts, Berkeley, CA, USA). The chi-squared test assessed the correlation between preoperative and postoperative parameters. The distributions of biochemical disease-free survival rates were calculated according to the Kaplan-Meier method, and the log-rank test was used to compare curves for groups. Age, clinical stage, Gleason score, volume of the prostate, neoadjuvant hormone therapy, and pretreatment serum PSA was analyzed to estimate the prognostic relevance in a multivariate Cox proportional-hazards regression model. All p values less than 0.05 reflected statistically significant differences.

Long Term Outcome

Long-term follow-up is essential to fully judge the efficacy of treatment for localized prostate cancer.Ten to 15 years of follow-up data is considered optimal, and follow-up information of this duration is available in a small number of series for both radical surgery and external-beam radiation. At this time, 7-year results are the longest available in the literature for cryoablation 14 . Until 10-year results are available, the case for long-term efficacy of cryoablation cannot be conclusively made. Nonetheless, the 7-year results have demonstrated a durable efficacy equivalent to that of other therapies for low-risk disease. In the treatment of intermediate- and high-risk disease, cryoablation may actually confer a superior benefit compared with other treatment modalities. What can explain this favorable comparison The higher the Gleason score, the greater the likelihood of a positive margin at the time of radical prostatectomy 31 . Similarly, a higher Gleason score is associated...

Telesurgery

The vital ingredient of successful telerobotic surgery lies in the speed of transfer of information from operator to robot and back again 1 . Time delay can significantly affect remote surgical performance, and if the lag time (operator-robot-operator) is more than 700 ms, the operator is unable to learn to compensate. With current high-speed connections, the delay for Earth-to-Earth connection may be of only 200 to 300 ms, which is hardly noticeable. The first telerobotic operation was performed by an Italian group, headed by Professor Rovetta 24 of Milan, who successfully performed a telerobotic prostate biopsy in 1995.

Salvage Cryoablation

The treatment of locally recurrent prostate cancer following radiation therapy (either external-beam radiotherapy or brachytherapy) with cryoablation is frequently referred to as salvage cryoablation. Radiation therapy, in the form of either external-beam radiotherapy or brachytherapy, is used to treat large numbers of men with localized prostate cancer in North America each year. Unfortunately, 25 to 93 of these patients have a relapse of their disease, many with isolated local recurrences 34,35 . The treatment options are limited salvage radical prostatectomy carries a high risk of significant complications, and hormonal therapy is palliative and not curative 36-38 . Over the past 10 years, cryoablation has been increasingly used in this group of patients. Although early reports were discouraging due to the high rate of significant complications 39-41 , more recent reports validate the benefit of this treatment, with significantly less morbidity than that originally reported 42, 43...

Discussion

In 1995, Madersbacher et al. reported the effect of HIFU (using the old Sonab-late 200) in an experimental study of 10 cases of histologically demonstrated, hypoechoic and palpable, localized prostate cancer 18 . The organs were subsequently removed in 2 weeks. The entire carcinoma had been ablated in two removed prostates, but in the other eight cases, a mean of 53 of the cancer tissue had been destroyed according to histopathological examination. In January 1999, we began HIFU treatment for localized prostate cancer using a modified Sonablate 200 device. Major improvements of our device included a reduction in the HIFU exposure cycle from 16sec (4 on 12 off) to 9 sec (3 on 6 off), which reduced the treatment time by 44 and the introduction of a novel transducer and electronics that splits a single ultrasound beam into multiple beams (termed split beam) to cover a larger tissue volume per exposure. The single beam has a focal region of 2mm x 2mm x 10mm (volume, 40mm3), while the...

The Future

Unlike radical prostatectomy and external-beam radiation, cryoablation can be performed in a targeted area of the prostate. Of necessity, the entire gland is removed during radical prostatectomy. Likewise, the entire gland is irradiated during external-beam radiation. Although most prostate cancers are multifocal One such study was reported recently by Onik et al. 50 . The side of the prostate with demonstrable cancer was aggressively frozen, and a more conservative freeze was performed on the opposite side. In this way, a reduction in morbidity and preservation of the neurovascular bundle were facilitated. All patients A variant of the cryosurgical ablation methods described above involves the use of gas-driven (rather than deep-frozen liquid gas) probes that are smaller in diameter. Termed Seednet, 12 to 17 of the 17-gauge (1.47-mm) cryoneedles are placed into the prostate through a brachytherapy-like template. The largest study published to date involved 106 patients with localized...

Quality of Life

QOL outcome is increasingly being recognized as an important component in evaluating treatment for prostate cancer. In patients for whom different treatments are deemed to be similarly effective, QOL outcomes frequently will determine the choice of treatment from the patient's point of view. We have recently published the long-term outcomes of QOL assessment in patients treated with cryoablation. The results indicate that the outcomes are comparable or superior to QOL outcome following other treatments 27, 28 . Two validated and commonly used measuring instruments were used to follow the patients the Colon Functional Assessment of Prostate Cancer (FACT-P) and the Sexuality Follow-up Questionnaire (SFQ).At 1 year following treatment, patient QOL measurements had returned to pretreatment levels in all areas, with the exception of sexual functioning. At 3 years posttreatment, baseline levels remained constant, with no delayed-onset morbidity.The major change observed at 3 years was the...

Patient Selection

It has become apparent over the past 10 years that careful patient selection is vitally important to ensure optimal outcomes. Initially, patients with bulky, localized recurrent cancers and those with significantly elevated PSA levels were treated with the hope of salvaging their condition. As pointed out by Katz and Rewcastle 44 and by Chin et al. 43 , selection criteria that increase the likelihood that the recurrence will be confined to the prostate are of paramount importance. Therefore, patients with PSA levels less than 10ng ml and with PSA doubling times greater than 1 year are those best suited for this procedure. Similarly, patients with nonbulky disease are more likely to be treated successfully. Higher Gleason scores prior to radiation or at the time of recurrence indicate a greater likelihood of distant disease and subsequent failure of this localized treatment. Patients who have had a prior transurethral resection of the prostate (TURP) should be advised of the 75 to 80...

Assessment of the Painful

Hip Adductor Tendonitis Mri

A thorough physical examination, including a baseline temperature and vital signs, should be performed. Patients who complain of hip pain and are febrile need to be worked up aggressively in order to rule out hip pyarthrosis. Though hip infections are rare in skeletally mature individuals without a prior history of hip surgery, one must always consider this diagnosis, especially with the growing number of immuno-compromised patients. Usually, pyarthrosis can be ruled out with a careful history and exam, but radiographs and laboratory studies are additionally helpful. Occasionally, a hip aspirate is required to eliminate the possibility of joint sepsis. Other rare causes of hip discomfort and fever include psoas abscess, prostatitis, pelvic inflammatory disease, and urinary tract infection. adnexal mass can often be palpated on exam, and an ultrasound can confirm this diagnosis.13 A patient with a femoral pseudoaneurysm can present with vague anterior groin discomfort that can be...

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...

Appendix Information on Recommended Measures Child Health Questionnaire

A variety of studies attest to the adequate reliability and validity of the questionnaire. In particular, the symptom scales have shown sensitivity to clinical change. The questionnaire was developed by an international group of researchers. In consequence, careful attention was given to ensuring that the questions had a similar meaning across languages and cultures. The modules for colorectal and prostate cancer are forthcoming 120 . each has an additional subscale containing items related to the cancer, its symptoms, or its treatment. A number of site-specific scales, including the FACT-C (colorectal) 135 and the FACT-P (prostate), 33 are available. 33. Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ (1997) Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument. Urology 50 920-928 47. Hara I, Kawabata G, Miyake H, Nakamura I, Hara S, Okada H, Kamidono S (2003) Comparison of quality of life following...

Reflexology In Disorders Of The Reproductive System

Zone Therapy Reflexology

PROBLEMS OF MEN HyjJfocele Varicocele Enlarged prostate Impotence Oligospermia Prostatic enlargement is a common disorder of elderly males. Prostate is a plum-sized gland that surrounds the first part of the urethra. An enlarged prostate may press upon the urethra to cause (a) an obstruction to the flow of urine which comes out drop-wise, (b) retention of some urine in the bladder due to which there is a constant urge to urinate, (c) sometimes, burning or pain while passing urine. (B) Specific treatment of the genital organs The genital organs (the penis, the testicles, the prostate) are located on the inner sides of the two heels (see the adjoining diagram).

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...

Therapeutic applications of monoclonal antibodies

In the early days of mAb development, it was anticipated that the potentially high specificity of mAbs would mean that they could be employed not only to identify small metastatic populations of tumor cells but also to kill them, either alone or in conjunction with a cytopathic agent, while leaving normal cells unharmed. This hope has largely not yet been realized and indeed many of the claims of tumor-associated epitopes defined by mAbs in the early 1980s remain unsubstantiated. There are several reasons for this lack of success. For example, the major tumors of humans are those of the epithelial cells of the colon, breast, lung and prostate, and it is now clear that many of the oncogenes activated within such cells code largely for intracellular proteins which are inaccessible to antibody therapy. This view is strengthened by the fact that such common tumors show no increase in frequency in immuno-suppressed individuals. Chemotherapeutic strategies have, meanwhile, advanced...

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...

Continence mechanisms

The bladder neck or internal urinary sphincter is automatic and unlike the external urinary sphincter are not under voluntary control (Fig. 19.2). For normal voiding, both these sphincters must relax. If the external sphincter is damaged it is possible to remain continent with the internal sphincter alone. The operation of transurethral resection of the prostate (TURP) removes the prostatic adenoma obstructing the prostate urethra, and it is common for the bladder neck and the internal sphincter to be resected as well. This leads to retrograde ejaculation following TURP

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....

Symptoms due to detrusor underactivity

If the bladder is chronically distended, it can lose the ability to contract during normal voiding. The sensory stimuli of the over-stretched bladder are lost and the bladder becomes a flaccid, painless storage bag. Voiding may be achieved by abdominal straining or direct suprapubic pressure. Overflow incontinence of urine may occur. This is seen in the end stages of outflow obstruction due to prostate disease or as part of an autonomic neuropathy (e.g. in a diabetic patient).

Computed tomography scan

In computed tomography (CT) scanning, a thin, collimated X-ray beam is directed through the patient and images detected via a series of X-ray detectors arranged circumfer-entially. It provides an excellent method of staging renal, ureteric and bladder cancers. Although also used to stage prostate cancer, it remains relatively inaccurate.

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.

Renal and Urogenital System

Urine flow at the outlet is another aging consideration. The male urogenital system undergoes a characteristic aging change in the hypertrophy of the prostate gland, associated with decreased secretion of prostatic fluid. The anatomical consequence is a constriction in the passage through which urine flows from the bladder.

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....

Role of Lipodation in Organisms

Aberrantly modified lipid protein will influence signal conduction. Ras protein mutants are found in 30 of all human tumor tissues. Among these tumors, 80 are malignant (Peters et al., 2002). The cause of this aberrant modification is spot mutation on the Ras protein. It is now unclear whether chemical signals or gene mutations result in Ras mutation. Nevertheless, progress has been made in the research of targeting protein lipodation for drug design. Farnesyltransferase inhibitor has pronounced inhibitory activity (Thutewohl et al., 2003), while there is no cytotoxic effect on normal cells. Also, palmitoylethyltransferase inhibitor demonstrates antitumor activity and also has an antitumor effect on breast and prostate cancer.

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.

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...

Inappropriate Antidiuretic Hormone Secretion

Inappropriate antidiuretic hormone secretion (IADHS) may occur in a variety of diseases, including malignancies, acute and chronic pulmonary diseases, central nervous system and endocrine disorders, acute psychosis, and surgical stress. It can be induced by drugs such as phenothiazines, cyclophosphamide, vincristine, thiazides, morphine, carbamazepine, and cisplatin. IADHS may accompany certain malignancies, particularly small-cell lung carcinoma, head neck carcinomas, brain tumors, and lymphomas. The symptoms of IADHS syndrome include anorexia, nausea, headache, confusion, with the possible end result being coma. Laboratory findings include serum hyponatremia, elevated urinary sodium concentrations with normal renal and adrenal homeostasis. Few cases of prostate cancer associated with IADHS syndrome have been reported, and tumors were either poorly differentiated or small cell carcinoma and were almost uniformly metastatic at the time of diagnosis. Most of the patients died a few...

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...

Hematologic Syndromes

The association of bleeding diathesis and intravascular coagulopathy abnormalities in patients with prostate cancer has been reported. Bleeding problems in the prostate cancer patient may result from the effects of the tumor on hemostatic mechanisms or from the treatment of the tumor by cytotoxic and other agents. Among the tumor-related bleeding problems are disseminated intravascular coagulation, primary fibrinolysis, thrombocytopenia, acquired platelet dysfunction, and circulating inhibitors or anticoagulants. Disseminated intravascular coagulation is associated with hypercoagulability state in most solid tumors, whereas in prostate cancer tumors the most common presentation is acute promyelocytic leukemia bleeding. Treatment-related bleeding disorders include the common problem of thrombocytopenia secondary to myelosup-pressive chemotherapy as well as the interesting micro-angiopathic hemolytic anemia syndrome associated with mitomycin C and other agents (de la Fouchardiere et al....

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.

Tumors with Sebaceous Differentiation

Sebaceous adenoma appears as multiple skin-colored, small, noncharacteristic papules over the face, neck, and trunk. The tumor is rare and its diagnosis must raise the possibility of Muir-Torre syndrome (49). The latter is an autosomal dominant condition characterized by multiple sebaceous tumors in association with multiple internal neoplasias. Several keratoacanthomas, basal cell, and squamous cell carcinomas have also been reported. Sebaceous tumors include sebaceous adenomas and sebaceous hyperplasias. Internal malignancies are usually low-grade carcinomas of the larynx, stomach, duodenum, colon, prostate, endometrium, lung, and kidney. On histopathological examination, there are incompletely differentiated sebaceous lobules sharply demarcated from the surrounding tissue.

Obesity and the Regulation of Body Mass

TIn the United States population, 30 of adults are obese and another 35 are overweight. (Obesity is defined in terms of body mass index (BMI) BMI weight in kg (height in m)2. A BMI below 25 is considered normal 25 to 30 is overweight, and greater than 30, obese.) Obesity is life-threatening. It significantly increases the chances of developing type II diabetes as well as heart attack, stroke, and cancers of the colon, breast, prostate, and endometrium. Consequently, there is great interest in understanding how body mass and the storage of fats in adipose tissue are regulated.

Might There Be Deleterious Consequences of Introducing DNA Hypomethylation in the Genome As a Cancer Therapy

Hypomethylation of DNA in pathological conditions of the human prostate. Cancer Res 1987 47(20) 5274-76. 41. Santourlidis S, Florl A, Ackermann R et al. High frequency of alterations in DNA methylation in adenocarcinoma of the prostate. Prostate 1999 39(3) 166-74.

TABLE 2542 Grading of Renal Injuries4

MEATAL BLOOD Blood at the meatus is associated with urethral injuries. Urethral injuries are almost exclusively seen in males. Posterior urethral injuries are commonly associated with pelvic fractures. A superiorly displaced prostate indicates disruption of the posterior urethra. Anterior urethral injuries are associated with straddle injuries and instrumentation.

TABLE 2543 Substances and Medications Associated with Urinary Discoloration

The initially voided urine may provide clues as to the location of injury. When possible, at least two specimens (initial stream and terminal stream) should be obtained. Initial hematuria suggests injury to the distal system (i.e., urethra or prostate). Terminal hematuria suggests bladder neck injury. Continuous hematuria suggests upper renal system (bladder, ureter, or kidney) injury.

Direct Invasion from Contiguous Primary Tumors

Antimesenteric Border Sigmoid Colon

Intrinsic involvement of the alimentary tract by an immediately contiguous neoplasm indicates that a locally aggressive tumor has usually broken through fascial planes.84,85 The most common primaries arise in the ovary, uterus, prostate, and kidney. of the prostate had rectal involvement. Young90 found 12 instances of rectal mucosal involvement at autopsy in 800 patients with prostatic carcinoma, an incidence of 1.5 . Annular type constriction of the rectum may cause partial to complete obstruction. Fig. 4-94. Circumferential invasion of the rectum by carcinoma of the prostate. (b) Frontal view. The superior border of the annular involvement of the rectum corresponds to the base of the urinary bladder (arrows), which is elevated by the enlarged prostate gland. Fig. 4-94. Circumferential invasion of the rectum by carcinoma of the prostate. (b) Frontal view. The superior border of the annular involvement of the rectum corresponds to the base of the urinary bladder (arrows), which is...

Intrinsic Pathway Activators

Vitamin D also suppresses expression of anti-apoptotic genes BCL-2, BCL-X, and MCL-1 in prostate cancer cell lines that contain the vitamin D receptor (VDR) (Guzey et al., 2002) and may underlie in part the antitumor activity observed recently in clinical trials of high dose 1a,25(OH)2 vitamin D (calcitriol) for treatment of hormone refractory prostate cancer (Johnson et al., 2002). Compounds that inhibit histone deactylases (HDACs), chromatin-modifying enzymes that interact with many transcriptions factors, also reduce the expression of BCL-2, BCL-X, or MCL-1 at a transcriptional level (Khan et al., 2004 Mori et al., 2004 Rosato et al., 2003). Clinical trials of HDAC inhibitors are progressing, with hints of activity documented for lymphoma and some solid tumors (Kelly et al., 2003). PPARg-modulating drugs also can reduce expression of BCL-2 or other anti-apoptotic BCL-2 family genes (83). Antisense oligodeoxynucleotides (ODNs) targeting the BCL-2 mRNA are undergoing clinical...

Applications of Microarray Analysis

In such a case, expression analysis can be used to give a detailed picture of the genes that are expressed in the two types of tumor. A training set (a small set of samples in each category) can be used to find specific patterns of gene expression that are characteristic for each type of tumor. New tumors can then be analyzed, and their expression profiles can be used to predict the group to which they belong. These approaches are used with great success to refine the clinical management of cancer patients. A 2001 study by S. Dhanasekaran, Delineation of Prognostic Biomarkers in Prostate Cancer, offers an example of this kind of work. Additional applications of microarrays are still being developed.

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 likely...

Clinical Evaluation

If no significant abnormalities are found, range of motion of the hips should then be studied. If rotation of the hip with the leg in extension is painful all other maneuvers should be done cautiously. If a hip or pelvic fracture or dislocation is identified in a trauma victim, assume that intra-abdominal, retroperitoneal, and urologic injuries have occurred as well, until it has been proved otherwise. Always perform a detailed neurovascular examination and a rectal examination, looking for displacement of the prostate in male patients. Associated femoral shaft fractures should be ruled out.

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...

Testing for Carcinogenicity and Teratogenicity

Biomarkers are detectable biochemical changes. A variety has been developed that can discriminate between cancer initiation, promotion, and progression. The binding of chemicals such as benzo a pyrene to DNA can be detected by use of radiolabeled compounds or by radioimmunoassay. Promotion has been correlated with increased prostaglandin synthesis and with changes in the levels of some enzymes, such as ATPase. A variety of chemicals is produced by malignant cancer cells. Fetal liver and hepatocarcinoma, and sometimes other organs, produce a-fetoprotein (AFP). Mammary carcinomas are associated with a group of chemicals, and prostate cancer is marked by elevated levels of prostate-specific antigen (PSA), which can be detected by a blood test.

Research Approach for Determining the Health Impact of Micronutrient Supplements

A major concern associated with clinical trials designed to evaluate the health effects of micronu-trients (as well as other dietary supplements and drugs) is that participants might take additional micronutrient supplements, which could influence trial outcomes. In the Prostate Cancer Prevention Trial (PCPT) of the drug finasteride, for example,

Action of the soybean isoflavone genistein

First, increasing the activity of PDH would drive mitochondrial oxPHOS toward ATP synthesis, and produce increased ROS levels in the process. In a normal cell, increased ROS production by increased mitochondrial activity would likely be countered by activation of the cellular antioxidant enzyme response system, but in cancer cells antioxidant enzymes appear to be less active and may be less able to adequately protect tumor cells from oxidative damage, and potentially promote apoptosis (109,110,122,130). Because tumor cell mitochondria are already dysfunctional, increased respiration activities activity driven by genistein stimulated PDH activity should produce increased amounts of cytosolic ROS into the cytosol, endangering numerous essential cytosolic components such as proteins and organelles. MnSOD is expressed at low levels in normal cells, but at high levels in tumors, perhaps in response to high ROS levels (131). However, expression of catalase, glutathione peroxidase (GPx), and...

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...

Clinical Manifestations

Trichomoniasis in men is largely asymptomatic men are considered asymptomatic carriers of T. vaginalis. Disease in men may be categorized into three groups an asymptomatic carrier who is identified by investigation of sexual contacts of infected women acute trichomoniasis, characterized by profuse purulent urethritis and mild symptomatic trichomoniasis, which is clinically indistinguishable from other causes of nongonococcal urethri-tis. 4 Complications in men include nongonococcal urethritis, prostatitis epydidymitis, urethral disease, and

Cancer Tomorrow and the Future

In the 15 years since the publication of the third edition of this textbook, a veritable explosion of knowledge has occurred in the fields of cell and molecular biology, genetics, computer technology and bioinformatics, and many other basic and applied fields. Simultaneously, there has been an explosion in our knowledge of neoplasia. This knowledge has possibly led to some concrete results in that the overall death rate from cancer in the United States decreased by 3 during the period 1990-1995 (Cole and Rodu, 1996) and in the European Union by about 7 between 1988 and 1996 (Levi et al., 2000). However, as was the case 15 years ago, there is still no magic bullet to cure cancer, unlike the antibiotics that are able to cure the majority of bacterial infections in the human. Just as it was 15 years ago, despite the explosion in knowledge, medical science continues to be frustrated in its effort to establish a truly effective therapy for the most common forms of malignant neoplasms in...

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...

Selected Issues in Clinical Development

It is to be hoped that new medicinal treatments will, by virtue of their being effective, have a measurable impact on health-related QOL (Fig. 8.38). Historically, the basis for new drug approval has accepted this hope as a reality by implicitly assuming that when biological evidence of efficacy exists, there will be health-related benefits to the patient. QOL end points, either as add-ons to a traditional efficacy study or as free-standing studies, have become increasingly important in supporting comparative product claims and drug pricing and reimbursement. QOL is not, however, necessarily different from efficacy. QOL may serve as basis for approval. The best examples of this are in the area of oncology. Traditional biological oncology end points, such as tumor response and time to event variables (especially survival), have historically served as bases for new drug approval. Although FDA Oncology Division guidances over the past 20 years have invoked QOL end points as an acceptable...

Cancer Epidemiological Evidence

The Linxian, China, intervention trial provided evidence that nutritional supplementation may lower the risk of certain cancers. A modest but significant reduction in cancer mortality was observed in a general population trial in those receiving daily (for 5.25 years) a combination of ft-carotene (15 mg), vitamin E (30 mg), and selenium (50 mg). The subjects who received this mixture had a 13 lower incidence of cancer and a 10 lower mortality from stomach and oesophageal cancer than did the subjects who did not receive the mixture. In the ATBC study, male smokers who took vitamin E supplements had a 34 lower incidence of prostate cancer and 41 lower mortality from prostate cancer than did those who did not take the supplements. In the United States, in a nested case-control study conducted to examine the association of a-tocopherol, 7-tocopherol, and selenium with the incidence of prostate cancer, a striking fivefold reduction in risk was observed for the men in the highest quintile...

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...

Selenium and Chronic Disease

Several supplementation and epidemiological case-control studies have suggested a possible link between increased selenium intakes or status and protection against certain cancers. First, in intercountry comparisons and studies comparing different regions of the United States having different soil selenium levels, there was a consistent correlation between lower selenium levels and higher risk of cancer. A study of 34,000 male health professionals in the eastern United States found that toenail selenium levels were inversely proportional to prostate cancer incidence, with diagnoses recorded > 2 years later, which helped to reduce confounding by reverse causality (i.e., the presence of cancer causing the low selenium levels). A study in China found that the incidence of hepatocellular carcinoma was lower in a community receiving selenite-fortified salt (15mg kg) than in adjacent control communities, and another intervention with selenium + vitamin E + fl-carotene supplements seemed...

The Folate Hydrolase Gene

The human folate hydrolase gene (FOLH1, identical with human prostate-specific membrane antigen, gene symbols PSM, PSMA alternative title and symbol glutamate carboxypeptidase II, GCP2) is located on chromosome 11p11 - p12 (70). The FOLH1 gene encompasses approximately 60 kb and consists of 19 exons (GenBank accession number AF007544) (70,71). The entire coding region has a length of 2.653 bp (GenBank accession number M99487) (72), with a predicted molecular mass of 84 kDa excluding carbohydrate. Two mRNAs of 2.8 kb and 1.5 kb have been detected in human tissues (73). In addition to the full-length transcript, a shorter mRNA lacking exon 18 has been observed, suggesting the presence of splice variants (73). The FOLH1 gene product consists of 750 amino acid residues with an apparent molecular weight of 100 kDa and is termed folylpoly-y-glutamate carboxypetidase (FGCP alternative titles and symbols prostate-specific

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...

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...

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...

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...