Foods to help if you have Prostate Problems

The 21 Day Prostate Fix

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

The 21 Day Prostate Fix Summary


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Author: Radu Belasco

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Treatment of Early Localized Prostate Cancer

The optimum management of patients with localized prostate cancer remains controversial. Three major treatment options are available radical prostatectomy, radical radiotherapy (external beam radiotherapy EBRT or brachy therapy), and active surveillance (also known as active monitoring and watchful waiting). Each treatment involves its own risk. Radical treatments can cause harmful side effects including incontinence, erectile dysfunction, and even death, whereas watchful waiting causes anxiety relating to the presence of cancer and carries a risk of disease progression. However, outcomes in terms of overall survival appear similar with each of the three modalities. There is relatively little randomized evidence concerning the effectiveness of the different management options for early prostate cancer. In a Scandinavian study 1 , men with early prostate cancer (stages T1b-c or T2) were randomly assigned to radical prostatectomy or watchful waiting. After a median follow-up of 6.2...

Evidence for the Genetic Etiology of Prostate Cancer

Evidence for familial aggregation of prostate cancer dates as far back as 1956 8 . Significant linkage in familial prostate cancer was first published in 1996 by a group from Johns Hopkins University, Baltimore, Maryland 9 . This group reported linkage at a locus on chromosome 1q24-25, which was named hereditary prostate cancer 1 (HPC1). Several large linkage studies have since been conducted, and the results revealed new loci and challenged others summarized in refs. 10-13 .

Surgical Treatment of Prostate Cancer

Surgery for prostate cancer has evolved, with the main purpose of curing one of the most common male malignancies at an early stage in its natural history, and preventing the morbidity otherwise associated with unchecked disease progression to more advanced, incurable stages. The operation by which this may be achieved, radical prostatectomy, advanced considerably during the 20th century through developments in anatomical knowledge and surgical experience. It is now a routine surgical procedure in urological oncology carried out through a range of surgical approaches, each with its own advantages and disadvantages. The first radical prostatectomy operations were done through a perineal approach, adapted from contemporaneous techniques for stone surgery. Theodore Bilroth is credited with the first radical prostatectomy, carried out in 1866 however, the use of this operation was slow to develop owing to its considerable morbidity and mortality. In 1905, Hugh Hampton Young 1 at the Johns...

Retropubic Prostatectomy

The retropubic approach to radical prostatectomy did not develop until Terence Millin's description of his now classical operation for benign disease, the transcapsular prostatectomy. He adapted this operation to total (radical) prostatectomy, which had not been possible with the transvesical procedures with which surgeons had hitherto become familiar 3 . During the ensuing years, the perineal and retropubic approaches for radical prostatectomy each had its advocates. Radical prostatectomy nevertheless remained a formidable procedure, particularly the retropubic approach, with the risk of uncontrolled hemorrhage from Santorini's plexus. In spite of encouraging cancer-specific outcomes in patients undergoing radical prostatectomy for organ-confined cancer, the surgical difficulties persisted, and rudimentary understanding of surgical anatomy precluded any substantial progress. Complications related, first, to the undocumented course of the periprostatic veins and bleeding consequent to...

Perineal Prostatectomy

Retropubic prostatectomy continues to be undertaken with excellent results, though some surgeons prefer the perineal approach. The per-ineal approach avoids the bleeding sometimes encountered from the dorsal venous complex, as the prostate is removed behind this plane. As a result, the anterior surgical margin can be compromised, and this may have some adverse therapeutic significance in some patients, particularly those with extensive or anterior tumors. Complications specific to this approach relate mostly to anal or rectal injury, with a risk of fecal incontinence, infection, and fistula, but such sequelae are uncommon. The perineal route does not allow for assessment or removal of pelvic lymph nodes however, when this is considered important, pelvic lymphadenectomy may need to be carried out as a prior open or laparoscopic procedure. Perineal prostatectomy, therefore, may not be ideal in

The Hormonal Treatment of Locally Advanced and Metastatic Prostate Cancer

The history of hormonal therapy for prostate cancer dates back to the 1890s, when patients with prostatic diseases, which included cancer, were treated by orchiectomy, and their condition improved. Scientific analyses of the results of treatment emerged nearly a century later, and, after enormous resistance from the urological surgical community, medical therapies for prostate cancer began to replace orchiectomy as a standard treatment for the condition. The urologists argued from the surgical viewpoint that Hormone Therapy for Prostate Cancer Some 20 years after the initial introduction of the concept of luteinizing hormone-releasing hormone (LHRH) agonist treatment for prostate cancer, treatment with these agents is now accepted as standard. So much so, that the sales of these drugs constituted the biggest oncology earner for big pharmaceutical companies in the late 1990s. These agents are conventionally thought of as acting to downregulate the pituitary gonadal axis. They do this...

The Treatment of Recurrent Prostate Cancer

There is clinical evidence of prostate-specific antigen (PSA) progression after a median period of 13 months' hormonal therapy. Some 2 years after this evidence emerges, clinical symptoms develop, to be followed a median of 7 months later by death, and this course of events is not what we want for our patients. The biological basis for relapse is of more than passing interest. If patients' biopsy specimens are compared at presentation and relapse, mutations are seen within the androgen receptor in 45 to 55 of patients. It is these mutations that facilitate tumor progression. The androgen receptor is a transcription factor that binds to coactivators and co-repressors together with heat shock proteins, and by this process initiates gene transcription. It may well be that in patients who do not have obvious mutations of the androgen receptor, mutations of coactivators or co-repressors of the androgen receptor are responsible for tumor progression (Fig. 8.1).

Chemotherapy in Prostate Cancer

Prostate cancer is now most frequently diagnosed malignancy and the second leading cause of cancer-related death 1 . Death rates have increased over the past 20 years and mortality may approach that of lung cancer within 15 years 2 . For patients with advanced disease, the response rate to hormonal therapy is about 80 , but this is not durable, and all patients will eventually develop hormone-refractory prostate cancer (HRPC) 3 . Chemotherapy has been shown to have palliative benefit in symptomatic HRPC, but has not yet been demonstrated to prolong survival. Median life expectancy for patients with HRPC is only 12 to 18 months, underscoring the urgent need for new therapeutic approaches 4 . Historically, the role of aggressive systemic chemotherapy in HRPC had been questioned because elderly patients with poor marrow reserve, concomitant illnesses, and poor performance status tolerated it poorly. Coupled with this, chemotherapy trials before 1991 reported response rates of only 5 . In...

Hormone Refractory Prostate Cancer

Hormone-refractory prostate cancer is defined as disease that progresses despite castrate testosterone levels, and is refractory to all hormonal manipulations including withdrawal of antian-drogen therapy. Until recently, there had been no standard chemotherapeutic approach for HRPC. Several agents had been evaluated in clinical trials, but many older studies suffered from methodological deficits such as small numbers of patients, heterogeneity of enrolled patients, and lack uniform response criteria 5 . Overall there have been very few recent phase III trials completed in HRPC (Table 9.1) making it difficult to draw firm conclusions about the efficacy of many regimens. However, it would appear that chemotherapy at a minimum does provide a palliative benefit. Table 9.1. Summary of recent (1996-2003) phase III trials in hormone refractory prostate cancer (HRPC) Table 9.1. Summary of recent (1996-2003) phase III trials in hormone refractory prostate cancer (HRPC) PSA, prostate-specific...

Early Proteomic Studies into the Prostate and Prostate Cancer

Until very recently the number of prostate-related proteomics or 2DGE-based publications was decidedly small, due to the inherent problems in carrying out such studies. In 1989 a study was carried out by Sherwood et al. 1 , comparing the profiles of proteins obtained from stromal and epithelial cells from patients undergoing prostatectomy for benign prostatic hyperplasia (BPH). Differences were noted for cytokeratin levels and also vimentin, which was shown to be present in stromal cells via immunoblotting, as were three potential markers of stromal cell types named SM1, SM2, and SM3. As the existing technology did not yet allow identification of these markers, no identities were obtained for them. In 1992 2DGE was carried out on isolated androgen receptor, revealing two isoforms of the receptor at the isoelectric point, pI 5.3 and 7.2 and molecular weight 90 to 95kd in both prostate and foreskin 2 . A further study by Xia et al. 3 discovered three isoforms of the androgen receptor...

Small Cell Tumors of the Bladder and Prostate

The vast majority of small round blue-cell tumors of the bladder and prostate prove to be either lymphomas or systemic infiltrates in patients with a known history of leukemia. These entities have been covered in detail in the preceding section. information provided, and in particular on the age of the patient. In children and adolescents, the most common small round blue-cell tumor of the bladder and prostate, other than leukemia and lymphoma, is embryonal rhabdomyosar-coma. Although there are reports of other rare primary or metastatic tumors occurring in the bladder and prostate, including primitive neu-roectodermal tumor (PNET), neuroblastoma, Wilms' tumor, and desmoplastic small round cell tumor 73-78 , these should be considered only after exclusion of the more common entities outlined above. In adults, the main differential diagnosis of nonlymphoid small round blue-cell tumors includes poorly differentiated carcinoma and neuroendocrine tumors such as car-cinoid and small cell...

Anatomy Of The Prostate Gland And Urinary Sphincter


The prostate gland is comprised of three glandular zones and one nonglandular region, the anterior fibromuscular stroma. The three glandular regions arise from different segments of the prostatic urethra (13). The transition zone constitutes about 5 of prostatic glandular tissue and is located on both sides of the prostatic urethra. It is in this zone that benign prostatic hyperplasia develops (14). The transition zone is separated from the central and peripheral zones of the prostate by the surgical capsule, which marks adequate depth of resection of adenomatous prostatic tissue when performing transurethral prostatectomy. The peripheral zone comprises about 70 of the mass of the glandular prostate, and it is in this zone that most prostate cancers arise (15). It is located at the posterior and lateral aspects of the prostate gland with its ducts exiting from the base of the verumontanum to the prostatic apex. The central zone constitutes about 25 of the glandular tissue around the...

Transurethral Resection of the Prostate and Open Prostatectomy


In many cases, prostatic hypertrophy extends beyond the verumonta-num (25,26) (Fig. 2). Thus, the verumontanum remains a critical landmark when performing a transurethral prostatectomy. If the resection is carried past the vera, violation of the distal urethral sphincter will occur, resulting in postoperative incontinence. The distal limit of resection should be at the verumontanum, even if a small rim of adenoma is left behind. This small amount of adenoma may provide some protection against stress urinary incontinence (27). Care should be taken to minimize bleeding to insure adequate visualization, and cautery should be employed judiciously in this area to avoid thermal muscle damage. Most frequently damage to the distal urethral sphincter occurs anteriorly between the 10 and 2 o'clock positions (16). When performing open prostatectomy for benign disease, great care must be taken to preserve the distal sphincteric mechanism. Most of these glands are quite large with adenomatous...

Prostate Ultrasonography

Prostate ultrasonography, also called transrectal or rectal ultrasound, is an ultrasound study of the prostate gland. This procedure is used to examine the size, shape, texture, and position of the prostate gland and its tissue, and to diagnose abnormal conditions. Prostate ultrasonography is also used to guide the physician in performing prostate biopsy, and placing radioactive seeds into the prostate gland for cancer treatment. Prior to prostate ultrasonography, the patient may be placed on antibiotics and given an enema to empty the rectum of stool. The patient is prepared for the procedure by being placed on the left side with the rectal area exposed. Following a rectal exam, a rectal probe equipped with a transducer and covered with a condom sheath is lubricated and inserted into the rectum. The condom sheath is filled with water in order to facilitate the transmission of sound waves between the prostate and the transducer. As the transducer is rotated along the prostate, images...

Epidemiology of Prostate Cancer

The epidemiology of prostate cancer has provided a number of clues to the etiology of the disease. The incidence of prostate cancer increases with age. However, there is a discrepancy between the clinical incidence of prostate cancer and prevalence of the disease at autopsy 4 . The frequency of autopsy-detected cancer has been reported to be 30 to 40 in men over the age of 50. The incidence also varies markedly throughout the world, with the United States, Canada, Sweden, Australia, and France having the highest rates and Asian populations the lowest 5 . These differences may be due to genetic factors, but environmental factors may also be at play. Japanese male immigrants in the United States have a higher mortality rate compared with those in Japan 6 dietary changes are thought to be a significant environmental factor 4,7 (Table 1.1). Prostate cancer risk, particularly that of early-onset disease, is affected by family history. The association, however, is not as marked as in breast...

Prostate Cancer Risk Reduction by Dietary Modification

Preventive medicine is currently a topical issue. Cardiovascular disease is a well-known example. The identification of atherosclerosis as one of the causative mechanisms of cardiovascular disease has resulted in important lifestyle modifications in diet, tobacco use, and exercise. This has led to a significant decrease in the incidence of heart disease in many countries. Prostate cancer potentially represents an ideal target for chemoprevention because of its long latency. Although the use of new biological strategies is being examined in the context of primary prevention and progression of prostate cancer, it has been suggested that nutrition may also have a role. However, does the weight of Diet and Prostate Cancer current scientific and clinical data support a relation between diet and prostate cancer Is there enough evidence for us to be able to advise dietary modifications, such as reduced fat and increased soy protein consumption, and the use of nutritional supplements, for...

Incidence Of Incontinence After Prostatectomy

The incidence of urinary incontinence is approximately 1-3 in patients undergoing transurethral resection of the prostate or open prostatectomy for benign disease (3,4). The incidence of incontinence following radical prostatectomy has been reported to range from 2.5 (5) to 87 (6). This wide discrepancy is a result of several factors. The definition of incontinence varies widely among series, ranging from any degree of wetting or restricted to total incontinence. In addition, the method of data acquisition has a significant effect on reported rates of incontinence. Studies that involve patient questionnaires and or direct patient input generally have higher rates of incontinence than data obtained by chart review or physician interview. In a sample of Medicare patients undergoing radical prostatectomy, 47 had leakage of urine daily, and 6 needed surgical intervention (7). Incontinence after prostatectomy has a significant negative impact on a patient's quality of life. Herr discovered...

Etiology Of Incontinence Following Prostatectomy

When considering the etiology of urinary incontinence, it is essential to identify that leakage may occur as a result of an abnormality of bladder and or sphincteric function. Urodynamic studies provide information concerning the relative contributions of bladder and or sphincteric dysfunction in patients with incontinence after prostatectomy. The presence of isolated bladder dysfunction as the predominant cause of incontinence following prostatectomy has been identified in reports utilizing urodynamic studies (42,43). These reports concluded that sphincteric weakness is not the major factor contributing to incontinence following prostatectomy. In contrast, sphincteric weakness alone has been implicated as the predominant cause of postprostatectomy incontinence (44,45) (see Table 1). Several factors have been proposed to explain for this discrepancy (45). Many studies documenting a high incidence of bladder dysfunction alone contain a large percentage of patients following...

Prostate Brachytherapy

Prostate brachytherapy involves placement of radioactive sources directly into the parenchyma of the prostate. It is a highly conformal form of therapy, permitting dose escalation to the target volume far exceeding that of other radiation modalities. The surrounding normal tissues are spared because of the rapid dose falloff with distance from the source (inverse square law). The evolution of TRUS imaging, a closed transper-ineal approach, and the increasing sophistication of computerized planning have resulted in a worldwide resurgence of interest in this treatment technique. Its appeal lies in its speed and convenience (it can be done as an outpatient procedure) and the low long-term risk of proctitis impotence is also less likely than after radical prostatectomy. Brachytherapy to the prostate can be delivered either with permanent seed implants or with removable implants,which are often delivered at a high dose rate with iridium wire. Permanent implants may be used alone as...

Sporadic and Familial Prostate Cancer Biochemical Failure and Differences in Survival

Gronberg et al. 122 tried to estimate the survival of men with FPC and compare them with prostate cancer cases unselected for family history. No significant differences in either overall or prostate cancer-specific survival between familial and sporadic cases were found. Tumor grade at diagnosis in familial cases did not differ from that in a population with prostate cancer unselected for family history. The conclusion, based on the result from this study, was that no differences in treatment between men with and without a positive family history of prostate cancer are justified. However,Kupelian et al. 123 ,in an analysis of the outcome after radical prostatectomy of patients with familial versus sporadic prostate cancer, observed that the former group has a higher likelihood of biochemical failure after radical prostatectomy. They concluded that this effect was independent of pretreatment or pathological factors. Currently, it may be reasonable to recommend that treatment plans...

The Molecular Biology of Prostate Cancer

Prostate cancer is the most frequently diagnosed malignancy among men in industrialized countries. In the United States, one in eight men will develop prostate cancer during their lifetime 1 , and in 1999 approximately 37,000 died from the disease 2 . In England and Wales, 17,000 cases are diagnosed and there are nearly 9000 deaths annually from prostate cancer 3 . Advances in our understanding of the molecular basis of cancer have led to the characterization of critical pathways regulating tumor growth, which should provide the potential for the development of more effective and less toxic targeted therapies. In 1941 Huggins and Hodges first demonstrated that malignant tumors arising from the prostate were responsive to androgen withdrawal. Since then, hormonal therapy has been established as the principal treatment modality for advanced disease. Over time,however,resistance to treatment occurs. As a result, there has been much interest not only in the molecular changes associated...

Diet and Prostate Cancer

Prostate cancer is the most commonly diagnosed malignancy in men in industrialized countries and the second leading cause of male cancer-related death. Given the trebling of death rates in the last 30 years and the relative lack of a survival benefit from the treatment of advanced disease, it is critical that we look at preventative stratagems to reduce death rates. Although aging is the most significant risk factor for prostate cancer with a virtually exponential increase in age-related incidence and mortality, prostate cancer is also characterized by a marked variation in its worldwide incidence. Superficially, it would seem to be difficult to separate environmental factors from racial factors in explaining this difference in the incidence of this tumor, but studies of migrant populations suggest that environment is overwhelmingly more significant than genetics in the origins of this cancer. For example, when migrants from a low-risk country such as Japan move to the United States,...

Rodent Prostate Cell Differentiation

Biochemical analysis exists on the rat prostate, but limited information is published on the secretory proteins of the mouse prostate. Also, no rodent analog for human PSA has been identified. The rat ventral lobe differs most significantly from the other lobes because its protein products are quite distinct (101-103). The rat anterior lobe produces many of the androgen-regulated proteins seen in the dorsolateral prostate (104). The seminal-vesicle secretion II (SVSII) is a major secretory product of both the seminal vesicle and the dorsolateral prostate (103,105), and Dorsal Prostate I and II are found in the dorsal prostate (104,106). Probasin (PB) is detected in all lobes of the prostate and the seminal vesicles, with lateral lobe expression the highest (100 ) followed by dorsal (33 ), anterior (14 ), ventral (4 ), and seminal vesicles (2 ) (103,107,108). Some of these secretory proteins are detected in the prostate between 2-3 wk of animal age (102 103) but the major increase in...

Human Prostate Cancer

The reproductive organs are not required for an individual's survival but are required for survival of the species. As the individual approaches adulthood, the prostate undergoes developmental changes, resulting in maturation of this gland at puberty. At this stage, the prostate becomes a differentiated gland that produces proteins and other substances fundamental for reproduction and survival of the species. By the age of 50, as many as 30 of all men will harbor microscopic foci of prostate adenocarcinoma (CaP), and the incidence increases with age. In the United States, CaP is clinically diagnosed in approx 10 of men during their lifetime (189,000 yr), where it will claim 31,900 lives each year (13 of male cancer deaths) (1). The recent rising incidence of CaP (2) has plateaued (3), but the high prevalence of this disease and the aging of the US population still makes this a cancer that demands prompt attention. The proliferation and differentiation of prostatic tissue is influenced...

Familial Prostate Cancer

Prostate cancer (PCa) is the most common cancer diagnosed in North American men, excluding skin cancers. It is estimated that, in 2004, approximately 230,110 new cases and 29,900 prostate cancer-related deaths will occur in the United States 1 . In Australia, one in 11 men will develop the disease during their lifetime 2 . The annual number of new cases registered in England and Wales increased by over threefold between 1971 and 2004, from 6174 to over 21,000 3 ( Everyman). Prostate cancer remains a major public health problem. Over the last 45 years, prostate cancer has been observed to run in families. Familial aggregation (at least two cases in the family) has been observed in around 20 of cases and a hereditary form of PCa in approximately 5 7 . Epi-demiological evidence shows familial clustering of PCa, and it is currently established that a positive family history is a strong risk factor. One of the major issues surrounding familial prostate cancer (FPC) includes...

Androgen Receptor and Prostate Cancer Etiology

The reason for the varying incidence of prostate cancer between racial groups is undoubtedly multifactorial, with the contribution of both genetic and environmental factors. African-American men have the highest risk of prostate cancer and Asian populations have the lowest 38 . 5a-Reductase, which converts testosterone into the more active androgen DHT activity, correlates with race, with low levels of activity in Japanese men and higher levels in African Americans and Caucasian 57 . Racial variations have also been found in the gene encoding 3b-hydrox-ysteroid dehydrogenase 2, which is involved in the breakdown of DHT, suggesting it may play a role in prostate cancer predisposition 58 .There has been much interest in possible racial differences in male testosterone levels however, studies have shown conflicting results 59,60 . Interestingly, although the incidence of clinical prostate cancer is high in the United States and low in Asian countries, the frequency of sub-clinical...

Diet and Prostate Cancer Biology

Although prostate cancer is primarily a disease of older men, neoplastic changes may occur in the prostatic epithelium as early as in the third decade. The time required for some of these early neoplastic transformations is likely to be long. Some dietary compounds display antioxi-dant properties, thus preventing peroxidation and generation of free radicals with potential DNA-damaging effects. Others are inhibitors of cell proliferation, apoptosis inducers, or enhancers of cellular differentiation. Some may act at a hormonal level, as the prostate is an androgen-regulated organ. In many cases, though, the precise pathways modulated by these compounds and mechanisms of DNA damage induced by carcinogenic agents are still poorly understood.

Screening for Prostate Cancer

Prostate cancer screening is one of the most controversial public health issues in urology. The natural aging of the population and the continued and widespread use of improved diagnostic tests, such as serum prostate-specific antigen (PSA), are resulting in an increase in the numbers of men diagnosed with localized prostate cancer. The issue of screening to identify organ-confined prostate cancer has provoked much public and scientific attention, and there is intense debate about its role in improving men's health. Despite constant pressure from strong advocates of screening, including the general public, special-interest groups, and certain aspects of the media, the findings from most reviews of the scientific evidence conclude that it is insufficient, at present, to recommend routine population screening because of the lack of evidence that this would improve either survival or the quality of men's lives. Particular concerns in these reviews relate to the lack of knowledge about...

Lymphoma of the Prostate

Primary lymphoma of the prostate is very rare, representing only approximately 0.2 to 0.8 of extranodal lymphomas and 0.1 of all prostate neoplasms 1,64,65 . Secondary involvement of the prostate by lymphoma or leukemia is more frequent,being found at postmortem in up to 8 of non-Hodgkin lymphomas and up to 20 of cases of CLL 66 . However, in most cases this involvement is not clinically apparent. In a series of 62 prostatic lymphomas, Bostwick et al. 67 found 35 to be primary (defined by presenting symptoms of prostatic enlargement, predominant involvement of the prostate, and no involvement of lymph nodes, blood, liver, or spleen within 1 month of diagnosis), 48 to be second

Serum Markers for Prostate Cancer

The discovery and development of PSA in the 1980s revolutionized the diagnosis of prostate cancer. The marker, which is simple to detect, easy to access, and relatively noninvasive for the patient, is an ideal find. It is now firmly established that PSA is one of the most reliable cancer markers currently in use. It is also true, however, that there are a very high number of false-positive and false-negative diagnoses obtained via PSA testing, and for this reason the use of PSA as a screening test in the United Kingdom has always been avoided. It is worthy of note, however, that its application in the United States has led to an increased number of diagnoses and arguably a drop in mortality. This demonstrates the value of such screening regimes in saving lives. It therefore follows that an accurate and informative blood test for prostate cancer would be invaluable in the clinics, allowing early diagnosis and possibly even informing the type of treatment required for each patient. In...

Does Screening for Prostate Cancer Reduce Mortality from the Disease

Since the introduction of the PSA test, screening for early prostate cancer has become prevalent in the United States, with, as expected, a sharp rise in the incidence of the disease in the early 1990s. This was contrasted by a static incidence rate in countries where screening was not widely practiced, such as the United Kingdom. However, by 1996 the U.S. started to experience a slow but constant decrease in the prostate cancer mortality rate, which was advocated by some as resulting from early aggressive intervention with the intensive screening program. This conclusion is flawed by a number of problems. First, in view of the protracted natural history of the disease, it is unlikely that early treatment could have caused this reduction in mortality within such a short time period. Second, similar reductions in mortality rates were observed in countries where screening had not been adopted, such as England and Wales, and the Netherlands, suggesting that other factors, including diet...

Radical Radiotherapy for Prostate Cancer

The incidence of prostate cancer is rising worldwide due to the ageing of the population and the increasing availability of prostate-specific antigen (PSA) screening. Prostate-specific antigen testing has led specifically to an increase in the proportion of patients diagnosed with early-stage (localized) prostate cancer. Radical radiotherapy is one of the curative treatment options for localized prostate cancer and it also has a role to play in locally advanced and even metastatic disease. This chapter reviews the relative merits of radiotherapy in comparison to the other management options for early prostate cancer and summarizes the staggering technological advances that have occurred in prostate radiotherapy over the last decade.

Soy Isoflavones and Breast or Prostate Cancer Risk

The observation that both breast and prostate cancers are common in the Western industrialized nations, while relatively rare in oriental countries such as China and Japan, suggests that some component of the oriental diet may include substances that protect against these cancers. In addition, studies of migrants from these low-risk countries to the U.S. revealed that risk of breast and prostate cancer increased to the level of Caucasians in the U.S. after only a few generations. Although the biologic evidence suggesting that soy may be important in the development of prostate cancer is quite strong, only a few epide-miologic studies have evaluated this relationship. Among men of Japanese ancestry living in Hawaii, risk of prostate cancer was reduced 65 in those men who ate tofu more than five times per week, in comparison with those who ate it less than once per week. However, the number of men in the study was small and the finding was of borderline statistical significance.45 Among...

Prostate Cancer Immediate vs Deferred Treatment

There continues to be controversy about the timing of treatment for localized, for locally advanced, and for metastatic prostate cancer. The decision for early radical treatments in localized disease has been based on the patient's age, general health, and preference. However, an increased understanding of the natural history of this cancer may allow us to select patients at risk for whom treatment might possibly improve survival while reducing the risk of treatment-related morbidity in those not at risk 1,2 . The survival benefits of radical treatments for localized prostate cancer still remain unclear. To date, no randomized controlled trial has demonstrated whether radical surgery or radiotherapy is more effective than watchful waiting in improving overall survival. There is evidence that radical prostatectomy may significantly reduce disease specific mortality when compared to watchful waiting, but watchful waiting may be a viable option for some men 2 . Results from hormonal...

Enlarged Prostate Gland

This condition is most common in men over 40 years old. It is caused by a swelling of the prostate gland, which is between the bladder and the urinary tube (urethra). Treatment for an enlarged prostate Note Both prostate trouble and gonorrhea (or chlamydia) can also make it hard to pass urine. In older men it is more likely to be an enlarged prostate. However, a younger man especially one who has recently had sex with an infected person probably has gonorrhea or chlamydia.

What Do Men with Prostate Cancer Think of Screening for the Disease

Public perception of screening for the disease varies. There is widespread pressure for the establishment of national screening programs, with resistance to this pressure often misinterpreted as attempts to save money, deceive the public, or even as sex discrimination. A recent interesting and elegant qualitative research study by Chapple et al. 35 highlighted these feelings, interviewing 52 men with prostate cancer from various geographical areas of the U.K. Although some factual conceptions were revealed, there were also many misconceptions, such as early diagnosis brings better chances of cure, 5-year survival figures in the U.S. are higher than in Britain because of PSA screening programs, PSA testing is not taking place because of lack of resources in the NHS, men should be tested for prostate cancer as women are for breast cancer, men with urinary tract symptoms should all be tested for prostate cancer, and the government is not spending enough money on prostate cancer...

Proteins Differing Between Normal and Cancerous Prostate

One of the most appealing studies that one can carry out with proteomics technology is the investigation of proteins with differing expression levels between normal and cancerous prostate. The first directly prostate-cancer related proteomics paper appeared in 1997, in which Partin et al. 4 identified a protein, PC-1, that was present in prostate cancer but not in normal or hyperplastic prostate. The protein, to which an antibody was subsequently raised, was then used in experiments to investigate its potential use in prostate cancer screening via immunohistochemistry. Despite encouraging results, this study does not appear to have been developed further. A study of prostate cancer can be further broken down into the investigation of different stages of cancer, from prostatic intraepithelial neoplasia (PIN) to hormone therapy-resistant cancer, and all stages in between. Although the technology now exists to make this task possible, the problems that dog any other similar study on...

Laparoscopic Prostatectomy

Laparoscopic radical prostatectomy has developed within the past 10 years, recognizing the many potential benefits of laparoscopic surgery. It was first described by Schuessler et al. 10 in 1992, and at that time presented significant challenges 11 . Reduction in the extent of surgical incisions, postoperative pain, and analgesic requirement, and shorter convalescence including reduced hospital stay contribute to its potential advantages. Disadvantages relate to the considerable specific skills and experience that need to be acquired and maintained. Procedure-specific advantages and disadvantages must also be considered in relation to open surgery 12 . Operative blood loss in laparoscopic prostatectomy may be minimal by comparison with the open procedure. In experienced hands blood transfusion is rarely required, though this may also apply for the open procedure. For the surgeon, laparoscopy provides an excellent magnified visual field via a monitor, although two-dimensional, and a...

Gene Therapy for Prostate Cancer

Prostate cancer has recently become the most commonly diagnosed male malignancy in industrialized countries and the second leading cause of cancer-related mortality in men. Over the last 30 years death rates from prostate cancer have more than doubled in England and Wales 1 . It is argued that disease confined to the prostate can be successfully treated by radiation or surgery, with adjuvant hormonal therapy. However, up to half of men with clinically localized disease are not cured by these approaches 2 . In the United Kingdom over 60 of men with prostate cancer have either locally advanced or metastatic disease at presentation and are incurable. These patients are treated by androgen ablation, but the efficacy of this approach is limited by the development of hormone-refractory disease. Although chemotherapy can have a role to play in patients with advanced prostate cancer, response rates are modest and the survival benefit marginal. There is thus clearly a need for novel therapies...

Genome Searches in Prostate Cancer

Predisposing genes by looking for co-segregation of markers with the disease in families. The attempt to identify prostate cancer susceptibility loci has been undertaken across the genome by numerous groups. The Union Biomed (ACTANE) group has defined age at onset and number of cases and focused on the collection of clinically significant PCa, because the disease manifests 10 years later on average than prostate-specific antigen (PSA)-detected disease, and hence men with clinically detected early-onset PCa could have had a raised PSA level at an earlier age 36 . Thus far, several GWSs have been reported for prostate cancer 9,11,13,65-80 . The significant results are summarized as follows

Principles of Radical Prostatectomy

Radical prostatectomy is generally carried out with the intent of achieving long-term disease-free survival and thereby cure of early-stage prostate cancer 20 . Secondary, but nevertheless important, concerns are the maintenance of quality of life, in particular continence and erectile function. In some countries, interest is growing in a potentially palliative role in patients with more advanced and noncurable disease. Favorable long-term survival in patients with pathologically organ-confined tumors has been recognized since Young's early experience 21 . In spite of early concerns, nerve sparing does not compromise cure rate 22 . Today, alongside the shift of pathological stage toward organ-confined disease at diagnosis, neurovascular bundles are rou

T XJuALXvIOSi Of Postprostatectomy Incontinence

Present prior to surgery The events occurring during leakage (activity, urgency or no sensation) as well as associated urinary symptoms (force of stream, complete emptying) are important factors. Day and nighttime pad usage should be documented to measure the severity of leakage. A pad-weight test may also more accurately quantify urine leakage. Any associated neurologic symptoms or history of previous incontinence therapy should be obtained. The physical examination should include focus on the neurologic status of the perineum and lower extremities. Rectal examination should be performed to rule out recurrence in cancer cases, and to assess the size of the prostate in patients following TURP. A urinalysis and residual urine should be obtained in all patients, and PSA testing should be considered in all patients with a history of prostate cancer to rale out recurrence. Urodynamic evaluation is essential to determine the etiology of incontinence following prostatectomy, and should be...

Hormone Therapy for Prostate Cancer

Prostate cancer is now the most prevalent of all male malignancies and the second most common cause of male cancer deaths. Death rates have trebled over the last 30 years, and changes in mortality during this period are shown in Table 8.1 1 . Prostate cancer is initially an androgen-dependent tumor, and treatment aims to reduce androgen supply to it. It is over a century since the first treatment for prostate cancer was introduced by an English surgeon, who castrated patients with benign and malignant prostatic conditions and observed the responses. Since that time there have been refinements of treatment so that we are now able to deal more humanely with this condition. We understand more about the toxicities of treatment and the value of second-line therapies. This has led to an improvement in survival. Our hope for the future is that new developments and therapeutic options will result from our increased understanding of the molecular basis of prostate cancer. This chapter surveys...

Prostate Specific Antigen PSA

Prostate specific antigen (PSA) is a protein found in normal prostate cells of all males. Identifying variations in the serum levels of this antigen is the most effective way to diagnose prostate cancer, identify tumor recurrence, and monitor the response to therapy for prostate carcinoma. The prostate-specific antigen and the prostatic acid phosphatase tests are used to identify and monitor tumors of the prostate. Variations from Normal. Caution must be used when interpreting PSA results. While increases in PSA levels occur in 80 of patients exhibiting prostate cancer, the degree of increase may represent very different diagnoses. Prostate cancer, benign prostatic hypertrophy, and prostatitis can display increased prostate-specific antigen results. Based on the normal range cited above, an increase in serum PSA levels of 4.0-8.0 ng mL may indicate benign prostatic hypertrophy or possible cancer of the prostate. Elevations in excess of 8.0 ng mL are highly suggestive of malignancy. As...

Rodent Prostate Cell Determination

The rodent prostate gland consists of four different lobes defined as ventral, dorsal, lateral, and anterior (coagulating gland), where the epithelial cells are specialized and express specific protein products. Each lobe is anatomically distinct, but the dorsal and lateral lobes, because of their size and proximity, are often examined collectively as the dorsolateral prostate. The rodent dorsolateral prostate is considered to be homologous to the human prostate peripheral zone (57), the most common site of prostate cancer in humans. In the rodent, the urogenital sinus (UGS) begins to develop in the embryo day (E) 10-11 of gestation, and testicular androgen production in the mouse begins E 12.5-13, peaking at E 17-18 gestation, thereafter declining until birth (58,59). 5a-reductase activity is detected in the UGS at E 14.5 (60), and coincides with Wolffian-duct differentiation into the epididymis, seminal vesicles, and ductus deferens as the Mullerian duct degenerates. Normal rodent...

Acute Prostatitis

PE rectal exam reveals enlarged, nodular prostate biopsy obtained to rule out carcinoma. Enlarged prostate with nodularity and calculi. Discussion Bacterial prostatitis is usually caused by the same gram- negative bacilli that cause UTIs in females 80 or more of such infections are caused by E. coli. Chronic bactcrial prostatitis is common in elderly males with prostatic hyperplasia and is a frequent cause of recurrent UTIs in males (most antibiotics poorly penetrate the prostate hence the bacteria are not totally eradicated and continuously seed the urinary tract).

Prostate biopsy

Prostate biopsy remains a controversial issue with no standardized consensus with regard to technique, number of biopsy cores and region of prostate to be biopsied. The larger the gland, the lesser the likelihood of CAP detection and the greater the false-negative rate. The rate of CAP detection increases from 23 to 31 in glands 50 cc to 38-50 in glands measuring


Apoptosis occurs in a hormone-sensitive manner in the prostate. Either androgen withdrawal or castration results in increased apoptotic death in the prostate glandular epithelium (173). Little is currently known about the roles of the Bcl2 family in the regulation of prostate apoptosis. While Bcl2 is not detected in normal prostate epithelial cells in humans, Bcl2 expression is detectable, and increases as prostate cancers become androgen-independent, raising the possibility that Bcl2 may have a role in neoplastic growth in this tissue (174). In support of this hypothesis, mice that overexpress a Bcl2 transgene in prostate epithelial cells have morphologically abnormal prostates, with an accumulation of cells in stromal and epithelial compartments (175). Understanding Bcl2 family function in the prostate may ultimately have useful value for treatment of prostatic cancer.

Somatic Genetic Changes

Although the molecular genetic changes responsible for prostate cancer development and progression is poorly understood, as with other solid tumors the number of changes increases with the stage of disease 9 , suggesting that the disease progresses as the result of an accumulation of genetic changes (Fig. 1.1). This may involve activation of dominant oncogenes-by amplification, translocations or point mutations, or inactivation of recessive tumor suppressor genes-loss of an allele (known as loss of het-erozygosity, LOH), allele inactivation by mutation, promoter hypermethylation, and haploinsufficiency.

The Androgen Receptor

The action of androgens in prostate cancer, as in the normal prostate, is mediated through the androgen receptor. Androgen deprivation is the accepted treatment for advanced prostate cancer and results in responses in 50 to 80 of patients. Unfortunately, despite initial responses to such treatment, prostate cancer inevitably progresses to an androgen-independent state within 13 months from starting treatment. As a result, much research has focused on androgen signaling in prostate cancers.

Other Cellular Matrix Interactions

The cadherins are a class of cell-adhesion molecules that are involved with cell-to-cell recognition, and thus help maintain epithelial tissue differentiation and structural integrity. Reduced expression of E-cadherin is associated with advanced stage and grade 54 of prostate Epitheliale ell Normal prostate tissue Prostate cancer tissue The Molecular Biology of Prostate Cancer cancers and also poor clinical outcome 9 . In a cellular model, inhibition of E-cadherin leads to disruption of normal contact inhibition of growth and an invasive phenotype 86 . a-Catenin associates with E-cadherin and can also be altered in prostate cancer 9 . CD44 is part of the CD family of transmembrane glycoproteins principally involved in cell-extracellular matrix interactions and is encoded on chromosome 11. In a rat model of prostate cancer CD44 behaves as a metastases suppressor gene 87 . Downregulation of CD44 expression also occurs in high-grade prostate cancer 9 . A proposed mechanism for CD44...

Treatment Versus Observation in Screen Detected Patients

Tions in BRCA2, were replicated, there would be a rationale for offering genetic counseling and testing for this disease. At present, these results should be replicated on a further sample set of blood samples from PCa cases diagnosed at young age prior to offering clinical diagnostic BRCA2 genetic counseling and testing, and this is in progress in the U.K. Familial Prostate Cancer Study 10 . The American Urological Association currently recommends that men at high risk of developing PCa, that is, those with a family history of the disease or men of African-American descent, begin receiving routine prostate cancer screening at age 40 124 . Its recommendation is that such men receive PSA testing and digital rectal examination (DRE) annually starting at age 50. This is recommended earlier if there is a family history of the disease or if one is of African-American descent, as above 125 . The main recent area of controversy is the utility of the PSA value, particularly at low levels (see...

There Should Be a Preclinical State More Amenable to Successful Treatment than Clinical Disease

This criterion remains unclear in prostate cancer, largely because of the rather loose definition of clinically significant disease. Despite the fact that with increasing age most men will develop microscopic foci of prostate cancer, only a small percentage of these slow-growing tumors will develop into invasive prostate cancer, and an even smaller proportion will cause premature death. It is hoped that the epidemiological investigation of prostate cancer will identify factors ideally amenable to intervention that cause the common microscopic form of the disease to progress to invasive disease. However, to date, the etiology of prostate cancer remains virtually unknown and continues to pose a major challenge to epidemiologists. Although both genetics and environment are likely to play a role in the evolution of the disease, the role of genetic factors in prostate cancer susceptibility has stimulated significant interest following a number of genetic linkage analyses based on families...

There Should Be an Accepted and Effective Treatment

Until recently, there was a significant lack of first-degree evidence through large randomized controlled trials that aggressive treatment of localized prostate cancer improves survival or quality of life. Outcomes for different treatment options in men with localized prostate cancer are difficult to interpret, because many of the published studies are observational, contain too small numbers, and are otherwise insufficiently robust. For example, men treated by watchful waiting may have been selected because they are older, with lower grade tumors, whereas those treated by radiotherapy may have been more likely to have more advanced tumors. Therefore, only data from well-conducted large randomized controlled trials can confidently be used to compare treatment options. Such a trial has been performed in Scandinavia, the results of which were published recently 25,26 . The trial randomized 695 men with early prostate cancer to either watchful waiting or radical prostatectomy, with a...

Epidemiologic and Clinical Studies

Most of the available clinical evidence regarding the effect of dietary fat intake on prostate cancer comes from observational rather than interven-tional studies. A close correlation exists between average per capita fat intake and prostate cancer mortality in numerous countries round the world 9 . Japanese and Chinese men who migrate to the United States experience dramatic increases in prostate cancer risk within one generation compared to their Caucasian neighbors 10 . Numerous case-control studies over the past 25 years have demonstrated a positive correlation between prostate cancer and increased fat or fat-type food consumption. Such studies include an analysis of 384 men diagnosed with prostate cancer between 1990 and 1992 in Quebec, Canada 11 . On average, after controlling for age, grade, clinical stage, initial treatment, and total energy intake, saturated fat consumption was significantly associated with disease-specific survival. Compared with men in the lower tercile of...

Studies in Seventh Day Adventists

These studies are reviewed below. However, as early as 1958, Wynder and Lemon examined cancer and heart disease in SDA hospital patients compared with non-SDA patients.18 In this early study, based on 564 SDA and 8128 non-SDA patients admitted to eight SDA hospitals throughout the U.S., lower risk of epidermoid lung, mouth, esophagus, larynx, and bladder cancer were found in the SDAs than in the non-SDAs. Colon and rectum cancer, however, were not found less frequently in the SDA than the non-SDA comparison group, while prostate and breast cancer were found somewhat more frequently in the SDA patient series. Interviews with study subjects indicated that only 41 of the SDA patients consumed any meat, whereas 95 of the general population consumed meat. Between the years 1958 and 1965, an updated analysis that examined mortality in the SDA population was conducted wherein various adjustments were made to make the SDA non-SDA comparison more valid. In...

Adjuvant or Salvage Radiotherapy After Surgery

Following radical prostatectomy, patients with positive resection margins, extraprostatic exten sion (pT3 disease), or seminal vesicle invasion are at increased risk of disease recurrence. There is increasing interest in the role of postoperative radiotherapy in these patients. Radiotherapy (RT) can be administered immediately following prostatectomy (adjuvant RT) or may be postponed until the PSA has risen to a level that is indicative of residual or recurrent prostate cancer (salvage RT). There are no published randomized clinical trials of postprostatectomy radiotherapy, and it is not known whether the results of immediate adjuvant radiotherapy and early salvage radiotherapy are equivalent. Most retrospective studies, however, show that both are generally well tolerated. Adjuvant radiotherapy is given postopera-tively to eradicate possible microscopic residual disease in the periprostatic tissues or adjacent pelvic lymph nodes. It may be considered in men with positive resection...

Alternative Explanations for Low Cancer Risk in Vegetarians

Data have suggested that colon cancer may be associated with cigarette smoking (but only after a long latency period).64-65 The more relevant question today may be which cancer sites are not associated with tobacco the list appears to be quite short and currently includes prostate, endometrium, and breast cancer. Screening Bias For some forms of cancer, screening is effective in early detection. Specifically, some of the female cancers such as cervix and breast, as well as prostate cancer in men may be detected more frequently in populations that have a greater than normal degree of access to screening programs. For example, in the Adventist Health Study in which cancer incidence was monitored among SDA between 1976 and 1982, elevated incidence of skin cancer, prostate, and cervix cancers was observed.28 These findings may not be a reflection of an actual increased biologic risk of these forms of cancer in SDAs, but an artifact of more intense screening for cancers among SDAs than in...

Combined Antiandrogen Treatment

Labrie, a French Canadian, has made a great contribution to prostate cancer treatment, and suggested that in a disease that is androgen sensitive it is important to eliminate all sources of androgen. Labrie advocated the use of a combination of an antiandrogen with an LHRH agonist in the treatment of prostate cancer. The sources of androgen supplied to the prostate are dietary, adrenal, and testicular. The use of an antiandro-gen, such as flutamide, potentially has the benefit of acting synergistically with GnRH agonist. Labrie's early work was not based on any randomized study, and so was not greeted with universal acceptance, but rather the opposite However, his opinion has been vindicated by randomized controlled trials and meta-analyses of these studies. The randomized trials show a 7-month survival advantage to combination antiandrogen treatment. The meta-analyses, however, do not look at survival advantage, but at overall 5-year survival, and these report a 3 benefit to...

Intermittent Hormonal Therapy

Among the most important quality of life issues for patients with prostate cancer is the loss of sexual function with treatment. For this reason many men delay treatment or take treatment intermittently. There is no evidence whatsoever that intermittent treatment is less successful than continuous therapy. Indeed, if one examines the effects of hormonal treatment on prostate cancer cells growing in culture, then a single exposure to antiandrogen therapy is seen There is no rational basis for continuous therapy, and so the intermittent treatment approach can be supported. This point was brought home to me by the clinical course of a patient advocate on one of the trust boards of the Prostate Cancer Charity. He presented with metastatic disease and took hormonal treatment for a period of 6 weeks. He responded well and discontinued treatment until he suddenly presented 4 years later with cord compression, a course of events that might have occurred if he had taken continuous therapy....

The Side Effects of Hormonal Therapy

In the treatment of any group of patients, there is a historical paradigm to clinical reportage. The initial publication describes an effect of a new treatment. The follow-up publications confirm this effect. A third group of publications then emerge comparing the effect of the new treatment to a standard therapy option, and then finally the side effects of the new treatment are reported. This has been the case with the hormonal treatment of prostate cancer. The initial reports of estrogen activity have been followed by overwhelming evidence of toxicity. This includes a 40 incidence of gastrointestinal tox-icity, gynecomastia that is not prevented by the irradiation of breast buds, and cardiovascular toxicity that is not prevented by low-dose anticoagulation 10 . Nevertheless, estrogens are still prescribed in the United Kingdom, although their prescription is proscribed in many other countries in the European Union. Hormone Therapy for Prostate Cancer Fig. 8.1. The androgen receptor...

Estramustine TaxaneBased Therapy

Chemotherapy in Prostate Cancer Table 9.2. Summary of phase II clinical trials of estramustine plus a taxane in patients with hormone-refractory prostate cancer Table 9.2. Summary of phase II clinical trials of estramustine plus a taxane in patients with hormone-refractory prostate cancer mustine and docetaxel or to mitoxantrone and prednisone, with the primary end point being overall survival. The docetaxel and estramustine arm again showed an improvement in overall survival (17.5 mo vs. 15.6 mo) compared with the mitoxantrone arm 32b . Based on these two large trials, taxane based therapy is quickly becoming the standard of care for hormone refractory prostate cancer.

Neoadjuvant Chemotherapy

The use of systemic chemotherapy earlier in the course of treatment, an effective strategy in some malignancies, has been explored to a small degree in prostate cancer. The objectives of neoadjuvant chemotherapy are to downstage the cancer, decrease the incidence of positive surgical margins, and eliminate micrometastases. In addition, chemotherapy may eradicate both androgen-independent clones and androgen-sensitive clones, the latter by synergizing with hormonal ablation. Several pilot neoadjuvant chemotherapy trials have now been reported, and suggest that from a surgical standpoint this is a feasible approach (Table 9.4). Pettaway et al. 38 treated patients with high-risk localized disease with 12 weeks of ketoconazole and doxorubicin alternating with vinblastine and estramustine (KAVE) and androgen ablation followed by radical prostatectomy (RP). The primary end point, a 20 pathological complete response (pCR), was not achieved, but there were fewer positive margins. Clark et al....

Technique and radiation

Each spectrum is derived from a voxel. A voxel is a small (0.24-0.34 cm3) volume of prostate, and MRSI produces arrays of contiguous voxels to map the whole prostate. Concentration of the resonating prostatic metabolites are recorded as peaks and the distribution patterns can help distinguish between benign and malignant prostatic tissue. Using specialized software, regions mapped by MRSI are then overlaid on the MRI images to allow correlation of areas of metabolic and anatomical abnormalities.

Angiogenesis Inhibitors

Chemotherapy in Prostate Cancer endothelial cells into the interstitial space, and subsequent endothelial proliferation and differentiation into mature blood vessels 52 . Several agents targeting angiogenesis have been tested in prostate cancer, including suramin, thalidomide, matrix metalloproteinase inhibitors, endostatin, angiostatin, vascular endothelial growth factor (VEGF) inhibitors, and cell adhesion inhibitors, to name a few. These are all currently in early stages of development.

Combinations of Targeted and Cytotoxic Therapy

Another interesting combination is high-dose calcitriol and docetaxel. Calcitriol, at supraphys-iological concentrations, is a natural ligand for the vitamin D receptor and its analogues and has several mechanisms of action. Calcitriol causes G0 G1 arrest, changes in p21 (Waf1) and p27 (kip1) expression, dephosphorylation of retinoblastoma protein, downregulation of bcl-2, inhibition of angiogenesis, induction of apop-tosis, and changes in several growth factor systems including EGF, transforming growth factor-b (TGF-b), and insulin-like growth factor (IGF). Preclinical studies suggest it enhances cytotoxic activity of docetaxel, paclitaxel, and platinum compounds, and is active in prostate cancer. In the study by Beer 56 , HRPC patients treated with oral calcitriol and docetaxel had PSA responses of 81 and tolerated it well. Currently a phase II III calcitriol study is underway. Trials are also currently underway evaluating the drug G3139 with docetaxel. G3139 is an antisense...

Meat And The Pathology Of Human Disease

The fat in red meats has been identified as having a very high content of saturated fat (Table 7.2). Thus, based on fat content alone, red meat could be considered an atherogenic risk factor that contributes to coronary heart disease and ischemic strokes. A number of prospective studies have linked red meat intake to higher rates of coronary heart disease and stroke.18-22 Recent laboratory data also raise the possibility that the low polyunsaturated to saturated fat ratio in red meats (Table 7.2) increases the permeability of the cell membrane to insulin receptors and thus increases insulin resistance.23-25 This mechanism suggests that increased red meat intake (relative to other meats or no meat intake) could potentially produce a hyperinsulinemic state that would contribute to a higher risk of diabetes, and perhaps certain cancers (prostate, colon, breast). In this context, it is noteworthy that Snowdon has reported a prospective association between red meat intake and increased...

Laser Capture Microscopy

Tissue obtained from prostate surgery is rarely homogeneous in cell type (a fact admitted in Alaiya et al.'s 10 report) and contains not only tumor cells but also possibly multiple clonal variants of the tumor, nontumorous epithelial cells, undifferentiated epithelial cells, and stro-mal cells. Such a sample, therefore, is likely to give confusing results, as the protein profiles obtained would be far from representative of any particular cell type, unless the cancer cells were in the vast majority and even then subtle but important differences may be lost. To overcome this problem, laser capture microdissection of tissue samples is now being used. This technique uses lasers to remove small sections, sometimes cell by cell, from tissue slices on slides, in order to allow a homogeneous sample to be obtained. The downside to this technique is the painstaking microscopy and the length of time needed to capture enough cells to make a proteomic study worth carrying out. However, there have...

New Diagnostic Markers

The holy grail of prostate cancer research is probably the discovery of new diagnostic markers. There are currently several markers available for diagnostic purposes in prostate cancer 22 , although mostly these are used in immunohistochemical grading of cancer, with an aim to indicating the grade, and possible aggressiveness of the cancer. Various secreted proteins are also known, and have even proved useful in the clinic, such as prostate-specific antigen (PSA). It is likely, given these examples, that other, more accurate markers of disease presence, stage, and prognosis exist, which may be detected using proteomic techniques. An organ with a very specific function such as the prostate produces a large number of proteins, enzymes, and possibly cell surface markers that are produced only by that organ, and therefore have the potential to indicate the aberrant growth or function of that organ and the cells that form it. Proteomic investigation of the prostate could therefore yield...

Nonviral Delivery Systems

Nonviral gene transfer systems include chemical methods, such as the use of liposomes, and physical methods, such as microinjection electropo-ration. Liposomes are relatively cheap, nontoxic, nonimmunogenic lipids, and can be used for DNA coating to protect DNA from degradation until it reaches the target cell. The lipid envelope fuses with the target cell membrane, and the gene is delivered directly to the cytoplasm. However, the low efficiency of transgene delivery is the main limiting step. On the other hand, the safety of this technique has been verified in a phase I study in which liposomes containing the interleukin-2 (IL-2) gene were injected into the prostates of patients with advanced prostate cancer 6 .

Relationship Between Mutations and Environmental Factors

Researchers have argued for years whether cancer is caused by faulty genes or by toxins in the environment. In a recent study on 44,788 pairs of twins, some identical and others fraternal, and including two pairs with BRCA2 mutations, Scandinavian investigators concluded that although heritable factors make a minor contribution to susceptibility to most types of cancers, they may have a larger effect on prostate, colorectal, and breast cancers. In their study, 27 percent of breast cancers could be attributed to heritable factors, but the frequency rates of BRCA1 and BRCA2 mutations were too low to explain more than a fraction of the genetic effects observed. The data suggests that defects in other inherited susceptibility genes were involved. The presence of the disease in an identical twin, however, is not a guarantee the other twin will get it. In this study, the risk was 11 18 percent in identical twins, whereas it

Anatomy and Pathogenesis of the Urethral Injury

The risk for urethral injury increases with the number of broken pubic rami and the coexistence of posterior pelvic bone disruption. However, the contributing pathogenesis of pelvic fractures and the specific urethral anatomy that is disrupted has not yet been completely and accurately defined. The traditional concept that the prostatomembranous junction is the weak point and that the shearing force of the injury produces separation at that point has been revised. Following rupture of the prostatic and bladder attachments, the compressed pelvis and its hematoma forces the prostate upward, resulting in membranous urethral cephalad retraction and displacement with rupture at the bulbomembranous junction. The fibrous gap between the prostate and the bulbous urethra involves primarily the membranous component and the proximal edge of the bulb. The proximal and distal urethral lumens may be thus mal-aligned in both an anteroposterior and a lateral displacement. Consequently,

Localization of BRCA1 and BRCA2

There are many known mutations of the normal BRCA1 allele. More than 500 BRCA1 sequence variants have been identified. BRCA2 is also subject to numerous mutations. BRCA2 mutations account for most of the hereditary breast cancer not linked to BRCA1, but have less association with ovarian cancer. They are, however, associated with male breast cancer, and possibly prostate, colon, and pancreatic cancers. Mutations of these genes, either by insertion or deletion of non-triplet bases, cause frame shifts that cause transcription of the gene to end prematurely, resulting in truncated proteins that cannot function properly.

Mass In Jugular Foramen

Gross Pathology Metastatic prostate carcinoma impinging on CN EX, X, XI at level of jugular foramen. Treatment Prostate carcinoma treated by orchiectomy and hormonal modalities radiation. Discussion Prostate carcinoma produces metastases in the axial skeleton with the possibility of involvement at all levels of the spine as well as the cranial bones.

DNA in Dis Diagnostic Medicine

These altered animals are known in general as 'transgenic' or 'knockout' mice, where certain genes have been added to or deleted from, respectively, the normal mouse set of chromosomes. Often very small changes to the total DNA of an organism will produce large changes in its physical appearance, behavior, or intelligence. Transgenic mice have proved useful for creating animal models of human disease, for instance prostate cancer, thyroid deficiency, obesity, lateral sclerosis, or Alzheimer's disease. Such genetically-altered mice may also be used to test new drugs which might potentially cure disease in humans.

Major Public Health Problem

Panic and the phobias make a significant contribution to the burden of disease. The original Burden of Disease study only included panic disorder, while the estimation of the burden of disease in Australia in 1999 56 included panic, agoraphobia and social phobia but not the specific phobias. These three disorders accounted for 28000 Disability Adjusted Life Years lost, 1.1 of the total burden of disease in Australia, and 8 of the burden of all mental disorders. Put in context, the burden of panic and phobias was half the burden of asthma and four times the burden of insulin-dependent diabetes and comparable to the burden of prostate cancer. There is another reason why phobias constitute a major public health problem. A number of authors reviewed refer to the early age of onset of the phobias, on the propensity of fears to be the forerunners of other mental disorders, and on the possibility that fears in adolescence will lead to a limitation on educational, vocational and marital...

Summary Consistent Evidence

Dutch and Australian studies, the disability attributed to panic and phobias is shown to be two-thirds that due to affective disorders. Phobias are difficult to treat because sufferers are slow to come for treatment and often afraid of confronting their fears when they get to treatment. The burden of panic and phobias is four times the burden of insulin-dependent diabetes and comparable to the burden of prostate cancer.

Strategies to restore p53 function to human cancers

Besides these strategies, one approach appears particularly appealing small chemical compounds that endow p53 cancer mutants with function by restoring the integrity of the p53 core domain. Such compounds are highly desirable, because of the high frequency of p53 mutations and the large number of patients who could potentially benefit. It has been estimated that every year approximately 360,000 patients in the USA and 2.6 million patients worldwide are diagnosed with cancers that contain p53 mutations 34, 35 . This subset of human cancers (including lung, prostate, colorectal, breast, head and neck, pancreatic, and gastric cancers) is often resistant to conventional therapies and difficult to treat at advanced stages 5, 18, 24, 31, 35, 38, 58 .

Histone Acetylation And Dna Methylation

Combined with PB, synergistic effects on growth inhibition were observed (Emionite et al., 2004). A similar combination, consisting of PB and 13-cis RA, has been considered for the treatment of prostate carcinoma. The combination of PB and 13-cis RA inhibits cell proliferation and increases apoptosis in vitro in an additive fashion as compared with single agents. Similar to what observed in the case of treatment with demethylating agents in breast carcinoma, prostate tumor cells treated with both PB and 13-cis RA reveal increased expression of RARb, suggesting a molecular mechanism for the biological additive effect. The combination of PB and 13-cis RA also inhibits prostate tumor growth in vivo as compared with single agents. Histo-logical examination of tumor xenografts reveals decreased in vivo tumor cell proliferation, an increased apoptosis rate, and a reduced microvessel density in the animals treated with combined drugs, suggesting an antiangiogenesis effect of this combination...

Caused by Benign Prostatic Hypertrophy

As part of the normal aging process, prostatic tissue continues to grow and can potentially cause a bladder outlet obstruction. Histologically, 50-80 of the prostate volume is composed of stromal tissue, with the glandular tissue comprising the remaining 20-50 . The alpha adrenergic blockers described previously act on the stromal tissue of the prostate. Finasteride (Proscar), a selective inhibitor of 5-alpha-reductase, decreases the conversion of testosterone to dihydrotestosterone. Therefore, it prevents the growth of the glandular component of the prostate. In several studies, Proscar has been shown to improve urinary symptoms and reduce the volume of the prostate in men with benign prostatic hyperplasia and enlarged glands (43-46). In a more recent study by McConnell et al. Proscar was noted to reduce symptoms and prostate volume, increase the urinary flow rate, and reduce the probability of surgery for acute retention (47). The usual dose is 5 mg once daily.

Renal Tumours Involving the Vena Cava Incidence

Traditionally, more than 40 of patients with RCC have died from their cancer, in contrast to the approximately 20 mortality rates associated with prostate and bladder carcinomas 16 . In addition, as for other relatively radioresistant solid tumours for which as yet there are no chemotherapy or immunotherapy treatments of proven and significant efficacy, surgery represents the only therapeutic option that is able to affect and favourably alter patient survival and prognosis of the disease. A subgroup of patients with special characteristics concerning prognosis and a surgically challenging condition are those where the renal tumour is associated with extension of a thrombus into the inferior vena cava (IVC) (5 ), with the extension possibly reaching above the diaphragm and into the right atrium (1 ) 14 .

Unexpected Iatrogenic Vascular Injuries

Since urological procedures concern the bladder, the prostate, the kidney and the ureters and considering the proximity of iliac vessels, IVC and the aorta to these structures, it is not surprising that vascular injuries complicate urological operations. Urological operations are responsible for a small number of iatrogenic vascular traumas (3-7 ) while vascular catheterization and general surgery are the predominant causes 26, 27 .

Characterization of tumors with single and multiple p53 mutations

When compared to other systems for p53 mutant identification, the yeast functional assay has greater sensitivity than electrophoresis-based methods (SSCP, DGGE) 113, 132, 197, 198 and is comparable to the GeneChip approach 213 . In addition, the yeast assay is rapid and relatively inexpensive and, furthermore, it enables functional defects in p53 to be assessed. Functional analysis based on transactivation capacity in yeast is robust and appears more sensitive than transient transfection gene reporter assays in mammalian cells. Over 100 different mutant p53 alleles isolated from clinical samples were found to lack transactivation function in the red white ADE2-based assays 31, 55, 172 . The tissues have included fresh and frozen specimens from brain (glioblastoma and astrocytoma), upper aero-digestive tract, breast, colon, bladder, prostate, lymphocytes, and skin 29, 30, 34, 46, 65, 93, 103, 123, 125, 134, 145, 151, 159, 160, 168, 172, 186, 204, 211, 215 . Included in these analyses...

Papillary Carcinoma Of The Bladder

Nodular, rock-hard, irregular area of induration in peripheral lobe of prostate on digital rectal exam midline furrow between prostatic lobes obscured extension to seminal vesicles detected. Markedly elevated prostate-specific antigen (PSA) and acid phosphatase. Transrectal US-Prostate hypoechoic masses in peripheral zone with extension to seminal vesicles. Nuc-Bone Scan hot lesions of spine, sacrum, and pelvic bones (axial skeleton). CT MR prostate mass with capsular penetration and enlarged seminal vesicles. Irregularly enlarged, firm, nodular prostate. Core Needle Biopsy-Prostate single layer of malignant neoplastic cells arranged haphazardly in adenoplastic stroma. Prostatectomy with radiation orchiectomy leuprolide androgens flutamide. A primary malignant neoplasm of the prostate commonly arising from the peripheral zone (70 ), it is the most common male cancer. Prognosis and treatment depend heavily on stage. Prostate canccr exhibits hematogenous dissemination, most commonly to...

Pathology and Biology

The majority of primary lymphomas of the prostate are DLBCLs, but primary prostatic small lymphocytic lymphomas (SLLs), follicular lymphomas, Burkitt lymphomas, MALT lymphomas, and mantle cell lymphomas have also been reported 64,65,67,70 . A similar spectrum of lymphomas affects the prostate secondarily during the course of disseminated disease, and rare cases of secondary prostatic peripheral T-cell lymphoma, myeloma, and classical Hodgkin lymphoma have also been documented 67 . Histologically, lymphomas within the prostate gland show patchy or diffuse stromal infiltration, with compression, but preservation, of ducts and acini. Intraepithelial infiltration of neoplastic cells is seen in some cases. The morphologic and immunophenotypic features of prostatic lymphomas are similar to those of extraprostatic disease 3 . No studies have specifically addressed the genetics of pro-static lymphomas. As mentioned above, leukemic cells not infrequently infiltrate the prostate, sometimes as...

Treatment and Outcome

Because of the rarity with which lymphoma presents in the prostate, little is known of its prognosis and optimal treatment. In the series of Bostwick et al. 67 , 47 of patients with follow-up died of lymphoma, with a lymphoma-specific 5-year survival of only 33 73 of patients with primary prostatic lymphoma developed extraprostatic disease 1 to 59 months from diagnosis. There were no significant differences in survival between patients receiving different therapies (chemotherapy, radiotherapy, chemotherapy and radiotherapy, surgery only), between patients with primary or secondary prostatic lymphoma, or between patients with different types of lymphoma. However, patients in this retrospective study were treated over a 58-year period, and it is unlikely that these data reflect the results that would be achieved using current stage and subtype-specific therapeutic regimens. Indeed, a number of more recent case studies have reported good outcomes for patients with high-grade prostatic...

Pathology and Immunohistochemical Profile

The morphology of small cell carcinoma of the prostate is identical to that seen in the bladder (see above) and lung. In about 50 of cases, the tumors are composed of a mixture of small cell carcinoma and acinar adenocarcinoma 110 . The small cell component is positive for CD56, neuron-specific enolase (NSE), and chromo-granin A, and shows dot-like positivity using CAM5.2, but is negative for PSA and prostatic acid phosphatase (PSAP). The acinar component shows the reverse immunoprofile. It has been suggested that primary small cell carcinoma of the prostate may be distinguished from a metastasis from the lung by the absence of staining for thyroid transcription factor-1 (TTF-1),but there

Promoters and Transgenes

Targeting oncogenes and tumor-suppressor genes to the prostate in transgenic mice represents a rational approach for developing new mouse models (156). For example, using the prostate-specific sPB promoter, the rasT24 gene was targeted to the prostate to create hyperplasia. However, no PIN was detected after 6 mo (154). Unfortunately, many of the gene promoters used to date do not function in a prostate-specific manner and tumors develop in other primary sites. A prostatic hyperplasia model was reported using the MMTV-LTR promoter coupled to the int-2 gene (157). Analysis of this model revealed that it represented a hyperplasia of the ampullary gland (135,158), a mouse gland that has no human counterpart. Using the MMTV promoter to express keratinocyte growth factor (kgf )in the prostate led to papillary hyperplasia after 9 mo, but also led to kgf expression in the seminal vesicles, vas deferens, mammary gland, salivary gland, and Harderian gland (159). The C3(1) promoter linked to...

Diagnosis and Evaluation of Urethral Strictures

Normal Retrograde Urethrogram Images

Patients with urethral strictures most often present with obstructive voiding symptoms or urinary tract infections, such as prostatitis or epididymitis some will also present with urinary retention. On close inquiry, many of these patients have tolerated obstructive voiding symptoms for prolonged periods before progressing to complete obstruction.

Carotenoid Cleavage Enzymes During Development And In Various Tissues Of The Adult

The key step in vitamin A formation is the oxidative cleavage of provitamin A carotenoids by Bcmo1. As described above, the gene for Bcmo1 was cloned from several species and it was shown that it is widely distributed throughout a plethora of vertebrate tissues, including the intestine, liver, kidney, prostate, testis, ovary, and skeletal muscle (Lindqvist and Andersson, 2002). It can also be found in monkey retina and human retinal pigment epithelial cells (Bhatti et al., 2003).

Sphincteric Incompetence

Doing Kegels With Catheter

Pelvic-floor muscle exercises called Kegel exercises can speed the recovery of continence following prostatectomy therefore, patients should be instructed and perform the exercises before prostatectomy (55). There are several studies which suggest the utility of electrical stimulation (56), behavior training (57), and biofeedback (58) in the management of incontinence after prostate surgery. Unfortunately, many of these studies contain only a small number of patients, and many patients still experience wetting requiring pad use even though considered improved. These conservative measures offer little promise in the correction of severe or total urinary incontinence. The ideal material for periurethral injection is one that is easily injected, biocompatible, and causes little or no inflammatory reaction. There should be no migration of the injected material, and it should maintain its bulking effect for a long period of time. Polytetrafluoroeth-ylene (Teflon) paste was one of the first...

Followup Prevention Of Complications

Patients are considered complicated because an uncomplicated infection is defined as community acquired without structural or neurologic abnormalities. UTIs are responsible for many uroseptic episodes in the SCI population. Many risks exist including instrumentation, intermittent catheterization, stones, urethral strictures, benign prostatic hyperplasia, and detrusor external sphincter dyssynergia. Other causes include bladder overdistention, vesicoureteral reflux, large postvoid residuals, and high voiding pressures. The aim in management is to prevent, not to treat. This is best done by ensuring the well-being of the patient, providing adequate urinary drainage, and preserving healthy bacterial commenseral environment. Antibiotics should only be used during episodes of clinical infection, not asymptomatic bacteriuria. Asymptomatic bacteriuria does not usually need to be treated unless the patient has either a urease-producing organism, vesicoureteral reflux, or both.

Endoscopic Urethroplasty

Metal Sounds For Urethral Dilatation

With the patient in the lithotomy position, the supra-pubic percutaneous tract is dilated and a metal sound is passed through the bladder neck into the prostatic urethra (O Fig. 11.1). A suprapubic flexible cystoscope, when available, can be used instead of a metal sound. At this point, a 20-Fr urethrotome, with its half sheath, is introduced into the urethra, and carefully advanced through the membranous urethra, into the pelvic hematoma (O Fig. 11.2). Under combined endoscopic and fluoroscopic guidance, the urethrotome meets the tip of the sound (or the light of the flexible cystoscope). Under endoscopic guidance, the urethrotome is further advanced into the prostatic urethra, while the sound is retracted to the bladder neck. The urethrotome is removed, leaving the half sheath in the bladder and urethra. Through the half sheath, an 18-Fr fenestrated silicon catheter is placed into the bladder, and left in place for 4-6 weeks. Hematoma extent and prostate position can be easily...

10years Results Buccal Bulbar Urethroplasty 2015

Bulbar Urethroplasty Surgery Image

Pelvic fractures or perineal injuries can produce long defects from the apex of the prostate to the mid bulbar urethra that cannot be bridged by standard anastomotic techniques because of a very lengthy defect, vascular compromise of the anterior urethra, or prior anterior urethral surgery and associated spongiofibrosis that interferes with From 1992 to the present, 13 patients ranging in age from 29 to 72 years have undergone urethral reconstruction using a perineal artery fasciocutaneous flap. The length of the stricture varied from 3 to 12 cm and follow-up ranges from 1 to 10 years. These strictures were located uniformly in the proximal bulbomembranous and prostato-membranous urethra. Seven patients underwent an onlay island patch flap. Five of these were referred after several prior failed repairs, and two patients had been treated with radiation therapy for carcinoma of the prostate. Two of these patients required combined addition of a buccal graft onlay. Four patients...

Positively Worded Questions The Most Common Question Type

An 85-year-old man has had urinary frequency, difficulty initiating stream and dysuria for the last two months. A rectal exam reveals an enlarged prostate. Prostate-specific antigen (PSA) is riot elevated. Which part of the prostate is most likely affected in this patient's condition (D) Posterior lobe of the prostate

Dvog Proximal Bulbar Urethroplasty

Navicularis Following Transurethral Resection of the Prostate Patients who present with an isolated meatal fossa stricture following transurethral resection of the prostate generally gain little from repetitive dilations however, reliable reconstruction of the meatus and fossa navicularis with nearly perfect functional and cosmetic results can be accomplished using several surgical techniques.

Behavioral Voiding Dysfunction Pseudodyssynergia

Bladder outlet obstruction may also occur in the setting of an anatomically normal male patient owing to a dynamic obstruction caused by a lack of coordination between the detrusor and bladder neck smooth muscle (bladder neck dyssynergia) or striated muscle external sphincter (pseudodyssynergia). While psydodyssynergia generally implies a condition in a neurologically intact patient, similar conditions may be the result of a neurologic lesion (detrusor external sphincter dyssynergia, DESD) or in neurologically intact children (Hinman's bladder). Although the exact etiology of this condition is unknown, it is generally considered to be a learned behavior of failed pelvic relaxation. It has been postulated that the condition may arise as reaction to a negative response to micturition such as pain, and frequently is seen in younger male patients who have been treated for long periods for chronic prostatitis. Although not an absolute part of the syndrome, there is a preponderance of...

Acute Tubular Necrosis

He also describes slow-onset dull pain in his left flank and blood in his urine. He was recently treated for recurrent UTIs, which were attributed to an enlarged prostate gland. His father died of chronic renal failure, and his paternal grandfather died of cerebral hemorrhage.

Epidemiologic Studies of Cancer in Vegetarian Societies

The Health Food Shoppers Study12 in the U.K. recruited both vegetarian (n 3790) and non-vegetarian (n 6088) study subjects. Participants were identified via health food shops, magazines, and vegetarian societies between 1973 and 1979. Follow-up was completed by record linkage with National Health Service Central Register through 1995. SMRs were calculated based on the national mortality rates for England and Wales. For all malignant neoplasms combined, the SMR was significantly reduced in both males and females (0.50 and 0.76, respectively). Risk of stomach and colorectal cancer death was also lower, although the SMR for breast, ovary, and prostate cancers were close to 1.0 (See Figure 4.3). Death rate ratios (and 95 confidence limits) comparing vegetarians with non-vegetarians within the study were reported for stomach, colorectal, lung, breast, and prostate cancers after adjustment for age, sex, and smoking status.14 The rate ratios were as follows for stomach, 1.23 (0.62-2.47) for...

Homoeopathy Medicine For Bladder Infiltration Of Rectosigmoid Tumor

Testicles Undescended Adult

The longitudinal section delineates the bladder more as a triangle (Fig. 54.3), with the prostate gland (42) and vagina, respectively, seen below the bladder (compare Fig. 58.1). Transabdominal sonography of the genital organs requires a filled urinary bladder (38), which displaces the air-contain-ing intestinal loops (46) cranially and laterally to avoid their interfering shadows (45) and serves as an acoustic window. The prostate gland (42) is located on the floor of the bladder anterior to the rectum (43) and is visualized on the suprapubic transverse section and on the sagittal longitudinal sec-lion (Fig. 56.1). ITie normal prostate gland should not exceed the approximate size of 3 x 3 x 5 cm or the approximate volume of 25 ml. In older men, an enlarged prostate gland is frequently encountered (Fig. 56.2), which interferes The enlarged prostate gland (42) elevates the bladder floor (38), but the urinary bladder remains outlined by a wall that is seen as a smooth line (Fig. 56.2)....