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Forex denmark indicators advanced drainage

Опубликовано в Forex indicator delta | Октябрь 2nd, 2012

forex denmark indicators advanced drainage

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The serum PSA should become and remain undetectable after successful radical prostatectomy surgery. If this cannot be achieved or if there are positive margins after surgery, salvage radiation therapy should be considered.

This is recommended based on the likelihood that the supplemental radiation may control the relatively small amount of cancer that might remain in the vicinity of the resected prostate. Typically, salvage radiation therapy is 60 to 70 Gy, which is substantially less than primary definitive radiation therapy.

Without treatment, metastatic disease can develop from microscopic cancer remnants after radical prostate surgery in about eight years, and overall survival averages about 10 to 13 years. Salvage radiation therapy may also be recommended if the PSA becomes detectable at a later date, indicating possible residual disease that was present but previously undetectable could now be growing in the immediate area of the prostatic bed.

Of course, there is no guarantee that all remaining cancer will be within the radiation field, and it should not be considered with clear evidence of distant metastatic tumor spread. Alternatively, some patients with only limited positive margins or extracapsular extension may choose close monitoring and delay the salvage radiation therapy until there is a PSA spike, rise, or other evidence of disease progression. However, this risks developing distant metastases that could have been prevented with earlier radiation treatment.

A genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer can help assess and reliably estimate an individual patient's relative risk in these situations. PSA doubling time is another prognostic indicator. A slow doubling time might reasonably suggest observation instead of therapy for lower-risk patients.

Patients with a rapid PSA doubling time generally have poorer outcomes. A meta-analysis compared the results of definitive radiation therapy for Blacks compared to Whites using seven different randomized clinical trials. It found that Black men actually had a higher overall success rate with radiation therapy. Identifying the location of recurrent disease can be difficult when there is a biochemical recurrence.

There is little point in salvage radiation therapy to the prostatic bed if there are distant metastases or spread outside the possible radiation field. Rates for erectile dysfunction vary greatly depending on pre-operative potency and age, as well as the type of surgery performed nerve-sparing or not and the use of penile rehabilitation techniques.

If radiation therapy is done first and fails, then salvage radical prostatectomy surgery becomes challenging and often impossible due to scarring, fibrosis, and loss of anatomical landmarks. However, cryotherapy would still be possible as a salvage treatment. The use of freezing technology to kill cancer cells is not new; it was first used in London in the 19th century for breast and cervical cancers.

Modern cryotherapy required the development of closed circulation liquid Nitrogen probes, and one of the first uses of this new technology was for benign prostatic hyperplasia in Cryotherapy provides very good tissue ablation and destruction but has some complications and is very technology-dependent. Early use of this technology was delayed due to the size of the original Nitrogen probes, the development of urethral injuries, and the inability to monitor the exact location of the probes and ice-ball in real-time.

These problems were solved by technological advances, including the use of transrectal ultrasound to visualize the size and shape of the ice ball, more precise freezing probe placement, the use of multiple strategically placed interstitial temperature sensors to prevent over-freezing, simultaneously utilizing multiple smaller probes based on Argon gas for freezing instead of the harder to use liquid nitrogen, adding a thaw cycle to the protocol, and the standard placement of urethral warming catheters to protect the urethra from injury.

Hormonal therapy can help reduce the prostate size but does not otherwise improve survival outcomes with cryotherapy. The incidence of erectile dysfunction is relatively high with cryotherapy, which is an issue that should be discussed with patients before treatment.

Cryotherapy can be the primary surgical therapy for prostate cancer, but it is probably most useful as a salvage surgical treatment after radiation therapy has failed. In these cases, evidenced by persistent or rising PSA after radiation treatment, additional radiation or radical surgery is often extremely difficult, hazardous, or no longer even possible.

Hormonal therapy is often used in such cases but is not a curative option. Cryotherapy has shown it can control tumors resistant to all other therapies, which will still be susceptible to ablation by alternating freeze-thaw cycles that disrupt cell membranes resulting in tissue destruction. In such cases, it is important to be sure that the malignancy is still confined to the prostate. Since cryotherapy cannot treat nodal involvement, lymph node dissections may be needed.

Focal or limited cryotherapy is a possible experimental option in selected patients. The goal of radiation therapy is to provide a lethal dose of radiation to the tumor without harming the surrounding normal tissue of the bladder and rectum. No post-radiation prostate biopsies are recommended unless additional local therapy is being considered. The current standard of care is to use conformal techniques, such as intensity-modulated radiation therapy IMRT and image-guided radiation therapy IGRT.

Such conformal techniques allow higher dosages to be given to the prostate and tumor while not significantly increasing exposure to the surrounding tissues to minimize late side effects. Treatment usually consists of daily exposures 5 days a week for up to 8 weeks.

This typically amounts to a minimum of 38 to 45 fractions of 1. The American College of Radiology recommends a total dose of 75 to 78 Gy. At our institution, our radiation oncologists use a total dose of Doses higher than 81 Gy are not recommended due to increased risks of radiation cystitis and proctitis.

The use of hormonal therapy in combination with radiation has demonstrated improved overall survival in intermediate and high-risk disease. It appears that hormonal therapy increases tumor radiosensitivity by interfering with DNA double-stranded break repair. That is why the addition of hormonal treatment with LHRH agonists or similar medications before starting radiation therapy is now generally considered the standard of care.

Preliminary data suggests adding enzalutamide to standard hormonal therapy will enhance this radio-sensitizing effect. Various drugs are being investigated as possible prostate cancer radio-sensitizers. Besides hormonal therapy and enzalutamide described above, these include statins, IL, parthenolide, and even green tea.

So far, none are currently recommended for clinical practice. Significant areas of concern include prostate size and potential radiation side effects on the bowel and bladder radiation proctitis and cystitis.

Managing hemorrhagic complications of radiation cystitis includes oral pentosan polysulfate and hyperbaric oxygen therapy. Severe hematuria may require cystoscopy and continuous bladder irrigation. There are also possible issues with fatigue and increased fracture risk. There is a slightly higher incidence of secondary malignancies after definitive radiation therapy. The role of stereotactic radiotherapy in prostate cancer is less well defined than standard external beam radiation.

With stereotactic therapy, the individual fractionated dosages are higher, typically 7 to 8 Gy each, which allows for a much reduced total treatment time, usually only about a week. Higher fractionated dosages beyond 8 Gy are not recommended as they have been associated with increased toxicity and side effects.

Stereotactic radiotherapy is less suitable for patients with very large prostate volumes greater than 75 to mL or prior TURP surgery. Most experts prefer real-time tracking, and early reports suggest using urethral catheterization during treatment planning and simulation improves urethral identification. Newer SABR delivery systems include gantry devices that are currently undergoing clinical trials. It is hypothesized that using SABR for metastatic cancer may be reasonable to reduce the seeding of additional tumors, which may ultimately increase overall and progression-free survival.

This strategy has already been shown to improve survival in metastatic non-small cell lung cancer but is still theoretical for use in prostate cancer. Stereotactic ablative radiation therapy SABR may increase the patient's immune response. The proposed mechanism is by releasing additional tumor antigens due to the larger fractional radiation dosage, which then prompts the increased immunological response.

Overall, stereotactic radiotherapy appears to be similar in efficacy to other definitive treatments for low and intermediate-risk prostate cancers. This treatment is a reasonable alternative for appropriate low and intermediate-risk patients who desire the markedly reduced treatment schedule and have access to the technology. There have not been sufficient numbers of higher-risk patients reported to date to comfortably recommend stereotactic radiation to the high-risk prostate cancer group, although early reports suggest improved biochemical PSA control compared to standard external beam radiation therapy.

Brachytherapy is another form of radiation therapy that involves surgically implanting tiny radioactive seeds into the prostate. Conceptually, this allows a higher total dose to be delivered to the prostate without increasing exposure to surrounding structures. It also allows for optimal treatment in patients where transportation and other issues make standard external beam therapy more difficult.

Most prostates will accept from 75 to seeds. Hormonal therapy can shrink the prostate if it is too large for therapy greater than 60 gm. When combined with brachytherapy, hormonal therapy has been shown to improve survival outcomes, so it is usually recommended. Seeds are placed transperineally using TRUS and a template plan that has been previously worked out by a radiation therapist or physicist. Radioactive materials used include iodine , palladium , and cesium Cesium has the shortest half-life.

High-Dose Rate Brachytherapy can also be done using hollow needles placed through the perineum, then loaded with iridium or similar. These typically are left in place for 24 to 40 hours, during which time the patient is admitted to a hospital. The newer trend is to treat with only 2 fractions per day, allowing the patient to go home at night. External beam radiation can then be used to treat regional lymph nodes and other areas outside the prostate not adequately controlled by the seeds alone.

Outcomes are similar to external beam radiation and radical prostatectomy surgery, but there are no head-to-head trials. However, some evidence suggests that brachytherapy might be somewhat more effective than an external beam, at least in some patients. The most common complications reported from brachytherapy include exacerbation of urinary tract and rectal problems along with erectile dysfunction and seed migration.

The use of stranded seeds, such as "Rapidstrands," significantly reduces the seed migration rate. The clinical impact of seed migration is still unclear. Proton Beam Therapy can theoretically deliver a higher radiation dose more precisely than standard techniques. While theoretically an improvement, there are no randomized trials comparing proton beam therapy directly with standard radiation treatment. The current recommendation from the American Society for Radiation Oncology states that the best available data suggests that outcomes are similar between proton beam therapy and standard intensity-modulated radiation therapy IMRT.

Carbon Ion Therapy is another type of particle beam irradiation under investigation in Japan. Preliminary data appears promising. Radiation therapy and radical prostatectomy surgery are both highly effective for controlling most cases of localized prostate cancer. Treatment selection is then based on other factors such as patient preference, co-morbidities, age, availability of high-quality therapy, and transportation issues. Technology is continually changing to optimize radiation delivery to cancer while minimizing side effects, peripheral exposure, spillage, and long-term complications.

It is difficult to compare radiation therapy and radical surgery results as we are looking now at the outcomes data from radiation therapy delivered 10 to 15 years ago when the technology was less advanced than what is typically given today. The best available data suggest no significant difference in overall survival in most cases of potentially curable, localized prostate cancer treated with either external beam radiation therapy, stereotactic radiotherapy, brachytherapy radioactive seed implants , or radical prostatectomy surgery.

Treatment of aggressive prostate cancers may involve radical prostatectomy, radiation therapy, high-intensity focused ultrasound, chemotherapy, oral chemotherapeutic drugs, cryosurgery, hormonal therapy, immunotherapy, or some combination of these. Early use of chemotherapy has been shown to be helpful in many patients presenting with aggressive or advanced, localized disease.

If cancer has spread beyond the prostate, treatment options significantly change. Hormonal therapy, limited radiation therapy, radiopharmaceuticals, immunotherapy, and chemotherapy are the standard treatments reserved for a disease that has spread beyond the prostate and is no longer considered curable.

For example, limited radiation therapy can dramatically help control prostatic bleeding or alleviate the excruciating bone pain from a metastatic cancer deposit. Most hormone-sensitive cancers eventually become resistant to hormonal therapy and resume growth. At this point, the disease is considered castrate-resistant prostate cancer CRPC and requires additional treatment, usually chemotherapy. Chemotherapy in the modern era typically consists of docetaxel in addition to modified hormonal therapy.

Bisphosphonates like zoledronic acid and rank ligand inhibitors like denosumab have improved quality of life and reduced pathological fractures in CRPC patients. Unfortunately, these agents have not been shown to improve survival.

Before using either of these agents, a dental checkup is recommended due to their association with osteonecrosis of the jaw. Calcium and vitamin D supplements are recommended when either medication is used. Calcium citrate is the preferred calcium supplement due to its increased solubility and absorption while 5, units of daily supplemental vitamin D is also suggested for these patients.

Radium Ra dichloride is a radiopharmaceutical that works particularly well on bone metastases from prostate cancer. Radium specifically targets the bone and is ineffective in visceral, soft tissue, and nodal disease. Therefore it should be used in castrate-resistant prostate cancer with bone metastases but without significant organ, soft tissue, or lymph node involvement. Radium therapy improves the quality of life, reduces bone fracture rates, and extends survival even if only for a relatively short time.

It can be used with all other prostate cancer therapies. However, some data suggest that there may be an increased risk of fractures and deaths associated with Radium when used together with abiraterone and prednisone. The technology binds a beta particle source with a PSMA-specific binder into a unique radioligand which seeks out PSMA expressing cells and exposes them and their immediate microenvironment to beta radiation. The treatment has a good safety profile and is relatively well tolerated.

It has been found to extend progression-free and overall survival in this extremely difficult group of patients by about 4 or 5 months. Note: The drug remains available even though its manufacturer, Dendreon, has declared bankruptcy.

It is an autologous, dendritic cell-based vaccine that targets prostatic acid phosphatase. It is the only vaccine-based therapy currently available for prostate cancer in the U. We need to develop reliable prostate cancer biomarkers to help determine which future immunotherapy will offer the most benefit for each patient.

PARP inhibitors, such as olaparib and rucaparib, prevent cancer cells from repairing DNA damage which facilitates apoptosis. They are considered a type of targeted therapy as they work best in patients with DDRG germline mutations. Olaparib showed a median survival benefit of about five months more than double the median progression-free survival compared to enzalutamide or abiraterone treatment alone and was most effective in patients with BRCA2 mutations on germline testing.

The activity of various protein kinases is associated with the development of androgen-independent castrate-resistant prostate cancer. Protein kinases are involved in the growth, proliferation, aggressiveness, and metastases of prostatic cancers.

Some are also involved in the androgen receptor signaling pathway and offer the possibility of changing the cellular response to androgen deprivation through specific protein kinase inhibitor therapy. Another PARP inhibitor niraparib shows good efficacy and safety in metastatic castration-resistant prostate cancer clinical trials.

Research is ongoing in the challenging area of identifying molecular biomarkers that could potentially predict the response to immunotherapy to allow for individual customization of such treatment for patients with advanced, aggressive, or metastatic prostate cancer. New immunotherapy treatments, such as immune checkpoint inhibitor combinations, bispecific T-cell engager immunological therapies, and chimeric antigen receptors, are under development and early test results appear promising.

Lutetium is just one of the first treatments based on this therapeutic modality. Another promising area of research involves prostate cancer stem cells. These are small populations of prostate cancer cells that induce tumor onset, growth, and development. They contribute to the development of resistance to chemotherapy and promote metastasis.

Upregulation of cell surface markers found on these prostatic cancer stem cells is closely associated with more rapid cancer growth, metastases, and an overall poor prognosis. The development of hormonal-resistant prostate cancer involves several families of chromatin modifiers. Targeting the bromodomain and extra-terminal protein family would be a promising, new, and novel approach to treating castrate-resistant prostate cancer. Our relative lack of knowledge of androgen resistance mechanisms and genetics means that such therapies are not likely in the near future.

Second-generation anti-androgens fail at least in part due to androgen-receptor mutations or splicing adjustments. These actions result in cell reactivation. Various mechanisms of reducing androgen receptor protein levels and activity are being investigated, including androgen receptor nuclear localization inhibition, N-terminal suppression, heat-shock protein blockage, and proteasome-mediated accelerated degradation.

Ipilimumab is a type of monoclonal antibody that activates cytotoxic T lymphocytes by direct blockage of CTLA-4 cytotoxic T-lymphocyte antigen T-cell receptor sites, which would otherwise downregulate the immune system. Ipilimumab is primarily used as immunotherapy for melanoma but has been found to have some activity in prostate cancer.

Two large ipilimumab prostate cancer trials showed an improvement in progression-free survival, but overall survival was not statistically improved. Nivolumab is another monoclonal antibody cancer therapy that inhibits the activity of PD-1 receptors on T-cells. This results in a net increase in T-cell activity and an enhanced anti-tumor immune response. Nivolumab plus ipilimumab showed minimal additional efficacy in treating prostate cancer, but when combined with docetaxel, there was an improved response in castrate-resistant prostate cancer patients.

Targeted, individually customized anticancer therapies offer great potential for controlling the malignancy and reducing side effects by delivering the cytotoxic material selectively only to malignant cells. One way of doing this is by using designed ankyrin repeat proteins DARP. These are non-immunoglobulin-based scaffold proteins designed to deliver a cytotoxic payload exclusively to prostate cancer cells. The toxin was rapidly internalized, and normal prostatic cells were left unharmed. Germline testing intends to identify heritable, genetic cancer predispositions, inform individual patients and family members of any increased cancer risks, suggest customized screenings for selected, affected individuals, help guide prognostic predictions, and to assist in treatment decisions.

Hereditary prostate cancer due to germline mutations has an autosomal dominant pattern or transmission and is typically characterized by early-onset. Germline testing should be offered to any prostate cancer patient when the results could have a therapeutic or clinical impact on that individual or any of his family.

It should also be considered in patients with intraductal or cribriform histology, as these findings are closely associated with BRCA mutations. Other patients at higher risk for germline mutations include those with Gleason pattern 5 histology, early age of cancer diagnosis, or a positive family history of cancer particularly breast, colorectal, ovary, pancreas, prostate, or uterus , especially if they appeared at a younger age or died from the malignancy.

The optimal timing for discussing germline testing with patients is unclear. We prefer to discuss it as early as possible once the patient becomes eligible. There are often delays in getting the tests and obtaining appointments with genetic counselors.

Trying to deal with these issues at the same time as receiving bad news about newly metastatic disease or increased cancer spread may be too much for many patients and families to handle. As long as patients meet the criteria, germline testing can be done at any time. Germline testing is not the same as somatic or tissue-based biomarkers and genetic alterations. While they are often complementary, the two tests are different, although they can be done simultaneously.

Therefore, these mutations are inheritable by their offspring and may also be found in family relatives. Somatic mutations are found in other cell types, such as prostate cells that are not directly involved in human reproduction and therefore cannot be inherited by any offspring.

As the indications for germline testing have expanded, the number of genetic counselors has not caused significant delays. This puts a greater burden on primary care practitioners, urologists, and oncologists to discuss germline testing with patients and causes difficulties ordering the tests themselves.

It is helpful to develop a working relationship with a genetic counseling service or a specific counselor to better coordinate patient management and identify optimal testing parameters, screening criteria, mutation panels, and laboratories.

Three or more first or second-degree relatives with Lynch-syndrome-related cancers especially if diagnosed by age 50 , including biliary, colorectal, endometrial, gastric, glioblastoma, ovarian, pancreas, small intestine, or urothelial cancer of the upper urinary tracts.

Curiously, African American men have shown a relatively low incidence of germline mutations despite their well-known genetic predisposition to aggressive prostate cancer compared to the general population. Knowing and understanding germline status will help clinicians adjust their monitoring and cancer screening protocol appropriately for specified groups and individuals, offer more aggressive adjunctive treatment earlier to affected patients identified with certain high-risk germline mutations, be able to offer new treatment approaches such as targeted genetic therapies at some point in the future to advanced cancer patients, and be able to counsel individual family members who have a higher inherited, genetic risk of malignancy.

There are about germline mutations that have been identified and linked to prostate cancer. Germline mutations are mostly of two general types. ATM ataxia telangiectasia mutated is a key DNA damage control response gene that is also associated with an increased risk of breast, colorectal, pancreatic, and stomach cancers and prostate.

ATM carriers have a high relative risk of metastatic prostate cancer of 6. They are also more likely to progress if placed on active surveillance. BRCA1 and BRCA2 breast cancer susceptibility gene mutations have been associated with a number of cancers, particularly breast and ovarian cancer. These are tumor suppressor genes that are involved in the repair of damaged DNA strands. Of Ashkenazi Jewish men who develop prostate cancer, 3. Patients with metastatic castration-resistant cancer and a BRCA2 mutation that progresses rapidly despite initial chemotherapy might benefit from PARP inhibitor therapy such as olaparib or rucaparib.

Mutations in this gene have been associated with an increased risk for breast, ovarian, colon, thyroid, kidney malignancies, and prostate cancer. In Sweden, the CHEK2 gene was found to be the most frequent genetic mutation in their prostate cancer population at 3. EpCAM epithelial cell adhesion molecule, also known as CD is over-expressed in many rapidly growing cancers, including prostate cancer.

It is involved in cell signaling, migration, cellular adhesion, proliferation rate, invasion capacity, metastatic potential, and differentiation. It also helps regulate androgen receptor activity. There is also evidence that HOXB13 mutations may block an important tumor suppressor gene and increase mitotic kinases, which would promote prostate cancer metastases.

KLK3 T appears to have only a relatively modest negative effect on prognosis by itself unless it is also associated with DDRG mutations where much more rapid progression of cancer is noted. They are most often associated with Lynch syndrome.

P53 mutations in localized prostate cancer are relatively rare and are more frequently seen in metastatic disease. P53 is generally considered a tumor suppressor gene. Its activity produces p21 protein, which acts to slow cell division. Loss of P53 activity reduces tumor androgen sensitivity, increases prostate cancer cell proliferation, and promotes tumor growth.

Therefore, P53 mutations are generally considered a late and ominous finding in prostate cancer. NBN mutations are found in 2. NBN is a relatively uncommon germline mutation but, when present, has a significant three-fold negative prognostic impact on prostate cancer survival. The validity of the NCCN guidelines on screening criteria and which mutations to include in germline testing has been called into question. This will depend on commercial availability, cost, insurance coverage, potential usability of the resulting information, availability of quality genetic counseling, and the overall reliability of the testing provided.

Genetic counseling services are also available online. Physicians who order germline tests are ultimately responsible for discussing the results with their patients and arranging for genetic counseling if appropriate. This extra burden on physicians, as well as a general lack of knowledge about germline testing, result interpretation, how to counsel patients, the need for outside laboratory resources for the actual testing, questions about insurance coverage, and the lack of genetic counselors, are all impediments to the more widespread and effective use of germline testing.

An important part of evaluating prostate cancer is determining the stage. Its components include the size and extent of the tumor, the presence of involved lymph nodes, the PSA level, the Gleason score from a biopsy or surgical specimen , and the presence of metastases. When cancer cells spread from the prostate to other parts of the body, they most commonly go to the bones and lymph nodes. CT scans, MRIs, bone scans, and PET scans can evaluate for any cancer spread within the abdomen and pelvis, particularly to the regional and para-aortic lymph nodes.

Performing a PSA test in this young age group would also help find the small percentage of men who develop very aggressive and highly lethal prostate cancer before age For example, the best-selling author of "American Assassin ," Vince Flynn, died of metastatic prostate cancer at age Getting his initial PSA test at age 50 would not have helped him. Various predictive tables and nomograms are now available to help predict outcomes, positive lymph nodes, and survival after radical prostatectomy, based on outcomes data from various sources.

They generally include some combination of age, Gleason score, biopsy information, and PSA level. They may also require other clinical information, such as the number of positive biopsies with the percentage of tumor involvement and clinical and pathological staging.

Three of the most popular nomograms available online for free include the following, which can be found at their respective academic institutional websites are:. Prostate cancer may directly extend into the bladder sub-trigonally, causing hydronephrosis and eventually renal failure if both ureters become obstructed.

When this happens, a decision needs to be made whether or not to proceed with treatment. This is typically late in the course of the disease. Forgoing surgical procedures at this point leads to renal failure, which is usually painless, as it occurs slowly and incrementally. Gradually increasing renal failure is usually a painless and natural way to expire peacefully.

Patients slowly become more lethargic and eventually go to sleep. This may be preferable to forcing them to endure increasingly severe and debilitating pain from advancing disease and bone metastases. Treating the ureteral blockage may improve survival temporarily, but typically for just a few months.

This is a very difficult and personal decision. There is no right or wrong answer, but there certainly is a choice. It is suggested that patients and families approaching this decision point review and discuss the options available, and make a decision long before it becomes necessary.

Treatment of hydronephrosis for obstructive prostate cancer may include surgical transurethral resection of the tumor inside the bladder over the expected location of the ureterovesical junction and intramural ureters. The resection only needs to be sufficient to unroof or expose the ureteral lumen, but this is not always technically possible due to the loss of landmarks, anatomical distortion, and potential lack of mobility of the scope due to cancer.

Once the ureteral lumen is exposed, a double J stent can be used to maintain urinary drainage. Double J stents can be challenging to place in these cases unless the ureteral lumen is surgically exposed or opened first. Nephrostomy tubes are another possible solution when one or both ureters cannot be identified or opened transurethrally. In such cases, antegrade placement of a double J stent from above is far easier than the standard transurethral retrograde method. Ultimately, only one kidney needs to be drained and made functional.

Studies have shown no survival advantage to treating both kidneys in these situations. While a positive tissue biopsy is always preferred before treatment, situations arise where it may not be practical or obtainable. Patients may present requiring treatment who have a history of prostate cancer treated elsewhere with no confirmatory records immediately available. Other patients may have had prior bad experiences with an earlier biopsy and are now refusing all-new diagnostic procedures.

Perhaps there are medical issues, such as a new cardiac stent or a history of pulmonary embolisms, which require an extended period of significant anticoagulants that preclude doing the biopsy. With the use of MRI imaging, genomic-analysis testing validated prostatic nomograms, and all of the other pre-biopsy predictive tests, it is not unreasonable to consider initiating some degree of prostate cancer treatment in selected cases even without absolute histological confirmation of malignancy if the likelihood of cancer is sufficiently high.

Such cases are likely to be infrequent, and patients need to be fully informed regarding the standard of care as well as the possibility of treatment complications and side effects without the absolute assurance that they have a prostatic malignancy that is sufficiently aggressive and dangerous to justify the therapy.

In patients who undergo treatment, the most important prognostic indicators are patient age and general health at the time of diagnosis, as well as the cancer stage, pre-therapy PSA level, and Gleason score. A poorer prognosis is associated with higher-grade disease, more advanced stage, younger age, increased PSA levels, and a shorter "PSA doubling time. There is no clear evidence that either radical prostate surgery or radiation therapy has a significant survival advantage over the other, so treatment selection has relatively little effect on life expectancy.

A study at the National Cancer Institute investigated the potential role of urinary thromboxane B2 TXB2 as a possible marker for aggressive prostate cancer. Thromboxane B2 is a metabolite of TXA2, a cyclooxygenase-derived eicosanoid associated with metastatic disease. In this study, men with prostate cancer were followed for a median of 8.

Investigators found a statistically significant and distinct association between high urinary TXB2 levels and mortality in African American men with prostate cancer but not in similar Caucasian American patients of European ancestry. They also found that aspirin appeared to reduce TXA2 synthesis and all-cause mortality in the high urinary TXB2 group suggesting a possible therapeutic benefit.

Palliative Care focuses on treating cancer symptoms and improving quality of life. The goal of palliative care is symptom control and pain relief rather than curing cancer. Cancer pain related to bone metastases may be treated with bisphosphonates, rank ligand inhibitors, opioids, radiopharmaceuticals, and palliative radiation therapy.

A common mistake is failing to get palliative care and Hospice services involved early enough in the course of the disease so they can start patient assistance immediately when needed, without undue delays.

Prostate-specific antigen PSA is a protein produced by the prostate and is abundant in semen. Its natural function is to divide seminogelin in the semen, which helps in liquefaction. The expression of PSA is androgen-regulated. It was originally used as a prostatic tissue stain to help determine the etiology of tumors of unknown origin. Later, serum levels of PSA were used as a prostate cancer screening tool because serum PSA levels start to increase significantly about seven to nine years before the clinical diagnosis of malignancy.

While a good indicator of prostatic disorders, PSA elevation is not specific for cancer as it is also elevated in benign prostatic hyperplasia, infection, infarction, inflammation prostatitis , and after prostatic manipulation. While it unquestionably increases prostate cancer detection rates, the value of PSA testing is less clear in avoiding overtreatment, improving quality of life, and lengthening overall survival, which is why routine PSA screening for prostate cancer remains quite controversial.

PSA testing became widely available in the United States in , and since then, prostate cancer detection rates have increased substantially. The current controversy is whether PSA screening provides sufficient benefits to offset the complications and side effects of "unnecessary" biopsies and curative therapies since most men with prostate cancer will have slow-growing, low-grade cancers for whom definitive, curative therapy often causes considerable harm with little or no survival benefit.

For men 55 to 69 years of age, the decision regarding whether to be screened for prostate cancer by PSA should be an individual one after a full discussion about the benefits, harms, and limitations of such screening. Routine PSA screenings are not recommended in men 75 years or over, based on the conclusion that definitive treatment of localized cancers for most older men has minimal effect on overall survival while adding significant treatment side effects and morbidities to many.

Many professional organizations now have guidelines and recommendations regarding PSA screening for prostate cancer. Most include a recommendation for an informed discussion with patients about the benefits and potential risks of screenings, biopsies, definitive therapy, and possible overtreatment. Some guidelines lower the age to stop routine screening at age 70 depending on health status and family history. Regardless, this is an individual decision best made by patients and family members after a thorough discussion of the pros and cons of continuing screening.

Screening options include a digital rectal exam and a prostate-specific antigen PSA blood test. Such screenings may lead to a biopsy with some associated risks. Transrectal ultrasound has no role in prostate cancer screenings. Here are some of the arguments for and against:. At least two separate PSA levels should be done before proceeding with more advanced testing. A patient with a negative initial tissue biopsy being considered for a repeat prostatic biopsy can best be further analyzed and risk-stratified by tissue-based genomic bioassay such as ConfirmMDx.

Men on active surveillance can be tracked and followed with genomic testing or serial PCA3 testing in addition to standard PSA levels. Patients with low-grade or intermediate-grade disease being considered for either active surveillance or definitive therapy would benefit most from the Prolaris test.

Patients with low-grade or intermediate-grade disease considering radical prostatectomy can be evaluated with either the Decipher, Oncotype Dx Prostate, Prolaris, or ProMark test. Patients who are post-radiation therapy or diagnosed with prostate cancer after TURP surgery can best be tracked with the Prolaris genomic biomarker test. Overall prognosis, cancer-specific survival, and risk of metastases are best assessed in post-radical prostatectomy patients with a genomic test that serves as a prognostic marker of cancer control outcomes such as either Decipher or Prolaris.

Patients should be encouraged to consider participation in prostate cancer clinical trials whenever possible. These can be found at several locations. For the most complete and comprehensive list of all open prostate cancer clinical trials in the United States, go to clinicaltrials. Prostate cancer diagnosis and treatment can be complex and is often controversial.

These and many more issues continue to challenge clinicians who deal with prostate cancer patients and men at risk for this common, potentially lethal male malignancy. The interprofessional team can optimize the treatment of these patients through communication and coordination of care. Primary care providers, urologists, oncologists, radiation oncologists, and nurse practitioners provide diagnoses and care plans.

Specialty care urologic nurses should work with the team to coordinate care and be involved in patient education and monitoring compliance. The interprofessional team can thus improve outcomes for patients with prostate cancer. This book is distributed under the terms of the Creative Commons Attribution 4.

Turn recording back on. Help Accessibility Careers. StatPearls [Internet]. Search term. Prostate Cancer Stephen W. Author Information Authors Stephen W. Affiliations 1 Creighton University Medical Center. Continuing Education Activity Worldwide, prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men. Introduction Worldwide, prostate cancer is the most commonly diagnosed male malignancy and the fourth leading cause of cancer death in men.

Etiology The known major risk factors are age, ethnicity, obesity, and family history. Men with a first-degree relative father or brother with prostate cancer have twice the risk of the general population. Risk increases with an affected brother more than with an affected father. Patients with a strong family history of prostate cancer tend to present with cancer at a younger age 2. In the United States, black men are more commonly affected than white or Hispanic men, and it is more deadly in blacks.

The incidence and mortality for Hispanic men with prostate cancer are one-third lower than non-Hispanic whites. No single gene is responsible for prostate cancer, although many genes have now been implicated.

Loss of p53 activity reduces tumor androgen sensitivity, increases prostate cancer cell proliferation, and promotes tumor growth. Therefore, p53 mutations are generally considered a late and ominous finding in prostate cancer. A Genetic Risk Score GRS , including high-risk genetic markers and SNPs, has been proposed to help with the risk stratification of prostate cancer, especially in families; but this type of testing is not yet ready for individual patient diagnostics.

Over Single Nucleotide Polymorphisms SNPs and other genes have been linked to an increased risk of prostate cancer. Clinically significant germline mutations will be reviewed later. There is little, if any, evidence that demonstrates an association between trans fat, saturated fat, or carbohydrate intake and prostate cancer. However, a lard diet high in unsaturated fats has been shown in a mouse model to significantly enhance the progression of prostate cancer.

Alcohol consumption appears to have little or no effect on prostate cancer risk. Vitamin supplements do not lower the risk, and in fact, some vitamins may increase it. High calcium intake is associated with advanced prostate cancer. Diets high in saturated fat and milk products seem to increase the cancer risk. Whole milk consumption after a diagnosis of prostate cancer has been linked to an increased risk of recurrence, especially in overweight men.

Lower vitamin D blood levels may increase the risk of developing prostate cancer. Red meat and processed meats also appear to have little effect overall, but some studies suggest increased meat consumption is associated with a higher risk. Fish consumption may lower prostate cancer deaths but does not affect the occurrence rate. However, high dietary omega-3 fatty acids from fish oil have been linked to an increased risk of clinically significant, high-grade prostate cancer.

Some evidence supports the belief that a vegetarian diet lowers rates of prostate cancer, but this is not considered a conclusive or significant influence. Increased soy products in the diet seem to reduce prostate cancer risk. These products contain phytoestrogens that may have a direct estrogenic effect or by inhibition of 5 alpha-reductase. Folic acid supplements have also not been shown to significantly affect the risk of developing prostate cancer.

Lycopene from tomatoes appears to have a protective effect against prostate cancer. Overall, a Mediterranean diet rich in anti-oxidants from olive oil, tomatoes, etc. It has also been shown to reduce Gleason Grade progression in patients on Active Surveillance for low-grade prostate cancer. This effect is increased in patients on androgen deprivation therapy. Regular aspirin, now used by an estimated This effect may be from both anti-inflammatory activities as well as reduced angiogenesis.

The beneficial effect of aspirin and NSAIDs appears to be more significant in aggressive prostate cancer and those with prostatitis. Veterans who have had Agent Orange exposure tended to present with prostate cancer at a younger age and higher clinical stage than veterans without such contact. However, overall outcomes were similar. Agent Orange exposure may increase the risk of prostate cancer recurrence, particularly following surgery.

Infections with chlamydia, gonorrhea, or syphilis seem to increase the risk of developing prostate cancer. Human Papilloma Virus HPV has been proposed to have a role in prostate cancer incidence, but the evidence is inconclusive. Epidemiology Prostate cancer is the most commonly diagnosed organ cancer in men and the second leading cause of male cancer death in the United States. Incidence rates have increased, although the death rate has decreased since , when PSA testing became widely available.

Ninety-nine percent of all prostate cancers occur in those over the age of 50, but it can be quite aggressive when it occurs in younger men. In the United States, prostate cancer is more common in African Americans at more than double the rate in the general population. It is less common in men of Asian and Hispanic descent than in Whites. In Europe, prostate cancer is the third most diagnosed cancer after breast and colorectal. In the United Kingdom, it is the second most common cause of male cancer death after lung cancer, similar to the situation in the United States.

The majority of new cases are diagnosed in men from 65 to 74 years of age There are currently 3,, men living in the United States with prostate cancer, and the overall risk of an individual male dying from prostate cancer is 1 in 39 or about 2.

Overall, the vast majority of men with prostate cancer will die from unrelated problems. Drop in the diagnosed incidence of low-grade prostate cancer. The incidence of seminal vesicle invasion, lymph node involvement, and positive surgical margins also increased after In particular, the incidence of lymph node involvement more than doubled after to 7.

Pathophysiology The prostate is roughly 3 centimeters long, about the size of a walnut, and weighs approximately 20 grams. The cancer cells grow and begin to multiply, initially spreading to the immediately surrounding prostate tissue forming a tumor nodule.

Such a tumor may grow outside the prostate extracapsular extension or may remain localized within the prostate for decades. Metastases to the bone are thought to be partially due to the prostatic venous plexus draining into the vertebral veins. Histopathology The Gleason Scoring System The Gleason prostate cancer score has been shown, over time, to be the most reliable and predictive histological grading system available.

Grade Group 1 Gleason Score less than or equal to 6 : Only individual discrete well-formed glands. Grade Group 5 Gleason Scores 9 or 10 : Lacks gland formation or with necrosis with or without poorly-formed, fused, or cribriform glands. History and Physical Early prostate cancer is usually asymptomatic.

In an attempt to improve on standard PSA testing alone, many alternative pre-biopsy screening tests are now available: [] Free and Total PSA: The percentage of free PSA in the blood can be a useful indicator of malignancy. Can the test be used for patients on active surveillance? If not, is the testing company doing or considering a study to evaluate its use in these patients? Can the test be repeated later if the PSA changes? If so, what degree of change in the PSA would warrant a repeat test?

How many ongoing studies and research is being done for further validation and utility of the test? Is the test designed to assess the risk of any prostate cancer or just Gleason pattern 4 and higher? Is the test result valid independently without the need to provide any clinical patient data? What about insurance coverage and patient cost? Does the company offer an indigent patient program? What is the expected percentage of "unreportable" test results that will require the patient to repeat the test?

Will the test results affect patient care or treatment? If not, then the test may be unnecessary. Low risk: Very low risk of Gleason 7 or higher disease, where a biopsy may safely be reasonably avoided. The negative predictive value is Increased risk: A biopsy should be considered due to the increased likelihood of finding clinically significant disease.

During prostate biopsies, transrectal ultrasound TRUS can sometimes see a potentially "suspicious hypoechoic area," but ultrasound alone is not a reliable diagnostic test for prostatic malignancy. TRUS is best used for directing the needle for prostate biopsies. In Europe, a positive MRI finding is sometimes sufficient to diagnose prostate cancer without necessarily requiring histological confirmation.

Prostate MRI is also used for surgical planning in men considering radical prostatectomy and improved biopsies instead of saturation biopsies when cancer is strongly suspected despite a negative initial TRUS-guided biopsy. MRI of the prostate may also have a role in active surveillance as an alternative to periodic or repeated biopsies.

Cognitive Recognition means that with an understanding of the anatomical location of the suspicious lesion, the urologist can use standard TRUS imaging and target the expected geographic area of the suspicious lesion even without being able to see it directly. The contribution from agricultural sources is estimated at t P year -1 with an uncertainty interval of — t P year In this context, stream bank erosion is regarded as part of the natural background contribution, although some of the eroded stream bank material is likely of agricultural origin.

However, the proportion of which cannot be quantified at present. A range of maps relating to the risk of phosphorus loss from land to water at fine spatial scale field scale and finer has been made available for local mitigation planning. For rivers, lakes and marine areas, an attempt has been made to assess the sensitivity of these water bodies to phosphorus inputs.

Here, phosphorus sensitivity should be understood as an assessment of how likely it is that the environmental quality of an aquatic area is significantly affected by changes in the input of phosphorus to this water body. The composition of plant communities in streams reflects a range of natural conditions, but different types of anthropogenic influences play an at least equally important role. In order to be able to assess the extent to which inorganic phosphorus can be critical for meeting the objectives of the Danish Macrophyte Index DVPI , a method is described based on plant traits that in the future will allow for a separation of the importance of inorganic phosphorus from other types of impact.

Assuming a strong relationship, it may in principle be possible to estimate the state of a given lake on the basis of catchment characteristics. This means that the use of such catchment data will be a very uncertain method for estimating the conditions of non-examined lakes. It is therefore currently not possible on the basis of these data and analyses, to develop a model that can be used to estimate the state of lakes with unknown conditions from information on properties of the lake catchments.

The mapping of the phosphorus sensitivity of marine areas was based on six indicators. These indicators form the basis for a categorisation of the phosphorus sensitivity of marine areas as scaled from the variation in the phosphorus sensitivity of Danish marine areas. The results of this mapping can support a qualitative assessment of the expected response of the individual marine areas to changes in phosphorus inputs relative to other Danish marine areas.

That a marine area is estimated to have a high level of phosphorus sensitivity based on one or more indicators does not preclude the area from being affected by other factors too. For example, a marine area with high phosphorus limitation can also be sensitive to changes in the nitrogen input.

Marine areas exhibiting high levels of phosphorus sensitivity are often characterised by a mainly phosphorus-limited algae growth, and the marine area being influenced by phosphorus input from its catchment area. However, major or long-term changes in the phosphorus input would be required to induce a shift in environmental state as either local sources have no significant effect or accumulation of phosphorus in the sediment over time has been so high that many years of low loading are required for a system change to take place.

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Skip to content Forex Indicators. Forex Indicators. Toggle Menu Close. Method of Volume Spread Analysis, which reveals manipulations and "smart money" transactions, is rapidly gaining popularity, but while years ago the traders studied the market on their own, now the VSA indicator can take some of the functions. Medium-term strategies are considered to be the most stable and simple, but many experts teach beginners to give preference to levels and volumetric analysis, and for some reason ignore time-tested reliable indicators.

Special modules for the analysis of the dynamics of balance and funds in the account are added to many modern terminals. Unfortunately, the MT4 terminal is outdated for this purpose, but the balance indicator can easily compensate for these shortcomings. Rubicon indicator is not just another custom indicator designed to perform some specific function, it can be considered a full-fledged trading strategy that is suitable for any timeframe and instruments.

Indicator QQE belongs to a class of rare algorithms that consistently work on any trading tools for decades. Traders buy and sell assets for currency in financial markets, and while there is no problem in assessing the value of the instrument on the commodity or stock exchange, Forex has got special cluster indicators for this purpose. You can often hear that the ultra-precise indicators are fantasy of the beginners who are searching for the "Holy Grail".

In part, this is a true remark, because even an accurate indicator sometimes fails, but critics are not telling the whole story here, as such indicators do exist. When educating new traders, many teachers and experienced speculators forget to mention that the indicators for beginners must meet several criteria, the most important of which being ease of setting and simplicity of formulas.

Technical indicators do not lose their relevance after first calculations on a sheet of paper and are used in our age of IT technologies in all terminals, which is quite natural, because they greatly simplify the process of finding trading signals. Novice traders often ask whether there are efficient indicators that can generate reliable signals to open orders. Of course, such algorithms exist, and today's publication will be dedicated to indicators like these.

Cyclical fluctuations are an integral feature of many physical and social processes, and the foreign exchange market, where thousands of traders and investors commit certain actions every second, is no exception to this rule. The price of any currency depends on the situation in the economy, and if in the 20th century the dynamics of price was mainly affected by the monetary policy of central banks, now you have to keep track of events around the world, and news indicator helps to do so.

The main goal of any trading strategy is not even searching for a particular signal to open a position, but rather filtering out the excess market noise that can "break" reliable patterns, and ZZ indicator is very good at handling this task. Join us:. Forex About the site. Forex indicators Forex indicators are auxiliary tools necessary for decision-making in difficult moments, when the behavior of a currency pair is ambiguous.

Volatility indicators: when market not the rival but partner. The choice of the oscillator or how to find the useful assistant. Efficient Indicators Exist!

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