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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Prostate cancer screening is an attempt to find unsuspected cancers. Initial screens may lead to more invasive follow-up tests such as a biopsy. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Such screening is controversial and, in some people, may lead to unnecessary disruption and possibly harmful consequences. Routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.
The United States Preventive Services Task Force (USPSTF) recommends against the PSA test for prostate cancer screening in healthy men regardless of age. They concluded that the potential benefit of testing does not outweigh the expected harms. The Centers for Disease Control and Prevention shared that conclusion. The American Society of Clinical Oncology and the American College of Physicians discourages screening for those who are expected to live less than ten to fifteen years, while in those with a greater life expectancy a decision should be made by the person in question based on the potential risks and benefits. In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment." American Urological Association (AUA 2013) guidelines call for weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a ten-year period against the known harms associated with diagnostic tests and treatment. The AUA recommends screening decisions in those 55 to 69 be based on shared decision making, and that if screening is performed it should occur no more often than every two years.
In those who are being regularly screened, 5-alpha-reductase inhibitor (finasteride and dutasteride) reduce the overall risk of being diagnosed with prostate cancer; however, there is insufficient data to determine if they have an effect on the risk of death and may increase the chance of more serious cases.
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.
The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
HGPIN is diagnosed from tissue by a pathologist, which may come from:
- a needle biopsy taken via the rectum and,
- surgical removal of prostate tissue:
- transurethral resection of the prostate - removal of extra prostate tissue to improve urination (a treatment for benign prostatic hyperplasia),
- radical prostatectomy - complete removal of prostate and seminal vesicles (a treatment for prostate cancer).
Blood tests for prostate specific antigen (PSA), digital rectal examination, ultrasound scanning of the prostate via the rectum, fine needle aspiration or medical imaging studies (such as magnetic resonance imaging) are "not" useful for diagnosing HGPIN.
The clinical diagnosis of BPH is based on a history of LUTS (lower urinary tract symptoms), a digital rectal exam, and exclusion of other causes of similar signs and symptoms. The degree of LUTS does not necessarily correspond to the size of the prostate. An enlarged prostate gland on rectal examination that is symmetric and smooth supports a diagnosis of BPH. However, if the prostate gland feels asymmetrical, firm, or nodular, this raises concern for prostate cancer.
Urinalysis is typically performed when LUTS are present and BPH is suspected to evaluate for signs of a urinary tract infection, glucose in the urine (suggestive of diabetes), or protein in the urine (suggestive of kidney disease). Bloodwork including kidney function tests and prostate specific antigen (PSA) are often ordered to evaluate for kidney damage and prostate cancer, respectively. However, checking blood PSA levels for prostate cancer screening is controversial and not necessarily indicated in every evaluation for BPH. Benign prostatic hyperplasia and prostate cancer are both capable of increasing blood PSA levels and PSA elevation is unable to differentiate these two conditions well. If PSA levels are checked and are high, then further investigation is warranted. Measures including PSA density, free PSA, rectal examination, and transrectal ultrasonography may be helpful in determining whether a PSA increase is due to BPH or prostate cancer. Ultrasound examination of the testes, prostate, and kidneys is often performed, again to rule out cancer and hydronephrosis.
Validated questionnaires such as the American Urological Association Symptom Index (AUA-SI), the International Prostate Symptom Score (I-PSS), and more recently the UWIN score (urgency, weak stream, incomplete emptying, and nocturia) are useful aids to making the diagnosis of BPH and quantifying the severity of symptoms.
Voiding position when urinating may influence urodynamic parameters (urinary flow rate, voiding time, and post-void residual volume). A meta-analysis found no differences between the standing and sitting positions for healthy males, but that, for elderly males with lower urinary tract symptoms, voiding in the sitting position:
- the post void residual volume was decreased
- the maximum urinary flow was increased, comparable with pharmacological intervention
- the voiding time was decreased
This urodynamic profile is associated with a lower risk of urologic complications, such as cystitis and bladder stones.
The diagnosis of IgG4-related prostatitis could be made from histological examination if prostate biopsy or surgery has been performed. The hallmark histopathological features of established IgG4-related disease are storiform fibrosis, a dense lymphoplasmacytic (lymphocytes and plasma cells) infiltrate rich in IgG4-positive plasma cells, and obliterative phlebitis.
However, identification depends on whether or not urologists and pathologists are aware of IgG4-related prostatitis/disease, as special immunostaining is required to identify the characteristic IgG4-positive plasma cells infiltration in prostatic tissue.
Several case reports of interstitial pneumonitis (which can progress to pulmonary fibrosis) in association with bicalutamide treatment have been published in the medical literature. Interstitial pneumonitis with bicalutamide is said to be an extremely rare event, and the risk is far less relative to that seen with nilutamide (which has an incidence rate of 0.5–2% of patients). In a very large cohort of prostate cancer patients, the incidence of interstitial pneumonitis with was 0.77% for nilutamide but only 0.04% (4 per 10,000) for flutamide and 0.01% (1 per 10,000) for bicalutamide. An assessment done prior to the publication of the aforementioned study estimated the rates of pulmonary toxicity with flutamide, bicalutamide, and nilutamide as 1 case, 5 cases, and 303 cases per million, respectively. In addition to interstitial pneumonitis, a single case report of eosinophilic lung disease in association with six months of 200 mg/day bicalutamide treatment exists. Side effects associated with the rare potential pulmonary adverse reactions of bicalutamide may include dyspnea (difficult breathing or shortness of breath), cough, and pharyngitis (inflammation of the pharynx, resulting in sore throat).
ASAP is considered an indication for re-biopsy; in one survey of urologists 98% of respondents considered it a sufficient reason to re-biopsy.
Bicalutamide may cause liver changes rarely, such as elevated transaminases and jaundice. In the study of 4,052 prostate cancer patients who received 150 mg/day bicalutamide as a monotherapy, the incidence of abnormal liver function tests was 3.4% for bicalutamide and 1.9% for standard care (a 1.5% difference potentially attributable to bicalutamide) at 3-year median follow-up. For comparison, the incidences of abnormal liver function tests are 42 to 62% for flutamide, 2 to 3% for nilutamide, and (dose-dependently) between 9.6% and 28.2% for , whereas there appears to be no risk with enzalutamide. In the trial, bicalutamide-induced liver changes were usually transient and rarely severe. The drug was discontinued due to liver changes (manifested as hepatitis or marked increases in liver enzymes) in approximately 0.3% to 1% of patients treated with it for prostate cancer in clinical trials.
The risk of liver changes with bicalutamide is considered to be small but significant, and monitoring of liver function is recommended. Elevation of transaminases above twice the normal range or jaundice may be an indication that bicalutamide should be discontinued. Liver changes with bicalutamide usually occur within the first 3 or 4 months of treatment, and it is recommended that liver function be monitored regularly for the first 4 months of treatment and periodically thereafter. Symptoms that may indicate liver dysfunction include nausea, vomiting, abdominal pain, fatigue, anorexia, "flu-like" symptoms, dark urine, and jaundice.
Out of millions of patient exposures, a total of five cases of bicalutamide-associated hepatotoxicity or liver failure, two of which were fatal, have been reported in the medical literature as of 2016. One of these cases occurred after only two doses of bicalutamide, and has been regarded as much more likely to have been caused by prolonged prior exposure of the patient to flutamide and . In the five reported cases of bicalutamide-associated hepatotoxicity, the dosages of the drug were 50 mg/day (three), 100 mg/day (one), and 150 mg/day (one). Relative to flutamide (which has an estimated incidence rate of 0.03% or 3 per 10,000), hepatotoxicity is far rarer with bicalutamide and nilutamide, and bicalutamide is regarded as having the lowest risk of the three drugs. For comparison, by 1996, 46 cases of severe cholestatic hepatitis associated with flutamide had been reported, with 20 of the cases resulting in death. Moreover, a 2002 review reported that there were 18 reports of hepatotoxicity associated with in the medical literature, with 6 of the reported cases resulting in death, and the review also cited a report of an additional 96 instances of hepatotoxicity that were attributed to , 33 of which resulted in death.
The clinical studies that have found elevated liver enzymes and the case reports of hepatotoxicity with bicalutamide have all specifically pertained to men of advanced age with prostate cancer. It is notable that older age, for a variety of reasons, appears to be an important risk factor for drug-induced hepatotoxicity. As such, the risk of liver changes with bicalutamide may be less in younger patients, for instance young hirsute women and transgender women. However, it has been reported on the basis of very limited evidence that this may not be the case with flutamide.
From a theoretical standpoint (on the basis of structure–activity relationships), it has been suggested that flutamide, bicalutamide, and nilutamide, to varying extents, all have the potential to cause liver toxicity. However, in contrast to flutamide, hydroxyflutamide, and nilutamide, bicalutamide exhibits much less or no mitochondrial toxicity and inhibition of enzymes in the electron transport chain such as respiratory complex I (), and this may be the reason for its much lower risk of hepatotoxicity in comparison. The activity difference may be related to the fact that flutamide, hydroxyflutamide, and nilutamide all possess a nitroaromatic group, whereas in bicalutamide, a cyano group is present in place of this nitro group, potentially reducing toxicity.
On a subsequent biopsy, given the diagnosis of ASAP, the chance of finding prostate adenocarcinoma is approximately 40%; this is higher than if there is high-grade prostatic intraepithelial neoplasia (HGPIN).
A CT scan can detect bone metastases before becoming symptomatic in patients diagnosed with tumors with risk of spread to the bones. Even sclerotic bone metastases are generally less radiodense than enostoses, and it has been suggested that bone metastasis should be the favored diagnosis between the two for bone lesions lower than a cutoff of 1060 Hounsfield units (HU).
IgG4-related disease responds well, and often dramatically, to glucocorticoid therapy, provided that advanced fibrotic lesions have not resulted in irreversible damage, and this has included resolution of radiologic findings. Men given glucocorticoids to treat IgG4-related disease at other anatomical sites sometimes report relief of their lower urinary tract symptoms, suggesting that IgG4-related prostatitis may be underdiagnosed.
Cases are however likely to get misdiagnosed as benign prostatic hyperplasia and to get treated alternatively with medications such as alpha blockers. The efficacy of alpha blockers in IgG4-related prostatitis remains unclear.
It is also known that disruption of the endocrine system by certain chemicals adversely affects the development of the reproductive system and can cause vaginal cancer. Many other reproductive diseases have also been link to exposure to synthetic and environmental chemicals. Common chemicals with known links to reproductive disorders include: lead, dioxins and dioxin-like compounds, styrene, toluene, BPA (Bisphenol A) and pesticides.
Examples of cancers of the reproductive system include:
- Prostate cancer - Cancer of the prostate gland
- Breast cancer - Cancer of the mammary gland.
- Ovarian cancer - Cancer of the ovary.
- Penile cancer - Cancer of the penis.
- Uterine cancer - Cancer of the uterus.
- Testicular cancer - Cancer of the testicle/(plural:testes).
- Cervical Cancer - Cancer of the cervix.
There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90–95% of prostatitis diagnoses. It is found in men of any age, with the peak incidence in men aged 35–45 years. CP/CPPS may be inflammatory (Category Ⅲa) or non-inflammatory (Category Ⅲb), based on levels of pus cells in expressed prostatic secretions (EPS), but these subcategories are of limited use clinically. In the inflammatory form, urine, semen, and other fluids from the prostate contain pus cells (dead white blood cells or WBCs), whereas in the non-inflammatory form no pus cells are present. Recent studies have questioned the distinction between categories Ⅲa and Ⅲb, since both categories show evidence of inflammation if pus cells are ignored and other more subtle signs of inflammation, like cytokines, are measured.
In 2006, Chinese researchers found that men with categories Ⅲa and Ⅲb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFβ1 and pro-inflammatory cytokine IFN-γ in their EPS when compared with controls; therefore measurement of these cytokines could be used to diagnose category Ⅲ prostatitis. A 2010 study found that nerve growth factor could also be used as a biomarker of the condition.
For CP/CPPS patients, analysis of urine and expressed prostatic secretions for leukocytes is debatable, especially due to the fact that the differentiation between patients with inflammatory and non-inflammatory subgroups of CP/CPPS is not useful. Serum PSA tests, routine imaging of the prostate, and tests for Chlamydia trachomatis and Ureaplasma provide no benefit for the patient.
Extraprostatic abdominal/pelvic tenderness is present in >50% of patients with chronic pelvic pain syndrome but only 7% of controls.
Healthy men have slightly more bacteria in their semen than men with CPPS. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS. The use of the four-glass test by American urologists is now rare, with only 4% using it regularly.
Men with CP/CPPS are more likely than the general population to suffer from Chronic Fatigue Syndrome (CFS), and Irritable Bowel Syndrome (IBS).
Experimental tests that could be useful in the future include tests to measure semen and prostate fluid cytokine levels. Various studies have shown increases in markers for inflammation such as elevated levels of cytokines, myeloperoxidase, and chemokines.
Some conditions have similar symptoms to chronic prostatitis: Bladder neck hypertrophy and urethral stricture may both cause similar symptoms through urinary reflux ("inter alia"), and can be excluded through flexible cytoscopy and urodynamic tests.
No treatment required. It is standard practice for men with infertility and category IV prostatitis to be given a trial of antibiotics and/or anti-inflammatories, although evidence of efficacy are weak. Since signs of asymptomatic prostatic inflammation may sometimes be associated with prostate cancer, this can be addressed by tests that assess the ratio of free-to-total PSA. The results of these tests were significantly different in prostate cancer and category IV prostatitis in one study.
A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is dependent on androgens like testosterone.
The goals of the treatment for bone metastases include pain control, prevention and treatment of fractures, maintenance of patient function, and local tumor control. Treatment options are determined by multiple factors, including performance status, life expectancy, impact on quality of life, and overall status of clinical disease.
Pain management
The World Health Organization's pain ladder was designed for the management of cancer-associated pain, and mainly involves various strength of opioids. Mild pain or breakthrough pain may be treated with nonsteroidal anti-inflammatory drugs.
Other treatments include bisphosphonates, corticosteroids, radiotherapy, and radionucleotides.
Percutaneous osteoplasty involves the use of bone cement to reduce pain and improve mobility. In palliative therapy, the main options are external radiation and radiopharmaceuticals. High-intensity focused ultrasound (HIFU) has CE approval for palliative care for bone metastasis, though treatments are still in investigatory phases as more information is needed to study effectiveness in order to obtain full approval in countries such as the USA.
Thermal ablation techniques are increasingly being used in the palliative treatment of painful metastatic bone disease. Although the majority of patients experience complete or partial relief of pain following external radiation therapy, the effect is not immediate and has been shown in some studies to be transient in more than half of patients. For patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications), thermal ablation techniques have been explored as alternatives for pain reduction. Several multi-center clinical trials studying the efficacy of radiofrequency ablation in the treatment of moderate to severe pain in patients with metastatic bone disease have shown significant decreases in patient reported pain after treatment. These studies are limited, however, to patients with one or two metastatic sites; pain from multiple tumors can be difficult to localize for directed therapy. More recently, cryoablation has also been explored as a potentially effective alternative as the area of destruction created by this technique can be monitored more effectively by CT than radiofrequency ablation, a potential advantage when treating tumors adjacent to critical structures.
Monthly injections of radium-223 chloride (as Xofigo, formerly called Alpharadin) have
been approved by the FDA in May 2013 for castration-resistant prostate cancer (CRPC) with bone metastases.
A Cochrane review of calcitonin for the treatment of metastatic bone pain indicated no benefit in reduction of bone pain, complications, or quality of life.
Hematospermia, the presence of blood in semen, is most often a benign symptom. Among men age 40 or older, hematospermia is a slight predictor of cancer, typically prostate cancer. No specific cause is found in up to 70% of cases.
A urogenital neoplasm is a tumor of the urogenital system.
Types include:
- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)
- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)
- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)
The term "prostatitis" refers, in its strictest sense, to histological (microscopic) inflammation of the tissue of the prostate gland. Like all forms of inflammation, it can be associated with an appropriate response of the body to an infection, but it also occurs in the absence of infection.
In 1999, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) devised a new classification system. For more specifics about each type of prostatitis, including information on symptoms, treatment, and prognosis, follow the links to the relevant full articles.
In 1968, Meares and Stamey determined a classification technique based upon the culturing of bacteria. This classification is no longer used.
The conditions are distinguished by the different presentation of pain, white blood cells (WBCs) in the urine, duration of symptoms and bacteria cultured from the urine. To help express prostatic secretions that may contain WBCs and bacteria, prostate massage is sometimes used.
Diagnosis is through tests of semen, expressed prostatic secretion (EPS) or prostate tissue that reveal inflammation in the absence of symptoms.
Proper treatment will usually relieve the symptoms, at least to some extent.