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Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of malignant cells that have metastasized. The oncoprotein BCL-2 is associated with the development of androgen-independent prostate cancer, due to its high levels of expression in androgen-independent tumours in advanced stages of the pathology.
The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.
The expression of Ki by immunohistochemistry may be a significant predictor of patient outcome for men with prostate cancer. An important part of evaluating prostate cancer is determining the stage , or how far the cancer has spread. Knowing the stage helps define prognosis and is useful when selecting therapies.
Its components include the size of the tumor, the number of involved lymph nodes , and the presence of any other metastases. The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. Several tests can be used to look for evidence of spread. Medical specialty professional organizations recommend against the use of PET scans , CT scans , or bone scans when a physician stages early prostate cancer with low risk for metastasis.
Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis —opposite to what is found in many other cancers that metastasize. After a prostate biopsy, a pathologist looks at the samples under a microscope.
If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities.
The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most-common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method sometimes used.
The data on the relationship between diet and prostate cancer is poor. Men who get regular exercise may have a slightly lower risk, especially vigorous activity and the risk of advanced prostate cancer. In those who are being regularly screened, 5-alpha-reductase inhibitors finasteride and dutasteride reduce the overall risk of being diagnosed with prostate cancer, but there are insufficient data to determine if they have an effect on the risk of death and they may increase the chance of more serious cases.
Prostate cancer screening is an effort to find unsuspected cancers in those without symptoms. The AUA recommends offering screening to 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. The first decision to be made in managing prostate cancer is whether treatment is needed. Prostate cancer, especially low-grade forms found in elderly men, often grows so slowly that no treatment is required.
Alternative approaches that delay active treatment and instead involve surveillance of diagnosed prostate cancers are termed expectant management. Watchful Waiting , which has palliative intent , and Active Surveillance , which has curative intent. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are age, general health, and a person's views about potential treatments and their possible side effects.
Because most treatments can have significant side effects , such as erectile dysfunction and urinary incontinence , treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A combination of the treatment options is often recommended for managing prostate cancer. Guidelines for treatment for specific clinical situations requires a good estimation of a person's long-term life expectancy.
Most of those who are newly diagnosed and made a treatment choice can not correctly answer over half of the questions. If radiation therapy is done first, and fails, then radical prostatectomy becomes a very technically challenging surgery and may not be feasible. On the other hand, radiation therapy done after surgical failure may have many complications.
In localized disease, it is unknown if radical prostatectomy is better or worse than watchful waiting. A meta-analysis on the effects of voiding position during urination in males with prostate enlargement showed that sitting was superior to standing.
Bladder emptying was significantly improved, while there was a trend towards a higher urinary flow and shorter voiding time. Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. This term implies careful observation of the tumor over time, with the intention of treatment for a cure if there are signs of cancer progression.
Active surveillance is not synonymous with watchful waiting , an older term which implies no treatment or specific program of monitoring, with the assumption that palliative , not curative, treatment would be used if advanced, symptomatic disease develops. Active surveillance involves monitoring the tumor for signs of growth or the appearance of symptoms.
The goal of surveillance is to avoid overtreatment and the sometimes serious, permanent side effects of treatment for a slow-growing or self-limited tumor that would never cause any problems for the person.
This approach is not used for aggressive cancers, but it may cause anxiety for people who wrongly believe that all cancer is deadly or themselves to have life-threatening cancer. Treatment of metastatic prostate cancer can be difficult. As the average life expectancy increases due to advances in the treatment of cardiovascular, pulmonary and other chronic diseases, it is likely that more elderly patients will be living long enough to suffer the consequences of their prostate cancer.
Therefore, there is currently much interest in the role of aggressive prostate cancer treatment modalities such as with surgery or radiation in the elderly population who have localized disease. If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors that treat prostate cancer use a variety of nomograms to predict the probability of spread.
Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. Cryotherapy the process of freezing the tumor , hormonal therapy , and chemotherapy may also be offered if initial treatment fails and the cancer progresses.
Sipuleucel-T , a cancer vaccine has been found to result in a benefit a four-month increase in survival for men with metastatic prostate cancer. Most hormone dependent cancers become resistant to treatment after one to three years and resume growth despite hormone therapy.
The cancer chemotherapic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. Both abiraterone and enzalutamide are currently being tested in clinical trials in those with CRPC who have not previously received chemotherapy. Only a subset of people respond to androgen signaling blocking drugs and certain cells with characteristics resembling stem cells remain unaffected.
It is possible that for further advances, a combination of androgen signaling blocking agent with stem-like cell directed differentiation therapy drug would prove ideal. Palliative care is medical care which focuses on treatment of symptoms of serious illness, like cancer, and improving quality of life. Pain is common in metastatic prostate cancer, and cancer pain related to bone metastases can be treated with bisphosphonates , medications such as opioids , and palliative radiation therapy to known metastases.
Spinal cord compression can occur with metastases to the spine and can be treated with steroids , surgery, or radiation therapy. Other symptoms that can be addressed through palliative care include fatigue, delirium , lymphedema in the scrotum or penis, nausea, vomiting, and weight loss. Prostate cancer rates are higher in developed countries than in the rest of the world. Many of the risk factors for prostate cancer are more common including longer life expectancy and diets high in red meat.
Also, where there is more access to screening programs, there is a higher detection rate. In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score.
In general, the higher the grade and the stage, the poorer the prognosis. Nomograms can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients suffering from cancers at various stages. In , Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23—37 months from the time of initiation of androgen ablation therapy.
Many prostate cancers are not destined to be lethal, and most men will ultimately not die as a result of the disease. Several tools are available to help predict outcomes, such as pathologic stage and recurrence after surgery or radiation therapy.
Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers. For example, studies have shown that a year-old man will lose 3. If he is both overweight and a smoker, he will lose 6. At this time, there is no evidence that either surgery or beam radiation has an advantage over the other in this regard, the lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less serious forms of cancer.
Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments, but data so far do not suggest that it does. People with low-grade disease Gleason were unlikely to die of prostate cancer within 15 years of diagnosis. Men with high-grade disease Gleason experienced high prostate cancer mortality within 15 years of diagnosis, regardless of their age at diagnosis, underscoring the very aggressive nature of poorly differentiated prostate cancer.
The average annual incidence rate of prostate cancer between and among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin,    but these high rates may be affected by increasing rates of detection. In such men, diagnosing prostate cancer is overdiagnosis —the needless identification of a technically aberrant condition that will never harm the patient—and treatment in such men exposes them to all of the adverse effects, with no possibility of extending their lives.
It is estimated that in , approximately , new cases and 29, prostate cancer—related deaths will occur in the United States. Prostate cancer is now the second leading cause of cancer death in men, exceeded by lung cancer and colorectal cancer. Age-adjusted incidence rates increased steadily from through , with particularly dramatic increases associated with the inception of widespread use of prostate-specific antigen PSA screening in the late s and early s, followed by a fall in incidence.
Between and , mortality rates appear to have stabilized. It has been suggested that declines in mortality rates in certain jurisdictions reflect the benefit of PSA screening, but others have noted that these observations may be explained by independent phenomena such as improved treatments. The estimated lifetime risk of a prostate cancer diagnosis is about Prostate cancer is the third leading cause of cancer in Canadian men.
In , around 4, died and 21, men were diagnosed with prostate cancer. In Europe in it was the 3rd most diagnosed cancer after breast and colorectal at , cases. In the United Kingdom it is also the second most common cause of cancer death after lung cancer, where around 35, cases are diagnosed every year and of which around 10, die of it. The first treatments of prostate cancer were surgeries to relieve urinary obstruction. Young at Johns Hopkins Hospital.
Transurethral resection of the prostate TURP replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function.
Radical retropubic prostatectomy was developed in by Patrick Walsh. In , Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. GnRH receptor agonists, such as leuprorelin and goserelin , were subsequently developed and used to treat prostate cancer. Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants.
External beam radiotherapy became more popular as stronger [X-ray] radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds for prostate cancer was first described in Systemic chemotherapy for prostate cancer was first studied in the s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by multiple regimens using a host of other systemic chemotherapy drugs.
A series of studies published in Science involved introduced viruses known to cause cancerous mutation in prostate cells: After 16 weeks, none of the luminal samples had undergone malignant mutation, while the basal samples had mutated into prostate-like tubules which had then developed malignancy and formed cancerous tumors, which appeared identical to human samples under magnification. This led to the conclusion that the prostate basal cell may be the most likely "site of origin" of prostate cancer.
People with prostate cancer generally encounter significant disparities in awareness, funding, media coverage, and research—and therefore, inferior treatment and poorer outcomes—compared to other cancers of equal prevalence. It also discovered that the waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.
The Times also noted an "anti-male bias in cancer funding" with a four-to-one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK. Disparities also extend into areas such as detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a report found 49 U. Prostate Cancer Awareness Month takes place in September in a number of countries.
A light blue ribbon is used to promote the cause. Alpharadin completed a phase 3 trial for CRPC patients with bone metastasis. A pre-planned interim analysis showed improved survival and quality of life. The study was stopped for ethical reasons to give the placebo group the same treatment. Alpharadin uses bone targeted Radium isotopes to kill cancer cells by alpha radiation. Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells.
Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. Some of the girls added that changing sanitary napkins in the school is embarrassing, and they avoid going to school those days. More than physical absence during menstruation, this study pointed out an important aspect that can affect school performance equally—the quality of presence at school, particularly the attention and concentration in the curricular activities.
Lack of small things required for maintaining the menstrual hygiene , like privacy, water supply and waste disposal, have been found as major reasons for absenteeism, though abnormal physical conditions pain, discomfort, heavy bleeding are also one. Lack of privacy has been pointed out by other studies also as a major problem El-Gilany et al.
Faces scale showed that Even after this only 4. Hence, knowledge and information about reproductive functioning and reproductive health problems amongst the adolescent is poor [ 11 ]. However a study on dysmenorrhea in Haryana reported that only 5. Few girls told that it cannot control the heavy flow they have during menstruation.
Similar observation that poverty, high cost of disposable sanitary pads and to some extent ignorance dissuaded the adolescent girls from using the menstrual absorbents available in the market was made in an Indian study [ 12 ]. It was found that those who knew about the sanitary pads are likely to use them instead of cloth if they could access and afford it.
The disposable pads usually have better absorption, are meant for single use and, hence are considered sanitary. However, with the cloths there is a tendency towards reuse and have the potential of harbouring infection agents that can cause pelvic infections. Proper washing and drying of re-used cloth does minimize the chance of infection, but it was explicit in the study that the drying practices were not optimal as they had to hide the cloth from others view. There was a Low consultation rate 33 Women have been found to consider health related morbities especially reproductive, to be normal and part of their destiny.
To this adds on culture of shame and silence. This whole cycle in turn leads to compromising with their health related morbidities in women and affecting their qualitative life in nut shell.
Discomfort related to menstruation due to pain has a strong impact on their routine life. Backache, stomach ache, nausea, irritability, skin disorders, diarrhea, anxiety, body ache and tension were the common symptoms experienced by the adolescent girls in the study population. They avoid many routine activities e. However activity limitation due to pain is more among the urban and rural girls as compared to slum girls. It is therefore justified to say that dysmenorrhea has an impact on quality life of adolescent girls [ 13 - 15 ].
VAS scale was used in questionnaire however more precise methods like menstrual disorder Questionaire MDQ may be used in future study. Please leave a message, we will get back you shortly. Home Publications Conferences Register Contact. Journal of Child and Adolescent Behavior.
Guidelines Upcoming Special Issues. Research Article Open Access. Knee osteoarthritis OA is a common age-related musculoskeletal disorder that has significant functional impact and has considerable societal costs through work loss, early retirement, and arthroplasty. Pathological changes in subchondral and periarticular bone, ranging from trabecular thickening to gross pathological disruption, 5 are prominent in OA and participate in disease progression.
The basis for considering that vitamin D might influence the course of knee OA arose from its known role in bone health, the importance of systemic 11 and local bone changes in OA, and epidemiologic observations from some studies suggesting slower rates of OA progression among those with higher vitamin D levels. Therefore, our goal was to determine through performance of a clinical trial whether vitamin D supplementation is associated with reductions in symptomatic and structural progression of knee OA.
This was a single center, randomized, placebo-controlled, double-blind, clinical trial with a planned enrollment of participants with symptomatic knee OA, testing the efficacy of a 2-year vitamin D intervention strategy for knee pain and cartilage loss, measured by magnetic resonance imaging MRI.
All patients provided written informed consent for participation in the trial. We recruited patients at Tufts Medical Center and through advertisements in local newspapers, public transportation systems, and radio stations. A sequential method of screening was implemented. A telephone prescreen interview assessed knee pain and whether the respondent had a planned knee or hip surgery, was participating in another study, and or had comorbidities.
Subsequent screening involved a visit that included knee radiographs and a blood test. Eligible individuals were aged 45 years or older with symptomatic knee OA, based on an affirmative response to a standardized question about long-term knee pain 14 and the presence of at least 1 osteophyte on a recent knee radiograph equivalent to Kellgren-Lawrence [KL] grade 2 Individuals meeting these criteria fulfill American College of Rheumatology classification criteria for knee OA.
Exclusion criteria included daily supplemental intake of vitamin D of more than IU, serum calcium level of more than Exclusionary comorbidities included lymphoma, sarcoidosis, tuberculosis, hyperparathyroidism, malabsorption disorders, glomerular filtration rate less than 30, history of inflammatory joint disease, pregnancy, and any that precluded MRI. We chose the knee with more severe disease based on the WOMAC pain score and radiographic grade, or, if these were identical, by randomization.
We operated a stratified randomization system by KL grade 2, 3, 4 , with 1: The randomization list was generated by the study statistician M. This list was concealed from the investigative team. We purchased cholecalciferol IU and identical placebo capsules from Tishcon Corp.
The pills were made according to good manufacturing principles and subjected to quality assurance testing. Oversight was provided by a data and safety monitoring board whose members were appointed by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
We obtained serum and urinary calcium levels and hydroxyvitamin D levels at each visit. This permitted dose adjustment for hypercalciuria or hypervitaminosis D but mandated withdrawal for hypercalcemia. Labeling and dispensation of study pills was performed by the research pharmacy. Monitoring of vitamin D and calcium laboratory test results was performed by the pathology department staff, independently of the clinical team.
Their reporting relationship was confined to the study statistician M. To maintain blinding in the event that a participant required a dose adjustment, we operated a double-dummy protocol, in which the statistician M.
We provided pill diaries to participants and performed pill counts at each visit. The use of concomitant nonsteroidal anti-inflammatory agents and analgesics was allowed and was recorded at each visit and in the daily logs.
Assessments occurred at a baseline visit and at months 2, 4, 8, 12, 16, 20, and The clinical assessments included a musculoskeletal examination, WOMAC questionnaire pain subscale range, ; 0, no pain; minimal clinically important improvement, 3. Physical function tests timed m walk and chair rise test and the Item Short-Form Health Survey SF questionnaire were collected at baseline and at 12 and 24 months.
Imaging included standardized semiflexed posteroanterior knee radiographs 19 at baseline and 24 months, knee and hip dual x-ray absorptiometry DXA; GE Lunar Prodigy Scanner , and magnetic resonance imaging MRI scans of the study knee at baseline, 12, and 24 months.
The sequences of relevance for bone marrow lesion assessment were sagittal, coronal, and axial intermediate-weighted fat-suppressed images with time to recovery of ms, time to echo of 31 ms, slice thickness of 3 mm, space thickness of 0. The sequences of relevance for cartilage volume assessment were 3-dimensional sagittal water excitation dual echo steady state images with time to recovery of Finally, sagittal and coronal intermediate-weighted sequences were collected with time to recovery of ms, time to echo of 40 ms, slice thickness of 3 mm, space thickness of 0.
We measured cartilage parameters in the tibia and femur within the index compartment of each knee, defined as the compartment with predominant pathology. To optimize sensitivity to change, we registered the baseline and follow-up images and specifically evaluated cartilage loss not gain. The reliability of knee cartilage volume measurements using MRI has been well documented. The intraclass correlation coefficients between the first and second analyses of cartilage loss were excellent 0.
We measured manually the dimensions of each bone marrow lesion using the sagittal and coronal intermediate-weighted fat-suppressed sequences according to a method we previously validated. We performed dual x-ray absorptiometry of the knees GE Lunar Prodigy and defined tibial subchondral regions of interest according to a standardized protocol and calculated a medial: We evaluated knee radiographs for global severity using the KL scale, 15 operated as follows: We measured radiographic knee joint space width JSW using semi-automated software 24 and static alignment according to a validated method.
In quality control testing, our measurements correlated at 0. This assay's sensitivity is less than 2. We analyzed the WOMAC pain scores across time using mixed-effects regression models for longitudinal repeated measures, 26 after first evaluating the effect of time and correlation.
Therefore, the repeated-measures model ultimately included the baseline KL grade, a quadratic time effect, treatment, and the interaction between time and treatment; the correlation within the repeated WOMAC scores was addressed by the random intercept.
In the repeated-measures models, the effect of treatment is captured by the time-treatment interaction and likelihood ratio tests were used to test for the significance of this. For structural end points, we analyzed the difference between baseline and follow-up using general linear models. Models were adjusted by KL score since randomization had been stratified by KL score. Imputations were performed separately for each treatment group and each outcome, using the baseline and 2-year measured outcome values, KL score, sex, age, race, and baseline values of body mass index and serum vitamin D.
To compare the number of adverse events across treatment groups and allowing for multiple events and clustering by participants, we used the negative binomial model, which can be formulated as a Poisson regression with a random effect for study patients. We estimated the potential effect of vitamin D on cartilage loss by modeling the rates of progression observed in the Framingham cohort 13 and extrapolating this to cartilage loss using equivalence data generated by Cicuttini et al.
For change in WOMAC pain, measured on a scale from 0 to 20, we anticipated a standard deviation of 4. We randomized participants from in-person screens Figure 1 , exceeding our targeted recruitment by 2 due to timing of enrollment. Twenty-four participant pairs received vitamin D dose changes as follows:
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