Myofascial pain is characterized by the presence of trigger points, tenderness to palpation, and local or referred pain, and commonly involves the pelvic floor muscles in men and women. Pelvic floor ...myofascial pain in the absence of local or referred pain has also been observed in patients with lower urinary tract symptoms, and we have found that many patients report an improvement in these symptoms after receiving myofascial-targeted pelvic floor physical therapy.
We sought to systematically review the literature for examination techniques used to assess pelvic floor myofascial pain in women.
We performed a systematic literature search using strategies for the concepts of pelvic floor disorders, myofascial pain, and diagnosis in Ovid MEDLINE 1946-, Embase 1947-, Scopus 1960-, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Cochrane Database of Systematic Reviews. Articles were screened by 3 authors and included if they contained a description of a pelvic myofascial physical examination.
In all, 55 studies met our inclusion criteria. Overall, examination components varied significantly among the included studies and were frequently undefined. A consensus examination guideline was developed based on the available data and includes use of a single digit (62%, 34/55) to perform transvaginal palpation (75%, 41/55) of the levator ani (87%, 48/55) and obturator internus (45%, 25/55) muscles with a patient-reported scale to assess the level of pain to palpation (51%, 28/55).
Physical examination methods to evaluate pelvic musculature for presence of myofascial pain varied significantly and were often undefined. Given the known role of pelvic floor myofascial pain in chronic pelvic pain and link between pelvic floor myofascial pain and lower urinary tract symptoms, physicians should be trained to evaluate for pelvic floor myofascial pain as part of their physical examination in patients presenting with these symptoms. Therefore, the development and standardization of a reliable and reproducible examination is needed.
Analytically validated assays to interrogate biomarker status in clinical samples are crucial for personalized medicine. PTEN is a tumor suppressor commonly inactivated in prostate cancer that has ...been mechanistically linked to disease aggressiveness. Though deletion of PTEN, as detected by cumbersome FISH spot counting assays, is associated with poor prognosis, few studies have validated immunohistochemistry (IHC) assays to determine whether loss of PTEN protein is associated with unfavorable disease.
PTEN IHC was validated by employing formalin fixed and paraffin-embedded isogenic human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100% sensitive and 97.8% specific for detecting genomic alterations in 58 additional cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples, and PTEN FISH or high resolution single nucleotide polymorphism microarray analysis was done on a subset of these cases.
PTEN protein loss, as assessed as a dichotomous IHC variable, was highly reproducible, correlated strongly with adverse pathologic features (e.g., Gleason score and pathologic stage), detected between 75% and 86% of cases with PTEN genomic loss, and was found at times in the absence of apparent genomic loss. In a cohort of 217 high risk surgically treated patients, PTEN protein loss was associated with decreased time to metastasis.
These studies validate a simple method to interrogate PTEN status in clinical specimens and support the utility of this test in future multicenter studies, clinical trials, and ultimately perhaps for routine clinical care.
...as further epidemiologic evidence for an association between trichomonosis and prostate cancer risk, African Americans, who have the highest incidence of trichomonosis 1, also have the highest ...risks of prostate cancer diagnosis and death 2. ...an accumulating body of evidence suggests that trichomonosis contributes to prostate carcinogenesis, a particularly more aggressive or fatal disease. ...we hypothesize and present preliminary data and published reports that T. vaginalis adherence or binding of specific trichomonad adhesin proteins to normal prostate epithelial cells (PECs) triggers a cell-signaling cascade through known proto-oncogenes, PIM1, c-MYC, and HMGA1, that may ultimately lead to prostate carcinogenesis 9-12.
Purpose
To begin to explore the possible roles of childhood diet and growth in prostate cancer (PCa) development, we investigated these exposures in relation to two known/suspected PCa risk factors, ...earlier pubertal timing and greater attained height, in the Longitudinal Studies of Child Health and Development.
Methods
We used biannual/annual height, weight, and dietary history data to investigate childhood diet, body mass index (BMI), birth length, and childhood height in relation to PCa risk factors (age at peak height velocity (APHV), height at age 13, and adult height) for 64 Caucasian American boys.
Results
In adjusted models, childhood fat and animal protein intake was positively associated with height at age 13 and adult height (
P
< 0.05). A childhood diet high in fat and animal protein and low in vegetable protein was also associated with earlier APHV (
P
< 0.05), whereas no associations were observed for childhood energy intake or BMI. Birth length and childhood height were positively associated with height at age 13 and adult height, and childhood height was inversely associated with APHV (
P
< 0.05).
Conclusion
Our findings suggest that both childhood diet and growth potential/growth contribute to earlier pubertal timing and taller attained height in males, supporting roles of these factors in PCa development.
The MYC onco-protein is a transcription factor that regulates cell proliferation, metabolism, protein synthesis, mitochondrial function and stem cell renewal. A region on chromosome 8q24 encompassing ...the MYC locus is amplified in prostate cancer, but this occurs mostly in advanced disease suggesting that MYC alterations occur late in prostate cancer. In contrast, MYC mRNA is elevated in most prostate cancers, even those of relatively low stage and grade (eg Gleason score 6) suggesting that MYC plays a role in initiation. However, since MYC protein levels are tightly regulated, elevated MYC mRNA does not necessarily imply elevated MYC protein. Thus, it is critical to determine whether MYC protein is elevated in human prostate cancer, and if so, at what stage of the disease this elevation occurs. Prior studies of MYC protein localization have been hampered by lack of suitable antibodies and controls. We utilized a new anti-MYC antibody coupled with genetically defined control experiments to localize MYC protein within human tissue microarrays consisting of normal, atrophy, PIN, primary adenocarcinoma, and metastatic adenocarcinoma. Nuclear overexpression of MYC protein occurred frequently in luminal cells of PIN, as well as in most primary carcinomas and metastatic disease. MYC protein did not correlate with gain of 8q24, suggesting alternative mechanisms for MYC overexpression. These results provide evidence that upregulation of nuclear MYC protein expression is a highly prevalent and early change in prostate cancer and suggest that increased nuclear MYC may be a critical oncogenic event driving human prostate cancer initiation and progression.
Purpose Urinary incontinence is one of the most commonly reported and distressing side effects of radical prostatectomy for prostate carcinoma. Several studies have suggested that symptoms may be ...worse in obese men but to our knowledge no research has addressed the joint effects of obesity and a sedentary lifestyle. We evaluated the association of obesity and lack of physical activity with urinary incontinence in a sample of men who had undergone radical prostatectomy. Materials and Methods Height and weight were abstracted from charts, and obesity was defined as body mass index 30 kg/m2 or greater. Men completed a questionnaire before surgery that included self-report of vigorous physical activity. Men who reported 1 hour or more per week of vigorous activities were considered physically active. Men reported their incontinence to the surgeon at their urology visits. Information on incontinence was abstracted from charts at 6 and 58 weeks after surgery. Results At 6 weeks after surgery 59% (405) of men were incontinent, defined as any pad use. At 58 weeks after surgery 22% (165) of men were incontinent. At 58 weeks incontinence was more prevalent in men who were obese and physically inactive (59% incontinent). Physical activity may offset some of the negative consequences of being obese because the prevalence of incontinence at 58 weeks was similar in the obese and active (25% incontinent), and nonbese and inactive (24% incontinent) men. The best outcomes were in men who were nonobese and physically active (16% incontinent). Men who were not obese and were active were 26% less likely to be incontinent than men who were obese and inactive (RR 0.74, 95% CI 0.52–1.06). Conclusions Pre-prostatectomy physical activity and obesity may be important factors in post-prostatectomy continence levels. Interventions aimed at increasing physical activity and decreasing weight in patients with prostate cancer may improve quality of life by offsetting the negative side effects of treatment.
Objective We sought to identify and summarize definitions of apical support loss utilized for inclusion, success, and failure in surgical trials for treatment of apical vaginal prolapse. Background ...Pelvic organ prolapse is a common condition affecting more than 3 million women in the US, and the prevalence is increasing. Prolapse may occur in the anterior compartment, posterior compartment or at the apex. Apical support is considered paramount to overall female pelvic organ support, yet apical support loss is often under recognized and there are no guidelines for when an apical support procedure should be performed and/or incorporated into a procedure designed to address prolapse. Study Design A systematic literature search was performed in 8 search engines: PubMed 1946-, Embase 1947-, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Review Effects, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov , Proquest Dissertations and Theses, and FirstSearch Proceedings, using key words for apical pelvic organ prolapse and apical suspension procedures through April 2016. Searches were limited to human beings using human filters and articles published in English. Study authors (M.R.L.M., J.L.L.) independently reviewed publications for inclusion based on predefined variables. Articles were eligible for inclusion if they satisfied any of the following criteria: (1) apical support loss was an inclusion criterion in the original study, (2) apical support loss was a surgical indication, or (3) an apical support procedure was performed as part of the primary surgery. Results A total of 4469 publications were identified. After review, 35 articles were included in the analysis. Prolapse-related inclusion criteria were: (1) apical prolapse (n = 20, 57.1%); (2) overall prolapse (n = 8, 22.8%); or (3) both (n = 6, 17.1%). Definitions of apical prolapse (relative to the hymen) included: (1) apical prolapse >–1 cm (n = 13, 50.0%); (2) apical prolapse >+1 cm (n = 7, 26.9%); (3) apical prolapse >50% of total vaginal length (–total vaginal length/2) (n = 4, 15.4%); and (4) cervix/apex >0 cm (n = 2, 7.7%). Sixteen of the 35 studies (45.7%) required the presence of symptoms for inclusion. A measurement of the apical compartment (relative to the hymen) was used as a measure of surgical success or failure in 17 (48.6%) studies. Definitions for surgical success included: (1) prolapse stage >2 in each compartment (n = 5, 29.4%); (2) prolapse >–total vaginal length/2 (n = 2, 11.8%); (3) apical support >–total vaginal length/3 (n = 1, 5.9%); (4) absence of prolapse beyond the hymen (n = 1, 5.9%); and (5) point C at ≥–5 cm (n = 2, 11.8%). Surgical failure was defined as: (1) apical prolapse ≥0 cm (n = 2, 11.8%); (2) apical prolapse ≥–1 cm (n = 2, 11.8%); (3) apical prolapse >–total vaginal length/2 (n = 3, 17.6%); and (4) recurrent apical prolapse surgery (n = 1, 5.9%). Ten (28.6%) of the 35 studies also included symptomatic outcomes in the definition of success or failure. Conclusion Among randomized, controlled surgical trials designed to address apical vaginal support loss, definitions of clinically significant apical prolapse for study inclusion and surgical success or failure are either highly variable or absent. These findings provide limited evidence of consensus and little insight into current expert opinion.
Background A recent nested case–control study found that the presence of antibodies against Trichomonas vaginalis, a common nonviral sexually transmitted infection, was positively associated with ...subsequent incidence of prostate cancer. We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality. Methods We conducted a case–control study nested within the Physicians’ Health Study that included 673 case subjects with prostate cancer and 673 individually matched control subjects who had available plasma samples. Plasma from blood samples collected at baseline was assayed for antibodies against T vaginalis with an enzyme-linked immunosorbent assay. We used conditional logistic regression to estimate the odds ratios (ORs) of incident prostate cancer, extraprostatic prostate cancer, and cancer that would ultimately progress to bony metastases or prostate cancer–specific death. Results Although not statistically significant, the magnitude of the association between T vaginalis–seropositive status and overall prostate cancer risk (OR = 1.23, 95% confidence interval CI = 0.94 to 1.61) was similar to that reported previously. Furthermore, a seropositive status was associated with statistically significantly increased risks of extraprostatic prostate cancer (OR = 2.17, 95% CI = 1.08 to 4.37) and of cancer that would ultimately progress to bony metastases or prostate cancer–specific death (OR = 2.69, 95% CI = 1.37 to 5.28). Conclusions This large prospective case–control study obtained further support for an association between a seropositive status for antibodies against T vaginalis and the risk of prostate cancer, with statistically significant associations identified for the risk of extraprostatic prostate cancer and for clinically relevant, potentially lethal prostate cancer.
Increased nucleolar size and number are hallmark features of many cancers. In prostate cancer, nucleolar enlargement and increased numbers are some of the earliest morphological changes associated ...with development of premalignant prostate intraepithelial neoplasia (PIN) lesions and invasive adenocarcinomas. However, the molecular mechanisms that induce nucleolar alterations in PIN and prostate cancer remain largely unknown. We verify that activation of the MYC oncogene, which is overexpressed in most human PIN and prostatic adenocarcinomas, leads to formation of enlarged nucleoli and increased nucleolar number in prostate luminal epithelial cells in vivo . In prostate cancer cells in vitro , MYC expression is needed for maintenance of nucleolar number, and a nucleolar program of gene expression. To begin to decipher the functional relevance of this transcriptional program in prostate cancer, we examined FBL (encoding fibrillarin), a MYC target gene, and report that fibrillarin is required for proliferation, clonogenic survival, and proper ribosomal RNA accumulation/processing in human prostate cancer cells. Further, fibrillarin is overexpressed in PIN lesions induced by MYC overexpression in the mouse prostate, and in human clinical prostate adenocarcinoma and PIN lesions, where its expression correlates with MYC levels. These studies demonstrate that overexpression of the MYC oncogene increases nucleolar number and size and a nucleolar program of gene expression in prostate epithelial cells, thus providing a molecular mechanism responsible for hallmark nucleolar alterations in prostatic neoplasia.
Prostate cancer research has been predominantly focused on adult exposures and risk factors. However, because the prostate develops during gestation and early life, exposure to external factors, such ...as obesity, during development could affect the prostate cancer progression in adults. Our previous work demonstrated that exposure to a high fat/high sugar (HF/HS) diet during gestation and until weaning stimulated prostate hyperplasia and altered the Pten/Akt pathway in adult mice fed a normal diet after weaning. Here, we asked whether maternal exposure to HF/HS would worsen prostate phenotypes in mice lacking Pten, a widely accepted driver of prostate cancer. We found that, at six weeks of age, both Chow (control)-and HF/HS-exposed Pten knockout mice showed evidence of murine PIN that included ducts with central comedo necrosis but that the HF/HS exposure did not influence murine PIN progression. The Pten knockout mice exposed to HF/HS in utero had significantly more mitotic cells than Pten knockouts exposed to Chow diet. In the Pten null background, the maternal HF/HS diet enhanced proliferation but did not have an additive effect on Akt activation. We observed neuroendocrine differentiation in Pten knockout mice, a phenotype that had not been previously described in this model.
PDF
