Treatment of category III A prostatitis with zafirlukast: a randomized controlled feasibility study

The cause of category III A prostatitis, chronic prostatitis/chronic male pelvic pain syndrome category A (CP/CPPS A), is uncertain. Treatments for it are based on consensus opinion rather than on scientific data. Our aim was to examine the effect of zafirlukast, a leucotriene antagonist, on the symptoms of CP/CPPS A in our genitourinary (GU) medicine unit. CP/CPPS A was diagnosed by comparative white cell counts of split urine (Stamey) analysis or by finding an excess of polymorphs in expressed prostatic fluid. Symptom change was assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Patients were given zafirlukast or placebo for four weeks in a random double-blind fashion. All patients also received doxycycline. In all, 31 patients were asked to participate and 17 entered the study. No difference in outcome could be shown between the active (10) and placebo (seven) patients. Zafirlukast cannot be demonstrated to be useful in the symptomatic treatment of CP/CPPS A. The problems of recruitment into this study (in spite of a large number of patients with prostatic type pain being seen in our unit) suggest that multicentre treatment trials using non-invasive diagnostic techniques such as the CPSI (rather than single GU medicine units diagnosing CP/CPPS A by uncomfortable direct prostatic testing) are likely to be the most effective and objective methods of undertaking treatment trials in the CP/ CPPS A field in the future.     

Is there a role for urodynamics in chronic nonbacterial prostatitis?

The etiology of chronic nonbacterial chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) is unclear. That may be why treatment with antibiotics and anti-inflammatory drugs often fail. The use of urodynamic testing in evaluating any patient with both pelvic/perineal pain coexistent with voiding symptoms can help identify voiding dysfunction. If identified, urodynamic voiding disorders, such as bladder neck obstruction and pseudodyssynergia, should be specifically treated to ameliorate symptoms. Through more research of nonbacterial CP/ CPPS, we will be able to further define the successful role of videourodynamics in men with this disease. The etiology of chronic nonbacterial chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) is unclear. That may be why treatment with antibiotics and anti-inflammatory drugs often fail. The use of urodynamic testing in evaluating any patient with both pelvic/perineal pain coexistent with voiding symptoms can help identify voiding dysfunction. If identified, urodynamic voiding disorders, such as bladder neck obstruction and pseudodyssynergia, should be specifically treated to ameliorate symptoms. Through more research of nonbacterial CP/ CPPS, we will be able to further define the successful role of videourodynamics in men with this disease.     

Chronic prostatitis and sensory urgency: Whose pain is it?

Difficulties encountered in diagnosing and effectively treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is frustrating for clinicians and patients. Scientific evidence cannot establish an exact relationship between the prostate and the symptoms of CP/CPPS, and the prostate continues to be the diagnosis of convenience in this complex syndrome in men. However, if the pain is not the prostate’s, whose pain is it? A heterogeneous group of insults can result in a common neurogenic pain response, resulting in recurring pain and voiding or sexual dysfunction. To add to this dilemma, certain life-threatening diagnoses, such as carcinoma-in-situ, is in the differential diagnosis and must be excluded. Urodynamics may be useful in evaluating and treating patients whose voiding symptoms predominate. However, many patients with CP/ CPPS will not have measurable abnormalities by conventional methods and likely suffer from a functional somatic syndrome that is best treated with a multimodality approach.     

Prostatitis revisited: new definitions,new approaches

Prostatitis syndromes represent an important health care problem resulting in considerable morbidity and expenditure of health care resources. Comparison of the traditional and consensus classification schemes demonstrates no changes in the traditional categories of acute bacterial prostatitis and chronic bacterial prostatitis. Examining only the EPS, however, results in diagnosis of half of the patients with inflammatory CP/CPPS. An optimal diagnostic strategy required evaluation of the VB3 and SFA in addition to the traditional EPS examination. Such precision is necessary for research studies, but whether such precision is important clinically remains unproved. The new interest in optimal evaluation and characterization of patients with chronic prostatitis and related conditions has resulted in important research initiatives examining the etiology and optimal treatment for this large group of patients.     

Chronic prostatitis/pelvic pain syndrome: A bladder dysfunction?

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is frustrating for both clinicians and patients. The prostate is not scientifically proven to cause the symptoms of CP/CPPS, yet the prostate continues to be the diagnosis of convenience in this complex syndrome in men. However, if the pain is not of prostatic origin, what causes it? A heterogeneous group of insults can result in a common neurogenic pain response, resulting in recurring pain and voiding or sexual dysfunction. To add to this dilemma, certain life-threatening diagnoses, such as carcinoma-in-situ, are in the differential diagnosis and must be excluded. Urodynamics may be useful in evaluating and treating patients whose voiding symptoms predominate, such as those with concomitant overactive bladder symptoms. However, many patients with CP/CPPS will not have measurable abnormalities by conventional methods and likely suffer from a functional somatic syndrome that is best treated with a multimodality approach.     

Role of bacteria in chronic prostatitis/ chronic pelvic pain syndrome

Throughout the past century, we have refined our understanding of prostatitis, moving from using a primarily clinical definition to considering it as a complex inflammatory condition. The inconsistency in identifying uropathogens in patients with symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has led to controversy in therapeutic management. There is compelling evidence that the normal prostate has minimal inflammation and no bacteria. Clinicians using the Meares/Stamey criteria identified uropathogens localized to the prostate in only 6% to 8% of CP/CPPS patients. This suggests that bacteria may have a role in less than 10% of men with CP/CPPS. That some patients respond to antimicrobials could suggest that eradication of bacteria reduces symptoms. However, the beneficial effect of antimicrobial drugs may not be due to their antibacterial action, but to their anti-inflammatory action. The normal prostate shows minimal inflammation, but only 50% of CP/CPPS patients exhibit prostatic leukocytosis. Prudence demands that we examine the function of the white blood cells—the cytokines produced. Several basic science advances allowed new avenues of research regarding the detection of molecular evidence of causative uropathogens. New research brings new controversy and unexpected findings, but further refines our understanding of the immune system and the CP/CPPS disease process.     

Acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic pain

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) afflicts 2%-10% of adult men. Available therapies offer little or no proven benefit. Because acupuncture represents an attractive “natural” therapy, we compared the efficacy of acupuncture to sham acupuncture for CP/CPPS.

Methods

Participants met US National Institutes of Health (NIH) consensus criteria for CP/CPPS, were aged ≥20 years old, and had a total score ≥15 on the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and symptoms for at least 3 of the preceding 6 months. They were randomized 1:1 to acupuncture or sham acupuncture. Treatment consisted of twice-weekly 30-minute sessions for 10 weeks (20 sessions total) without needle stimulation, herbs, or adjuvants. The primary response criterion was a 6-point decrease from baseline to week 10 in NIH-CPSI total score (range 0-43).

Results

Thirty-two (73%) of 44 participants responded in the acupuncture group compared with 21 (47%) of 45 sham group participants (relative risk 1.81, 95% confidence interval, 1.3-3.1, P = .02). Long-term responses 24 weeks after completing therapy without additional treatment occurred in 14 (32%) of 44 acupuncture group participants and in 6 (13%) of 45 sham group participants (relative risk 2.39, 95% confidence interval, 1.0-5.6, P = .04).

Conclusions

After 10 weeks of treatment, acupuncture proved almost twice as likely as sham treatment to improve CP/CPPS symptoms. Participants receiving acupuncture were 2.4-fold more likely to experience long-term benefit than were participants receiving sham acupuncture.     

Complications of Chronic Prostatitis

Chronic prostatitis (CP) is a pelvic condition in men that needs to be distinguished from other forms of prostatitis, such as acute and chronic bacterial prostatitis. CP is characterized by pelvic or perineal pain lasting longer than 3 months without evidence of urinary tract infection. Symptoms may wax and wane and pain may radiate to the back and perineum, causing discomfort while sitting. Dysuria, frequency, urgency, arthralgia, myalgia, unexplained fatigue, abdominal pain, and burning sensation in the penis may be present. Post-ejaculatory pain, mediated by nerves and muscles, is a hallmark of the condition and serves to distinguish CP/chronic pelvic pain syndrome (CPPS) patients from men with benign prostatic hyperplasia and healthy men. Some patients report low libido, sexual dysfunction, and erectile difficulties. The symptoms of CP/CPPS appear to result from interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems. Some researchers have suggested that CPPS is a form of painful bladder syndrome/interstitial cystitis (PBS/IC). Therapies shown to be effective in treating IC/PBS (eg, quercetin) have shown some efficacy in CP/CPPS. Recent research has focused on genomic and proteomic aspects of the related conditions. There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90% to 95% of prostatitis diagnoses. Its peak incidence is in men 35 to 45 years old. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases began using the umbrella term urologic chronic pelvic pain syndromes to refer to pain syndromes associated with the bladder (eg, IC/PBS) and prostate gland (eg, CP/CPPS). The prognosis for CP/CPPS has improved greatly with the advent of multimodal treatment, including phytotherapy, pelvic nerve myofascial trigger point release, anxiety control, and chronic pain therapy.     

Acupuncture for chronic prostatitis/ chronic pelvic pain syndrome

Chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is prevalent in urological practice and has a significant impact on quality of life. Standard therapies often fail to achieve sustainable amelioration of symptoms. This article attempts to show that neuromodulatory treatment in the form of electroacupuncture can be a minimally invasive and effective treatment for CP/CPPS that is refractory to standard therapies. This neuromodulatory therapy lends support to the hypothesis that the end stage of CP/CPPS may be a neuropathic pain syndrome.     

Apremilast in the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Pilot Study

Objective: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease with an uncertain cause and limited effective treatments. Apremilast (Celgene Corporation, Summit, NJ, USA) is a selective phosphodiesterase type 4 (PDE4) inhibitor that modulates the immune system. An open‐label, one‐arm, pilot study was conducted to explore its potential for improving CP/CPPS symptoms. Methods: Males ≥ 18 years of age were treated with 20 mg oral apremilast twice daily for up to 12 weeks. Outcomes were measured with Global Response Assessment (GRA), pain visual analog scale (VAS), Chronic Prostatitis Symptom Index (CPSI), Pittsburgh Sleep Quality Index (PSQI), SF‐12 mental (MCS) and physical (PCS) health‐related quality of life subscales, and voiding diaries. Repeated measures and paired t‐tests evaluated changes from baseline to end of treatment, and at a final visit 4 weeks off the drug. Results: Seventeen men (94% Caucasian; mean age 48.2 ± 10 years) were treated (mean 115.8 ± 56.1 doses). Mean VAS (3.4 ± 2.0 vs 1.8 ± 1.7; P = 0.0011), PSQI (9.4 ± 4.4 vs 7.4 ± 4.2; P = 0.037) and CPSI (26.1 ± 5.0 vs 17.2 ± 8.3; P = 0.0016) scores improved from baseline to end of treatment. Incontinence episodes per day improved slightly (P = 0.042). When only those completing at least 8 weeks of treatment were examined (n = 9), significant changes in CPSI, VAS, and PSQI were still observed. At the final visit, 8/9 (88.9%) men also reported some improvement in pain related to sex. Side‐effects were generally mild and well tolerated. Conclusion: These results suggest that apremilast may improve CP/CPPS symptoms with only mild side‐effects. However, placebo controlled studies are necessary to determine efficacy.     

慢性前列腺炎／慢性骨盆疼痛综合征的相关危险因素分析

目的探讨慢性前列腺炎／慢性骨盆疼痛综合征（CP/CPPS）发病的危险因素。方法选择360例临床确诊的CP/CPPS患者及年龄匹配的非CP/CPPS患者360例（对照组）,采用自行设计调查表进行病例对照研究,内容主要包括吸烟及饮酒情况、受教育程度、居住地、婚姻状况,采用非条件多元Logstic回归模型测量各因素与CP/CPPS发病的相关性。结果与不吸烟者比较,吸烟者发生CWCPPS的危险性升高,吸烟量和吸烟时间均与CP/CPPS发病率呈明显正相关;与不饮酒者相比,饮酒者发生CP/CPPS的危险性降低,随饮酒量和时间增长,CP/CPPS发病危险有下降趋势;CP/CPPS发病危险性受教育程度为初中以下者高于初中以上者,居住农村者高于居住城区者,已婚者高于未婚者。结论吸烟是CP/CPPS发病的危险因素,饮酒为保护性因素,文化程度低、居住条件差及已婚等因素可增加CP／CPPS发病的危险性。     

The Association of Abuse and Symptoms Suggestive of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Results from the Boston Area Community Health Survey

Objective To determine the effect of reported sexual, physical, or emotional abuse on the symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to determine the effect of race/ethnicity on these patterns. Methods The Boston Area Community Health (BACH) survey used a multi-stage stratified cluster sample to randomly sample 5,506 adults aged 30–79 from the city of Boston. BACH recruited 2,301 men (700 Black, 766 Hispanic, and 835 White). Interviewers administered questions approximating the National Institutes of Health chronic prostatitis symptom index (CPSI), and symptoms suggestive of CP/CPPS were measured by the definition of perineal and/or ejaculatory pain and CPSI pain score of 4+. Questions about previous abuse were obtained from a validated self-administered questionnaire during the home visit. Logistic regression was used to determine the effect of abuse on the likelihood of a man having symptoms suggestive of CP/CPPS. Results The prevalence of symptoms suggestive of CP/CPPS was 6.5%. Men who reported having experienced sexual, physical, or emotional abuse had increased odds (1.7–3.3) for symptoms suggestive of CP/CPPS. Previous abuse increased both the pain and urinary scores from the CPSI. Conclusion Symptoms suggestive of CP/CPPS are not uncommon in a community-based population of men. For men presenting with symptoms suggestive of CP/CPPS, clinicians may wish to consider screening for abuse.     

Economic impact of chronic prostatitis

There are four types of prostatitis, including type I (acute bacterial prostatitis), type II (chronic bacterial prostatitis), type III (chronic prostatitis/chronic pelvic pain syndrome, or CP/CPPS), and type IV (asymptomatic inflammatory prostatitis). These prostatitis conditions account for approximately 2 million office visits each year to primary care physicians and urologists. The annual cost to treat prostatitis is approximately $84 million. Compared with control subjects, men with prostatitis incur significantly greater costs, predominantly due to increased outpatient visits and pharmacy expenses. CP/CPPS is the most common type of prostatitis. The condition is characterized by chronic, idiopathic pelviperineal pain. Due to the lack of effective treatments for CP/CPPS, the per-person costs associated with the condition are substantial and are similar to those reported for peripheral neuropathy, low back pain, fibromyalgia, and rheumatoid arthritis. Costs appear to be higher in men with more severe symptoms. Indirect costs (eg, work and productivity loss) are incurred by many patients with CP/CPPS. Identification of effective treatments for CP/CPPS would be expected to substantially reduce the costs associated with the condition.     

The implications of cytokines in chronic prostatitis and chronic pelvic pain syndrome

Although the etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unclear, inflammation may explain some of the causative and propagating features. Cytokines may play a role by recruiting inflammatory cells and, ultimately, inducing symptoms. This paper reviews the role of cytokines in the pathophysiology and management of CP/CPPS. The clinical relevance of measuring cytokines in expressed prostatic secretions or semen remains unclear; there is no established diagnostic or management role for measuring cytokines in CP/CPPS at this time. However, further studies in this area are warranted.     

Chronic prostatitis/chronic pelvic pain syndrome: national survey of genitourinary medicine clinics

We sought to determine current practice in the diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in genitourinary medicine departments in the UK, using a detailed questionnaire survey. Evaluable responses were received from 147 (69%) clinics. Seventy-nine (54%) clinics reported seeing >10 new CPPS patients per year. A broad range of investigations was reported to be used in the diagnosis of CPPS. Whilst 89 (61%) clinics reported using the four-glass test in diagnosis, 46 (32%) reported using the test in >90% of patients with CPPS, and 42 (29%) reported never using the test. In the treatment, doxycycline or ciprofloxacin were reported to be first line treatment by 98% clinics, mostly in 4-6 week courses; however, great variation was recorded in second-line choices and use of non-antibiotic approaches. This survey demonstrates that patients with CPPS are regularly diagnosed and managed in genitourinary clinics in the UK, with wide variations in diagnostic and treatment practices.     

慢性前列腺炎/盆腔疼痛综合征患者白细胞雄激素受体的改变及意义

目的探讨慢性前列腺炎/盆腔疼痛综合征(CP/CPPS)的发生与性激素及雄激素受体(AR)的关系。方法采用放射配体结合分析法检测78例CP/CPPS患者(CP/CPPS组)和32例正常对照者(对照组)外周血白细胞AR,同时采用放射免疫法检测患者血清睾酮(T)和雌二醇(E2)水平。结果CP/CPPS组与对照组血清E2和T水平无差异,外周血白细胞AR含量CP/CPPS组低于对照组(P<0.01),CP/CPPS组E2/T高于对照组,P<0.05。CP/CPPS患者CP症状指数评分(CPS I)与白细胞AR含量呈负相关(r=-0.512,P<0.01。结论CP/CPPS的发生、发展与E2、T比例失调及白细胞AR下调有密切的关系。     

The treatment of prostatitis

PURPOSE: Prostatitis are frequently recognized in general practice and often are a diagnosis and therapeutic challenge. We review here the updated knowledge on diagnosis and therapy of prostatitis. CURRENT KNOWLEDGE AND KEY POINTS: Prostatitis are divided into acute bacterial prostatitis (I), chronic bacterial prostatitis (II), chronic prostatitis/ chronic pelvic pain syndrome (III) and asymptomatic inflammatory prostatitis. Chronic prostatitis/ chronic pelvic pain syndrome are divided into : inflammatory (IIIA) and noninflammatory (IIIB). Treatment of prostatitis should follow evidence based guidelines recently published. Acute prostatitis should be treated by ciprofloxacine 500 mg tid or ofloxacine 200 mg bid or cotrimoxazole 960 mg bid for 4 weeks (CIII). When bacteremia occurs third generation cephalosporin with gentamicin should be used (CIII). In chronic bacterial prostatitis ciprofloxacine 500 mg tid or ofloxacine 200 mg bid or norfloxacine 400 mg bid or cotrimoxazole 960 mg bid for 4 weeks may be used (BIII). FUTURE PROSPECTS AND PROJECTS: Molecular techniques should improve the etiological diagnosis of prostatitis and their treatment.     

Acute pancreatitis precedes chronic pancreatitis in the majority of patients: Results from the NAPS2 consortium

IntroductionThe mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort.MethodsWe evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP.ResultsThere were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3–5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier.ConclusionsNearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.     

Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis

AIM: To determine the efficacy of Mac-2 binding protein(Mac-2bp) for diagnosis of chronic pancreatitis.METHODS: Fifty-nine healthy volunteers(HV), 162 patients with chronic pancreatitis(CP), and 94 patients with pancreatic ductal adenocarcinoma(PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer(including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay(carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic(ROC) analyses.RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV(P 0.0001) and PDAC patients(P 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp. CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.