Autonomic neurophysiologic implications of disorders comorbid with bladder pain syndrome vs myofascial pelvic pain.

AIMS: The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences. METHODS: We compared the presence and relative time of onset of 27 other medical conditions in women with BPS, MPP, both syndromes, and healthy subjects. Analysis included an adjustment for multiple comparisons. RESULTS: Among 107 female subjects (BPS alone = 32; BPS with MPP = 36; MPP alone = 9; healthy controls = 30), comorbidities differentially associated with BPS included irritable bowel syndrome (IBS), dyspepsia, and chronic nausea, whereas those associated with MPP included migraine headache and dyspepsia, consistent with the distinct autonomic neurophysiologic signatures of the two disorders. PTSD (earliest), anxiety, depression, migraine headache, fibromyalgia, chronic fatigue, and IBS usually preceded BPS or MPP. PTSD and the presence of both pelvic pain disorders in the same subject correlated with significantly increased comorbid burden. CONCLUSIONS: Our study suggests a distinct pattern of comorbid conditions in women with BPS. These findings further support our hypothesis of primary vagal defect in BPS as compared with primary sympathetic defect in MPP, suggesting a new model for chronic these pelvic pain syndromes. Chronologically, PTSD, migraine, dysmenorrhea, and IBS occurred early, supporting a role for PTSD or its trigger in the pathophysiology of chronic pelvic pain.

Sensory mapping of pelvic dermatomes in women with interstitial cystitis/bladder pain syndrome.

AIM: To describe a sensory map of pelvic dermatomes in women with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We hypothesized that if IC/BPS involves changes in central processing, then women with IC/BPS will exhibit sensory abnormalities in neurologic pelvic dermatomes. METHODS: Women with IC/BPS and healthy controls underwent neurologic examination that included evaluation of sharp pain sensitivity and vibration in dermatomes T12, L1, L2, S1-5. Peripheral nervous system sensitivity to pressure, vibration, and pinprick were scored using numeric rating scales (NRS). Bilateral comparisons were made with Wilcoxon signed-rank test and comparisons between groups were made by the Mann-Whitney U-test. RESULTS: Total of 74 women with IC/BPS and 36 healthy counterparts were included. IC/BPS and control groups had similar age (43.0 ± 14.1 and 38.6 ± 15.3 years, P = 0.14) and BMI (28.9 ± 8.0 kg/m2 and 26.9 ± 8.4 kg/m2 , P = 0.24), respectively. Women with IC/BPS reported hyperalgesia (elevated bilateral NRS pain intensity) in all pelvic dermatomes compared to healthy controls. S4-S5 region had the highest pain intensity in all participants. All IC/BPS participants exhibited vibration sensation hypoesthesia, at least unilaterally, in all of the pelvic dermatomes except L1 compared to healthy controls. CONCLUSION: This detailed map of neurologic pelvic dermatomes in women with IC/BPS found hyperalgesia in all pelvic dermatomes, and some evidence of vibration sensation hypoesthesia, compared to healthy controls. These findings support the hypothesis that IC/BPS may involve changes in central signal processing biased towards nociception.

Racial Disparities in Partial Nephrectomy Persist Across Hospital Types: Results From a Population-based Cohort.

OBJECTIVE: To assess the national utilization of partial nephrectomy (PN) for T1a renal masses across different racial groups by hospital type. Although clinical guidelines recommend PN for small renal masses (SRMs), racial disparities persist in the use of PN. High-volume and academic hospitals have been associated with greater use of PN for SRMs. However, it is unknown whether racial disparities persist in the use of PN across different types of hospitals. METHODS: Using the National Cancer Database, we identified patients with localized T1a renal cancer (≤4 cm) from 1998 to 2011. The primary outcome was receipt of PN among patients surgically treated for SRMs. Multivariable logistic regression analyses were used to assess for racial differences in treatment with PN stratified by hospital characteristics. RESULTS: Among 118,207 patients diagnosed with clinical T1a renal masses, 36.5% underwent PN (n = 43,134). Overall, a greater proportion of white patients underwent PN (37.3%) compared with African-American (32.4%) and Hispanic (33.7%) patients with SRMs (P <.001). When stratified by hospital type, disparities persisted in the use of PN; African-American patients had lower adjusted odds ratios for being treated with PN when treated at comprehensive community cancer (odds ratio: 0.90; P = .003) and academic (odds ratio: 0.65; P <.001) hospitals compared with white patients. CONCLUSIONS: In this population-based cohort, we found that racial disparities persist across all types of hospitals in the use of PN for SRMs. Further research is needed to identify, and target for intervention, the factors contributing to racial disparities in the surgical management of SRMs.

Variation in Surgical Margin Status by Surgical Approach among Patients Undergoing Partial Nephrectomy for Small Renal Masses.

PURPOSE: We assessed the relationship of surgical margins across different surgical approaches to partial nephrectomy in patients with clinical T1a renal cell carcinoma in a population based cohort. MATERIALS AND METHODS: We used NCDB (National Cancer Database) to identify all patients who underwent partial nephrectomy for clinical T1a renal cell carcinoma (tumor size less than 4 cm) from 2010 to 2011. The primary outcome was surgical margin status in patients treated with partial nephrectomy by the open, laparoscopic or robotic approach. Multivariable logistic regression analysis was done to identify patient, hospital and surgical factors associated with positive surgical margins. RESULTS: Partial nephrectomy was done in 11,587 patients, including open, laparoscopic and robotic nephrectomy in 5,094 (44%), 1,681 (14%) and 4,812 (42%), respectively. Mean±SD age was 56±12 years. Overall 806 patients (7%) had positive surgical margins. The positive surgical margin prevalence was 4.9%, 8.1% and 8.7% for the open, laparoscopic and robotic approaches, respectively (p<0.001). Laparoscopic and robotic partial nephrectomy had a higher adjusted OR for positive surgical margins (OR 1.81 and 1.79, respectively, each p<0.001) than open nephrectomy. When stratified by hospital type, differences in positive surgical margin rates remained, such that patients treated at academic medical centers who underwent laparoscopic and robotic partial nephrectomy had a higher adjusted OR (1.38, p=0.074 and 1.73, p<0.001, respectively) than patients treated with open partial nephrectomy. CONCLUSIONS: Laparoscopic and robotic partial nephrectomy is associated with higher positive surgical margin rates compared to open partial nephrectomy for clinical T1a renal cell carcinoma. The effect of margin status on long-term oncologic outcomes in this context remains to be determined.

Autonomic testing of women with interstitial cystitis/bladder pain syndrome.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by urinary urgency, frequency, nocturia, pain worse as the bladder fills and improved after emptying. These features might suggest abnormal autonomic bladder control mechanisms. We compared the structural integrity of the autonomic nervous system (ANS) in IC/BPS and control subjects. METHODS: IRB-approved study at University Hospitals Case Medical Center, Cleveland, OH to evaluate the structural integrity of the ANS in adult females. Testing included cardiovascular response to deep breathing, Valsalva maneuver, 30 min head up tilt, and sudomotor test. RESULTS: Differences in ANS integrity for IC/BPS subjects and controls were determined by modified Composite Autonomic Severity Score (CASS) that includes sudomotor, adrenergic and cardiovascular indices. Baseline heart rate (HR) and HRs from each of three 10 min upright segments of a tilt test were compared and trend analyses performed using t tests. Healthy and IC/BPS subjects were demographically similar. The two groups did not differ in modified-CASS scores but elevated average peak heart rate was evident during baseline (supine; p = 0.057) for IC/BPS subjects prior to a tilt test. Difference at baseline was maintained at each interval during the tilt, with nearly identical slopes across intervals. The preliminary nature of this report denotes a small sample size and important differences may not be detected. CONCLUSIONS: The findings show no structural ANS abnormalities in IC/BPS subjects. Higher baseline HR supports the concept of functional rather than structural change in the ANS, such as abnormality of sympathetic/parasympathetic balance that will require further evaluation.

Interstitial Cystitis - Elucidation of Psychophysiologic and Autonomic Characteristics (the ICEPAC Study): design and methods.

BACKGROUND AND PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is relatively common and associated with severe pain, yet effective treatment remains elusive. Research typically emphasized the bladder's role, but given the high presence of systemic comorbidities, the authors hypothesized a pathophysiologic nervous system role. This paper reports the methodology and approach to study the nervous system in women with IC/BPS. The study compares neurologic, urologic, gynecologic, autonomic, gastrointestinal, and psychological features of women with IC/BPS, their female relatives, women with myofascial pelvic pain (MPP), and healthy controls to elucidate the role of central and peripheral processing. METHODS AND RESULTS: In total, 228 women (76 IC/BPS, 76 MPP, 38 family members, and 38 healthy controls) will be recruited. Subjects undergo detailed screening, structured neurologic examination of limbs and pelvis, tender point examination, autonomic testing, electrogastrography, and assessment of comorbid functional dysautonomias. Interpreters are blinded to subject classification. Psychological and stress response characteristics are examined with assessments of stress, trauma history, general psychological function, and stress response quantification. As of December 2012, data collection is completed for 25 healthy controls, 33 IC/BPS ± MPP, eight MPP, and three family members. Recruitment rate is accelerating and strategies emphasize maintaining and encouraging investigator participation in study science, internet advertising, and presentations to pelvic pain support groups. CONCLUSION: The study represents a comprehensive, interdisciplinary approach to sampling autonomic and psychophysiologic characteristics of women with IC/BPS. Despite divergent opinions on study methodologies based on specialty experiences, the study has proven feasible to date and different perspectives have proved to be one of the greatest study strengths.

Autonomic testing in healthy subjects: preliminary observations.

INTRODUCTION: Autonomic testing is used clinically. Yet, the prevalence of "abnormal" variants in the healthy population has not been reported. RESULTS: We report the results of autonomic testing in healthy females >18 years, in whom we found decrease or absent sudomotor function in 1-2 locations. CONCLUSIONS: These findings should caution physicians in the interpretation of autonomic testing. This report underscores the need of larger studies to determine the prevalence of these findings.

Autonomic dysfunction in women with chronic pelvic pain.

We compared the Autonomic Symptom Profile results in 16 women with chronic pelvic pain (CPP) and 15 age-matched healthy subjects. Moderately severe generalized autonomic symptomology occurs in women with CPP, but not in controls. Further study including autonomic testing is needed to confirm results and explore the mechanism of dysfunction.