Bio

Bio


Dr. Philip Hanno specializes in the treatment of urologic chronic pain syndromes including bladder pain syndrome/interstitial cystitis and chronic pelvic pain syndrome in men (nonbacterial prostatitis). He sees patients with voiding dysfunction, urinary tract infection, and general urologic problems as well. From 1981 to 1990 he was an Associate Professor of Urology at the Hospital of the University of Pennsylvania and Chief of Urology at the Philadelphia Veterans Administration Medical Center. For the next decade he was Chairman of Urology at Temple University School of Medicine. After a year as a medical officer in the Food and Drug Administration in Washington, he returned to the University of Pennsylvania in 1999 as Professor of Urology. He came to Stanford in October 2016.

He has studied bladder pain syndrome both from a basic science and clinical perspective for much of his career and has published extensively on the syndrome. He is co-chair of the Medical Advisory Board of the Interstitial Cystitis Association and on the executive board of the International Society for the Study of Bladder Pain Syndrome (ESSIC). He is the past Chair of the Bladder Pain Syndrome Guideline Committee of the American Urological Association.

Dr. Hanno focuses on the non-operative management of common urologic conditions with his special interest being helping patients with urologic chronic pain syndromes.

Clinical Focus


  • Urology

Academic Appointments


Administrative Appointments


  • Chief of Urology, Philadelphia Veterans Administration Medical Center (1981 - 1990)
  • Chairman Department of Urology, Temple University School of Medicine (1990 - 1998)
  • Director, Center for the Study of Male Sexual Dysfunction, Hospital of University of Pennsylvania (1981 - 1990)
  • Director, Women's Center for the Evaluation and Treatment of Interstitial Cysitis, Hospital of the University of Pennsylvania (1985 - 1990)
  • Director Infection, Inflammation, and Interstitial Cystitis Program, Hospital of the University of Pennsylvania (1999 - 2016)
  • Medical Director, Clinical Effectiveness and Quality, University of Pennsylvania Health System (2000 - 2005)
  • Patient Safety Officer, Clinical Practices of the University of Pennsylvania (2006 - 2007)

Honors & Awards


  • Best Reviewer, Journal of Urology (2013)
  • Most Outstanding Reviewer, Journal of Urology (2008)
  • Honorable Mention: Best Reviewers, Journal of Urology (2006)
  • Immergut Honorary Lectureship, Maimonides Medical Center, Brooklyn (1996)
  • Most Valuable Player Award, Interstitial Cystitis Association (1993)
  • Special Award, Interstitial Cystitis Association (1990)
  • Second Prize, "Urinary Tract Infection in Pregnancy", Philadelphia Urologic Society Essay Contest (1980)
  • Third Prize, "The Effect of Preexisting Bacteriuria on t Bladder Resistance to Superinfection", Philadelphia Urologic Society Essay Contest (1979)
  • First Prize, "Heparin as an Antibacterial Agent in the Rabbit Bladder", Philadelphia Urological Society Essay Contest (1978)

Boards, Advisory Committees, Professional Organizations


  • Executive Committee, International Society for the Study of Bladder Pain Syndrome (ESSIC) (2010 - Present)
  • Editorial Board, Urology Times (1990 - Present)
  • Co-Director MultiDisciplinary Approach to the Study of Chronic Pelvic Pain, NIDDK of National Institutes of Health (2008 - 2014)
  • Bone, Reproductive, and Urologic Drugs Advisory Panel, voting Ad Hoc member, Food and Drug Administration (2000 - Present)
  • Chair Painful Bladder Committee, International Consultation on Urinary Incontinence (2004 - Present)
  • Medical Advisory Board, International Painful Bladder Foundation (2005 - Present)
  • Co-Chair Medical Advisory Board, Interstitial Cystitis Association (1997 - Present)
  • Program Committee, American Urological Association (2004 - 2004)
  • Education Council, American Urological Association (2003 - 2005)
  • Chairman of Audio-Visual Committee, American Urological Association (2003 - 2005)
  • Chairman, Video Library, American Urological Association (1998 - 2003)
  • Vice Chairman, Audio Visual Committee, American Urological Association (1995 - 2003)
  • Video Education Committee, American College of Surgeons (2006 - 2011)
  • Examination Committee, American Board of Urology (1989 - 1993)

Professional Education


  • Residency:Hospital of the University of Pennsylvania General Surgery Residency (1975) PA
  • Medical Education:Baylor College of Medicine Registrar (1973) TX
  • Board Certification: Urology, American Board of Urology (1982)
  • Fellowship:University of Pennsylvania Dept of GME (1980) PA
  • Residency:University of Pennsylvania Dept of GME (1976) PA
  • Residency:Baylor College of Medicine Surgery Residency (1974) TX
  • fellowship, Southeast Hampshire Health District, England, Urology (1981)
  • Residency, University of Pennsylvania, Urology (1980)
  • MPH, Medical College of Wisconsin, Health Care Administration (2005)
  • MD, Baylor College of Medicine, Medicine (1973)
  • BA, University of Pennsylvania, Economics (1970)

Research & Scholarship

Current Research and Scholarly Interests


Design clinical trials to evaluate new treatments for bladder pain syndrome

Publications

All Publications


  • LEGENDS IN UROLOGY CANADIAN JOURNAL OF UROLOGY Hanno, P. 2019; 26 (6): 10008–11
  • Targeting the SHIP1 Pathway Fails to Show Treatment Benefit in Interstitial Cystitis/Bladder Pain Syndrome: Lessons Learned from Evaluating Potentially Effective Therapies in This Enigmatic Syndrome JOURNAL OF UROLOGY Nickel, J., Moldwin, R., Hanno, P., Dmochowski, R., Peters, K. M., Payne, C., Wein, A. 2019; 202 (2): 301–8
  • Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Aguiniga, L. M., Yang, W., Yaggie, R. E., Schaeffer, A. J., Klumpp, D. J., Clemens, J., Hanno, P., Kirkali, Z., Kusek, J. W., Landis, J., Lucia, M., Moldwin, R. M., Mullins, C., Pontari, M. A., van Bokhoven, A., Osypuk, A. A., Dayton, R., Triolo, C. S., Jonscher, K. R., Sullivan, H. T., Wilson, R., Grasmick, Z. D., Bavendam, T. G., Barrell, T., Doe, R., Farrar, J. T., Fernando, M., Gallagher, L., Hou, X., Howard, T., Jemielita, T., Kuzla, N., Newcomb, C., Robinson-Garvin, N., Smith, S., Stephens-Shields, A., Wang, Y., Wang, X., (Vania) Apkarian, A., Arroyo, C., Bass, M., Cella, D., Farmer, M. A., Fitzgerald, C., Gershon, R., Griffith, J. W., Heckman, C. J., Jiang, M., Keefer, L., Lloyd, R., Marko, D. S., Michniewicz, J., Miller, R., Parrish, T., Tu, F., Yaggi, R., Mayer, E. A., Rodriguez, L., Alger, J., Ashe-McNalley, C. P., Ellingson, B., Heendeniya, N., Kilpatrick, L., Cara, K., Kutch, J., Labus, J. S., Naliboff, B. D., Randal, F., Smith, S. R., Kreder, K. J., Bradley, C. S., Eno, M., Greiner, K., Luo, Y., Lutgendorf, S. K., O'Donnell, M. A., Ziegler, B., Schrepf, A., Hardy, I., Magnotta, V., Erickson, B., Clauw, D. J., As-Sanie, S., Berry, S., Grayhack, C., Halvorson, M. E., Harris, R., Harte, S., Ichesco, E., Oldendorf, A., Scott, K. A., Williams, D. A., Buchwald, D., Afari, N., Bacus, T., Edwards, T., Krieger, J., Maravilla, K., Miller, J., Patrick, D., Qin, X., Richey, S., Risques, R., Robertson, K., Ross, S. O., Spiro, R., Strachan, E., Sundsvold, T. J., Sutherland, S., Yang, C. C., Andriole, G. L., Lai, H., Bristol, R. L., Gereau, R. W., Hong, B. A., Klim, A. P., Sutcliffe, S., Vetter, J., Song, D. G., Milbrandt, M., Haroutounian, S., Vijairania, P., Parker (Chaturvedi), K., Hung, T., Colditz, G., Gardner, V. C., Henderson, J. P., Spitznagle, T. M., Pakpahan, R., James, A., Yan, Y., Langston, M., Hong, B., Mueller, S., Crowley, J., Vogt, S., Hultgren, S., Nguyen, N., Blasche, G., Qiu, C., Cupps, L., Bok, S., Hooten, T. M., Grullon, L., Atis, N., Ness, T. J., Deutsch, G., Den Hollander, J., Corbitt, B. D., Bradley, L., North, C. S., Downs, D., Anger, J., Ackerman, J., Ackerman, A., Cha, J., Eilber, K., Freeman, M., Funari, V., Kim, J., Van Eyk, J., Yang, W., Moses, M. A., Briscoe, A. C., Briscoe, D., Curatolo, A., Froehlich, J., Lee, R. S., Sachdev, M., Solomon, K. R., Steen, H., Mackey, S., Bagarinao, E., Foster, L. C., Hubbard, E., Johnson, K. A., Martucci, K. T., McCue, R. L., Moericke, R. R., Nilakantan, A., Noor, N., Nickel, J., Ehrlich, G. D., MAPP Res Network Study Grp 2019; 317 (2): R289–R300

    Abstract

    Corticotropin-releasing factor (CRF) regulates stress responses, and aberrant CRF signals are associated with depressive disorders. Crf expression is responsive to arachidonic acid (AA), where CRF is released from the hypothalamic paraventricular nucleus (PVN) to initiate the hypothalamic-pituitary-adrenal axis, culminating in glucocorticoid stress hormone release. Despite this biological and clinical significance, Crf regulation is unclear. Here, we report that acyloxyacyl hydrolase, encoded by Aoah, is expressed in the PVN, and Aoah regulates Crf through the aryl hydrocarbon receptor (AhR). We previously showed that AOAH-deficient mice mimicked interstitial cystitis/bladder pain syndrome, a condition frequently associated with comorbid anxiety and depression. With the use of novelty-suppressed feeding and sucrose preference assays to quantify rodent correlates of anxiety/depression, AOAH-deficient mice exhibited depressive behaviors. AOAH-deficient mice also had increased CNS AA, increased Crf expression in the PVN, and elevated serum corticosterone, consistent with dysfunction of the hypothalamic-pituitary-adrenal axis. The human Crf promoter has putative binding sites for AhR and peroxisome proliferator-activated receptor (PPARγ). PPARγ did not affect AA-dependent Crf expression in vitro, and conditional Pparγ knockout did not alter the AOAH-deficient depressive phenotype, despite previous studies implicating PPARγ as a therapeutic target for depression. In contrast, Crf induction was mediated by AhR binding sites in vitro and increased by AhR overexpression. Furthermore, conditional Ahr knockout rescued the depressive phenotype of AOAH-deficient mice. Finally, an AhR antagonist rescued the AOAH-deficient depressive phenotype. Together, our results demonstrate that Aoah is a novel genetic regulator of Crf mediated through AhR, and AhR is a therapeutic target for depression.

    View details for DOI 10.1152/ajpregu.00029.2019

    View details for Web of Science ID 000481616900008

    View details for PubMedID 31017816

  • Phenotyping of interstitial cystitis/bladder pain syndrome. International journal of urology : official journal of the Japanese Urological Association Akiyama, Y., Hanno, P. 2019; 26 Suppl 1: 17–19

    Abstract

    Interstitial cystitis/bladder pain syndrome is a chronic, potentially debilitating condition characterized by pain perceived to be related to the bladder in conjunction with lower urinary tract symptoms, and includes a wide variety of clinical phenotypes with diverse etiologies. Currently the only clinically relevant proven phenotype of interstitial cystitis/bladder pain syndrome is the Hunner lesion. Whether the presence of Hunner lesions is a hallmark of a distinct disease cohort or a potentially transient feature of non-Hunner lesion phenotype has been debated but remains controversial. There are few documented examples of a patient converting between the two forms. Growing clinical and basic evidence supports eliminating the Hunner lesion phenotype from the bladder pain syndrome umbrella and considering it a distinct disease. The Hunner lesion phenotype is characterized by distinct bladder histology, including subepithelial chronic inflammatory changes and epithelial denudation, and specific clinical characteristics (older onset age, severe bladder-centric symptoms, reduced bladder capacity, and favorable response to the lesion-targeted therapies). To define the Hunner lesion phenotype, it is necessary to develop an atlas of standardized images of cystoscopic (and, if possible, pathological) appearances of Hunner lesions. A true potential and clinically relevant phenotype of interstitial cystitis/bladder pain syndrome may be patients with non-bladder-centric symptoms, characterized by the affect dysregulation and somatic symptoms, and a greater bladder capacity in absence of Hunner lesions. In the present workshop, we concluded that the Hunner lesion is a valid phenotype and can reasonably be considered a disease in its own right. Assessment of bladder capacity and the extent of symptoms (bladder beyond or bladder centric) may help phenotyping of interstitial cystitis/bladder pain syndrome. Proper phenotyping is essential for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome, and for facilitating research.

    View details for DOI 10.1111/iju.13969

    View details for PubMedID 31144756

  • Editorial Comment from Dr Hanno to Interstitial cystitis, bladder pain syndrome, hypersensitive bladder, and interstitial cystitis/bladder pain syndrome - clarification of definitions and relationships INTERNATIONAL JOURNAL OF UROLOGY Meijlink, J. 2019; 26: 25

    View details for DOI 10.1111/iju.13992

    View details for Web of Science ID 000470929700012

  • Editorial Comment from Dr Hanno to Hunner lesion versus non-hunner lesion interstitial cystitis/bladder pain syndrome INTERNATIONAL JOURNAL OF UROLOGY Homma, Y. 2019; 26: 34

    View details for DOI 10.1111/iju.13993

    View details for Web of Science ID 000470929700015

  • Bladder pain syndrome: World guidelines and harmonization Hanno, P. WILEY. 2019: 80
  • Editorial Comment from Dr Hanno to Interstitial cystitis, bladder pain syndrome, hypersensitive bladder, and interstitial cystitis/bladder pain syndrome - clarification of definitions and relationships. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 25

    View details for DOI 10.1111/iju.13991

    View details for PubMedID 31144741

  • Editorial Comment from Dr Hanno to Intravesical tacrolimus in treatment of intractable bladder pain syndrome/interstitial cystitis-a pilot study. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 72

    View details for DOI 10.1111/iju.14003

    View details for PubMedID 31144763

  • Editorial Comment to Low bladder capacity is an important predictor for comorbidity of interstitial cystitis with hunner's lesion in patients with refractory chronic prostatitis/chronic pelvic pain syndrome. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 56

    View details for DOI 10.1111/iju.13999

    View details for PubMedID 31144748

  • Editorial Comment from Dr Hanno to Hunner lesion versus non-hunner lesion interstitial cystitis/bladder pain syndrome. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 34

    View details for DOI 10.1111/iju.13994

    View details for PubMedID 31144751

  • Editorial Comment from Dr Hanno to Pathophysiology of interstitial cystitis. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 16

    View details for DOI 10.1111/iju.13986

    View details for PubMedID 31144760

  • Editorial Comment to Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome. International journal of urology : official journal of the Japanese Urological Association Hanno, P. 2019; 26 Suppl 1: 40

    View details for DOI 10.1111/iju.13995

    View details for PubMedID 31144743

  • Optimization of DNA extraction from human urinary samples for mycobiome community profiling PLOS ONE Ackerman, A., Anger, J., Khalique, M., Ackerman, J. E., Tang, J., Kim, J., Underhill, D. M., Freeman, M. R., Clemens, J., Hanno, P., Kirkali, Z., Kusek, J. W., Landis, J., Lucia, M., Moldwin, R. M., Mullins, C., Pontari, M. A., Lucia, M., van Bokhoven, A., Osypuk, A. A., Dayton, R., Triolo, C. S., Jonscher, K. R., Sullivan, H. T., Wilson, R., Grasmick, Z. D., Mullins, C., Kusek, J. W., Kirkali, Z., Bavendam, T. G., Landis, J., Barrell, T., Doe, R., Farrar, J. T., Fernando, M., Gallagher, L., Hanno, P., Hou, X., Howard, T., Jemielita, T., Kuzla, N., Moldwin, R. M., Newcomb, C., Pontari, M. A., Robinson-Garvin, N., Smith, S., Stephens-Shields, A., Wang, Y., Wang, X., Klumpp, D. J., Schaeffer, A. J., Apkarian, A., Arroyo, C., Bass, M., Cella, D., Farmer, M. A., Fitzgerald, C., Gershon, R., Griffith, J. W., Heckman, C. J., Jiang, M., Keefer, L., Lloyd, R., Marko, D. S., Michniewicz, J., Miller, R., Parrish, T., Tu, F., Yaggi, R., Mayer, E. A., Rodriguez, L. V., Alger, J., Ashe-McNalley, C. P., Ellingson, B., Heendeniya, N., Kilpatrick, L., Cara, K., Kutch, J., Labus, J. S., Naliboff, B. D., Randal, F., Smith, S. R., Kreder, K. J., Bradley, C. S., Eno, M., Greiner, K., Luo, Y., Lutgendorf, S. K., O'Donnell, M. A., Ziegler, B., Schrepf, A., Hardy, I., Magnotta, V., Clauw, D. J., Clemens, J., As-Sanie, S., Berry, S., Grayhack, C., Halvorson, M. E., Harris, R., Harte, S., Ichesco, E., Oldendorf, A., Scott, K. A., Williams, D. A., Buchwald, D., Afari, N., Bacus, T., Edwards, T., Krieger, J., Maravilla, K., Miller, J., Patrick, D., Qin, X., Richey, S., Risques, R., Robertson, K., Ross, S. O., Spiro, R., Strachan, E., Sundsvold, T. J., Sutherland, S., Yang, C. C., Andriole, G. L., Lai, H., Bristol, R. L., Gereau, R. W., Hong, B. A., Klim, A. P., Sutcliffe, S., Vetter, J., Song, D. G., Milbrandt, M., Haroutounian, S., Vijairania, P., Parker (Chaturvedi), K., Tran Hung, Colditz, G., Gardner, V. C., Henderson, J. P., Spitznagle, T. M., Pakpahan, R., James, A., Yan, Y., Langston, M., Hong, B., Mueller, S., Crowley, J., Vogt, S., Hultgren, S., Nang Nguyen, Blasche, G., Qiu, C., Cupps, L., Bok, S., Hooten, T. M., Grullon, L., Atis, N., Ness, T. J., Deutsch, G., Den Hollander, J., Corbitt, B. D., Bradley, L., North, C. S., Downs, D., Anger, J., Ackerman, J., Ackerman, A., Cha, J., Eilber, K., Freeman, M., Funari, V., Kim, J., Van Eyk, J., Yang, W., Moses, M. A., Briscoe, A. C., Briscoe, D., Curatolo, A., Froehlich, J., Lee, R. S., Sachdev, M., Solomon, K. R., Steen, H., Mackey, S., Bagarinao, E., Foster, L. C., Hubbard, E., Johnson, K. A., Martucci, K. T., Mccue, R. L., Moericke, R. R., Nilakantan, A., Noor, N., Nickel, J., Ehrlich, G. D., NIH Multidisciplinary Approach Stu 2019; 14 (4): e0210306

    Abstract

    Recent data suggest the urinary tract hosts a microbial community of varying composition, even in the absence of infection. Culture-independent methodologies, such as next-generation sequencing of conserved ribosomal DNA sequences, provide an expansive look at these communities, identifying both common commensals and fastidious organisms. A fundamental challenge has been the isolation of DNA representative of the entire resident microbial community, including fungi.We evaluated multiple modifications of commonly-used DNA extraction procedures using standardized male and female urine samples, comparing resulting overall, fungal and bacterial DNA yields by quantitative PCR. After identifying protocol modifications that increased DNA yields (lyticase/lysozyme digestion, bead beating, boil/freeze cycles, proteinase K treatment, and carrier DNA use), all modifications were combined for systematic confirmation of optimal protocol conditions. This optimized protocol was tested against commercially available methodologies to compare overall and microbial DNA yields, community representation and diversity by next-generation sequencing (NGS).Overall and fungal-specific DNA yields from standardized urine samples demonstrated that microbial abundances differed significantly among the eight methods used. Methodologies that included multiple disruption steps, including enzymatic, mechanical, and thermal disruption and proteinase digestion, particularly in combination with small volume processing and pooling steps, provided more comprehensive representation of the range of bacterial and fungal species. Concentration of larger volume urine specimens at low speed centrifugation proved highly effective, increasing resulting DNA levels and providing greater microbial representation and diversity.Alterations in the methodology of urine storage, preparation, and DNA processing improve microbial community profiling using culture-independent sequencing methods. Our optimized protocol for DNA extraction from urine samples provided improved fungal community representation. Use of this technique resulted in equivalent representation of the bacterial populations as well, making this a useful technique for the concurrent evaluation of bacterial and fungal populations by NGS.

    View details for DOI 10.1371/journal.pone.0210306

    View details for Web of Science ID 000465519100004

    View details for PubMedID 31022216

    View details for PubMedCentralID PMC6483181

  • A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network JOURNAL OF CLINICAL MEDICINE Nickel, J., Stephens-Shields, A. J., Landis, J., Mullins, C., van Bokhoven, A., Lucia, M., Henderson, J. P., Sen, B., Krol, J. E., Ehrlich, G. D., Clemens, J., Hanno, P., Kirkali, Z., Kusek, J. W., Pontari, M. A., Klumpp, D. J., Schaeffer, A. J., Apkarian, A., Cella, D., Farmer, M. A., Fitzgerald, C., Gershon, R., Griffith, J. W., Heckman, C. J., Jiang, M., Keefer, L., Marko, D. S., Michniewicz, J., Parrish, T., Tu, F., Mayer, E. A., Rodriguez, L., Alger, J., Ashe-McNalley, C. P., Ellingson, B., Heendeniya, N., Kilpatrick, L., Kutch, J., Labus, J. S., Naliboff, B. D., Randal, F., Smith, S. R., Kreder, K. J., Bradley, C. S., Eno, M., Greiner, K., Luo, Y., Lutgendorf, S. K., O'Donnell, M. A., Ziegler, B., Clauw, D. J., As-Sanie, S., Berry, S., Halvorson, M. E., Harris, R., Harte, S., Ichesco, E., Oldendorf, A., Scott, K. A., Williams, D. A., Buchwald, D., Afari, N., Krieger, J., Miller, J., Richey, S., Ross, S. O., Spiro, R., Sundsvold, T. J., Strachan, E., Yang, C. C., Andriole, G. L., Lai, H., Bristol, R. L., Colditz, G., Deutsch, G., Gardner, V. C., Gereau, R. W., Hong, B. A., Hooton, T. M., Ness, T. J., North, C. S., Spitznagle, T. M., Sutcliffe, S., Barrell, T., Creighton, T., Fluharty, L., Hou, X., Robinson, N., Stephens, A., Wang, Y., Osypuk, A. A., Dayton, R., Jonscher, K. R., Sullivan, H. T., Wilson, R., Moses, M. A., Briscoe, A. C., Briscoe, D., Curatolo, A., Froehlich, J., Lee, R. S., Sachdev, M., Solomon, K. R., Steen, H., Mackey, S., Bagarinao, E., Foster, L. C., Hubbard, E., Johnson, K. A., Martucci, K. T., McCue, R. L., Moericke, R. R., Nilakantan, A., Noor, N., Bavendam, T. G., MAPP Res Network 2019; 8 (3)

    Abstract

    We surveyed urine microbiota of females diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) and matched control participants enrolled in the National Institutes of Health (NIH) Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network using the culture-independent methodology. Midstream urine specimens were analyzed with the Plex-ID molecular diagnostic platform that utilizes polymerase chain reaction⁻electrospray ionization⁻time-of-flight⁻mass spectrometry (PCR-ESI-TOF MS) to provide a comprehensive identification of bacterial and select fungal species. IC/BPS and control participants were evaluated for differences (presence, diversity, and abundance) in species and genus. Urine specimens obtained from 181 female IC/BPS and 182 female control participants detected a total of 92 species (41 genera). Mean (SD) species count was 2.49 (1.48) and 2.30 (1.28) among IC/BPS and control participants, respectively. Overall species composition did not significantly differ between IC/BPS and control participants at any level (p = 0.726 species level, p = 0.222 genus level). IC/BPS participants urine trended to an overabundance of Lactobacillus gasseri (p = 0.09) detected but had a lower prevalence of Corynebacterium compared with control participants (p = 0.002). The relative abundance data analysis mirrored the prevalence data differences with no significant differences in most species or genus abundance other than Lactobacillus gasseri and Corynebacterium (p = 0.08 and p = 0.001, respectively). No cause and/or effect conclusion can be drawn from this observation, but it suggests that a more comprehensive evaluation (vaginal, bowel, catheterized bladder and/or tissue-based specimens) of the lower urinary tract microbiota in IC/BPS patients is warranted.

    View details for DOI 10.3390/jcm8030415

    View details for Web of Science ID 000464435800001

    View details for PubMedID 30917614

    View details for PubMedCentralID PMC6462969

  • Targeting the SHIP1 Pathway Fails to Show Treatment Benefit in Interstitial Cystitis/Bladder Pain Syndrome: Lessons Learned from Evaluating Potentially Effective Therapies in This Enigmatic Syndrome. The Journal of urology Nickel, J. C., Moldwin, R., Hanno, P., Dmochowski, R., Peters, K. M., Payne, C., Wein, A. 2019: 101097JU0000000000000192

    Abstract

    PURPOSE: In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome.MATERIALS AND METHODS: Subjects with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point scale despite treatment were randomized to 100 or 200 mg of an oral SHIP1 activator or placebo once daily for 12 weeks. Maximum pain scores and urinary frequency were recorded in an e-diary. The ICSI (O'Leary-Sant Interstitial Cystitis Symptom Index) and BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) questionnaires were administered. Safety was monitored through 12 weeks of treatment.RESULTS: A total of 298 female subjects with moderate to severe symptoms of interstitial cystitis/bladder pain syndrome were treated with 100 or 200 mg SHIP1 activator orally once daily for 12 weeks. Treatment demonstrated no difference in maximum daily bladder pain compared to placebo. There was no treatment benefit over that of placebo in the secondary end points of urinary voiding frequency, the BPIC-SS, the ICSI and a global response assessment. Exploratory analysis in 87 male subjects yielded a similar result, that is no difference from placebo. Treatment was generally well tolerated at both doses.CONCLUSIONS: SHIP1 activation is a safe but ineffective therapeutic approach to interstitial cystitis/bladder pain syndrome. Although this was a negative trial, the important lessons learned from this study in respect to inflammatory phenotype differentiation, including the potential importance of cystoscopy based classification, will improve current treatment in patients with interstitial cystitis/bladder pain syndrome and allow for better future trial design in those with this difficult urological chronic pain syndrome.

    View details for PubMedID 31090511

  • Legends in Urology. The Canadian journal of urology Hanno, P. 2019; 26 (6): 10008–11

    View details for PubMedID 31860416

  • Reply by Authors. The Journal of urology Nickel, J. C., Moldwin, R., Hanno, P., Dmochowski, R., Peters, K. M., Payne, C., Wein, A. 2019; 202 (2): 308

    View details for DOI 10.1097/01.JU.0000559828.17255.79

    View details for PubMedID 31090509

  • 6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: EVALUATION AND TREATMENT OF URINARY INCONTINENCE, PELVIC ORGAN PROLAPSE AND FAECAL INCONTINENCE NEUROUROLOGY AND URODYNAMICS Abrams, P., Andersson, K., Apostolidis, A., Birder, L., Bliss, D., Brubaker, L., Cardozo, L., Castro-Diaz, D., O'Connell, P. R., Cottenden, A., Cotterill, N., de Ridder, D., Dmochowski, R., Dumoulin, C., Fader, M., Fry, C., Goldman, H., Hanno, P., Homma, Y., Khullar, V., Maher, C., Milsom, I., Newman, D., Nijman, R. M., Rademakers, K., Robinson, D., Rosier, P., Rovner, E., Salvatore, S., Takeda, M., Wagg, A., Wagner, T., Wein, A. 2018; 37 (7): 2271–72

    View details for PubMedID 30106223

  • RANDOMIZED, PLACEBO-CONTROLLED, CLINICAL TRIAL IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME SHOWS COMMON SYMPTOM PRESENTATION BUT HIGHER RATES OF HUNNER LESIONS IN EUROPEAN PATIENTS Moldwin, R. M., Hanno, P., Biagi, H., Butterfield, N. WILEY. 2018: S109–S110
  • Relationship between Chronic Nonurological Associated Somatic Syndromes and Symptom Severity in Urological Chronic Pelvic Pain Syndromes: Baseline Evaluation of the MAPP Study JOURNAL OF UROLOGY Krieger, J. N., Stephens, A. J., Landis, J. R., Clemens, J. Q., Kreder, K., Lai, H. H., Afari, N., Rodriguez, L., Schaeffer, A., Mackey, S., Andriole, G. L., Williams, D. A. 2015; 193 (4): 1254-1262

    Abstract

    We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria.Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors.Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p < 0.001).Nonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes.

    View details for DOI 10.1016/j.juro.2014.10.086

    View details for PubMedID 25444992

  • The MAPP research network: design, patient characterization and operations BMC UROLOGY Landis, J. R., Williams, D. A., Lucia, M. S., Clauw, D. J., Naliboff, B. D., Robinson, N. A., van Bokhoven, A., Sutcliffe, S., Schaeffer, A. J., Rodriguez, L. V., Mayer, E. A., Lai, H. H., Krieger, J. N., Kreder, K. J., Afari, N., Andriole, G. L., Bradley, C. S., Griffith, J. W., Klumpp, D. J., Hong, B. A., Lutgendorf, S. K., Buchwald, D., Yang, C. C., Mackey, S., Pontari, M. A., Hanno, P., Kusek, J. W., Mullins, C., Clemens, J. Q. 2014; 14

    Abstract

    The "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described.The primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as "positive" controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended follow-up study for 161 of the UCPPS participants is ongoing.The MAPP Research Network represents a novel, comprehensive approach to the study of UCPPS, as well as other concomitant NUAS. Findings are expected to provide significant advances in understanding UCPPS pathophysiology that will ultimately inform future clinical trials and lead to improvements in patient care. Furthermore, the structure and methodologies developed by the MAPP Network provide the foundation upon which future studies of other urologic or non-urologic disorders can be based.ClinicalTrials.gov identifier: NCT01098279 "Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)". http://clinicaltrials.gov/show/NCT01098279.

    View details for DOI 10.1186/1471-2490-14-58

    View details for Web of Science ID 000340005200001

    View details for PubMedID 25085119

    View details for PubMedCentralID PMC4126395

  • Randomized Multicenter Clinical Trial of Myofascial Physical Therapy in Women With Interstitial Cystitis/Painful Bladder Syndrome and Pelvic Floor Tenderness JOURNAL OF UROLOGY FitzGerald, M. P., Payne, C. K., Lukacz, E. S., Yang, C. C., Peters, K. M., Chai, T. C., Nickel, J. C., Hanno, P. M., KREDER, K. J., Burks, D. A., MAYER, R., Kotarinos, R., Fortman, C., Allen, T. M., Fraser, L., Mason-Cover, M., Furey, C., Odabachian, L., Sanfield, A., Chu, J., Huestis, K., TATA, G. E., Dugan, N., Sheth, H., Bewyer, K., Anaeme, A., Newton, K., Featherstone, W., Halle-Podell, R., Cen, L., Landis, J. R., PROPERT, K. J., Foster, H. E., Kusek, J. W., Nyberg, L. M. 2012; 187 (6): 2113-2118

    Abstract

    We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome.A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated.A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported.A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

    View details for DOI 10.1016/j.juro.2012.01.123

    View details for Web of Science ID 000303821300051

    View details for PubMedID 22503015

    View details for PubMedCentralID PMC3351550

  • Early Termination of a Trial of Mycophenolate Mofetil for Treatment of Interstitial Cystitis/Painful Bladder Syndrome: Lessons Learned JOURNAL OF UROLOGY Yang, C. C., Burks, D. A., Propert, K. J., Mayer, R. D., Peters, K. M., Nickel, J. C., Payne, C. K., FitzGerald, M. P., Hanno, P. M., Chai, T. C., Kreder, K. J., Lukacz, E. S., Foster, H. E., Cen, L., Landis, J. R., Kusek, J. W., Nyberg, L. M. 2011; 185 (3): 901-906

    Abstract

    We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome.A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries.Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls.In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.

    View details for DOI 10.1016/j.juro.2010.10.053

    View details for Web of Science ID 000287133900050

    View details for PubMedID 21238993

    View details for PubMedCentralID PMC3408599

  • Effect of Amitriptyline on Symptoms in Treatment Naive Patients With Interstitial Cystitis/Painful Bladder Syndrome JOURNAL OF UROLOGY Foster, H. E., Hanno, P. M., Nickel, J. C., Payne, C. K., Mayer, R. D., Burks, D. A., Yang, C. C., Chai, T. C., Kreder, K. J., Peters, K. M., Lukacz, E. S., FitzGerald, M. P., Cen, L., Landis, J. R., Propert, K. J., Yang, W., Kusek, J. W., Nyberg, L. M. 2010; 183 (5): 1853-1858

    Abstract

    Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports.We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment.A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01).When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.

    View details for DOI 10.1016/j.juro.2009.12.106

    View details for Web of Science ID 000276747600068

    View details for PubMedID 20303115

    View details for PubMedCentralID PMC2861998

  • Sexual function is a determinant of poor quality of life for women with treatment refractory interstitial cystitis JOURNAL OF UROLOGY Nickel, J. C., Tripp, D., Teal, V., Propert, K. J., Burks, D., Foster, H. E., Hanno, P., Mayer, R., Payne, C. K., Peters, K. M., Kusek, J. W., Nyberg, L. M. 2007; 177 (5): 1832-1836

    Abstract

    Interstitial cystitis significantly negatively impacts quality of life. The demographic and clinical factors associated with decreased quality of life in these patients have not been well studied.Women with moderate/severe interstitial cystitis enrolled in a clinical trial of intravesical bacillus Calmette-Guerin were studied. Demographic data and responses to questionnaires were evaluated at baseline, including the O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, University of Wisconsin Interstitial Cystitis Inventory, Medical Outcomes Study sexual functioning scale, and the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Three composite indexes were constructed (from the O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, pain/urgency Likert scales and 24-hour voiding diary) to document the severity, frequency and bother of pain, urinary urgency and frequency (frequency composite index). Linear and multivariate regression models were used to examine predictors of the physical composite and mental composite scales of the Medical Outcomes Study Short Form Health Status Survey. Medical Outcomes Study sexual functioning scale data were available for 163 of the 217 women in the trial.Physical composite scale (median 36) and mental composite scale (median 42) were lower than the standard population value of 50. Multivariate models showed that employment, pain composite index and Medical Outcomes Study sexual functioning scale (all p<0.001) predicted physical composite scale, while only Medical Outcomes Study sexual functioning scale (p<0.001) remained a strong predictor of mental composite scale.Sexual functioning, employment and pain issues predict mental and physical quality of life. In particular, this study identifies sexual functioning as a primary predictor of mental quality of life in women with long-standing interstitial cystitis. It is suggested that sexual functioning may be a salient therapeutic target in the multifaceted treatment of patients with interstitial cystitis.

    View details for DOI 10.1016/j.juro.2007.01.060

    View details for Web of Science ID 000245764900066

    View details for PubMedID 17437831

  • A randomized controlled trial of intravesical bacillus Calmette-Guerin for treatment refractory interstitial cystitis JOURNAL OF UROLOGY MAYER, R., Propert, K. J., Peters, K. M., Payne, C. K., Zhang, Y. W., Burks, D., Culkin, D. J., Diokno, A., Hanno, P., Landis, J. R., Madigan, R., Messing, E. M., Nickel, J. C., Sant, G. R., Warren, J., WEIN, A. J., Kusek, J. W., Nyberg, L. M., Foster, H. E. 2005; 173 (4): 1186-1191

    Abstract

    We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively.A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates.Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.

    View details for DOI 10.1097/01.ju.0000152337.82806.e8

    View details for Web of Science ID 000227687600027

    View details for PubMedID 15758738