| 1. |
- Fall, Magnus, 1941, et al.
(författare)
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Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report
- 2020
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 54:2, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype. Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes. Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other. Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.
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| 2. |
- Fall, Magnus, 1941, et al.
(författare)
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Interstitial cystitis is bladder pain syndrome with Hunner's lesion.
- 2014
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Ingår i: International journal of urology. - : Wiley. - 0919-8172. ; 21:Suppl 1, s. 79-82
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Tidskriftsartikel (refereegranskat)abstract
- The contents and understanding of the term, interstitial cystitis, have undergone major changes during the past 100 years, moving from a chronic, true inflammatory bladder disorder to an extensive syndrome with lower urinary tract pain. Comments on this development are presented. From examples in the literature, some important features of classic interstitial cystitis are outlined. The more inclusive attitude of later decades has drawn desirable attention to the entire spectrum of disorders resulting in bladder pain. The wish to include all of them into one handy entity has unfortunately resulted in much scientific and clinical confusion, though. It is noted that originally interstitial cystitis represented the Hunner type of disease. Today, there is agreement that the classic type of interstitial cystitis with Hunner's lesions, bladder pain syndrome type 3C according to current terminology, stands out as a well-defined phenotype; it has to evaluated separately in clinical studies and practice, as treatment requirements differ importantly between this and other phenotypes.
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| 3. |
- Logadottir, Yr, et al.
(författare)
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Bladder pain syndrome/interstitial cystitis ESSIC type 3C : High expression of inducible nitric oxide synthase in inflammatory cells
- 2013
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813 .- 1651-2065. ; 47:1, s. 52-56
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Bladder pain syndrome/interstitial cystitis (BPS/IC) includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated ESSIC type 3C, the non-Hunner type of BPS/IC appears different in a number of respects. In a previous study, measuring luminal nitric oxide (NO) in the bladder of patients with BPS/IC, it was reported that all patients with ESSIC type 3C had high levels of NO. The aim of the present study was to investigate the source of inducible nitric oxide synthase (iNOS) and thereby the cellular origin of NO production via iNOS. Material and methods. Immunohistochemistry, with two different anti-iNOS antibodies, was used to study10 patients with BPS/IC ESSIC type 3C who expressed high levels of intraluminal NO. These results were compared with four patients with non-Hunner BPS/IC. To substantiate further the involvement of iNOS in this condition, the protein expression of nitrotyrosine, a marker for iNOS activation, was also assessed. Results. On routine histopathology, the tissues of type 3C patients exhibited inflammatory infiltrates of varying intensity. Strong immunoreactivity for both iNOS and nitrotyrosine was noted within the urothelium but also within the inflammatory infiltrates in the lamina propria of these subjects. Conclusions. The findings of a clearly detectable protein expression of iNOS in both the urothelium and the inflammatory infiltrates in bladder biopsies from patients with BPS/IC ESSIC type 3C suggest that the production of NO, in this entity, may occur in different tissue compartments.
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| 4. |
- Logadottir, Yr
(författare)
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Bladder pain syndrome/interstitial cystitis. Studies on classic BPS/IC, ESSIC type 3C, with special reference to the role of nitric oxide
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients presenting with symptoms of Bladder Pain Syndrome (BPS) are challenging to the urologist. Previously known as Interstitial Cystitis (IC), this syndrome has been extensively debated and investigated. IC mainly affects women, only 1 or 2 out of 10 patients are males. There is a need of consensus on classification since there are quite diverging opinions. BPS/IC is divided in two main subgroups, classic ulcerative and non-ulcerative forms, which have different histopathological, immunological and neurobiological features and respond differently to a variety of treatments. The symptoms are similar, with chronic pain related to bladder filling and urinary frequency. The International Society for the Study of BPS (ESSIC) has proposed diagnostic criteria, classification and nomenclature based on how the diagnosis was established. Classic IC is now referred to as BPS Type 3C, which indicates that the patient has a Hunner lesion, is diagnosed with cystoscopy, bladder hydrodistention under general anaesthesia, and histopathological examination of bladder tissue sample. For simplicity, the remaining group will here be referred to as non-Hunner BPS patients. The aims of this thesis were; to further describe a patient population with the diagnosis of BPS/IC, to investigate the nitric oxide (NO) production in the BPS/IC urinary bladder, to analyse the source of NO production, to localise the presence of the iso-enzyme, inducible Nitric Oxide Synthase (iNOS), and to survey inflammatory mediators in the bladder tissue of BPS ESSIC Type 3C/classic IC patients compared to healthy controls. The hallmark of BPS Type 3C compared to non-Hunner BPS patients is the ulceration in the mucosa and the inflammation in the bladder wall, including increased mast cell count. This is not found in the non-Hunner group of patients. The Hunner BPS Type 3C patients are older by 10 to 20 years at diagnosis and have markedly smaller bladder capacity when measured under general anaesthesia. The end stage is a fibrotic small bladder. This does not happen in non-Hunner BPS. We have shown that the BPS Type 3C bladder produces large quantities of NO, which is not the case in non-Hunner BPS patients or healthy controls. The iso-enzyme iNOS, believed to be the catalyst in NO production, is found in large amounts within the inflammatory infiltrate of the BPS Type 3C bladder, as well as in the urothelial cells, in both BPS groups and healthy controls. The spectrum of inflammatory markers in the bladder wall of BPS Type 3C patients indicates that the inflammation is similar to what is seen in certain diseases believed to be of autoimmune origin. The paper on cytokine responses in BPS/IC Type 3C, with increase in mRNA expression of interleukin-17, opens up novel research avenues with expectations for new pharmacological targets for the treatment of this condition.
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| 5. |
- Logadottir, Yr, et al.
(författare)
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Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis.
- 2012
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Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 46:5, s. 365-70
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Bladder pain syndrome/interstitial cystitis (BPS/IC) is one of the most bothersome conditions in urological practice. This syndrome includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated European Society for the Study of Interstitial Cystitis (ESSIC) type 3C, the non-Hunner type of BPS/IC appears different concerning demographic, endoscopic and histological findings, as well as the response to all forms of treatment. The objective of this study was to determine whether there are additional dissimilarities in clinical presentation between the main phenotypes of BPS/IC. Material and methods. In total, 393 BPS/IC patients (210 type 3C and 183 non-Hunner), diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases and ESSIC criteria, were studied by surveying the clinical records including micturition diaries. Results. In this clinical material, BPS/IC ESSIC type 3C accounted for 55% of cases. Patients with non-Hunner disease were on average 20 years younger at the time of diagnosis. Furthermore, there was a marked and significant difference in bladder capacity under general anaesthesia (p < 0.0001). Conclusions. The findings in the present series, together with previously published reports by this group and by others, confirm the striking differences between the main forms of BPS/IC and underline the indispensability of adequate subtyping in clinical studies.
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| 6. |
- Logadottir, Yr, et al.
(författare)
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Cytokine Expression in Patients with Bladder Pain Syndrome/Interstitial Cystitis ESSIC Type 3C
- 2014
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Ingår i: Journal of Urology. - Philadelphia, USA : Elsevier. - 0022-5347 .- 1527-3792. ; 192:5, s. 1564-1568
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls.Materials and Methods: Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-alpha, TGF-beta and IFN-gamma was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count.Results: IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-alpha, TGF-beta and IFN-gamma mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C.Conclusions: Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications.
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| 7. |
- Logadottir, Yr, et al.
(författare)
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Cytokine responses in BPS/IC Type 3C
- 2014
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Ingår i: International journal of urology. - : Wiley-Blackwell. - 0919-8172 .- 1442-2042. ; 21:Suppl.1, s. A23-A23
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Logadottir, Yr, et al.
(författare)
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Inflammation characteristics in bladder pain syndrome ESSIC type 3C/classic interstitial cystitis
- 2014
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Ingår i: International journal of urology. - Hoboken : Wiley-Blackwell. - 0919-8172 .- 1442-2042. ; 21:Suppl. 1, s. 75-78
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Interstitial cystitis is regarded as a heterogenous syndrome with two distinguishable forms: the non-ulcer and the classic form of interstitial cystitis, the latter with Hunner's lesions; or bladder pain syndrome type 3C and non-Hunner bladder pain syndrome, respectively.Methods: A cohort of 379 patients diagnosed with interstitial cystitis was studied. Nitric oxide release from the bladder was measured using a chemiluminescence nitric oxide analyzer. Bladder biopsies from the patients and healthy controls were analyzed by routine histopathological examination. Biopsies from a subset of patients and controls were also analyzed by immunohistochemistry and cytokine gene expression by real-time polymerase chain reaction.Results: Patients with bladder pain syndrome type 3C/classic interstitial cystitis had considerably higher levels of nitric oxide as compared with non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients and healthy individuals, and showed histologically a chronic inflammation in the bladder mucosa, with abundant mast cell infiltration in all layers of the bladder wall. No inflammation was noted in non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients. The isoenzymes inducible nitric oxide synthase, the catalyst in the nitric oxide production, was strongly expressed in the inflammatory cells in the bladder mucosa of bladder pain syndrome type 3C/classic interstitial cystitis patients. In addition, the expression of the pro-inflammatory cytokines interleukin-6 and interleukin-17A messenger ribonucleic acid, and of anti-inflammatory interleukin-10 messenger ribonucleic acid showed significantly increased levels in bladder pain syndrome type 3C/classic interstitial cystitis compared with healthy controls.Conclusion: Bladder pain syndrome type 3C/classic interstitial cystitis is a distinct inflammatory disease and in many aspects shares features of inflammatory autoimmune diseases. These findings could open up novel research avenues with expectations for new targets for pharmacological treatment.
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| 9. |
- Logadottir, Yr, et al.
(författare)
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Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis.
- 2004
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Ingår i: J Urol. - : Ovid Technologies (Wolters Kluwer Health). ; 171:3
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Purpose Interstitial cystitis (IC) is one of the most bothersome conditions in urological practice. There are 2 subtypes, classic and nonulcer IC, with similar symptoms but different outcomes with respect to clinical course and response to treatment. Histologically there are fundamental differences between the 2 subtypes, classic IC presenting a severe abnormality of the urothelium and characteristic inflammatory cell infiltrates while inflammation is scant in nonulcer IC. Regulation of urinary nitric oxide synthase activity has been proposed to be of importance for immunological responses in IC. We present evidence of a profound difference between the 2 subtypes concerning nitric oxide production, mirroring the differences in inflammatory response in IC. Materials and Methods A total of 17 patients with both subtypes and active disease as well as patients with disease in remission were included in the study, all diagnosed according to National Institute for Diabetes and Digestive and Kidney Diseases criteria. Luminal nitric oxide was measured in the bladder of patients using a chemiluminescence nitric oxide analyzer. Results All patients with classic IC had high levels of NO. None of the other patients had any significant increase in NO levels in the bladder. The NO level in patients with classic IC was not related to symptoms but rather to the assignment to this specific subgroup of IC. The highest levels of NO were found in patients in the initial phase of classic IC. Conclusions The difference in NO evaporation between classic and nonulcer IC allows for subtyping of cases meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria without performing cystoscopy. The findings in the present series together with previous findings clearly demonstrate that the 2 subtypes of IC represent separate entities. This separation further emphasizes the need to subtype all cases included in all scientific matters, ensuring that the 2 subtypes are evaluated separately in clinical studies. Key Words: cystitis, interstitial; nitric oxide
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| 10. |
- Whitmore, K. E., et al.
(författare)
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Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome
- 2019
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Ingår i: International Journal of Urology. - : Wiley. - 0919-8172 .- 1442-2042. ; 26, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- Background Global consensus on the standardization of terminology for interstitial cystitis/bladder pain syndrome is lacking and is in the formative stages. The Workshop on Hunner lesion versus non-Hunner lesion at the 2018 International Consultation on Interstitial Cystitis Japan discussed prevalence, performance and outcome of endoscopy, the role of histopathology, and markers. Methods A panel of experts reviewed the literature regarding Hunner lesion vs. non-Hunner lesion interstitial cystitis/bladder pain syndrome. Results The prevalence of Hunner lesion has been reported to be 5-57%. Older age and smaller anatomic bladder capacity were associated with Hunner lesions. Cystoscopy using local anesthesia is not adequate in diagnosing interstitial cystitis but is needed to rule out confusable diseases. Cystoscopy with hydrodistention and redistention of the bladder is considered standard. A Hunner lesion is visualized as a quite typical inflammatory reaction: a reddened mucosal area with small vessels radiating towards a central scar, splitting at distension, usually associated with a waterfall bleeding pattern. Biopsies from the inflamed area show inflammatory infiltrates, granulation tissue, detrusor mastocytosis, and fibrin deposits. Ablation of Hunner lesions includes transurethral resection of lesions, fulguration, laser ablation, and cortical steroid injections. Mast cell density is a somewhat controversial matter, described differently in different studies: marked increase in Hunner lesion vs. non-Hunner lesion in the majority of studies, no difference in a few. Nitric oxide appears to be a definitive marker in distinguishing Hunner lesion vs. non-Hunner lesion disease. Macrophage migration inhibitory factor is elevated in Hunner lesion patients. Increased level of urinary proinflammatory genes expression has also been found in Hunner lesion subjects. Conclusions Hunner lesion patients are clinically and pathologically distinct from non-Hunner lesion bladder pain syndrome patients. RAMS P, 1988, NEUROUROLOGY AND URODYNAMICS, V7, P403
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