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International Journal of Molecular... Nov 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disease that induces mental stress, lower urinary symptoms, and pelvic pain, therefore resulting... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disease that induces mental stress, lower urinary symptoms, and pelvic pain, therefore resulting in a decline in quality of life. The present diagnoses and treatments still lead to unsatisfactory outcomes, and novel diagnostic and therapeutic modalities are needed. Although our understanding of the etiology and pathophysiology of IC/BPS is growing, the altered permeability of the impaired urothelium, the sensitized nerves on the bladder wall, and the chronic or intermittent sensory pain with inaccurate location, as well as pathologic angiogenesis, fibrosis, and Hunner lesions, all act as barriers to better diagnoses and treatments. This study aimed to summarize the comprehensive information on IC/BPS research, thereby promoting the progress of IC/BPS in the aspects of diagnosis, treatment, and prognosis. According to diverse international guidelines, the etiology of IC/BPS is associated with multiple factors, while the presence of Hunner lesions could largely distinguish the pathology, diagnosis, and treatment of non-Hunner lesions in IC/BPS patients. On the basis of the diagnosis of exclusion, the diverse present diagnostic and therapeutic procedures are undergoing a transition from a single approach to multimodal strategies targeting different potential phenotypes recommended by different guidelines. Investigations into the mechanisms involved in urinary symptoms, pain sensation, and bladder fibrosis indicate the pathophysiology of IC/BPS for further potential strategies, both in diagnosis and treatment. An overview of IC/BPS in terms of epidemiology, etiology, pathology, diagnosis, treatment, and fundamental research is provided with the latest evidence. On the basis of shared decision-making, a multimodal strategy of diagnosis and treatment targeting potential phenotypes for individual patients with IC/BPS would be of great benefit for the entire process of management. The complexity and emerging evidence on IC/BPS elicit more relevant studies and research and could optimize the management of IC/BPS patients.
Topics: Humans; Cystitis, Interstitial; Quality of Life; Pelvic Pain; Urinary Bladder; Chronic Pain; Fibrosis
PubMed: 36498919
DOI: 10.3390/ijms232314594 -
International Journal of Urology :... Jun 2020Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and... (Review)
Review
Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating B cells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a non-inflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.
Topics: Animals; Cystitis, Interstitial; Cystoscopy; Models, Animal; Pelvic Pain
PubMed: 32246572
DOI: 10.1111/iju.14229 -
Nature Reviews. Urology Mar 2019Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is... (Review)
Review
Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS.
Topics: Biomedical Research; Chronic Pain; Cystitis, Interstitial; Humans; Interdisciplinary Research; Male; Pelvic Pain; Prostatitis; Syndrome
PubMed: 30560936
DOI: 10.1038/s41585-018-0135-5 -
The Journal of Spinal Cord Medicine Nov 2017Spinal cord injury (SCI) is a devastating condition that can lead to significant neurological impairment and reduced quality of life. Despite advancements in our... (Review)
Review
CONTEXT
Spinal cord injury (SCI) is a devastating condition that can lead to significant neurological impairment and reduced quality of life. Despite advancements in our understanding of the pathophysiology and secondary injury mechanisms involved in SCI, there are currently very few effective treatments for this condition. The field, however, is rapidly changing as new treatments are developed and key discoveries are made.
METHODS
In this review, we outline the pathophysiology, management, and long-term rehabilitation of individuals with traumatic SCI. We also provide an in-depth overview of emerging therapies along the spectrum of the translational pipeline.
EVIDENCE SYNTHESIS
The concept of "time is spine" refers to the concept which emphasizes the importance of early transfer to specialized centers, early decompressive surgery, and early delivery of other treatments (e.g. blood pressure augmentation, methylprednisolone) to affect long-term outcomes. Another important evolution in management has been the recognition and prevention of the chronic complications of SCI including respiratory compromise, bladder dysfunction, Charcot joints, and pressure sores through directed interventions along with early integration of physical rehabilitation and mobilization. There have also been significant advances in neuroprotective and neuroregenerative strategies for SCI, many of which are actively in clinical trial including riluzole, Cethrin, stem cell transplantation, and the use of functional electrical stimulation.
CONCLUSION
Pharmacologic treatments, cell-based therapies, and other technology-driven interventions will likely play a combinatorial role in the evolving management of SCI as the field continues to evolve.
Topics: Adult; Humans; Male; Neuralgia; Neurological Rehabilitation; Postoperative Complications; Spinal Cord Injuries; Spinal Fusion; Syringomyelia; Urinary Bladder, Neurogenic
PubMed: 28571527
DOI: 10.1080/10790268.2017.1329076 -
Advanced Science (Weinheim,... Jun 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder...
Interstitial cystitis/bladder pain syndrome (IC/BPS) has a significant impact on quality of life, but the etiopathogenesis remains largely unknown. The bladder microenvironment of patients with IC/BPS to obtain biological evidence supporting diagnosis and novel therapy is systematically characterized. Single-cell RNA sequencing (scRNA-seq) and image mass cytometry (IMC) are applied to bladder biopsies of the IC/BPS cohort. A total of 42 distinct cell clusters are identified from different groups. The increased hyperactivated Th1-biased response, but not Th2-biased response, and decreased immunosuppressive Treg are elucidated in the bladder microenvironment of non-Hunner-type IC (NHIC)/Hunner-type IC (HIC). M2/M2-like macrophage extends in the HIC and M1-like macrophage extends in NHIC, all of which secrete a range of chemokines with different pattern. The pro-inflammatory mediators, TNF-α, produced by tissue-resident macrophages and IL6, by the inflammatory fibroblasts are identified as key mediators of IC/BPS pathogenesis. Additionally, a regulatory network between different cell types is observed as a shift from structural cell communication in unaffected normal bladder to a Macrophage-Endothelial-dominated interactome in NHIC/HIC. The results demonstrate the high heterogeneity in NHIC/HIC, and provide an essential resource for diagnosis, and treatment of IC/BPS in the future by highlighting the importance of the microenvironment of bladder mucosa.
Topics: Cystitis, Interstitial; Humans; Quality of Life; Single-Cell Analysis; Urinary Bladder
PubMed: 35470584
DOI: 10.1002/advs.202106063 -
Annals of the Royal College of Surgeons... Nov 2022We report a rare complication involving a healthy 45-year-old male patient who underwent an emergency laparoscopic appendicectomy for acute perforated gangrenous...
We report a rare complication involving a healthy 45-year-old male patient who underwent an emergency laparoscopic appendicectomy for acute perforated gangrenous appendicitis. The patient was catheterised pre- procedure and the ports were inserted under vision. Upon completion of the procedure, a 15 Fr Robinson drain was left in the pelvis and was fed through the suprapubic port hole. Postoperatively the patient developed worsening, generalised abdominal pain and high output from the drain. The patient was re-catheterised but the computed tomography (CT) cystogram did not show any injury to the bladder. The drain fluid creatinine was noted to be raised (>4,000), indicating that urine was leaking into the drain. Conventional cystogram confirmed a contrast leak from the dome around the drain. Flexible cystoscopy confirmed that the drain had transversed the vesicourachal diverticula. The drain was pulled back and converted to a suprapubic catheter with the patient subsequently being discharged. Vesicourachal diverticula is a rare and often asymptomatic anomaly. When undertaking laparoscopic surgery, precautions should be taken to prevent port site injury such as catheterising the patient to ensure the bladder is empty and inserting the ports under direct vision. It is safer to visualise muscle rather than peritoneum during port insertion. In this case, the bladder diverticula was noticed extraperitoneally. Though the indirect CT cystogram reported no injury, this was unreliable as the bladder was not distended which led to the subtle injury being missed. Traditional cystogram should be considered in cases with a negative CT cystogram and a strong suspicion of bladder injury.
Topics: Male; Humans; Middle Aged; Urinary Bladder; Diverticulum; Urinary Bladder Diseases; Cystoscopy
PubMed: 35446699
DOI: 10.1308/rcsann.2021.0344 -
Advances in Clinical and Experimental... Aug 2017Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis, chronic... (Review)
Review
Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis, chronic infection or urolithiasis and will often result in progressive deterioration of renal function. Most cases of UPJO are congenital; however, the disease can be clinically silent until adulthood. Other causes, both intrinsic and extrinsic, are acquired and include urolithiasis, post-operative/inflammatory/ischemic stricture, fibroepithelial polyps, adhesions and malignancy. In the past, the most frequent symptom of UPJO in neonates and infants was a palpable flank mass. Nowadays, thanks to the widespread use of maternal and prenatal ultrasound examinations, asymptomatic hydronephrosis is diagnosed very early. In adults and older children symptoms may include intermittent abdominal or flank pain, nausea, vomiting and hematuria. In addition to high specificity and sensitivity in detecting UPJO, modern technologically advanced equipment such as ultrasound, magnetic resonance imaging and computed tomography provides a lot of information about the function of the affected kidney and the anatomy of the surrounding tissues. Treatment options for UPJO include a wide spectrum of approaches, from active surveillance or minimally invasive endourologic techniques to open, laparoscopic or robotic pyeloplasty. The main goal of therapy is to relieve symptoms and maintain or improve renal function, but it is difficult to define treatment success after UPJO therapy.
Topics: Humans; Hydronephrosis; Kidney Pelvis; Prognosis; Risk Factors; Ureteral Obstruction; Urinary Bladder; Urodynamics
PubMed: 29068584
DOI: 10.17219/acem/59509 -
Purinergic Signalling Sep 2022P2 purinergic receptors are involved in the normal function of the kidney, bladder, and prostate via signaling that occurs in response to extracellular nucleotides.... (Review)
Review
P2 purinergic receptors are involved in the normal function of the kidney, bladder, and prostate via signaling that occurs in response to extracellular nucleotides. Dysregulation of these receptors is common in pathological states and often associated with disease initiation, progression, or aggressiveness. Indeed, P2 purinergic receptor expression is altered across multiple urologic disorders including chronic kidney disease, polycystic kidney disease, interstitial cystitis, urinary incontinence, overactive bladder syndrome, prostatitis, and benign prostatic hyperplasia. P2 purinergic receptors are likewise indirectly associated with these disorders via receptor-mediated inflammation and pain, a common characteristic across most urologic disorders. Furthermore, select P2 purinergic receptors are overexpressed in urologic cancer including renal cell carcinoma, urothelial carcinoma, and prostate adenocarcinoma, and pre-clinical studies depict P2 purinergic receptors as potential therapeutic targets. Herein, we highlight the compelling evidence for the exploration of P2 purinergic receptors as biomarkers and therapeutic targets in urologic cancers and other urologic disease. Likewise, there is currently optimism for P2 purinergic receptor-targeted therapeutics for the treatment of inflammation and pain associated with urologic diseases. Further exploration of the common pathways linking P2 purinergic receptor dysregulation to urologic disease might ultimately help in gaining new mechanistic insight into disease processes and therapeutic targeting.
Topics: Adenosine Triphosphate; Carcinoma, Transitional Cell; Humans; Inflammation; Male; Pain; Receptors, Purinergic P2; Urinary Bladder Neoplasms; Urologic Diseases
PubMed: 35687210
DOI: 10.1007/s11302-022-09875-1 -
American Journal of Physiology.... Mar 2018Chronic abdominal and pelvic pain are common debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly... (Review)
Review
Chronic abdominal and pelvic pain are common debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles (the collection, storage, and expulsion of waste). These visceral organs are located in close proximity to one another and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation, or diarrhea are primary symptoms for patients with irritable bowel syndrome or inflammatory bowel disease. Chronic pelvic pain and urinary urgency and frequency are primary symptoms experienced by patients with lower urinary tract disorders such as interstitial cystitis/painful bladder syndrome. It is becoming clear that these symptoms and clinical entities do not occur in isolation, with considerable overlap in symptom profiles across patient cohorts. Here we review recent clinical and experimental evidence documenting the existence of "cross-organ sensitization" between the colon and bladder. In such circumstances, colonic inflammation may result in profound changes to the sensory pathways innervating the bladder, resulting in severe bladder dysfunction.
Topics: Abdominal Pain; Animals; Chronic Pain; Colitis; Colon; Ganglia, Spinal; Humans; Nociceptors; Pelvic Pain; Prognosis; Risk Factors; Urinary Bladder; Urinary Bladder Diseases; Urination; Urodynamics
PubMed: 29146678
DOI: 10.1152/ajpgi.00272.2017 -
Molecular Pain 2021Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section...
Although elevated estradiol levels facilitate chronic pelvic pain in animal models, it remains to be determined whether sex steroid levels are altered in a cross-section of women with chronic pelvic pain (CPP) and those at-risk for developing CPP. We sought to determine if sex steroid levels are increased in women with menstrual pain and whether those changes were more extreme in two groups of women with worsened pelvic pain profiles: a) dysmenorrhea plus evidence of bladder pain sensitivity and b) bladder pain syndrome. Serum samples were collected during the mid-luteal phase to measure estradiol, progesterone, testosterone, and sex hormone-binding globulin. We also compared quantitative sensory testing profiles to evaluate how sex steroid differences influence proposed pain sensitivity mechanisms. Women with combined dysmenorrhea and bladder sensitivity had higher estradiol concentrations than controls (487 [IQR 390 - 641] vs 404 [336 - 467] pmol/L, = 0.042). Bladder pain syndrome participants had greater sex hormone-binding globulin than controls (83 [71 - 108] vs 55 [42 - 76 nmol/L; = 0.027). Levels of pain sensitivity and mood were different across the groups, but the only significant relationship to sex steroids was that sex hormone-binding globulin was correlated to somatic symptoms ( = 0.26, = 0.03). These findings show women potentially at-risk for CPP and women with diagnosed CPP exhibit altered circulating levels of sex steroids. Because these hormonal differences appear to be independent of mood or pain sensitivity, the role of sex steroids in the emergence of CPP may be via sensitization of visceral afferents.
Topics: Animals; Cystitis, Interstitial; Dysmenorrhea; Female; Humans; Pain Threshold; Pelvic Pain; Urinary Bladder
PubMed: 34689649
DOI: 10.1177/17448069211035217