Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn’t it effective in all patients?

Botulinum toxin A (BTA) is currently used to treat a variety of painful disorders, including painful bladder syndrome/interstitial cystitis (PBS/IC). However, BTA is not consistently effective in all patients. This may be due to the disparity of causes of pain, but this may also relate to the processes by which BTA exerts anti-nociceptive effects. This review discusses mechanisms by which BTA may inhibit pain and studies of the use of BTA in PSB/IC patients. It is doubtful that any single treatment will effectively control pain in PBS/IC patients, and it is highly probable that multiple strategies will be required, both within individual patients and across the population of PBS/IC patients. The purpose of this review is to discuss those mechanisms by which BTA acts, with the intent that alternative strategies exploiting these mechanism, or work through alternative pathways, can be identified to more effectively treat pain in PBS/IC patients in the future.     

Patient-centred standardization in interstitial cystitis/bladder pain syndrome—a PLEA

Standardization has an impact on all links in the healthcare chain and directly affects patients with regard to diagnosis, treatment, eligibility for reimbursement, social benefits and care. Furthermore, patients are also affected if research goes down inappropriate pathways due to inaccurate terminology and definitions. Complex healthcare coding and electronic medical record systems and global reliance on the internet and search machines mean that new terminology or changes now need in some way to be designed to last or to be updated in a way that will cause least disruption, while still allowing for evolution, since changes have far more ramifications today than they ever did in the past. Official recognition of a condition is vital, so coding must be correct and uniform across all authorities. Potential problems must be anticipated at an early stage in the process. In order to achieve global consensus, stakeholders from all parts of the world need to communicate and collaborate with all viewpoints taken into consideration. Patients and their advocacy groups should be involved in standardization processes to ensure that all aspects of a condition are covered, that no patients or symptoms are excluded and that there is no adverse impact on the patient in practical terms following implementation. The trend today is for patients to be more involved in healthcare and decision-making. We must ensure that standardisation and guidelines do not get left behind in this process of development either now or in the future. However, it is necessary to find some way of training patient representatives to enable them to participate fully in standardization and guidelines and also to encourage them to do so.     

What’s new in the aetiopathogenesis of vasculitis?

The cause of the majority of childhood vasculitides is unknown although it is likely that a complex interaction between environmental factors and inherited host responses trigger the disease and determine the vasculitis phenotype. Epidemiological clues continue to implicate infectious triggers in Kawasaki syndrome (KS) and Henoch Schőnlein purpura (HSP). Several genetic polymorphisms have now been described in KS and HSP which predispose to disease or predict disease severity. Anti-neutrophil cytoplasmic antibodies (ANCA) are now known to be directly involved in the pathogenesis of vascular injury in ANCA-associated vasculitides, although why some individuals develop ANCA in the first instance is not yet understood. Endothelial injury and repair are active areas of research in vasculitis. It is now possible to track endothelial injury non-invasively in children with vasculitis using surrogate markers of endothelial injury. The vasculogenic pathways involved in vascular repair following vasculitis, including endothelial progenitor cells, are beginning to be studied. It is anticipated that an improved understanding of the aetiopathogenesis of vasculitis in the young will ultimately shape future novel diagnostic and therapeutic approaches and will help us predict which children may develop premature arteriosclerosis in later life.     

Angiogenic factors,bladder neuroplasticity and interstitial cystitis—new pathobiological insights

Vascular endothelial growth factor (VEGF) is essential for normal embryonic development, and maintenance of adult vascular function. Originally described as a vascular permeability factor, VEGF alters tight cell junctions and contributes to maintenance of bladder permeability. VEGF and its receptors are not only expressed in bladder blood vessels but also in apical cells and intramural ganglia. VEGF receptors are fundamentally altered by inflammation and bladder diseases such as interstitial cystitis (IC). Experimental results indicate that VEGF exerts direct effects on bladder nerve density and function. Regardless of the etiology or initiating cause for IC, it is hypothesized that the urinary bladder responds to injury by increasing the production of VEGF that acts initially as a survival mechanism. However, VEGF also has the capacity to increase vascular permeability leading to glomerulations, edema, and inflammation. Moreover, due to elevated numbers of VEGF receptors in the urothelium, the increased levels of VEGF further increase bladder permeability and establish a vicioCus cycle of disease pathophysiology.     

Endoscopic ablation of Hunner’s lesions in interstitial cystitis patients

Introduction:

We report our experience with endoscopic ablation of Hunner’s lesions in women with interstitial cystitis (IC).

Methods:

A chart review was performed on 14 patients with IC symptoms who were identified to have bladder lesions and underwent endoscopic ablation. A Hunner’s lesion was identified as an area of erythema that reproduced the patients’ pain when touched by the cystoscope. Pathology reports were reviewed and improvement in pain was used as the main outcome measure.

Results:

Of the 14 patients, 12 had more than 50% symptomatic improvement and 8 patients reported 100% improvement. Mean improvement was 76%. In all patients who improved, the biopsy specimen showed inflammatory cystitis, often with epithelial denudation. Four patients had symptomatic recurrence, but all had improvement after repeat ablation.

Conclusion:

Endoscopic ablation of Hunner’s lesions improves symptoms in IC patients. Recurrence of symptoms should prompt repeat cystoscopy to identify recurrent lesions, as repeat ablation offers symptomatic improvement.     

In what type of interstitial cystitis/bladder pain syndrome is DMSO intravesical instillation therapy effective?

Background

Dimethylsulfoxide (DMSO) is the most-used agent for intravesical instillation. We conducted this retrospective clinical study to determine in what type of the interstitial cystitis (IC)/bladder pain syndrome (BPS) DMSO was effective.

Methods

We combined DMSO with hydrodistension in 2003 and from 2004 we performed hydrodistension alone. Hydrodistension had been performed in 7 cases of IC/BPS with Hunner’s lesions (H group) and 7 cases of IC/BPS without Hunner’s lesions (non-H group), and they served as the control group (C group; n=14). There was also a DMSO group (D group; n=14) that consisted of an H group of 7 cases and an non-H group of 7 cases in which the hydrodistension had been immediately followed by intravesical instillation of 50% DMSO 50 mL. Before, and 2, 6, 12, 18, and 24 months (M) after the intervention, the patients were asked to complete a 4-day frequency-volume chart (FVC) and the O’Leary-Sant IC symptom index (ICSI) questionnaire and IC problem index (ICPI) questionnaire, and to rate their pain on a visual analogue scale (VAS).

Results

All parameters were improved after hydrodistension in both the C group and the D group. However, comparison of the C group and D group according to whether Hunner lesions were present showed that there were no significant differences in any of the postoperative parameters between the non-H groups in the C group and D group, but in the H groups, average and maximum voided volume were significantly higher and the ICSI, ICPI, and VAS scores were lower in the D group. Moreover, the significant differences increased with the duration of the postoperative period.

Conclusions

DMSO intravesical instillation therapy was useful in both maintaining and improving the effectiveness of hydrodistension in IC/BPS with Hunner lesions. However, DMSO did not have any particular efficacy in the treatment of IC/BPS in the absence of Hunner lesions.     

The role of reconstructive surgery in patients with end-stage interstitial cystitis/bladder pain syndrome: is cystectomy necessary?

Introduction

Interstitial cystitis is a debilitating condition that has a profound effect on quality of life. Although many approaches to treatment have been explored, no consistently effective treatment has been identified. Reconstructive surgery is offered to patients with refractory IC/BPS; however, expert opinion is divided as to whether simultaneous cystectomy is necessary to achieve symptomatic cure. The aim of this study was to report our experience in the surgical management of IC/BPS in a university teaching hospital.

Methods

The hospital inpatient enquiry (HIPE) system was used to identify patients with IC/BPS who underwent surgery between 1997 and 2013. Medical records were examined and patients were invited to complete three symptom-based questionnaires.

Results

Twelve patients were identified (8 female, 4 male). Reconstructive procedures included urinary diversion without cystectomy (9) and augmentation ileocystoplasty (4). One patient failed to have a sustained improvement in symptoms following ileocystoplasty and later underwent successful urinary diversion. All other patients noted a “marked improvement” in overall symptoms on global response assessment (GRA) and the resolution of bladder pain on a visual analogue sale (VAS). There were no persistent symptoms or complications related to the retained bladder following diversion.

Conclusion

Our study adds to the existing evidence that cystectomy is not necessary to provide symptomatic cure in patients with end-stage IC/BPS. Urinary diversion without cystectomy is a highly effective operation and a successful outcome was achieved in all patients. Ileocystoplasty may be offered in carefully selected cases.

     

What’s new in the field of prostate cancer chemoprevention?

Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.     

What’s new in burn-associated infections?

Infection remains the most common cause of death in the severely burned patient. The systemic immunosuppression following burn injury allows infection to occur in any organ system, but predominantly in the lungs. In addition, the loss of the skin barrier permits microorganisms to colonize and invade the burn-injured tissue. The use of topical antimicrobial agents and early burn wound excision have significantly decreased the occurrence of invasive burn wound infection. Even so, burn wounds must be examined each day, and a biopsy should be performed of any area showing local signs indicative of infection. If histologic examination of the biopsy tissue confirms invasive infection, local and systemic interventions are required. Candida is a common colonizer of the burn wound, but rarely invasive. Aspergillus species are the most common filamentous fungi found in invasive burn wound infections. Viral infections are uncommon, but should be in the differential diagnosis of patients with cutaneous herpetic lesions and signs of systemic sepsis with no other apparent source. Pneumonia is the most common organ-specific life-threatening infection of extensively burned patients. Staphylococcus aureus was the most frequent causative organism at the United States Army Institute of Surgical Research Burn Center during 1996–1997. Other causes of infection, such as suppurative thrombophlebitis, should be in the differential diagnosis of the septic burn patient with no obvious source. Infection control procedures, including scheduled surveillance cultures, utilization of cohort nursing care, and strict enforcement of patient and staff hygiene, should be instituted at all burn centers.     

Interstitial cystitis/bladder pain syndrome/hypersensitive bladder: Worldwide confusion! What has gone wrong and how can we put it right for the sake of the patients?

The international interstitial cystitis, bladder pain syndrome and hypersensitive bladder world is facing major problems. While healthcare is ultimately about making sick people feel better, this is still not happening for our patients who are not receiving the individually tailored treatment that they need. So, what has gone wrong, and why is there so much confusion everywhere? Since the first NIDDK research criteria were published over 30 years ago, there has been no major breakthrough either in treating the patients or even in truly understanding what bladder condition(s) we are dealing with. For the sake of the patients, it is imperative to take action now and make a fresh, determined start with meaningful, international, multi‐stakeholder collaboration to determine how to proceed further to take the necessary decisions, solve the problems and achieve real global consensus and real progress to help the real patients with their real symptoms.     

What’s new in obstetric anesthesia in 2017?

The Gerard W. Ostheimer lecture is delivered every year at the annual meeting of the Society for Obstetric Anesthesia and Perinatology. The lecture aims to provide the anesthesiologist who provides obstetric anesthesia care with a review of the most relevant articles that were published in the preceding calendar year. This article highlights the literature published in 2017 related to maternal mortality, maternal cardiac arrest, cesarean delivery and labor analgesia.