VOLUME 3; ISSUE 1 2024 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE This publication is intended for registered healthcare professionals only.
5mg propiverine hydrochloride
VOLUME 3; ISSUE 1 2024 Editor Prof Shingai Mutambirwa - Urologist MBChB, MMed (Urology) Medunsa Head of Urology - Sefako Makgatho Health Sciences University Chairman - The South African Urological Association Academic committee Chairman - Medical and Scientic Advisory Board of The Prostate Cancer Foundation Editorial Board Dr. Sheynaz Bassa - Clinical and Radiation Oncologist MBChB (Univ of Natal), FC Rad (Onc) SA Head of Department: Radiation Oncology Steve Biko Academic Hospital and The University of Pretoria Dr Jireh Serfontein - Medical Sexologist MBChB (Pret.), Dip HIV Management, MMed Sexual Health (Univ. Sydney) Clinical head: My Sexual Health Pretoria Editorial and Publishing Ofce Maria Philippou Randburg 2194 Enquiries 082 3355 444 Publisher Maria Philippou Andrew Oberholzer Disclaimer All rights reserved. No editorial matter published in Urology, Urooncology and Sexology Update may be reproduced in any form or language without written permission from the publishers. While every effort is made to ensure accurate reproduction, the Prostate Cancer Foundation, the authors, publishers and their employees or agents shall not be responsible or in any way liable for any errors, omissions or inaccuracies in the publication whether arising from negligence or for any consequences arising there from. The inclusion or exclusion of any product does not mean that the Prostate Cancer Foundation, the publisher or the editorial board advocates or rejects its use either generally or in any particular eld or elds. This publication is intended for registered healthcare professionals only. If you received this publication or a link to this publication in error, please do not directly or indirectly use, print, copy, forward, or disclose any part of this publication. Please delete the copy or link to the publication and notify the publisher. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE CONTENTS 1 Efcacy and safety of propiverine in patients with overactive bladder and neurogenic detrusor overactivity Fundamentals of Hyperbaric Medicine (Simon Frasier University) New Developments in Prostate Cancer The benets of support groups for prostate cancer patients and the experience of one practicebased support group in Cape Town for patients undergoing a robotic assisted laparoscopic radical prostatectomy (RALP) Reframing sexuality for men on androgen deprivation therapy: managing sexual side effects New appointments and announcements An update on the robotic surgery program at the urology department, University of Stellenbosch, Tygerberg Hospital 2 6 15 16 19 28 24 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Supported by:
2 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Denition Overactive bladder (OAB) is dened by the International Continence Society (ICS) as a syndrome of urinary urgency with or without urgency incontinence, usually accompanied by increased frequency more than eight micturitions/24 hours and nocturia. The diagnosis of OAB is only applicable in the absence of other conditions which could be causing the symptoms. These include urinary tract infections, bladder stones, interstitial cystitis or metabolic disease such as diabetes mellitus. Symptoms Denitions of overactive bladder symptoms Impact on Quality of Life OAB appears to have a signicant impact on quality of life (QOL) and affects activities of daily living, mental health and sexual function. However, there appears to be a reluctance on the part of many patients to seek help due to ignorance about effective treatments that are available. The EpiLUTS study showed that the motivation to seek medical help is associated with the number of symptoms, how bothersome the symptoms were and the patient's age. Older patients are more likely to seek help. Incidence Overactive bladder is a common chronic condition occurring in both men and women. Approximately 17% of the adult population is affected, with the prevalence increasing with age. Diagnosis In South Africa, urologists generally perform a patient history, targeted examination, urine dipstix/urine MCS and ultrasound of the abdomen as standard of care. UDS/owmetry and cystoscopy may be needed in specic cases as part of the evaluation for LUTS and OAB. Efficacy and safety of propiverine in patients with overactive bladder and neurogenic detrusor overactivity This article is a summary of the article by Saygisever-Faikoglu K, Faikoglu G, Ozcan FO, et al. Efcacy and safety of propiverine in patients with overactive bladder and neurogenic detrusor overactivity. Pharm Pharmacol Int J. 2022;10(2):51-58 and an article by Mutambirwa S, Overactive Bladder in Men. Published in a previous edition of this publication. Symptom Urinary urgency Urgency incontinence Increased frequency Nocturia Description A sudden and compelling urge to urinate that is difcult to postpone Involuntary urinary incontinence accompanied by urgency or occurring immediately after urgency Frequent urination during the day reported by patients The need to wake up one or more times during the night to urinate Age >60 years >75 years Incidence in men 19.1% 42% Incidence in women 18.3% 31%
5mg propiverine hydrochloride
4 However urodynamic evaluation is the gold standard: “Urodynamic evaluation is still considered to be the gold standard for quantitating the degree of obstruction, related detrusor contractile dysfunction, and simultaneous pressure/ow analysis”. Roger R. Treatment First-Line Treatment Behavioural therapies are recommended as rst-line treatment. This includes bladder training, bladder control strategies, pelvic oor muscle training and uid management. In OAB patients, pelvic oor muscle training is primarily used as an urgency suppression technique, aimed at inuencing, and minimizing the “urge” symptoms of OAB, which is usually more sudden, intense, and unpleasant than the normal sensation to void. Patients are taught to contract their pelvic muscle oor (PMF) rapidly, and in some instances also to contract for prolonged durations (where there is also stress incontinence) to help inhibit urgency producing detrusor (bladder contractions. Other urgency suppression techniques that share dermatomal and myotome distribution with S2-4 (for e.g. heel raises, adductor squeezes, rubbing inner thighs and direct penile/perineal manual compression) may be used in combination with the quick re PMF contractions to suppress the urge”. Second-Line Treatment (Pharmacological Management) The best outcomes are achieved through a combination of pharmacological interventions and behavioural modications. Antimuscarinics are the pharmacological treatment of choice for overactive bladder. These include: propiverine, darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, and trospium chloride. Propiverine, oxybutynin, tolterodine, and trospium are available in both immediate-release (IR) and extended-release (ER) formulations, while oxybutynin is also available in a sustained-release patch form for transdermal administration). The anticholinergics block the parasympathetic acetylcholine pathway and thereby reduce the intensity of detrusor muscle contractions. However, they are not specic to the muscarinic receptors in the bladder. Blockade of M2 causes side effects such as inhibition of salivary secretion (dry mouth), dry eye causing blurred vision for near objects, tachycardia, drowsiness, decreased cognitive function, and inhibition of gut motility resulting in constipation. propiverine has been shown to have a lower afnity for M2 receptors, which are effective in cardiac functions, compared to tolterodine, oxybutynin, darifenacin, and trospium. A comparison of binding afnity (pKi) of antimuscarinic compounds for the human recombinant receptor subtype M2 Mode of action Propiverine and oxybutynin are the only two antimuscarinics agents that have a dual mode of action. In addition to its antimuscarinic effects, propiverine can also inhibit the purinergic mechanism, which is another factor responsible for detrusor contraction. Potential Drug Drug Interactions Propiverine can be considered a weak inhibitor of cytochrome P450 (CYP3A4) and signicant increases in the concentrations of other drugs metabolised by this pathway are therefore not expected. Pharmacokinetics The pharmacokinetics are not altered in patients with severe renal impairment (CC<30 mL/min) or mild to moderate liver failure from fatty liver disease, and in elderly patients (60–85 years) compared to young healthy adults. No dose adjustment is required with propiverine in patients with mild to moderate renal impairment. No dose adjustment is recommended in patients with severe renal impairment unless the dose exceeds 30mg/day. No dose adjustment is required in patients with mild liver failure. Efcacy The efcacy of propiverine is well documented in numerous clinical studies. In a metanalysis by Huang W et al. “Propiverine was effective for urgency, frequency, and urgency incontinence, suggesting that it contributes to improving overall OAB symptoms, especially by improving urgency and urgency incontinence episodes; propiverine may have improved the daily living activities impaired by OAB”. In dose determination studies done by Mazur D et al, there was a 50% improvement observed in the efcacy parameters in the group given 15 mg/day, while the efcacy reached 80% in the group given 30 mg/day. In a study done by Thuroff JW et al, the subjective improvement in OAB patients with the use of propiverine was shown to be 77%. In addition, a decrease in max detrusor pressure and an increase in max bladder capacity were observed compared to placebo. Propiverine Tolterodine Oxybutynin Darifenacin Trospium 5.4 8 7.8 7.4 9.2 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
5 A study done by Kessler-Zumpe PL et al, demonstrated that 12 weeks of treatment with the slow-release form of propiverine (ER 30 mg) reduced the frequency of urinary incontinence within 24 hours by 68.3%. The efcacy of propiverine is enhanced when combined with α-blockers. Lee KS et al, demonstrated this in a multicentre, randomized, double-blind study of the α1 adrenoceptor antagonist doxazosin and propiverine in patients with obstruction due to benign enlargement of the prostate and overactive bladder. This study concluded that the combination of antimuscarinics and α1 adrenoceptor antagonists is effective and safe in patients with obstruction due to benign enlargement of the prostate and overactive bladder. Side effects The most common side effect of antimuscarinic drugs compared to placebo is dry mouth. Other side effects include constipation, pruritus, and headache. However, constipation may be the most bothersome side effect, particularly in the elderly where it can impact their QOL. There are a number of studies that show a decrease in the frequency of side effects, especially dry mouth, with the long-term use of propiverine. The impact of Propiverine on various parameters Conclusion Propiverine is an effective treatment option with a favourable side effect prole for the symptomatic treatment adult patients with overactive bladder or neurogenic detrusor overactivity. Patients using propiverine 45 mg have been observed to experience signicantly less frequent urinary urgency, urinary frequency, incontinence, and nocturia (p<0.0001) compared to patients using 30 mg. Both propiverine 45 mg and propiverine 30 mg have similar tolerability. Parameter frequency mean urinary volume IPSS symptoms of storage Effect 23.5% to 14.3% 32.3%-19.2% 41.3% vs. 32.6% P value p=0.004 p=0.004 p=0.029 Parameter Blurred vision Effect in the elderly on heart rate and PQ, QRS, QT, or QTc intervals in resting and ambulatory ECGs Cognitive function Psychomotor parameters such as alertness, attention, reaction times, complex acoustic and optical reaction times Post-void residual (PVR) in patients with overactive bladder Effect of Propiverine No clinical difference in the incidence of blurred vision side effects when comparing propiverine to placebo control groups No signicant differences between placebo and the propiverine group No signicant changes observed in post-void residual measures, higher brain function scales, parameters, and motor functions measured by CIBIC (Clinician's Interview-Based Impression of Change) No signicant difference was found between the placebo and propiverine groups None UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
6 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE The application of Hyperbaric Oxygen Therapy as an Adjunct Treatment in the Management of Radiation Injuries The exact causes of radiation injuries are complex and still only partially understood. Vascular changes characterised by obliterative endarteritis are however observed in virtually all organs which (1) demonstrate radiation damage . Though there might be no immediate outward signs of tissue destruction, it is agreed that the onset of damage (2) induced by radiation exposure is immediate . While numerous studies on the link between cytokines and radiation injuries have been conducted in animal models, the practical application of these observed associations is difcult with no single marker able to (1,3) reliably estimate future radiation damage . Radiation damage/injury may be accurately predicted based on the source and length of exposure to radiation, and the type of tissue that was exposed to radiation. Although predictable, the multiple sources and dosages involved in radiation treatment results in difculty in selecting one specic treatment option for these patients resulting in signicant variation in treatment (2) recommendations . The Nature of Radiation Injury Radiation injuries are all complex. Radiation injuries can be classied as acute, sub-acute or delayed (4) complications . Acute radiation injuries are due to direct and almost immediate cellular toxicity. This cellular toxicity directly affects the mitotic/reproductive health of the cells, caused by free radical mediated damage to cellular DNA. Acute injuries are usually self-limiting but may cause debilitating symptoms and are usually managed symptomatically. Sub-acute injuries are typically identiable in only a small number of organ systems (i.e: radiation pneumonitis post- lung cancer treatment). While sub-acute injuries are typically selflimiting and managed symptomatically, they may persist for several months, evolve, and become delayed complication injuries. Delayed radiation complications are typically only noted after a latent period of six months or more and may only develop years post-radiation exposure. Delayed injuries are often precipitated by additional tissue insult such as surgery within the radiation eld. While classication of injuries may assist in the management thereof this is not to say that acute radiation injuries may not resolve or evolve to become chronic injuries (5) indistinguishable from delayed radiation injuries . Cystitis Cystitis is any inammatory condition of the urinary bladder usually presenting with mild discomfort in the lower abdomen, which may result in a wide range of clinical manifestations from asymptomatic to life-threatening. Two types of cystitis are most common etiologically: infectious cystitis (more common - caused by bacteria) and sterile (or noninfectious) cystitis, often secondary to irritation by (6,7) chemical agents or the result of radiation injury . Radiotherapy-induced haemorrhagic cystitis (RHC), while rare (occurring in approximately 3–6.5% of patients), can arise from 6 months to 20 years after (8,9,10) radiation therapy , while chemotherapy-induced haemorrhagic cystitis (CHC) has also been proven to cause chemotherapy-limiting haematuria (cyclophosphamide or others (11,12,13) oxazaphosphorines) . The treatment of CHC, traditionally through the introduction of Mesna (2mercaptoethanesulfonic acid), has decreased the (12) incidence of CHC to less than 5% . Causal factors aside, haemorrhagic cystitis (HC) is a signicant impairment of a patients' quality of life often resulting in multiple, mostly emergency, admissions to hospitals. Bladder irrigation while Fundamentals of Hyperbaric Medicine (Simon Frasier University) Daniel M Botha Biokinetics (Hons) (U.J.) Daniel qualied with a post-graduate degree in Biokinetics in 2013 following studies in psychology, biomedical Science and health sciences and completed Fundamentals of Hyperbaric Medicine through Simon Frasier University in 2022. Daniel is currently completing his master's degree in public health with a research dissertation on prostate cancer. Daniel's primary focus is medical screenings and chronic disease rehabilitation. He is the clinical director of Dr Botha and Associates, the clinical Manager of Lyra wellbeing's executive medical programmes and he is a member of the Prostate Cancer Foundation's Medical and Scientic Advisory Board. He has a passion for men's health and competes in triathlons.
8 successful has often been aligned with the use of systemic or intravesical agents such as hyaluronic acid, aminocaproic acid, formalin or prostaglandins (14) which often present with limited success . Pathology of CHC and RHC Radiation and cyclophosphamide-induced HC is a severe and potentially life-threatening complication of certain radiation treatment modalities. The management thereof can be highly challenging with well-known urological treatment options and the number of these are expected to increase during the (15) next decades . This is expected to parallel a rise in complications and side effects, such as RHC, oedema, ulceration, neovascularisation, and haemorrhagic necrosis are an acute reaction as an inammatory response in both CHC and RHC causing urothelial damage. Since the 1970s the prophylactic application of Mesna has been applied as a standard protocol for prevention of haemorrhagic complications. Mesna neutralises acrolein and its toxic effects to the urothelium, decreasing CHC urotoxicity (caused directly by renal excretion of acrolein, metabolites of oxazaphosphorine alkylated (15) drugs) . In RHC however, urothelial damage is caused by radiolysis of water. The concentration of highly reactive free oxygen radicals increases which causes cell membrane injury by lipid peroxidation, precipitating immediate cell death. Delayed cell death through replication failures is perpetuated directly (by radiation energy) and indirectly (by (8) oxygen radicals) through DNA damage . This DNA damage is dose related. This acute reaction can escalate with progressive endarteritis and vascular rarefaction (hypovascular) resulting in critical ischaemia with a reduction in oxygen concentration of up to 70-80%. This ischaemia of the mucosal tissue leads to necrosis and shedding of cells because of impaired healing capacity. In this case compensatory teleangiectasia develops and causes persistent haematuria and impaired bladder (17,18) capacity through brotic repair . These processes can occur as late as 20 years post-radiation (19) therapy . Hyperbaric Oxygen Therapy Hyperbaric oxygen therapy (HBOT) is a wellestablished treatment for several validated conditions (13 Class A evidence). Hyperbaric oxygen therapy is performed in a hyperbaric chamber, which increases and maintains the atmosphere absolute (ATA) pressure as the chamber is pressurised with either pure 100% oxygen (monoplace chamber) or air (multiplace chamber). The pressure may vary between centres but is usually only effective from 2.4 ATA. For most on label treatments, patients lie in the hyperbaric chamber daily (5-6 days a week), for a duration of 60 to 90minutes for up to 30 to 45 sessions. Studies on the indications of HBOT have demonstrated positive effects in the treatment of hypoxia, oxidative stress, inammation-induced brain damage, stroke, Alzheimer's disease, and chronic (15) Lyme disease, and cancer complications . Monoplace chambers deliver oxygen to the patient's tissues utilising the respiratory and vascular systems through direct breathing of 100% volume concentration (v/v) of oxygen used to pressurise the chamber. Multiplace chambers, pressurised with air (21% v/v) deliver 100% v/v oxygen to the patient's tissues through the respiratory and vascular systems via a breathing aid such as a mask or hood. In addition to the gas concentration of the chamber, the temperature and humidity are managed in accordance to the change in pressure in the chamber (when the pressure rises, the temperature and humidity also rise). It is therefore important for the chamber operator to measure the changing pressure and maintain the temperature and humidity. The only disadvantage of HBOT may be the logistical difculties of a patient attending a hospital or centre with South African Undersea and Hyperbaric Medicine Association (SAUHMA) registered pressured (16,17,18,19) oxygen chamber on a daily basis . The Effect Hyperbaric Oxygen on Irradiated Tissues Hyperbaric oxygen therapy (HBOT) is a promising but still extremely under-utilised treatment option for patients suffering with RHC, CHC and HC in whom standard management has proven unsuccessful. A cause and consistent manifestation of radiation injury (24,25) is vascular obliteration and stromal brosis . Stimulating angiogenesis is an important mechanism of HBOT which makes this an effective treatment modality for radiation injury. Hyperbaric Oxygen therapy induces neovascularization in hypoxic tissues(20) and has been proven to enhance vascularity and cellularity in heavily radiated tissues(21). The use of HBOT for radiation cystitis is based on the fact that radiation causes cellular hypoxia of the bladder tissues. With the administration of 100% v/v oxygen under high pressures, the pathophysiology of radiation cystitis can be reversed. As an indirect demonstration of vascular improvement, it has been demonstrated that HBOT patients often demonstrate an increase in transcutaneous oxygen measurements as well as (22) increased vascular density . Since HBOT has been proven to be cancer neutral, it was proven that prophylactic HBOT can also reduce the effect of brosis through pre-radiation injury application(23, 24, 25). Hyperbaric oxygen therapy has been demonstrated to induce broblast proliferation, neovascularisation and therefore angiogenesis, granulation tissue formation, and optimisation of the (17,18,19) cellular immune functions Tissue oxygenation occurs principally via diffusion of oxygen from the capillaries. The application of as little as 2.4 ATA (1 ATA sea level + 1.4 ATA / 13-15 meters of sea water (MSW)) has been proven to increase dissolved oxygen in the plasma. At 2.4 ATA this is a 1015-fold increase in O2 available to the tissues promoting capillary angiogenesis thus increasing the regeneration of damaged urothelium with success (26,27,28,29) rates of 73 to 96% . The increase in the pO2, encourages and mediates the repair processes of macrophages, broblasts and granulocytes, as well as induces neo-angiogenesis, achieving 80% of the UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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10 normal capillary density. Hyperbaric oxygen therapy causes anti-oedematous vasoconstriction (30) without secondary ischaemia . Resolution of haematuria has been measured at rates of as high as 75-96% in RHC research groups in both prospective and retrospective study (26,30,31,32,33) designs . These results are maintained even after a median long-term follow-up period of 68 months, conrming excellent long-term results of the application of HBOT(34). In CHC reported case reports a complete resolution of haematuria was described to have occurred for 11–36 months post- (35,36,37,38) HBOT treatment . It was noted in further studies that HBOT demonstrated more success in patients exposed to lower radiation doses (62Gy) versus patients with high dosage radiotherapy (39,40) (76Gy) . It was however noted that some papers indicate that success rate in RHC would be (35,36,37,38) dependent on the number of HBOT sessions . HBOT Protocols Although different treatment protocols reduce the comparability of treatment outcomes, standardised protocols (modied US Navy Recompression Treatment Tables) have, for the most part been applied in the South African setting. For the most part, treatment recommendations presented by the U.S. Navy Diving Manual, U.S. (41) Navy Recompression Treatment tables, (1999) should be followed as closely as possible, unless it becomes evident that these treatment guidelines are not being effective for a specic condition. Only a Diving Medical Ofcer (DMO)/Hyperbaric trained specialist (HBOT Specialist) may recommend changes to treatment protocols other than those described in the tables set out for HBOT by the U.S. Navy Diving Manual. Treatment “Table 9” (Figure 1) is the shortest of the ofcial HBOT treatment tables providing 90minutes of oxygen breathing at 2.4 ATA. This table is used based only on the recommendation of a DMO/HBOT Specialist cognisant of the patient's (41) medical condition and preferred outcomes . individuals suffering from cyanide poisoning, carbon monoxide poisoning, gas gangrene, smoke inhalation, necrotizing soft-tissue infections, severe injuries, arterial gas embolism arising from surgery or diagnostic procedures, thoracic trauma or those whose requiring accelerated healing for whatever reasons. All HBOT treatments shall be done under (41,47) the cognisance of a DMO/HBOT Specialist . “Table 1” is an example of treatment protocols for some of the approved Indications for HBOT, taken from the Undersea and Hyperbaric Medical Society's Hyperbaric Oxygen Therapy Committee (42,47) Report-2003 . These guidelines include not only the approved conditions but eludes to the frequency of treatment, and the advised minimum and maximum number of treatments (subject to (41,47) the DMO/HBOT Specialist's clinical opinion) . Figure 1: Treatment Table 9. Hyperbaric oxygen treatment (41) table Taken from: U.S. Navy Diving Manual, (1999)(41) • 90minutes of oxygen breathing at 2.4 ATA (45 feet/13-15msw). • Descent rate – 6 Meters/Min. (2.15minutes) • The total treatment time (60/90min) begins on arrival at 2.4 ATA or 13-15msw • Ascent rate – 6 Meters/Min (2.15minutes) – This rate may be slowed to 0.3048 m/min depending upon the patient's medical condition. • The patient may breathe air or oxygen during ascent. • If patient cannot tolerate oxygen at 13-15msw, this table can be modied UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
11 (47) Table 1: Guidelines for Approved Indications for Conducting Hyperbaric Oxygen Therapy (47) Taken from: Undersea and Hyperbaric Medical Society's Hyperbaric Oxygen Therapy Committee Report-2003 • QD = 1 time in 24 hours Hyperbaric Oxygen Therapy • BID = 2 times in 24 hours Hyperbaric Oxygen Therapy • TID = 3 times in 24 hours Hyperbaric Oxygen Therapy Indication Carbon Monoxide Poisoning and Smoke Inhalation Gas Gangrene (Clostridial Myonecrosis) Crush Injury, Compartment Syndrome, and other Acute Traumatic Ischemia Enhancements of Healing in Selected Wounds Necrotizing Soft-Tissue Infections (subcutaneous tissue, muscle, fascia) Osteomyelitis (refractory) Radiation Tissue Damage (osteoradinecrosis) Skin Grafts and Flaps Thermal Burns Treatment Table Treatment Table 5 or Table 6 as recommended by the DMO Treatment Table 5 TID × 1 day then BID × 4-5 days Treatment Table 9 TID × 2 days BID × 2 days QD × 2 days Treatment Table 9 QD or BID Treatment Table 9 BID initially, then QD Treatment Table 9 QD Treatment Table 9 QD Treatment Table 9 BID initially, then QD Treatment Table 9 TID × 1 day, then BID Minimum # Treatments 1 5 3 10 5 20 20 6 5 Maximum # Treatments 5 10 12 60 30 60 60 40 45 While HBOT is indicated for the management of radiation tissue damage the treatment modality, like all treatments, has both relative and absolute contraindications for use. The previously accepted contraindications were, in 2013, revised by the Complimentary Medicine Association (CMA) to 1 absolute and 6 relative contraindications (the absence of these conditions does not (41,42,47) automatically qualify one for treatment) . Absolute contraindication (42) • Untreated pneumothorax Relative contraindications: (42) • Intraventricular external drainage • Fracture of the skull base with cerebrospinal (42) uid leakage • Serious infection of the upper respiratory (42) Tract • High blood pressure (SBP > 180 mmHg, DBP > (42) 110 mmHg) • Patients with chronic obstructive pulmonary (42) disease with CO2 retention (44) • Pregnancy Oxygen Toxicity and Adjusting of Protocols A standard “Table 9” treatment is composed of 3 x 30minute periods of 100% v/v oxygen at a pressure of 2.4 ATA. These episodes of are interrupted by 2 x 5minutes air (21% v/v) breaks, to reduce oxygen (41,42,43) toxicity (as per Figure 1) . As with the addition of time to tables/protocols (i.e: extension of US Navy recompression treatment “Table 6”, due to non-resolution of diving related symptoms), so, might a table be altered to suit both the patients' treatment schedules, facility management as well as to decrease the risk of oxygen toxicity. As such, some HBOT facilities will reduce the 90minute protocol (with two air-breaks, as described above and in Figure 1) to a 60minute protocol with no air breaks at all. This therapeutic reduction in time in turn reduces the risk of CNS toxicity, developing claustrophobia, and allows more time for adjunct treatments to be carried out. The primary advantage of inclusion of HBOT in a treatment regime is that there are minimal to no severe side- (39,41,42,47) effects post treatment . HBOT and Radiation Injury Most studies focusing on CHC and RHC utilised (30,31,40) between 30 to 40 HBOT treatment sessions with a median of 34 treatments. It was however noted that the higher the number of HBOT sessions the greater the opportunity for excellent long-term (46) success/resolution of the injury . Data does however suggest that fewer HBOT sessions, a median of 27 to 40, may sufcient in CHC (35,37,38,45) patients . The elapsed time between the onset of haematuria and the initiation of HBOT is discussed as another success factor for RHC, with shorter pre-treatment intervals (6 to 8 months) (29,34) demonstrating signicantly greater results, whereas the relationship between CHC symptom development and elapsed time to HBOT treatment could not demonstrate a signicant relationship to treatment success (most likely due to the acute nature of CHC). Success is noted in CHC cohorts with intervals ranging from 47 days after the onset of symptoms to up to four months between rst (36) symptoms and the initiation of HBOT . The inuence of patient age, while controversial, does UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
12 not appear to impact treatment outcomes of HBOT with complete remission rates of haematuria reported in cases from 15 to 82 years of (29,34,36,37,38,46) age . Conclusions drawn on the effect of HBOT on CHC/RHC were, in many studies, dened as complete (no further macro-haematuria during the period of follow-up), or partial resolution of haematuria (dened as a lower RTOG (description of radiation-caused side effects in a reproducible way)/EORTC (summary score, calculated from the mean of 13 of the 15 QLQ-C30 scales) or Gray score than before HBOT) with the long-term efciency and safety of HBOT creating an inviting option for patients suffering from RHC or (29,30,31,35,37,38,40,45). CHC Final thoughts The early administration of HBOT has demonstrated a higher effectiveness after onset of haematuria as (38,46) well as a decrease in the recurrence thereof . It is postulated that this is due to the fact that early intervention with HBOT may enhance tissue regeneration and prevent chronic sloughing and (36,44) scarring of hypoxic bladder tissue . It is emphasised further that treatment with HBOT does not cause damage to the bladder tissue, as may be the case with other treatment modalities (i.e: cystoscopic coagulation, or instillations with chemical agents), this; due to the fact that HBOT is the only treatment modality that promotes tissue (36,44) healing and angiogenesis . The benet of the addition of HBOT into radiation injury treatment protocols is that even if HBOT fails to resolve the symptoms of radiation cystitis, it causes no additional damage, and offers an option for other treatment modalities to be attempted. Hyperbaric Oxygen Therapy demonstrates itself as a valuable systemic treatment option particularly in patients with other radiation-induced conditions (i.e: proctitis, scar complications, etc.), as HBOT may (27,40) improve or resolve multiple conditions at once , with no need for a combination of several individual treatments. As ill-advised as it may be to delay treatment, HBOT presents itself as an excellent option for treatment of radiation effects as HBOT has proven to be effective in cases where several other conservative therapies have been exhausted. It is the opinion of the author that HBOT is a safe and effective treatment for radiation cystitis/proctitis, but in the South African setting, the availability of SAUHMA accredited HBOT facilities is limited. References 1. Rubin P. Frankelstein. J., Shapiro. D., (1992). Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes. Int Journal of Radiation Oncol Biol Phys; 24: pp93-101 2. Janes. L.A., Iqbal. U., Vercruysse. G.A., (2024). A Case Of Local Radiation Injury In The Creation Of Lichtenburg Art, Journal of burn care & research: ofcial publication of the American Burn Association, 10.1093/jbcr/irae008 3. Trott. K.R., (1984). Chronic damage after radiation therapy: Challenge to radiation biology.Int. Radiation Oncol Biol Phys; 10: pp907-913 4. Rubin. P., Casarrett, G. W., (1968). Clinical Radiation Pathology. Vol 1, pp 58-61, Philadelphia Pa. WB Saunders. 5. Derr. W., Hendry. H., (2001). Consequential late effects in normal tissues. Radiotherapy and oncology, 61: pp223-31. 6. Haldar. S., Dru. C., Bhowmick. N.A., (2014). Mechanisms of hemorrhagic cystitis. Am J Clin Exp Urol; 2(3): pp199-208 7. Norkool. D.M., Hampson. N.B., Gibbons. R. P., Weissman. R M., (1993) , Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis, J Urology;150 (2 Pt 1): pp332-334. 8. Corman. J.M., McClure. D., Pritchett. R., Kozlowski. P., Hampson. N.B., (2003). Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen. J Urol; 169(6): pp2200 9. Levenback. C., Eifel. P.J., Burke. T.W., Morris. M., Gershenson. D.M., (1994). Hemorrhagic cystitis following radiotherapy for stage Ib cancer of the cervix. Gynecol Oncol; 55(2): pp206–210. 10. Mendenhall. W.M., Henderson. R.H., Costa. J.A., Hoppe. B.S., Dagan. R., Bryant. C.M., Nichols. R.C., Williams. C.R., Harris. S.E., Mendenhall. N.P., (2013) Hemorrhagic Radiation Cystitis. American journal of clinical oncology [Epub ahead of print]. 11. Lima. M.V., Ferreira. F.V., Macedo. F.Y., De Castro Brito. G.A., Ribeiro. R.A., (2007). Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis. Cancer Chemother Pharmacol; 59(5): pp643–650. 12. Korkmaz. A., Oter. S., Deveci. S., Goksoy. C., Bilgic. H., (2001). Prevention of further cyclophosphamide induced hemorrhagic cystitis by hyperbaric oxygen and mesna in guinea pigs. 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14 New Developments in prostate cancer Promontory Therapeutics Completes Enrolment of Phase 2 Trial of PT-112 in Late-Line Patients with Metastatic CastrationResistant Prostate Cancer The target enrolment of 109 patients across clinical sites in the United States and France has been met for PT-112 according to the developers ofnPromontory Therapeutics. PT-112 is a small-molecule conjugate of pyrophosphate being studied for use in patients with late-stage metastatic castrationresistant prostate cancer (mCRPC). "This clinical trial is the largest study to date of PT-112 and will establish the optimal dose in line with the FDA's Project Optimus, as well as proof of concept in our late-line mCRPC patient population," said Promontory Therapeutics Chief Medical Ofcer Johan Baeck, MD, in the news release. PT-112 is the rst small-molecule conjugate of pyrophosphate in clinical development in oncology. PT-112 has numerous advantages — including its tolerability and inhibition of ribosomal biogenesis which leads to immunogenic cell death, through the release of damage associated molecular patterns that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumour microenvironment. The primary outcome for the study is to dene the recommended dose level and schedule for pivotal studies. Secondary outcomes include disease control rate, objective response, and duration of response. References A study evaluating the safety, pharmacokinetics, and clinical effects of intravenously administered PT-112 injection in subjects with advanced solid tumours and subsequent dose expansion cohorts. ClinicalTrials.gov. Last updated August 14, 2023. Accessed March 8, 2024. https://clinicaltrials.gov/study/NCT02266745 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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16 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE The benefits of support groups for prostate cancer patients and the experience of one practice-based support group in Cape Town for patients undergoing a robotic assisted laparoscopic radical prostatectomy (RALP) Prostate cancer is known to cause signicant psychosocial distress, with 30-50% of men reporting a psychosocial burden due to their diagnosis, regardless of disease stage or 1 progression. The initial diagnosis of cancer is usually highly stressful for men and their families. This is followed by the anxiety of making a decision about the best treatment option (in settings where options are available), followed by coping with side effects that are often highly embarrassing and frustrating for men. The subsequent ongoing monitoring further adds to the anxiety and stress, particularly “PSA anxiety” for men post treatment for localised prostate cancer. The impact of prostate cancer treatments on sexual function and masculinity should not be underestimated as they can signicantly affect a man's self-esteem and partner relationships. Online and in-person prostate cancer support groups have been shown to improve quality of life, yet they remain underutilised by patients and clinicians. Men are often reluctant to discuss their experiences and express their emotions in face-to-face conversations. Online support groups have the advantage of offering a degree of anonymity and therefore, potentially, a safer environment for men to discuss what are often deeply personal issues. “The underlying connecting element of a support group is the mutual benet gained by expressing one's own experience of having cancer while at the same time participating in 3 the experiences of others.” Jablotschkin M et al. Traditionally, support groups have been run by non-prot organisations or by individual survivors who have felt the need to bring men with prostate cancer together. South Africa's diverse patient groups (those accessing private healthcare vs those accessing public healthcare) can make it challenging to nd common ground and even a common language for support group members. Patients undergoing active treatments for localised disease generally fall into two main groups, namely, those undergoing a radical prostatectomy and those undergoing brachy therapy. One example of a highly successful support group in South Africa is a group that was started in September 2017 by Dr Conray Moolman and one of his patients, Paddy O'Brien. At the time, Paddy was scheduled for a robotic prostatectomy and wanted to connect with other patients that had undergone the procedure. He was provided with some phone numbers but felt that this would be too intrusive, so suggested to Dr Dr Conray Moolman is a fully qualied da Vinci Robotic Surgeon. He did his training in Belgium and performs robotic nerve-sparing prostatectomies to manage prostate cancer. He is also one of a few urological surgeons in South Africa trained to perform robotic partial nephrectomy for kidney cancer. He is part of the Cape Urology practice in the Southern Suburbs of Cape Town performs all his robotic surgeries at Life Kingsbury Hospital in Cape Town Ex school principal and now a successful entrepreneur, Paddy discovered that he had stage 3 prostate cancer after undergoing surgery to treat a procedure for an enlarged prostate. Before undergoing a robotic prostatectomy, he felt the need to interact with men who had been on this journey. This resulted in the establishment of a highly successful email support group which now has over 260 members. He joined The Prostate Cancer Foundation in 2019 the Western Cape Patient Affairs Board Chairman. By the editorial team
17 Moolman that they start an email support group. New patients were invited to join as they were scheduled for the RALP. This enabled the men to be better prepared for what was coming. Paddy's unique ability to make new members feel welcome and to encourage open honest discussions has been one of the key ingredients for the group's success. Paddy also attributes the groups success to the recruitment process. “Dr Moolman's receptionist invites new members to sign up as they are scheduled for the procedure. This constant ow of new members joining the group encourages existing members to reect again on their own emotions and at least offer experiential advice or reection.” The group started with a handful of members and has since grown to over 260. For many men the support group is useful before and after surgery, and particularly for seeking support with post RALP side effects. Sometimes it's as simple as seeking advice on what incontinence pads to buy or asking other men how they have managed their erectile dysfunction. Once they have recovered, they often move on. Fortunately, there is a small group of men who remain active, and they are essential to the group's success as they encourage new patients who are about to undergo treatment and support them during the recovery phase. We asked some of the group members how they have benetted by belonging to the group: “As a RALP patient, with post op Radiation and 18 months of ADT treatment, I feel that the group has provided me with an invaluable source of support. Reading the members shared perspectives and views is often extremely thought provoking. The feelings shared typically range from shock, bewilderment, anger, frustration, determination, empathy, and sometimes good humour. These emotions and the online views expressed are moderated with condentiality and tact. It is reassuring to realise that I am not alone in this battle. It has been important for me to understand that although this feels like an extremely private health challenge, there are so many of us on a similar journey. All of us are wrestling with our own physical and psychological challenges resulting from our unique prostate cancer treatments. All in all, the honest sharing of views is constructive as it provides us with a deeper ongoing understanding of prostate cancer. It certainly helps me feel supported and less isolated as I continue this roller coaster path to recovery. “ “For me the support group shows me that I am not alone with the Big C and others care when asked for advice. On the other hand, I see the many different paths which our members go through. Everybody has a (slightly) different story to tell.” “It helped me so much when I joined the group and received advice and thoughts of the members regarding the route for me to take. During those difcult times it made such a difference to me making a decision between surgery or radiation.” “Having recently been diagnosed with Stage 2 Prostrate Cancer, I heard about a group of fellow survivors of the same condition and their journeys. So I asked to be added to the group. After explaining my short journey, it has been very informative to hear everyone else's story. I have found it very helpful to understand what challenges each person has gone through in their recovery.” In 2019 the Prostate Cancer Foundation approached Paddy and Conray with the idea of expanding the support group to include patients who had approached the Foundation to join a support group, irrespective of what treatment they had undergone or who their treating doctor was. Although this worked initially, there was a loss of focus. One of the major reasons for the success of the RALP group has been the common bond that men feel due to having the same treatment. Support groups are not without their challenges, every patient has a different experience, and they are not all good. One patient's negative experience (often given without providing the full context) or misinformation can put off other patients. This is where the importance of a well-informed moderator becomes critical. In one particular instance, a patient on Dr Moolman's RALP support group, who had undergone a salvage RALP after failed brachytherapy, attempted to warn all men on the group of the horric incontinence rates caused by a RALP and to avoid the procedure at all costs. It is well known that incontinence rates for men undergoing a salvage RALP after brachytherapy are considerably higher than for men who are undergoing a RALP without any other previous treatment, but the patient failed to provide this background information. When this occurs a group moderator is UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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