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Non-muscle-invasive Bladder Cancer

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Non-muscle-invasive Bladder Cancer Part 1 Comprehensive Review Article Prof. Dr. Semir. A. Salim. Al Samarrai EPIDEMIOLOGY, AETIOLOGY AND PATHOLOGY: Epidemiology Bladder cancer (BC) is the seventh most commonly diagnosed cancer in the male population worldwide, while it drops to tenth when both genders are considered [1]. The worldwide age-standardised incidence rate (per 100,000 person/years) is 9.5 in men and 2.4 in women [1]. In the European Union the age-standardised incidence rate is 20 for men and 4.6 for women [1]. Worldwide, the BC age-standardised mortality rate (per 100,000 person/years) was 3.3 for men vs. 0.86 for women [1]. Bladder cancer incidence and mortality rates vary across countries due to differences in risk factors, detection and diagnostic practices, and availability of treatments. The variations are, however, partly caused by the different methodologies used and the quality of data collection [2]. The incidence and mortality of BC has decreased in some registries, possibly reflecting the decreased impact of causative agents [3]. Approximately 75% of patients with BC present with a disease confined to the mucosa (stage Ta, CIS) or submucosa (stage T1); in younger patients (< 40 years of age) this percentage is even higher [4]. Patients with TaT1 and CIS have a high prevalence due to long-term survival in many cases and lower risk of cancer-specific mortality compared to T2-4 tumours [1,2]. Aetiology Tobacco smoking is the most important risk factor for BC, accounting for approximately 50% of cases [2,3, 5–7]. The risk of BC increases with smoking duration and smoking intensity [6]. Low-tar cigarettes are not associated with a lower risk of developing BC [6]. The risk associated with electronic cigarettes is not adequately assessed; however, carcinogens have been identified in urine [8]. Environmental exposure to tobacco smoke is also associated with an increased risk of BC [2]. Tobacco smoke contains aromatic amines and polycyclic aromatic hydrocarbons, which are renally excreted. Occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons and chlorinated hydrocarbons is the second most important risk factor for BC, accounting for about 10% of all cases. This type of occupational exposure occurs mainly in industrial plants which process paint, dye, metal, and petroleum products [2, 3, 9, 10]. In developed industrial settings these risks have been reduced by work-safety guidelines; therefore, chemical workers no longer have a higher incidence of BC compared to the general population [2, 9, 10]. Recently, greater occupational exposure to diesel exhaust has been suggested as a significant risk factor (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.08–2.40) [11]. While family history seems to have little impact [12] and, to date, no overt significance of any genetic variation for BC has been shown; genetic predisposition has an influence on the incidence of BC via its impact on susceptibility to other risk factors [2, 13–17]. This has been suggested to lead to familial clustering of BC with an increased risk for first- and second-degree relatives (hazard ratio [HR]: 1.69; 95% CI: 1.47−1.95) [18]. Although the impact of drinking habits is uncertain, the chlorination of drinking water and subsequent levels of trihalomethanes are potentially carcinogenic, also exposure to arsenic in drinking water increases risk [2, 19]. Arsenic intake and smoking have a combined effect [20]. The association between personal hair dye use and risk remains uncertain; an increased risk has been suggested in users of permanent hair dyes with a slow NAT2 acetylation phenotype [2] but a large prospective cohort study could not identify an association between hair dye and risk of most cancer and cancer-related mortality [21]. Dietary habits seem to have limited impact, recently protective impact of flavonoids has been suggested and a Mediterranean diet, characterised by a high consumption of vegetables and non-saturated fat (olive oil) and moderate consumption of protein, was linked to some reduction of BC risk (HR: 0.85, 95% CI: 0.77−0.93) [22–27]. The impact of an increased consumption of fruits has been suggested to reduce the risk of BC; to date, this effect has been demonstrated to be significant in women only (HR: 0.92; 95% CI: 0.85–0.99) [28]. Exposure to ionizing radiation is connected with increased risk; a weak association was also suggested for cyclophosphamide and pioglitazone [2, 19, 29]. The impact of metabolic factors (body mass index, blood pressure, plasma glucose, cholesterol, and triglycerides) is uncertain [30]. Schistosomiasis, a chronic endemic cystitis based on recurrent infection with a parasitic trematode, is also a cause of BC [2]. PATHOLOGICAL STAGING AND CLASSIFICATION SYSTEMS: Definition of non-muscle-invasive bladder cancer LE 2a 3 3 Tumours confined to the mucosa and invading the lamina propria are classified as stage Ta and T1, respectively, according to the Tumour, Node, Metastasis (TNM) classification system [31]. Intra-epithelial, highgrade (HG) tumours confined to the mucosa are classified as CIS (Tis). All of these tumours can be treated by transurethral resection of the bladder (TURB), eventually in combination with intravesical instillations and are therefore grouped under the heading of NMIBC for therapeutic purposes. The term ‘non-muscle-invasive BC’ represents a group definition and all tumours should be characterised according to their stage, grade, and further pathological characteristics. Tumour, Node, Metastasis Classification (TNM) The latest TNM classification approved by the Union International Contre le Cancer (UICC) (8th Edn.) is referred to (Table 1) [31]. Table 1: 2017 TNM classification of urinary bladder cancer T1 subclassification The depth and extent of invasion into the lamina propria (T1 sub-staging) has been demonstrated to be of prognostic value in retrospective cohort studies [32, 33]. Its use is recommended by the most recent 2016 World Health Organization (WHO) classification [34]. T1 sub-staging methods are based either on micrometric (T1e and T1m) or histo-anatomic (T1a and T1b) principles; the optimal classification system, however, remains to be defined [34, 35]. Carcinoma in situ and its classification Carcinoma in situ is a flat, HG, non-invasive urothelial carcinoma. It can be missed or misinterpreted as an inflammatory lesion during cystoscopy if not biopsied. Carcinoma in situ is often multifocal and can occur in the bladder, but also in the upper urinary tract (UUT), prostatic ducts, and

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Overactive Urinary Bladder

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Overactive Urinary Bladder Diagnostic and Evaluation Comprehensive Review Article Part 2 Prof. Dr. Semir. A. Salim. Al Samarrai Taking a thorough clinical history is fundamental to the process of clinical evaluation. Despite the lack of high-level evidence to support taking a history, there is universal agreement that it should be the first step in the assessment of anyone with lower urinary tract symptoms (LUTS). The history should include a full evaluation of LUTS, as well as sexual, gastrointestinal and neurological symptoms. Details of urgency episodes, the type, timing and severity of urinary incontinence (UI), and some attempt to quantify symptoms should also be made. The history should help to categorise LUTS as storage, voiding and post-micturition symptoms, and classify UI as stress urinary incontinence (SUI), urge urinary incontinence (UUI), mixed urinary incontinence (MUI) or overflow incontinence; the latter being defined as “the complaint of UI in the symptomatic presence of an excessively (over-) full bladder (no cause identified)” [1]. The history should also identify patients who need referral to an appropriate clinic/specialist. These may include patients with associated pain, haematuria, history of recurrent urinary tract infection (UTI), pelvic surgery or radiotherapy, constant leakage suggesting a fistula, new-onset enuresis or suspected neurological disease. A neurological, obstetric and gynaecological history may help to understand the underlying cause and identify factors that may affect treatment decisions. Guidance on history-taking and diagnosis in relation to UTIs, neuro-urological conditions and chronic pelvic pain (CPP) can be found in the relevant EAU Guidelines [2,3,4]. Patients should also be asked about other comorbidity as well as smoking status, previous surgical procedures and current medications, as these may affect LUTS. There is little evidence from clinical trials that carrying out a clinical examination improves outcomes, but widespread consensus suggests that clinical examination remains an essential part of assessment of patients with LUTS. Examination should include abdominal examination, to detect an enlarged urinary bladder or other abdominal mass, and digital examination of the vagina and/or rectum. Pelvic examination in women includes assessment of oestrogen status, pelvic floor muscle (PFM) function and careful assessment of any associated pelvic organ prolapse (POP). A cough stress test is necessary to look for stress urinary incontinence (SUI). Among women with genital prolapse, the cough test was found to show good agreement with urodynamic studies (UDS) in the detection of SUI. Urethral mobility can be assessed. Pelvic floor muscle contraction strength can also be assessed digitally. A focused neuro-urological examination should also be routinely undertaken. Patient questionnaires include symptom scores, symptom questionnaires/scales/indices, patient-reported outcome measures (PROMs) and health-related quality of life (QoL) measures. Questionnaires should have been validated for the language in which they are being used, and, if used for outcome evaluation, should have been shown to be sensitive to change. The US Food and Drug Administration (FDA) published guidance for industry on PROM instruments (questionnaires) in 2009 [5]. Patient bladder diaries include measurement of the frequency and severity of LUTS and is an important step in the evaluation and management of LUT dysfunction. Bladder diaries are a semi-objective method of quantifying symptoms, such as frequency of urinary incontinence (UI) events, number of nocturia episodes, etc. Fluid intake and voided volume measurement can be used to support diagnoses and management planning, for example in overactive bladder (OAB), and for identifying 24-hour or nocturnal polyuria. The optimum number of days required for bladder diaries appears to be based on a balance between accuracy and compliance [6,7]. Diary durations between three and seven days are routinely reported in the literature. The urinalysis and urinary tract infection investigations are a very important steps in the evaluation and therapy of UTI. Reagent strip (dipstick) urinalysis may indicate proteinuria, haematuria or glycosuria, or suggest UTI requiring further assessment. Urine dipstick testing is a useful adjunct to clinical evaluation in patients in whom urinary symptoms are suspected to be due to UTI. Urinalysis negative for nitrite and leukocyte esterase may exclude bacteriuria in women with LUTS [8], and should be included, with urine culture when necessary, in the evaluation of all patients with LUTS. Urinary incontinence or worsening of LUTS may occur during UTI [9] and existing UI may worsen [10]. The rate and severity of UI were unchanged after eradication of asymptomatic bacteriuria in nursing home residents [11]. The post-void residual volume measurement is also important step in the evaluation and management of OAB and obstruction LUT-Disorders. Post-void residual (PVR) volume is the amount of urine that remains in the bladder after voiding. It is a measure of voiding efficiency, and results from a number of contributing factors. The detection of significant PVR volume is important because it may worsen symptoms and, more rarely, may be associated with UTI, upper urinary tract (UUT) dilatation and renal insufficiency. Both BOO and/or detrusor underactivity (DU) can potentially contribute to the development of significant PVR volume. Post-void residual volume can be measured by catheterisation or ultrasound (US). Most studies investigating PVR volume have assessed mixed populations including those with neurogenic UI. In general, the data on PVR volume can be applied with caution to women with non-neurogenic LUTS. The results of studies investigating the best method of measuring PVR volume [11-16] have led to the consensus that US measurement of PVR volume is preferable to catheterisation due to its favourable risk–benefit profile. In peri- and postmenopausal women without significant LUTS or pelvic organ symptoms, 95% had a PVR volume < 100 mL [17]. In women with UUI, PVR volume > 100 mL was found in only 10% of cases [18]. Other research has found that a high PVR volume is associated with pelvic organ prolapse (POP), voiding symptoms and an absence of SUI [17, 19–21]. In women with SUI, the mean PVR volume was 39 mL measured by catheterisation and 63 mL measured by US, with 16% of women having PVR volume > 100 mL [22]. Some authors have suggested that it is reasonable to consider a PVR volume > 100 mL to be significant, although many women may remain

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Overactive Urinary Bladder

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Overactive Urinary Bladder Epidemiology, aetiology, pathophysiology Comprehensive Review Article Part 1 Prof. Dr. Semir. A. Salim. Al Samarrai Overactive bladder is defined by the International Continence Society (ICS) as “urinary urgency, usually accompanied by frequency and nocturia, with or without (Urge Urinary Incontinence (UUI), in the absence of Urinary Tract Infection (UTI) or other obvious pathology” [1]. Overactive bladder is a chronic condition and can have debilitating effects on QoL. The hallmark urodynamic feature is Detrusor Overactivity (DO), although this may not be demonstrated in a large proportion of Overactive Bladder (OAB) patients, which may partly be due to failure to reproduce symptoms during urodynamic assessment. The EPidemiology of InContinence (EPIC) study was one of the largest population-based surveys of the prevalence of LUTS and OAB [2]. It was a cross-sectional telephone survey of adults aged > 18 years conducted in five countries, including Canada, Germany, Italy, Sweden and the UK. The study included > 19,000 participants and demonstrated an overall prevalence of OAB symptoms of 11.8% (10.8% in men and 12.8% in women). Other studies have reported prevalences of up to 30 to 40%, with rates generally increasing with age [3]. Various theories have been proposed to explain the pathophysiology of OAB, mainly relating to imbalances in inhibitory and excitatory neural pathways to the bladder and the urethra or sensitivity of bladder muscle receptors. However, no definite identifiable causes have been established. Overactive bladder is generally classified into wet and dry, based on the presence or absence of associated Urinary Incontinence (UI). Evaluation of symptoms of OAB follows the general pathway of evaluation of women with LUTS. The Diaries are particularly helpful in establishing and quantifying symptoms of frequency, urgency and UI, and may be valuable in assessing change over time or response to treatment. Several observational studies have demonstrated a close correlation between data obtained from bladder diaries and standard symptom evaluation [4–7]. The optimum number of days required for bladder diaries appears to be based on a balance between accuracy and compliance. Diary duration of three to seven days is routinely used in the literature. The Urodynamics is essential in establishing the presence of DO, but its absence does not preclude diagnosis of OAB, which is based on symptoms alone. A Cochrane review of seven RCTs showed that use of urodynamic tests increased the likelihood of prescribing drugs or avoiding surgery. However, there was no evidence that this influence on decision-making altered the clinical outcome of treatment [8]. A sub-analysis of an RCT comparing fesoterodine to placebo [9] showed that the urodynamic diagnosis of DO had no predictive value for treatment response. A single report (SR) and meta-analysis indicated that the urinary tract nerve growth factor (Urinary NGF) and Brain-divided neurotrophic factor or abneurin are members of the neurotrophic family of growth factors were increased in female OAB patients as urinary biomarker compared to healthy controls, whereas no difference was found for the prostaglandins E2 (PGE2) level normalized to the concentration of the urinary creatine was elevated and higher in the BPH/OAB than in the BPH/non-groups [10]. The current data is inadequate to assess any other potential biomarkers, such as urinary malondialdehyde (UMDA), ATP, and cytokines, in the management of OAB in female patients. Further studies are needed to establish their potential as diagnostic and management tools in OAB women. The conservative management of the overactive bladder has long been recommended as first in clinical practice, because they usually carry the lowest risk of harm. While this remains true for non-pharmacological conservative treatments [e.g., pelvic floor muscle training (PFMT)], increasing concerns regarding the adverse events of some pharmacological treatments used to treat LUTS (e.g., anticholinergic drugs), particularly regarding cognitive function, have emerged and patients should be fully counselled regarding this potential risk. It is possible that improvement of associated disease may reduce the severity of the lower urinary tract symptoms (LUTS), especially in elderly patients, which are associated with multiple comorbid conditions including: • cardiac failure; • chronic renal failure; • diabetes; • chronic obstructive pulmonary disease; • neurological disease; • general cognitive impairment; • sleep disturbances, e.g., sleep apnoea; • depression; • metabolic syndrome. The Lifestyle factors that may be associated with UI include obesity, smoking, level of physical activity, regulation of bowel habit and fluid intake. Modification of these factors may improve symptoms of OAB. The caffeine intake in many drinks contain caffeine are particularly coffee, tea and cola. Conflicting epidemiological evidence of urinary symptoms being aggravated by caffeine intake has focused on whether caffeine reduction improves LUTS [11, 12]. A scoping review of fourteen interventional and twelve observational studies reported that reduction in caffeine intake may reduce symptoms of urgency, but the certainty of evidence was low, with significant heterogeneity in study populations [13]. The fluid intake modification are particularly restriction, and is a strategy commonly used by people with OAB to relieve symptoms. Any advice on fluid intake given by HCPs should be based on 24-hour fluid intake and urine output measurements as retrieved from the bladder diary. From a general health point of view, it should be advised that fluid intake should be sufficient to avoid thirst and that an abnormally low or high 24-hour urine output should be investigated. The few RCTs that have been published provide inconsistent evidence [14-16]. In most studies, the instructions for fluid intake were individualised and it was difficult to assess participant adherence. All available studies were in women. An RCT showed that a reduction in fluid intake by 25% improved symptoms in patients with OAB but not UI [16]. Personalised fluid advice compared to generic advice made no difference to continence outcomes in people receiving anticholinergics for OAB, according to an RCT comparing drug therapy alone to drug therapy with behavioural advice [17]. Patients should be warned of the potential consequences of fluid restriction such as worsening of constipation or development of UTI. The obesity and overweight have been identified as a risk factors for LUTS in many epidemiological studies [18, 19]. There is

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Prostate Cancer Salvage Therapy Comprehensive Review Article Part 7

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Prostate Cancer Salvage Therapy Comprehensive Review Article Part 7 Prof. Dr. Semir. A. Salim. Al Samarrai Salvage radiotherapy combined with androgen deprivation therapy (cTxcN0, without PET/CT): Data from RTOG 9601 suggest both CSS and OS benefit when adding 2 years of bicalutamide (150 mg o.d.) to SRT [1]. However, SRT combined with either goserelin or placebo showed similar DSS and OS rates [2]. Table 1 provides an overview of these two RCTs. Table 1. Randomised controlled trials comparing salvage radiotherapy combined with androgen deprivation therapy vs. salvage radiotherapy alone Target volume, dose, toxicity There have been various attempts to define common outlines for ‘clinical target volumes‘ of PCa [3–6] and for organs at risk of normal tissue complications [7]. A benefit in biochemical PFS but not metastasis-free survival has been reported in patients receiving whole pelvis SRT (± ADT) but the advantages must be weighed against possible side effects [8]. Two RCT’s were recently published (Table 2). Intensity-modulated radiation therapy plus IGRT was used in 57% of the patients in the SAKK-trial [9] and in all patients of the Chinese trial [10]. No patient had a PSMA PET/CT before randomisation. Table 2. Randomized trials investigating dose escalation for SRT without ADT and without PET-CT Salvage RT is associated with toxicity. In one report on 464 SRT patients receiving median 66.6 (max. 72) Gy, acute grade 2 toxicity was recorded in 4.7% for both the GI and GU tract. Two men had late grade 3 reactions of the GI tract, but overall, severe GU tract toxicity was not observed. Late grade 2 complications occurred in 4.7% (GI tract) and 4.1% (GU tract), respectively, and 4.5% of the patients developed moderate urethral stricture [11]. Salvage RT with or without ADT (cTx CN0/1) with PET/CT In a prospective multi-centre study of 323 patients with BCR, PSMA PET/CT changed the management intent in 62% of patients as compared to conventional staging. This was due to a significant reduction in the number of men in whom the site of disease recurrence was unknown (77% vs. 19%, p < 0.001) and a significant increase in the number of men with metastatic disease (11% vs. 57%) [12]. Metastasis-directed therapy for rcN+ (with PET/CT) Radiolabelled PSMA PET/CT is increasingly used as a diagnostic tool to assess metastatic disease burden in patients with BCR following prior definitive therapy. A review including 30 studies and 4,476 patients showed overall estimates of positivity in a restaging setting of 38% in pelvic LNs and 13% in extra-pelvic LN metastases [13]. The percentage positivity of PSMA PET/CT was proven to increase with higher PSA values, from 33% (95% CI: 16–51) for a PSA of < 0.2 ng/mL, to 45% (39–52), 59% (50–68), 75% (66–84), and 95% (92–97) for PSA subgroup values of 0.2–0.49, 0.5–0.99, 1.00–1.99, and > 2.00 ng/mL, respectively [13]. Salvage lymph node dissection The surgical management of (recurrent) nodal metastases in the pelvis has been the topic of several retrospective analyses [14-16] and a systematic review [17]. The reported 5-year BCR-free survival rates ranged from 6% to 31%. Five-year OS was approximately 84% [17]. Biochemical recurrence rates were found to be dependent on PSA at surgery and location and number of positive nodes [18]. Addition of RT to the lymphatic template after salvage LN dissection may improve the BCR rate [19]. Management of PSA failures after radiation therapy Therapeutic options in these patients are ADT or salvage local procedures. A systematic review and metaanalysis included studies comparing the efficacy and toxicity of salvage RP, salvage HIFU, salvage cryotherapy, SBRT, salvage LDR brachytherapy, and salvage HDR brachytherapy in the management of locally recurrent PCa after primary radical EBRT [20]. The outcomes were BCR-free survival at 2 and 5 years. Salvage radical prostatectomy Salvage RP after RT is associated with a higher likelihood of adverse events (AEs) compared to primary surger because of the risk of fibrosis and poor wound healing due to radiation [21]. Oncological outcomes In a systematic review of the literature, Chade, et al., showed that SRP provided 5- and 10-year BCR-free survival estimates ranging from 47–82% and from 28–53%, respectively. The 10-year CSS and OS rates ranged from 70–83% and from 54–89%, respectively. Pathological T stage > T3b (OR: 2.348) and GS (up to OR 7.183 for GS > 8) were independent predictors for BCR (see Table 3). Table 3. Oncological results of selected salvage radical prostatectomy case series Morbidity Compared to primary open RP, SRP is associated with a higher risk of later anastomotic stricture (47 vs. 5.8%), urinary retention (25.3% vs. 3.5%), urinary fistula (4.1% vs. 0.06%), abscess (3.2% vs. 0.7%) and rectal injury (9.2 vs. 0.6%) [22]. In more recent series, these complications appear to be less common [21,23,24]. Functional outcomes are also worse compared to primary surgery, with urinary incontinence ranging from 21% to 90% and ED in nearly all patients (see table 4) [23,24]. Table 4. Peri-operative morbidity in selected salvage radical prostatectomy case series Stereotactic ablative body radiotherapy (CyberKnifeR or linac-based treatment) is a potentially viable new option to treat local recurrence after RT. Carefully selected patients with good IPSS-score, without obstruction, good PS and histologically proven localised local recurrence are potential candidates for SABR. Table 5 summarises the results of the two larger SABR series addressing oncological outcomes and morbidity. Table 5. Treatment-related toxicity and BCR-free survival in selected SABR studies including at least 50 patients Salvage high-intensity focused ultrasound Salvage HIFU has emerged as an alternative thermal ablation option for radiation-recurrent PCa. Being relatively newer than SCAP the data for salvage HIFU are even more limited. A systematic review and metaanalysis included 20 studies (n = 1,783) assessing salvage HIFU [20]. The overwhelming majority of patients (86%) received whole-gland salvage HIFU. The adjusted pooled analysis for 2-year BCR-free survival for salvage HIFU was 54.14% (95% CI: 47.77–60.38%) and for 5-year BCR-free survival 52.72% (95% CI: 42.66–62.56%). However, the certainty of the evidence was low. Table 6 summarises the results of a selection of the largest series on salvage HIFU to

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Prostate Cancer Hormonal therapy Comprehensive Review Article Part 6

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Prostate Cancer Hormonal therapy Comprehensive Review Article Part 6 Prof. Dr. Semir. A. Salim. Al Samarrai Hormonal therapy: Different types of hormonal therapy The hormonal therapy is the fourth modality of PCA treatment, there are different types of hormonal therapy. Androgen deprivation can be achieved by suppressing the secretion of testicular androgens in different ways. This can be combined with inhibiting the action of circulating androgens at the level of their receptor which has been known as complete (or maximal or total) androgen blockade (CAB) using the old-fashioned antiandrogens [1]. Testosterone-lowering therapy (castration): Castration level The testosterone-lowering therapy (castration) aims to decrease the testosterone level to castration level, which means the castration level of testosterone is < 50 ng/dL (1.7 nmol/L), which was defined more than 40 years ago when testosterone testing was less sensitive. Current methods have shown that the mean value after surgical castration is 15 ng/dL [2]. Therefore, a more appropriate level should be defined as < 20 ng/dL (1 nmol/L). Bilateral orchiectomy The castration modality with Bilateral orchiectomy or subcapsular pulpectomy is still considered the primary treatment modality for ADT. It is a simple, cheap and virtually complication-free surgical procedure. It is easily performed under local anaesthesia, and it is the quickest way to achieve a castration level which is usually reached within less than twelve hours. It is irreversible and therefore does not allow for intermittent treatment [3]. Oestrogens One of the hormonal therapy modality is the treatment with oestrogens results in testosterone suppression and is not associated with bone loss [4]. Early studies tested oral diethylstilboestrol (DES) at several doses. Due to severe side effects, especially thromboembolic complications, even at lower doses these drugs are not considered as standard first-line treatment [5–7]. Luteinising-hormone-releasing hormone agonists Long-acting LHRH agonists are currently the main forms of ADT. These synthetic analogues of LHRH are delivered as depot injections on a 1-, 2-, 3-, 6-monthly, or yearly, basis. The first injection induces a transient rise in luteinising hormone (LH) and follicle-stimulating hormone (FSH) leading to the ‘testosterone surge’ or ‘flare-up’ phenomenon which starts two to three days after administration and lasts for about one week. This may lead to detrimental clinical effects (the clinical flare) such as increased bone pain, acute bladder outlet obstruction, obstructive renal failure, spinal cord compression, and cardiovascular death due to hypercoagulation status [8]. Luteinising-hormone-releasing hormone antagonists Luteinising-hormone-releasing hormone antagonists immediately bind to LHRH receptors, leading to a rapid decrease in LH, FSH and testosterone levels without any flare. The practical shortcoming of these compounds is the lack of a long-acting depot formulation with, so far, only monthly formulations being available. Degarelix is a LHRH antagonist. The standard dosage is 240 mg in the first month followed by monthly injections of 80 mg. Most patients achieve a castrate level at day three [9]. Relugolix is an oral gonadotropin-releasing hormone antagonist. It was compared to the LHRH agonist leuprolid in a randomised phase III trial [10]. The primary endpoint was sustained testosterone suppression to castrate levels through 48 weeks. There was a significant difference of 7.9 percentage points (95% CI: 4.1–11.8) showing non-inferiority and superiority of relugolix. The incidence of major adverse cardiovascular events was significantly lower with relugolix (prespecified safety analysis). Relugolix has been approved by the FDA [11]. The anti-androgens The anti-androgens are oral compounds and classified according to their chemical structure as: • steroidal, e.g., cyproterone acetate (CPA), megestrol acetate and medroxyprogesterone acetate; • non-steroidal or pure, e.g., nilutamide, flutamide and bicalutamide. Both classes compete with androgens at the receptor level. This leads to an unchanged or slightly elevated testosterone level. Conversely, steroidal anti-androgens have progestational properties leading to central inhibition by crossing the blood-brain barrier. The steroidal anti-androgens These compounds are synthetic derivatives of hydroxyprogesterone. Their main pharmacological side effects are secondary to castration (gynaecomastia is quite rare) whilst the non-pharmacological side effects are cardiovascular toxicity (4–40% for CPA) and hepatotoxicity. Non-steroidal anti-androgens Non-steroidal anti-androgen monotherapy with e.g., nilutamide, flutamide or bicalutamide does not suppress testosterone secretion and it is claimed that libido, overall physical performance and bone mineral density (BMD) are frequently preserved [12]. Non-androgen-related pharmacological side effects differ between agents. Bicalutamide shows a more favourable safety and tolerability profile than flutamide and nilutamide [800]. The dosage licensed for use in CAB is 50 mg/day, and 150 mg for monotherapy. The androgen pharmacological side effects are mainly gynaecomastia (70%) and breast pain (68%). However, non-steroidal anti-androgen monotherapy offers clear bone protection compared with LHRH analogues and probably LHRH antagonists [12,13]. All three agents share the potential for liver toxicity (occasionally fatal), requiring regular monitoring of patients’ liver enzymes. New androgen pathway targeting agents (ARTA) Once on ADT the development of castration-resistance (CRPC) is only a matter of time. It is considered to be mediated through two main overlapping mechanisms: androgen-receptor (AR)-independent and AR-dependent mechanisms. In CRPC, the intracellular androgen level is increased compared to androgen sensitive cells and an over-expression of the AR has been observed, suggesting an adaptive mechanism [14]. This has led to the development of several new compounds targeting the androgen axis. In mCRPC, AAP and enzalutamide have been approved. In addition to ADT (sustained castration), AAP, apalutamide and enzalutamide have been approved for the treatment of metastatic hormone sensitive Pca (mHSPC) by the FDA and the EMA. For the updated approval status see EMA and FDA websites [15–19]. Finally, apalutamide, darolutamide and enzalutamide have been approved for non-metastatic CRPC (nmCRPC) at high risk of further metastases [20–24]. Abiraterone acetate Abiraterone acetate is a CYP17 inhibitor (a combination of 17α-hydrolase and 17,20-lyase inhibition). By blocking CYP17, abiraterone acetate significantly decreases the intracellular testosterone level by suppressing its synthesis at the adrenal level and inside the cancer cells (intracrine mechanism). This compound must be used together with prednisone/prednisolone to prevent drug-induced hyperaldosteronism [15,18]. Apalutamide, darolutamide, enzalutamide (alphabetical order) These agents are novel non-steroidal anti-androgens with a higher affinity for the AR receptor than bicalutamide. While previous non-steroidal anti-androgens still allow transfer of ARs to the nucleus and

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Prostate Cancer Treatment Deferred (active surveillance/watchful waiting), Surgical & Radiation Therapy Comprehensive Review Article Part 5

Prostate Cancer Treatment Deferred Part 5

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Prostate Cancer Treatment Deferred (active surveillance/watchful waiting), Surgical & Radiation Therapy Comprehensive Review Article Part 5 Prof. Dr. Semir. A. Salim. Al Samarrai Figure 1. Active Surveillance and Long-Term Outcomes in Early Stage Prostate Cancer Treatment modalities: The treatment modalities contain different criterias, after first modality in the deferred treatment (active surveillance/watchful waiting). Deferred treatment (active surveillance/watchful waiting) In localised disease a life expectancy of at least 10 years is considered mandatory for any benefit from active treatment. Data are available on patients who did not undergo local treatment with up to 25 years of follow-up, with endpoints of overall survival (OS) and cancer specific survival (CSS). Several series have shown a consistent CSS rate of 82–87% at 10 years [1–6], and 80–95% for T1/T2 and ISUP grade < 2 PCas [512]. In three studies with data beyond 15 years, the DSS was 80%, 79% and 58% [3,5,6], and two reported 20-year CSS rates of 57% and 32%, respectively [3,5]. The observed heterogeneity in outcomes is due to differences in inclusion criteria, with some older studies from the pre-PSA era showing worse outcomes [5]. In addition, many patients classified as ISUP grade 1 would now be classified as ISUP grade 2–3 based on the 2005 Gleason classification, suggesting that the above-mentioned results should be considered as minimal. Patients with well-, moderately- and poorly differentiated tumours had 10-year CSS rates of 91%, 90% and 74%, respectively, correlating with data from the pooled analysis [7]. Observation was most effective in men aged 65–75 years with low-risk PCa [8]. Co-morbidity is as important as age in predicting life expectancy in men with PCa. Increasing co-morbidity greatly increases the risk of dying from non-PCa-related causes and for those men with a short life expectancy. In an analysis of 19,639 patients aged > 65 years who were not given curative treatment, most men with a CCI score > 2 had died from competing causes at 10 years follow-up regardless of their age at time of diagnosis. Tumour aggressiveness had little impact on OS suggesting that patients could have been spared biopsy and diagnosis of cancer. Men with a CCI score < 1 had a low risk of death at 10 years, especially for well or moderately-differentiated lesions [9]. This highlights the importance of assessing co-morbidity before considering a biopsy. In screen-detected localised PCa the lead-time bias is likely to be greater. Mortality from untreated screen-detected PCa in patients with ISUP grade 1–2 might be as low as 7% at 15 years follow-up [10]. Consequently, approximately 45% of men with PSA-detected PCa are suitable for close follow-up through a robust surveillance programme. There are two distinct strategies for conservative management that aim to reduce over-treatment: AS and WW (Table 1). Table 1. Definitions of active surveillance and watchful waiting Active surveillance Active surveillance aims to avoid unnecessary treatment in men with clinically localised PCa who do not require immediate treatment, but at the same time achieve the correct timing for curative treatment in those who eventually do [11]. Patients remain under close surveillance through structured surveillance programmes with regular follow-up consisting of PSA testing, clinical examination, MRI imaging and repeat prostate biopsies, with curative treatment being prompted by pre-defined thresholds indicative of potentially life-threatening disease, which is still potentially curable, while considering individual life expectancy. Watchful waiting refers to conservative management for patients deemed unsuitable for curative treatment from the outset, and patients are clinically ‘watched’ for the development of local or systemic progression with (imminent) disease-related complaints, at which stage they are then treated palliatively according to their symptoms in order to maintain QoL. Several cohorts have investigated AS in organ-confined disease, the findings of which were summarised in a systematic review [12]. More recently, the largest prospective series of men with low-risk PCa managed by AS was published [13]. Table 2 summarises the results of selective AS cohorts. Table 2. Active surveillance in screening-detected prostate cancer (large cohorts with longer-term follow-up) It is clear that the long-term OS and CSS of patients on AS are extremely good. However, more than one-third of patients are ‘reclassified’ during follow-up, most of whom undergo curative treatment due to disease upgrading, increase in disease extent, disease stage, progression or patient preference. Watchful waiting The Outcome of watchful waiting compared with active treatment showed the SPCG-4 study which was a RCT from the pre-PSA era, randomising patients to either WW or RP (Table 3) [14]. Table 3. Outcome of SPCG-4 at a median follow-up of 23.6 years The study found radical prostatectomy (RP) to provide superior cancer-specific survival (CSS), overall survival (OS) and biochemical progression-free survival (PFS) compared to watchful waiting (WW) at a median follow-up of 23.6 years (range 3 weeks–28 years). The overall evidence indicates that for men with asymptomatic, clinically localised PCa and with a life expectancy of < 10 years based on co-morbidities and/or age, the oncological advantages of active treatment over WW are unlikely to be relevant to them. Consequently, WW should be adopted for such patients. Radical Prostatectomy The second treatment modality with radical prostatectomy showed that the goal of RP by any approach is the eradication of cancer while, whenever possible, preserving pelvic organ function [15]. The procedure involves removing the entire prostate with its capsule intact and SVs, followed by vesico-urethral anastomosis. Surgical approaches have expanded from perineal and retropubic open approaches to laparoscopic and robotic-assisted techniques; anastomoses have evolved from Vest approximation sutures to continuous suture watertight anastomoses under direct vision and mapping of the anatomy of the dorsal venous complex (DVC) and cavernous nerves has led to excellent visualisation and potential for preservation of erectile function [16]. The main results from multi-centre RCTs involving RP are summarised in Table 4. Table 4. Oncological results of radical prostatectomy in organ-confined disease in RCTs Pre-operative preparation: Pre-operative patient education As before any surgery appropriate education and patient consent is mandatory prior to RP. Peri-operative education has been shown to improve long-term patient satisfaction following RP [17]. Augmentation of standard verbal

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Prostate Cancer PART 2

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Prostate Cancer Classification Comprehensive Review Article Part 2 Prof. Dr. Semir. A. Salim. Al Samarrai The objective of a tumour classification system is to combine patients with a similar clinical outcome. This allows for the design of clinical trials on relatively homogeneous patient populations, the comparison of clinical and pathological data obtained from different hospitals across the world, and the development of recommendations for the treatment of these patient populations. Throughout these Guidelines the 2017 Tumour, Node, Metastasis (TNM) classification for staging of PCa (Table 1) [1], Table 1. Clinical Tumour Node Metastatis (TNM) classification of PCa and the EAU risk group classification, which is essentially based on D’Amico’s classification system for PCa, are used (Table 2) [2]. Table 2. EAU risk groups for biochemical recurrence of localized and locally advanced prostate cancer The latter classification is based on the grouping of patients with a similar risk of biochemical recurrence (BCR) after radical prostatectomy (RP) or external beam radiotherapy (EBRT). Magnetic resonance imaging and targeted biopsy may cause a stage shift in risk classification systems [3]. Clinical T stage only refers to digital rectal examination (DRE) findings; local imaging findings are not considered in the TNM classification. Pathological staging (pTNM) is based on histopathological tissue assessment and largely parallels the clinical TNM, except for clinical stage T1 and the T2 substages. Pathological stages pT1a/b/c do not exist and histopathologically confirmed organ-confined PCas after RP arempathological stage pT2. The current Union for International Cancer Control (UICC) no longer recognises pT2 substages [1]. Of note: the EANM recently proposed a ‘miTNM’ (molecular imaging TNM) classification, taking into account prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET/CT) findings [4]. The prognosis of the miT, miN and miM substages is likely to be better to their T, N and M counterparts due to the ‘Will Rogers phenomenon’; the extent of this prognosis shift remains to be assessed as well as its practical interest and impact [5]. In the original Gleason grading system, 5 Gleason grades (ranging from 1–5) based on histological tumour architecture were distinguished, but in the 2005 and subsequent 2014 International Society of Urological Pathology (ISUP) Gleason score (GS) modifications Gleason grades 1 and 2 were eliminated [6,7]. The 2005 ISUP modified GS of biopsy-detected PCa comprises the Gleason grade of the most extensive (primary) pattern, plus the second most common (secondary) pattern, if two are present. If one pattern is present, it needs to be doubled to yield the GS. For three grades, the biopsy GS comprises the most common grade plus the highest grade, irrespective of its extent. The grade of intraductal carcinoma should also be incorporated in the GS [8]. In addition to reporting of the carcinoma features for each biopsy, an overall (or global) GS based on the carcinoma-positive biopsies can be provided. The global GS takes into account the extent of each grade from all prostate biopsies. The 2014 ISUP endorsed grading system limits the number of PCa grades, ranging them from 1 to 5 (see Table 2 and table 3) [8,9]. Table 3. International Society of Urological Pathology 2014 grade (group) system Further sub-stratification of the intermediate-risk group can be made and specifically the National Cancer Center Network (NCCN) Guidelines subdivide intermediate-risk disease into favourable intermediate-risk and unfavourable intermediate-risk, with unfavourable features including ISUP grade 3, and/or > 50% positive biopsy cores and/or at least two intermediate-risk factors [10]. The descriptor ‘clinically significant’ is widely used to differentiate PCa that may cause morbidity or death from types of PCa that do not. This distinction is particularly important as insignificant PCa that does not cause harm is so common [11]. Unless this distinction is made, such cancers are at high risk of being overtreated, with the treatment itself risking harmful side effects to patients. The over-treatment of insignificant PCas has been criticised as a major drawback of PSA testing [12]. However, defining what is clinically significant and what is insignificant PCa is difficult. In large studies of RP specimens which showed only ISUP grade 1 disease, extra prostatic extension (EPE) was extremely rare (0.28% of 2,502 cases) and seminal vesicle (SV) invasion or lymph node (LN) metastasis did not occur at all [13,14]. International Society for Urological Pathology grade 1 disease itself can therefore be considered clinically insignificant. Whilst ISUP grade 1 bears the hallmarks of cancer histologically, ISUP grade 1 itself does not behave in a clinically malignant fashion. However, ISUP grade 1 is first diagnosed at biopsy and guides management decisions, not after the prostate has been removed. The current standard practice of MRI-targeted and template biopsies has reduced diagnostic inaccuracy [15], however sampling error may still occur such that higher grade cancer could be missed. This should be especially considered if the prior MRI showed a suspicious lesion, but only ISUP grade 1 was found at biopsy. Another complexity in defining insignificant cancer is that ISUP grade 1 may progress to higher grades over time, becoming clinically significant at a later biopsy [16]. Therefore, although ISUP grade 1 itself can be described as clinically insignificant, it is important to take into account other factors, including imaging prior to biopsy and adequate sampling core number. When combined with low-risk clinical factors (see Table 2), ISUP grade 1 represents low-risk PCa, with its recommendation of preferred management being active surveillance (AS) or watchful waiting (WW). It should be noted, therefore, that defining ISUP grade 1 as insignificant cancer does not mean it should be ignored, but safely observed. Epidemiological and autopsy data also suggest that a proportion of ISUP grade 2 PCas would remain undetectable during a man’s life [17] and therefore may be overtreated. In current guidelines deferred treatment may be offered to select patients with intermediate-risk PCa [10], but evidence is lacking for appropriate selection criteria [18]. Recent papers have defined clinically significant cancer differently, commonly using ISUP grade 2 and above and even ISUP grade 3 and above, demonstrating the lack of consensus and evolution of its definition [19-22]. Some papers

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Prostate Cancer

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Prostate Cancer Epidemiology and Aetiology Comprehensive Review Article Part 1 Prof. Dr. Semir. A. Salim. Al Samarrai Prostate cancer is the second most commonly diagnosed cancer in men, with an estimated 1.4 million diagnoses worldwide in 2020 [1,2]. The frequency of autopsy-detected PCa is roughly the same worldwide [3]. A systematic review of autopsy studies reported a prevalence of PCa at age < 30 years of 5% (95% confidence interval [CI]: 3–8%), increasing by an odds ratio (OR) of 1.7 (1.6–1.8) per decade, to a prevalence of 59% (48–71%) by age > 79 years [4]. The incidence of PCa diagnosis varies widely between different geographical areas, being highest in Australia/New Zealand and Northern America (age-standardised rates [ASR] per 100,000 of 111.6 and 97.2, respectively), and in Western and Northern Europe (ASRs of 94.9 and 85, respectively), largely due to the use of prostate-specific antigen (PSA) testing and the aging population. The incidence is low in Eastern and South-Central Asia (ASRs of 10.5 and 4.5, respectively), but rising [5]. Rates in Eastern and Southern Europe were low but have also shown a steady increase [2,3]. Incidence and disease stage distribution patterns follow biological-, genetic-, and/or lifestyle factors [6]. There is relatively less variation in mortality rates worldwide, although rates are generally high in populations of African descent (Caribbean: ASR of 29 and Sub-Saharan Africa: ASRs ranging between 19 and 14), intermediate in the USA and very low in Asia (South-Central Asia: ASR of 2.9) [2]. Family history and ethnic background are associated with an increased PCa incidence suggesting a genetic predisposition [7,8]. Only a small subpopulation of men with PCa have true hereditary disease. Hereditary PCa (HPCa) is associated with a six to seven year earlier disease onset but the disease aggressiveness and clinical course does not seem to differ in other ways [7,9]. In a large USA population database, HPCa (in 2.18% of participants) showed a relative risk (RR) of 2.30 for diagnosis of any PCa, 3.93 for early-onset PCa, 2.21 for lethal PCa, and 2.32 for clinically significant PCa (csPCa) [10]. These increased risks of HPCa were higher than for familial PCa (> 2 first- or second-degree relatives with PCa on the same side of the pedigree), or familial syndromes such as hereditary breast and ovarian cancer and Lynch syndrome. The probability of high-risk PCa at age 65 was 11.4% (vs. a population risk of 1.4%) in a Swedish population-based study [11]. The Identification of Men with a Genetic Predisposition to Prostate Cancer (IMPACT) study, which evaluated targeted PCa screening (annually, biopsy recommended if PSA > 3.0 ng/mL) using PSA in men aged 40–69 years with germline BRCA1/2 mutations found that after 3 years of screening, BRCA2 mutation carriers were associated with a higher incidence of PCa, a younger age of diagnosis, and more clinically significant tumours compared with non-carriers [12]. The influence of BRCA1 mutations on PCa remained unclear. No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 non-carriers. Limitations of the IMPACT study include the lack of magnetic resonance imaging (MRI) data and targeted biopsies as it was initiated before that era. A wide variety of exogenous/environmental factors have been discussed as being associated with the risk of developing PCa or as being aetiologically important for the progression from latent to clinical PCa [13]. Japanese men have a lower PCa risk compared to men from the Western world. However, as Japanese men move from Japan to California, their risk of PCa increases, approaching that of American men, implying a role of environmental or dietary factors [14]. However, currently there are no known effective preventative dietary or pharmacological interventions. The single components of metabolic syndrome (MetS), hypertension (p = 0.035) and waist circumference > 102 cm (p = 0.007), have been associated with a significantly greater risk of PCa. The association between metformin use and PCa is controversial. At population level, metformin users (but not other oral hypoglycaemic agents) were found to be at a decreased risk of PCa diagnosis compared with neverusers (adjusted OR: 0.84, 95% CI: 0.74–0.96) [15]. In 540 diabetic participants of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, metformin use was not significantly associated with PCa and therefore not advised as a preventive measure (OR: 1.19, p = 0.50) [16]. The ongoing Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial assesses metformin use in advanced PCa (Arm K) [17]. Figure 1. Risk Factors of Prostatic Cancer. A meta-analysis of 14 large prospective studies did not show any association between blood total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol levels and the risk of either overall PCa or high-grade PCa [18]. Results from the REDUCE study also did not show a preventive effect of statins on PCa risk [19]. Within the REDUCE study, obesity was associated with lower risk of low-grade PCa in multivariable analyses (OR: 0.79, p = 0.01), but increased risk of high-grade PCa (OR: 1.28, p = 0.042) [20]. This effect seems mainly explained by environmental determinants of height/body mass index (BMI) rather than genetically elevated height or BMI [21]. The association between a wide variety of dietary factors and PCa have been studied, but there is paucity of quality of evidence (table 1). Table 1. Main dietary factors that Have been associated with PCa Although it seems that 5-ARIs have the potential of preventing or delaying the development of PCa (~25%, for ISUP grade 1 cancer only), this must be weighed against treatment-related side effects as well as the potential small increased risk of high-grade PCas, although these do not seem to impact PCa mortality [39–42]. None of the available 5-ARIs have been approved by the European Medicines Agency (EMA) for chemoprevention. Hypogonadal men receiving testosterone supplements do not have an increased risk of PCa [43]. A pooled analysis showed that men with very low concentrations of free testosterone (lowest 10%) have a belowaverage risk (OR: 0.77) of PCa [44]. A significantly higher rate of ISUP

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دكتور علاج التهاب بولية في دبي :أفضل مركز مسالك بولية في دبي

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دكتور التهابات المسالك البولية عند الرجل: دليلك الشامل لـ علاج التهاب بولية في دبي واختيار أفضل مركز مسالك بولية مثل مركز سمير السامرائي في الامارات دبي مدينة دبي الطبية هل تخيلت يوماً أن 50% من الرجال فوق سن الخمسين سيعانون من أعراض تتطلب زيارة أخصائي مسالك بولية، وأن نسبة كبيرة منها تبدأ بالتهاب بسيط؟ تتطلب حالات التهاب البولية علاجاً متخصصاً لضمان عدم تحولها إلى مشكلات مزمنة. في دبي، يُعتبر البروفيسور سمير السامرائي من الرواد في هذا المجال. يركز البروفيسور على التشخيص الدقيق للمسبب الجرثومي وغير الجرثومي للالتهابات، ويطبق أحدث البروتوكولات العالمية لـ علاج هذه الحالات بفعالية وأمان، بما في ذلك التهابات المثانة والبروستاتا المتكررة. “دعني أسألك سؤالاً يلامس عمق راحتك اليومية: متى كانت آخر مرة شعرت فيها بأن جسدك لم يعد يسمح لك بالعيش بكامل حريتك؟ ذلك الشعور الحارق عند التبول، أو الإحراج المتكرر بسبب الحاجة الملحة للذهاب إلى الحمام، تلك الأعراض المزعجة التي تهمس لك بأن شيئاً ما ليس على ما يرام في الجهاز البولي، تبدأ صغيرة ثم تتضخم لتسرق نومك وتركيزك وحرية حركتك في مدينة دبي السريعة. إنه شعور مؤلم، يحمل في طياته الخوف والقلق من المجهول، أو ربما الحرج الذي يمنعنا كرجال من الحديث عن مشاكلنا الصحية الحميمة. نحن نبحث عن علاج، ولكننا في الحقيقة نبحث عن الطمأنينة، وعن دكتور ليس مجرد طبيب، بل أخصائي يرى فينا إنساناً كاملاً لا مجرد حالة طبية. هذا البحث عن دكتور علاج التهاب بولية في دبي ليس رفاهية، بل ضرورة لاسترداد جودة الحياة. إذا كنت تتساءل الآن: ‘هل أنا بحاجة حقاً إلى أفضل أخصائي أم الأمر بسيط؟’ فإن إجابتك تكمن في معرفة أن إهمال التهاب بولية بسيط قد يتحول إلى مشكلة مزمنة أو أكثر تعقيداً. هذا الدليل الإنساني هو مرآتك لتبدأ رحلة البحث بثقة، وتجد الخيار الأفضل بين أطباء المسالك البولية المتميزين في الإمارات.” معايير اختيار دكتور المسالك البولية الأمثل في دبي والشارقة رحلة البحث عن دكتور علاج التهاب بولية في دبي أو حتى في الشارقة يجب أن تكون منهجية ومركزة. نحن نبحث عن خبراء يجمعون بين المعرفة الأكاديمية العميقة والخبرة العملية الواسعة. التخصص والخبرة: ما بعد درجة طبيب عام في مجال المسالك البولية والكلى، لا يكفي أن يكون الدكتور طبيباً عاماً. الأفضل هو الاستشاري أو الأخصائي الذي قضى سنوات في دراسة الحالات المعقدة. الدرجات الأكاديمية والتخصصية: ابحث عن دكتور حاصل على درجات عليا مثل الدكتوراه أو الزمالة الأوروبية/الأمريكية. هذا ما يميز أفضل أطباء دبي مثل الدكتور عبد الناصر أو الدكتور محمد أو غيرهم من الخبراء في المنطقة. الخبرة في علاج الالتهاب المتكرر: التهابات المسالك البولية عند الرجل غالباً ما تكون متكررة أو مزمنة. الأخصائي الأفضل هو الذي يملك خبرة في تجاوز العلاج التقليدي بالمضادات الحيوية للوصول إلى السبب الجذري (مثل تضخم البروستاتا، أو حصوات الكلى الدقيقة). نماذج الخبرة الدولية: العديد من المراكز المرموقة في الإمارات تستقطب خبراء دوليين من الأردن، ألمانيا، أو المملكة المتحدة. هذه الخبرات المتعددة الثقافات تضمن لك أحدث البروتوكولات العلاجية العالمية. دكتور علاج التهاب بولية في دبي البنية التحتية للمركز: تقنيات علاج الالتهاب المتقدمة لا يقتصر التميز على الدكتور وحده، بل يمتد إلى الـ clinic أو المركز الذي يعمل به. يجب أن يوفر أفضل مركز مسالك بولية تكنولوجيا التشخيص وعلاج متقدمة. التشخيص الدقيق: يجب أن يوفر المركز أجهزة تصوير متقدمة (كالسونار ثلاثي الأبعاد والتصوير بالرنين المغناطيسي) ودراسات ديناميكا البولية لتحديد سبب التهاب المسالك البولية بدقة متناهية. التعاون مع المختبرات: سرعة ودقة تحليل عينات البولية (زرع البول) أمر حاسم في علاج التهاب المسالك. المراكز الكبرى مثل ميدكير في الشارقة ودبي، أو المراكز التابعة لـ دليلي ميديكال توفر خدمات مختبرية سريعة وموثوقة. مركز سمير السامرائي في دبي مدينة دبي الطبية: نموذج للريادة في المسالك البولية دكتور علاج التهاب بولية في دبي عندما نتحدث عن أفضل مركز مسالك بولية في دبي، يبرز اسم مركز سمير السامرائي في الامارات دبي مدينة دبي الطبية كواحد من الأسماء التي تحظى بسمعة كبيرة. البروفيسور سمير السامرائي هو أفضل أخصائي الجهاز البولي، متخصص في جراحة المسالك البولية والعقم. يتمتع بخبرة ممتازة في تشخيص وإدارة اضطرابات الجهاز البولي المختلفة، والتي قد تؤثر على جودة حياة المرضى. البروفيسور السامرائي حصل على شهادته من ألمانيا، ويقدم في العيادة رعاية متنوعة لجميع الأعمار، بما في ذلك الأطفال. فضلاً، احجز موعدك مع الطبيب للحصول على أعلى مستوى من الرعاية الطبية، بما في ذلك علاج اورام المسالك البولية. البروفيسور سمير السامرائي: تخصص دقيق وخبرة طويلة البروفيسور سمير السامرائي يمثل نموذجاً للاستشاري المتخصص، والذي غالباً ما يتميز بأنه: صاحب خبرة عقود: سنوات الخبرة الطويلة في طب المسالك البولية تعني أنه قد تعامل مع مجموعة واسعة من الحالات المعقدة والبسيطة. تخصص في أمراض الذكورة والأورام: بالإضافة إلى علاج التهاب بولية، يتخصص الدكتور السامرائي في مجالات دقيقة مثل أورام المسالك البولية والعقم والضعف الجنسي، مما يجعله خياراً شاملاً للكثير من الرجال. موقع متميز في مدينة دبي الطبية: الوجود في هذا الموقع الحيوي يضمن سهولة الوصول والالتزام بأعلى المعايير التنظيمية لهيئة الصحة. لماذا تختار مركزاً استشارياً متخصصاً؟ دكتور علاج التهاب بولية في دبي اختيار مركز يحمل اسم دكتور استشاري معروف يعني أنك ستتلقى رعاية متخصصة، لا سيما في حالات التهابات المسالك البولية عند الرجل التي غالباً ما تكون ناتجة عن مشاكل أخرى كامنة (مثل البروستاتا) تحتاج إلى تشخيص وعلاج متكامل. علاج التهاب بولية في مثل هذه المراكز يتم عبر بروتوكولات حديثة وموجهة للسبب، لا مجرد التخفيف من الأعراض. التهاب المسالك البولية عند الرجل: التحدي والحلول الدقيقة دكتور علاج التهاب بولية في دبي بالنسبة للرجل، التهاب المسالك البولية هو أكثر من مجرد إزعاج؛ هو إشارة يجب الانتباه إليها بحذر، وقد يشير إلى مشكلة أعمق في البروستاتا أو الكلى. متى يتحول الالتهاب البولي البسيط إلى حالة معقدة؟ دكتور علاج التهاب بولية في دبي التهاب البولية عند الرجال يجب التعامل معه بجدية أكبر من النساء. إذا لم يتم علاجه بشكل فعال، قد يتطور إلى: التهاب البروستاتا (Prostatitis): وهو غالبًا ما يكون سببًا ونتيجة في نفس الوقت لالتهاب المسالك البولية عند الرجل. يتطلب هذا التهاب علاجاً مختلفاً وممتداً. التهاب الكلى (Pyelonephritis): وهو حالة خطيرة تهدد وظائف الكلى وتتطلب تدخلاً طبياً عاجلاً، وهنا يبرز دور أفضل دكتور كلى ومسالك بولية. خطوات العلاج المنهجية التي يتبعها أفضل دكتور دكتور علاج التهاب بولية في دبي لا يقتصر علاج التهاب بولية على وصف المضاد الحيوي فحسب. أفضل أخصائي يتبع نهجاً شاملاً: زرع البول والمزرعة: لتحديد نوع البكتيريا بدقة والمضاد الحيوي الأفضل والأكثر فعالية (حساسية ومقاومة). التصوير التشخيصي: لإجراء فحوصات معمقة لغدة البروستاتا، والمثانة،

دكتور علاج التهاب بولية في دبي :أفضل مركز مسالك بولية في دبي قراءة المزيد »

اختيار أفضل دكتور مسالك بولية بدبي: خبرة عالية وخدمات متطورة

أفضل دكتور استشاري مسالك بولية في دبي: خبرة ِوخدمات متطورة

Uncategorized / myar nasser

دكتور التهابات المسالك البولية عند الرجل: دليلك لاختيار أفضل دكتور استشاري مسالك بولية في دبي والخدمات المتميزة في مركز سمير السامرائي في الامارات دبي مدينة دبي الطبية هل تعلم أن نحو 40% من الرجال سيعانون من أعراض مزعجة مرتبطة بالجهاز البولي في مرحلة ما من حياتهم؟ عندما تبحث عن افضل دكتور استشاري مسالك بولية في دبي، فإن معايير الخبرة والتخصص الدقيق تقودك مباشرة إلى البروفيسور سمير السامرائي. يتميز البروفيسور بمسيرة مهنية حافلة، حيث تخصص في علاج وجراحة أمراض المسالك البولية وأورامها، مقدماً نهجاً علاجياً متقدماً يضمن أفضل النتائج والتعافي السريع للمرضى. “الحياة في دبي، هذه المدينة النابضة بالحيوية والسرعة، تجعلنا نركز على الإنجاز والعمل، وننسى أحياناً الإشارات الصامتة التي يرسلها جسدنا. ولكن، ماذا لو استيقظت يوماً لتجد أن الألم أو الانزعاج في الجهاز البولي قد أصبح عبئاً يثقل كاهلك، يسرق راحتك، ويقيد حركتك؟ هل شعرت يوماً بالقلق الذي يتسلل إلى قلبك عندما تجد نفسك مضطراً للبحث عن دورة مياه بشكل متكرر، أو تشعر بحرقة لا تحتمل، وتتساءل: “ما الذي يحدث لي؟” إنها لحظات الوحدة والألم التي تجعلك تتمنى لو أنك تستطيع أن تجد يداً خبيرة تمسك بك، وتطمئنك بأن الحل قريب وبجودة عالمية. هذا القلق ليس مجرد عارض صحي، بل هو شعور إنساني عميق يلامس خصوصيتنا وكرامتنا، ويجعلنا نبحث عن أفضل عناية ممكنة. في رحلة البحث هذه، تحديد أفضل دكتور استشاري مسالك بولية في دبي هو الخطوة الأولى نحو استعادة حياتك بكل أبعادها. هذا المقال ليس مجرد قائمة، بل هو خارطة طريق إنسانية لمساعدتك على اتخاذ قرار صحي سليم ومدروس، يبدأ بالثقة وينتهي بالشفاء، بعيداً عن التشتت والاجتهادات غير الموثوقة.” البروفيسور سمير السامرائي هو أفضل دكتور استشاري مسالك بولية في دبي، ويُعدّ ضمن نخبة أفضل أطباء دبي في هذا المجال. يقدم البروفيسور السامرائي، من خلال مركزه الطبي، رعاية شاملة ومتخصصة في علاج أمراض المسالك البولية والجهاز البولي والتناسلي. دكتور السامرائي، بخبرته الواسعة، يقدم علاجاً متطوراً لمختلف أمراض المسالك البولية المعقدة، ما يجعله وجهة موثوقة للبحث عن أفضل مستويات رعاية بولية. ما هي معايير البحث عن أفضل طبيب مسالك بولية في دبي؟ في سوق الرعاية الصحية التنافسي في دبي، يمكن أن يصبح البحث عن أفضل دكتور أمراً شاقاً. نحن لا نبحث فقط عن طبيب؛ نحن نبحث عن شريك صحي يتمتع بالخبرة، والمهارة، والأهم من ذلك، التعاطف الإنساني. إن صحة الجهاز البولي وسلامته (بما في ذلك الكلى، الحالب، المثانة، والإحليل، بالإضافة إلى الأعضاء التناسلية الذكرية) تتطلب تخصصاً دقيقاً ووعياً بالتطورات العالمية. الخبرة والتخصص الدقيق: الركيزة الأساسية ليس كل أطباء المسالك البولية متماثلين. يجب التمييز بين طبيب عام للمسالك البولية ودكتور استشاري يمتلك سنوات طويلة من الخبرة والتدريب في تخصص دقيق. فمثلاً، مشكلة مثل التهابات المسالك البولية عند الرجل قد تتطلب فهماً أعمق لاحتمالية ارتباطها بالبروستاتا أو عوامل أخرى. الشهادات والبوردات: تحقق من حصول الدكتور على شهادات عليا أو زمالات من بوردات عالمية (مثل البورد الأوروبي أو الأمريكي) أو بوردات عربية معترف بها (مثل البورد العراقي الذي يحمله بعض الأطباء المرموقين في دبي). هذه الشهادات تعكس مستوى عالٍ من التأهيل والالتزام. التخصص الفرعي: هل يركز الدكتور على جراحة أورام الكلى، أم حصوات المسالك، أم أمراض الذكورة والعقم؟ اختيار دكتور متخصص في حالتك تحديداً يرفع بشكل كبير من فرص نجاح العلاج. فمثلاً، دكتور التهابات المسالك البولية عند الرجل المتخصص في أمراض الذكورة والبروستاتا سيكون خياراً مثالياً. يُعدّ البروفيسور سمير السامرائي واحدًا من أفضل دكتور استشاري مسالك بولية في دبي، حيث يمتلك خبرة تمتد لأكثر من أربعين عامًا في علاج أمراض المسالك البولية والتناسلية. أسّس مركز السامرائي الطبي في مدينة دبي الطبية ليكون من أبرز المراكز المتخصصة في رعاية وعلاج أمراض المسالك البولية عند الرجال والنساء على حد سواء. يشتهر الدكتور بخبرته الواسعة في جراحة المسالك البولية والمناظير الحديثة، ويُعدّ من بين أطباء دبي القلائل الذين يجمعون بين المهارة الجراحية والعلم الأكاديمي المتقدم. كما يقدّم المركز خدمات متكاملة تشمل التشخيص الدقيق، والعلاج الدوائي والجراحي، بإشراف مباشر من البروفيسور، لضمان أعلى مستويات الرعاية الطبية وأفضل النتائج في مجال المسالك البولية. التقنيات الحديثة والابتكار في العلاج تتميز دبي بتبنيها لأحدث التقنيات الطبية. أفضل المراكز والأطباء هم من يتقنون استخدام: جراحة الروبوت الجراحي: لعمليات استئصال البروستاتا أو الكلى، لما توفره من دقة متناهية وفترة تعافي أقصر. تقنيات الليزر: لتفتيت حصوات الكلى والحالب أو لعلاج تضخم البروستاتا الحميد. المناظير المتقدمة: للتشخيص والعلاج بأقل تدخل جراحي ممكن. البعد الإنساني والثقة: ما لا تقوله الشهادات إن البحث عن أفضل دكتور ليس مجرد بحث عن مهارة جراحية؛ بل هو بحث عن شخص يستطيع أن يتفهم خوفك، ويجيب على أسئلتك بوضوح وصبر. يجب أن تشعر بالراحة التامة والثقة في طبيبك. التواصل الفعال: يجب أن يشرح لك الدكتور حالتك وخيارات العلاج بلغة واضحة وغير معقدة. التعاطف: الطبيب الأفضل هو الذي يعالج المريض وليس المرض فقط. دبي والتميز في رعاية المسالك البولية: مراكز وأطباء استشاريون تعتبر مدينة دبي الطبية وبعض المراكز الكبرى في الإمارة نقطة جذب للخبراء العالميين في مجال المسالك البولية. إن تركيز دبي على جودة الرعاية الصحية قد جعلها مقصداً للبحث عن أفضل أطباء المسالك البولية في المنطقة. مركز سمير السامرائي: نموذج للخبرة المتميزة في الامارات دبي الطبية يُعتبر ذكر مركز سمير السامرائي في الامارات دبي مدينة دبي الطبية جزءاً أساسياً من البحث عن التميز في هذا المجال. مثل هذه المراكز، التي تحمل أسماء أطباء استشاريين ذوي سمعة عالمية، غالباً ما تمثل نقطة ارتكاز للباحثين عن الرعاية المتخصصة. لماذا هذه المراكز تتصدر؟ غالباً ما يكون السبب هو الجمع بين الخبرة الفردية لـ الدكتور المؤسس أو الرئيسي، وتوفير أحدث الأجهزة التشخيصية والعلاجية، بالإضافة إلى الالتزام بأعلى معايير الرعاية الدولية. هذه المراكز توفر بيئة علاجية متكاملة، لا سيما في حالات التهابات المسالك البولية عند الرجل المعقدة أو أمراض البروستاتا وحصوات المسالك. التفرد في الرعاية: التخصص في مثل هذه المراكز يضمن أنك لن تكون مجرد رقم، بل حالة طبية تستدعي دراسة وتخطيطاً علاجياً دقيقاً وشخصياً. نماذج لأطباء استشاريين بارزين في دبي هناك عدد من الأسماء اللامعة التي تظهر في صدارة نتائج البحث عن أفضل دكتور استشاري مسالك بولية في دبي، والتي تتميز بمواصفات عالمية: أطباء المسالك البولية وجراحة الذكورة: يتميز بعض الأطباء الاستشاريين في دبي بدمج تخصص المسالك البولية مع جراحة الذكورة، مما يجعلهم الخيار الأفضل للتعامل مع المشاكل المتعلقة بالبروستاتا، العقم، والضعف الجنسي، بالإضافة إلى التهابات المسالك البولية عند الرجل. الأطباء ذوي الخلفية الدولية: يتمتع العديد من الاستشاريين في دبي بخلفيات تدريبية قوية من ألمانيا، والمملكة المتحدة، والولايات المتحدة الأمريكية، مما

أفضل دكتور استشاري مسالك بولية في دبي: خبرة ِوخدمات متطورة قراءة المزيد »