Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

AhRR methylation contributes to disease progression in urothelial bladder cancer.

BACKGROUND: Bladder Cancer (BCa) is the tenth most incident malignancy worldwide. BCa is mostly attributed to environmental exposure and lifestyle, particularly tobacco smoking. The Aryl Hydrocarbon Receptor Repressor (AhRR) participates in the induction of many enzymes involved in metabolizing carcinogens, including tobacco smoke components. Additionally, studies have shown that smoking demethylates the (AhRR) gene in blood, suggesting AhRR demethylation as a specific serum smoking biomarker. OBJECTIVE: This study aimed to validate AhRR demethylation as a smoking biomarker in the target tissue and investigate its contribution to bladder carcinogenesis. METHODS: AhRR percent methylation was tested for its association with patient smoking status and oncogenic outcome indicators, particularly p53, RB1, and FGFR3 activating mutations, muscle-invasiveness, and tumor grade, in 180 BCa tissue-based DNA. RESULTS: Results showed significantly higher AhRR percent methylation in muscle-invasive compared to non-muscle invasive tumors (42.86% vs. 33.98%; p= 0.011), while lower AhRR methylation was significantly associated with FGFR3 Codon 248 mutant genotype compared to wild-type (28.11% ± 9.44 vs. 37.87% ± 22.53; p= 0.036). All other tested associations were non-statistically significant. CONCLUSIONS: Although AhRR methylation did not predict smoking status in BCa tumors, it may be a contributor to carcinogenesis and disease progression. Our findings constitute the basis for further research.

Plexiform Penile Neurofibroma: A Case Report of a Rare Entity in a Pre-Pubertal Child.

Neurofibromatosis is a group of genetic disorders and consists of 2 forms: Neurofibromatosis type 1 (NF-1) and Neurofibromatosis type 2. The most common is the NF-1 which is also known as von Recklinghausen's disease. The presentation and clinical manifestations of this condition vary greatly. It is usually characterized by café-au-lait spots and neurofibromas. In this report, the case of a 12-year-old boy with NF-1 is presented. The boy has several café-au-lait spots along with inguinal and axillary freckles. He was found to have a rare and unusual neurofibroma of the penis.

Slow N-acetylation as a possible contributor to bladder carcinogenesis.

Bladder cancer (BCa) is an exophytic tumor that presents as either noninvasive confined to the mucosa (NMIBC) or invading the detrusor muscle (MIBC), and was recently further subgrouped into molecular subtypes. Arylamines, major BCa environmental and occupational risk factors, are mainly metabolized by the genetically polymorphic N-acetyltransferases 1, NAT1 and NAT2. In this study, we investigated the association between N-acetyltransferases genetic polymorphism and key MIBC and NMIBC tumor biomarkers and subtypes. A cohort of 250 males with histologically confirmed urothelial BCa was identified. Tumors were genotyped for NAT1 and NAT2 using real-time polymerase chain reaction (PCR), and characterized for mutations in TP53, RB1, and FGFR3 by PCR-restriction fragment length polymorphism. Pathology data and patients' smoking status were obtained from medical records. Pearson χ2 and Fisher exact tests were used to check for associations and interactions. Results show that NAT1 G560 A polymorphism is significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .001), higher tumor grade (high grade vs low grade; P = .011), and higher FGFR3 mutation frequency within the MIBC subgroup (P = .042; .027). NAT2 G857 A polymorphism is also found to be significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .041). Our results indicate that slow N-acetylation is a contributor to bladder carcinogenesis and muscle-invasiveness. These findings highlight NAT1 as a biomarker candidate in BCa and a potential target for drug development.

Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations.

PURPOSE: Prostate cancer care in the Middle East is highly variable and access to specialist multidisciplinary management is limited. Academic tertiary referral centers offer cutting-edge diagnosis and treatment; however, in many parts of the region, patients are managed by non-specialists with limited resources. Due to many factors including lack of awareness and lack of prostate-specific antigen (PSA) screening, a high percentage of men present with locally advanced and metastatic prostate cancer at diagnosis. The aim of these recommendations is to assist clinicians in managing patients with different levels of access to diagnostic and treatment modalities. METHODS: The first Advanced Prostate Cancer Consensus Conference (APCCC) satellite meeting for the Middle East was held in Beirut, Lebanon, November 2017. During this meeting a consortium of urologists, medical oncologists, radiation oncologist and imaging specialists practicing in Lebanon, Syria, Iraq, Kuwait and Saudi Arabia voted on a selection of consensus questions. An additional workshop to formulate resource-stratified consensus recommendations was held in March 2019. RESULTS: Variations in practice based on available resources have been proposed to form resource-stratified recommendations for imaging at diagnosis, initial management of localized prostate cancer requiring therapy, treatment of castration-sensitive/naïve advanced prostate cancer and treatment of castration-resistant prostate cancer. CONCLUSION: This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.

Classic Testicular Seminoma in Men Aged 50 Years or Over: A Case Report and Review of the Literature.

Testicular cancer is the most frequent solid tumor detected in young adult men. Germ cell tumors (GCTs), particularly seminomas, are the most common type of testicular neoplasms seen in that age population. Most publications have reported decreasing incidence of GCTs in patients above forty years of age. Since the biologic activity of seminomas appears similar across ages, recommended management of senior adults involves a multimodal therapy of radical inguinal orchiectomy with radiation or cytotoxic treatment as needed. Attenuating chemotherapy dosages are critical to ensure better tolerability of associated adverse events. Here we report a case series of 2 men older than fifty years of age with metastatic testicular seminoma. We aim to emphasize a rare clinical entity encountered in the senior adult population.

Primary Mature Cystic Teratoma Compressing the Prostate in a 28-Year-Old Male: A Case Report and Literature Review.

Primary mature retroperitoneal teratomas are rare tumors most commonly occurring in adult females. These tumors are usually asymptomatic since they have no attachments to specific organs. We present a rare case of a 28-year-old male with 2-month history of lower urinary tract symptoms, who was found to have a primary mature cystic teratoma abutting the prostate.

Percutaneous nephrolithotomy in a case of retrorenal colon: A descriptive approach and literature review.

INTRODUCTION: Percutaneous nephrolithotomy procedure is generally used to treat stones resistant to other treatment modalities. Colonic perforation even though rare, is a serious complication that increases patient's morbidity. This case report describes the case of a patient with retrorenal colon who underwent percutaneous nephrolithotomy for management of pelvis/lower calyceal staghorn stone. CASE PRESENTATION: A 63-year-old female patient presented for the management of a staghorn pelvis-lower calyceal stone. The patient had a preoperative computed tomography scan of the abdomen and pelvis that showed an incidental finding of left retrorenal colon. Under computed tomography scan guidance, a nephrostomy tube was successfully placed by an interventional radiologist, and then she underwent percutaneous nephrolithotomy. CONCLUSION: This case report aims to stress on the importance of doing a computed tomography scan whenever a prior abdominal surgery is performed. We strongly believe that gastrointestinal injuries could be avoided by using computed tomography guided access in high risk patients.

A Dynamic Anatomical Description of the Parietal Pleura Setting Safety Limits for Intercostal Percutaneous Access.

PURPOSE: We came up with a dynamic anatomical study intended to validate the safety of intercostal approach used by our center to access the upper pole of the kidney during percutaneous surgery. MATERIALS AND METHODS: A total of 101 patients presenting randomly to the radiology department for CT evaluation of the abdomen and superior pelvis were involved in this study. Deep inspiration and expiration sequences in the prone position were evaluated to establish the location of the parietal pleura in relation to different anatomical landmarks. Three-dimensional reconstruction was performed to simulate the access needle course through the retroperitoneum. RESULTS: Our data show that the position of parietal pleura is invariably higher on the right side irrespective of anatomical relation or respiratory changes. Higher position of the parietal pleura was noted in all considered landmarks upon full expiratory sequences. Using the midclavicular line as a landmark, our data show that on the right side, the parietal pleura was higher than the 10th intercostal space (ICS) in 100% of patients. Going up to the level of the ninth and eighth ICS, the pleura is higher in 89.1% and 66.3% of patients, respectively. Moreover, on the left side, the level of the parietal pleura was higher than the 11th ICS in 100% of patients. Reaching the 10th ICS, the parietal pleura still is higher in 92.07% of cases. Going up to the ninth ICS reduces the margin to 64.35% and using the eighth ICS would convey a margin of 24.7%. CONCLUSIONS: Supracostal access for percutaneous nephrolithotomy carries a risk of pulmonary complications, limiting its use worldwide. We have shown in this study that using the differences in inspiration and expiration along with the right anatomical landmarks could substantially lower the risk of complications. However, regardless of the side or landmark used, supracostal access is safe in >90% of cases.

Non-Angled Intercostal Percutaneous Access Under Full Expiration: Safety Is Not an Issue Anymore.

OBJECTIVE: Percutaneous nephrolithotomy (PCNL) is a well-established procedure for the management of urinary calculi and can be performed intercostally or subcostally. Favoring one approach vs the other is still debatable, and literature has been inconclusive regarding the efficacy and safety of both approaches. Hence, this study aims to assess the safety and efficacy of direct non-angled intercostal technique performed under full expiration and to compare it to the subcostal approach. METHODS: PCNL was conducted among 361 patients during 2010-2015 at Saint George Hospital University Medical Center in Beirut, Lebanon. PCNL was done by one operator and by following a standard technique. After reviewing the medical records, 304 patients were included. Data analysis was conducted using Stata/IC 10.0. Bivariate analysis was conducted using Pearson's Chi-square, and logistic regression model was run. Alpha level was set at 0.05. RESULTS: Of the total patients, 54.6% and 45.4% underwent intercostal (Group I) and subcostal (Group II) access, respectively. Mean drop in hemoglobin in Group II was 1.9 g/dL vs 1.48 g/dL in Group I (p-value = 0.0040). The mean difference in operation time between group I (88.61 minutes) and group II (102.58 minutes) was statistically significant (p-value = 0.0064). Patients were stone free in 88.05% of the intercostal cases and 78.52% of the subcostal cases. Group II patients were twice more likely to have residual stones compared to Group I (p-value = 0.029). No statistical significance was observed in postoperative complications among both groups. In addition, no cases of pneumothorax were reported. CONCLUSION: Compared to subcostal access, intercostal approach under full expiration is a safe technique that provides optimal approach to the intrarenal collecting system and allows less angulation, less bleeding, and yields higher stone clearance with minimal complications. When performed by a well-trained urologist, intercostal access should be advocated in PCNL to obtain a direct non-angled access to the tip of the desired posterior calix.

CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population.

Urinary bladder cancer incidence in Lebanon ranks among the highest in the world. Cytochrome P450 2E1 (CYP2E1), NAD(P)H quinone oxidoreductase1 (NQO1), and N-Acetyltransferase1 (NAT1), are drug-metabolizing enzymes (DMEs) involved in the metabolism of carcinogens, such as arylamines and heterocyclic amines, implicated in bladder cancer. The present study attempts to investigate the role of these DMEs genetic polymorphism in bladder cancer risk among Lebanese men. 54 cases and 106 controls were recruited from two hospitals in Beirut. An interview-based questionnaire was administered to assess suspected environmental and occupational risk factors. PCR-RFLP was performed on blood-based DNA samples to determine DMEs genotypes. Associations between bladder cancer and putative risk factors were measured using adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Results showed CYP2E1 c1/c1, NAT1*14A, and smoking, to be risk factors for bladder cancer. No significant differences in frequency distribution of the NQO1 genotypes were found in cases versus controls. The odds of carrying the CYP2E1 c1/c1 genotype were 4 times higher in cases compared to controls (OR=3.97, 95% CI: 0.48-32.7). The odds of carrying at least one NAT1*14A allele were 14 times higher in cases versus controls (OR=14.4, 95% CI: 1.016-204.9). Our study suggests CYP2E1 c1/c1, NAT1*14A, and smoking, as potential risk factors for bladder cancer in Lebanese. Further studies with larger samples must be conducted to confirm these findings.

Urinary bladder cancer risk factors: a Lebanese case- control study.

BACKGROUND: Bladder cancer is the second most incident malignancy among Lebanese men. The purpose of this study was to investigate potential risk factors associated with this observed high incidence. METHODS: A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently selected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposure data were collected using a structured face-to-face interview questionnaire. Blood samples were collected to determine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariate and multivariate logistic regression, along with checks for effect modification. RESULTS: The odds of having bladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure to occupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The odds of prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showed different clustering patterns of NAT1 alleles. No significant differences between cases and controls were found for consumption of alcohol, coffee, tea, or artificial sweeteners. CONCLUSIONS: This is the first case-control study investigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factors in the literature, particularly smoking and occupational exposure to diesel. The herein observed associations should be used to develop appropriate prevention policies and intervention strategies, in order to control this alarming disease in Lebanon.

N-Acetyltransferase 1 (NAT1) Genotype: A Risk Factor for Urinary Bladder Cancer in a Lebanese Population.

In Lebanon, bladder cancer is the second most incident cancer among men. This study investigates a possible association between N-acetyltransferase 1 (NAT1) genotype, a drug-metabolizing enzyme coding gene, and bladder cancer in Lebanese men. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently identified and selected from the same settings. Data was collected using interview questionnaire and blood analysis. NAT1 genotypes were determined by PCR-RFLP. Statistical analysis revolved around univariate, bivariate, and multivariate logistic regression models, along with checks for effect modification. Results showed NAT1(∗)14A allele, smoking, occupational exposure to combustion fumes, and prostate-related symptoms, to be risk factors for bladder cancer. The odds of carrying at least one NAT1(∗)14A allele are 7 times higher in cases compared to controls (OR = 7.86, 95% CI: 1.53-40.39). A gene-environment interaction was identified for NAT1(∗)14A allele with occupational exposure to combustion fumes. Among carriers of NAT1(∗)14A allele, the odds of bladder cancer dropped to 2.03 from 3.72. Our study suggests NAT1(∗)14A allele as a possible biomarker for bladder cancer. Further research is recommended to confirm this association.

Comparative study of degree of renal trauma between Amplatz sequential fascial dilation and balloon dilation during percutaneous renal surgery in an animal model.

OBJECTIVES: To compare two commonly used methods of dilation, the Amplatz sequential fascial (ASF) and the balloon dilator, in a porcine model. METHODS: Fourteen kidneys from 9 female pigs were used for this experiment. One kidney of each pig underwent ASF dilation and the other underwent balloon dilation using the Nephromax balloon. This was achieved after percutaneous renal puncture with an 18-gauge needle under fluoroscopic guidance. The effects of both methods of dilation were assessed immediately in 1 pig, after 24 hours in 3 pigs, at 4 weeks in 4 pigs, and at 6 weeks in 1. The animals were killed, and the kidneys were removed for gross and histologic examination. RESULTS: Grossly, the ASF dilated tracts appeared rounded and the balloon dilated tracts appeared V-shaped with lateral fragmentation within 24 hours. No obvious gross differences were noted at 4 to 6 weeks between the two methods of dilation, with both appearing as fine scars. Histologically, minor differences were seen at 4 to 6 weeks, with slightly more abscesses and larger scar formation in the kidneys that underwent ASF dilation than in the balloon dilation group. CONCLUSIONS: In this porcine animal model, the degree of renal trauma induced by the ASF dilators and the balloon dilators during percutaneous renal surgery seems to be comparable. The acute and chronic renal parenchyma effects of both methods of tract dilation were almost similar. The choice of nephrostomy tract dilation should be by physician preference.

[A five-year experience in conformational radiotherapy in the treatment of prostate cancer. Evaluation of acute toxicity in 131 patients]. / Radiothérapie conformationnelle dans le traitement du cancer de la prostate. Evaluation de la toxicité aiguë chez 131 patients.

PURPOSE: To evaluate the urinary and rectal toxicity secondary to 3D conformal radiotherapy for prostate cancer. MATERIAL AND METHODS: Between 1998 and 2003, 131 men with prostate cancer underwent 3D conformal radiotherapy with or without androgen deprivation. The different stages were: 2 T1b ; 40 T1c; 19 T2a; 16 T2b; 18 T2c; 33 T3a; 1 T3b and 2 T3c with Gleason score: 4-6 = 47%, 7 = 36% and 8-9 in 17% of the cases. The median patient age was 66 (48-87). Pretreatment PSA level was respectively < 10 ng/ml (41%). 10-20 ng/ml (30%) and > 20 ng/ml (29%). Of the 131 patients, 98 received androgen ablation therapy before radiation. The total radiation dose varied between 66 and 74 Gy, delivered with 18MV photons of the linear accelerator, the median follow up was 33 months (5-67). RESULTS: According to the RTOG grading (gr) for acute toxicity, we noticed 3gr 3 genitourinary (GU) toxicity and no gr3 gastro intestinal (GI) toxicity. There were 36 gr 1 and 12 gr 2 GI toxicity, 41 gr 1 and 22 gr 2 GU toxicity. The mean prostate volume was 41 cc for patients who received androgen ablation and 56 cc for the others (p < 0.002). The percentage of volume receiving more than 50 Gy (V50) was calculated, the median V50 was 32% (5-67) for the rectum and 35% (5-79) for the bladder CONCLUSION: The toxicity profile in this study is in the same range than those of the literature and of our previous study concerning our first 50 patients with prostate cancer treated with 3D conformal radiotherapy.