Anastasios Karatzas

Percutaneous Nephrolithotomy Under a Multimodal Analgesia Regime

OBJECTIVES To evaluate the possibility of performing percutaneous nephrolithotomy (PCNL) under a multimodal analgesia regime. PATIENTS AND METHODS During a period of 3 years, 51 patients requiring PCNL were enrolled in the study. All patients received a multimodal analgesic regime that included paracetamol, a COX(2) inhibitor, epidural morphine, and infiltration of the surgical field with local anesthetics. Percutaneous renal tract access was created with ultrasound guidance. All patients were informed about the possibility of experiencing short periods of discomfort or pain, and all patients completed a visual analog pain scale questionnaire postoperatively. RESULTS All 51 patients completed the study, and the procedure was well tolerated. Intraoperative problems or postoperative complications were attributed mainly to the procedure itself (PCNL) rather than to the analgesic regimen administered. We observed no morphine-related side effects. Patients were transferred directly back to the ward immediately after the operation. The use of analgesics postoperatively was minimal. CONCLUSIONS The use of our multimodal analgesia regime is a well-tolerated and safe alternative to general or regional anesthesia for patients undergoing PCNL.

Systemic therapy of metastatic bladder cancer in the molecular era: current status and future promise.

Importance of the field: Platinum-based chemotherapy is considered the standard-of-care first-line therapy for metastatic bladder cancer. Despite the initial high response rate, the vast majority of patients eventually progress and succumb to their disease, urging the need for development of novel therapies. Areas covered in this review: This article discusses the main signaling pathways implicated in the pathogenesis of bladder carcinomas, reviews recently completed and ongoing clinical trials, and anticipates the future direction of molecularly targeted agents. What the reader will gain: This manuscript presents the current status of conventional chemotherapy in advanced bladder cancer, and provides a comprehensive review of molecular targeted agents currently in clinical development for this disease. Take home message: Improved understanding of the biology of urothelial carcinogenesis has paved the way for the development of novel molecularly targeted therapies, several of which are currently tested in clinical trials. In this regard, VEGF and EGFR pathways are emerging as important therapeutic targets for metastatic bladder cancer, either alone or in combination with conventional chemotherapeutics. Other therapies, including aurora kinase inhibitors, endothelin receptor antagonists, RAS/MAPK pathway inhibitors and novel immunologic strategies, may also prove helpful in the treatment of this disease.

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

BACKGROUND Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. PATIENTS AND METHODS 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. RESULTS No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P>0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7)+TA(6)/TA(6)) (P=0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P=0.55). CONCLUSION Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men.

A giant inguinoscrotal bladder hernia as a cause of chronic renal failure: A rare case

INTRODUCTION Giant inguinoscrotal bladder hernias are very rare and require surgical intervention. They usually do not cause any specific symptoms and thus, they are often misdiagnosed. If left untreated though, they might lead to severe medical conditions, such as renal failure. PRESENTATION OF CASE We present the case of a 71-year-old male patient suffering from a giant inguinoscrotal mass, accompanied by symptoms of the lower urinary track (LUTS) and chronic renal failure. DISCUSSION In our case, the patient presented with bladder hernia causing non specific symptoms of renal failure. In contrast to acute renal failure, a chronic renal impairment most often comes with no specific symptoms and thus, it can be present for many years before the diagnosis is made. It is evident that such serious conditions should be suspected and treated. CONCLUSION Inguinoscrotal bladder hernias may be associated with severe medical conditions, such as renal deterioration, and should be considered in the differential diagnosis of renal failure, when accompanied by any inguinal, scrotal, or low abdominal wall hernia.

Analgesia during Extracorporeal Shockwave Lithotripsy: Fentanyl Citrate versus Parecoxib Sodium

BACKGROUND AND PURPOSE Shockwave-induced pain may become an important issue during extracorporeal shockwave lithotripsy (SWL), although the new generation of lithotriptors generally produces less pain than previous models. The aim of the study was to compare the analgesic effect of a cyclooxygenase-2-specific inhibitor (parecoxib sodium) with that of our standard method of analgesia (fentanyl citrate) in patients who needed pain relief when undergoing SWL. PATIENTS AND METHODS Fifty-eight patients who were undergoing SWL for renal calculi were randomized to receive intravenously either fentanyl citrate (group A, n = 30) or parecoxib sodium (group B, n = 28) when they felt that their pain during the session became intolerable. Lithotripsy was recommenced 10 minutes after administration of analgesia. The severity of pain before and after administration of the analgesic regimens was evaluated using a five-level verbal scale. The effectiveness of each drug was evaluated with respect to degree of pain relief and ensuing tolerance of the procedure to completion, as well as the need for supplementary analgesia (half the standard dose of fentanyl citrate). RESULTS The patients in the two groups were comparable with regard to age, sex, body mass index, and stone size. There was no statistically significant difference in the maximum energy level achieved as well as in the total number of shock waves given in the two groups. Administration of fentanyl citrate resulted in alleviation of pain and completion of SWL in 27 patients (90%), whereas parecoxib sodium was effective in five patients (17.8%) (P < 0.01). The remaining 23 patients in group B received supplementary analgesia, and 22 completed the lithotripsy session. CONCLUSIONS Parecoxib sodium was not as effective as fentanyl citrate in alleviating pain during SWL. Its use, however, may lower the dose of opioid-based analgesia in this group of patients.

Molecular Pathogenesis of Non Muscle-Invasive Bladder Cancer: Implications for Novel Targeted Therapies

Approximately 70% to 80% of patients with urothelial carcinomas of the bladder are initially diagnosed with non-muscle invasive disease. Superficial, non-muscle invasive bladder cancers (NMIBCs) are managed with cystoscopic transurethral resection of all visible lesions followed by intravesical chemotherapy and/or immunotherapy. Despite this treatment, up to 70% of these tumors will recur within five years and 15% will ultimately progress to muscle-invasive disease, suggesting that novel therapeutic strategies are necessary. Recent studies have greatly advanced our understanding of urothelial carcinogenesis and have highlighted the distinct molecular pathogenesis of NMIBCs versus muscle-invasive bladder tumors. It is now clear that diverse genetic and epigenetic events are driving the oncogenesis of NMIBCs, thereby attesting to their potential as therapeutic targets for these tumors. This article reviews the molecular pathogenesis of NMIBCs, discusses recently completed and ongoing clinical trials and anticipates the future direction of molecular targeted agents in this disease.

Impact of Stapling Devices on Radical Cystectomy: Comparative Study Between Low- and High-Volume Surgeons

OBJECTIVES To compare effectiveness in terms of blood loss and operative time of stapling devices among surgeons with different levels of surgical volume. METHODS We evaluated a group of 29 male patients with invasive bladder cancer who underwent radical cystectomy by two groups of surgeons. The first group included two high-volume surgeons, and the second group two low-volume surgeons. All cystectomies were performed using the multifire autosuture articulated vascular Endo-GIA. We compared patients with a series of 28 patients who had undergone radical cystectomy during the same period using standard technique by the same surgeons. Blood loss was defined as the difference between the hemoglobin at the beginning and at the end of cystectomy. RESULTS In the group of high-volume surgeons, the mean operative time was 81.4 +/- 17 minutes and 79.3 +/- 20 minutes for the classical and stapler arm, respectively (P = 0.551). In the low-volume surgeons group, the mean operative time was 114.3 +/- 22 minutes and 92.4 +/- 12 minutes for the two methods (P = 0.003). The mean intraoperative blood loss in the experienced surgeons was 2.3 +/- 0.82 g/dL and 1.49 +/- 0.66 g/dL for the classical and stapler arm, respectively (P = 0.008). In the group of low-volume surgeons, the difference in hemoglobin was 3.02 +/- 0.84 g/dL and 1.91 +/- 0.6 g/dL for the two methods (P = 0.02). CONCLUSIONS Stapling devices seem to make cystectomy safer and faster in surgeons with different surgical volumes. The group of low-volume surgeons benefited more.

Previous Bladder Cancer History in Patients with High-Risk, Non–muscle-invasive Bladder Cancer Correlates with Recurrence and Progression: Implications of Natural History

Purpose The purpose of this study was to assess the correlation of previous bladder cancer history with the recurrence and progression of patients with high-risk non–muscle-invasive bladder cancer treated with adjuvant Bacillus Calmette–Guérin (BCG) and to evaluate their natural history. Materials and Methods Patients were divided into two groups based on the existence of previous bladder cancer (primary, non-primary). A logistic regression analysis was used to identify the possible differences in the probabilities of recurrence and progression with respect to tumor history, while potential differences due to gender, tumor size (> 3 cm, < 3 cm), stage (pTa, T1), concomitant carcinoma in situ (pTis) and number of tumors (single, multiple) were also assessed. Univariate and multivariate models were employed. In addition, Kaplan-Meier survival analysis was used to compare recurrence- and progression-free survival between the groups. Results A total of 192 patients were included (144 with primary and 48 with non-primary tumors). The rates of recurrence and progression for patients with primary tumors were 27.8% and 12.5%, respectively. The corresponding percentages for patients with non-primary tumors were 77.1% and 33.3%, respectively. The latter group of patients displayed significantly higher probabilities of recurrence (p=0.000; 95% confidence interval [CI], 4.067 to 18.804) and progression (p=0.002; 95% CI, 1.609 to 7.614) in a univariate logistic regression analysis. Previous bladder cancer history remained significant in the multivariate model accounting for history, age, gender, tumor size , number of tumors, stage and concomitant pTis (p=0.000; 95% CI, 4.367 to 21.924 and p=0.002; 95% CI, 1.611 to 8.182 for recurrence and progression respectively). Kaplan-Meier curves revealed that the non-primary group hadreduced progression- and recurrence-free survival. Conclusion Previous non–muscle-invasive bladder cancer history correlates significantly with recurrence and progression in patients with high-risk non-muscle-invasive disease treated with adjuvant BCG.

Is There a Role for Double J Stent Culture in Contemporary Urology

Introduction: To present the incidence of bacterial colonization on ureteral double J stents (DJS); isolate the uropathogens; define the rate of multi-resistant bacteria strains (MRBS) and present their clinical importance. Materials and Methods: The whole body of 105 DJSs was examined for the presence of uropathogens. Results: The main etiology for stent placement was lithiasis (57.1%). The most frequently cultured microorganisms were staphylococcus (28.6%). Forty-four stents hosted MRBS. 25 (23.8%), 10 (9.5%) and 8 (7.6%) of the patients were affected by malignancy, diabetes mellitus and chronic renal failure respectively. Apart from the female gender, none of the examined factors (age, duration of stenting and chronic diseases) was correlated with the colonization or the presence of MRBS. Eleven of the 61 stented patients (18%) who were operated upon developed a febrile urinary tract infections (UTI). In 7 of them the stent hosted MRBS (63.6%). After taking into consideration the sensitivity report, we altered our initial empirical antibacterial prophylaxis to targeted antibacterial treatment in the patients with MRBS with rapid remission of their infection and no urosepsis event. Conclusion: The knowledge of bacteriologic flora of DJS can be very helpful in an evidence-based prophylactic and therapeutic practice. Stent examination could be recommended in high-risk cases of developing UTI and sepsis after a urologic operation.

Do Calcium Supplements Predispose to Urolithiasis

Purpose of ReviewThe purpose of this study was to investigate the role of calcium supplements, with or without vitamin D, in urinary stone formation in healthy population and in osteoporotic patients as well. Moreover, this review aims to clarify whether or not, and above which dose, they are associated with the risk of lithiasis.Recent FindingsA research in Medline, Embase, and Scopus databases up to September 2015 was conducted using the following keywords: calcium, supplements, vitamin D, complications, lithiasis, and urinary stone. All types of studies were taken into account (cohort studies, reviews, meta-analyses), and in case they fulfilled the inclusion criteria, they were included in our review.The analysis of the data showed that calcium supplements, probably in association with anti osteoporotic treatment, do not create a predisposition towards lithiasis formation among women suffering from osteoporosis, neither among non-osteoporotic older men. In healthy postmenopausal as well as younger women, the supplements might increase susceptibility to urinary stone formation in long-term basis. The consumption of calcium supplements with the meals could play a protective role in women and younger males. There is certain evidence that supplements containing citrate may be more beneficial over the rest of calcium supplements, particularly when consumed during the meal.SummaryOsteoporotic women and healthy men are not at risk of stone formation. On the contrary, healthy women should be aware of the potential risk of developing urinary lithiasis in long-term basis.