Paul W Ladenson, M.D.

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0002745/paul-ladenson

Effects of Na and Ca on the generation and conduction of excitation in the ureter erectile dysfunction treatment implant video purchase sildenafil overnight delivery. Effect of sodium deficiency on the action potential of the smooth muscle of ureter erectile dysfunction pumps side effects buy discount sildenafil 50 mg on-line. Gene expressions and mechanical functions of 1 adrenoceptor subtypes in mouse ureter erectile dysfunction caused by lack of sleep order sildenafil 25 mg free shipping. Mechanical function and gene expression of 1 adrenoceptor subtypes in dog intravesical ureter erectile dysfunction doctors in texas purchase sildenafil 25 mg with amex. Effect of four different alpha (1)-adrenoceptor antagonists on alpha-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters erectile dysfunction age graph generic sildenafil 100 mg with mastercard. Changes in interstitial cell of Cajal­like cells density in congenital ureteropelvic junction obstruction. Characterization of beta-adrenergic receptor subtypes of the upper and lower renal pelvis in rabbits. A simple method for measurement of ureteric peristaltic function in vivo and the effects of drugs acting on ion channels applied from the ureter lumen in anesthetized rats. Stimulation of voltage-dependent contractions by calcium channel activator Bay K8644 in the human urinary tract in vitro. Involvement of Rho-kinase in the contractile mechanism of human ureteral smooth muscle. Dual capsaicin effects on ureteric motility: low dose inhibition mediated by calcitonin gene­related peptide and high dose stimulation by tachykinins Multiple tachykinins (neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea pig. Co-localization of tachykinins and calcitonin gene­related peptide in capsaicin-sensitive afferents in relation to motility effects on human ureter in vitro. Recovery curve and conduction of action potentials in the ureter of the guinea pig. Characteristics of transient outward currents in single smooth muscle cells from the ureter of the guinea pig. Localization of nitric oxide synthase and hemoxygenase and functional effects of nitric oxide and carbon monoxide in the pig and human intravesical ureter. The nitric oxide synthase/nitric oxide and heme oxygenase/carbon monoxide pathways in the human ureter. Evaluation of urothelial stretchinduced cyclooxygenase-2 expression in novel human cell culture and porcine in vivo ureteral obstruction models. N-398 (a selective cyclooxygenase-2 inhibitor) decreases agonist-induced contraction of the human ureter via calcium channel inhibition. Direct effects of vardenafil on the ureter: in vitro investigation and potential clinical applications of intraluminal administration. Receptor-mediated stimulation and inhibition of adenylate cyclases: the fat cell as a model system. Naftopidil and tolterodine in the medical expulsive therapy for intramural ureteral stones: a prospective randomized study. Tamsulosin for ureteral stones: a systematic review and meta-analysis of a randomized controlled trial. Activin A is an endogenous inhibitor of ureteric bud outgrowth from the wolffian duct. Nonadrenergic noncholinergic excitatory innervation of the guinea-pig renal pelvis. A pharmacological analysis of calcium channels involved in phasic and tonic responses of the guinea-pig ureter to high potassium. Effect of Bay K8644 and ryanodine on the refractory period, action potential and mechanical response of the guinea-pig ureter to electrical stimulation. Effect of cromakalim and glibenclamide on spontaneous and evoked motility of the guinea-pig isolated renal pelvis and ureter. Effect of indomethacin and deendothelisation on vascular responses in the renal artery. Relaxation of human ureteral smooth muscle in vitro by modulation of cyclic nucleotide-dependent pathways. The influence of potassium, sodium, and chloride on the membrane potential of the smooth muscle of taenia coli. The action potential in the smooth muscle of the guinea pig taenia coli and ureter studied by the double sucrose-gap method. The transcription factors Etv4 and Etv5 mediate formation of the ureteric bud tip domain during kidney development. Effects of artificial calculosis on rat ureter motility: peripheral contribution to the pain of ureteric colic. Spatial and temporal variations in pacemaking and conduction in the isolated renal pelvis. Identification of the major membrane currents in freshly dispersed single smooth muscle cells of guinea-pig ureter. The whole cell Ca2+ channel current in single smooth muscle cells of the guinea-pig ureter. Pyeloureteral motility and ureteral peristalsis: essential role of sensory nerves and endogenous prostaglandins. Modulators of internal Ca2+ stores and the spontaneous electrical and contractile activity of the guinea pig renal pelvis. Spontaneous electrical and Ca2+ signals in typical and atypical smooth muscle cells and interstitial cell of Cajal­like cells of mouse renal pelvis. Characterization of the spontaneous electrical and contractile activity of smooth muscle cells in the rat upper urinary tract. The effect of K channel blockers on the spontaneous electrical and contractile activity in the proximal renal pelvis of the guinea pig. Electrical characterization of interstitial cells of Cajal­like cells and smooth muscle cells isolated from the mouse ureteropelvic junction. Regional differences in the density and subtype specificity of endothelin receptors in rabbit urinary tract. Ureteral urine transport: changes in bolus volume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs. Effects of noradrenaline, isoproterenol, and acetylcholine on ureteral resistance. Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea pig. Structural changes of collagen components and diminution of nerves in congenital ureteropelvic junction obstruction. The dynamics of the renal pelvis and ureter with reference to congenital hydronephrosis. Selective cyclooxygenase-2 inhibitors reduce ureteral contraction in vivo: a better alternative for renal colic Experimental diabetes upregulates the expression of ureteral endothelin receptors. The role of protein kinase C in cell surface signal transduction and tumor production. Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction. I: Studies of denervated ureter with particular reference to ureteroureteral anastomosis. Longitudinal and thickness measurement of the normal distal and intravesical ureter in human fetuses. The intravesical ureter in children with vesicoureteral reflux-a morphological and immunohistochemical characterization. Activation of tracheal smooth muscle contraction: synergism between Ca2+ and activators of protein kinase C. Excitatory motor and electrical effects produced by tachykinins in the human and guinea-pig isolated ureter and guinea-pig renal pelvis. Identification of c-kit positive cells in the mouse ureter: the interstitial cells of Cajal of the urinary tract. The motor effect of the capsaicinsensitive inhibitory innervation of the rat ureter. Tachykinins and calcitonin gene­related peptides as co-transmitters in local motor responses produced by sensory activation in the guinea pig isolated renal pelvis. Degradation of different molecular species of phosphatidylinositol in thrombin-stimulated human platelets. Valves of the ureter as a cause of primary obstruction of the ureter: anatomic, embryologic, and clinical aspects. Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Cajal-like cells in the upper urinary tract: comparative study in various species. Effects of isoproterenol and butylscopolamine on the friction between an artificial stone and the intra ureteral wall in anesthetized rabbits. Angiotensin induces the urinary peristaltic machinery during the perinatal period. Function and distribution of autonomic receptors in canine ureteral smooth muscle. Initiation and propagation of stimulus from the renal pelvic pacemaker in pig kidney. Characterization of adrenoceptor subtypes involved in regulation of ureteral fluid transport. Obstruction and normal re-canalization of the ureter in the human embryo, its relation to congenital ureteric obstruction. Glial cell-line derived neurotrophic factor is required for bud initiation from ureteric epithelium. Comparison of the effects of nifedipine on ureter and coronary artery isolated from the dog. Comparative effects of diltiazem and glycerol trinitrate on isolated ureter and coronary artery of the dog. Chemosensitivity of nociceptive, mechanosensitive afferent nerve fibres in the guinea-pig ureter. Capsaicin treatment induces selective sensory degeneration and increased sympathetic innervation in the rat ureter. Substance P and calcitonin gene­ related peptide in the ureter of chicken and guinea-pig: distribution, binding sites and possible functions. Modulation by stereoselective inhibition of cyclooxygenase of electromechanical coupling in the guinea-pig isolated renal pelvis. Effect of 18beta-glycyrrhetinic acid on electromechanical coupling in the guinea-pig renal pelvis and ureter. Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction. Expression level and role in ureteral contraction of alpha 1-adrenoceptor subtypes in human ureter. Characterization of 1 adrenoceptor subtypes mediating contraction in human isolated ureters. Intrapelvic pressure and renal function studies in experimental chronic partial ureteric obstruction. Loss of interstitial cells of Cajal and gap junction protein connexin 43 at the vesicoureteral junction in children with vesicoureteral reflux. Rho-kinase inhibition and electromechanical coupling in rat and guinea-pig ureter smooth muscle: Ca2+dependent and -independent mechanisms. The in vivo effects of histamine and Benadryl on the peristalsis of the canine ureter and plasma potassium levels. Matrix metalloproteinases and their inhibitors regulate in vitro ureteric bud branching morphogenesis. Defective in vitro contractility of ureteropelvic junction in children with functional and obstructive urine flow impairment. Corticosteroids and tamsulosin in the medical expulsive therapy of symptomatic distal ureter stones: single drug or association Distribution and functional effects of neuropeptide Y on equine ureteral smooth muscle and resistance arteries. Histochemical and functional evidence for a cholinergic innervation of the equine ureter. Untersuchungen uber die Einwirkung von Bakterientoxinen auf der uberlebenden Meerschweinchenureter. Embryology and anatomy of the vesicoureteric junction with special reference to the etiology of vesicoureteral reflux. An in vitro study of human ureteric smooth muscle with the alpha1-adrenoceptor subtype blocker. Attempts at altering ureteral activity in the unanesthetized, conditioned dog with commonly employed drugs. Role of tamsulosin in treatment of patients with Steinstrasse developing after extracorporeal shock wave lithotripsy. Ureteric pressure variations at different flow rates and varying bladder pressures in normal dogs. Mediation of contraction and relaxation by alpha- and beta-adrenoceptors in the ureterovesical junction of the sheep. The effect of adrenergic and cholinergic agents and their blockers upon ureteral activity. Dynamics of the upper urinary tract: effects of changes in bladder pressure on ureteral peristalsis. Ureteric bud outgrowth in response to ret activation is mediated by phosphatidylinositol 3-kinase. The effect of ureteral distension on peristalsis: studies on human and sheep ureters. Preliminary observations on the mechanical and electrical activity of the rat ureter.

Prognostic relevance of tumour size in T3a renal cell carcinoma: a multicentre experience erectile dysfunction causes heart disease discount sildenafil generic. Active treatment of localized renal tumors may not impact overall survival in patients aged 75 or older erectile dysfunction treatment uk buy cheap sildenafil 100 mg online. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease erectile dysfunction age 27 order sildenafil 50 mg with mastercard. Limited warm ischemia during elective partial nephrectomy has only a marginal impact on renal functional outcomes impotence what does it mean buy sildenafil american express. Differential use of partial nephrectomy for intermediate and high complexity tumors may explain variability in reported utilization rates erectile dysfunction in the morning order sildenafil in india. Differential expression in clear cell renal cell carcinoma identified by gene expression profiling. Renal function assessment in the era of chronic kidney disease: renewed emphasis on renal function centered patient care. Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: assessment of 241 patients with > 15-year follow-up. Association of abnormal preoperative laboratory values with survival after radical nephrectomy for clinically confined clear cell renal cell carcinoma. Therapy and outcome of small cell carcinoma of the kidney: report of two cases and a systematic review of the literature. Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases. Renal cell carcinoma clinically involving adjacent organs: experience with aggressive surgical management. Analysis of clinicopathologic predictors of oncologic outcome provides insight into the natural history of surgically managed papillary renal cell carcinoma. Growth kinetics of renal masses: analysis of a prospective cohort of patients undergoing active surveillance. Parathyroid hormone-related protein is an essential growth factor for human clear cell renal carcinoma and a target for the von Hippel-Lindau tumor suppressor gene. Use of the spontaneous Tsc2 knockout (eker) rat model of hereditary renal cell carcinoma for the study of renal carcinogens. Long-term followup of patients with renal cell carcinoma treated with radio frequency ablation with curative intent. Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer specific survival for patients with pT3 renal cell carcinoma-can the 2002 primary tumor classification be improved A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. Primary osteogenic sarcoma of the kidney-a case report and review of the literature. Outcomes of small renal mass needle core biopsy, nondiagnostic percutaneous biopsy, and the role of repeat biopsy. Stage specific guidelines for surveillance after radical nephrectomy for local renal cell carcinoma. Safety and efficacy of mini-margin nephronsparing surgery for renal cell carcinoma 4-cm or less. Long-term results of resection of renal cell cancer with extension into inferior vena cava. The genetic basis of kidney cancer: implications for management and use of targeted therapeutic approaches. Zoledronic acid delays the onset of skeletalrelated events and progression of skeletal disease in patients with advanced renal cell carcinoma. Repeat partial nephrectomy on the solitary kidney: surgical, functional and oncological outcomes. Comparison of standardized and nonstandardized nuclear grade of renal cell carcinoma to predict outcome among 2,042 patients. A review of prognostic pathologic features and algorithms for patients treated surgically for renal cell carcinoma. Systematic review of oncological outcomes following surgical management of localised renal cancer. Analysis of repeat nephron sparing surgery as a treatment option in patients with a solid mass in a renal remnant. Fuhrman grade has no added value in prediction of mortality after partial or radical nephrectomy for chromophobe renal cell carcinoma patients. Contemporary clinical epidemiology of renal cell carcinoma: insight from a population based case-control study. Active chemotherapy for collecting duct carcinoma of the kidney: a case report and review of the literature. Parenchymal volume preservation and ischemia during partial nephrectomy: functional and volumetric analysis. Prognostic significance of tumor thrombus level in patients with renal cell carcinoma and venous tumor thrombus extension. Sarcomatoid-variant renal cell carcinoma: treatment outcome and survival in advanced disease. Kidney preserving surgery in renal cell tumors: indications, techniques and results in 152 patients. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. Axitinib versus sorafenib as secondline treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Comparative analysis of minimally invasive partial nephrectomy techniques in the treatment of localized renal tumors. A prospective study of laparoscopic radical nephrectomy for T1 tumors-is transperitoneal, retroperitoneal or hand assisted the best approach Chromophobe renal cell carcinoma: clinical, pathological and molecular biological aspects. Simplified perfusion strategy for removing retroperitoneal tumors with extensive cavoatrial involvement. Population based analysis of the increasing incidence of kidney cancer in the United States: evaluation of age specific trends from 1975 to 2006. Effect of renal cancer size on the prevalence of metastasis at diagnosis and mortality. Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi. Effect of angiotensin-converting enzyme inhibition on nephropathy in patients with a remnant kidney. Long-term followup after nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease. Expression of nm23-H1 gene product in sarcomatous cancer cells of renal cell carcinoma: correlation with tumor stage and expression of matrix metalloproteinase-2, matrix metalloproteinase-9, sialyl Lewis X, and c-erbB-2. Unexplained spontaneous regression and alpha-interferon as treatment for metastatic renal carcinoma. Primary bilateral T-cell renal lymphoma presenting with sudden loss of renal function. Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer. Survival analysis of 130 patients with papillary renal cell carcinoma: prognostic utility of type 1 and type 2 subclassification. Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. Renal vein or inferior vena caval extension in patients with renal cortical tumors: impact of tumor histology. Renal manifestations of tuberous sclerosis complex: incidence, prognosis, and predictive factors. Subclassification of renal cell neoplasms: an update for the practising pathologist. Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer. New strategies in kidney cancer: therapeutic advances through understanding the molecular basis of response and resistance. The effect of sunitinib on primary renal cell carcinoma and facilitation of subsequent surgery. Percutaneous radio frequency ablation of renal tumors in patients with von Hippel-Lindau disease: preliminary results. Expression of insulin-like growth factor I receptor and survival in patients with clear cell renal cell carcinoma. High expression levels of surviving protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma. Development and evaluation of BioScore: a biomarker panel to enhance prognostic algorithms for clear cell renal cell carcinoma. Symptoms as well as tumor size provide prognostic information on patients with localized renal tumors. Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. Adrenal sparing surgery during radical nephrectomy in patients with renal cell cancer: a new algorithm. Renal cell carcinoma presenting with paraneoplastic hypercalcemic coma: a case report and review of the literature. Laparoscopic versus open partial nephrectomy for the treatment of pathological T1N0M0 renal cell carcinoma: a 5-year survival rate [see comment]. Positive surgical parenchymal margin after laparoscopic partial nephrectomy for renal cell carcinoma: oncological outcomes. Five new cases of juvenile renal cell carcinoma with translocations involving Xp11. Genetic basis for kidney cancer: opportunity for disease-specific approaches to therapy. Collecting duct carcinoma of the kidney: are imaging findings suggestive of the diagnosis Bellini duct carcinoma: further evidence for this rare variant of renal cell carcinoma. The medical and oncological rationale for partial nephrectomy for the treatment of T1 renal cortical tumors. Percutaneous biopsy of renal masses: sensitivity and negative predictive value stratified by clinical setting and size of masses. Percutaneous radiofrequency ablation versus percutaneous cryoablation: long-term outcomes following ablation for renal cell carcinoma. A renal mass in the setting of a nonrenal malignancy: when is a renal tumor biopsy appropriate Young age is an independent prognostic factor for survival of sporadic renal cell carcinoma. A new protocol for the followup of renal cell carcinoma based on pathological stage. Ipsilateral adrenal involvement from renal cell carcinoma: retrospective study of the predictive value of computed tomography. Outcome of surgical treatment of isolated local recurrence after radical nephrectomy for renal cell carcinoma. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy. Population-based study of renal cell carcinoma in children in Germany, 1980-2005: more frequently localized tumors and underlying disorders compared with adult counterparts. Laparoscopic partial nephrectomy with segmental renal artery clamping: technique and clinical outcomes. Sarcomatoid renal cell carcinoma: a comprehensive review of the biology and current treatment strategies. Overall survival advantage with partial nephrectomy: a bias of observational data Intraoperative thrombus embolization during nephrectomy and tumor thrombectomy: critical analysis of the University of California-Los Angeles experience. Eastern Cooperative Oncology Group performance status predicts bone metastasis in patients presenting with renal cell carcinoma: implication for preoperative bone scans. Effect of parenchymal volume preservation on kidney function after partial nephrectomy. Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma. Preoperative embolization of retroperitoneal hemangiopericytomas as an aid in their removal. Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava. Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma. Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion. Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy.

This pain is typically dull and believed to be secondary to a gradual onset of obstruction and hydronephrotic distention erectile dysfunction treatment supplements order 50 mg sildenafil overnight delivery. In some patients erectile dysfunction normal age buy sildenafil toronto, pain can be acute and can mimic renal colic erectile dysfunction causes of buy 50 mg sildenafil free shipping, typically ascribed to the passage of clots that acutely obstruct the collecting system erectile dysfunction injections side effects buy line sildenafil. These common symptoms of localized disease (hematuria erectile dysfunction drugs canada order sildenafil toronto, dysuria) and of advanced upper tract tumors (weight loss, fatigue, anemia, bone pain) are similar in type and frequency to those of bladder cancer. However, flank pain caused by obstruction by tumor or clot is more prevalent in upper tract tumors, having been reported in 10% to 40% of cases (Babaian and Johnson, 1980; McCarron et al, 1983; Richie, 1988; Williams, 1991; Melamed and Reuter; 1993). About 15% of patients are asymptomatic at presentation and are diagnosed when an incidental lesion is found on radiologic evaluation. Patients may also have symptoms of advanced disease, including flank or abdominal mass, weight loss, anorexia, and bone pain. RadiologicEvaluation Although intravenous pyelography has been the traditional means for diagnosis of upper tract lesions, this has been supplanted by computed tomographic urography. It also has a higher degree of accuracy in determining the presence of renal parenchymal lesions. Radiolucent filling defects, obstruction or incomplete filling of a part of the upper tract, and nonvisualization of the collecting system are the typical findings suggestive of an upper urinary tract tumor. Identification of filling defects, which account for 50% to 75% of cases, typically requires the intravenous administration of contrast material (Murphy et al, 1981; Fein and McClennan; 1986). The differential diagnosis of these defects includes blood clot, stones, overlying bowel gas, external compression, sloughed papilla, and fungus ball. The impact of hydronephrosis and nonvisualization for renal pelvis tumors versus ureteral tumors as indicators of a higher stage is uncertain. Nonvisualization is reported in 20% of renal pelvis tumors, only 33% of which are invasive (McCarron et al, 1983). Nonvisualization is reported in 37% to 45% of ureteral tumors and carried a 60% risk of invasion in one series (McCarron et al, 1983). In other reports there is no correlation of nonvisualization and stage (Batata and Grabstald, 1976; Anderstrom et al, 1989). Hydronephrosis with or without an associated filling defect is linked with invasion in 80% of ureteral tumors (McCarron et al, 1983; Cho et al, 2007). Radiolucent, noncalcified lesions may require additional evaluation by retrograde urography or ureteroscopy, with or without biopsy and cytology. Overall, retrograde urography has an accuracy of 75% in diagnosis of an upper tract malignant neoplasm (Murphy et al, 1981). An incompletely filled or obstructed renal infundibulum or calyx, occurring in 10% to 30% of cases, again typically requires retrograde urography or ureteroscopy to confirm the diagnosis. Evaluation of the contralateral kidney is important not only because of possible bilaterality of the disease but also because it allows a determination of the functionality of the contralateral kidney. Some have suggested that ultrasonography has sensitivity equal to that of urography in evaluating patients with painless gross hematuria for upper tract malignant disease (Yip et al, 1999; Data et al, 2002). Cystoscopy Because upper urinary tract tumors are often associated with bladder cancers, cystoscopy is mandatory in the evaluation to exclude coexistent bladder lesions. Although pyelovenous and pyelolymphatic migration has been reported with ureteroscopy, this phenomenon appears to be uncommon and should not preclude its use (Lim et al, 1993). As with bladder tumors, 55% to 75% of ureteral tumors are low grade and low stage (Cummings, 1980; Richie, 1988; Williams, 1991). Also, like bladder cancers, approximately 85% of renal pelvic tumors are papillary and the remainder sessile. Invasion of the lamina propria or muscle (stage T1 or T2) occurs in 50% of papillary and in more than 80% of sessile tumors. Overall, 50% to 60% of renal pelvic tumors are invasive into either the lamina propria or muscle. In ureteral tumors, invasion is also more common than in bladder tumors (Anderstrom et al, 1989; Williams, 1991). In addition to visualization of the tumor, ureteroscopy allows more accurate biopsy of suspected areas, with either biopsy forceps or brushing. Despite reports of changes in grade or stage from diagnostic biopsy (Smith et al, 2011) to subsequent resection, reasonable histologic correlation (78% to 92%) between the ureteroscopic biopsy specimen and the final pathologic specimen has been established (Keeley et al, 1997c; Guarnizo et al, 2000; Brown et al, 2007). It appears that fresh samples obtained ureteroscopically provide the best chance of predicting eventual pathologic findings. In one study, a cell block from biopsy specimens was prepared when a visible tumor was present, and grades of ureteroscopic biopsy specimens were compared with grades and stages of surgical specimens in 42 cases. Of 30 low- or moderate-grade specimens, 27 (90%) proved to be low- or moderate-grade urothelial carcinoma; 11 of 12 high-grade specimens (92%) proved to be high-grade urothelial cancer, and 8 (67%) were invasive (T2 or T3) (Keeley et al, 1997c). Because of the small size and shallow depth of ureteroscopic biopsy specimens, a precise correlation with eventual tumor stage is difficult. Therefore, in predicting the tumor stage, a combination of the radiographic studies, the visualized appearance of the tumor, and the tumor grade provides the surgeon with the best estimation for risk stratification. Although, as stated earlier, grading of the tumors may be fairly accurate, staging is much more problematic. Of 40 urothelial tumors staged in one series (40% in the renal pelvis, 20% in the proximal ureter, and 40% in the distal ureter), ureteroscopic grade matched surgical grade in 78% of cases and was less than surgical grade in the remaining 22%. Lamina propria was present in 68% of biopsy specimens (62% of cup biopsies and 100% of loop biopsies), but tumors thought to be Ta were upstaged to T1 to T3 in 45% of cases at the time of complete resection of the lesion (Guarnizo et al, 2000). Therefore, accurate tumor grading on ureteroscopic biopsy may help in estimating tumor stage. In one series, a biopsy specimen showing grade 3 tumor accurately predicted tumor stage in more than 90% of cases (Skolarikos et al, 2003). Is ureteroscopy (with or without biopsy) necessary in all cases of suspected upper tract tumors In fact, ureteroscopy should probably be reserved for situations in which the diagnosis remains in question after conventional radiographic studies and for those patients in whom the treatment plan may be modified on the basis of the ureteroscopic findings, for example, endoscopic resection. Although there is no evidence that ureteroscopy diminishes the prognosis of a patient destined to proceed to nephroureterectomy, and although the risks of tumor seeding, extravasation, and dissemination are low in experienced hands, these risks are real and should preclude ureteroscopy when it is unnecessary (Hendin et al, 1999). AntegradeEndoscopy In some cases of upper tract tumors, percutaneous access to the renal pelvis may be required for diagnosis or treatment. In such cases, antegrade urography and ureteroscopy may be useful for tumor resection, biopsy, or simple visualization. Larger-caliber scopes that can be passed into the renal pelvis in this manner may be particularly helpful in resecting or debulking larger volumes of tumor in this area (Streem et al, 1986; Blute et al, 1989). One must remember, however, that tumor cell implantation in the retroperitoneum and along the nephrostomy tube tract has been reported after these procedures (Tomera et al, 1982; Huang et al, 1995). In general, the sensitivity of voided urine (or bladder wash) cytology is directly related to tumor grade. Overall accuracy estimates of the sensitivity of cytology have ranged from about 20% for grade 1 tumors to 45% and 75% for grade 2 and grade 3 tumors, respectively (Murphy and Soloway, 1982; Konety and Getzenberg, 2001). Even if a voided cytology specimen is abnormal in a patient with an upper tract filling defect, one must be cautious in determining the site of origin of the malignant cells. Ureteral catheterization for collection of urine or washings may provide more accurate cytologic results. However, even in this setting, a substantial false-negative or false-positive result (22% to 35%) can be expected (Zincke et al, 1976). It would appear that saline washing provides a better cell yield and improves cytologic results secondary to the release by hydroscopic forces of loosely adherent cells from the urothelium. Still better accuracy can be achieved by brush biopsy through a retrograde catheter or ureteroscope. Sensitivity in the 90% range with specificity approaching 90% may be possible with these techniques (Streem et al, 1986, Blute et al, 1989). Brush biopsies have, however, also been reported to result in severe complications, including massive hemorrhage and perforation of the urinary tract with extravasation (Blute et al, 1981). It appears that the exposure of urothelial cells to ionic, highosmolar contrast agents as in retrograde pyelography may worsen cytologic abnormalities. Thus, it is probably prudent to obtain cytologic specimens before the use of these agents (Terris, 2004). The histologic characteristics and biology of upper tract tumors still affect treatment decisions, technologic improvements notwithstanding. The entity of benign papilloma, which responds favorably regardless of the extent of treatment, is well described in older series of upper tract tumors (Bloom et al, 1970; Batata and Grabstald, 1976). N0 No regional lymph node metastases N1 Metastasis to a single lymph node, 2 cm or less in greatest dimension. N2 Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. It is unclear whether the differences between upper tract papillomas and bladder papillomas are biologic or semantic. Approximately 85% of renal pelvis tumors are papillary; the remainder are sessile. However, the stage of upper tract tumors is T1 or T2 in approximately 50% of papillary and 80% of sessile lesions, respectively (Cummings, 1980; Richie, 1988; Williams, 1991). Thus, 50% to 60% of renal pelvis tumors are invasive, in contrast to most bladder tumors, which are noninvasive; 55% to 75% of ureteral tumors are low grade and low stage, but invasion is still more common than among bladder tumors (Anderstrom et al, 1989; Williams, 1991). Patients with upper urinary tract tumors are most often in the sixth or seventh decade of life on presentation and thus are usually older than patients with bladder tumors (Melamed and Reuter, 1993). Tumors of the renal pelvis are slightly more common than ureteral tumors (Batata and Grabstald, 1976; Richie, 1988; MaulardDurdux et al, 1996). Ureteral tumors occur in the distal, middle, and proximal segments in 70%, 25%, and 5% of cases, respectively (Babaian and Johnson, 1980; Anderstrom et al, 1989; Williams, 1991; Messing and Catalona, 1998). After conservative treatment, ipsilateral upper tract tumor recurrence is common in a proximal-to-distal direction and is seen in 33% to 55% of patients (Mazeman, 1976; Johnson and Babaian, 1979; Babaian and Johnson, 1980; Cummings, 1980; McCarron et al, 1983). This high rate of ipsilateral recurrence results in part from a multifocal field change, which is even more pronounced than in bladder cancer. Molecular techniques demonstrate that downward seeding of tumor accounts for some recurrences (Harris and Neal, 1992). In a review of all 768 cases of upper tract tumor reported in western Sweden from 1971 to 1998, the rate of metachronous bilateral tumors was 3. The occurrence of bladder tumors after upper tract tumors, and vice versa, is another expression of the field change, multifocal risk that affects initial treatment decisions. The incidence of upper tract tumor after bladder tumor is 2% to 4% with a mean time to occurrence of 70 months (Shinka et al, 1988; Oldbring et al, 1989; Melamed and Reuter, 1993; Herr et al, 1996). Upper tract tumors are reported in 3% to 9% of patients after cystectomy for bladder cancer in older series (Zincke and Neves, 1984; Mufti et al, 1988). Three particular forms of upper tract urothelial tumors, two associated with environmental exposure (aristolochic acid nephropathy, which includes Balkan and Chinese herbal nephropathy, as well as those seen in arsenic-endemic regions), analgesic abuse, and those associated with Lynch syndrome, have an even higher tendency to multiple and bilateral recurrences than do sporadic tumors (Markovic, 1972; Petkovic, 1975; Mahoney et al, 1977; Johansson and Wahlquist, 1979; Melamed and Reuter, 1993; Stewart et al, 1999; Tan et al, 2008; Hubosky et al, 2013). The typically low-grade nature of the tumors and the frequent renal insufficiency seen in Balkan nephropathy underscore the importance of conservative treatment when possible. The degree of scarring of renal papillae seen in phenacetin abuse correlates in a dose-dependent manner with the risk of high tumor grade and progression. Calcification of renal papillae after analgesic abuse is associated with development of squamous carcinoma of the renal pelvis (Stewart et al, 1999). Extranodal extension in patients with nodal involvement appears to predict clinical outcomes (Fajkovic et al, 2012). Tumor grading has also been divided into low grade and high grade (Epstein et al, 1998). Papillomas and papillary urothelial neoplasms of low malignant potential are also described. Certainly, tumors of high grade are more likely to invade into the underlying connective tissue, muscle, and surrounding tissues. Upper tract tumors spread in the same ways as bladder tumors do, through lymphatic and hematogenous routes and by direct extension into contiguous structures, and most metastatic recurrences develop in the first 2 to 3 years after surgery (Brown et al, 2006). The common metastatic sites are the lungs, liver, bones, and regional lymph nodes. The thin muscle layer of the renal pelvis and ureter may allow earlier penetration of invasive upper tract tumors than is seen in bladder neoplasms (Cummings, 1980; Richie, 1988). The renal parenchyma may be a barrier, slowing distant spread of stage T3 renal pelvis tumors. In contrast, periureteral tumor extension carries a high risk of early tumor dissemination along the periureteral vascular and lymphatic supply. Improved survival of patients with stage T3 renal pelvis tumors versus ureteral tumors has been reported by several investigators (Batata and Grabstald, 1976; Guinan et al, 1992a; Park et al, 2004). Guinan and colleagues (1992a) confirmed this observation among 611 patients treated at 97 hospitals and in a collection of 250 cases reported in the literature. The 5-year survival rates for patients with stage T3 tumors of the renal pelvis and ureter were 54% and 24%, respectively. In a multivariate analysis, patients with ureteral tumors had a higher local and distant failure rate than did those with renal pelvis tumors of the same stage and grade (Park et al, 2004). Some have proposed subclassification of renal pelvis tumors into pT3a for infiltration of the renal parenchyma and pT3b for invasion of peripelvic adipose tissue, because the patients with pT3b have an increased risk of recurrence (Roscigno et al, 2012). Renal pelvis and upper ureteral tumors spread initially from hilar to para-aortic and paracaval nodes, whereas distal ureteral tumors spread to pelvic nodes (Batata et al, 1975; Heney et al, 1981; Nocks et al, 1982; Mahadevia et al, 1983; McCarron et al, 1983; Jitsukawa et al, 1985; Geiger et al, 1986). There remains disagreement as to whether the location of an upper tract tumor affects prognosis. Some have argued that when renal pelvic and ureteral tumors are matched for stage, there is no significant difference in prognosis (Hall et al, 1998b; Isbarn et al, 2009). Other studies have suggested that renal pelvic tumors have a better prognosis than ureteral cancers, even when adjusted for stage (Park et al, 2004; Ouzzane et al, 2011a). Tumor Architecture Papillary tumors seem to have better outcomes than sessile lesions (Remzi et al, 2009; Fritsche et al, 2012).

McCullough (1989) anecdotally reported that postural drainage may assist in the elimination of retained fragments from dependent calyces impotence curse order sildenafil 25 mg with amex. Brownlee and associates (1990) subsequently treated patients with residual lower pole fragments with controlled inversion therapy erectile dysfunction questions and answers order sildenafil with mastercard, using intravenous hydration impotence homeopathy treatment generic sildenafil 50 mg on line, inversion erectile dysfunction treatment time buy sildenafil 25 mg online, and percussion erectile dysfunction treatment jaipur 50 mg sildenafil buy amex. They reported that 40% of patients with residual lower pole fragments treated with this regimen became stone free compared with 3% in the observation group; the observation group was then treated with this regimen as part of a crossover design, and 43% were rendered stone free. More recently, pharmacotherapy with potassium citrate and thiazide diuretics has been described (Soygur et al, 2002; ArrabalMartin et al, 2006). However, at this point in time none of these techniques has gained widespread acceptance. Treatment success was defined as stone-free or residual fragments less than 3 mm, and patients with acute infundibulopelvic angles (<30 degrees) were excluded. Smaller ureteroscopes with improved tip deflection and better stone manipulation instruments aid in accessing and fragmenting lower pole stones. Nitinol stone baskets have been used to reposition stones from the lower pole to more optimal intrarenal positions for lithotripsy, such as the middle or upper pole calyces (Kourambas et al, 2000). Stonefree rates approaching and exceeding 90% have been reported when stones were repositioned out of the lower pole, compared with stone-free rates closer to 80% when stones were fragmented in situ within the lower pole (Kourambas et al, 2000; Schuster et al, 2002). It is the interplay of these factors and the familiarity of the urologist with each surgical technique that ultimately determine the best treatment modality for a given patient. At that point, depending on the size of the stone relative to the ureter throughout its course, the stone will begin to obstruct the kidney. The first manifestation of this is an increase in the intra­collecting system pressure, which will stretch the renal pelvis, calyces, and renal capsule. This increase in intraluminal pressure will increase the hydrostatic pressure exerted on the walls of the renal pelvis and ureter, which can cause the failure of normal peristalsis. Pressure will subsequently decrease to the levels that were present before obstruction developed, usually within 12 to 24 hours. Accordingly, the renal colic episode caused by a stone is often limited to severe pain from the acute renal stretch, followed by gradual resolution of the pain. Open ureteral stone surgery is rarely performed when access to minimally invasive modalities exists and is often reserved for instances in which less invasive options have failed. Key to the passage of a stone is ureteral peristalsis, not hydrostatic pressure (Lennon et al, 1997). When the ureter is not otherwise obstructed, the chief determinant of stone passage is the diameter of the stone in its transverse orientation (Ueno et al, 1977). Next most important is the location of the stone within the ureter at presentation, with a review of the literature demonstrating a 71% chance of passage of a distal ureteral stone versus 22% for proximal stones (Morse and Resnick, 1991). Additional evidence supports the idea that the likelihood of spontaneous passage may be directly related to stone location at the time of presentation (Hubner et al, 1993; Coll et al, 2002). Thus, leukocytosis in these patients may or may not represent an actual infection. The chief determinant of the optimal treatment for calculi in these locations is size. As previously mentioned, those which are more proximal and greater in size are significantly less likely to pass spontaneously. For stones that do not move in a reasonable time frame, or in the setting of recurring severe pain, or if the patient prefers, surgical therapy is indicated. For stones larger than 1 cm, rates of complete stone clearance drop in both groups, to 68% for proximal and 76% for mid-ureter stones. Calculi 1 cm or smaller again demonstrated higher success rates in both groups than did larger stones. A further breakdown of selected studies assessing stone-free rates after ureteroscopy for proximal ureteral stones is shown in Table 53-3. It is interesting to note that the likelihood of postoperative results requiring additional procedures was 1. PretreatmentAssessment the pretreatment assessment, including medical history, imaging, and laboratory testing, for ureteral stones is similar to that for renal stones, and the reader is directed to the previous section on this topic in the renal calculi section of this chapter. Particular attention should be directed toward the duration of symptoms, given the fact that long-term obstruction can result in irreversible nephron loss. Any suggestion of fever in the setting of a ureteral stone strongly suggests the presence of infection proximal to the point of obstruction, and, regardless of how the patient appears at presentation, there should be a low threshold to proceed with urgent or immediate urinary tract drainage. Depending on the exact location within the ureter and calyx for percutaneous entry, such stones may be amenable to either rigid or flexible endoscopy. The opportunity to clear stone fragments using the access tract may offer optimal success for these challenging stones. Lastly, laparoscopic and robotic ureterolithotomy have been described for proximal and mid-ureteral calculi, with success rates for stone clearance in selected cases of 93% to 100% (Hemal et al, 2010; Yasui et al, 2013). It is important to note that stones in a mid-ureteral location are typically handled in much the same way as proximal calculi, although some considerations relative to the pelvic anatomy will apply. In addition, proximal migration of these stones can sometimes present a challenge with semirigid instrumentation. When considering stones 1 cm or smaller, an overall success rate of 86% was noted, whereas stones larger than 1 cm yielded a success rate of 74% (Preminger et al, 2007). A further breakdown of selected studies assessing stone-free rates after ureteroscopy for distal ureteral stones is shown in Table 53-4. Treatment by Stone Composition As discussed earlier with respect to renal calculi, stone composition, if known or able to be predicted radiologically, can be useful in selecting the most appropriate therapy. Therefore, where possible to obtain prior stone composition data or prediction of composition based on radiologic studies, this should be undertaken so as to best inform the patient regarding choices of therapy. It should be clear that it is imperative to tailor therapy choices to the individual patient, after careful discussion of outcomes of treatment: success rates, adjunctive procedures, and treatmentrelated morbidity. Both patient factors (body habitus, coagulation status, medical comorbidities) and stone factors (location, burden, composition) must be considered when selecting the optimal treatment for ureteral calculi. Guidance as to ideal management is limited, as only case reports or small series have been reported in adults. Duplicated Collecting System Duplication anomalies of the collecting system arise from ureteral bud abnormalities during gestation, occurring with an incidence of approximately 0. This principle explains that in complete duplications, separate ureters enter the bladder with the more medial and inferior orifice draining the upper pole while the more lateral and superior orifice drains the lower pole. In incomplete duplications, there is only one ureteral orifice on that side within the bladder, with a variable level of bifurcation of the separate ureters which lead to the upper and lower moieties. In the setting of a complete duplication, retrograde pyelography should be performed for each orifice to confirm which ureter contains the stone to be treated, and then treatment proceeds as usual. In partial duplications, retrograde pyelography should be performed to locate the level of bifurcation in addition to the stone, with recognition of the fact that an intramural ureter location of the division of the two systems is most common (Rich, 1988). This can potentially inhibit visualization if the retrograde catheter is past the point of bifurcation. In this situation, ureteroscopy, following dilation of the ureteral orifice when necessary, can be used to directly inspect for the other moiety of the second ureter. In such cases, simultaneous stenting of both upper and lower pole ureteral segments may be necessary. The first description of this condition in the literature was by Caulk in 1923 (Caulk, 1923). Subsequently a number of attempts to classify megaureter were undertaken, culminating in the consensus of a committee made up of members of the American Academy of Pediatrics, Society of Pediatric Urological Surgeons, and the Society for Pediatric Urology. These criteria have remained the most comprehensive system for classifying the megaureter (Stephens, 1977). Under this system, megaureters can be identified as refluxing, obstructed, and nonrefluxing and nonobstructed. The majority of megaureters that are obstructed or refluxing are discovered when symptomatic during childhood and may require surgical repair. The most typical operative repair has been ureteral reimplantation with, or without, tapering, but a recent report suggests that short-segment megaureters may be able to be successfully managed with endoureterotomy (Christman et al, 2012). Megaureter has been associated with stones in both the pediatric population and rarely the adult population (Rosenblatt et al, 2009). Ureteral Stricture or Stenosis the presence of intrinsic ureteral obstruction will certainly affect the selection of ideal stone treatment in a number of ways. Second, the mechanism that is chosen to deal with the obstruction may facilitate and/ or dictate how the stone will be managed. Finally, the physical properties of the stricture may mandate a particular course of action. Most important, not every narrow point that is encountered in the ureter reflects a pathologic stricture, particularly when a stone may be impacted there. Inflammatory reaction and ureteral spasm may account for a significant portion of apparent obstructions that are encountered. In these situations, it is critical to recognize that overdilation of the ureter via endoscopic approach may cause localized ureteral injury (Eshghi, 1988). Despite this concern, balloon dilation of the ureter, when required for ureteroscopy, is safe and effective in the vast majority of patients (Huffman and Bagley, 1988). If the area of obstruction is felt to reflect spasm, placing a stent to allow passive dilation will facilitate a second-stage procedure in both pediatric and adult patients (Hubert and Palmer, 2005; Rubenstein et al, 2007). Attempts to definitively treat the obstructing stone should be postponed until the patient is stabilized and the infection is completely treated. Measures to treat the stone before patient stabilization and clearance of the infection risk worsening sepsis and death. In these instances, a urine culture from the obstructed segment is helpful to guide subsequent antibiotic therapy. Methods of dealing with ureteral strictures are covered elsewhere in this text and may provide the primary guidance for dealing with a ureteral stricture; a postureteroscopy stricture is obviously significantly different from a radiation-induced one. Endoureterotomy can be performed at all levels of the ureter; however, it will have a lower rate of long-term success in longer strictures (Wolf et al, 1997). Few data have been reported on the concomitant use of ureteroscopic laser lithotripsy at the time of an endoureterotomy or endopyelotomy, though there is a recognized potential for stone fragments to come to rest in the periureteral space and cause granulomatous inflammatory reaction and recurrent stricture (Dretler and Young, 1993). Alternatively, consideration may lead one to proceed with open, laparoscopic, or robotic-assisted laparoscopic treatment for both the stricture and the stone in the same session. Numerous reports of laparoscopic and robotic-assisted ureterolithotomy have been reported, and the identical techniques and approaches used for management of a ureteral stricture can be used to also treat a ureteral stone in the same session (Dogra et al, 2013; Nasseh et al, 2013; Singh et al, 2013). Renal Function Assessment of underlying renal function becomes most important when there is suspicion that nephrectomy rather than stone removal is the treatment of choice. This scenario is encountered most frequently with staghorn stones, a history of recurrent pyelonephritis or renal abscess episodes, or xanthogranulomatous pyelonephritis and with chronic, relatively asymptomatic renal obstruction from ureteral stones. Renal imaging can provide clues to poor underlying renal function, including renal cortical atrophy or thinned renal parenchyma. In these instances, further functional renal studies, such as diuretic renography, can be used to quantify remaining renal function. In equivocal cases, temporary relief of obstruction with ureteral stenting or percutaneous nephrostomy is warranted, after which renal function can be reassessed. The general consensus is that symptomatic upper tract stones located in renal units with approximately 15% or less split function should be considered for nephrectomy, and stone-specific, nephron-sparing treatments should not be pursued. Considering the available evidence, as long as adequate renal function exists and nephrectomy is not being entertained, stone TechnicalFactors Please see the Expert Consult website for details. Certain patient conditions, anatomic aberrations, and underlying comorbidities assume significant importance in counseling patients on the relative risks and benefits of the different treatment options, as each can influence surgical outcomes and complications. It is interesting to note that offending bacteria may reside deep within stones and prove impossible to eradicate without complete stone removal. Because of this, it may be difficult to completely sterilize the urine before stone surgery, in which case at least a short course of preoperative, culture-directed antibiotics is recommended. Parker and associates (2004) studied the cost associated with treating proximal ureteral stones and found that ureteroscopy was less costly, again as a consequence of its superior initial treatment success. Several investigators have approached the question of costeffective treatment for ureteral calculi by constructing decision analysis models. Lotan and associates (2002) also constructed a decision analysis model to determine the most cost-effective treatment for ureteral stones. Thus, taken all together, ureteroscopy is the most cost-effective treatment strategy for ureteral stones at all locations, after observation fails. The treatment of patients with ureteral calculi depends on multiple surgical technologies, and the availability of certain equipment will affect the possible options for treatment. Few operating environments will have all possible lithotripters, ureteroscopes, lithotrites, or stone-retrieval devices immediately available. The majority of urologists and patients with stone disease in the United States do not have direct access to a fixed lithotripter on an unlimited basis. Therefore, treatment decisions may need to be modified according to lithotripter availability. Patients with symptomatic ureteral stones and no immediate lithotripter access have several options: They may be clinically observed with pain and emetic control; they can undergo placement of an internal ureteral stent to relieve the symptoms of renal colic (but then may develop stent-related morbidities); or they may have primary ureteroscopic removal of the stone, provided the requisite endoscopic equipment is available. Because of recent pressures to decrease resource use, there is increasing emphasis in the modern medical environment on the reduction of cost. Such economic pressures have promoted the movement toward less invasive, more cost-effective therapy for patients with ureteral stones. Rather, they should be based on stone-specific characteristics, renal anatomic factors, and other more relevant clinical factors. Solitary Kidney the main considerations in treating stones in congenitally, surgically, and functionally solitary kidneys include having a lower threshold to treat asymptomatic renal stones and ensuring sufficient renal drainage after stone treatment. By virtue of the fact that only one kidney exists or is functioning, a single, obstructing stone leads to total urinary obstruction and demands urgent attention. It is for this reason that proactive treatment of asymptomatic stones, which might otherwise be observed when two functioning kidneys exist, is recommended in solitary kidneys.

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