Adipose tissue composition determines its computed tomography radiodensity.

OBJECTIVES: Adipose tissue radiodensity in computed tomography (CT) performed before surgeries can predict surgical difficulty. Despite its clinical importance, little is known about what influences radiodensity. This study combines desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and electrospray ionization (ESI) with machine learning to unveil how chemical composition of adipose tissue determines its radiodensity. METHODS: Patients in the study underwent abdominal surgeries. Before surgery, CT radiodensity of fat near operated sites was measured. Fifty-three fat samples were collected and analyzed by DESI-MSI, ESI, and histology, and then sorted by radiodensity, demographic parameters, and adipocyte size. A non-negative matrix factorization (NMF) algorithm was developed to differentiate between high and low radiodensities. RESULTS: No associations between radiodensity and patient age, gender, weight, height, or fat origin were found. Body mass index showed negative correlation with radiodensity. A substantial difference in chemical composition between adipose tissues of high and low radiodensities was observed. More radiodense tissues exhibited greater abundance of high molecular weight species, such as phospholipids of various types, ceramides, cholesterol esters and diglycerides, and about 70% smaller adipocyte size. Less radiodense tissue showed high abundance of short acyl-tail fatty acids. CONCLUSIONS: This study unveils the connection between abdominal adipose tissue radiodensity and its chemical composition. Because the radiodensity of the fat around the surgical site is associated with surgical difficulty, it is important to understand how adipose tissue composition affects this parameter. We conclude that fat tissue with a higher content of various phospholipids and waxy lipids is more CT radiodense. CLINICAL RELEVANCE STATEMENT: This study establishes the connection between the CT radiodensity of adipose tissue and its chemical composition. Clinicians may use this information for preoperative planning of surgical procedures, potentially modifying their surgical approach (for example, performing partial nephrectomy openly rather than laparoscopically). KEY POINTS: • Adipose tissue radiodensity values in computed tomography images taken prior to the surgery can potentially predict surgery difficulty. • Fifty-three human specimens were analyzed by advanced mass spectrometry, molecular imaging, and machine learning to establish the key features that determine Hounsfield units' values of adipose tissue. • The findings of this research will enable clinicians to better prepare for surgical procedures and select operative strategies.

Parenchymal echotexture changes as a predictor of viability in testicular torsion.

INTRODUCTION: Preoperative test that can predict the salvageability of the torsed testis may add essential information to the surgeon managing testicular torsion (TT), this can assist with patients' and parents' expectations, particularly with nonviable testes. We aimed to examine if parenchymal echotexture changes in preoperative ultrasound can predict irreversible hemorrhagic necrosis. MATERIALS AND METHODS: Preoperative ultrasound studies of 154 patients with TT were reviewed by 3 raters (2 radiologists and 1 urologist). The raters were asked to categorize the affected testicular parenchymal echotexture into one of the following categories: (1) normal (identical to the contra-lateral testis), (2) homogenous hypoechoic, or (3) focal heterogeneous echotexture. Testis non-viability was defined macroscopically during surgical exploration and correlated with the US results. Sensitivity, specificity, and positive and negative predicting values of the proposed diagnostic test were calculated. Cohen's kappa coefficient was used to determine inter-rater agreement. RESULTS: A total of 54/154 patients had a nonviable testis. Mean of 59.5% cases was classified as category 1, 27.3% cases as category 2, and 13.2% cases as category 3. Testicular necrosis was 12%, 34%, and 92% in each category, respectively. Category 3 classified non-viability with a mean specificity of 99.3% and with a high inter-rater agreement level (Cohen's kappa coefficient of 0.830). Mean positive predictive value of 97% and mean negative predictive value of 74.3%. The mean sensitivity of this test however was low 39.7%. CONCLUSION: Ultrasound finding of focal parenchymal echotexture heterogeneous changes is highly specific although not sensitive, for nonviable testis. The presence of this finding reassures non-viability in over 99%.

[NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY - MIGHT IT BE OFFERED SELECTIVELY?]

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.

Initial experience in combined ultra-mini percutaneous nephrolithotomy with the use of 120-W laser and the anti-retropulsion "Moses effect": the future of percutaneous nephrolithotomy?

The purpose is to present our preliminary results where ultra-mini PCNL (UMPCNL) with the new 120-watt laser with the anti-retropulsion (Lumenis® MOSES Pulse™120H Holmium: YAG laser) was used for the first time to our knowledge. Twelve patients underwent ultra-mini PCNL in prone position under general anesthesia using a 12-F nephroscope with a 14-F Access sheath in our tertiary center. The fragmentation was performed with a 500 µm laser fiber using the 120-watt Lumenis® MOSES Pulse™120H Holmium: YAG laser). Efficacy was considered in terms of stone-free rates (SFR), complication rate, duration of the operation, and hospital stay. Our SFR was 91.6% with 11 patients out of 12 being completely free of any residual stone. The duration of the operation was 86.4 ± 36.8 (40-165) min, whereas the mean laser time (real stone fragmentation laser time) was 755.7 ± 954.7(241-3425) sec. The total laser energy used was 39.7 ± 52 KJoules (11.3-182). The fluoroscopy time and radiation doses were 358.5 ± 180.4 (154-750) sec and 64.7 ± 41.2 (14.7-159.0) mGy, respectively. The mean reduction in levels of hemoglobin postoperatively was 0.6 ± 0.3 (0.1-0.9) g/dL, and no complications were observed. The combination of UMPCNL with the new 120-watt laser and the unique anti-retropulsion technology (Lumenis® MOSES Pulse™120H Holmium: YAG laser) delivered very promising results and it could be the future of PCNL.

A study of prostate volumes in patients with spinal cord injury.

AIMS: To evaluate the development of benign prostatic hyperplasia (BPH) in patients with spinal cord injury (SCI) and to deduce the role of the nervous system in this process. METHODS: Prostate volumes (PVs) of 65 men older than 30 years of age who sustained SCI were determined from CT scans. Correlations of PVs with SCI level, age, age during SCI and duration of paralysis were calculated. RESULTS: Average patient's age during SCI was 37.7 (±19) years and during measurement of PV 54.8 (±15.3) years. PVs of patients with SCI were similar to expected age-adjusted volumes (29.7 ± 24 mL vs 29.9 ± 5.7 mL, P = 0.95). We dichotomized the cohort into two groups: High SCI (T5 and above) and low SCI (T6 and below) with almost identical: number of patients, age of SCI and duration of paralysis. Patients with lower injuries, had significantly smaller PVs when compared both to patients with higher injuries (19.4 ± 6.3 and 39.8 ± 30, P = 0.0006) and to age-adjusted normal PVs (19.4 ± 6.3 and 29.2 ± 5.8, P = 0.0005). Correlation of PV with age was found in patients higher injuries (R2 = 0.26, p = 0.003) but not in patients with lower (R2 = 0.08, P = 0.11). Moreover, patients with lower SCI had significantly smaller prostate even compared to expected PVs during SCI (18.7 ± 4.6 cc vs 27.8 ± 6.9 cc, P = 0.00006). CONCLUSIONS: Low SCI stops and reverses age related increase in PV. This phenomenon does not occur in high SCIs. This suggests that continuous support of the nervous system is essential for sustaining BPH and raises the possibility of finding a non-hormonal pharmacological intervention for reversing BPH.

'Very-low-risk' bladder tumours - a new entity?

OBJECTIVE: To evaluate the homogeneity of the 'low-risk' bladder cancer group in an attempt to optimise follow-up protocols. PATIENTS AND METHODS: Between June 1998 and December 2008, 211 patients (mean [sd] age of 66.7 [12.8] years) underwent transurethral resection of low-risk bladder cancer. Postoperative follow-up included cystoscopy at 3 and 12 months after surgery, then annually for a total of 5 years, and then annual ultrasonography indefinitely. RESULTS: After a median follow-up of 10 years, 65 patients (30.7%) developed tumour recurrence and three (1.4%) stage progressions. In all, 84 patients (40%) had tumours of ≤1 cm; these patients were significantly younger than patients with 1.1-3 cm tumours (64.6 vs 68.3 years, P = 0.03). Their 5-year recurrence-free survival rate was significantly higher (92% vs 70% in patients with larger tumours, P < 0.001). The median time to recurrence was 5.7 years in patients with smaller tumours and 3.6 years in patients with larger tumours (P = 0.03). Only 43.7% of the recurrences in patients with small tumours occurred within 5 years, compared to 75.5% in patients with larger tumours. CONCLUSIONS: Patients with low-risk bladder cancer make an inhomogeneous group. They can be stratified according to tumour size. Patients with tumours of ≤1 cm are younger, have lower risk of tumour recurrence, and most of their recurrences arise beyond the recommended 5-year surveillance period. It seems that these patients can be classified separately to a 'very-low-risk' group. Follow-up in these cases can be based on prolonged non-invasive evaluations.

[ACTIVE SURVEILLANCE IN RECURRENT LOW-RISK BLADDER TUMORS].

OBJECTIVES: To report our experience with the active surveillance policy in patients with recurrent low-risk bladder tumors. METHODS: The files of 52 patients who underwent active surveillance instead of immediate surgical resection were reviewed. Different variables concerning tumor growth rate were evaluated. RESULTS: A total of 75 surveillance periods were documented in 52 patients (mean age 75.6 years S.D. 10.45 years, 37 males and 14 females), Mean surveillance period length was 16.5 months (S.D. 16.1). All tumors resected after surveillance were found in stage Ta and in low-grade except one tumor which was high-grade; 70 active surveillance periods ended with tumor resection, and 5 patients were still under surveillance when the research ended; 27 surveillance periods (37.7%) ended because of the growth of additional tumors. Active surveillance therefore spared 27 surgeries. The rate of tumor growth during surveillance depended on the tumor's largest diameter at the beginning of surveillance. If initial tumor diameter was smaller than 5 mm (68 cases), the median tumor growth rate was 1.12 mm3/month (IRQ: 0-6.55). If the initial tumor diameter was ≥5 mm (7 cases), the median tumor growth rate was 137.14 mm3/month (IRQ: 2.21-1787.5, p < 0.05). CONCLUSIONS: Small, recurrent papillary bladder tumors pose minimal risk to the patient. An active surveillance policy, without immediate resection of the tumor is safe, can spare surgeries and can be considered in patients presenting with small papillary recurrence.

[PERCUTANEOUS TREATMENT OF SMALL RENAL TUMORS BY THERMAL ABLATION].

INTRODUCTION: Kidney cancer accounts for approximately 2-3 % of all types of cancers. Renal tumors prevalence and especially the prevalence of small renal tumors, is on the rise. About half of the tumors currently diagnosed are smaller than 4 cm. Minimally invasive methods of radiofrequency ablation technology were recently developed for the treatment of small renal tumors and are characterized by reducing the surgical and anesthetic risk. The ablation is performed with a percutaneous approach guided by ultrasound, CT or MRI. We reviewed the results of this treatment. METHODS: A total of 75 patients with a mean age of 69.5 years (27 - 90) were treated using RF during the period 2007-2014. The average tumor diameter was 28.4 mm (11-58 mm); 40 tumors were exophytic and 30 were central. Monitoring protocol after treatment included imaging after 1, 3, 6, 12 months subsequent to treatment and later annually; median follow-up time was 21 months (1 - 97). RESULTS: Evidence of tumor recurrence was observed in 9 patients (11.4%); 8 were treated successfully by another RF session. Cases in which recurrence was observed were characterized by a tumor larger than 30 mm (5/9) and adjacent to renal cysts (3/9); 5 of the lesions were central (endophytic) (P=0.5). One patient died due to metastatic RCC and a metastatic disease developed in two additional patients who died of other causes. CONCLUSIONS: It is possible to destroy most of the small renal tumors by RF ablation. When the tumor size is up to 30 mm, a 94% long-term cure may be reached. In the event of renewed growth of the tumor, the treatment can be repeated with good results. In light of short-term experience, it is recommended to limit this treatment to older patients, with a short life expectancy or when anesthetic risks prohibit surgery.

H19 non-coding RNA in urine cells detects urothelial carcinoma: a pilot study.

CONTEXT: Urothelial carcinoma (UC) is common and highly recurrent. Diagnosis and follow-up involve invasive cystoscopies. OBJECTIVE: To evaluate H19 RNA in urine cells as diagnostic tool for UC. MATERIALS AND METHODS: RT-PCR analysis of urine samples from healthy volunteers and UC patients. RESULTS: H19 RNA was unequivocally detected in the urine of 90.5% of patients and 25.9% of controls. H19 copies were three orders of magnitude higher in patients. Receiver operating characteristic analysis showed an area under the curve of 0.933. CONCLUSIONS: This pilot study shows that urinary cell H19 is a highly sensitive test for UC and pending verification could transform patient management.

Diagnostic Challenges of Kidney Cancer: A Systematic Review of the Role of Positron Emission Tomography-Computerized Tomography.

PURPOSE: Positron emission tomography-computerized tomography is a leading imaging modality for many types of solid tumors. The ability to characterize molecular processes noninvasively during a relatively fast whole-body scan is the major advantage of this technology. We reviewed the literature in an attempt to clarify the usefulness of positron emission tomography-computerized tomography in patients with a renal mass. MATERIALS AND METHODS: We searched PubMed® for articles published from 2004 through September 2015 using the keywords "renal," "kidney," "mass," "tumor," "cancer," and "PET/CT." RESULTS: A total of 158 relevant articles were included in the review. Most diagnostic studies used (18)F-fluorodeoxyglucose, a marker of glucose metabolism, as the radiotracer. The results were substandard, with sensitivity rates in the range of 31.5% to 77% for diagnosis of renal cell carcinomas. There were higher success rates for diagnosis of clear cell carcinomas. Carbonic anhydrase IX is an enzyme expressed in 95% of clear cell carcinomas but not in normal renal tissue or in benign or nonclear cell malignancies. A chimeric mouse-human antibody to carbonic anhydrase IX labeled with (124)I-girentuximab was demonstrated to diagnose clear cell tumors with sensitivity of 86.2% and specificity of 85.9%. For diagnosis of metastases positron emission tomography-computerized tomography with (18)F-fluorodeoxyglucose was observed to be more accurate than computerized tomography alone (94% vs 89%). Studies with other tracers also reveal encouraging results. Positron emission tomography-computerized tomography holds great promise in predicting prognosis and response to tyrosine kinase inhibitors. Current tyrosine kinase inhibitor treatments usually induce only mild lesion shrinkage. Thus, assessment of response based on changes in size of metastases is insufficient. Low (18)F-fluorodeoxyglucose uptake before treatment and decreased uptake after 2 cycles of treatment are associated with better survival. Using labeled medications as radiotracers before actual treatment may assist in selection of the most effective medication for a specific patient. CONCLUSIONS: Positron emission tomography-computerized tomography with (18)F-fluorodeoxyglucose currently has lower sensitivity compared to enhanced computerized tomography for diagnosis of primary renal masses but better sensitivity for diagnosis of metastases. Predicting and monitoring response to targeted therapy could direct the clinician toward drug selection or modification during therapy. The possibility of treating patients with advanced renal cell carcinoma with (124)I-girentuximab attached to (177)Lu, a strong ß-emitter, is investigated.

External Validation of CROES Nephrolithometry as a Preoperative Predictive System for Percutaneous Nephrolithotomy Outcomes.

PURPOSE: We externally validated CROES (Clinical Research Office of the Endourological Society) nephrolithometry and evaluated the predictive accuracy of the nomogram. MATERIALS AND METHODS: Data were collected on patients who underwent percutaneous nephrolithotomy between January 2012 and February 2015. The CROES nomogram was applied to all patients and externally validated. The AUC and calibration plot were used for discrimination and clinical validity assessment. RESULTS: A total of 176 patients were included in study. Mean ± SD patient age was 55.2 ± 13.9 years and the mean stone burden was 640.0 ± 911.4 mm(2). The CROES nomogram was significantly associated with stone number, location and burden, and the number of implicated calyces, punctures and tracts. The postoperative treatment success rate was 85.8%. The number of stones, number of implicated calyces and CROES score were independent predictors of treatment success. The estimated AUC was 0.715 and the model provided good calibration. CONCLUSIONS: The CROES nomogram is an accurate tool to estimate renal stone complexity. CROES nephrolithometry provides great accuracy to predict postoperative efficacy.

Pregnancy Rates after Testicular Torsion.

PURPOSE: To our knowledge the effect of testicular torsion on the pregnancy rate is unknown. In this study we focused on the pregnancy rate, which is the ultimate index of fertility status. MATERIALS AND METHODS: We reviewed the records of 273 patients who presented to our emergency room with testicular torsion between 1994 and 2014. Study inclusion criteria included being in a relationship with the intent to conceive for at least 1 year, age greater than 25 years and a normal contralateral testis. Patients with primary infertility, those who were unwilling to participate or unreachable and those with a history of undescended testis and/or varicocele were excluded from analysis. Patients were contacted by telephone and interviewed according to a standardized questionnaire. Pregnancy rates in the orchiopexy and orchiectomy groups were compared to each other and to the accepted pregnancy rate in the literature. RESULTS: A total of 63 patients met study inclusion criteria, including 41 and 22 in the orchiopexy and orchiectomy groups, respectively. The pregnancy rate in the orchiopexy and orchiectomy groups was 90.2% and 90.9%, respectively (p = 1.0). The accepted pregnancy rate in the general population is 82% to 92%. Mean ± SD time to pregnancy in the orchiopexy and orchiectomy groups was 6.6 ± 5.50 and 7.2 ± 5.4 months, respectively (p = 0.27). CONCLUSIONS: Several studies suggest decreased fertility potential in patients with a history of testicular torsion. However, in the current study in couples in which the male had a history of testicular torsion the pregnancy rate and the interval to pregnancy were within the accepted range of the general population.

Percutaneous nephrolithotomy for staghorn stones: Which nomogram can better predict postoperative outcomes?

PURPOSE: To identify independent predictors for postoperative stone-free status after percutaneous nephrolithotomy (PCNL) for staghorn stones and to compare Guy's, CROES and STONE nomograms regarding their predictive ability and accuracy specifically for staghorn stones. METHODS: Data of 286 patients who underwent PCNL in our department were collected and analyzed. Several parameters, including the three nomograms, were analyzed to reveal independent predictors for postoperative stone-free status. The area under the curve was used to assess the predictive ability of the independent predictors. RESULTS: A total of 73 staghorn calculi were identified with mean stone burden of 1253.5 mm(2). Mean Guy's, CROES and STONE score was 3.34, 125.8 and 9.95, respectively. Postoperative stone-free rate was 65.8 %. In univariate analysis, all three nomograms were significantly associated with stone-free status. However, STONE was the only significant independent predictor in multivariate analysis. STONE also revealed the highest predictive accuracy compared to Guy's and CROES nomogram. CONCLUSIONS: STONE nephrolithometry was found to be the only predictor for stone-free rate after PCNL for staghorn stones compared to Guy's and CROES nomograms.

Impact of Androgen Deprivation Therapy on Sexual and Hormonal Function in Patients Receiving Radiation Therapy for Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. OBJECTIVES: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT METHODS: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. RESULTS: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). CONCLUSIONS: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by depression and lack of education. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy.

Timing of Orchidopexy for Undescended Testis in Israel: A Quality of Care Study.

BACKGROUND: Strong evidence suggests that in order to prevent irreversible testicular damage surgical correction (orchidopexy) for undescended testis (UDT) should be performed before the age of 1 year. OBJECTIVES: To evaluate whether orchidopexy is delayed in our medical system, and if so, to explore the pattern of referral for orchidopexy as a possible contributing factor in such delays. METHODS: We conducted a retrospective chart review of all children who underwent orchidopexy for UDT between 2003 and 2013 in our institution. We collected data on the age at surgery and the child's health insurance plan. We also surveyed pediatricians from around the country regarding their pattern of UDT patient referral to a pediatric urologist or surgeon for surgical correction. RESULTS: A total of 813 children underwent orchidopexy in our institute during the study period. The median age at surgery was 1.49 years (range 0.5-13). Only 11% of the children underwent surgery under the age of 1 year, and 53% between the ages of 1 and 2 years. These findings were consistent throughout the years, with no difference between the four health insurance plans. Sixty-three pediatricians who participated in the survey reported that they referred children to surgery at a median age of 1 year (range 0.5-3 years). CONCLUSIONS: Our results demonstrate delayed orchidopexy in our medical system. There is a need to improve awareness for early specialist consultation in order to facilitate earlier surgery and better care.

[FACTORS PREDICTING OVERALL AND DISEASE-FREE SURVIVAL AFTER SURGERY FOR INVASIVE BLADDER CANCER].

OBJECTIVES: To evaluate the prognosis of patients who underwent surgery for invasive bladder cancer and to search for prognostic factors. METHODS: The files of all the patients who underwent radical or partial cystectomy for invasive bladder cancer between 1992 and 2014 were reviewed. The effect of various prognostic factors was evaluated by uni- and multivariate analyses. RESULTS: A total of 160 patients were included in the study and were followed for a median period of 25.5 months after surgery. The overall 2 years and 5 years survival rates were 70% and 61.2% respectively. The disease-free 2 years and 5 years survival rates were 64.4% and 61.9% respectively. The overall 2 years and 5 years survival rates of patients with disease limited to the bladder (≥T2N0) were 88.2% and 82.4% and of patients with disease extending beyond the bladder (≤T3N0) 56.5% and 45.7% respectively. Factors that were found to be significantly associated with overall survival were: TNM stage, co-morbidity (Charlson 6-11) and the tumor's diameter. No association was found between: disease presentation, smoking habits, positive cytology, the tumor being primary or secondary, variant histology, the presence of endophytic growth pattern, the presence of CIS, hydronephrosis, positive lymph nodes on pre-operative imaging, surgery type (radical or partial cystectomy) and adjuvant chemotherapy. CONCLUSIONS: The survival rates of the locally treated patients match the reported rates in the literature. Tumors' T stage were found to be the strongest prognostic factor. Tumors' diameter was found to be an independent prognostic factor. This is reported here for the first time in the literature.

History of Ureteral Stenting Negatively Affects the Outcomes of Extracorporeal Shockwave Lithotripsy. Results of a Matched-pair Analysis.

To evaluate the impact of ureteral stenting history to the outcomes of extracorporeal shockwave lithotripsy, we retrospectively analysed patients who underwent shockwave lithotripsy with Dornier Gemini lithotripter between September 2010 and August 2012. Forty seven patients (group A) who had a double J stent which was removed just before the procedure were matched-paired with another 47 patients (group B) who underwent shockwave lithotripsy having no stent history. The correlation between ureteral stenting history and stone-free rates was assessed. Stone-free rates were 68.1% and 87.2% for patients of group A and B, respectively (p=0.026). Postoperative complications were not different between groups. Multivariate analysis revealed that stone size (p=0.007), stone location (p=0.044) and history of ureteral stenting (p=0.046) were independent predictors for stone clearance after shockwave lithotripsy. Ureteral stents adversely affect shockwave lithotripsy outcome, even if they are removed before the procedure. Stenting history should divert treatment plan towards intracorporeal lithotripsy.

Mixed high and low grade bladder tumors--are they clinically high or low grade?

PURPOSE: The pathological grade of bladder cancer has an immense impact on patient treatment and prognosis. While most bladder tumors show pure high or low grade patterns, some show a mixed pattern. We explored the incidence and clinical significance of this phenomenon. MATERIALS AND METHODS: A total of 642 patients with a mean age of 67.5 years underwent transurethral resection of nonmuscle invasive bladder tumors between June 1998 and December 2008, including 156 and 454 with low and high grade lesions, respectively. In 32 patients (5%) mixed grade tumors were found, defined as low grade tumors with 10% or less of a high grade component. All patients were followed a median of 60 months postoperatively. RESULTS: Mean age, the proportion of men and the proportion of stages Ta/T1 in patients with mixed grade tumors were between those of the high and low grade groups. Five-year recurrence-free survival was similar for high, low and mixed grade tumor types (56.9%, 63.8% and 66.4%, respectively, p=0.252). Five-year progression-free survival was significantly lower in patients with high grade disease (73.9%, p<0.0001) but similar in those with high and mixed grade tumors (99% and 96.9%, respectively, p=0.167). Similarly, disease specific survival was significantly worse in patients with high grade tumors (p<0.0001) but similar in those with high and mixed grade lesions (p=0.679). CONCLUSIONS: Mixed grade is found in about 5% of nonmuscle invasive tumors, representing a patient group with unique clinical features. The clinical course of patients with mixed grade tumors parallels that of patients with low grade tumors.

DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer.

PURPOSE: H19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial. MATERIALS AND METHODS: A total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months. RESULTS: All patients were evaluable for adverse effects and 39 were evaluable for efficacy. Complete tumor ablation was achieved in 33% of patients and in 64% there were no new tumors at 3 months. Median time to recurrence was 11.3 months in all cases but significantly longer (22.1 months) when analyzed by response status at 3 months. Adverse events were mild. The study was limited by the small number of patients. CONCLUSIONS: BC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.