Complications of laparoscopic partial nephrectomy.

OBJECTIVES: We report our experience with laparoscopic partial nephrectomy (LPN) to identify preoperative factors associated with an increased risk of postoperative complications. MATERIALS AND METHODS: Among patients undergoing LPN, we analyzed demographic and preoperative tumor characteristics as the exposure variables and postoperative complications as the outcomes. Multivariable logistic regression modeling identified variables associated with increased risk of complications. RESULTS: Of 336 consecutive patients undergoing LPN, 120 (35.7%) had a complication, including 22 (6.6%) with major complications, 12 (3.6%) developing urine leak, 29 (8.6%) requiring blood transfusion, and 11 (3.3%) undergoing nephrectomy. There were no perioperative deaths. On univariable analysis, larger tumor diameter increased the odds of any complication (odds ratio [OR] 2.3, P = 0.007), hemorrhage (OR 1.4, P = 0.007), and urine leak (OR 1.7, P = 0.001). Each 1 cm increase in tumor diameter was associated with a 33% increased odds of a major complication (P = 0.04). In a multivariable model, changes in tumor diameter increased the odds of any complication (OR 2.4, P = 0.006) and hemorrhage (OR 1.5, P = 0.01); tumor depth was a better predictor of a major complication (OR 1.1, P = 0.004). In the multivariable model, advanced age also was associated with hemorrhage (OR 2.6, P = 0.05). CONCLUSIONS: Tumor diameter, depth of tumor penetration, and advanced patient age are associated with increased odds of complications in patients undergoing LPN. This information is important for counseling patients preoperatively regarding their risk of complications following LPN and in selecting the appropriate intervention for a particular tumor.

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy.

OBJECTIVE: Carcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower. RESULTS: Concomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients. CONCLUSION: The presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.

Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?

OBJECTIVES: To evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU). METHODS: Data on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts. RESULTS: Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both). CONCLUSIONS: Local symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.

Histotripsy of VX-2 tumor implanted in a renal rabbit model.

INTRODUCTION: Histotripsy is an extracorporeal focused ultrasound (US) technology that uses controlled cavitation to induce nonthermal mechanical tissue fractionation. Feasibility of histotripsy ablation of normal renal tissue in an in vivo rabbit model has previously been demonstrated. Our specific objective in this study was to characterize the histologic effects of histotripsy on VX-2 tumor implanted in the kidneys of an in vivo rabbit model. METHODS: VX-2 tumor was implanted below the renal capsule in 15 New Zealand white rabbits. Two weeks after implantation, tumors were localized with diagnostic US imaging. Targeted volumes within the observed tumor were treated with short (3 micros) pulses of 1 MHz acoustic energy at a repetition frequency of 300 Hz. Twenty tumors were treated with histotripsy and 7 served as tumor controls. Three normal kidneys were also treated with histotripsy. Kidneys and lungs were harvested, grossly inspected, and processed for histopathologic analysis. RESULTS: Real-time US imaging confirmed presence of cavitation during all histotripsy treatments. Examination of tumor and kidney specimens revealed 100% tumor growth with an average tumor diameter of 7 mm (range 2-12). In 16 of 20 tumors treated with histotripsy, acellular zones of debris and finely disrupted cellular architecture were present on histology. Kidneys harvested 24 hours after treatment revealed an extensive inflammatory reaction. CONCLUSIONS: Transcutaneous application of histotripsy to implanted VX-2 tumor in rabbit kidney produced fractionation of malignant tissue. These findings support the further study and development of histotripsy for potential oncologic application.

Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract.

BACKGROUND: Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series. OBJECTIVE: To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU. DESIGN, SETTING, AND PARTICIPANTS: Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as >10% of the tumour area. INTERVENTION: Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes. MEASUREMENTS: Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses. RESULTS AND LIMITATIONS: Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p<0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p=0.037 and p=0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%). CONCLUSIONS: Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting.

Prostate histotripsy in an anticoagulated model.

OBJECTIVES: To further explore the phenomenon of minimal bleeding after histotripsy by performing extensive prostate histotripsy treatments in anticoagulated canines. Histotripsy is a noninvasive ultrasound technology which induces microbubble formation (cavitation) within tissues producing mechanical tissue fractionation. During initial in vivo feasibility canine studies of prostate ablation, minimal hematuria was observed. METHODS: Histotripsy was performed on 9 canine subjects pretreated with 6 mg of oral warfarin for 3-5 days using an extracorporeal 750 kHz therapeutic ultrasound transducer delivering acoustic pulses to the prostatic urethra and periurethral parenchyma. After 7-28 days, the subjects were euthanized, transrectal prostate ultrasound was performed, and the prostate was harvested. Serum hemoglobin and International Normalization Ratio were measured immediately before histotripsy treatment and at euthanasia. RESULTS: Mean treatment International Normalization Ratio was 4.6 (median, 2.4; range, 1.2-11.3). There was no clinically significant change in hemoglobin concentration at euthanasia compared with baseline. At harvest, histologic sections of the prostate revealed a large cavity corresponding to the planned treatment volume incorporating the prostatic urethra and parenchyma in all subjects. Urine was clear within 2 days of treatment, and no blood clots were seen. CONCLUSIONS: Despite therapeutic and supratherapeutic anticoagulation, histotripsy resulted in minimal bleeding despite significant fractionation and tissue debulking of the prostate. These results have prompted further studies to understand the mechanism of nonthermal hemostasis underlying histotripsy.

Multi-session retrograde endoscopic lithotripsy of large renal calculi in obese patients.

OBJECTIVES: To establish the safety and efficacy of planned multi-session retrograde endoscopic lithotripsy (REL) for the treatment of large renal calculi in the morbidly obese. METHODS: We retrospectively reviewed charts of patients who underwent multi-session REL procedures from 2003 to 2008. Inclusion criteria included body mass index > 35, total linear stone diameter > 2.0 cm, and patients with a preoperative plan to perform multi-session ureteroscopy. A total of nine patients (six with staghorn calculi) underwent 21 separate procedures. Stone size was measured on preoperative imaging and was defined as length in greatest diameter. Stone free was defined as the complete absence of residual stone on postoperative imaging. RESULTS: Mean body mass index of the patients was 47.8 kg/m2. Mean total linear stone diameter was 3.8 cm. Three of nine patients (33%) were stone free after their final treatment. Mean decrease in stone size from preoperative imaging was 3.3 cm (83%). There were no intraoperative complications. Mean length of follow up was 0.88 years. CONCLUSIONS: Multi-session REL is a safe alternative to percutaneous nephrolithotomy (PCNL) in obese patients with very large stones, including staghorn calculi. We recognize that the stone free rate in this series is lower than would be expected with REL for smaller stone burdens or with PCNL. Due to the limitations imposed by both the patient's general medical conditions as well as technical considerations, these patients are left with few options for treatment. Our experience is that management with staged ureteroscopy offers a reduction in stone burden and in some patients a stone free status that provides an acceptable patient outcome.

Clinical interpretation of the Expanded Prostate Cancer Index Composite-Short Form sexual summary score.

PURPOSE: The Expanded Prostate Cancer Index Composite is a validated health related quality of life instrument that is commonly administered after prostate cancer treatment. We classified Expanded Prostate Cancer Index Composite-Short Form sexual summary scores into clinically meaningful groups. MATERIALS AND METHODS: A development cohort of 561 patients undergoing radical prostatectomy was used to define sexual summary groups by correlation with their responses on the Sexual Health Inventory for Men. A separate validation cohort of 430 patients was used to compare Expanded Prostate Cancer Index Composite-Long Form sexual bother scores among these sexual summary groups. RESULTS: A sexual summary group score of 0 to 33, 34 to 45, 46 to 60, 61 to 75 and greater than 75 correlated with Sexual Health Inventory for Men groups of severe--1 to 7, moderate--8 to 11, mild/moderate--12 to 16, mild--17 to 21 and no erectile dysfunction--22 to 25, respectively. In the validation group mean sexual bother scores in each of the 5 sexual summary groups were significantly different from each other after controlling for patient age, stage, hormone treatment, marital status and nerve sparing (p <0.0001). CONCLUSIONS: Expanded Prostate Cancer Index Composite-Short Form sexual summary scores can be categorized into 5 groups for which excellent correlation is found with similar validated groups based on the Sexual Health Inventory for Men. Also, sexual bother scores are significantly different among the groups, showing that they represent discrete, clinically relevant cutoffs. This will help patients and physicians interpret Expanded Prostate Cancer Index Composite scores and help define potency for comparison among various prostate cancer treatments.

Advances in bioadhesives, tissue sealants, and hemostatic agents.

The use of bioadhesives, tissue sealants, and hemostatic agents has allowed for increased use of minimally invasive techniques for complex reconstructive urologic procedures. Hemostatic agents can facilitate clot formation through enzymatic reactions with host factors, mechanical compression, or a combination of the two. Tissue sealants and bioadhesives act through polymerization between themselves and adjacent tissues. This article reviews the unique features, mechanism of action, safety profile, and prototypical applications of the agents most commonly used in urologic surgery.