Shock Wave Lithotripsy in Pediatric Stone Disease: A 15-Year Single-Center Experience with 2 Types of Lithotripters.

INTRODUCTION AND OBJECTIVES: We report our experience with pediatric shock wave lithotripsy (SWL) using two types of lithotripters: Dornier HM3 (HM3) and Dornier Lithotripter SII (DLS). STUDY DESIGN: We retrospectively reviewed the charts of children who underwent SWL between 2002 and 2016. Patients were divided into two groups based on the type of the lithotripter: during 2002-2009, we used the electrohydraulic HM3 lithotripter which was replaced in 2009 with the DLS electromagnetic lithotripter. Clinical and perioperative parameters were compared. RESULTS: Our cohort included 107 children who underwent SWL. Average age was 11.5 ± 5.1 years. Average stone size was 10.6 ± 4.9 mm. HM3 was used in 38% of children and DLS2 in 62% (n = 41 and 66, respectively). There were no significant differences in age, gender, stone size, or location between the groups. The total SFR did not differ statistically between HM3 and DLS (83% vs. 74%, p = 0.35). SFR after one SWL was higher with the HM3 (78% vs. 62%, p = 0.093). Re-treatment rate was 22% and 17% (HM3 vs. DLS, p = 0.61). Complication rates were low, with renal colic being the most common (HM3 10%, DLS 20%, NS). CONCLUSIONS: SWL in the pediatric population using the DLS showed good results with low complication rates that are equivalent to the gold standard HM3.

Tailoring Antibiotic Prophylaxis for Ureteroscopic Procedures Based on Local Resistance Profiles May Lead to Reduced Rates of Infections and Urosepsis.

INTRODUCTION AND OBJECTIVES: Urinary tract infections (UTI) following ureteroscopy (URS) occur in about 4% of patients. Due to the resistant bacterial strains we encounter in our institution, we retrospectively examined whether a double-drug antibiotic prophylactic treatment (APT) can reduce urosepsis after URS. MATERIALS AND METHODS: Between February 2015 and March 2016, we performed 344 URS for stone treatment. Starting from September 2015, we changed the APT. Exclusion criteria included procedures involving percutaneous nephrolithotomy, pediatric or pregnant patients, and patients with preoperative clinical UTI. RESULTS: Fifty-seven patients were excluded. Group 1 (n = 106) were the last to receive the conventional APT (oral ciprofloxacin), while the second group (n = 181) were the first to receive the new -regimen (intravenous gentamycin and ampicillin). A distinct percentage of both groups had a preoperative positive urine culture (29% in group 1 and 19% in group 2). Seven of 9 septic events developed in patients with preoperative positive urine culture (p < 0.001). Patients undergoing retrograde intrarenal surgery were at increased risk for sepsis when treated with conventional APT (p < 0.01). Post-URS sepsis was 7.5% using the conventional APT and 0.5% with the new APT (p < 0.0001). CONCLUSIONS: A distinct number of patients undergoing URS stone treatment have positive preoperative urine cultures. "One size fits all" APT is not sufficient according to our data. A regimen tailored to the local antibiotic resistance of the uropathogens can lower the rate of sepsis.

Transurethral Resection of the Prostate in Younger Men: Effectiveness and Long-term Outcomes.

OBJECTIVES: This study aims to investigate the efficacy and outcomes of transurethral resection of the prostate (TURP) in the context of younger male patients. METHODS: Males aged ≤55 who underwent TURP at Rambam Health Care Campus from January 2011 to August 2023 were retrospectively reviewed. Clinicodemographic characteristics, indications for surgery, uroflowmetry, pressure-flow study, and early and late postoperative outcomes were collected. Patients with urethral or bladder abnormalities were excluded. Chi-square and Fisher's exact tests were employed for bivariate analysis. RESULTS: Inclusion criteria were met by 58 men who underwent TURP at a median age of 52 years (interquartile range [IQR] 49.5-54). Median prostate size was 35 mL (24.5-56), with median prostate-specific antigen of 1.4 ng/mL (0.65-3.1). A total of 60% of patients used α-blockers, and 19% used 5α-reductase inhibitors pre-surgery. Overall, 54 (93.1%) had severe lower urinary tract symptoms (LUTS), with 34 (59%) being predominantly emptying and 20 (35%) storage. Most surgeries were performed for refractory LUTS in 38 (66%), followed by urinary retention in 16 (28%). At 6 weeks, 57 (98%) patients were catheter-free. The maximum flow rate and residual volume showed significant improvement from a median of 6.85 mL/s to 17.9 mL/s (P<0.001), and from 120 mL to 10 mL (P=0.0142), respectively. Pathology revealed benign prostatic hyperplasia in 53 (91.4%), and inflammation in 5 (8.5%). A total of 13 auxiliary procedures were required in 12 patients (20.7%) during follow-up: 7 transurethral bladder neck incisions, 3 re-TURP, 1 meatus widening, and 1 patient required artificial urinary sphincter implantation followed by simple cystectomy for end-stage bladder. CONCLUSIONS: In young men, TURP showed short-term gains in flowmetry and catheter removal rates, but a sustained need for subsequent procedures in the long run. In this unique population, patients should be carefully selected, and alternative, less aggressive, interventions should be considered.

Can Endoscopic Appearance, Selective Cytology, and Pathological Sampling During Ureteroscopy Accurately Predict Tumor Grade of Upper-Tract Urothelial Carcinoma?

OBJECTIVE: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU). METHODS: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report. RESULTS: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the "solid"-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease. CONCLUSIONS: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.

Fluorescence-assisted cytological testing (FACT): Ex Vivo viral method for enhancing detection of rare cancer cells in body fluids.

Cytological analysis of body fluids is currently used for detecting cancer. The objective of this study was to determine if the herpes virus carrying an enhanced green fluorescent protein (EGFP) could detect rare cancer cells in body fluids against millions of normal cells. Human cancer cells suspended with normal murine cells were infected with NV1066 at a multiplicity of infection (MOI) of 0.5 and 1.0 for 18 h. Fluorescent microscopy and flow cytometry were used for EGFP detection of cancer cells. EGFP-expressing cells were confirmed as cancer cells with specific markers by immunohistochemistry staining. Limits of detection of cancer cells in body fluid were measured by serial dilutions. Applicability of technique was confirmed with samples from patients with malignant pleural effusions. NV1066 expressed EGFP in 111 human cancer cell lines detected by fluorescent microscopy at an MOI of 0.5. NV1066 selectively infected cancer cells and spared normal cells as confirmed by immunohistochemistry. Sensitivity of detecting fluorescent green cells was 92% (confidence interval [CI] 83% to 97%) at a ratio of 1 cancer cell to 1 million normal cells. EGFP-positive cells were detected by fluorescent microscopy in patients' malignant pleural effusion samples. Our data show proof of the concept that NV1066-induced EGFP expression allows detection of a single cancer cell against a background of 1 million normal cells. This method was demonstrated to be a reliable screening tool for human cancer cells in a suspension of normal murine cells as well as clinical specimens of malignant pleural effusions.

First-in-man Safety and Efficacy of the ClearRing Implant for the Treatment of Benign Prostatic Hyperplasia.

BACKGROUND: Although effective for benign prostatic hyperplasia (BPH), transurethral resection of the prostate (TURP) can be associated with side effects including prolonged recovery, storage and voiding symptoms, and a risk of acute urinary retention. OBJECTIVE: To test a new minimally invasive device for the treatment of lower urinary tract symptoms (LUTS) due to BPH, involving implantation of a C-shaped nitinol ring (ClearRing) in a circular incision in the prostatic tissue using an electrocuting blade over a dilatation balloon. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter single-arm clinical trial involving 29 men with severe symptomatic BPH. INTERVENTION: Implantation of a ClearRing device under regional anesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness in alleviating LUTS was assessed in terms of International Prostate Symptom Score (IPSS) at baseline and 3, 6, and 12 mo after the procedure. To evaluate changes from baseline, a general estimating equation model was fitted to IPSS, the Quality of Life (QOL) scale, Benign Prostatic Hyperplasia Impact Index, maximum flow rate (Qmax), and postvoid residual volume. Statistical significance was defined as p<0.05. RESULTS AND LIMITATIONS: The average age was 71.4 yr, prostate size was 35-50cm3, and IPSS was 21.6. All procedures were successfully completed with one implant in 28 patients and two implants in one patient. No serious complications occurred. Patients experienced symptom relief by 3 mo that was sustained to 12 mo. Mean IPSS, QOL, and Qmax improved by 45%, 41%, and 40% by 3 mo, and 53%, 52%, and 49% by 12 mo, respectively (p<0.05). Adverse events were mild and transient. There were no reports of loss of antegrade ejaculation or any effects on erectile function. Implantation positioning failed in 11/29 patients, who then underwent uneventful TURP. After modification of the delivery device, the success rate for implant positioning improved from 5/13 patients to 13/16 patients. Study limitations include the single-arm nature and the low patient number. CONCLUSIONS: We demonstrated preliminary feasibility of the ClearRing device for minimally invasive treatment of BPH in men. Further studies are needed to confirm the safety and efficacy of this approach. PATIENT SUMMARY: In this study we tested outcomes after implantation of a ClearRing device in patients with benign prostatic hyperplasia. We found that the device was safe and effective. However, there was a high rate of implantation failure due to malpositioning, which was significantly improved following modification of the delivery device.

Detection of bladder cancer in human urine by metabolomic profiling using high performance liquid chromatography/mass spectrometry.

PURPOSE: The current use of cystoscopy for screening and detecting bladder cancer is invasive and expansive. Various urine based biomarkers have been used for this purpose with limited success. Metabolomics, ie metabonomics, is the quantitative measurement of the metabolic response to pathophysiological stimuli. This analysis provides a metabolite pattern that can be characteristic of various benign and malignant conditions. We evaluated high performance liquid chromatography coupled online with a mass spectrometer metabolomic approach to differentiate urine samples from healthy individuals and patients with bladder cancer. MATERIALS AND METHODS: Urine specimens were collected from 48 healthy individuals and 41 patients with transitional cell carcinoma, and stored at -80C. Samples were analyzed using an Agilent 1100 Series high performance liquid chromatography system (Agilent Technologies, Santa Clara, California) coupled online with a hybrid triple-quad time-of-flight QSTAR XL mass spectrometer. At the time of analysis samples were thawed and centrifuged. The resulting total ion chromatograms of each sample were submitted for statistical analysis. For data interpretation in this study 2 statistical methods were used, that is principal component analysis and orthogonal partial least square-discriminate analysis. RESULTS: Using positive ionization mass spectrometry orthogonal partial least square-discriminate analysis correctly predicted 48 of 48 healthy and 41 of 41 bladder cancer urine samples, while principal component analysis, which is an unsupervised profiling statistical method, confirmed these results and correctly predicted 46 of 48 healthy and 40 of 41 bladder cancer urine samples. CONCLUSIONS: The results of this proof of concept study in a relatively small number of subjects indicate that metabolomics using high performance liquid chromatography-mass spectrometry has the potential to become a noninvasive early detection test for bladder cancer.

The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate.

INTRODUCTION: Radical prostatectomy (RP) is associated with erectile dysfunction (ED). A single, placebo-controlled, human study has assessed the effects of regular sildenafil use after RP and demonstrated an increased chance of preservation of preoperative erectile function. Aim. This study was undertaken to define the effects of such a regimen in an animal model. METHODS: Using the cavernous nerve (CN) crush injury model, animals were divided into a number of groups: no CN injury (sham), bilateral CN injury exposed to either no sildenafil (control) or sildenafil at two doses (10 and 20 mg/kg) subcutaneously daily for three different durations (3, 10, 28 days). MAIN OUTCOME MEASURES: At these time points, CN electrical stimulation was used to assess erectile function by mean intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio. For the structural analyses, whole rat penes were harvested. Staining for Masson's trichrome was utilized to calculate the smooth muscle-collagen ratio. Immunohistochemical antibody staining was performed for endothelial (CD31 and eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed to analyze the AKT/eNOS pathway. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used for the assessment of apoptotic indices and the CN architecture was evaluated by transmission electron microscopy (TEM). RESULTS: Erectile function was improved with sildenafil in a time- and dose-dependent fashion with maximization of erectile function recovery occurring with daily 20 mg/kg at the 28-day time point. Sildenafil use resulted in smooth muscle-collagen ratio protection and CD31 and eNOS expression preservation. Sildenafil reduced apoptotic indices significantly compared with control. Animals exposed to sildenafil had increased phosphorylation of akt and eNOS. Tem demonstrated distinct differences in architecture between control and sildenafil groups toward an increased amount of myelinized nerve fibers. CONCLUSIONS: Sildenafil use in the CN crush injury model preserves erectile function that appears to be mediated predominantly through preservation of smooth muscle content and endothelial function as well as through reduction in apoptosis.

Expanding the Utilization of Robotic Procedures in Urologic Surgery.

Although the word "robot" was coined in 1921, only close to 70 years later were robotic devices developed to assist during surgery. Urology has always been at the forefront of endoscopic, minimally invasive, and robotic developments in medicine. Robotic prostatectomy signaled the emerging role of robotic surgery in urology, but since then it has been applied to every urologic laparoscopic procedure.

Initial Clinical Experience with a Modulated Holmium Laser Pulse-Moses Technology: Does It Enhance Laser Lithotripsy Efficacy?

OBJECTIVE: The Lumenis® High-power Holmium Laser (120H) has a unique modulated pulse mode, Moses™ technology. Moses technology modulates the laser pulse to separate the water (vapor bubble), then deliver the remaining energy through the bubble. Proprietary laser fibers were designed for the Moses technology. Our aim was to compare stone lithotripsy with and without the Moses technology. METHODS: We designed a questionnaire for the urologist to fill immediately after each ureteroscopy in which the Lumenis 120H was used. We compared procedures with (n=23) and without (n=11) the use of Moses technology. Surgeons ranked the Moses technology in 23 procedures, in comparison to regular lithotripsy (worse, equivalent, better, much better). Laser working time and energy use were collected from the Lumenis 120H log. RESULTS: During 4 months, five urologists used the Lumenis 120H in 34 ureteroscopy procedures (19 kidney stones, 15 ureteral stones; 22 procedures with a flexible ureteroscope, and 12 with a semi-rigid ureteroscope). Three urologists ranked Moses technology as much better or better in 17 procedures. In 2 cases, it was ranked equivalent, and in 4 cases ranking was not done. Overall, laser lithotripsy with Moses technology utilized laser energy in less time to achieve a satisfying stone fragmentation rate of 95.8 mm3/min versus 58.1 mm3/min, P=0.19. However, this did not reach statistical significance. CONCLUSION: The new Moses laser technology demonstrated good stone fragmentation capabilities when used in everyday clinical practice.

Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.

5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer.

Oncolytic herpes viruses are attenuated, replication-competent viruses that selectively infect, replicate within, and lyse cancer cells and are highly efficacious in the treatment of a wide variety of experimental cancers. The current study seeks to define the pharmacologic interactions between chemotherapeutic drugs and the oncolytic herpes viral strain NV1066 in the treatment of pancreatic cancer cell lines. The human pancreatic cancer cell lines Hs 700T, PANC-1, and MIA PaCa-2 were treated in vitro with NV1066 at multiplicities of infection (MOI; ratio of the number of viral particles per tumor cell) ranging from 0.01 to 1.0 with or without 5-fluorouracil (5-FU) or gemcitabine. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Viral replication was measured using a standard plaque assay. Six days after combination therapy, 76% of Hs 700T cells were killed compared with 43% with NV1066 infection alone (MOI = 0.1) or 0% with 5-FU alone (2 micromol/L) (P < .01). Isobologram and combination-index analyses confirmed a strongly synergistic pharmacologic interaction between the agents at all viral and drug combinations tested (LD5 to LD95) in the three cell lines. Dose reductions up to 6- and 78-fold may be achieved with combination therapy for NV1066 and 5-FU, respectively, without compromising cell kill. 5-FU increased viral replication up to 19-fold compared with cells treated with virus alone. Similar results were observed by combining gemcitabine and NV1066. We have demonstrated that 5-FU and gemcitabine potentiate oncolytic herpes viral replication and cytotoxicity across a range of clinically achievable doses in the treatment of human pancreatic cancer cell lines. The potential clinical implications of this synergistic interaction include improvements in efficacy, treatment-associated toxicity, tolerability of therapeutic regimens, and quality of life. These data provide the cellular basis for the clinical investigation of combined oncolytic herpes virus therapy and chemotherapy in the treatment of pancreatic cancer.

[Nephron sparing surgery as a treatment modality for renal angiomyolipoma].

OBJECTIVE: There is no consensus concerning the indications for active treatment (selective angioembolization (SAE) or surgery) versus observation alone, and the treatment modality for patients with renal angiomyolipoma (AML). Our study aimed to analyze the results of long-term follow-up of patients with renal AML treated by nephron-sparing surgery (NSS). MATERIALS AND METHODS: The medical records of thirteen patients with renal AML were retrospectively reviewed for clinical and histopathologic features. There were twelve women and one man (mean age 55 years) who were treated by NSS in our medical center between the years 1993-2001. RESULTS: One patient with tuberous sclerosis had bilateral multifocal tumors, another patient that presented with shock and retroperitoneal bleeding underwent an urgent NSS. Overall, eight patients were symptomatic at diagnosis. The mean tumor diameter was 5.5 cm (range 2.5-13 cm). There was no need to perform nephrectomy in any of the patients. Two patients had enucleation of more than one tumor in the same session. In one case the adrenal gland was surrounded by the AML and was removed with the specimen. No other serious complications were recorded. Four patients required blood transfusions. The mean follow-up period was 26 months (range: 6-62 months) and during that time there was no evidence of recurrence or decreased renal function. Only one patient developed AML in the contralateral kidney, there was one case of incisional hernia and another patient continued to suffer from flank pain. CONCLUSIONS: The results of the present study suggest that NSS is a safe and effective treatment modality for renal AML.

Bladder tumor antigen stat test in non-urothelial malignant urologic conditions.

BACKGROUND: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine. OBJECTIVES: To evaluate the BTA stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity. METHODS: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by the BTA stat test and cytology. RESULTS: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for the BTA stat test varied among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%. CONCLUSIONS: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.

[The role of nephron sparing surgery for renal cancer].

AIM: A contemporary review of the indications, techniques and outcome of the nephron sparing surgical approach in the management of solid renal masses. MATERIAL AND METHODS: Pertinent articles were reviewed using the MEDLINE. RESULTS: Nephron sparing surgery is increasingly being used to treat patients with solid renal lesions. The technical success rate of nephron sparing surgery is excellent, and operative morbidity and mortality are low. For renal cell carcinoma, long-term cancer-free survival is comparable to radical nephrectomy, particularly in patients with low stage disease. The reported incidence of multifocal renal cell carcinoma is approximately 15%, and it depends on tumor size, histology and stage. The risk of multifocal disease is low (less than 5%), when the maximal diameter of the primary tumor is 4 cm or less. Minimally invasive modalities of tumor resection or destruction show promising results, however they should be reserved for selected patients and await improvement in technology. Only when long-term follow-up data is available these methods might become routine clinical practice. CONCLUSIONS: Nephron sparing surgery provides effective therapy for patients in whom preservation of renal function is a relevant clinical consideration. Accumulating data in appropriately selected patients suggest a long-term functional advantage gained by the maximal preservation of unaffected renal parenchyma without sacrificing cancer control.

The effect of urinary bladder catheterization on patient care in an internal medicine department.

INTRODUCTION: Recommendations for urinary catheterization in newly hospitalized patients are inconsistent and unclear. METHODS: The authors studied prospectively consecutive patients who were catheterized in an internal medicine department over a 3-month period, with follow-up for 6 months or until the catheter was removed. Patient records were reviewed to determine if catheterization was definitely not indicated by commonly accepted criteria. After chart review, a category of possibly not indicated was defined as having no demonstrable effect on patient care. RESULTS: There were 17.7% patients (122/691) catheterized during their admission. According to accepted criteria, definite inappropriate catheterization occurred in 18 patients (14.7%). There were an additional 69 patients (56.6%) with unclear clinical benefits, hospitalized because of fever, acute congestive heart failure, a cerebral vascular accident or respiratory insufficiency due to exacerbation of chronic obstructive lung disease. During hospitalization, attempts to remove the catheter failed in 13 patients, 4 of who remained with the catheter permanently, complicated by urosepsis in 1 patient. CONCLUSION: Over 50% of the patients had acceptable indications for catheterization but no demonstrable benefit from the procedure. In such patients, the uncertain benefits of catheterization should be balanced by potential complications. Additional studies are warranted to determine the effect of acute urinary catheterization on patient care.

Functional sequelae of cavernous nerve injury in the rat: is there model dependency.

INTRODUCTION: The rat model of cavernous nerve (CN) injury has been developed in an effort to define the functional and structural consequences of neural trauma in the corpus cavernosum. However, there is no universally accepted method of inducing nerve injury in this model, with neurotomy and crush models being used currently. To address this issue, we induced CN injury using various techniques in an effort to compare the hemodynamic sequelae of these injuries. METHODS: Twenty-five adult male Sprague-Dawley rats were divided into five groups: (1) control: laparotomy only; (2) exposure: laparotomy and exposure of cavernous nerves bilaterally without nerve manipulation; (3) neurotomy; bilateral neurotomy; (4) bulldog crush: bilateral nerve crush with bulldog vascular clamp; and (5) hemostat nerve crush: bilateral nerve crush with a hemostat. Ten days later, a second operation was performed during which systemic mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured in response to CN stimulation proximal to the site of injury. Hemodynamic endpoints assessed included ICP/MAP ratio, rate of tumescence, and rate of detumescence. RESULTS: The ICP/MAP ratio (mean +/- 95% confidence interval) in the control group was 70 +/- 4%. ICP/MAP ratios were significantly reduced in all CN injury groups compared with control group: exposure: 41 +/- 10% (P < 0.001); neurotomy: 35 +/- 15% (P < 0.001); bulldog crush: 39 +/- 13% (P < 0.001); hemostat crush: 31 +/- 9% (P < 0.0001). No significant difference existed in ICP/MAP ratios between the injury groups. Of note, the exposure group also demonstrated significant functional alterations. The rates of tumescence and detumescence were significantly reduced in all groups compared with the control group. CONCLUSION: No significant difference in the magnitude and consistency of hemodynamic alterations has been demonstrated in all CN injury models assessed in this study.

Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. METHODS: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. RESULTS: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. CONCLUSION: These findings support the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM.

Comparison of nephron-sparing surgery in central versus peripheral renal tumors.

OBJECTIVES: To determine the feasibility of nephron-sparing surgery (NSS) in patients with centrally located tumors. METHODS: A retrospective cohort study of 118 patients who underwent NSS between 1993 and 2002 (35 patients with centrally located tumors and 83 with peripherally located tumors) was performed. Kaplan-Meier curves were constructed to evaluate freedom from local recurrence and disease-specific survival in patients with conventional histologic subtype tumors. The Wilcoxon test was used to compare the curves (two-tailed P < or =0.05 was considered to be statistically significant). RESULTS: Intraoperatively, in patients with centrally located tumors, the need to close the collecting system (P = 0.035) and for blood transfusions (P = 0.033) was greater. Two perioperative deaths occurred in patients with peripherally located tumors. Two patients with centrally located tumors subsequently underwent nephrectomy. Of the patients with centrally located tumors, 1 patient had a positive margin, 2 patients had local recurrence, and 1 patient developed metastasis. No positive surgical margins or local recurrence was found in patients with peripherally located tumors, although 4 patients developed distant metastasis. Kaplan-Meier curves for patients with conventional histologic subtype tumors demonstrated a statistically significant difference for local recurrence (P = 0.04), but not for survival (P = 0.71). The mean follow-up time was 38.8 and 43.8 months for patients with centrally located and peripherally located tumors, respectively. CONCLUSIONS: NSS can be used to postpone, or eliminate the need for, nephrectomy in 94.3% of patients with centrally located tumors and can achieve oncologic disease control similar to that for exophytic lesions. These data indicate that NSS should be considered even for patients with centrally located tumors, taking into account that performing such surgery is a challenging task.