Malignant Epithelioid Mesothelioma of the Tunica Vaginalis Testis Presenting as Hydrocele in a Kidney Transplant Recipient.

Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental.

10-cm mature cystic teratoma of the bladder in 48-year-old female misdiagnosed as bladder calculus: Management with robotic partial cystectomy.

Cystic teratomas are a common ovarian neoplasm that are rarely found in other locations of the body, namely the sacrococcygeal region and anterior mediastinum. Localization to the urinary bladder is exceedingly rare, with only a few cases documented in the literature. Cystic teratomas are usually asymptomatic and found incidentally, but localization to the bladder can present as irritative lower urinary tract symptoms and/or mimic urinary tract calculi. We report the rare case of a mature cystic teratoma of the urinary bladder, presenting as foul-smelling urine with recurrent urinary tract infections and microhematuria, that was originally misdiagnosed as a bladder calculus.

Prospective evaluation of refurbished flexible ureteroscope durability seen in a large public tertiary care center with multiple surgeons.

OBJECTIVE: To evaluate the durability and cost of maintenance for outsourced, refurbished flexible ureteroscopes. MATERIALS AND METHODS: Ureteroscope usage and repair were prospectively recorded over a 365-day period at a large 836-bed public hospital. Cases were performed by 14 different urologists using either refurbished DUR-8 or DUR-8 Elite model ureteroscopes. Retrograde cases involving calculi, urothelial carcinoma, stricture, and diagnostic evaluations were included. Ureteroscope repairs were performed by a single outsourced repair vendor, not the original manufacturer. RESULTS: A total of 501 ureteroscopic cases involving 550 ureteroscope usages were performed over a 365-day period. Semirigid ureteroscopes were used for 281 (56.1%) cases and refurbished flexible ureteroscopes for 220 (43.9%). The reason for the ureteroscopy was calculi in 386 (77.0%) cases, urothelial carcinoma in 32 (6.4%), stricture in 36 (7.2%), and diagnostic in 47 (9.4%). No repairs were needed during this period for semirigid scopes. Ureteral access sheaths were used in 82 (37.7%) of the cases. A total of 32 instances of catastrophic breakage occurred. Each newly refurbished ureteroscope was used for an average of 6.9 times before incurring further damage requiring repair. CONCLUSION: Refurbished flexible ureteroscopes that have undergone comprehensive repair are extremely fragile in the setting of multiple surgeon users in a large public hospital that uses central processing for sterilization and storage. This poor durability results in significant maintenance, repair, and administrative inconvenience that should be considered along with the purchase price.

Laparoscopic-guided radiofrequency ablation is safe for the treatment of enhancing renal masses among patients prescribed antithrombotic agents.

Patients undergoing laparoscopic-guided radiofrequency ablation (LRFA) for the treatment of a renal mass are commonly prescribed antithrombotic agents for the management of comorbid medical diseases. We retrospectively evaluated the safety of LRFA in this group. From October 2005 to June 2010, 109 patients underwent LRFA. Antithrombotic therapy was prescribed to 52 of these patients. Agents were managed the week of surgery per current practice guidelines from the American College of Chest Physicians. Intraoperatively, patients prescribed at least one antithrombotic agent lost a median of 10 mL of blood, while patients not on an antithrombotic agent also lost 10 mL of blood (P = .828). Both groups had a similar rate of procedure-related complications (intraoperative, P = 1.00; postoperative, P = .673). No patient required a blood transfusion or experienced a postoperative thromboembolic event. In conclusion, when current practice guidelines are followed, LRFA is safe among patients prescribed antithrombotic agents.

Initial clinical experience with use of ureteral access sheaths in the diagnosis and treatment of upper tract urothelial carcinoma.

OBJECTIVE: To describe our experience with ureteral access sheaths in the diagnosis and treatment of upper tract urothelial carcinoma. METHODS: We retrospectively identified a patient cohort who underwent ureteroscopy for suspicion of upper tract urothelial carcinoma and identified those with placement of a ureteral access sheath. Records were reviewed for demographic information, comorbidity data, operative complications, and pathology results. The histologic grade of ureteroscopic biopsies and nephroureterectomy specimens were evaluated for concordance. RESULTS: A total of 125 patients underwent 235 procedures for known or suspected upper tract urothelial carcinoma. Access sheaths were used in patients in whom significant urothelial lesions were noted in the proximal upper urinary tract. A total of 64 patients underwent 85 sheath-inclusive procedures. Sheath deployment was successful in 83 (97.6%) of the 85 procedures. Biopsies yielded specimen adequate for histopathologic diagnosis in 75 (90.4%) of 83 cases. No ureteral access sheath-related complications were noted. Of the 125 patients, 34 underwent removal of 35 renal units. The concordance of tumor grade between biopsy and nephroureterectomy specimens was 88.6% (P=.0002). CONCLUSION: Ureteral access sheaths are safe for use in the diagnosis and treatment of upper tract urothelial carcinoma. Sheath placement facilitated the acquisition of multiple biopsy specimens adequate for histopathologic evaluation. Our technique precluded the need for repeat ureteroscopy to establish a diagnosis. Biopsies obtained through an access sheath were highly predictive of tumor grade in nephroureterectomy specimens.

Management of renal masses with laparoscopic-guided radiofrequency ablation versus laparoscopic partial nephrectomy.

BACKGROUND AND PURPOSE: Laparoscopic-guided radiofrequency ablation (LRFA) has been introduced as a minimally invasive nephron-sparing management option for renal tumors. Many patients who desire treatment present with multiple comorbidities, which poses a therapeutic challenge. Our purpose is to determine if multipass LRFA is comparable, in terms of surgical risk and immediate postoperative outcomes, to laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: A retrospective study identified 36 and 33 patients who underwent LRFA and LPN, respectively. Perioperative demographic data, tumor characteristics, and follow-up data were evaluated. Statistical analysis was performed using the Student t test and chi-square analysis. RESULTS: Age, American Society of Anesthesiology score, and Charlson Comorbidity Index were significantly higher in the LRFA group than the LPN group (P < 0.001). Average tumor size was 2.8 cm and 3.1 cm for the LRFA and LPN groups, respectively. There were no significant differences in change between the preoperative and postoperative creatinine/glomerular filtration rate values or perioperative complication rates for the groups. Estimated blood loss and length of stay were significantly lower for the LRFA group than the LPN group (P < 0.05). Follow-up ranged 6 to 23 months and 6 to 58 months for the LRFA and the LPN groups, respectively. There has been no evidence of tumor recurrence in the follow-up period. CONCLUSIONS: We present our initial report comparing patients undergoing LRFA v LPN for the management of renal tumors. Our preliminary results with our experience with multipass laparoscopic-guided RFA demonstrate that this technique can be safely used in an elderly, higher risk population. Long-term follow-up is needed to determine oncologic efficacy.

Diagnostic yield of renal biopsy immediately prior to laparoscopic radiofrequency ablation: a multicenter study.

INTRODUCTION: Ablative therapy is increasing for the management of small renal masses. Laparoscopic as well as percutaneous cryotherapy and radiofrequency ablation (RFA) have been utilized. Herein we review our experience with renal biopsy immediately prior to laparoscopic RFA. METHODS AND MATERIALS: A prospectively collected database containing all patients who underwent laparoscopic RFA by three different surgeons at two different institutions was reviewed. Renal biopsies were performed in each patient during transperitoneal laparoscopy after mobilization of the kidney and prior to RFA. The biopsy needle was passed percutaneously via a sheath through the abdominal wall. Multiple core biopsies (3-5) were taken under visual and ultrasonic guidance. All were submitted for permanent pathologic sectioning. RESULTS: 138 patients underwent renal biopsy prior to RFA. Mean tumor size was 3.0 cm (range 1.0-6.9). The mean age was 72 years (range 39-90). There were 42 females and 96 males. Mean blood loss was 28 ml (0-400 ml). Only 5 patients lost more than 50 ml, and in each case the bleeding was associated with complicated renal mobilization and dissection prior to biopsy. Final pathology revealed renal cell carcinoma in 95, oncocytic neoplasm in 26, and angiomyolipoma in 9.8 patients were considered to have nondiagnostic biopsies. In this group, final pathology revealed benign cysts in 3, inconclusive specimens in 3, fibrosis in 1, and normal tissue in 1. Hence, a clear diagnosis was possible in 130 of 138 patients, which is 94.2%. RCC was diagnosed in 68.8% of the patients, and in 73.1% of the conclusive biopsies. Eight patients had perioperative complications, including low-grade fevers (2) perirenal/retroperitonal hematoma (2), pleural tear/pneumothorax (2), CHF exacerbation, and wound infection. CONCLUSIONS: In our multicenter experience, renal biopsy of 138 renal lesions at the time of laparoscopic RFA had a diagnostic yield of 94.2%. RCC was diagnosed in 68.8% of the patients, and in 73.1% of the conclusive biopsies.

Preparation of artificial kidney stones of reproducible size, shape, and mass by precision injection molding.

PURPOSE: To prepare artificial kidney stones of defined shape, size, mass, and material composition via precision injection molding of Ultracal 30 cement slurries into an inexpensive biodegradable mold. MATERIALS AND METHODS: A calcium alginate and silica-based mold was used to prepare casts of varying shapes in a reproducible manner. Ultracal 30 cement slurries mixed 1:1 with water were injected into these casts and allowed to harden. The artificial stones were recovered and their physical properties determined. Ex-vivo and in-vivo responses to holmium laser lithotripsy were examined. RESULTS: Spheres, half spheres, cylinders, cubes, tapered conical structures, and flat angulated structures were prepared with high precision without post-molding manipulations. Large spheres of average mass 0.661 g (+/- 0.037), small spheres of average mass 0.046 g (+/- 0.0026), and hexagons of average mass 0.752 g (+/- 0.0180) were found to have densities (1610-1687 kg/m(3)) within the expected range for Ultracal 30 cement stones. Ex-vivo holmium laser lithotripsy of small spheres in saline showed uniformly reproducible efficiencies of comminution. Implantation of a tapered conical stone into the ureter of a porcine model demonstrated stone comminution in vivo consistent with that seen in the ex-vivo models. CONCLUSIONS: We present an environmentally safe, technically simple procedure for the formation of artificial kidney stones of predetermined size and shape. The technique does not require the use of hazardous solvents or postprocedural processing of the stones. These stones are intended for use in standardized experiments of lithotripsy efficiency in which the shape of the stone as well as the mass can be predetermined and precisely controlled.

First prize: direct real-time temperature monitoring for laparoscopic and CT-guided radiofrequency ablation of renal tumors between 3 and 5 cm.

PURPOSE: To evaluate our experience with radiofrequency ablation (RFA) of renal tumors in the range of 3 to 5 cm. PATIENTS AND METHODS: A series of 96 patients underwent 104 tumor laparoscopic or percutaneous CT-guided RFAs. We identified 37 tumors between 3 and 5 cm at the time of the ablation. Non-conducting temperature probes, independent of the radiofrequency (RF) electrode, were placed at the peripheral and deep margins of the tumor in order to achieve real-time temperature monitoring of the ablation zone. All ablations were continued until the peripheral and deep temperature probes reached 60 degrees C. RESULTS: All 37 patients (100%) achieved complete necrosis at the initial session. There were two radiographic failures at 9 months and 30 months that required a second treatment (95% radiographic success rate). Tissue samples taken at the time of the re-treatment (one partial nephrectomy with numerous biopsies of the deep and peripheral margins and one repeat ablation with eight core biopsies) showed no evidence of viable tumor with hematoxylin and eosin or nicotinamide adenine dinucleotide viability stains. The average length of follow-up was 11.3 months (range 1-44 months). No patient with localized disease at the time of the RFA developed local extension or metastatic disease in follow-up. CONCLUSIONS: The majority of renal tumors between 3 and 5 cm can be ablated with complete necrosis in a single session. Placement of independent temperature probes at the peripheral and deep margins of the tumor provides real-time monitoring that assists in the deployments of the RF electrode and determining the appropriate duration of the ablation cycles. Attention to real-time thermometry decreases the need for repeat sessions to achieve complete necrosis for larger tumors. Likewise, real-time thermometry decreases the incidence of overtreatment of normal parenchyma and prevents collateral damage to adjacent vital structures (ureter, pancreas, bowel, spleen, nerves) outside the desired zone of ablation.

Frequency of ureteroscope damage seen at a tertiary care center.

PURPOSE: There is controversy regarding ureteroscope durability. Little is known regarding the subsequent durability of a flexible ureteroscope after major damage has been incurred and the ureteroscope has been repaired. Maintenance and repair are associated with significant cost. We reviewed and assessed the frequency and cause of ureteroscope damage at our medical center. MATERIALS AND METHODS: From December 2001 we prospectively recorded the specific use of all ureteroscopes and any resultant damage at a single tertiary care institution. We then reviewed a total of 601 ureteroscopic cases involving 654 semirigid and flexible ureteroscope uses from December 2001 to November 2004. Cases were performed by multiple residents and fellows under the supervision of 3 attending urologists (CML, RJL and VGB). Retrograde and antegrade cases involving stones, urothelial carcinoma, strictures and diagnostic evaluations were included. Repairs for the respective ureteroscopes were performed by the original manufacturer. RESULTS: A total of 53 reports of damage (8.1% of total uses) were recorded. Major damage when the scope was deemed unusable and required repair was seen in 39 cases (6.0%). Four newly purchased flexible ureteroscopes were entered into the study and they provided 40 to 48 uses before the initial repair was needed. After these new ureteroscopes underwent comprehensive repair for major damage they averaged only 11.1 uses (median 8) before needing repair again. Older model ureteroscopes that underwent repair before being entered into our study averaged between 4.75 and 7.7 uses before being sent for subsequent repair. Of the total of 39 breakages 39 for which ureteroscopes were sent for repair 14 (35.9%) were the result of errant laser firing, 11 (28.2%) were the result of excessive torque, 8 (20.5% 8) were the result of decreased flexion in the distal tip or another loss of function without obvious iatrogenic cause, 3 (7.7%) were the result of multifocal catastrophic damage involving laser firing and excessive torque, and 3 (7.7%) were the result of cleaning and processing outside of the ureteroscopy suite. CONCLUSIONS: The most important risk factors for predicting the number of uses expected from a ureteroscope at our institution is ureteroscope age and whether the ureteroscope has undergone comprehensive repair as the result of prior damage. Our analysis suggests that after damage occurs to a ureteroscope more damage occurs with greater frequency. The cost of maintaining previously used ureteroscopes should be carefully considered in comparison to the cost of purchasing a new ureteroscope.

Endoscopic management of 10 separate fibroepithelial polyps arising in a single ureter.

INTRODUCTION: Fibroepithelial polyps of the ureter, usually of congenital or inflammatory origin, are rare entities. These polyps are often solitary, but cases of multiple polyps have also been reported. Treatment of these entities has evolved with emerging surgical techniques and technologies. SURGICAL TECHNIQUE: We describe our surgical technique for minimally invasive treatment of multiple polyps arising in a single ureter. The base of each polyp is ablated with a 365-microm holmium laser fiber operating at 10 W, and each polyp is removed from the ureteral wall with 3F grasping forceps. Hemostasis is achieved with laser coagulation. Ureteral stones are removed concurrently with a 2.4F basket. A 12/14F ureteral access sheath is used to facilitate the multiple passes of the ureteroscope and the removal of the polyps and stones from the proximal ureter. All 10 polyps were removed from the proximal portion of a single ureter. The ureteral stent was removed at 6 weeks, and follow-up intravenous urography at 6 months and ureteroscopy at 11 months showed no residual polyps or stones. The wall of the ureter was well healed, with no evidence of stricture. CONCLUSIONS: We have demonstrated a specific minimally invasive technique that can be used to treat even highly complex cases involving upper urinary tract fibroepithelial polyps.

Conservative management of a splenic injury related to percutaneous nephrostolithotomy.

INTRODUCTION: Injury to intraperitoneal organs is unusual during percutaneous renal surgery. We report a splenic injury during upper pole percutaneous renal access for nephrostolithotomy that was managed conservatively. METHODS: A 52-year-old male with left upper pole renal stones associated with a narrow upper pole infundibulum underwent upper pole renal access prior to percutaneous nephrostolithotomy (PCNL). The access was performed in the 10th to 11th intercostal space, and the patient underwent PCNL with stone clearance. Plain film radiography after percutaneous access and PCNL revealed no pneumothorax or hydrothorax. The patient was discharged on postoperative day one with the nephrostomy tube in place. RESULTS: On postoperative day 5, the patient was evaluated for persistent flank pain and bleeding from the nephrostomy tube. Computerized tomography revealed a transsplenic percutaneous renal access. The patient was admitted to the hospital, and the general surgery service was consulted. The patient was placed on strict bedrest. His hematocrit was within normal limits and remained stable. The nephrostomy tube was kept in place for 2 weeks. A pullback nephrostogram revealed no perirenal leak, and no evidence was present of acute bleeding. Follow-up computerized tomography on the same day revealed no evidence of acute bleeding. The patient was discharged without further complications and remains stone free at 1-year follow-up. CONCLUSIONS: A transsplenic renal access that was dilated and through which a successful left percutaneous nephrostolithotomy was performed is a highly unusual complication related to upper pole left renal access. We were able to manage this complication with conservative measures.

Differential selectivity of hyaluronidase inhibitors toward acidic and basic hyaluronidases.

Hyaluronidase (HAase), a class of enzymes which degrade hyaluronic acid (HA), are involved in the spread of infections/toxins, ovum fertilization, and cancer progression. Thus, HAase inhibitors may have use in disease treatments. We evaluated 21 HAase inhibitors against HYAL-1, testicular, honeybee, and Streptomyces HAases. Among these inhibitors, polymers of poly (styrene-4-sulfonate) (PSS) (i.e., molecular weight 1400-990,000 or PSS 1400-PSS 990,000) and O-sulfated HA (sHA) derivatives (sHA2.0, 2.5, and 2.75) were the most effective. HYAL-1 and bee HAases were the most sensitive, followed by testicular HAase; Streptomyces HAase was resistant to all inhibitors, except PSS 990,000 and VERSA-TL 502 (i.e., PSS 10(6) dalton). The length of the PSS polymer determined their potency (e.g., IC50 for HYAL-1, PSS 990,000: 0.0096 microM; PSS 210 no inhibition; IC50 for testicular HAase, PSS 990,000: 0.042 microM; PSS 210 no inhibition). The presence, but not the number, of sulfate groups on the sHA molecule determined its potency (e.g., IC50 for HYAL-1: sHA2.0, 0.019 microM; sHA2.75, 0.0083 microM). Other known HAase inhibitors, such as gossypol, sodium-aurothiomalate, 1-tetradecane sulfonic acid, and glycerrhizic acid, were not effective. Both PSS and sHA inhibited HAases by a mixed inhibition mechanism (i.e., competitive + uncompetitive) and were 5- to 17-fold better as uncompetitive inhibitors than as competitive inhibitors. These results demonstrate that HAase inhibitors show selectivity toward the different types of HAases, which could be exploited to inhibit specific HAases involved in a variety of pathophysiologic conditions.

Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells.

Many tumors constitutively express high levels of the inducible form of proinflammatory enzyme, cyclooxygenase-2 (COX-2). Increased COX-2 expression is associated with tumor cell resistance to many cytotoxic chemotherapy drugs. Furthermore, increased resistance to cytotoxic antitumor drugs is also known to be dependent on associated stromal cells in many tumors. We investigated whether prostate tumor-associated stromal cells, marrow-derived osteoblasts, affect cytotoxicity of 2 antitumor drugs, COL-3 and docetaxel (TXTR), and whether it is dependent on COX-2 activity. We further examined whether inhibiting the activity of COX-2 negate the stroma-induced decrease in drug sensitivity in tumor cells. COX-2-specific inhibitor celecoxib (CXB) was used to inhibit COX-2 activity and associated alteration in cell death signaling was investigated. Coculturing PC-3ML cells with osteoblasts decreased the cytotoxicity of the tested antitumor drugs and was associated with increased COX-2 activity in PC-3ML cells. A significant decrease in drug-induced PGE(2) increase and an increase in cytotoxicity were observed when cells were treated with COL-3 or TXTR combined with CXB. Cytotoxicity of single or combination treatment increased apoptosis, which was associated with caspase-3 and -9 activation, PARP cleavage, increased BAD protein, but decreased protein levels of XIAP and BCL-(xL). Oral administration of CXB (40 mg/kg) to mice with PC-3ML tumors for 42 days increased tumor latency, decreased tumor growth and enhanced tumor control with COL-3 or TXTR. Overall, a synergistic enhancement of antitumor activity in combination treatment was observed in vitro and an additive effect in vivo. These observations suggest a potential clinical use of combined dosing of COX-2 inhibitors and cytotoxic drugs at lower, nontoxic dose than currently used to treat advanced prostate cancer.

Regulation of hyaluronidase activity by alternative mRNA splicing.

Hyaluronidase is a hyaluronic acid-degrading endoglycosidase that is present in many toxins and the levels of which are elevated in cancer. Increased concentration of HYAL1-type hyaluronidase correlates with tumor progression and is a marker for grade (G) 2 or 3 bladder cancer. Using bladder tissues and cells, prostate cancer cells, and kidney tissues and performing reverse transcription-PCR, cDNA cloning, DNA sequencing, and in vitro translation, we identified splice variants of HYAL1 and HYAL3. HYAL1v1 variant lacks a 30-amino acid (aa) sequence (301-330) present in HYAL1 protein. HYAL1v1, HYAL1v2 (aa 183-435 present in HYAL1 wild type), HYAL1v3 (aa 1-207), HYAL1v4 (aa 260-435), and HYAL1v5 (aa 340-435) are enzymatically inactive and are expressed in normal tissues/cells and G1 bladder tumor tissues. However, HYAL1 wild type is expressed in G2/G3 tumors and in invasive tumor cells. Stable transfection and HYAL1v1-specific antibody confirmed that the HYAL1 sequence from aa 301 to 330 is critical for hyaluronidase activity. All tumor cells and tissues mainly express HYAL3 variants. HYAL3v1 lacks a 30-aa sequence (299-328) present in HYAL3 protein, that is homologous to the 30-aa HYAL1 sequence. HYAL3v1, HYAL3v2 (aa 251-417 present in HYAL3 wild type), and HYAL3v3 (aa 251-417, but lacking aa 299-328), are enzymatically inactive. Although splicing of a single independent exon generates HYAL1v1 and HYAL3v1, internal exon splicing generates the other HYAL1/HYAL3 variants. These results demonstrate that alternative mRNA splicing controls cellular expression of enzymatically active hyaluronidase and may explain the elevated hyaluronidase levels in bladder/prostate cancer.