Robert I. Carey

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 PGE2 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.

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.

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.

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.

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.

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.

Patient Positioning and Trocar Placement for Robotic Urologic Procedures

Robotic-assisted laparoscopic urologic surgery is fast becoming established as a standard of care for many urologic diseases. As more experience and long-term follow-up of procedures is accumulating, the safety of robotic technology is becoming well established. In this chapter we wish to describe logistical issues pertaining to patient positioning for the two areas of commonly performed urologic operations: those in the pelvis (prostate/ureter/bladder), and those for the upper tract (kidney/ureter/adrenal), in and around the kidney. General principles of patient positioning and port placement will be described followed by specific examples of complex situations, and how to overcome them.

Patient Positioning for Robotic Urologic Procedures

Advances in robotic-assistedlaparoscopic surgery have exponentially increased since the introduction of the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA). “Robotic” surgery has become more prevalent in many centers of surgical excellence around the world. The radical retropubic prostatectomy for treatment of prostate cancer has become a focal point of experience for robotic-assisted operations in the pelvis. The most common robotic-assisted renal operation has been the dismembered pyeloplasty. Although necessary long-term follow-up of these procedures has not yet been achieved, it is becoming increasingly apparent that robotic technology is changing the standard of care for complex urologic procedures. In this chapter, we describe logistical issues pertaining to patient positioning for these two most commonly performed urologic operations. Emphasis will be placed on patient and staff safety issues, ergonomics, and optimizing surgical exposure.

Extracorporeal shock-wave lithotriptors: why newer may not be better

BACKGROUND Since the introduction of the first litho triptor (HM3; Dornier MedTech, Kennesaw, GA) for extracorporeal shock-wave lithotripsy (ESWL), a series of lithotriptors have been developed to increase patient comfort, including the Lithostar® Plus (LSP; Siemens Medical Solutions, Erlangen, Germany) and the Modulith® SLX (SLX; Storz Medical, Kreuzlingen, Switzerland), which has the additional feature of a broader shock-wave aperture. Faced with these technological advancements, Gerber and colleagues asked the question, is newer always better?