Bochdalek-type Diaphragmatic Hernia Leading to High-grade Kidney Obstruction.

A 94-year-old female presented with sharp right flank pain. Imaging demonstrated herniation of the right renal pelvis and proximal ureter into a large diaphragmatic hernia. She underwent ureteral stent placement with resolution of her symptoms. Congenital diaphragmatic hernias can cause a variety of pulmonary, cardiac, and gastrointestinal symptoms. This is 1 of only 3 cases in the literature of unilateral kidney obstruction due to herniation of the renal pelvis and proximal ureter into a Bochdalek-type diaphragmatic hernia. Ureteral stenting is a good option to decompress the kidney. Hernia reduction and primary diaphragm repair remain the definitive treatment.

Detection of live circulating tumor cells by a class of near-infrared heptamethine carbocyanine dyes in patients with localized and metastatic prostate cancer.

Tumor cells are inherently heterogeneous and often exhibit diminished adhesion, resulting in the shedding of tumor cells into the circulation to form circulating tumor cells (CTCs). A fraction of these are live CTCs with potential of metastatic colonization whereas others are at various stages of apoptosis making them likely to be less relevant to understanding the disease. Isolation and characterization of live CTCs may augment information yielded by standard enumeration to help physicians to more accurately establish diagnosis, choose therapy, monitor response, and provide prognosis. We previously reported on a group of near-infrared (NIR) heptamethine carbocyanine dyes that are specifically and actively transported into live cancer cells. In this study, this viable tumor cell-specific behavior was utilized to detect live CTCs in prostate cancer patients. Peripheral blood mononuclear cells (PBMCs) from 40 patients with localized prostate cancer together with 5 patients with metastatic disease were stained with IR-783, the prototype heptamethine cyanine dye. Stained cells were subjected to flow cytometric analysis to identify live (NIR(+)) CTCs from the pool of total CTCs, which were identified by EpCAM staining. In patients with localized tumor, live CTC counts corresponded with total CTC numbers. Higher live CTC counts were seen in patients with larger tumors and those with more aggressive pathologic features including positive margins and/or lymph node invasion. Even higher CTC numbers (live and total) were detected in patients with metastatic disease. Live CTC counts declined when patients were receiving effective treatments, and conversely the counts tended to rise at the time of disease progression. Our study demonstrates the feasibility of applying of this staining technique to identify live CTCs, creating an opportunity for further molecular interrogation of a more biologically relevant CTC population.

Comprehensive overview of axitinib development in solid malignancies: focus on metastatic renal cell carcinoma.

The landscape of treatment for metastatic renal cell carcinoma (mRCC) continues to evolve. Although several new drugs have been approved for the treatment of this disease in recent years, mRCC remains incurable. Thus, the search continues for new effective therapies. One such novel compound is axitinib (Inlyta, Pfizer), a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor. Following phase I testing in advanced solid tumors (where hypertension, stomatitis, and diarrhea were the dose-limiting toxicities), use of axitinib has been further developed through phase II testing in thyroid, breast, lung, and renal cancers. Recently, the phase III AXIS (Axitinib [AG 013736] as Second Line Therapy for Metastatic Renal Cell Cancer) trial demonstrated an improvement in progression-free survival for patients with mRCC who were treated with axitinib versus sorafenib (Nexavar, Bayer) as second-line therapy. This article describes the preclinical and clinical evolution of axitinib, with an emphasis on its development and role in mRCC.

Functional outcomes and complications in patients with bladder cancer undergoing robotic-assisted radical cystectomy with extracorporeal Indiana pouch continent cutaneous urinary diversion.

OBJECTIVE: To evaluate the functional outcomes and complications for patients with bladder cancer undergoing robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion. METHODS: From February 2004 to March 2010, 34 patients underwent robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion reconstruction. After surgery, the complications were identified, categorized, and graded using an established 5-grade modification of the original Clavien grading system, and continence was assessed. Descriptive statistics were used in evaluating the outcomes. Fischer's exact test was used in the comparison of early and late Clavien grade III complications. RESULTS: Overall, 175 (123 early and 52 late) complications after surgery were reported in 32 (94%) of 34 patients. Within 90 days of surgery, 31 (91%) of 34 patients experienced ≥ 1 early complication. Of 34 patients, 15 (44%) reported ≥ 1 late complications (>90 days). Most (85% and 69%, respectively) early and late complications were graded as minor (grade II or less). Fewer patients with early complications required an additional intervention (grade III) compared with patients with late complications (14% vs 31%; P = .116). The most common complication in both intervals was infection, reported in 22% and 37% of patients with early and late complications, respectively. The continence data for 31 patients at a mean follow-up of 20.1 months (median 12.0) showed that all but 1 patient (97%) had daytime and nighttime continence. CONCLUSION: Patients undergoing robotic-assisted laparoscopic radical cystectomy with Indiana pouch continent cutaneous urinary diversion reconstruction have comparable complication rates and functional outcomes compared with patients in the open series.

Novel therapies for metastatic renal cell carcinoma: efforts to expand beyond the VEGF/mTOR signaling paradigm.

With six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease. However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues.

Controlling the dorsal venous complex during robotic prostatectomy.

INTRODUCTION: The objective of our study was to determine whether dorsal venous complex (DVC) control technique influences positive apical margins following robotic assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: One thousand fifty-eight patients who underwent RALRP at City of Hope from June 2007 to October 2009 were assessed. Endoscopic stapling and suture ligature of the DVC were compared. Positive apical margins were identified and compared based on DVC-control technique. Recurrence probability was estimated using the Kaplan-Meier method, and logistic regression analysis was used to predict the odds of positive apical margins. RESULTS: Of 1058 patients, 633 (60%) underwent endoscopic stapling, and 425 (40%) had suture ligature. The groups had similar baseline characteristics including age and body mass index. We observed a statistically different PSA (5.4 ng/mL versus 5.2 ng/mL, p = 0.03) and operative time (2.8 hours versus 2.7 hours, p = 0.02) between stapling and suture groups, but the actual difference was small. Operative time, Gleason score, pathologic stage, and overall positive margin rates were not significantly different between groups. Positive apical margins were observed in 39 (6%) and 27 (6%) patients in the staple and suture groups, respectively. Multivariate analysis showed that the positive apical margin rate was greater in patients with higher pathologic stage and final pathological Gleason score. CONCLUSIONS: During RALRP, there is no difference in positive apical margin rate when the DVC is controlled using either endoscopic stapling or suture ligature. However, patients with a higher pathologic stage and final pathologic Gleason score are at higher risk for positive apical surgical margins.

Robotic-assisted laparoscopic radical cystectomy in the octogenarian.

BACKGROUND: The advanced age and comorbidities often associated with bladder cancer patients creates a difficult scenario regarding further management. Robotic-assisted laparoscopic radical cystectomy (RALRC) has had favorable results as a minimally invasive treatment option. We studied perioperative outcomes of RALRC in octogenarians to discern if there is any added benefit in this patient population. METHODS: One hundred and sixty robotic cystectomies have been performed between October 2003 and June 2010. We identified 24 octogenarians who underwent RALRC and form the cohort of the study. RESULTS: Mean patient age was 84.7 years and mean BMI was 24 kg/m². Most of the patients in the study had serious medical comorbidities, as 82.6% of them had an ASA classification ≥ 3 and 95.6% had Charlson scores ≥ 3. There was one open conversion and two patients had positive surgical margins. There were a total of 45 complications in the study, with 14 major complications observed in the 90-day period after surgery. There were five patients who had no complications, and two patients expired as a result of multiple organ failure. At 24 months the overall, disease-free and disease-specific survivals were 51.1%, 64.3%, and 79%, respectively. The 90-day mortality rate was 8.7%. CONCLUSIONS: Octogenarians undergoing RALRC have a significant risk of morbidity and mortality. The relationship between advanced age and oncologic outcomes or complications needs to be discerned further as it relates to the octogenarian. Further study is needed to delineate the safety and efficacy of this approach.

Recent advances in the therapy of castration-resistant prostate cancer: the price of progress.

Within the past two years, three agents have garnered approval from the US FDA for the specific treatment of metastatic castration resistant prostate cancer (mCRPC) - (1) abiraterone, (2) cabazitaxel and (3) sipuleucel-T. In separate phase III studies, each agent led to an improvement in overall survival (OS) of 2-4 months over a suitable comparator. With these costly therapies all having potential application in the patient with mCRPC, multiple entities (industry, government, and the general public) must strategize to determine how the cost burden of these agents can be balanced with the potential gains for the individual patient. Herein, we provide a framework with which to approach this dilemma.

New therapies for castrate-resistant prostate cancer.

INTRODUCTION: Prostate cancer is the second leading cause of cancer death in men in the USA, and most of these deaths will occur as a result of castrate-resistant prostate cancer (CRPC) that has progressed despite androgen deprivation therapy. There has been better understanding of castration resistance and molecular mechanisms of prostate cancer progression recently, leading to new treatment strategies. AREAS COVERED: This review focuses on emerging and new therapies for castrate-resistant prostate cancer, including hormonal therapy, immunotherapy and cytotoxic agents. EXPERT OPINION: New treatment strategies have been developed in recent years and, with improved understanding of advanced CRPC, additional targeted treatments are expected in the near future. Further cost effectiveness research of these treatments is warranted before dissemination of these promising agents.

Initial series of robot-assisted laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer.

Robotic technology has enabled urologists to perform a variety of laparoscopic surgeries. Robotic surgery offers enhanced optical magnification and visualization with precise surgical movements. We report the first case series of robot-assisted laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous testicular cancer in three consecutive patients. All procedures were performed using a modified template nerve-sparing approach. The mean patient age was 31 yr. Estimated blood loss was 150-200 ml; operative time was 150-240 min. Length of stay was 2 d, and there were no perioperative complications. This early series in carefully selected and well-informed patients represented a limited experience. These results may not be applicable to all surgeons. Further long-term follow-up with a larger number of patients are warranted to validate these preliminary findings.

Oncologic outcomes for complete robot-assisted laparoscopic management of upper-tract transitional cell carcinoma.

BACKGROUND AND PURPOSE: The gold standard for treatment of upper-tract transitional cell carcinoma (TCC) is nephroureterectomy. For distal ureteral TCC, distal ureterectomy with ureteral reimplantation represents a treatment option. Multiple minimally invasive techniques have been introduced with the goal of replicating these open procedures. Currently, there is a paucity of literature for the use of robot-assisted laparoscopic (RAL) management of upper-tract TCC. We evaluated our experience with RAL management of upper-tract TCC. PATIENTS AND METHODS: A retrospective chart review was performed on all patients who underwent complete RAL nephroureterectomy or distal ureterectomy with ureteral reimplantation at our institution. RESULTS: Eleven patients with a mean age of 67.4 years underwent RAL nephroureterectomy. Mean operative time was 326 minutes (range 243-470 minutes), estimated blood loss 200 mL (range 100-400 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 15.2 months (range 2-31 months), four patients experienced recurrence, and two ultimately died from metastatic disease. Four patients with a mean age of 73.5 years underwent RAL distal ureterectomy with ureteral reimplantation for distal ureteral TCC. Mean operative time was 311 minutes (range 225-446 minutes), estimated blood loss 200 mL (range 100-350 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 30.5 months (range 12-48 months), only one patient, whose pathology exhibited carcinoma in situ within periureteral tissue, required adjuvant treatment for recurrent disease. CONCLUSIONS: RAL nephroureterectomy and distal ureterectomy with ureteral reimplantation are feasible options for patients with upper-tract TCC with promising short-term oncologic outcomes.

Robotic assisted laparoscopic salvage prostatectomy for radiation resistant prostate cancer.

PURPOSE: We report on outcomes of robotic assisted laparoscopic radical prostatectomy as salvage local therapy for radiation resistant prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients who underwent robotic assisted laparoscopic radical prostatectomy for biopsy proven prostate cancer after primary radiation treatment. Patient characteristics, intraoperative and perioperative data, and oncological and functional outcomes were assessed. RESULTS: A total of 18 patients were identified with a median followup of 18 months (range 4.5 to 40). Primary treatment was brachytherapy in 8 patients and external beam radiation in 8, while 2 underwent proton beam therapy. Median age at salvage robotic assisted laparoscopic radical prostatectomy was 67 years (range 53 to 76). Median preoperative prostate specific antigen was 6.8 ng/ml (range 1 to 28.9) and median time to surgery after primary treatment with radiation was 79 months (range 7 to 146). Median operative parameters for estimated blood loss, surgery length and hospital stay were 150 ml, 2.6 hours and 2 days, respectively. No patient required conversion to open surgery or a blood transfusion, or experienced a rectal injury. Perioperative complications occurred in 7 patients (39%) of which the most common was urine leak identified by postoperative cystogram. Five patients (28%) had a positive surgical margin. Although some patients had limited followup, 6 (33%) were continent and 67% were free of biochemical progression. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy can be performed safely as salvage local therapy after failed radiation therapy. Outcomes are comparable to those of large series of open salvage prostatectomy.

Four-arm robotic partial nephrectomy for complex renal cell carcinoma.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains challenging to even experienced laparoscopists. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery (NSS). We represented our technique and results of robotic partial nephrectomy (RPN) for hilar, endophytic, and multiple renal tumors. MATERIALS AND METHODS: Between May 2006 and March 2008, 29 patients with complex renal tumors underwent RPN, including hilar (n = 14), endophytic (n = 12) and multiple tumors (n = 3).The hilar vessels were clamped with laparoscopic bulldog with warm ischemia. Follow-up ranged from 3 to 23 months (mean of 15 mo). The perioperative data and pathologic results were retrospectively reviewed. RESULTS: Robotic partial nephrectomy procedures were performed successfully without complications. The mean diameter of tumors was 3.0 cm (range 2.0-4.0). The mean operative time was 197 minutes (range 172-259), and the mean blood loss was 220 ml (range 100-370). The mean warm ischemia time (WIT) was 25 min (range 16-43). The hospital stay averaged 2.5 days (range 2-3). Histopathology confirmed clear-cell carcinoma (n = 21), chromophobe cell carcinoma (n = 4), hybrid oncocytic tumor (n = 2), oncocytoma (n = 1), and cystic renal cell carcinoma (n = 1). All cases had negative surgical margins. At the 3-23 months (mean of 15 mo) follow-up, no patients experienced a significant change of glomerular filtration rate compared to preoperative levels and there was no evidence of tumor recurrence. CONCLUSION: Robotic partial nephrectomy is a safe and feasible procedure. RPN is a preferred approach for complex renal tumors when NSS is indicated. For complex and technical challenging renal tumors, robotic assistance may provide patients the benefit of minimally invasive surgery.

Beyond castration and chemotherapy: novel approaches to targeting androgen-driven pathways.

In castrate-resistant prostate cancer, beyond chemotherapy, existing guidelines suggest only supportive care. However, recent evidence suggests that continued targeting of androgen-dependent pathways may be an efficacious approach. Clinical data is now available for two mechanistically distinct agents (abiraterone and MDV3100) that both ultimately target these pathways. Abiraterone is a potent and irreversible inhibitor of CYP17, a critical enzyme in androgen biosynthesis. Phase II studies indicate substantial declines in PSA amongst castrate-resistant patients treated with abiraterone, both prior to and following cytotoxic chemotherapy. In contrast to abiraterone, MDV3100 is a direct inhibitor of the androgen receptor, binding the receptor irreversibly with substantially higher affinity as compared to bicalutamide. A recent phase I/II trial of MDV3100 in castrate-resistant prostate cancer demonstrated tolerability of the agent with activity at the lowest dose level. On the basis of these compelling data, both abiraterone and MDV3100 will be examined in the phase III setting.

Training of urologic oncology fellows does not adversely impact outcomes of robot-assisted laparoscopic prostatectomy.

PURPOSE: Robot-assisted laparoscopic prostatectomy (RALP) is an increasingly popular treatment choice among men with clinically localized prostate cancer and has resulted in the need to adequately train urologists to perform the procedure. We reviewed the City of Hope experience to determine if the extent of fellow involvement in the procedure has an adverse effect on surgical outcomes. PATIENTS AND METHODS: We reviewed the charts of 1833 patients who underwent RALP at the City of Hope from January 2004 to September 2007. During the academic year, each fellow has participated in 300 or more RALP with a systematic stepwise approach to learning the operation. The procedure is divided into six segments arranged by the sequence of learning. We examined intraoperative and perioperative outcomes stratified by quartiles of the academic year corresponding to the fellows' progress through the different segments of the operation. RESULTS: No differences were found across quartiles of the academic year for intraoperative or perioperative complications, length of hospital stay, continence rates at 1 year, time to continence, and prostate-specific antigen-free recurrence rates. In the 1st and 3rd quarters of the academic year, from July to September and January to March, there were slightly longer operative times with a mean of 2.9 hours compared with the 2nd and 4th quarter mean of 2.8 hours (P = 0.01). The 3rd quarter also demonstrated slightly higher estimated blood loss of 280 mL compared with the overall mean of 262 mL (P = 0.02). During the 3rd quarter of the year, the fellows are reliably performing bladder neck division, urethral anastomosis, and beginning to learn the dissection of the neurovascular bundles. CONCLUSIONS: We found that in a high-volume center for RALP, urologic oncology fellows can be trained to perform the procedure with no significant adverse impact on patient clinical outcomes.

Comparison of extraperitoneal and intraperitoneal augmentation enterocystoplasty for neurogenic bladder in spinal cord injury patients.

OBJECTIVES: Augmentation enterocystoplasty is the standard treatment for patients with neurogenic bladder who have failed medical management. Our "extraperitoneal" approach involves a small peritoneotomy to obtain the segment of bowel for augmentation, and a standard "clam" enterocystoplasty. We compared operative and postoperative parameters and clinical outcomes of this technique with the standard intraperitoneal technique. METHODS: We retrospectively reviewed charts of 73 patients with neurogenic voiding dysfunction refractory to medical management who underwent augmentation enterocystoplasty alone or in conjunction with additional procedures. A total of 49 patients underwent extraperitoneal augmentation and 24 patients underwent intraperitoneal augmentation. Operative and postoperative parameters including time of surgery, estimated blood loss, need for blood transfusion, time for return of bowel function, and length of hospital stay were examined. Clinical outcomes including early and late postoperative complications, and continence status were also analyzed. RESULTS: Median follow-up was 2.5 years. Patients in the extraperitoneal group had significantly shorter operative time (3.9 vs. 5.6 h, P < 0.0001); shorter hospital stay (8.0 vs. 10.5 days, P = 0.009); and shorter time to return of bowel function (3.5 vs. 4.9 days, P = 0.0005). There was no significant difference in complication rates. Postoperative continence was equally improved in both groups. When only patients with no prior abdominal surgery were compared, the findings were analogous: shorter operative time, shorter length of stay, sooner return of bowel function, and no difference in complication rate. CONCLUSIONS: The extraperitoneal technique provides an equally effective method of bladder augmentation to the standard technique with easier early postoperative recovery.

Robotic-assisted endoscopic inguinal lymphadenectomy.

INTRODUCTION: Open inguinal lymphadenectomy is a well-established therapeutic and diagnostic option for patients with invasive penile squamous cell carcinoma who are at risk of regional and distant metastases. We report the use of endoscopic robotic-assisted bilateral inguinal lymph node dissections in a patient with palpable inguinal nodes despite oral antibiotics. TECHNIQUE: A 2-cm mid-thigh incision was made to develop a plane just deep to Camper's (fatty) fascia. Once a sufficient working space was created to place 3 robotic ports and 1 assistant port, subcutaneous gas was instilled, and the robotic device was docked and used to perform the dissection. The surgical approach replicated the principles of open techniques such that the contents of the femoral canal were dissected to the inguinal ligament superiorly, the sartorius muscle laterally, and the adductor longus muscle medially to include both superficial and deep lymph nodes in the dissection template. CONCLUSIONS: To our knowledge, this is the first report of an endoscopic robotic-assisted inguinal lymph node dissection. A minimally invasive approach circumventing the need for thick skin flaps, the improved flexibility afforded by robotic instruments, and the improved magnification could decrease the morbidity associated with inguinal lymphadenectomy while maintaining oncologic principles.

Robotic salvage cystectomy in the nonagenarian.

Radical cystectomy with pelvic lymphadenectomy remains the standard treatment for muscle-invasive bladder cancer. However, bladder preservation with radiotherapy, with or without chemotherapy, represents an alternative treatment strategy. In patients that fail this bladder conservation treatment, salvage cystectomy is then indicated to treat persistent or recurrent cancer. We report our experience with robotic-assisted laparoscopic salvage radical cystoprostatectomy with pelvic lymph node dissection in a 91-year-old man. This minimally invasive approach for treatment of persistent bladder cancer refractory to chemoradiation, even in the nonagenarian, is a safe and viable alternative to traditional open surgery.

The impact of prostate gland weight in robot assisted laparoscopic radical prostatectomy.

PURPOSE: We determined whether prostate weight has an impact on the pathological and operative outcomes of robot assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS: We reviewed the records of 1,847 consecutive patients who underwent robot assisted laparoscopic radical prostatectomy at our institution. Variables were compared across quartile distributions of prostate size as defined by weight, including group 1-less than 30 gm, group 2-30 to 49.9, group 3-50 to 69.9 and group 4-70 or greater. Factors assessed in this analysis were patient age, body mass index, prostate specific antigen, Gleason score, pathological stage, margin status, operative time, blood loss, transfusion rate, length of stay and rehospitalization rate. RESULTS: Patients with a larger prostate (group 4) were older (mean age 66.2 years), had higher pretreatment prostate specific antigen (median 6.5 ng/ml), lower Gleason score (mean 6.3), longer operative time (mean 3.2 hours), higher estimated blood loss (median 250 cc) and longer hospital stay (p = 0.0002). There was a trend toward higher risk disease based on D'Amico risk stratification and positive margin status in group 1, although evidence of extracapsular extension was more common in groups 2 and 3. There was no association between prostate size and body mass index, lymph node status, blood transfusion rate, seminal vesicle involvement and rehospitalization rate. CONCLUSIONS: Robot assisted laparoscopic radical prostatectomy in patients with an enlarged prostate is feasible with slightly longer operative time, urinary leakage rates and hospital stay. Pathologically larger prostates are generally associated with lower Gleason score and risk group stratification. One-year continence rates and biochemical recurrence rates are similar across all groups.

Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history.

Superficial "non-muscle-invasive" bladder tumors represent a heterogeneous group of cancers, including those that are (1) papillary in nature and limited to the mucosa, (2) high grade and flat and confined to the epithelium, and (3) invasive into the submucosa, or lamina propria. The goal of treatment is 2-fold: (1) to reduce tumor recurrence and the subsequent need for additional therapies and the morbidity associated with these treatments and (2) to prevent tumor progression and the subsequent need for more aggressive therapy. This update reviews important contemporary concepts in the etiology, molecular mechanisms, classification, and natural history of superficial bladder cancer.