Siamak Daneshmand

INTRODUCTION AND OBJECTIVES: Partial cystectomy (PC) for bladder cancer can have adequate local control in highly selected patients. However, recurrence rates are high and many patients ultimately require radical cystectomy (RC). The prognosis following RC for this specific population has not been previously reported. This study examined the prognostic indicators at the time of RC for this population. METHODS: A retrospective review of the University of Southern California bladder cancer database identified 93 patients who underwent RC for bladder cancer recurrence subsequent to a PC performed at an outside hospital. Information was collected on clinicopathologic and treatment covariates. Data on tumor stage on both the PC and RC tumor specimens were also recorded. Patients with distant metastases, other pelvic cancers, gross disease remaining, or those who had a “palliative” RC were excluded. A group of 2,222 RC patients without prior PC were used to compare the clinicopathologic covariates. RESULTS: Of the 93 patients, 77 met the inclusion criteria. Median follow-up for all patients was 11 years (range, 0-37 years). Median time from PC to RC was 1.45 years (range, 0.1-18.1 years). 5and 10-year recurrence-free survivals were 66 1.1% and 63.0 1.2% for RC only versus 54.3 6.8% and 48.8 6.4% for prior PC (p 0.012). 5and 10-year overall survivals were 57.7 1.1% and 42 1.2% for RC only versus 42.3 5.7% and 33.5 5.6% for prior PC, though this difference did not reach statistical significance (p 0.11). For patients with extravesical extension at RC, the 5-year overall survival was 42.4 2.5% for the RC-only group versus 12.5 8.3% for the prior-PC group (p 0.009). There was no statistically significant difference in survival between the two groups in patients with organ-confined disease. A multivariate analysis for all patients undergoing RC using age, sex, pathologic stage, and prior PC as covariates identified all variables as being significant for survival (p 0.001, p 0.034, p 0.001, and p 0.012, respectively). A similar multivariate analysis for all patients undergoing RC using the above covariates identified sex (p 0.024), pathologic stage (p 0.001) and prior PC (p 0.004) as being significant for recurrence. CONCLUSIONS: In patients with extravesical bladder cancer at radical cystectomy, having undergone a previous partial cystectomy confers an increased risk of recurrence and death. This difference in survival is not seen in patients with organ-confined disease even after having undergone previous partial cystectomy.

Orthotopic urinary diversion has been performed for more than three decades. Although it is considered to be the gold standard form of diversion in many centers of expertise, the ileal conduit remains the most commonly performed urinary diversion. Variations in philosophy and experience heavily influence the discussion with patients regarding choice of diversion. Over the past decade, there has been a significant improvement in understanding factors that influence outcomes following orthotopic diversion. This chapter reviews the techniques of orthotopic urinary diversion with a detailed description of modern post-operative management focusing on enhanced recovery protocols.

Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity. To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. Open midline EP-RPLND was performed using a standardized technique. Perioperative and long-term outcomes were analyzed. Complications were graded using the Clavien-Dindo classification. A descriptive analysis using SAS software was performed. A total of 68 patients underwent midline EP-RPLND successfully (98.6%). The median age was 28 yr (range 17-55). On preoperative imaging the size of the retroperitoneal mass or lymphadenopathy was <2cm in 29...

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used...

The management of clinical stage II seminoma has evolved with a recent emphasis on minimizing long-term morbidity while achieving oncologic cure. In this review we discuss the available management options for clinical stage II seminoma with an emphasis on the emerging role of surgery in this patient population. Historically, treatment options available to clinical stage II seminoma patients were limited to radiotherapy and chemotherapy. Survival rates with these options are excellent; however, both are associated with significant long-term morbidities including cardiovascular, pulmonary, and neurologic toxicities. Additionally, higher rates of secondary malignancies are witnessed in this young patient population, decades after successful treatment of the primary cancer. Recently, retroperitoneal lymph node dissection has been proposed as a first-line treatment option for patients with low-volume metastatic seminoma. The SEMS and PRIMETEST trials are two studies examining the role of primary retroperitoneal lymph node dissection in clinical stage II seminoma, and early data show significant promise.

Introduction: Adrenal myelolipomas are benign lesions that contain hematopoietic and fatty elements. They are usually hormonally inactive and asymptomatic until they reach large sizes. With the routine use of cross-sectional imaging, these lesions are now being discovered with increasing frequency. Materials and Methods: We performed a comprehensive review of the literature using the PubMed database containing the key word adrenal myelolipoma. Results: We identified 492 articles written from 1956 to 2006 and reviewed 93 in detail including the authors' own experience. In this review, we highlighted the salient diagnostic features of adrenal myelolipomas and offered a guide for management of these benign lesions. Conclusion: Adrenal myelolipomas may grow over time, but they can usually be followed without surgical excision. In some cases, very large myelolipomas can present with pain and can be confused with necrotic adrenal carcinomas, thus necessitating their surgical removal.

Simple Summary Bladder cancer is one of the most common malignancies in the United States with a majority of patients diagnosed with non-muscle invasive bladder cancer (NMIBC). Despite early detection and regular surveillance of most cases, recurrence and progression rates remain high. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Through the collection of prospective and randomized controlled trials, we demonstrated that tumor resection with either PDD and NBI exhibited greater diagnostic sensitivity compared to WLC alone. Our findings underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC. Abstract Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NM...

Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasio...

Seizures in patients with glioblastoma are associated with worse quality of life. However, their incidence, clinical characteristics, and prognostic implications are less well characterized. This study was undertaken to provide a contemporary experience along with benchmark data relevant to the above in patients with glioblastoma. It also sought to reexplore improved survival with seizures, as observed by others. In this single-institution study, patients with glioblastoma from 2010 through 2014 had their medical records reviewed in detail. Among 122 patients, 58 (48%) had a seizure history. Of these, 67% had more than 1, 41% had generalized seizures, and most received antiseizure medication (most commonly levetiracetam). The median survival for patients with seizures was 1.66 years and 0.87 years for those without (hazard ratio for risk of death with seizures: 0.72; 95% confidence interval: 0.43, 1.21; P = .22 by the log-rank test). Seizures are common in patients with glioblastoma...

Our aim was to assess survival dependent on pathologic response after neoadjuvant chemotherapy (NAC) in a large multicenter patient cohort, with particular focus on the difference between absence of residual cancer (pT0) and the presence of only non-muscle invasive residual cancer (pTa, pTis, pT1). We retrospectively reviewed records of patients with urothelial cancer who received NAC and underwent radical cystectomy (RC) at 19 contributing institutions from 2000-2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival (OS) was compared between pT0 and pTa/Tis/T1 patients. Multivariable Cox proportional hazards regression model for OS was generated to evaluate hazard ratios (HRs) for variables of interest. Of 1543 patients undergoing NAC and RC during the study period, 257 were pT0N0 and 207 were pTa/Tis/T1N0. The Kaplan-Meier mean estimates of OS for pT0 and pTa/Tis/T1 patients were 186.7 mo. (95% CI [145.9-227.6]) (median 241.1) and 138 mo. (95% CI [118.2-157.8]) (median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for OS, pTa/Tis/T1N0 status (HR: 0.36 [95% CI, 0.23-0.67]) and pT0N0 status (HR: 0.28 [95% CI, 0.17-0.47]) compared to pT2N0 pathology, positive surgical margin (HR: 1.75 [95% CI, 1.07-2.86]), and receiving MVAC regimen compared to "other" regimen (HR: 0.45 [95% CI, 0.27-0.76]) were predictors of OS. pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients receiving NAC and RC. We did not discern a statistically significant difference in OS when comparing these two endpoints.

The impact of cardiopulmonary bypass (CPB) usage in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We sought to determine the impact of cardiopulmonary bypass (CPB) on overall and cancer specific survival, as well as surgical complication rates, and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without CPB. We retrospectively analyzed 362 patients with RCC and with level III or IV tumor thrombus from 1992 to 2012 in 22 US and European centers. Cox proportional hazards models were used to compare overall and cancer-specific survival between patients with and without CPB. Perioperative mortality and complications rates were assessed using logistic regression analyses. The median overall survival was 24.6 months in non-CPB patients and 26.6 months in CPB patients. Overall survival and cancer-specific survival (CSS) did not differ significantly in both groups, neither in univariate analysis nor when adju...

Although Muscle Invasive Bladder Cancer (MIBC) is increasing in incidence, treatment has largely remained limited to radical cystectomy with or without cisplatin-based neoadjuvant and/or adjuvant chemotherapy. We reviewed the current and recent clinical trials evaluating perioperative chemotherapy, targeted therapy, and novel therapeutic regimens for MIBC patients undergoing radical cystectomy. An overview of perioperative MIBC management was conducted initially using MEDLINE. The Clinical Trials Registry and MEDLINE were further searched specifically for perioperative MIBC chemotherapy, targeted therapy, and other novel therapeutic approaches. Trials involving non-perioperative management, operative management other than radical cystectomy, multiple tumors, or purely superficial or metastatic disease were excluded from selection. These criteria were not specifically fulfilled for mTOR inhibitor and immune therapy trials. Only phase III chemotherapy and phase II targeted therapy tri...

Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those wi...

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Surgical resection of residual masses after chemotherapy remains a critical component of the management of patients with metastatic germ cell tumors. There are clear indications for postchemotherapy retroperitoneal lymph node dissection (PC-RPLND), which remains one of the most challenging procedures performed by urologists. Surgeons tackling these cases should be intimately familiar with retroperitoneal anatomy and the indications for adjunctive procedures, and must be adept at vascular techniques to safely extirpate tumors while minimizing morbidity. In their article, Umbreit et al have reported their institutional intraoperative and postoperative complications during PC-RPLND over an 18-year period. The series is well annotated and the reporting of intraoperative complications using a validated tool is novel. One point of discussion regarding the analysis is the retrospective nature of classifying intraoperative “complications.” Although a suture repair of the vena cava is considered to be a complication in the study by Umbreit et al, others may view it as a necessary part of surgery when peeling masses off the great vessels in the presence of a significant desmoplastic reaction. Umbreit et al rightfully mention that quality reporting is a “benchmark” of quality surgical and value-based health care delivery. Indeed, as operative reports are dissected for keywords such as “inadvertent injury” or “laceration,” surgeons need to be increasingly aware of the verbiage used to describe intraoperative events. A mass that is densely adherent to the great vessels inevitably will lead to cavotomies or aortotomies that require suture repair. Are these “intraoperative adverse events” or an expected part of the complex dissection? Reporting these as adverse events has implications for coding, performance-based reimbursement, and other safety measures. A surprising finding of the report by Umbreit et al is that when corroborating the “adjuvant” procedures with the intraoperative complications, several of them appear to have been planned. There were no Clavien-Dindo classification grade 4 aortic or vena cava complications, meaning that all vena cava resections and aortic replacements were planned and not considered to be intraoperative complications. It is extraordinary that among >450 cases, there were no intraoperative changes in plans reported due to an inability to separate tumors from major vessels. Another limitation of the study by Umbreit et al was that some surgeons may not have reported a minor injury during the case in the surgical report. Ileus remains one of the most common complications after this type of surgery (27% in the series by Umbreit et al). The midline extraperitoneal approach, which is feasible even with large retroperitoneal masses, has virtually eliminated the risk of ileus and can significantly decrease gastrointestinal-related complications and the length of hospital stay. Although documenting and reporting will not change how we recommend this surgery to our patients, I agree it is important to discuss the relative risk of each complication during counseling.

PURPOSE OF REVIEW Retroperitoneal lymph node dissection (RPLND) and retroperitoneal tumor resection for germ cell cancer are complex operations requiring experience and expertise in surgical techniques necessary to achieve complete resection while minimizing morbidity. This article reviews the intricacies of RPLND for testis cancer. RECENT FINDINGS Surgical management of advanced testis cancer begins with an intimate understanding of retroperitoneal anatomy and the various techniques necessary to safely extirpate tumors. Preoperatively patients should undergo comprehensive counseling and obtain up-to-date imaging along with tumor markers to assist in surgical planning and evaluation of extraretroperitoneal (ERP) disease. Surgeons must be well versed in nerve-sparing techniques to maintain ejaculatory function. Newer techniques using a midline extraperitoneal technique minimizes morbidity and length of hospital stay. Special consideration should be given to the possibility of encountering ERP disease in advanced germ cell tumors, with management of these cases in tertiary care centers with multidisciplinary teams. SUMMARY The perioperative care of the testis cancer patient undergoing RPLND is complex. The goal is to achieve complete resection to render patients disease free while minimizing surgical and long-term morbidity. Advanced testis cancer patients should be managed at tertiary care facilities with surgical expertise and access to multidisciplinary care.

OBJECTIVES To evaluate the role of blue light (BL) cystoscopy in detecting invasive tumors that were not visible on white light (WL) cystoscopy. MATERIALS AND METHODS Using the multi-institutional Cysview registry database, patients who had at least one white light negative/blue light positive lesion with invasive pathology (≥T1) as highest stage tumor were identified. All white light negative/blue light positive lesions and all invasive tumors in the database were used as denominators. Relevant baseline and outcome data were collected. RESULTS Of the 3514 lesions (1257 unique patients), 818 (23.2%) lesions were WL negative (WL-)/BL positive (BL+), of those, 55 (7%) lesions were invasive (48 T1,7 T2) (47 unique patients) including 28/55 (51%) de novo invasive lesions (26 unique patients). 21/47 (45%) patients had WL-/BL+ concommitant CIS and/or another T1 lesions. Of 22 patients with WL-/BL+ lesion who underwent cystectomy, high risk pathologic features leading to cystectomy was only visible on BL cystoscopy in 18 (82%) patients. At time of cystectomy, 11/22 (50%) patients showed pathologic upstaging including 4/22 (18%) patients with node positive disease. CONCLUSIONS A considerable proportion of invasive lesions are only detectable by BL cystoscopy and rate of pathologic upstaging is significant. Our findings suggest an additional benefit of BL cystoscopy in detection of invasive bladder tumors that has implications for treatment approach.

Treatment of testicular cancers has for the most part remained unchanged over the past several decades. The pioneering work of scientists, clinicians and surgeons in the 1970s and 1980s led the path to what is now established treatment algorithms for the various stages of disease. Over the past two decades, however, there has been a steady change from adjuvant therapy for stage I disease to active surveillance with resultant decrease in long-term morbidity. Focus has shifted from improving the established high cure rates to decreasing the burden of treatment, deescalating imaging intensity and improving delivery of care. There are new insights into the molecular pathogenesis of the disease, new treatment options for low-stage metastatic seminoma and new serum markers that will further change the treatment paradigms. In this issue, we have not only included the main areas of modern management of early stage as well as metastatic testicular germ cell tumors but also we incorporated surveillance strategies in stage I disease and included a section on epigenetic alterations of testicular germ cell tumors. Another section describes the developing role of miRNA, a novel biomarker in the management of germ-cell tumors.

Purpose of review The current review covers recent research examining the utility of preoperative frailty assessments to predict worse postoperative outcomes after radical cystectomy. It also discusses how to implement frailty assessments into routine clinical practice. Recent findings Frailty is associated with worse postoperative outcomes after radical cystectomy, including increased complications and nonhome discharge. Although the majority of these studies have been retrospective using a frailty index, prospective studies using a preoperative frailty assessment have also shown frailty to be associated with worse outcomes. Preoperative frailty assessments based on patients’ physiologic fitness, such as the Fried Frailty Criteria or psoas muscle volume, have been the best predictors of worse outcomes on prospective cohorts. However, no study to date has directly compared a prospective frailty assessment and frailty index to determine the most effective tool for routine clinical care. National guidelines are lacking on how to assess frailty preoperatively before radical cystectomy. Summary Frailty has been consistently shown to correlate with worse postoperative outcomes after radical cystectomy. Although the most effective and efficient method for preoperative assessment has yet to be determined, assessments based on physiologic fitness are likely to be most useful. Improved guidelines will likely increase implementation of frailty assessments into routine management.

The role of cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) in the targeted therapy (TT) era is controversial. To assess if CN versus no CN is associated with improved overall survival (OS) in patients with mRCC treated in the TT era and beyond, characterize the morbidity of CN, identify prognostic and predictive factors, and evaluate outcomes following treatment sequencing. Medline, EMBASE, and Cochrane databases were searched from inception to June 4, 2018 for English-language clinical trials, cohort studies, and case-control studies evaluating patients with mRCC who underwent and those who did not undergo CN. The primary outcome was OS. Risk of bias was evaluated using the Cochrane Collaborative tools. We identified 63 reports on 56 studies. Risk of bias was considered moderate or serious for 50 studies. CN was associated with improved OS among patients with mRCC in 10 nonrandomized studies, while one randomized trial (CARMENA) found tha...

PURPOSE OF REVIEW Management of extraretroperitoneal (ERP) germ cell tumor (GCT) is a complex clinical scenario faced by urologic oncologists. This article reviews the indications and approach to management of ERP GCT masses. RECENT FINDINGS ERP GCT management starts with chemotherapy, and for any residual masses, a careful consideration of surgical intervention versus salvage chemotherapy. Decision-making regarding residual ERP masses hinges on tumor markers, and also the anatomical location. These factors should be contextualized by the patient's risk for teratoma or active GCT, which will impact outcome and thus weigh on decision-making conversations with patients who have advanced disease. Technical challenges of surgical management in the postchemotherapy setting also apply in ERP mass resection. The risks of surgical management in the lung and liver, in particular, add special considerations for morbidity. Surgical resection is often the only recourse for a patient who may have chemoresistant disease and may be an important step in achieving cure. SUMMARY Surgical management of ERP GCT requires multidisciplinary input, and the urologic oncologist can help guide management with particular emphasis on the indication, timing, and approach to surgical resection.

The role of surgery in metastatic bladder cancer (BCa) is unclear. In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making. A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed. The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreduct...

To evaluate the association between intraoperative fluid intake and postoperative complications in patients who underwent radical cystectomy (RC) for bladder cancer with an enhanced recovery protocol. 287 patients underwent open RC with enhanced recovery protocol (ERAS) from 2012 to 2016. 107 were excluded; non-urothelial (30), palliative (37), had adjunct procedures or not-consented (40). We prospectively evaluated intraoperative fluid intake (crystalloid, colloid and blood) and correlated with length of stay, 30- and 90-day complications. 180 patients enrolled into the study with median age of 70 years (78% male). 71% underwent orthotopic diversion. Median intraoperative crystalloid and colloid intake were 4000 and 500 cc, respectively. Nineteen percent of patients received blood transfusion. Median length of stay was 4 days. The overall 30- and 90-day complication rates were 59 and 75%, respectively. Multivariate logistic regressions controlling for a subset of clinically relevan...

To investigate the incidence and microbiology of urinary tract infection (UTI) within 90 days following radical cystectomy (RC) and urinary diversion. We reviewed 1133 patients who underwent RC for bladder cancer at our institution between 2003 and 2013; 815 patients (72%) underwent orthotopic diversion, 274 (24%) ileal conduit, and 44 (4%) continent cutaneous diversion. 90-day postoperative UTI incidence, culture results, antibiotic sensitivity/resistance and treatment were recorded through retrospective review. Fisher's exact test, Kruskal-Wallis test, and multivariable analysis were performed. A total of 151 urinary tract infections were recorded in 123 patients (11%) during the first 90 days postoperatively. 21/123 (17%) had multiple infections and 25 (20%) had urosepsis in this time span. Gram-negative rods were the most common etiology (54% of positive cultures). 52% of UTI episodes led to readmission. There was no significant difference in UTI rate, etiologic microbiology...