Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy. CASE PRESENTATION: A 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months. CONCLUSION: Our patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

Stem Cell Theory of Cancer: Clinical Implications of Epigenomic versus Genomic Biomarkers in Cancer Care.

Biomarkers play a crucial role in the diagnosis, prognosis, and therapeutics of cancer. We use biomarkers to identify, image, monitor, and target cancer. In many respects, the discovery of pertinent biomarkers that distinguish fulminant from indolent neoplasms and sensitive from refractory malignancies would be a holy grail of cancer research and therapy. We propose that a stem cell versus genetic theory of cancer may not only enable us to track and trace the biological evolution of cancer but also empower us to attenuate its clinical course and optimize the clinical outcome of patients with cancer. Hence, a biomarker that identifies cancer stem cells (CSCs) and distinguishes them from non-CSCs may serve to elucidate inter-tumoral and intra-tumoral heterogeneity, elevate the values and utility of current prognostic and predictive tests, and enhance drug versus therapy development in cancer care. From this perspective, we focus on CSC biomarkers and discuss stemness or stem-like biomarkers in the context of a unified theory and a consideration of stem cell versus genetic origin. We review their role in primary and mixed tumors, in the elaboration of tumor subtypes, and in the imaging and monitoring of minimal residual diseases. We investigate how scientific theories influence the direction of scientific research and interpretation of experimental results, and how genomics and epigenomics affect the dynamics and trajectories of biomarkers in the conduct of cancer research and in the practice of cancer care.

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy.

A simple way to understand the immune system is to separate the self from non-self. If it is self, the immune system tolerates and spares. If it is non-self, the immune system attacks and destroys. Consequently, if cancer has a stem cell origin and is a stem cell disease, we have a serious problem and a major dilemma with immunotherapy. Because many refractory cancers are more self than non-self, immunotherapy may become an uphill battle and pyrrhic victory in cancer care. In this article, we elucidate cancer immunity. We demonstrate for whom, with what, as well as when and how to apply immunotherapy in cancer care. We illustrate that a stem cell theory of cancer affects our perspectives and narratives of cancer. Without a pertinent theory about cancer's origin and nature, we may unwittingly perform misdirected cancer research and prescribe misguided cancer treatments. In the ongoing saga of immunotherapy, we are at a critical juncture. Because of the allure and promises of immunotherapy, we will be treating more patients not immediately threatened by their cancer. They may have more to lose than to gain, if we have a misconception and if we are on a wrong mission with immunotherapy. According to the stem cell theory of cancer, we should be careful with immunotherapy. When we do not know or realize that cancer originates from a stem cell and has stem-ness capabilities, we may cause more harm than good in some patients and fail to separate the truth from the myth about immunotherapy in cancer care.

Stem Cell Origin of Cancer: Implications of Oncogenesis Recapitulating Embryogenesis in Cancer Care.

From this perspective, we wonder about the clinical implications of oncology recapturing ontogeny in the contexts of neoantigens, tumor biomarkers, and cancer targets. We ponder about the biological ramifications of finding remnants of mini-organs and residuals of tiny embryos in some tumors. We reminisce about classical experiments showing that the embryonic microenvironment possesses antitumorigenic properties. Ironically, a stem-ness niche-in the wrong place at the wrong time-is also an onco-niche. We marvel at the paradox of TGF-beta both as a tumor suppressor and a tumor promoter. We query about the dualism of EMT as a stem-ness trait engaged in both normal development and abnormal disease states, including various cancers. It is uncanny that during fetal development, proto-oncogenes wax, while tumor-suppressor genes wane. Similarly, during cancer development, proto-oncogenes awaken, while tumor-suppressor genes slumber. Importantly, targeting stem-like pathways has therapeutic implications because stem-ness may be the true driver, if not engine, of the malignant process. Furthermore, anti-stem-like activity elicits anti-cancer effects for a variety of cancers because stem-ness features may be a universal property of cancer. When a fetus survives and thrives despite immune surveillance and all the restraints of nature and the constraints of its niche, it is a perfect baby. Similarly, when a neoplasm survives and thrives in an otherwise healthy and immune-competent host, is it a perfect tumor? Therefore, a pertinent narrative of cancer depends on a proper perspective of cancer. If malignant cells are derived from stem cells, and both cells are intrinsically RB1 negative and TP53 null, do the absence of RB1 and loss of TP53 really matter in this whole narrative and an entirely different perspective of cancer?

Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer.

PURPOSE: Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC). METHODS: A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05. RESULTS: Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models. CONCLUSIONS: Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.

Clinical indications for necessary and discretionary hospital readmissions after radical cystectomy.

BACKGROUND: To assess predictors, indicators and medical necessity of readmissions after neoadjuvant chemotherapy and radical cystectomy in order to identify opportunities for reducing readmission rates. METHODS: Records for patients treated with cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy between 2007 and 2017 were reviewed for 90-day complications and readmission. Readmissions were classified as necessary vs. discretionary based on independent clinician review. The association between postoperative complications and necessary or discretionary readmission were examined with adjusted regression models. RESULTS: Among a total of 250 patients, 76 patients (30.4%) were readmitted within 90 days of surgery (19 discretionary and 57 necessary). Age, insurance coverage, and comorbidity were similar between readmitted and non-readmitted patients. Readmission was more likely after neobladder than ileal conduit (39% vs. 23%, P = 0.02). Major (grade ≥ 3) complications within 90-day of surgery including index admission and post-discharge period were significantly more common among re-admitted patients compared to patients who were not readmitted (40% in necessary, 21% in discretionary, 3% in none, P < 0.001). Median length of stay on readmission was twice as long in necessary cases compared to discretionary cases (5 vs. 2.5 days, P < 0.001). Gastrointestinal and infectious complications were associated with discretionary readmission in adjusted analyses, while infectious, renal/genitourinary and thromboembolic complications were associated with necessary readmission. CONCLUSIONS: Twenty-five percent of readmissions were categorized as discretionary and were driven primarily by low-grade gastrointestinal complications, marginal oral intake and failure to thrive, suggesting that better coordinated post-discharge supportive care could help avoid a substantial proportion of readmissions.

The Factors Affecting Expansion of Reactive Tumor Infiltrating Lymphocytes (TIL) From Bladder Cancer and Potential Therapeutic Applications.

Tumor infiltrating lymphocytes (TIL) therapy was shown to provide durable objective response in patients with metastatic melanoma. As a fundamental first step to bring TIL therapy to clinical use, identification of patients whose tumors yield optimal numbers of reactive TIL is indispensable. We have previously shown that expansion of tumor reactive TIL from primary bladder tumors and lymph node metastases is feasible. Here, we performed TIL harvesting from additional surgical specimens (additional 31 primary tumors and 10 lymph nodes) to generate a heterogenous cohort of 53 patients with bladder cancer (BC) to evaluate the tumor characteristics that lead to tumor-reactive TIL expansion. Among a total of 53 patients, overall TIL growth from tumor samples were 37/53 (69.8%) and overall anti-tumor reactive TIL were 26/35 (74.3%). Mixed urothelial carcinoma is associated with higher anti-tumor reactivity of expanded TIL than pure urothelial carcinoma (89.5% vs. 56.3%, p=0.049). The anti-tumor reactivity of expanded TIL from primary tumors previously treated with BCG immunotherapy were lower (33.3% vs. 82.6%, p=0.027) although T-cell phenotype (CD3+, CD4+, CD8+, and CD56+) was similar regardless prior of BCG therapy. Addition of agonistic 4-1BB antibody in culture media with IL-2 improved the number of expanded TIL from primary tumors previously treated with BCG immunotherapy. There was no significant difference between basal and luminal subtype tumors in terms of viable and reactive TIL growth. Our study demonstrates that TIL expansion is feasible across all BC patients and BC subtypes, and we suggest that TIL therapy can be a reasonable treatment strategy for various manifestations of BC.

Expansion of tumor-infiltrating lymphocytes (TIL) from penile cancer patients.

Penile cancer is a rare but highly lethal cancer, and therapeutic options for patients presenting with lymph nodal disease are very limited. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) was shown to provide durable objective response in patients with metastatic melanoma and TIL have been expanded from solid tumors at rates between 70 and 90% depending on the specific diagnosis. We evaluated whether TIL could be expanded from surgical specimens of patients with penile cancer. Tumor samples from metastatic lymph nodes obtained at the time of inguinal lymph node dissection were collected, minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. The phenotype of expanded TILs was assessed by flow cytometry and their anti-tumor reactivity was assessed by IFN-γ ELISA. TIL were expanded from 11 out of 12 (91.6%) samples of metastatic lymph nodes. Expanded TIL were predominantly CD3+ (mean 67.5%, SD 19.4%) with a mean of 46.8% CD8+ T cells (SD 21.1%). Five out of 11 samples (45.4%) from expanded TIL secreted IFN-γ in response to autologous tumor. TIL expansion and phenotype of expanded T cell lymphocytes were independent of previous HPV infection and treatment with neoadjuvant chemotherapy. This is the first report demonstrating successful expansion of tumor-reactive TIL from penile cancer patients, which support development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.

Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility.

OBJECTIVES: To evaluate the safety and feasibility of focal bipolar radiofrequency ablation in men with localized prostate cancer. METHODS: A review of 10 patients treated with a novel bipolar radiofrequency ablation probe integrated in a coil design (Encage; Trod Medical, Bradenton, FL, USA) between 2011 and 2017 in two prospective pilot trials. All men had clinical stage T1c prostate cancer, prostate-specific antigen <10 ng/mL and Gleason score ≤7. Ablation was carried out under general anesthesia, and bipolar probes were inserted transperineally under transrectal ultrasound guidance. Treatment-related adverse events, quality of life and negative biopsy rate were evaluated at 6 months after ablation. The Wilcoxon signed-rank test was used to compare baseline and post-treatment symptom scores. RESULTS: The median age was 58 years (range 50-64 years) and the median prostate volume was 49.65 cc (range 21-68 cc). Prostate cancer with a Gleason score of 6 (3 + 3) and 7 (3 + 4) was noted in seven and three patients, respectively. The median number of radiofrequency ablation cycles was 2.5 (range 2-5). All patients were catheter-free and able to void the day of surgery. Within 6 months after ablation, all adverse events were low grade, with the exception of one grade 3 hematuria that required cystoscopy without coagulation. Six months after ablation bowel, urinary and hormonal functions, and overall satisfaction remained stable. Erectile dysfunction occurred in two out of four patients who had normal sexual function before the procedure. Neither urinary incontinence nor urinary infection was noted. CONCLUSIONS: This first report on focal bipolar radiofrequency ablation documents a safe and feasible treatment option for selected patients with localized prostate cancer.

Understanding genomics and the immune environment of penile cancer to improve therapy.

The incidence of penile squamous cell carcinoma (PSCC) has increased in developed countries over the past decades owing to increased human papilloma virus (HPV) exposure. Despite successful surgical treatment of locoregional PSCC, effective treatment options for advanced disease are limited. The prognosis of patients with bulky nodal and metastatic PSCC is dismal and new management approaches are urgently needed. Genomic analyses have provided transformative knowledge on the genomic and molecular landscape and tumour microenvironment of PSCC. Around one-quarter of patients with metastatic PSCC have clinically actionable genomic alterations in mechanistic target of rapamycin, DNA repair and receptor tyrosine kinase pathways. These patients might benefit from combined and sequential targeted therapies. HPV vaccination might be another therapeutic option as PSCC is genetically similar to other HPV-driven cancers. In addition, 40-60% of PSCC tumours show strong PDL1 expression, and the frequency of mutational signatures suggestive of immunotherapy resistance is low, pointing to potential utility of immunotherapy for PSCC. Finally, identification of the composition of the penile microbiota and its biological role might lead to new cancer prevention and treatment strategies.

Contemporary management of early stage testicular seminoma.

Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (≤5 cm in greatest dimension), RT or combination chemotherapy are the standard of care. Given high comparable survival rates, preventing treatment-related toxicity and second malignancy, and limiting quality of life deficits associated with intense treatment has gained much greater importance. Clinical trials are currently testing the feasibility of retroperitoneal lymph node dissection (RPLND) for low volume CS IIA/IIB metastatic testicular seminoma to this end. Likewise, one cycle of chemotherapy is being evaluated as an adjuvant approach to reduce recurrence rates in CS I disease with unfavorable risk factors. Moreover, recent genomic and molecular studies have recently identified novel signatures and a potential biomarker for testicular seminoma. In this review, we first summarize the evolution of early stage seminoma management and discuss the effectiveness and drawbacks of contemporary treatment strategies. We further outline future perspectives and potential challenges in management of early stage testicular seminoma.

Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy.

PURPOSE: Programmed cell death-1 ligand-1 (PD-L1) expression has been associated with prognostic implications in urologic malignancies. We aimed to investigate prognostic significance of pre- and post-treatment PD-L1 expression in patients treated with BCG for high-grade non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection + ≥ 6 BCG instillations between 2004 and 2017. PD-L1 immunohistochemistry (IHC) scoring was done on 0-3 scale, and cut-off for positive and high-level PD-L1 expression was set to ≥ 1% and ≥ 5% staining of tumor-infiltrating immune cells (IC), respectively. Clinicopathologic characteristics and oncologic outcomes [recurrence-free (RFS) and progression-free survival (PFS)] were compared, stratified by PD-L1 positivity. The prognostic role of PD-L1 was assessed using Kaplan-Meier, and univariate and multivariate Cox regression analyses. RESULTS: Pre-treatment, 46.2% and 6.8% of high-grade NMIBC demonstrated positive and high-level PD-L1 expression, respectively. Positive PD-L1 expression was associated with submucosal invasion and refractory-tumor recurrence. PD-L1 expression was not associated with RFS or PFS in regression analysis. Post-treatment, 55.1% and 11.6% of recurrent tumors demonstrated positive and high-level PD-L1 expression, respectively. Down-regulation of PD-L1 expression was noted in patients with refractory recurrence (p = 0.012). CONCLUSION: Pre-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD-L1 expression did not have prognostic value for PFS or RFS; therefore, further research is necessary to identify novel biomarkers for prediction of disease outcomes in high-grade NMIBC.

Treating advanced penile cancer: where do we stand in 2019?

PURPOSE OF REVIEW: Penile squamous cell carcinoma (PSCC) remains a challenging malignancy to treat and there is an urgent need of significant improvements at all levels of medical care. In the current review, we summarized the significant obstacles encountered during management of PSCC and discussed the clinical relevance of novel findings and their potential to address these obstacles. RECENT FINDINGS: The recent genetic and immunological advances suggest that patients with PSCC can benefit from available targeted therapy and immunotherapy options. Moreover, evidence has accumulated over time suggesting that majority of the patients diagnosed with PSCC suffer from psychosocial problems and impaired rehabilitation. SUMMARY: Effective prevention strategies against PSCC are urgently needed especially in developing countries given the limited therapeutic options. About a quarter of patients with metastatic PSCC appear to benefit from available targeted therapies and about half of the patients can be a suitable candidate for immune checkpoint blockade as half of the PSCC cases exhibit PD-L1 expression. Moreover, increased public awareness, healthcare provider education and social support programs may help patients suffering from PSCC coping with the psychosocial burdens of the disease.

Clinicopathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer following definitive therapy.

OBJECTIVE: To demonstrate the effect of clinicopathological factors on 68Ga-PSMA-11 PET/CT positivity at the time of biochemical recurrence (BCR) of localized prostate cancer (PCa) following definitive therapy. METHODS: We retrospectively reviewed our institutional database for PCa patients who had BCR and subsequently underwent 68Ga-PSMA-11 PET/CT between April 2014 and February 2018. A total of 51 patients who were metastasis-free before PSMA imaging and previously treated with definitive therapy (radical prostatectomy or external beam radiotherapy) for localized disease (pT1c-T3b pN0-1 cM0) were included. RESULTS: 37 out of 51 patients (72.5%) had positive 68Ga-PSMA-11 PET/CT scans. Age at diagnosis, Gleason score (GS), D'Amico risk status of PCa, initial PSA level before treatment and PSA doubling time were not associated with PSMA positivity. Pre-scan PSA levels of > 0.2 ng/ml and PSA velocity of ≥ 1 ng/ml/year were significantly associated with increased PSMA positivity, whereas history of androgen deprivation therapy showed a trend towards significance. The optimal cutoffs for distinguishing between positive and negative scans were ≥ 0.71 ng/ml for pre-scan PSA and ≥ 1.22 ng/ml/yr for PSA velocity. In multivariable analysis, log pre-scan PSA and pre-scan PSA level > 0.2 ng/ml remained significant predictors for PSMA positivity, whereas the association of PSA velocity and of ADT was lost. CONCLUSIONS: In BCR of localized PCa following definitive therapy, pre-scan PSA was strongly associated with positive 68Ga-PSMA-11 scan, even at PSA levels ranging from 0.2 to 1.0 ng/ml. Therefore, clinical and pathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer need to be further elucidated.

Predictors of Recurrence and Complications in Pediatric Pyeloplasty.

OBJECTIVE: To assess the predictors of recurrence and complications, we retrospectively analyzed our experience in primary pediatric pyeloplasty. Management of pyeloplasty failure is challenging both for patients and for surgeons, especially in pediatric cases. Early detection of recurrence and early manipulation may help preserving renal function. METHODS: We analyzed 490 renal units who underwent primary dismembered pyeloplasty with eligible data between June 2001 and October 2016 retrospectively. Patient's demographic features, operative data, clinical findings, complications, and recurrence rates were evaluated. RESULTS: Mean age at operation and the mean follow-up time after pyeloplasty was 33.9 (±43.5) and 47.6 (±37.7) months. Our recurrence and complication rates were 6.7% and 11.4%, respectively. Urinary tract infection (7.8%), diversion-related complications (1.8%), and urinoma (1.4%) were the most common complications. Presence of preoperative diversion (P = .020) and presence of early complications (P < .001) after pyeloplasty were significantly related to recurrence. Complication rates were found less in children with transanastomotic diversions (P = .002) and children without preoperative diversion (P = .005). The analysis of patients in chronological order revealed an increase in prenatal diagnosis in the recent years (P < .001). Recurrence and complications were not related to age, gender, side, preoperative radionuclide renal scan results, hydronephrosis grade, surgery type, and surgical findings. CONCLUSION: Early postoperative complication is a predictor of recurrence after pediatric pyeloplasty. Transanastomotic diversion reduces the complication rates. Presence of a preoperative diversion increases both complication rates and recurrence rates after pyeloplasty.

Prospects and progress of immunotherapy for bladder cancer.

INTRODUCTION: With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer. Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer. They also provide the currently available data evaluating checkpoint inhibitors for bladder cancer, and discuss ongoing trials and future perspectives for urothelial carcinoma treatment. Expert opinion: The introduction of checkpoint inhibitors into the management of bladder cancer marks a significant milestone for this disease. Checkpoint inhibitors have the potential to impact patients across multiple disease states from non-muscle-invasive disease to metastatic tumors refractory to conventional treatment. That being said, validated biomarkers, including genetic signatures, to accurately predict response, and the establishment of optimal sequencing and combination of these immunotherapeutic agents with chemo/radiotherapy are urgently needed.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer.

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology.

Local recurrence of renal cell carcinoma that simulated multiple renal arteriovenous fistulas after laparoscopic partial nephrectomy: Report of a rare case.

Herein we report a patient who was initially thought to have renal arteriovenous fistulas 3 months after laparoscopic partial nephrectomy for a small renal mass. After timely intervention using selective renal artery embolization, computed tomography 9 months post-surgery showed persistent renal arteriovenous fistulas and nodular lesions in the perirenal fat. The patient then underwent radical nephrectomy, and histopathological examination showed underlying recurrent clear cell renal cell carcinoma invading the intraparenchymal arteries and veins, which was simulating multiple high-flow renal arteriovenous fistulas.