Totally retroperitoneal approach for robot-assisted nephroureterectomy with bladder cuff without repositioning.

INTRODUCTION: Robot-assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary. MATERIALS AND SURGICAL TECHNIQUES: RANU via the retroperitoneal approach was selected for two patients diagnosed with high-grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively. DISCUSSION: By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.

[Advanced Bladder Cancer with Multiple Pulmonary Metastases Treated with Paclitaxel/Ifosfamide/Nedaplatin Therapy : Two Case Reports].

The standard treatment for advanced urothelial carcinoma includes platinum-based chemotherapy and programmed cell death protein 1 or programmed death ligand 1 inhibitors. However, urothelial carcinomas are often associated with both intrinsic and acquired resistance to these treatments. Paclitaxel, ifosfamide, and nedaplatin (TIN) chemotherapy has been proven to be effective as the second- or third-line treatment for platinum-resistant advanced urothelial cancer. Herein, we report two cases of patients with advanced bladder cancer resistant to platinum-based chemotherapy or pembrolizumab, who were treated with TIN chemotherapy. The first case was in a 66-year-old woman treated with gemcitabine and cisplatin (GC) chemotherapy followed by gemcitabine, paclitaxel, and cisplatin chemotherapy for multiple pulmonary metastases after radical cystectomy. Following reduction in pulmonary metastases after six courses of TIN treatment, metastasectomy and two courses of adjuvant TIN treatment were administered, with no recurrence for eight years. The other case was in a 70-year-old man treated with GC chemotherapy and pembrolizumab for invasive bladder cancer and multiple pulmonary metastases. We treated this patient with salvage pelvic exenteration. Pulmonary metastases significantly decreased after six courses of TIN chemotherapy. After a partial response for seven months; the patient died due to a novel cerebellar metastasis after six courses of TIN chemotherapy. Thus, we conclude that TIN chemotherapy can be considered as a third line treatment for advanced urothelial cancer resistant to platinum-based chemotherapy and pembrolizumab.

Extracellular vesicles secreted from bone metastatic renal cell carcinoma promote angiogenesis and endothelial gap formation in bone marrow in a time-dependent manner in a preclinical mouse model.

Introduction: Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. Materials and methods: We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Results: Treatment of mice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. Conclusion: EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner.

Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction.

OBJECTIVES: Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of advanced urothelial carcinoma. However, the tolerability and outcomes of pembrolizumab in patients with severe renal dysfunction [creatinine clearance (CrCl) <30 ml/min] are unclear because no clinical trials included such patients. We analyzed the safety profile and outcomes of these patients in the real world. METHODS: We extracted data for 739 pembrolizumab-treated patients from a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Using propensity score matching, the overall survival (OS) and adverse events (AEs) of patients with CrCl <30 and ≥30 were compared. RESULTS: Ninety-two patients (12.4%) had CrCl <30 ml/min. The median number of doses was similar between the CrCl ≥ 30 and CrCl <30 groups (5 and 4, respectively), and there was no difference in the frequency of grade ≥2 treatment-related AEs between the groups (35.5% vs. 35.7%). The overall response rate was similar between the groups (27.2% vs. 29.7%, P = 0.184). Using propensity score matching, the median OS times in the CrCl ≥30 and CrCl <30 groups were 10.3 (95% confidence interval [CI] = CI 7.3-13.0) and 8.1 months (95% CI = 5.4-14.6, P = 0.626), respectively. The 1-year OS rates in these groups were 41.5% and 38.2%, respectively, and the 2-year OS rates were 21.3% and 20.2%, respectively. In multivariate Cox regression analysis, performance status ≥2 (hazard ratio [HR] = 5.56, 95% CI = 2.64-11.71, P < 0.0001) and neutrophil-to-lymphocyte ratio ≥3 (HR = 2.20, 95% CI =1.15-4.19, P = 0.013) were independently associated with patient prognosis in the CrCl <30 group. CONCLUSIONS: This report illustrated that pembrolizumab can be safely administered to patients with severe renal dysfunction, who had similar outcomes as patients without severe renal dysfunction.

Preoperative ipilimumab/nivolumab combination therapy reduced operation risk by downstaging the inferior vena cava tumor thrombus extending to the right atrium in a metastatic renal cell carcinoma: A case report.

The success of immune checkpoint inhibitors in metastatic renal cell carcinoma (RCC) has renewed interest in studying these agents in preoperative settings. Here, we present a case of metastatic RCC with an inferior vena cava (IVC) tumor thrombus extending to the right atrium. Preoperative systemic therapy with ipilimumab/nivolumab was initiated for four cycles. The IVC tumor thrombus level was significantly downstaged from IV to I according to the Mayo classification, which enabled us to perform cytoreductive nephrectomy and IVC thrombectomy without extracorporeal circulation. Preoperative ipilimumab/nivolumab may lead to significant downstaging of caval tumor thrombus in metastatic RCC.

Functional and genomic characterization of patient-derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma.

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus.

[A Case of Small Cell Carcinoma of the Bladder].

A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with cisplatine + etoposide (EP), total cystectomy was performed. The pathological findings revealed small cell carcinoma of the bladder (ypT2N0M0). Eleven months after the operation, thoracoabdominal computed tomography (CT) showed right pelvic lymph node metastasis. He underwent 9 courses of EP chemotherapy, and everolimus, finally, Amrubicin was administered. Amrubicin might be useful for small cell carcinoma of the bladder.

[Deep and Durable Response After Discontinuation of Nivolumab/Ipilimumab Combination Therapy for Metastatic Renal Cell Carcinoma : A Case Report].

A 47-year-old man was referred to our hospital for epigastric pain and cough, and was given a diagnosis of left clear cell renal carcnoma with multiple pulmonary metastases based on the results of renal tumor biopsy (cT3aN0M1). He received nivolumab/ipilimumab combination therapy, but developed diarrhea (grade 3) on day71, and treatment was discontinued. However, a deep and durable response after discontinuation of treatment was shown, and we were able to perform nephrectomy on day336. He is undergoing nivolumab therapy for pulmonary metastases.

[The Safety of Laparoscopic Radical Cystectomy during Initial Phases in a Japanese Multicenter Cohort].

We evaluated the safety of laparoscopic radical cystectomy (LRC) during initial phases and its learning curve in a Japanese multicenter cohort by studying 436 patients who underwent LRC with no robot assistance at 10 institutions in Japan. We divided the patients into three groups according to cumulative surgical volume at each institution (first 10 cases, 11-30 cases, after 31 cases in each institution), and compared perioperative and pathologic variables among the three groups. The first, second, and third groups included 100, 166, 170 patients, respectively. The preoperative variables were similar in the three groups except for the rate of neoadjuvant chemotherapy. The methods of LRC procedure, such as urinary diversion, the extent of lymph node dissection, and concomitant urethrectomy or nephroureterectomy, were similar in the three groups. Mean operative time was 629, 562 and 531 minutes, respectively, and mean blood loss was 755, 650 and 435 ml, respectively. Both values decreased over time with the institution's experience. There was no significant difference among the three groups in the rate of positive surgical margin, the number of retrieved lymph nodes, and the rate of intra- and postoperative complications. LRC was safely performed during initial phases with an acceptable complication rate and without compromising oncological results, although operative time was longer and blood loss increased.

[A Case of Renal Cell Carcinoma withIpsilateral Renal Pelvic Metastasis Mimicking Double Cancer].

A 71-year-old man with left flank pain was referred to our hospital. Computed tomography (CT) revealed a left renal tumor, left renal pelvic wall thickening, bilateral adrenal gland swelling, multiple pulmonary nodules, and a bone metastatic tumor. Further, positron emission tomography/CT revealed increased 18F fluorodeoxyglucose uptake in the left renal tumor, multiple pulmonary nodules, and bone metastatic tumor. Accordingly, we performed biopsies of the thickening of the left renal pelvic wall and bone metastatic tumor, and histological examinations revealed an unknown type carcinoma and bone metastasis from clear cell carcinoma. Without a precise preoperative diagnosis of the thickening of the left renal pelvic wall, laparoscopic left nephrectomy was performed, and the renal and renal pelvic wall tumors were diagnosed as clear cell carcinoma on pathological examination. Therefore, we made a final diagnosis of renal cell carcinoma with lung, bone, and renal pelvic metastases. Although axitinib was administered, cervical spine metastasis developed. Unfortunately, the patient died from disease progression five months following the surgery.

Dysregulated HAI-2 Plays an Important Role in Renal Cell Carcinoma Bone Metastasis through Ligand-Dependent MET Phosphorylation.

MET, a c-met proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis. In a previous study, we reported increased expression of MET and matriptase, a novel activator of HGF, in bone metastasis. In this study, we employed a mouse model of renal cell carcinoma (RCC) bone metastasis to clarify the significance of the HGF/MET signaling axis and the regulator of HGF activator inhibitor type-2 (HAI-2). Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of mice to prepare the mouse model of bone metastasis. The formation of bone metastasis was confirmed by whole-body bioluminescent imaging, and specimens were extracted. Expression of HGF/MET-related molecules was analyzed. Based on the results, we produced HAI-2 stable knockdown 786-O cells, and analyzed invasiveness and motility. Expression of HGF and matriptase was increased in bone metastasis compared with the control, while that of HAI-2 was decreased. Furthermore, we confirmed increased phosphorylation of MET in bone metastasis. The expression of matriptase was upregulated, and both invasiveness and motility were increased significantly by knockdown of HAI-2. The significance of ligand-dependent MET activation in RCC bone metastasis is considered, and HAI-2 may be an important regulator in this system.

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma.

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC.

[Advanced Adenocarcinoma of the Bladder after Augmentation Gastrocystoplasty].

A 29-year-old woman had undergone gastrocystoplasty with Mitrofanoff appendicovesicostomy for urethral trauma at 9 years of age. Since then, she was being followed up for performing clean intermittent self-catheterization at regular intervals. Twenty years after the surgery, she presented with gross hematuria. Ultrasonographic findings revealed bilateral hydronephrosis. Cystoscopy and computed tomography (CT) revealed invasive bladder cancer with pelvic lymph node metastases. A biopsy confirmed the diagnosis of adenocarcinoma with signet ring cell carcinoma. Subsequently, neo-adjuvant combination chemotherapy with TS-1 and cisplatin (CDDP) was initiated, which was followed by open radical cystectomy with extended pelvic lymphadenectomy. The tumor was found to infiltrate from the anastomotic site into the entire native bladder and histopathological diagnosis was muscle invasive adenocarcinoma with neuroendocrine differentiation and lymph node metastasis (ypT3bN2). TS-1 was continued as adjuvant chemotherapy and the patient did not have any evidence of recurrence for 12 months postoperatively.

[A Case of Rapidly Progressive Metastatic Castration-Resistant Prostate Cancer : Durable Control by Early Induction of Carboplatin and Paclitaxel].

A 60-year-old man visited the previous hospital with difficulty of urination in July 2004. Serum prostate specific antigen (PSA) was 5.4 ng/ml and he was diagnosed with prostate adenocarcinoma, Gleason Score 4＋4＝8, cT1cN0M0. Although radical prostatectomy was recommended, he refused any treatment and never visited that hospital again. He was admitted to our hospital for exacerbation of dysuria with anal pain newly appeared in March 2005, when it was found that his disease had progressed to cT4N0M1b (thoracic spine, sacroiliac joint and ischium). Serum PSA decreased and the primary lesion shrunk after androgen deprivation therapy (ADT), whereas the left ischial lesion enlarged and serum carcinoembryonic antigen (CEA) and alkaline phosphatase (ALP) were elevated. For the castration-resistant progression, 30 Gy of local irradiation to the left ischial lesion and systemic chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) were administered, which led the patient to complete radiological and biochemical remission. The chemotherapy was discontinued in 2009 after the 18th course, and then ADT was also discontinued in 2010. The patient remains free from radiological or biochemical evidence of disease at the latest follow up in December 2014.

Role of IL13RA2 in Sunitinib Resistance in Clear Cell Renal Cell Carcinoma.

Vascular endothelial growth factor (VEGF) and mammalian target of rapamycin are well-known therapeutic targets for renal cell carcinoma (RCC). Sunitinib is an agent that targets VEGF receptors and is considered to be a standard treatment for metastatic or unresectable clear cell RCC (ccRCC). However, ccRCC eventually develops resistance to sunitinib in most cases, and the mechanisms underlying this resistance are not fully elucidated. In the present study, we established unique primary xenograft models, KURC1 (Kyoto University Renal Cancer 1) and KURC2, from freshly isolated ccRCC specimens. The KURC1 xenograft initially responded to sunitinib treatment, however finally acquired resistance. KURC2 retained sensitivity to sunitinib for over 6 months. Comparing gene expression profiles between the two xenograft models with different sensitivity to sunitinib, we identified interleukin 13 receptor alpha 2 (IL13RA2) as a candidate molecule associated with the acquired sunitinib-resistance in ccRCC. And patients with high IL13RA2 expression in immunohistochemistry in primary ccRCC tumor tends to have sunitinib-resistant metastatic site. Next, we showed that sunitinib-sensitive 786-O cells acquired resistance in vivo when IL13RA2 was overexpressed. Conversely, shRNA-mediated knockdown of IL13RA2 successfully overcame the sunitinib-resistance in Caki-1 cells. Histopathological analyses revealed that IL13RA2 repressed sunitinib-induced apoptosis without increasing tumor vasculature in vivo. To our knowledge, this is a novel mechanism of developing resistance to sunitinib in a certain population of ccRCC, and these results indicate that IL13RA2 could be one of potential target to overcome sunitinib resistance.

[Pelvic lymph node dissection in robot-assisted laparoscopic radical prostatectomy: safety and adequacy in introductory series].

To evaluate the safety and adequacy of pelvic lymph node dissection (LND) in robot-assisted laparoscopic radical prostatectomy (RALP) in an institutional introductory case series, we retrospectively reviewed the first 135 patients with clinically localized prostate cancer who underwent RALP with no LND (n＝78), limited LND (LLND, n＝40), or extended LND (ELND, n＝17). Data were collected foroperating time itemized by each surgical procedure, estimated blood loss, lymph node yield, total postoperative drainage amount, postoperative days to drainage tube removal and urethral catheter removal, perioperative complication, and postoperative hospital stay. LLND and ELND took a median of 19 (interquartile range 15-22) and 69 (60.5-91) min, respectively. Total operating time was significantly longer (p＜0.0001) for those with ELND (median 329 min ; interquartile 272-375) than those with no LND (239 ; 195-292) and LLND (281 ; 230-314). Lymph node yield was 7 (5-9) and 23 (12-30) for LLND and ELND, respectively, which was equivalent to the yield of lymph nodes dissected in open prostatectomy ashistorical and institutional control. Although total drainage amount was significantly greater and drainage tube was placed significantly longer in the ELND group, there were no significant differences in time to urethral catheter removal and postoperative hospital stay among the groups. There were no severe perioperative complications associated with LND except for prolonged lymph fistula in each case of the LLND and ELND groups. In conclusion, LND can be performed safely and adequately in introductory RALP cases.

An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration, and metastasis of prostate cancer.

EP4 is one of the prostaglandin E2 receptors, which is the most common prostanoid and is associated with inflammatory disease and cancer. We previously reported that over-expression of EP4 was one of the mechanisms responsible for progression to castration-resistant prostate cancer, and an EP4 antagonist ONO-AE3-208 in vivo suppressed the castration-resistant progression regulating the activation of androgen receptor. The aim of this study was to analyze the association of EP4 with prostate cancer metastasis and the efficacy of ONO-AE3-208 for suppressing the metastasis. The expression levels of EP4 mRNA were evaluated in prostate cancer cell lines, LNCaP, and PC3. EP4 over-expressing LNCaP was established, and their cell invasiveness was compared with the control LNCaP (LNCaP/mock). The in vitro cell proliferation, invasion, and migration of these cells were examined under different concentrations of ONO-AE3-208. An in vivo bone metastatic mouse model was constructed by inoculating luciferase expressing PC3 cells into left ventricle of nude mice. Their bone metastasis was observed by bioluminescent imaging with or without ONO-AE3-208 administration. The EP4 mRNA expression levels were higher in PC3 than in LNCaP, and EP4 over-expression of LNCaP cells enhanced their cell invasiveness. The in vitro cell invasion and migration were suppressed by ONO-AE3-208 in a dose-dependent manner without affecting cell proliferation. The in vivo bone metastasis of PC3 was also suppressed by ONO-AE3-208 treatment. EP4 expression levels were correlated with prostate cancer cell invasiveness and EP4 specific antagonist ONO-AE3-208 suppressed cell invasion, migration, and bone metastasis, indicating that it is a potential novel therapeutic modality for the treatment of metastatic prostate cancer.

Improvement of prognosis in patients with metastatic renal cell carcinoma and Memorial Sloan-Kettering Cancer Center intermediate risk features by modern strategy including molecular-targeted therapy in clinical practice.

OBJECTIVES: To identify the patient subgroups benefitting the most from the modern strategy including molecular-targeted therapy among patients with metastatic renal cell carcinoma (mRCC) in clinical practice. METHODS: Retrospective analysis of 144 patients with mRCC diagnosed between 1992 and 2011 at Kyoto University Hospital was conducted. Multivariate analysis using the Cox proportional hazards model was conducted to identify prognostic factors associated with overall survival (OS). Subgroup analysis was conducted to identify patients who benefitted the most from molecular-targeted therapy. RESULTS: Independent factors associated with worse OS are: tumors of histological type other than clear-cell, decreased hemoglobin (Hb), elevated lactate dehydrogenase (LDH), elevated C-reactive protein (CRP), and metastases at ≥ 3 sites. Median OS of patients treated with molecular-targeted therapy alone or with prior immunotherapy and those treated with immunotherapy alone was 57, 45 and 28 months, respectively. Molecular-targeted therapy had more effect on OS than immunotherapy alone among female patients, patients with Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate risk features, and patients with metastatic progression less than 1 year after initial diagnosis of RCC, compared with their counterparts. CONCLUSIONS: The modern strategy including molecular-targeted therapy may improve OS in patients with mRCC and MSKCC intermediate risk features in clinical practice, relative to those with other risk features. However, the prognosis for patients with tumors of histological type other than clear-cell, decreased Hb, elevated LDH, elevated CRP, or metastases at ≥ 3 sites remains poor even in the modern molecular-targeted era. Novel treatment strategies are necessary to improve prognosis in these patients.

Role of mammalian target of rapamycin inhibitor in the treatment of metastatic epithelioid angiomyolipoma: a case report.

Epithelioid angiomyolipoma has malignant potential; however, no effective therapy has been established for advanced cases. A 50-year-old woman with a history of right nephrectomy for epithelioid angiomyolipoma was referred to our institution. Computed tomography and magnetic resonance imaging showed multiple tumors in her lung, liver and pelvic cavity. The liver and pelvic tumor specimens obtained by needle biopsy confirmed the diagnosis of epithelioid angiomyolipoma recurrence. The patient was treated with everolimus (10 mg/day). Three months later, pulmonary lesions disappeared; liver and pelvic tumors significantly shrank in size, but the pelvic tumor gradually enlarged again. We carried out surgical resection of the residual liver and pelvic cavity tumors. Although the mammalian target of rapamycin inhibitor seems to be effective for treating epithelioid angiomyolipoma, its long-term effects remain unknown. Thus, aggressive administration of a multidisciplinary treatment including molecular target therapy and surgical resection is required to improve the prognosis of epithelioid angiomyolipoma.