Patient-specific simulations and navigation systems for partial nephrectomy.

Partial nephrectomy (PN) is the standard treatment for T1 renal cell carcinoma. PN is affected more by surgical variations and requires greater surgical experience than radical nephrectomy. Patient-specific simulations and navigation systems may help to reduce the surgical experience required for PN. Recent advances in three-dimensional (3D) virtual reality (VR) imaging and 3D printing technology have allowed accurate patient-specific simulations and navigation systems. We reviewed previous studies about patient-specific simulations and navigation systems for PN. Recently, image reconstruction technology has developed, and commercial software that converts two-dimensional images into 3D images has become available. Many urologists are now able to view 3DVR images when preparing for PN. Surgical simulations based on 3DVR images can change surgical plans and improve surgical outcomes, and are useful during patient consultations. Patient-specific simulators that are capable of simulating surgical procedures, the gold-standard form of patient-specific simulations, have also been reported. Besides VR, 3D printing is also useful for understanding patient-specific information. Some studies have reported simulation and navigation systems for PN based on solid 3D models. Patient-specific simulations are a form of preoperative preparation, whereas patient-specific navigation is used intraoperatively. Navigation-assisted PN procedures using 3DVR images have become increasingly common, especially in robotic surgery. Some studies found that these systems produced improvements in surgical outcomes. Once its accuracy has been confirmed, it is hoped that this technology will spread further and become more generalized.

Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research.

Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers.

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment.

Re-Challenging with Nivolumab in Metastatic Renal Cell Carcinoma After Immune-Related Interstitial Pneumonia: A Case Report.

BACKGROUND The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. CASE REPORT Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1bN0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. CONCLUSIONS For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.

[ARTIFICIAL URINARY SPHINCTER IMPLANTATION AFTER ILEAL NEOBLADDER RECONSTRUCTION: A CASE REPORT].

A 62-year-old man was referred to our department for artificial urinary sphincter (AUS) implantation as treatment for total incontinence after laparoscopic radical prostatectomy. Preoperative cystoscopy revealed bladder tumor that was proven to be high-grade micropapillary urothelial carcinoma by transurethral resection. We performed radical cystectomy with ileal neobladder reconstruction, followed by AUS implantation to treat incontinence. The AUS implantation procedure was performed 5 months after total cystectomy and resulted in significant continence recovery. To date, AUS implantation after neobladder reconstruction has not been reported in Japan, although some case series have described this procedure overseas. In our view, AUS implantation is a useful therapeutic option for incontinence in patients undergoing neobladder reconstruction.

Comparative effectiveness of surgery and radiotherapy for survival of patients with clinically localized prostate cancer: A population-based coarsened exact matching retrospective cohort study.

Radical prostatectomy and radiotherapy are currently the main treatment options for localized prostate cancer. However, no large cohort study comparing surgery and radiation has been performed in Japan or Asia. The objective of the current study was to compare the survival outcomes of patients with clinically localized prostate cancer and in elderly and young patients receiving surgery and radiotherapy. The survival outcomes of patients with localized prostate cancer (age at diagnosis ≤79 years, clinical T1-3) initially treated with surgery or radiotherapy were retrospectively analyzed. Data were collected from the population-based cancer registry of the Kanagawa Prefecture, Japan. A 1:1 coarsened exact matching of age at diagnosis, clinical T stage and cancer differentiation was performed between the two treatment groups. Patients were also categorized into two subgroups by age using a cutoff of 70 years for analysis. The cohort comprised 4,810 patients aged 50-79 years. No significant difference in cancer-specific survival (CSS) was observed between the two groups (P=0.612). However, the surgery group had significantly better overall survival (OS; P=0.004). When stratified for age, similar tendencies were observed in the elderly group (aged 70-79 years; CSS, P=0.961 and OS, P=0.007). No significant difference in either CSS or OS was identified in the younger group (P=0.550 and P=0.408, respectively). Intrinsic deaths were more likely to occur in elderly patients treated with radiotherapy than those undergoing surgery (69.3 vs. 78.2%; P=0.128). The results indicated that surgery provided significantly better OS than radiotherapy, particularly among the elderly. However, no significant difference was observed in CSS. These results should be interpreted with caution, given that some important factors were unavailable in the present study, such as prostate-specific antigen values and Gleason scores. Prospective trials evaluating these therapies are warranted.

C-reactive protein at 1 month after treatment of nivolumab as a predictive marker of efficacy in advanced renal cell carcinoma.

PURPOSE: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab. METHODS: After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined. RESULTS: The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline. CONCLUSION: Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.

A lower psoas muscle volume was associated with a higher rate of recurrence in male clear cell renal cell carcinoma.

BACKGROUND: Sarcopenia is defined as a low skeletal muscle volume. Recent studies have reported that sarcopenia is associated with a poor prognosis in various cancers. The purpose of this study is to evaluate the correlation between the psoas muscle volume and recurrence-free survival in patients with localized clear cell renal cell carcinoma (ccRCC). METHODS: A total of 316 male patients with localized ccRCC who underwent radical nephrectomy at Yokohama City University Hospital (Yokohama, JAPAN) and Kanagawa Cancer Center (Yokohama, JAPAN) between 2002 and 2018 were enrolled in this study. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area on the contralateral side of the tumor on axial CT, which was calculated at the level of L4 (mm2) divided by the square of the body height (m2). We divided patients into two groups based on the median PMI (409.64mm2/m2). RESULTS: The lower PMI group showed poorer recurrence-free survival (RFS) than the higher PMI group (p = 0.030). Regarding 5-year RFS, a lower PMI was a significant predictor of recurrence (p = 0.022, hazard ratio (HR): 2.306) and a multivariate analysis revealed that a lower PMI (4 cm (p = 0.044, HR: 2.341), and pathological stage >2 (p<0.001, HR: 3.660) were independent risk factors for poor RFS. CONCLUSIONS: The presence of sarcopenia (lower PMI) was found to be associated with poor RFS in male ccRCC patients. The PMI might serve as a measure of patient frailty and might be useful for prognostic risk stratification in ccRCC.

[A CASE OF EXTRASKELETAL EWING'S SARCOMA IN THE RETROPERITONEUM].

A 23-year-old man was admitted to our hospital with a huge pelvic tumor. MRI showed a tumor mixed with a solid component and polycystic cyst with maximum diameter of about 20 cm. Percutaneous tumor needle biopsy was performed and diagnosis was Ewing sarcoma. At that time, operation is extremely difficult, so the neoadjuvant chemotherapy with ifosfamide, etoposide, Adriamycin, and vincristine were administered. After 6 courses, MRI showed tumor reduction to maximum diameter of 10 cm. We planned tumor resection with total cystectomy for radical resection, but we also tried to preserve bladder considering the young age and quality of life. Although the bladder was partially resected, tumor resection was succeeded without removing surrounding organs. Histopathological examination revealed viable cells remained, but more than 95% was disappeared and the surgical margins were negative. Here we report a case of extra skeletal Ewing sarcoma in the retroperitoneum that was treated with chemotherapy and surgery without scarifying surrounding organs.

Outcome of Palliative Urinary Diversion and Observation for Malignant Extrinsic Ureteral Obstruction.

Background: Urologists are often referred to manage the extrinsic malignant ureteral obstruction (MUO) caused by nonurological malignancies. Usually palliative urinary diversion (ureteral stent or nephrostomy) will be performed; however, in the cases of no symptom or poor prognosis, observation (OBS) without any intervention will be selected. There are few reports about outcome of the OBS policy for MUO. Objective: To evaluate the outcome of palliative urinary diversion or OBS for MUO. Design: We retrospectively reviewed the selection of treatment and the prognosis. Setting/Subjects: A total of 151 cases were introduced to our department as MUO between April 2011 and December 2016. Measurements: The patients were divided to immediate palliative urinary diversion (immediate-DIV) or OBS. The latter patients were subdivided to OBS followed by deferred palliative urinary diversion (deferred-DIV), and observation only (OBS-only). Results: There was no significant difference between immediate-DIV and OBS about overall survival (OS) from the consultation. In OBS group, deferred-DIV did not prolong prognosis from the consultation more than OBS-only. In the same way, there was no significant difference between immediate-DIV and deferred-DIV in OS from the intervention. Unfavorable prognostic factors for OS were lack of anticancer treatment after consultation, symptoms of MUO, and gastrointestinal cancer. When we classified the patients by these factors, the group with three factors showed significantly poorer prognosis than the others. Conclusion: Immediate-DIV or OBS did not influence the prognosis in the whole patients. Three prognostic factors that will be judged by urologists easily might be useful for the indication and timing of palliative urinary diversion.

[PREDICTIVE AND PROGNOSTIC SIGNIFICANCE OF PRE-TREATMENT LYMPHOCYTE COUNT IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA TREATED WITH PLATINUM-BASED FIRST-LINE CHEMOTHERAPY].

(Purpose) Pre-treatment low lymphocyte count may result from cytokine secretion by the tumor microenvironment, in association with aggressive tumor biology. We sought to establish the prognostic impact of the absolute lymphocyte count (ALC) in advanced urothelial carcinoma. (Patients and method) We retrospectively reviewed 63 patients with unresectable or metastatic urothelial carcinoma who were treated with platinum-based first-line systemic chemotherapy between January 2011 and April 2018. We evaluated the importance of the ALC in patients who underwent systematic chemotherapy. (Results) Thirty-eight patients (60%) died from urothelial carcinoma, with a median follow-up interval of 12.2 months. The median overall survival (OS) duration was 15.3 months. The mean ALC in the stable and progressive disease group was lower than that in the complete and partial response group (1,312 /µL and 1,666 /µL, respectively, p=0.004). The ALC of 1,460 /µL was determined as the cut-off on Receiver operating characteristic curve analysis. The log-rank test revealed that the lymphocytopenia group (ALC <1,460 /µL) showed significantly poorer prognoses than the non-lymphocytopenia group (p=0.001). Multivariate analyses showed that lymphocytopenia was an independent poor prognostic factor (hazard ratios of 3.46, p=0.002). (Conclusions) Pre-treatment low lymphocyte count is an independent poor prognostic factor in patients with urothelial carcinoma who underwent platinum-based first-line systemic chemotherapy.

Clear cell adenocarcinoma of the prostatic urethra: A case report.

INTRODUCTION: Clear cell adenocarcinoma of the prostatic urethra in men is an extremely rare disease, with only eight case reports published. CASE PRESENTATION: A 56-year-old man visited our hospital for gross hematuria. Urinary cytology detected class V, cystoscopy showed no abnormal findings, and contrast-enhanced computed tomography also showed no abnormal findings in his upper urinary tract except for a low-enhancement lesion on his left prostate lobe. Magnetic resonance imaging revealed a cystic lesion surrounding the prostate that was suspected of being urethral or prostate cancer, so transurethral resection was performed. A papillary tumor was detected at the prostatic urethra, and after resecting this tumor, a cavity showing multiple tumors was observed. The final pathological diagnosis was clear cell adenocarcinoma. Laparoscopic radical cystectomy and urethrectomy were thus performed. The pathological diagnosis was the same as at the primary tumor site. CONCLUSION: We herein report a case of clear cell adenocarcinoma of the prostatic urethra.

Functional paraganglioma of the bladder: Both radiographic-negative and laboratory-negative case.

INTRODUCTION: Paraganglioma has been determined to be an extra-adrenal pheochromocytoma. Paraganglioma of the bladder is a rare entity, accounting for 0.06% of all bladder tumors. CASE PRESENTATION: A 58-year-old woman had been annually followed up since being diagnosed with rectal cancer 5 years ago. In January 2018, follow-up computed tomography detected a bladder tumor, and she was referred to our department for a further examination. Cystoscopy revealed a submucosal tumor on her right bladder wall. We performed transurethral resection of the bladder tumor. When we first marked the tumor margin, the systolic blood pressure increased, so we abandoned resection. We performed meta-iodobenzylguanidine scintigraphy and acid urinary collection, neither of which revealed any abnormal findings. We therefore performed open partial cystectomy based on a clinical diagnosis of paraganglioma of the bladder. The pathological findings revealed paraganglioma of the bladder. CONCLUSION: We herein report a case of paraganglioma of the bladder.

Case of acute respiratory distress syndrome in a patient with an extragonadal germ cell tumor without lung metastasis in which choriocarcinoma syndrome was suspected.

INTRODUCTION: Choriocarcinoma syndrome is caused by bleeding from metastatic germ cell tumors with choriocarcinoma components. Here, we report a case of acute respiratory distress syndrome, which arose after first-line chemotherapy for an extragonadal germ cell tumor without lung metastasis. CASE PRESENTATION: A 41-year-old male visited our institution with chief complaints of back pain and weight loss. Computed tomography showed multiple lymph node metastases in the retroperitoneal cavity. There were no lung metastases. A lymph node biopsy resulted in a diagnosis of choriocarcinoma. Bleomycin etoposide cisplatin therapy was started as induction chemotherapy. On the first day, he was diagnosed with acute respiratory distress syndrome due to choriocarcinoma syndrome. We administered high-dose hydrocortisone therapy for 3 days. The patient's respiratory status improved. CONCLUSION: In patients who are at high risk of developing choriocarcinoma syndrome, induction chemotherapy might lead to the development of acute respiratory distress syndrome due to the release of cytokines despite the absence of lung metastasis.

[A CASE OF METASTATIC KIDNEY CANCER FOR WHICH THE EFFICACY OF NIVOLUMAB THERAPY WAS MAINTAINED EVEN AFTER THE DEVELOPMENT OF INTERSTITIAL PNEUMONIA].

The patient was a 52-year old man who underwent laparoscopic radical nephrectomy for kidney cancer. Left adrenal and lung metastases occurred 5 and 11 years after the surgery, respectively. Various molecular-targeted therapies were ineffective, so nivolumab treatment was started 12 years after the surgery. Treatment was discontinued when the patient developed interstitial pneumonia after three courses of nivolumab treatment. After steroid treatment for interstitial pneumonia, both the symptoms and findings of the imaging tests improved quickly. On the other hand, while the effect of Partial Response (PR) was evident in the lungs and adrenal glands, on the basis of the image assessments performed after three courses of treatment, the effect was maintained without regrowth even at the last follow-up, 10 months after discontinuing the treatment.

Nephrectomy for Metastatic Kidney Tumor in Patients with Differentiated Thyroid Cancer: A Report of Two Cases.

The occurrence of renal tumors originating from thyroid cancer is extremely rare with a few effective treatments for renal metastases. Here, we report the cases of two patients with differentiated thyroid cancer who underwent nephrectomy for a metastatic kidney tumor. Case 1 was a 74-year-old man who was diagnosed with right kidney tumor 10 years after initial surgery for papillary thyroid cancer (PTC). Right nephrectomy was performed, and the pathology was metastatic PTC. Case 2 was a 68-year-old woman who was diagnosed with left kidney tumor 24 years after surgery for follicular thyroid carcinoma (FTC). Left nephrectomy was performed, and the pathology was metastatic FTC. Nephrectomy for single renal metastasis could be considered a treatment option if the patients' general condition is positive.

Hereditary leiomyomatosis and renal cell cancer without cutaneous manifestations in two Japanese siblings.

Hereditary leiomyomatosis and renal cell cancer is a rare genetic disorder characterized by cutaneous and uterine leiomyomatosis, and an aggressive type 2 papillary renal cell carcinoma. The disease is caused by a germline mutation in the fumarate hydratase gene. We report a familial hereditary leiomyomatosis and renal cell cancer in two siblings. A 34-year-old woman underwent nephrectomy for treatment of a renal cell carcinoma. The patient's sister had been diagnosed with renal cell carcinoma at 28 years-of-age and died of the disease. Neither sister had apparent skin tumors. Histopathology of the renal cell carcinomas of the siblings showed tubulocystic and papillary architectures with high nuclear grades. Immunostaining showed no fumarate hydratase expression in either tumor. Genomic DNA sequencing of the patient showed a germline mutation in the fumarate hydratase gene (c.675delT). Although there is no epidemiological information on Asian hereditary leiomyomatosis and renal cell cancer, physicians should be aware that typical cutaneous leiomyomatosis might not always be present in patients with hereditary leiomyomatosis and renal cell cancer.

Renal Cell Carcinoma in a Horseshoe Kidney Treated with Laparoscopic Partial Nephrectomy.

INTRODUCTION: Horseshoe kidney is one of the most common congenital renal fusion anomalies. Due to its poor mobility and abnormal vasculature form, surgeons should pay close attention to all anatomical variations. CASE PRESENTATION: An 83-year-old woman was referred to our hospital because of left renal tumor in a horseshoe kidney incidentally found by her previous hospital. We performed laparoscopic partial nephrectomy. The pathological diagnosis was clear cell renal cell carcinoma. G2 INFα V-pT1a with a negative surgical margin. No evidence of recurrence has been noted, and the renal function is well preserved at 28 months after surgery. CONCLUSION: When performing laparoscopic partial nephrectomy for renal carcinoma, especially a horseshoe kidney, preoperative imaging is crucial for identifying the location of the renal vessels.

Significant response to nivolumab for metastatic chromophobe renal cell carcinoma with sarcomatoid differentiation: a case report.

BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial. We report a case in which the use of nivolumab as the seventh-line therapy elicited a significant response in the treatment of metastatic CRCC with sarcomatoid differentiation. CASE PRESENTATION: We report a case of a 41-year-old woman with metastatic CRCC with sarcomatoid differentiation. She was treated with sunitinib, pazopanib, everolimus, sorafenib, axtinib, and temsirolimus, but treatment was discontinued because of disease progression or strong adverse events. Seventh-line treatment with nivolumab was initiated and significant clinical improvement was noted after 4 cycles. The treatment was well-tolerated with no significant side effects and the patient continues with nivolumab treatment at present. CONCLUSIONS: Nivolumab may be an attractive treatment option for non-ccRCC patients with sarcomatoid differentiation that exhibited aggressive characteristics and poor prognosis. Further investigation is warranted.

Time-dependent change in relapse sites of renal cell carcinoma after curative surgery.

We investigated time-dependent changes in the relapse features of renal cell carcinoma (RCC) after curative surgery. Between 1985 and 2015, 1398 patients with RCC (1226 clear cell RCC, 89 papillary RCC, and 53 chromophobe RCC) underwent curative surgery at Yokohama City University Hospital and its affiliated hospitals. We retrospectively reviewed the clinicopathologic factors of patients with relapse after surgery. Median follow-up was 56.3 months. Recurrence occurred in 245 patients (217 clear cell RCC, 12 papillary RCC, and 3 chromophobe RCC). Papillary RCC and chromophobe RCC had no recurrence beyond 5 years after surgery, but 20 cases of clear cell carcinoma had recurrence beyond 10 years after surgery. The typical recurrence sites of clear cell RCC were lung (46.6%), bone (17.9%), liver (7.6%), and lymph nodes (6.5%). The proportion of recurrences at these typical sites was 83.9% for recurrences within 5 years, 76.3% between 5 and 10 years, and 40.0% beyond 10 years. In contrast, the proportion of retroperitoneal organ recurrence, including contralateral kidney, pancreas, and adrenal glands, increased with increasing time after surgery. Interestingly, the hazard ratio of typical site relapse decreased whereas that of retroperitoneal organ relapse increased in a time-dependent manner. In summary, clear cell RCC showed potential to relapse beyond 10 years after surgery. Recurrence at typical sites decreased whereas retroperitoneal organ recurrence increased in a time-dependent manner. Clinicians should check for recurrence at various sites beyond 10 years, especially in clear cell RCC.