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Patients on chronic dialysis for end-stage renal disease (ESRD) show an increased incidence of renal cell carcinoma (RCC). We investigated the clinicopathological characteristics and outcomes of 54 patients who underwent nephrectomy for RCC due to ESRD between 1992 and 2019. The patients consisted of 44 men and 10 women, with a median age of 62.9 years. The median duration of dialysis before surgery was 12.9 years. The clinical stage of the 54 RCCs was stage I in 44, stage II in 1, stage III in 1, and stage IV in 8. With a median follow-up of 5.1 years after surgery, the 5-year cancer-specific and overall survival rates were 84.3 and 61.8%, respectively. Patients with symptomatic RCC had a longer period of dialysis, presented with larger tumors of higher grade and stage, and had worse prognosis compared with those with incidentally discovered RCC. Cox proportional hazards analysis performed with clinicopathological features and symptomatic/incidental detection showed that older age and symptomatic RCC were independently associated with worse overall survival. Our data show that early detection is important for a good prognosis.

We investigated the clinical characteristics of patients who developed kidney injury after starting treatment with immune checkpoint inhibitors (ICI) for urologic malignancies. The study included 118 patients who were treated with ICI at our hospital. They consisted of 65 with renal cell carcinoma, 52 with urothelial carcinomas and 1 with adrenocortical carcinoma with high-frequency microsatellite instability. Immune-related kidney injury was observed in 13 patients (11.0%), including stage 1, 2 and 3 kidney injuries in 9, 0 and 4 patients, respectively. In univariate analyses, ≥stage 4 chronic kidney disease (CKD) before ICI treatment and proton pump inhibitor use were significantly associated with all stages of kidney injury, whereas ≥stage 4 CKD and ICI combination therapy were significantly associated with kidney injury at ≥ stage 2. Of the 4 patients who developed ≥stage 2 kidney injury, histological examination was done only for 2 because renal biopsy was contraindicated in the other 2 due to prior nephrectomy. Steroid pulse therapy was performed for 3 patients but provided complete recovery only in 1. We should be aware of the risk for immune-related kidney injury in patients with baseline CKD (≥stage 4) and receiving ICI combination therapy. Precise diagnosis by histological examination can often be challenging due to a history of nephrectomy.

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

A 52-year-old man complained of asymptomatic gross hematuria and cough. Chest and abdominal computed tomography (CT) revealed a right renal tumor, mediastinal lymph node metastasis, and right endobronchial metastasis. The right endobronchial metastasis was causing obstructive atelectasis in the lower lobe of the right lung. After tumor biopsy, the pathological diagnosis was clear cell renal cell carcinoma. Combination immunotherapy with ipilimumab and nivolumab was initiated, but CT showed enlargement of the metastatic lesion and lung abscess after two courses of treatment. The therapy was then switched to axitinib. Six days after initiation of axitinib, the lung abscess perforated into the pleural cavity, which resulted in the formation of pleural empyema with fistula. Ten days after initiation of axitinib, obstruction of the bronchus was relieved due to shrinkage of the right endobronchial metastasis, which resulted in development of a pneumothorax. Placement of a thoracic drainage tube and administration of an antimicrobial agent improved the pneumothorax and inflammatory response, but the drainage tube could not be removed. Long-term insertion of the thoracic drainage tube considerably diminished the patient's quality of life, and after 4 months, he was transferred to another hospital to receive the best supportive care., 本論文の要旨は第243回日本泌尿器科学会関西地方会において発表した.

We compared brain metastasis of renal cell carcinoma (RCC) in patients who received tyrosine kinase inhibitors (TKIs) ; 17 received local therapy, while 16 did not. The median survival rate was 19 months in the local therapy group and 11 months in the tyrosine kinase inhibitor alone group, showing no significant difference (p＝0.52). Symptoms such as paralysis, headache, and dysarthria occurred due to brain metastasis. These symptoms improved in 8 out of 10 patients in the local therapy group. There were no cases of grade 3 or higher complications due to local therapy. Although local therapy did not prolong the overall survival, an improvement in symptoms was observed, suggesting that it is acceptable as palliative treatment.

A 46-year-old woman was referred to our hospital with a left-sided renal tumor pointed out by ultrasonography at the time of a medical checkup．Computed tomography revealed a mass measuring 88×77×68 mm on the upper pole of the left kidney. She was diagnosed with cT2aN0M0 clear cell renal cell carcinoma. Laparoscopic left nephrectomy was performed uneventfully. Histopathological diagnosis was clear cell renal cell carcinoma, G2, v1, pT2. Four months after surgery, lung metastases appeared, and systemic therapy was given sequentially as follows ; sunitinib for 2 months, nivolumab for 8 months, axitinib for 17 months, and pazopanib for 2 months．However, metastases progressed, and a re-administration of nivolumab was planned. The nivolumab re-treatment resulted in a marked reduction in multiple lung metastases despite the previous failure by nivolumab treatment. There are few reports on the therapeutic effect of re-administration of nivolumab. We report a case of successful treatment by re-administration of nivolumab.

A woman in her seventies complained of chest pain during exertion and visited a local hospital. Computed tomographic scan showed right renal cell carcinoma with inferior vena cava (IVC) tumor thrombus extending above the diaphragm, and the patient was referred to our hospital. She was diagnosed with right renal cell carcinoma cT3cN0M0, with level IV IVC thrombus by Mayo classification. Axitinib and pembrolizumab were administered against intractable advanced renal cell carcinoma. The dose of axitinib was reduced due to grade 3 liver dysfunction. Right nephrectomy together with IVC thrombectomy was performed because the primary lesion had shrunk, and the level of IVC thrombus had become level III. The pathological results were clear cell carcinoma, pT3c, G3, Fuhrman grade3, INFA, v1, and ly0. Axitinib and pembrolizumab might be a presurgical option against an intractable renal cell carcinoma with an IVC thrombus.

A 71-year-old man was referred to our hospital for treatment of a 2 cm-sized right renal mass incidentally found by computed tomography (CT) and was diagnosed with right renal cell carcinoma cT1aN0M0. Contrast-enhanced CT revealed that the aorta was completely occluded below the inferior mesenteric artery origin, and Leriche syndrome was diagnosed. CT angiography showed several collateral arteries along the abdominal wall. A robot-assisted laparoscopic partial nephrectomy was performed to treat renal cell carcinoma. Preoperatively, we marked the collateral arteries using ultrasonography to avoid injury during trocar insertion. We did not observe any decrease in blood flow in the right leg during the operation. The pathological diagnosis was clear cell renal cell carcinoma. Leriche syndrome is a chronic occlusive disease involving the infrarenal aorta and the iliac arteries. Since lower limb blood flow is dependent on collateral circulation, it is important to avoid injuring the collateral arteries during surgery., 本論文の要旨は，第240回日本泌尿器科学会関西地方会にて発表した．

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. Renal MTSCC has many similarities with papillary renal cell carcinoma (pRCC), and it is therefore often difficult to make a differential diagnosis between them. Herein, we report a case of renal MTSCC. The patient was a 76-year-old woman. Computed tomography revealed a left renal tumor. Magnetic resonance imaging (MRI) demonstrated an iso-intensity or high signal intensity mass on T2-weighted images, high signal intensity on diffusion-weighted images, and weak and gradual enhancement. We diagnosed the patient with left renal cell carcinoma (cT1bN0M0) and performed laparoscopic left nephrectomy in May 2019. The histopathological diagnosis was renal MTSCC. Six months after surgery, the patient remains free of recurrence and of metastasis. MRI is effective for the preoperative differentiation of renal MTSCC from pRCC since renal MTSCC presents an iso-intensity or high signal intensity on MRI T2-weighted images reflecting the mucin component in the intervening stroma within the tumor.

A man in his 60s was diagnosed with clear cell carcinoma of the right kidney with multiple lung metastases, tumor thrombus of the inferior vena cava (IVC), and invasion of the duodenum and pancreas. Ipilimumab plus nivolumab was administered as first-line therapy. After 3 treatment courses, computed tomography (CT) demonstrated a slight decrease in the size of the primary tumor and lung metastases. However, the patient became hemodynamically unstable due to persistent duodenal bleeding during treatment despite frequent blood transfusions. Axitinib was then initiated as second-line therapy. The duodenal bleeding ceased 10 days after starting axitinib and his anemia remissed. Subsequent CT showed further decrease in the size of the primary tumor and lung metastases. The patient underwent right nephrectomy after improvement of nutrition. IVC thrombectomy, and pancreaticoduodenectomy. The lung metastases disappeared on postoperative imaging and no additional treatment was provided. Twelve months after surgery, he was in good health and showed no signs of recurrence.

We report the case of a 61-year-old man who was incidentally diagnosed with a left pelvic ectopic kidney with renal tumor. Computed tomography showed a hypervascular tumor at the posterior surface of the ectopic kidney with five arterial and two venous supply vessels. On preoperative examination, this patient had respiratory dysfunction. For these reasons, an open radical nephrectomy was performed. Histological examination revealed a clear cell renal cell carcinoma, pT1aN0M0, G1, and a Fuhrman nuclear grading system grade of G2. No evidence of disease was observed 15 months after surgery.

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to −20%, and 8 ≦−20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to −20%, and ≦−20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p

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.

A 69-year-old man was referred to our hospital for a right renal pelvic tumor noted on a computed tomography (CT) scan at another hospital. Urine cytology was negative. Dynamic CT revealed a right renal pelvic tumor and, accidentally, a small left renal tumor enhanced in the arterial phase and washed out in the venous phase. No defect in the urinary tract was found on retrograde urography, and upper urinary cytology was negative. The patient’s level of IgG4 was high, but other tumor markers were negative. We judged the right renal pelvic tumor to be an extrapelvic lesion, probably IgG4-related disease. We temporarily followed up the right renal pelvic tumor but performed retroperitoneal left partial nephrectomy for the small left renal tumor. Histopathology led to a diagnosis of clear cell renal cell carcinoma. Follow-up CT showed no change in the right renal pelvic tumor. We diagnosed the right renal tumor as IgG4-related disease and began steroid administration. After one monthof administration, the IgG4 value and the size of the tumor were reduced.

Peritoneal dissemination or metastasis is a relatively rare presentation of renal cell carcinoma. We report four cases of advanced renal cell carcinoma with peritoneal metastases treated with nivolumab. Three cases showed an objective response in the metastatic lesions including peritoneal sites. After nivolumab administration, the computed tomography scan showed a transient enlargement of peritoneal lesions in two cases, which could be considered as pseudoprogression. Temporal changes of neutrophil-tolymphocyte ratio, C-reactive protein, and eosinophil ratio during the clinical course reflected the treatment effect of nivolumab in these patients, indicating that these could be potential biomarkers of the response. To our knowledge, this is the first case series showing therapeutic activity of nivolumab against peritoneal metastases in patients with renal cell carcinoma.

A 68-year-old man was referred to our hospital with a right-sided renal tumor identified by ultrasonography at the time of his medical check-up. Computed tomography revealed a well-circumscribed but distorted mass measuring 64×45×57 mm in the right kidney with para-aortic lymph node swelling. Laparoscopic right nephrectomy with para-aortic lymphadenectomy was performed. Histopathological diagnosis was mucinous tubular and spindle cell carcinoma (MTSCC) (pT3a) without lymph node metastasis (pN0). Postoperatively, metastases were identified in the lungs, and the vertebral and iliac bones. The patient was treated with axitinib. The lung nodule progressed and left sacrum metastases appeared even after treatment with axitinib. Therefore, nivolumab was administered as second-line treatment. The metastases in the lungs, as well as vertebral and iliac bone showed complete response to this therapy. MTSCC of the kidney is a rare low-grade renal cell carcinoma without any established systemic therapy for metastatic or unresectable lesions. We report a case of metastatic MTSCC in a patient who showed a favorable response to nivolumab treatment. This is the first report to describe successful treatment of metastatic MTSCC with anti-programmed cell death 1 antibody.

A 69-year-old male with the complaint of a cough was referred to our hospital from a clinic where he was found to have simultaneous metastases of the left kidney tumor. We performed left cytoreductive nephrectomy, and administered sunitinib after the surgery. The first line treatment was not effective. Then we changed the therapeutic agent to pazopanib as the second line treatment. Lung and lymph node metastases gradually shrunk, but he developed right vision disorders and was diagnosed with bilateral metastatic retinal tumors. First, irradiation to the right eye was performed while discontinuing pazopanib. Sudden treatment withdrawal caused his general condition to worsen temporally, but irradiation could be continued by resuming administration of pazopanib. As a consequence, the progression of the visual field disorder was suppressed by the additional ophthalmologic treatment. Renal cell carcinoma choroidal metastases are rare, but we need to consider them when the patient has vision disorders.

Randomized phase III trials demonstrated superiority of targeted therapy with tyrosine kinase inhibitors over cytokine-based therapy as first-line therapy for metastatic renal cell carcinoma. However, the rate of complete response (CR) with targeted therapy is smaller than that with cytokine-based therapy. A 47-year-old man was referred to our hospital with a 12 cm left renal tumor and polycythemia. He was diagnosed with renal cancer, cT3aN0M1, with multiple lung metastases. He underwent cytoreductive nephrectomy, with the histopathological diagnosis of clear cell renal cell carcinoma, Fuhrman nuclear grade 2, INFb, pT2b. Three months postoperatively, spontaneous regression of lung metastases was observed. Seventeen months postoperatively, a 17×13 mm retroperitoneal tumor facing the pancreas recurred. CR of the recurrent tumor was achieved by targeted therapy with sunitinib for 12 months. This CR was maintained for 32 months after the discontinuation of targeted therapy with sunitinib.

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.

A 66-year-old man had undergone multiple treatments for metastatic renal cell carcinoma, including 11 cycles of nivolumab, which was discontinued because of disease progression. About three weeks after discontinuing nivolumab, he reported suffering from worsening of dyspnea. Pulse oximetry showed no desaturation. His cardiovascular and pulmonary functions were normal. His dyspnea slowly worsened with no underlying diagnosis. Two months after symptoms developed, he was diagnosed with isolated adrenocorticotropic hormone deficiency. His dyspnea disappeared soon after receiving hydrocortisone. Nivolumab-induced isolated adrenocorticotropic hormone deficiency may not present with typical symptoms, and can occur even after discontinuing nivolumab. Cortisol levels should be routinely monitored in patients who receive nivolumab.

A 66-year-old man underwent nephrectomy for right renal cell carcinoma (cT3bNOMl (PUL)). Thereafter, he was treated with sunitinib for lung metastasis as the first-line therapy for 5 months and then axitinib as the second-line therapy for 2 months. Because lung metastasis progressed despite molecular targeted therapies, nivolumab was used as the third-line treatment. Three months later, he complained of painful stiffness in hands and wrist joints symmetrically. He was diagnosed as having rheumatoid arthritis. Treatment with nivolumab was discontinued and prednisolone and methotrexate were started. Although the painful stiffness in joints was improved l month later, synovitis remained partially 6 months after starting treatment of disease with anti-rheumatic drugs. Therefore, treatment for rheumatoid arthritis was continued. On the other hand, because the lung lesion had progressed 2 months after discontining nivolumab, everolimus was used as the fourth-line therapy.

Although fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely used as a powerful tool in clinical oncologic imaging, its application in urological malignancies is limited. Recently, choline PET/CT has been successfully used for prostate cancer restaging. Here, we report the utility of choline PET/CT for the detection and monitoring of metastatic disease in two cases of renal cell carcinoma (RCC). A 53-year-old woman and a 45-year-old woman underwent FDG and choline PET/CT for evaluation of metastatic lesions in lymph nodes and bone following left and right RCC, respectively, and choline PET/CT demonstrated significantly higher uptake when compared with FDGPET/CT in both cases. Choline PET/CT accurately reflected the remission and progression of diseases in their clinical course, indicating that choline PET/CT could be a useful imaging modality in metastatic RCC.

A 62-year-old woman underwent laparoscopic radial nephrectomy for the left renal cell carcinoma in September 2008. In July2016, the patient developed asymptomatic gross hematuria. Computed tomography (CT) revealed the enlargement of the left ureteral stump and an 11mm nodule in the superior lobe of the right lung. Since [F-18] fluoro-D-glucose-positron emission tomography-CT FDG PET-CT demonstrated a lung tumor, we decided to perform right upper lobectomybyvideo-assisted thoracoscopic surgeryin September. The patient was diagnosed with metastatic renal cell carcinoma. We then removed the left ureteral stump and performed partial cystectomy in November. A pathological examination revealed that the tumor was metastatic clear cell renal cell carcinoma invading the muscle layer. Two months later, the patient developed gross hematuria again. Cystoscopy revealed a 1cm tumor around the scar of partial cystectomy. Transurethral resection was performed, and a pathological examination revealed metastatic renal cell carcinoma. We herein report this case of renal cell carcinoma in which recurrence occurred in the ureteral stump, 8 years after radical nephrectomy.

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, low-grade renal epithelial neoplasm. MTSCC has a lower malignant potential and shows relatively good prognosis, but can be difficult to distinguish from other renal cell carcinoma (RCC) subtypes. Here, we report two cases of metastatic and recurrent renal MTSCC diagnosed after long-term follow-up. Case 1 was a 79-year-old man with a history of macroscopic hematuria in whom a right kidney mass was detected and diagnosed as RCC (cT3bN0M0). After a radical nephrectomy, microscopic findings showed that the tumor consisted of spindle cells arranged in tubular patterns embedded in sarcomatoid tissues ; we diagnosed it as unclassified RCC with sarcomatoid differentiations (pT3aN0M0). Thereafter, metastases were twice detected and resected completely. The patient had no evidence of disease at his most recent follow-up, 10 years 1 month after the initial surgery. Case 2 was in a 72-year-old man in whom a right kidney mass, swollen lymph nodes, and a lung node were incidentally detected. This tumor was diagnosed as RCC (cT4N2M1), and radical nephrectomy and lymph node dissections were carried out. From the microscopic findings, we diagnosed papillary RCC type-2 (pT3aN2M1). After the surgery, pleural and bone metastases was detected. Despite sequential treatments with IFN-α and sunitinib, the patient suffered indolent-growing metastases and died at 5 years 6 months after operation. As these patients had relatively good prognoses despite assumed aggressive RCC subtypes, we reviewed their pathological findings. In both cases, tumor samples showed tubules lined by short cuboidal cells that were set within myxoid stromata and spindle cells ; we finally diagnosed these cases as renal MTSCC.

A 61-year-old man with a left renal mass, which was detected by ultrasound during a routine health examination, was referred to our department. The patient had a surgical history of two pneumothorax operations, and the patient's brother also had a history of pneumothorax surgery. A case of Birt-Hogg-Dubé (BHD) syndrome was suspected based on patient history. The pathological diagnosis of the resected tumor, which used robot-assisted laparoscopic partial nephrectomy, was determined to be chromophobe renal cell carcinoma (grade 2, pT1a). BHD syndrome was confirmed by genetic testing, where a nonsense mutation of exon 9 in the FOLLICULIN (FLCN) gene was detected. The patient is currently alive 10 months after surgery.

We present a case of renal cell carcinoma growing into the renal pelvis with a fibrin cap in the ureter and bladder. A 66-year-old man presented to our hospital with anemia and gross hematuria. Computed tomography showed a large left renal tumor and space-occupying lesions in the left renal pelvis and ureter. Cystoscopy showed a 2 cm-restiform mass protruding from the left ureteral orifice. We performed open left nephroureterectomy, and there was a 3 cm white mass with a smooth surface in the bladder. Pathological examination of the resected mass revealed clear cell carcinoma with urinary collecting system invasion and fibrin cap in the ureter and bladder. As a result, it would have been difficult to make the diagnossis of renal cell carcinoma preoperatively if we had performed biopsy of the mass in the bladder or ureter. The patient was diagnosed as having lung metastases 5 months after surgery. Urinary collecting system invasion has been considered an independent prognostic factor in pT3 renal cell carcinoma.

We report a case of successful treatment of recurrence of peritoneal dissemination with axitinib. A 55-year-old man presented at our hospital with the chief complaint of remarkable abdominal fullness 18 months after right radical nephrectomy, which had been performed at another hospital for the treatment of renal cell carcinoma. The pathological diagnosis was papillary renal cell carcinoma type 1, pT3aN0M0. A large amount of ascites was detected by computed tomography, and recurrence of peritoneal dissemination was diagnosed (ascites cytology : class V). Sunitinib was started as a first-line treatment, but 1 month later, this was discontinued because of an adverse event (hyponatremia) and a lack of efficacy. As a second line therapy, axitinib 10 mg/day p. o. was administered. The ascites markedly decreased, and the disease status has remained stable after 18 months of treatment. To our knowledge, this is the first study to demonstrate the efficacy of axitinib in treating peritoneal dissemination.

An 83-year-old man with an indwelling lumbar-peritoneal (L-P) shunt (for idiopathic normal-pressure hydrocephalus) underwent retroperitoneal laparoscopic radical right nephrectomy for renal cell carcinoma (pT1aN0M0). Peritoneal perforation occurred intraoperatively, and he developed postoperative disturbance of consciousness. Computed tomography showed mild ventricular enlargement, which was attributed to L-P shunt failure secondary to increased pneumoperitoneum pressure. His level of consciousness was improved when we raised his head. Few reports have discussed complications observed during retroperitoneal laparoscopic surgery in patients with an indwelling L-P shunt. This case report discusses this topic along with a discussion of previously reported findings.

Interstitial lung disease (ILD) is a common side effect of the mechanistic target of rapamycin inhibitor everolimus. Most cases of everolimus-induced ILD are mild and reversible. As per guidelines, even if Common Terminology Criteria for Adverse Events grade 1 or 2 everolimus-induced ILD occurs, either continuation of everolimus without dose reduction or readministration at a low dose is possible. However, the pathophysiology of everolimus-induced ILD is unknown. We present a case of everolimus-induced ILD with spontaneous remission during treatment in a patient with metastatic renal cell carcinoma. At autopsy, there was no evidence of remodeling or chronic inflammation in the lungs. Cryptogenic interstitual pneumonia and broncholitis obliterans with organizing pneumonia can be suspected as a pattern of mild everolimus-induced ILD. This case report provides evidence that everolimus-induced ILD is reversible fromthe pathological perspective.

A 75-year-old man with a history of chronic kidney disease (CKD) visited our emergency room after the sudden onset of severe right lower abdominal pain and nausea. Computed tomography (CT) showed right perirenal hematoma and renal tumor, which was diagnosed as a spontaneous rupture of the right renal tumor. It was difficult to correctly diagnose the tumor as benign or malignant with magnetic resonance imaging (MRI). Because of CKD, a shunt was implanted, and dynamic enhanced CT was performed. Dynamic enhanced CT showed a slightly enhanced area of the tumor, and it was diagnosed as renal cell carcinoma (RCC). Radical nephrectomy was performed, and he has not experienced recurrence within 7 months after the surgery. Pathological diagnosis was papillary renal carcinoma. Spontaneous renal hemorrhage is relatively uncommon, but the most common cause of spontaneous renal hemorrhage is renal cell carcinoma (26.1%). CT is useful for diagnosis, but it is not highly accurate. Therefore, it is necessary to discuss surgical indication carefully.

We performed a study on renal cell carcinoma (RCC) detected by abdominal ultrasonography during routine health check-up at Sapporo Teishin Hospital. The study included a total of 13, 127 ultrasonographic examinations performed on 4, 339 patients who visited our hospital for routine health check-ups during a 21- year period from April 1995 to March 2016. RCC was suspected from ultrasonographic findings and later histopathologically diagnosed in 11 patients in this group (detection rate 0.25%). Patients were male, aged 37 to 64 (median, 52.1 years). None of the patients had subjective symptoms, and all were negative for microscopic hematuria. Greatest dimensions of tumors were 18 to 40 mm (mean, 28 mm) ; anechoic rims, which are a characteristic ultrasonographic finding in RCC, were identified in 8 patients (72. 7%), intratumoral cysts were identified in 8 patients (72.7%), and protrusions from the surface of the kidney were identified in 9 patients (81. 8%). Regarding vascular distribution of renal tumors during Doppler ultrasonography, peripheral patterns or mixed penetrating and peripheral patterns were identified in 100% of cases (8/8). All 11 patients were diagnosed histopathologically with clear cell renal cell carcinoma, and the histological grade was G1 in 6 patients, G1＞G2, in 1 patient G2＞G1, in 1 patient and G2 in 3 patients. All 11 tumors were classified as pT1a pathological stage according to the TNM classification, and no regional lymph node metastases or distant metastases were identified. We consider that ultrasonography plays an integral role in the early detection of RCC during check-ups and examinations.

We retrospectively investigated the surgical outcomes of renal cell carcinoma (RCC), perioperative complications, and residual renal function in patients receiving laparoscopic non-ischemic partial nephrectomy using a microwave tissue coagulator (MTC). Between January 2002 and December 2015, laparoscopic non-ischemic partial nephrectomy using MTC was performed in 49 patients. The histological diagnosis was RCC in 38 patients, angiomyolipoma in 4, oncocytoma in 2, and others in 5. A histologicallyproven positive surgical margin was observed in 1 (2.0%). Postoperative urine leakage occurred in 1, and it was treated conservatively. The mean follow-up period was 32.0 months. Although there was no patient who died of RCC, local recurrence occurred in 2 patients (4.1%) during the follow-up period. One of these 2 patients had a positive surgical margin. Deterioration of the residual renal function was not observed. Laparoscopic non-ischemic partial nephrectomy using MTC was safe and useful in terms of cancer control and preservation of renal function.

A 51-year-oldwoman with a right renal mass was referredto our hospital. Computedtomographic (CT) scan demonstrated a 30 mm-diameter renal mass with delayed enhancement. She underwent a robotassistedlaparoscopic right partial nephrectomy. The pathological examination showedthat tumor cells with eosinophilic, clear cytoplasm formedtubules of various sizes containing colloid-like material, which resembled the findings of thyroidfollicular carcinoma. The tumor was immunoreactive for vimentin andcytokeratin (CK) 7, whereas it lackedreactivity for thyroidtranscription factor-1 (TTF-1) or thyroglobulin. No tumors were detectedin the thyroidglandor other organs of the patient. Subsequently, the diagnosis of thyroidlike follicular carcinoma of the kidney (TLFCK) was determined. At 4 months postoperatively, the patient is alive with no evidence of disease recurrence. TLFCK is an extremely rare subtype of renal cancer, and only 26 cases have been reportedpreviously. We provide a brief literature review on this cancer.

We report a case of hydrocephalus due to brain metastasis from renal cell carcinoma treated with axitinib. A 65-year-old man had undergone right radical nephrectomy for renal cell carcinoma in 2010. The pathological diagnosis indicated clear cell carcinoma G3, pT1a. After adjuvant treatment with interferon-α, computed tomography, in 2011, revealed multiple lung metastases. He was administered sorafenib. Because of progressive lung metastases, sunitinib was administered. The lung metastases were progressive and bone scan revealed multiple bone metastases. The patient was administered axitinib 10 mg/day in February 2014. Brain metastases were found in both the lateral ventricles in the same month and were controlled using axitinib. The patient, however, experienced adverse events such as diarrhea and hand foot syndrome, and the axitinib dosage was titrated. Cognitive function declined rapidly in August 2015. Brain magnetic resonance imaging revealed hydrocephalus due to brain metastasis from renal cell carcinoma. Axitinib was administered again. Cognitive function improved within approximately 10 days. Furthermore, hydrocephalus improved, and the patient was discharged on the 21st day.

A 76-year-old man came to the department of gastrointestinal medicine with lower left abdominal discomfort and constipation. A crossed fused ectopic kidney with a renal tumor in the left upper pole of the kidney was detected by computed tomography. We performed left partial nephrectomy safely in spite of the complicated shape and complexity of the blood vessels. The pathological diagnosis was clear cell renal cell carcinoma, pT3a, with a negative surgical margin. After surgery, renal function was well preserved.

A 36-year-old woman had undergone left radical nephrectomy followed by interferon-α and sunitinib for the treatment of renal cell carcinoma with para-aortic lymph node and lung involvements (papillary renal cell carcinoma, G3, cT3aN1M1) in the previous hospital. She was referred to our hospital for further treatment and received serial molecular targeted agents (everolimus, sorafenib, sunitinib) and radiation therapy for right ischial and femoral bone metastases. Then she was found to have multiple metastatic lesions in the lungs and carcinomatous pleural effusion associated with dyspnea. After failure of pleurosclerosis with OK-432, the pleural effusion markedly reduced by axitinib administration, but the pleural effusion relapsed a few days after axitinib was discontinued. For this reason, axitinib was maintained in spite of appearance of new metastatic lesions in the brain. The pleural effusion was well-controlled for 16 months but she died of progressive disease, including metastatic lesions in the brain and in the lungs.

We report a case of recurrent renal cancer in the autografted kidney, treated with percutaneous cryoablation. A 59-year-old man who had bilateral renal tumors underwent radical left nephrectomy, ex vivo right partial nephrectomy and auto-transplantation at the right ileal fossa in our hospital 11 years ago. Histopathological examination showed clear cell renal cell carcinoma in bilateral kidneys (pT1bN0M0). He had been followed at another hospital without tumor recurrence for 11 years. In 2014, an enhanced CT scan revealed a renal tumor with a diameter of two centimeters in the autografted kidney, which was thought to be a recurrence of the initial renal cancer. He was referred to our hospital for further evaluation and treatment. He underwent percutaneous renal tumor biopsy, which confirmed renal cancer recurrence, followed by percutaneous cryoablation. Three months after cryoablation, an enhanced CT showed that the enhancement lesion in the autografted kidney had disappeared, and these findings were confirmed pathologically by absence of malignancy by a subsequent needle biopsy. The level of serum creatinine (sCr) was 1.16 md/dl immediately before cryoablation and 1.46 mg/dl at three months after cryoablation. Nine months after cryoablation, the patient had no reccurence and renal function was stable (sCr 1.43 mg/dl).

A 67-year-old man presented at our hospital with severe edema on the left side of his neck, chest and brachial regions. He had a history of right radical nephrectomy due to renal cell carcinoma (RCC, clear cell subtype, stage II) 15 years earlier. Thereafter, metastases to the pancreatic tail and right lung, and left lung metastasis were removed at 8 years and 11 years, respectively, after the nephrectomy. Four years earlier, he had also undergone total gastrectomy for gastric carcinoma (poorly differentiated adenocarcinoma, stage IV) and subsequent maintenance chemotherapy for gastric carcinoma. Follow-up computed tomography (CT) disclosed bilateral lung metastases and a pancreatic head metastasis. Cytology of pleural effusion on admission suggested pleuritis carcinomatosa from RCC. Clinical diagnosis was bilateral lung and pancreatic head metastases, pleuritis carcinomatosa and left subclavian vein thrombosis due to RCC metastasis. Maintenance chemotherapy for gastric carcinoma was replaced by Sunitinib 50 mg for RCC but he died of progressive disease 20 days later. Immunohistochemical study of the tissue from autopsy revealed lung metastasis and pancreatic head metastasis from both RCC and gastric carcinoma as well as multiple visceral metastases, pleuritis carcinomatosa and left subclavian vein thrombosis due to gastric carcinoma. Cause of death was acute respiratory failure due to pulmonary tumor embolism and pulmonary edema. Immunohistochemical study from autopsy was able to reveal the exact diagnosis, and immunohistochemical studies may be helpful in diagnosing the exact origin of metastasis and selecting appropriate treatmentsin patientswith multiple cancers.

A 73-year-old male patient underwent a right nephrectomy for renal cell carcinoma in 2008, and interferon-alpha was initiated as adjuvant treatment. Computed tomography (CT) scans showed lymphadenopathy above the left diaphragm, and treatment with interferon-2 was subsequently initiated in 2009. Nasal bleeding manifested in February 2010, and CT scans showed a soft-tissue density mass mainly located in the ethmoid sinus. A biopsy of the lesion was performed, and metastatic renal cell carcinoma was diagnosed. Treatment with sorafenib was consequently initiated and the paranasal metastasis showed a temporary partial response (PR). However, the metastatic lesion increased in size and caused repeated nasal bleeding that required blood transfusion. Although treatment with everolims was initiated, adverse events, such as rush, hypertensionnemia, and anemia due to nasal bleeding, developed. Treatment with axitinib was subsequently initiated. However, because adverse events, such as severe diarrhea, renal dysfunction and proteinuria manifested, the dose of axitinib was gradually decreased, and a periodic drug withdrawal schedule (11 days on, 3 days off) was finally initiated, which controlled these adverse events. The metastatic lesions showed a PR for 31months following axitinib administration.

A 71-year-old woman underwent left radical nephrectomy for renal cell carcinoma (clear cell carcinoma, pT1bN0M0) ten years previously. She noticed a tumor on the tip of her tongue and was admitted for dental and oral surgery. The tumor was about 10 mm in size, and tumor resection was done. It was pathologically diagnosed as clear cell carcinoma, which was metastasis of renal cell carcinoma. Computer tomography scan during the same period revealed left hilar lymph node and bilateral lung metastases. We chose to use sunitinib as the treatment for the metastases. Computer tomography revealed a complete response (CR) after sunitinib treatment was given for 10 months, and we are still continuing the treatment to maintain the CR status.

Surgical management with radical nephrectomy and thrombectomy has often been performed in renal cell carcinoma (RCC) with tumor thrombus infiltrating the inferior vena cava (IVC). We retrospectively reviewed the outcomes of IVC resection without venous reconstruction in patients with RCC and IVC thrombus at our institution. Eight patients with right RCC underwent radical nephrectomy and IVC resection superior to the level of the renal vein without venous reconstruction from August 2005 to February 2015. Thoracotomy, liver mobilization, and extracorporeal circulation were performed based on the IVC thrombus level. We assessed surgical outcomes, perioperative complications, and survival. At presentation, four patients had level IIIa IVC thrombus, three had level IIIb IVC thrombus, and one had level IV IVC thrombus. Perioperative imaging showed that three of the four patients who underwent neoadjuvant molecular targeting therapy achieved down-staging of the tumor thrombus level. The median operative time was 406 min, and the median estimated blood loss was 3, 135 ml. With regard to IVC resectionassociated perioperative complications, one patient needed extracorporeal circulation with IVC ligation and Pringle maneuver owing to low blood pressure. Another patient underwent temporary hemodialysis for 8 days after surgery. There were no perioperative deaths, and none of the patients required permanent hemodialysis. Three patients survived the mean observation period of 25 months, including one patient with no recurrence. Three patients achieved long-term survival of more than 2 years. IVC resection without venous reconstruction may be a feasible option for patients with RCC and IVC tumor thrombus. Further study is needed to determine the most appropriate candidates for this procedure.

A 63-year-old male with a past history of left nephrectomy due to clear cell renal cell carcinoma at the age of 57 was admitted for further evaluation. Enhanced abdominal computed tomography revealed that there were several hypervascular tumors in the pancreas and a single hypervascular tumor in the gallbladder. Laparoscopic cholecystectomy was performed to obtainpathological diagnosis. Microscopically, the tumor in the gallbladder was filled with clear cells and was diagnosed as metastatic gallbladder cancer from the previous clear cell renal cell carcinoma. Metastatic renal cell carcinoma to the gallbladder is extremely rare, with reported frequencies of less than0. 6% in687 autopsies. We hereinreport a case inwhich cholecystectomy enabled a successful diagnosis and review the reported 22 cases in Japanese patients.

The objective of this study was to determine whether alternative sunitinib schedules (AS) could prolong survival of patients with advanced renal cell carcinoma (RCC) compared to the traditional 4-weeks-on/2- weeks-off schedule (TS). Between August 2008 and December 2014, 58 patients with advanced RCC were treated with sunitinib. We retrospectively reviewed the records of the patients who received first-line sunitinib. The progression-free survival, overall survival, relative dose intensity and toxicity in the AS and TS groups were compared. A total of 38 patients were included in the analysis. AS was used for 22 patients who started to receive sunitinib beginning in December 2012. For these patients, sunitinib was administered with a 2-weeks-on/1-week-off, 2-weeks-on/2-weeks-off or 2-weeks-on/3-weeks-off schedule according to the adverse events and clinical characteristics of each patient. The median progression-free survival was 5 months (95% CI : 3-7) for TS compared to 12 months (95% CI : 7-17) for AS (p＝0.0020). The median overall survival was 17 months (95% CI : 10-20) for TS compared to 57 months (95% CI : 25-57) for AS (p＝0.0006). There was no significant difference between the TS and AS groups (64% versus 71%). The incidence of Grade ≥3 thrombocytopenia in the AS group was smaller than that in the TS group (44% versus 27%). Treatment with sunitinib using AS may provide a better outcome than that with TS. Prospective, randomized trials should be conducted to confirm this speculation.

Oncocytic papillary renal cell carcinoma isa variant of papillary renal cell carcinoma (PRCC). We herein report two cases treated with retroperitoneoscopic partial nephrectomy. Histologically, tumor cells of both cases exhibit round and regular nuclei with CK7 positive areas in the cytoplasm typical of TYPE1 PRCC and eosinophilic granular cytoplasm with E-cadherin positive areas in the cytoplasmic membrane, which indicates TYPE2 PRCC. Out of 46 cases reported in the literature, only one died of disease, which revealsitslow malignant potential.

Metastatic renal cell carcinoma (mRCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKIs), the novel targeted agents have been used for the treatment of mRCC and have shown efficacy. Interferon (IFN)-α is also one of the most frequently used agents in immunotherapy. However, drug resistance needs to be overcome to achieve a sufficiently positive effect. Interleukin-6 (IL-6), which induce suppressor of cytokine signaling-3 (SOCS3) expression, is one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). To analyze the influence of IL-6 in drug resistance of RCC, anti-IL-6 receptor antibody was used in combination with IFN or TKIs. The SOCS3 mRNA expression level was significantly increased by IFN-α stimulation in 786-O RCC cells which were resistant to IFN, but not in ACHN cells that were sensitive to IFN. The overexpression of SOCS3 by gene transfection in ACHN significantly inhibited the growth-inhibitory effect of IFN-α. An in vivo study demonstrated that co-administration of SOCS3-targeted siRNA promoted INF-α-induced cell death and growth suppression in 786-O cell xenograft. SOCS3 could be a key component in the resistance to interferon treatment of renal cell carcinoma. Because SOCS3 is rapidly up-regulated by IL-6 and a negative regulator of cytokine signaling, IL-6 expression on RCC cells was also analyzed and the 786-O cells showed the high level of IL-6 mRNA expression under the condition of interferon stimulation. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells by interferon stimulation accompanied with phosphorylation of STAT1 and inhibited SOCS3 expression. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumor growth in a xenograft model. We also hypothesized that TKI resistance and IL-6 secretion are causally connected. And we found that 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. A combination therapy with tocilizumab and TKI suppresses 786-O tumor growth and inhibits angiogenesis in vivo more efficient than TKI alone. Our findings suggest that IL-6 could induce drug resistance on RCC, and combination therapy of IL-6R inhibitors and IFN/TKIs may represent a novel therapeutic approach for RCC treatment.

A 71-year-old man with a right renal tumor underwent nephrectomy. The procedure was converted from laparoscopy to open surgery due to profound bleeding from the renal vein. Pathological diagnosis was clear cell carcinoma G2pT3b v1 ly1 INFα. Three years after surgery, a 5 cm tumor in the abdominal wall was found on computed tomography (CT). A mild uptake was shown on positron emission tomography/CT and as the tumor was located near the surgical wound, recurrence of the renal cell carcinoma was suspected. However, desmoid tumor was suggested by the pathological examination of the tumor biopsy. En-bloc resection of the mass was carried out and the pathological examination showed an array of proliferating and tangling atypical spindle-shaped tumor cells. Immunohistochemical staining of the tumor cells was positive for vimentin, but negative for CD34, c-kit, and s100. Pathological diagnosis was desmoid tumor. There has been no recurrence so far. Desmoid tumor, despite its extremely low incidence, should be considered in a postoperative neoplasm.

A 68-year-old man underwent radical nephrectomy for renal cell carcinoma of the right kidney 12 years ago. He was diagnosed as having a recurrent tumor of the contralateral kidney and a single metastatic pulmonary lesion by diagnostic imaging on the annual checkup. He visited us in order to receive nephron sparing surgery. Since the preoperative abdominal computed tomography showed tumor thrombus invading intothe intrarenal vein, ex vivo partial nephrectomy and auto-transplantation was performed. Although he received transit hemodialysis during the postoperative 10 days, his renal function, thereafter became stable without hemodialysis. Eighty-seven days later he underwent right lower lobectomy. At postoperative 6 months he has no local recurrence or distant metastasis and maintains well-preserved renal function.

An 81-year-old man had undergone radical nephrectomy for a renal cell carcinoma (RCC) in October 1998. Twelve years postoperatively, he developed diplopia and photophobia. Orbital metastasis of RCC was suspected and sunitinib treatment was given for 16 months. Computer tomography revealed a partial response of metastatic tumor for the first 2 months and stable disease for the next 12 months. However, it enlarged in the last 2 months. Total resection of right metastatic orbital tumor with deep lateral orbital decompression was done in January 2012. He has been well and without any local recurrence, distant metastasis or vision loss for 24 months.

Clinicopathological features and prognosis of metastatic renal cell carcinoma (mRCC) vary by histopathological type. In this study, we analyzed these relationships with regard to non-clear cell RCC (nccRCC). We also analyzed the therapeutic trends for patients with mRCC. We initially identified 367 patients who were diagnosed with RCC and treated in our hospital between 2001 and 2013 ; 55 patients of whom were diagnosed with nccRCC. We reviewed their backgrounds, histopathological types and outcomes. Median age at diagnosis for patients with nccRCC was significantly younger (58.5 years) than for those with clear-cell RCC (66.3 years ; P=0.008) ; however, these histological types did not significantly differ by sex, affected side or rate of mRCC. Of the 55 nccRCC cases, 19 were mRCC, including 5 of the 8 cases of papillary type-2 RCC, and all patients who had either collecting duct carcinoma, sarcomatoid RCC or Xp11 translocation RCC. The most common metastatic site was lymph nodes. Although patients with papillary type-1 and Xp11 translocation RCC had relatively good prognoses, those with papillary type-2, collecting duct carcinoma and sarcomatoid RCC had poor prognoses. Among the 9 patients with nccRCC who received molecular targeted therapy, median survival was 13.3 months. Although existing therapeutic agents may be effective for some patients with nccRCC, identification of new target molecules and innovative drug development are needed in the future.