Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy.

BACKGROUND: Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy. METHODS: We monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy. RESULTS: A preoperative increase of the serum level of sIL-2R was correlated with a higher preoperative serum level of programmed cell death 1 (PD-1)-ligand 1 (PD-L1), increased expression of phosphorylated Akt by the primary tumor, and a worse response to IFN-alpha/sequential VEGF-targeting therapy, as well as being an independent prognostic factor for a shorter overall survival time by multivariate analysis. Over time, the serum sIL-2R level largely reflected the tumor response to therapy. CONCLUSIONS: Monitoring the serum level of sIL-2R may help to predict the biological behavior of ccRCC, its response to IFN-alpha/sequential VEGF-targeting therapy, and the prognosis.

The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells.

BACKGROUND: Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. METHODS: We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. RESULTS: Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. CONCLUSIONS: These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.

Prostate volume and biopsy tumor length are significant predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy.

BACKGROUND: Gleason pattern 3 less often has molecular abnormalities and often behaves indolent. It is controversial whether low grade small foci of prostate cancer (PCa) on biopsy could avoid immediate treatment or not, because substantial cases harbor unfavorable pathologic results on prostatectomy specimens. This study was designed to identify clinical predictors for classical and redefined insignificant cancer on prostatectomy specimens in Japanese men with favorable pathologic features on biopsy. METHODS: Retrospective review of 1040 PCa Japanese patients underwent radical prostatectomy between 2006 and 2013. Of those, 170 patients (16.3%) met the inclusion criteria of clinical stage ≤ cT2a, Gleason score (GS) ≤ 6, up to two positive biopsies, and no more than 50% of cancer involvement in any core. The associations between preoperative data and unfavorable pathologic results of prostatectomy specimens, and oncological outcome were analyzed. The definition of insignificant cancer consisted of pathologic stage ≤ pT2, GS ≤ 6, and an index tumor volume < 0.5 mL (classical) or 1.3 mL (redefined). RESULTS: Pathologic stage ≥ pT3, upgraded GS, index tumor volume ≥ 0.5 mL, and ≥ 1.3 mL were detected in 25 (14.7%), 77 (45.3%), 83 (48.8%), and 53 patients (31.2%), respectively. Less than half of cases had classical (41.2%) and redefined (47.6%) insignificant cancer. The 5-year recurrence-free survival was 86.8%, and the insignificant cancers essentially did not relapse regardless of the surgical margin status. MRI-estimated prostate volume, tumor length on biopsy, prostate-specific antigen density (PSAD), and findings of magnetic resonance imaging were associated with the presence of classical and redefined insignificant cancer. Large prostate volume and short tumor length on biopsy remained as independent predictors in multivariate analysis. CONCLUSIONS: Favorable features of biopsy often are followed by adverse pathologic findings on prostatectomy specimens despite fulfilling the established criteria. The finding that prostate volume is important does not simply mirror many other studies showing PSAD is important, and the clinical criteria for risk assessment before definitive therapy or active surveillance should incorporate these significant factors other than clinical T-staging or PSAD to minimize under-estimation of cancer in Japanese patients with low-risk PCa.

Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma.

BACKGROUND: The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. METHODS: To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. RESULTS: Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. CONCLUSIONS: These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.

Renal metanephric adenoma mimicking papillary renal cell carcinoma on computed tomography: a case report.

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.

Effects of fasudil, a Rho-kinase inhibitor, on contraction of pig bladder tissues with or without urothelium.

OBJECTIVES: To investigate the effects of fasudil, a Rho-associated serine-threonine protein kinase inhibitor, on contraction of the pig urinary bladder tissues with or without urothelium. METHODS: Cumulative concentration-response curves (CRCs) to carbachol were obtained with and without 3-10 microM fasudil. Drug effects were evaluated in detrusor with and without urothelium. Inhibitory responses to fasudil were also examined in tissues precontracted with KCl and carbachol, and in response to electrical field stimulation, in pig bladder with and without urothelium. RESULTS: In detrusor without urothelium, maximum contraction (E(max)) decreased after administration of fasudil at 3 or 10 micromol/L (both P < 0.01), or 30 micromol/L (72.5 + or - 7.43%, 58.4 + or - 8.04% and 68.4 + or - 9.6%, respectively, of the first curve). In detrusor with urothelium, E(max) decreased significantly (all P < 0.05) after the addition of 3, 10 or 30 micromol/L of fasudil (84.9 + or - 6.7%, 67.9 + or - 5.2% and 35.2 + or - 4.1%, respectively). In tissues precontracted with 80 mmol/L KCl or 100 micromol/L carbachol, tension after administration of fasudil (1 nmol/L to 100 micromol/L) decreased (by approximately 40%), only after administration of fasudil at high concentration (>1 micromol/L), in detrusor both with and without urothelium. In tissues with and without urothelium, responses to electrical field stimulation at 1-50 Hz decreased significantly in a concentration-dependent manner after addition of fasudil (3 to 30 micromol/L). CONCLUSIONS: Fasudil seems to provoke relaxation of the bladder detrusor via both urothelium-dependent and independent pathways.

[A new treatment: thermal therapy for chronic fatigue syndrome].

Thermal therapy using far-infrared ray dry sauna was performed for patients with chronic fatigue syndrome (CFS). Symptoms such as fatigue, pain, and low-grade fever were dramatically improved on two patients. And prednisolone administration was discontinued and became socially rehabilitated 6 months after discharge. On other 11 patients with CFS, physical symptoms such as fatigue and pain improved, too. Furthermore, we reported that repeated thermal therapy had relaxation effect and diminishes appetite loss and subjective complaints in mildly depressed patients. These results suggest that repeated thermal therapy may be a promising method for the treatment of CFS.

Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study.

Objective Chronic fatigue syndrome (CFS) is a complex disorder, with no consensus on therapeutic options. However, Waon therapy has been reported to be an effective treatment. The purpose of this study was to evaluate changes in the cerebral blood flow (CBF) before and after Waon therapy in CFS patients and to investigate the correlation between such changes and the therapeutic efficacy of Waon therapy. Methods Eleven patients (2 men and 9 women, mean age 27 years old) diagnosed with CFS participated in the study. The disease duration was 8-129 months, and the performance status was 5-8 (on a scale of 0-9). All patients underwent CBF scintigraphy using brain single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD) before and after Waon therapy. CBF changes after Waon therapy were evaluated using a statistical analysis of imaging data, which was performed with a statistical parametric mapping software program (SPM5). Results Waon therapy reduced symptoms in all 11 patients. We also observed an increase in the CBF within the prefrontal region, orbitofrontal region, and right temporal lobe. These results indicated that an improvement in clinical symptoms was linked to an increase in the CBF. Conclusion The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients and that Waon therapy improved the cerebral function and symptoms in CFS patients by increasing the regional CBF. To our knowledge, this is the first report to clarify the CBF changes in CFS patients before and after Waon therapy.

Abnormal 18F-FDG uptakes in the prostate due to two different conditions of urine reflux: a mimicker of prostate cancer.

A 69-year-old man with lung cancer underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for staging. FDG PET/CT showed high uptakes in the prostate gland with calcification, and magnetic resonance imaging was recommended to check the prostatic malignancy. T2-weighted images revealed midline cystic lesion at the base to midgland level and cystic lesion in right apical peripheral zone. We suspected urine reflux conditions. Voiding cystourethrography demonstrated those cystic lesions were communicating with the urethra. Therefore these lesions were diagnosed as the prostatic utricle cyst and the dilated prostatic duct in peripheral zone. We conclude that the urine reflux condition should be recognized as a prostate benign lesion with FDG accumulation.

Higher preoperative serum levels of PD-L1 and B7-H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF-targeted therapy and unfavorable prognosis of renal cell carcinoma.

Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer. Although antivascular endothelial growth factor (VEGF) therapies achieve impressive responses in some patients, many tumors eventually develop resistance to such therapy. The B7 family molecules such as CTLA-4, PD-1, and PD-L1 are pivotal players in immune checkpoints that positively or negatively regulate various immune responses. Recently, immunotherapy based on blocking immune checkpoints with anti-CTLA4, anti-PD-1, or anti-PD-L1 antibodies has been proposed as a potential new approach to the treatment of metastatic RCC. Higher expression of PD-L1 and B7-H4 in the tumors is associated with a poor prognosis in RCCs, however, the clinical impact of serum levels of B7 family molecules has not been elucidated in patients with metastatic RCCs receiving VEGF-targeted agents. We assessed the preoperative serum levels of B7 family molecules, including CD80, CD86, PD-1, PD-L1, B7-H3, B7-H4, and CTLA-4, and CD28 in RCC patients, and determined their relations with various clinicopathological characteristics. Elevated preoperative serum levels of PD-L1 and B7-H4 were correlated with less differentiated tumors, higher invasive and metastatic potential, a worse response to anti-VEGF therapy, and shorter overall survival. These findings suggested that investigating preoperative serum levels of PD-L1 and B7-H4 might not only be useful to assess the biological aggressiveness of RCCs, but also to predict the efficacy of anti-VEGF therapy and the eventual prognosis, indicating the future design of clinical trials of therapies targeting immune checkpoint in advanced RCCs.

Repeated thermal therapy diminishes appetite loss and subjective complaints in mildly depressed patients.

OBJECTIVE: We observed that repeated thermal therapy improved appetite loss and general well-being in patients with chronic heart failure. The purpose of this study is to clarify the effects of repeated thermal therapy in mildly depressed patients with appetite loss and subjective complaints. METHODS: Twenty-eight mildly depressed inpatients with general fatigue, appetite loss, and somatic and mental complaints were randomly assigned to thermal therapy group (n = 14) or nonthermal therapy group (n = 14). Patients in the thermal therapy group were treated with 60 degrees C far-infrared ray dry sauna for 15 minutes and were then kept at bed rest with a blanket for 30 minutes once a day, 5 days a week for a total of 20 sessions in 4 weeks. RESULTS: Four weeks after admission, somatic complaints, hunger, and relaxation scores significantly improved (p < .001, p < .0001, p < .0001, respectively) and mental complaints slightly improved (p = .054) in the thermal therapy group compared with the nonthermal therapy group. Furthermore, the plasma ghrelin concentrations and daily caloric intake in the thermal therapy group significantly increased compared with the nonthermal therapy group (p < .05). CONCLUSIONS: These findings suggest that repeated thermal therapy may be useful for mildly depressed patients with appetite loss and subjective complaints.

Glucose tolerance predicts short-term refeeding outcome in females with anorexia nervosa.

OBJECTIVE: Little is known about biologic predictors of refeeding outcome in anorexia nervosa (AN). Because nutritional status mirrors glucose metabolism during an oral glucose tolerance test (OGTT) in AN, this study investigated whether pretreatment glucose response patterns during the OGTT might be associated with refeeding progress in patients with AN. METHODS: Sixty-four female patients with anorexia (33 restrictors and 31 binge/purgers) and 13 healthy control subjects underwent an OGTT before nutritional rehabilitation, including desensitization to fear of energy intake of 1000 to 1600 kcal/day. Patients were divided into flat-type responders, impaired glucose tolerance (IGT)-type responders, and normal-type glucose responders. Daily energy intake, weekly weight gain, and the duration of desensitization period were evaluated until the 12th week. RESULTS: The patients with anorexia consisted of 20 flat-type, 21 IGT-type, and 23 normal- type responders. Normal-type responders required a shorter time to complete the desensitization period than other responders (p = .003 for restrictors, p < .001 for binge/purgers). In terms of refeeding progress, significant group effects for daily energy intake and weekly weight gain were evident in restrictors (p = .006, p = .028, respectively) and binge/purgers (p < .001, p = .003, respectively); normal-type responders showed good refeeding progress compared with other responders in both AN subtypes. CONCLUSIONS: The present study found a close relationship between pretreatment glucose responses, therapeutic progress of desensitization to fear of energy intake, and refeeding progress in both AN subtypes. Our findings suggest that glucose tolerance may be a useful predictor of short-term refeeding outcome in this disorder.

The effects of repeated thermal therapy for two patients with chronic fatigue syndrome.

OBJECTIVE: This paper describes the successful treatment of two patients with chronic fatigue syndrome (CFS) using repeated thermal therapy. METHODS: Two patients with CFS underwent treatment with prednisolone (PSL), with no satisfactory effect. They were subjected to thermal therapy that consisted of a far-infrared ray dry sauna at 60 degrees C and postsauna warming. The therapy was performed once a day, for a total of 35 sessions. After discharge, these subjects continued the therapy once or twice a week on an outpatient basis for 1 year. RESULTS: Symptoms such as fatigue, pain, sleep disturbance, and low-grade fever were dramatically improved after 15 to 25 sessions of thermal therapy. Although PSL administration was discontinued, the subjects showed no relapse or exacerbation of symptoms during the first year after discharge. The patients became socially rehabilitated 6 months after discharge. CONCLUSIONS: These results suggest that repeated thermal therapy might be a promising method for the treatment of CFS.

Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain.

We investigated changes in regional cerebral blood flow (rCBF) before and after weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison with findings in normal subjects. We assessed resting rCBF using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 12 AN-R patients and 11 controls. Each patient was examined at two time points, at the beginning of treatment and after weight gain (average examination interval=88+/-26 days). Control subjects were examined only once. Before treatment, the AN-R group had lower rCBF in the bilateral anterior lobes, including the anterior cingulate cortex (ACC), and in the right parietal lobe, the insula, and the occipital lobes. After weight gain, the patients showed significant increases in the right parietal lobe and decreases in the basal ganglia and cerebellum in accordance with significant improvement in body weight and eating attitudes. However, they showed persistent decreases in the ACC area even after weight gain compared with findings in the controls. A significant positive correlation was observed between body mass index and rCBF in the occipital lobes in the patients. These results suggest that weight gain is associated with a normalization of rCBF in a number of brain areas, but that the low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.

Effects of Waon therapy on chronic fatigue syndrome: a pilot study.

OBJECTIVE: Chronic fatigue syndrome (CFS) is a disabling condition of unknown etiology, and no definitive therapy has been identified to date. We developed Waon therapy, a form of thermal therapy using a far-infrared dry sauna, and in this study herein examined its feasibility and safety in patients with CFS. METHODS: Ten consecutive inpatients with CFS stayed in a 60°C sauna for 15 minutes and then rested on a bed under a blanket for an additional 30 minutes outside the sauna room. The treatments were performed once a day, five days a week for four weeks. Perceived fatigue, the primary outcome measure, was evaluated using a numerical rating scale before, during (two weeks after the commencement of therapy) and after therapy. The pain level, evaluated using a numerical rating scale, mood, assessed using the Profile of Mood States questionnaire, and performance status, assessed using a scale developed for CFS patients were also examined before and after therapy. RESULTS: Perceived fatigue significantly decreased after therapy, although no significant reductions were observed during therapy. In addition, a negative mood, including anxiety, depression and fatigue, and the performance status significantly improved after therapy. However, the levels of pain and vigor did not change significantly. No patients reported any adverse effects during the therapy. CONCLUSION: These findings suggest that Waon therapy may be a useful and safe treatment for CFS.

Uncoupling protein-2/uncoupling protein-3 gene polymorphism is not associated with anorexia nervosa.

Energy expenditure abnormalities have been observed in anorexia nervosa (AN). The uncoupling proteins (UCPs) have been implicated as having a role in energy metabolism and thermogenesis, and an association between a marker flanking the UCP-2/UCP-3 gene cluster and AN has been reported. Also known are insertion/deletion and -866G/A polymorphisms in the UCP-2 gene, and the -55C/T polymorphism in the UCP-3 gene. Differences in these alleles are reportedly related to changes in energy expenditure, body mass index, fat tissue accumulation and obesity. Therefore, this case-control association analysis was done to determine whether any of these UCP-2/3 gene polymorphisms are related to a predisposition to AN. In analysis of a cohort of 106 female Japanese AN sufferers and 126 normal female controls, we found no between-group differences in the polymorphism frequencies of these groups. The hypothesis that differences in the UCP-2/3 gene influence the susceptibility to AN was not supported.

Clinical implications of thermal therapy in lifestyle-related diseases.

Systemic thermal therapy, such as taking a warm-water bath and sauna, induces systemic vasodilation. It was found that repeated sauna therapy (60 degrees C for 15 min) improved hemodynamic parameters, clinical symptoms, cardiac function, and vascular endothelial function in patients with congestive heart failure. Vascular endothelial function is impaired in subjects with lifestyle-related diseases, such as hypertension, hyperlipidemia, diabetes mellitus, obesity, and smoking. Sauna therapy also improved endothelial dysfunction in these subjects, suggesting a preventive role for atherosclerosis. In animal experiments, sauna therapy increases mRNA and protein levels of endothelial nitric oxide synthase (eNOS) in aortas. In normal-weight patients with appetite loss, repeated sauna therapy increased plasma ghrelin concentrations and daily caloric intake and improved feeding behavior. In obese patients, the body weight and body fat significantly decreased after 2 weeks of sauna therapy without increase of plasma ghrelin concentrations. On the basis of these data, sauna therapy may be a promising therapy for patients with lifestyle-related diseases.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma arising from the male urethra. A case report and review of the literature.

Primary non-Hodgkin's lymphomas rarely arise from the lower urinary tract, the urethra being the most uncommon site of origin. Herein, we report the immunohistochemical findings of a case of primary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising from the male urethra. To clarify the clinicopathological findings of primary urethral lymphoma, we reviewed 14 previously reported cases. A 56-year-old man presented with gross hematuria. Cystourethroscopy demonstrated a nodular bulge of the urethral wall. Histologically, a transurethral biopsy specimen showed a dense lymphoplasmacytoid infiltrate in the urethral mucosa. The tumor cells were composed of centrocyte-like cells, plasma cells and plasmacytoid cells. A few plasma cells contained intracytoplasmic pseudoinclusions (Dutcher bodies). Immunohistochemical study revealed monotypic intracytoplasmic kappa-light chain in the plasma cells and plasmacytoid cells. The patient received a total of 50 Gy extrabeam irradiation. Follow-up 21 months later did not disclose any sign of local or other recurrences.

[A case report: testicular pure seminoma metastasized to costal bone after 2 years post-operatively].

A 32-year-old man underwent orchiectomy for his right testicular tumor (pure seminoma, pT1, stage A(I)). Pelvic and para-aortic lymph nodes were irradiated with 18 Gy as adjuvant therapy. Two years later, he developed low back pain. Computed tomography, magnetic resonance imaging and bone scans showed an enhanced mass at the 10th left costa. Aspiration cytology showed seminoma. After administration of chemotherapy with bleomycin, etoposide and cisplatinum, following high dose chemotherapy with peripheral blood stem cell transplantation, the costal lesion was diminished and symptoms relieved. Then radical costectomy was performed. A histopathological study showed non-viable cells of seminoma. Post-operative progress was uneventful. Testicular pure seminoma with bone metastasis is rare, and to our knowledge, only 9 cases have been reported.

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report.

BACKGROUND: Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. METHODS: We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. RESULTS: Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. CONCLUSION: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).