Hiroki Fukuhara

Sequential molecularly targeted drug therapy including axitinib for a patient with end-stage renal failure and metastatic renal cell carcinoma

A 62‐year‐old male patient with end‐stage renal disease and metastatic renal cell carcinoma (RCC) was referred to our hospital. Sequential targeted therapy consisting of sorafenib, sunitinib, and everolimus was administered, but the patients disease gradually progressed. Axitinib was subsequently administered at a decreased dose of 6 mg/day for 2 weeks, after which the dose was escalated to 10 mg/day. Axitinib therapy was maintained for a total of 6 months without severe adverse effects. Sequential molecularly targeted drug therapy including axitinib, with careful monitoring, is one possible treatment option for patients with metastatic RCC with renal impairment.

Prognostic utility of seasonal changes for diagnosis of ureteral stones

Table 1 shows the results of the multivariate analysis with seven and eight (seven independent variables + seasonal factor) independent variables. All factors were associated with the presence of ureteral stones in the univariate analysis. The baseline and extended models were created with multiple logistic regression using each intercept and coefficient (Table 1). The optimal cut-off value of the ROC curves indicating the diagnostic performance of the baseline and extended models was 0.703. The AUC was 0.9667 [95% confidence interval (CI), 0.9448–0.9878] for the baseline model and 0.9737 (95% CI, 0.9553–0.9921) for the extended model. The sensitivity, specificity, PPV and NPV of the baseline model were 0.913, 0.962, 0.985, and 0.805, respectively, and those of the extended model were 0.983, 0.955, 0.983, and 0.955, respectively. Although both models were excellent for prediction of ureteral stones, the AUC for the extended model was significantly higher than that for the baseline model (p = 0.0057). Notably, the sensitivity improved from 0.913 to 0.983 and the NPV improved from 0.805 to 0.955 in the extended model after addition of the seasonal factor to the baseline model. The diagnostic performance between the baseline and extended models was compared with an arbitrary cut-off value of 0.703 using the continuous NRI and IDI methods. By incorporating the seasonal factor into the baseline model, 25 of 31 patients diagnosed with ureteral stones and classified as <0.703 were reclassified to a better category (≥0.703), and only one of 128 patients diagnosed with alternative disease and classified as <0.703 was reclassified incorrectly (≥0.703). This result suggests that the seasonal factor more effectively reclassified the patients with the ureteral stones without moving the patients with alternative diseases. The continuous NRI was 0.209 (95% CI, 0.074–0.343; p = 0.0023), and the IDI was 0.053 (95% CI, 0.035–0.072; p < 0.001), demonstrating that the extended Dear Editor,

Long-term administration of single-agent carboplatin (AUC 4) for advanced testicular seminoma safely achieved complete response in an 80-year-old man with chronic heart failure: A case report

Carboplatin is often used instead of cisplatin as an alternative treatment for advanced testicular cancer. However, the safety, optimal dose, and optimal duration of this agent are unclear in patients with cardiac complications. We report the safety and effectiveness of long-term single-agent carboplatin for the treatment of testicular cancer in a patient with chronic heart failure (CHF). An 80-year-old man was referred to our institution for evaluation of painless swelling of the left scrotum. Computed tomography revealed lung metastases. Left radical inguinal orchiectomy was performed, and pathologic examination revealed a pure seminoma. Because he had CHF, there was high possibility of onset of acute heart failure secondary to fluid administration. Thus, single-agent carboplatin (AUC 4) was selected for therapy. A complete response was achieved after 8 of 13 cycles, and no serious adverse events occurred, including cardiac problems. Neither recurrence nor metastasis was detected during the 6-month follow-up. Low-dose, long-term carboplatin is likely effective for patients who are unfit for cisplatin administration because of comorbidities, especially CHF.

MP88-18 ERK5 IS A PROMISING THERAPEUTIC TARGET FOR CLEAR CELL RENAL CELL CARCINOMA

RASAL2 methylation or c-FOS mRNA or VEGFA mRNA in RCC tissues. Overexpression of RASAL2 in 786-O cells could inhibit the recruitment and tube formation of HUVECs, while RASAL2 knockdown (KD) in ACHN cells enhanced the recruitment and tube formation of HUVECs in vitro. Also, overexpression of RASAL2 could inhibit tumorigenecity of xenografts. Mechanistically, RASAL2 KD could enhance the phosphorylation of GSK3 and upregulate the expression of c-FOS and VEGFA. Furthermore, RASAL2 was inversely correlated with VEGFA and CD31 in tissues from human RCC specimens and xenografts. CONCLUSIONS: RASAL2 was downregulated in RCC tissues, which could lead to tumor angiogenesis via p-GSK3/c-FOS/VEGFA signaling pathway. Therefore, RASAL2 could be a potential target to prevent patients with RCC from resistance to anti-vascular therapy.

Levels of 4EBP1/eIF4E Activation in Renal Cell Carcinoma Could Differentially Predict Its Early and Late Recurrence

Micro‐Abstract A subset of patients who undergo curative surgery for localized clear cell renal cell carcinoma (ccRCC) will experience early or late recurrence. Tumor viability depends on protein synthesis via the eukaryotic initiation factor (eIF)4E‐binding protein 1 (4EBP1/eIF4E) axis. Activation levels of the axis in ccRCC tissues could differentially affect tumor recurrence and the timing of recurrence after curative nephrectomy. Background The objective was to explore the predictive markers of late recurrence (LR) > 5 years after curative nephrectomy for renal cell carcinoma (RCC). Patients and Methods We retrospectively examined the data from 303 patients with localized clear cell RCC treated surgically at our institution from 1993 to 2011. Activation of the eukaryotic initiation factor (eIF)4E‐binding protein 1 (4EBP1)/eIF4E axis at the mammalian target of rapamycin complex 1 (mTORC1) was evaluated in the tumor specimens. Weak, intermediate, and strong immunohistochemistry staining grades were defined for 4EBP1, phosphorylated 4EBP1, and eIF4E. The effects of clinicopathologic factors and activation level grades on tumor recurrence were analyzed using multivariate Cox regression models. To validate the present findings, we investigated clinical data from The Cancer Genome Atlas and protein/phosphoprotein data from corresponding patients from The Cancer Proteome Atlas. Results Of the 303 patients, 31 and 16 patients developed early recurrence (ER, ≤ 5 years) and LR, respectively. The activation levels were comparable among the subcategories of pathologic TN stage, Fuhrman grade, and microvascular and capsular invasion. Pathologic stage ≥ T1b, Fuhrman grade 3/4, and an intermediate or strong activation level correlated significantly with overall recurrence and ER. Strong activation of the axis and pathologic stage ≥ T1b were identified as independent predictors of LR. Only 2 patients with weak activation experienced recurrence (1 each with ER and LR). Similar results were confirmed by the analyses of The Cancer Genome Atlas and The Cancer Proteome Atlas data. Conclusion The activation level of the axis in RCC tissues could independently predict for recurrence and differentially affect the timing of recurrence.

Successful Treatment with Paclitaxel, Carboplatin, and Gemcitabine as Second-line Chemotherapy for Recurrent Urothelial Carcinoma of the Bladder with Glandular Differentiation After Radical Cystectomy: A Case Report

Urothelial carcinoma of the bladder (UCB) with glandular differentiation is a histological variant (HV) that is more likely to have positive extravesical tumors or nodes than those in pure UCB. Cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is more effective for pure UCB; however, few reports are available on second-line chemotherapy for recurrence of UCB with HV. Here we report a 65-year-old Japanese male diagnosed with local recurrence UCB with HV after NAC + RC who safely achieved complete response with paclitaxel, carboplatin, and gemcitabine combination chemotherapy.

SAFETY AND EFFICACY OF CONTINUOUS ADMINISTRATION OF ANTITHROMBOTIC DRUGS DURING TRANSURETHRAL RESECTION OF BLADDER TUMORS

(Objectives) We evaluated the safety and efficacy of continuous administration of antithrombotic drugs during transurethral resection of bladder tumors (TURBT). (Methods) We performed a retrospective review of 351 TURBT procedures performed at our institute from April 2011 to October 2015. Among these, antithrombotic drugs were continued in 31 TURBT cases throughout their perioperative period (continuation group), antithrombotic drugs were discontinued in 26 TURBT cases (discontinuation group), and bridging anticoagulation therapy with heparin after interruption of antithrombotic drugs was performed in 4 TURBT cases (heparin bridging group). The safety and efficacy of continuous administration of antithrombotic drugs during TURBT was evaluated by comparing the rate of perioperative complications, median operative time, duration of hematuria, urethral catheter placement, duration of stay after surgery, and by comparing the duration of stay among the three groups. (Results) The median operative time was 40.0 min in the continuation group, 39.0 min in the discontinuation group, and 31.0 min in the heparin bridging group with no significant differences. There were no significant differences in the median duration of hematuria (1.00 days vs. 1.00 days vs. 1.00 days), urethral catheter placement (3.00 days vs. 2.50 days vs. 2.00 days), or stay after TURBT (4.00 days vs. 3.50 days vs. 3.00 days) among the continuation, discontinuation, and heparin bridging groups. The median duration of stay was 6.00 days in the continuation group, 7.00 days in the discontinuation group, and 16.0 days in the heparin bridging group with significant differences between the continuation group vs. the heparin bridging group and the discontinuation group vs. the heparin bridging group. The rate of complications was 6 (19.4%) in the continuation group and 3 (11.5%) in the discontinuation group with no significant differences. However, a serious complication, cerebral infarction leading to hemiplegia, occurred in the discontinuation group. (Conclusion) Continuous administration of antithrombotic drugs during TURBT is considered to be safe and useful because it may prevent serious thromboembolism without adversely affecting the perioperative course.

Rise in ambient temperature predisposes aging, male Japanese patients to renal colic episodes due to upper urolithiasis

Abstract Objective: Urolithiasis is a common urological problem, and its incidence has been increasing worldwide, including in Japan. Relationships between stone etiology and rise in ambient temperature have been reported, but it remains unclear how age and gender affect these relationships. Materials and methods: A retrospective examination was conducted of the medical archives of 1005 patients (aged ≥15 years) with acute renal colic diagnosed with urolithiasis upon image examination who consecutively visited emergency departments in three hospitals. The patients were categorized into six groups according to age: younger than 30, 30–39, 40–49, 50–59, 60–69, and 70 years and older. The net difference and fold increase in the number of patients in summer (July to September) versus in winter (December to February) were calculated. Results: Overall, the actual number of the patients varied according to the temperature rise throughout the year and among the age groups. Net increases in the number of patients were observed in all age groups for both genders, apart from 30–39-year-old women. The age group of 50–59 years considerably outnumbered all other groups. A significant statistical correlation was detected between the fold increase and male aging using Spearman’s rank correlation analysis (ρ = 0.94, p = 0.017), but not in females (ρ = –0.03, p = 1). Conclusions: These results support a positive association between ambient temperature rise and increase in the incidence of renal colic due to urolithiasis in Japan, and indicate that aging and gender affect the association differently.

Internal validation of a scoring system to evaluate the probability of ureteral stones: The CHOKAI score

Objective The CHOKAI and STONE scores are prediction models for ureteral stones. The aims of the present study were to evaluate the diagnostic performance, to examine the optimal cut‐off value, and to compare the diagnostic performance of each model. Methods Patients who presented to our emergency department with renal colic were considered for this prospective study. We analyzed the predictive performance of both STONE and CHOKAI scores at their optimal cut‐off values, using receiver operating characteristic (ROC) curve and area under the curve (AUC), as well as sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR−) at the optimal cut‐off value. Results Of the 96 patients who met the inclusion criteria, 79 were definitively diagnosed with ureteral stones. All patients were of Japanese descent. The AUC of the CHOKAI score was 0.971 at an optimal cut‐off value of 6, showing a sensitivity of 0.911, specificity of 0.941, LR+ of 15.49, and LR− of 0.094. The AUC of the STONE score was 0.873 at an optimal cut‐off value of 8, showing a sensitivity of 0.823, specificity of 0.824, LR+ of 4.662, and LR− of 0.215. The AUC of the CHOKAI score was significantly higher than that of the STONE score (p = 0.010). Of the 73 patients with a CHOKAI score of ≥6, 98.6% had ureteral stones, and of the 68 patients with a STONE score of ≥8, 95.6% had ureteral stones. Conclusions The simplified CHOKAI score is a useful tool to screen for ureteral stones in patients with renal colic.

A case of myxoid adrenocortical neoplasm: computed tomography and magnetic resonance imaging characteristics

Myxoid adrenocortical neoplasms are rare; to our knowledge, only 56 cases have been reported in the literature. Therefore, distinguishing benign from malignant cases is challenging. Although the histopathological features of myxoid adrenocortical neoplasia have been amply demonstrated, their imaging characteristics are yet to be reported. We describe here these characteristics for such a neoplasm. Our patient, a 70-year-old male, was found to have a 3-cm left adrenal incidentaloma through a non-enhanced computed tomography. Attenuation measurements were 22 Hounsfield units on precontrast imagery, and percentage enhancement washout was 92%. Magnetic resonance imaging showed no loss of signal intensity in T1-weighted out-of-phase images, but high signal intensity on T2-weighted and diffusion-weighted images. Left adrenalectomy was performed and the pathological diagnosis was confirmed as myxoid adrenocortical neoplasm. The imaging characteristics reported here will be beneficial to the differential diagnosis of myxoid adrenocortical neoplasms based upon image analysis and will help distinguish benign from malignant neoplasms.