Shoichiro Ohta

Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection

Purpose Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and Methods Urine specimens were collected at 18 multinational sites from subjects prior to cystoscopy or tumor resection, and from healthy and other control subjects without evidence of bladder cancer. The levels of 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5‐mRNA model to predict cancer status. The performance of the GeneXpert® Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. Results In the independent test cohort the assay ROC curve AUC was 0.87 (95% CI 0.81–0.92). At an example cutoff point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the hematuria and surveillance patient populations, respectively. Conclusions We developed a 90‐minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.

Effect of low glycemic index food and postprandial exercise on blood glucose level, oxidative stress and antioxidant capacity

Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia.

Efficacy of once or twice weekly administration of epoetin κ in patients receiving hemodialysis: A retrospective study

Several clinically approved recombinant erythropoietin (rEPO) preparations, such as epoetin-β, epoetin-δ and the epoetin-α derivative, darbepoetin-α, have been commercially produced. Since the expiration of patent protection, a number of novel rEPO biosimilars have been approved on the world market. In 2010, epoetin-κ, which is biosimilar to epoetin-α, was clinically approved. Epoetin-κ is a biopharmaceutical product that is based on serum-free media following master cell bank preparation. The present study analyzes the results obtained during a six-month observation period, in which the administration of epoetin-β was switched to that of epoetin-κ. In a cohort of patients receiving chronic dialysis, who were clinically in a state of relative calm and were in control of their renal anemia, it was possible to sustain good control of the anemia by reducing the frequency of the epoetin-β administration from the conventional and empirically determined three times a week to twice a week, and further to once a week. Furthermore, the good control was maintained upon changing from the administration of epoetin-β to that of epoetin-κ. Moreover, three months subsequent to this switch, the degree of instability observed among the patients had decreased. Despite the fact that the situation following the changeover requires further investigation, it may be concluded that the results obtained in this study are indicative of the clinical equivalence and efficacy of epoetin-κ.

Evaluation of Thymidylate Synthase Expression in Prostate Cancer

Thymidylate synthase (TS), a key enzyme in DNA synthesis, is over-expressed in a variety of cancer cells. 5-Fluorouracil, an anticancer agent clinically used against various cancers, including prostate cancer, inhibits DNA synthesis by binding TS. In this study, we investigated expression of TS in prostate cancer and its prognostic significance. Seventy-five prostatic tissue specimens were obtained from patients who had undergone prostate biopsy for diagnosis of prostate cancer. We analyzed the cancerous tissue specimens for TS expression using immunohistochemistry. TS expression was significantly increased in patients with bone metastasis. No relationship was found between expression of TS and the other clinicopathological findings. Because TS expression could be used as a prognostic parameter in patients with prostate cancer, an accurate prediction of prognosis might help to select patients for more intensive surgical, hormonal, or chemotherapeutic approaches, including 5-fluorouracil. Additional prospective studies are warranted to define the role of TS in selecting patients for adjuvant therapy for prostate cancer.

Remarkable Response to Neoadjuvant Therapy with Methotrexate, Vinblastine, Adriamycin, and Cisplatin for Undifferentiated Bladder Carcinoma: A Case Report and Literature Review

We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

Laparoscopic Varicocelectomy Carried Out with the LigaSure Device in 52 Patients.

We describe the effective use of the bipolar vessel-sealing device: LigaSure for the division of the internal spermatic vessels in a laparoscopic varicocelectomy. A total of 52 males with varicocele (left-side n = 49, and bilateral n = 3) were included in this study. Blunt dissection was used to isolate the packet of spermatic vessels. The packet of spermatic vessels was divided using a bipolar diathermy system, the LigaSure Precise. It was clear that the operative time was significantly reduced compared to the method using clips, which was done before the development of this kind of device. In another experiment to examine the effect of vessel sealing, it was confirmed that the LigaSure has performance comparable to the clips. Despite the result that the Harmonic scalpel was less effective in vessel sealing, our study found it difficult to determine which is superior, LigaSure or clips, in terms of operative time, relapse rate and complication.