Publications by authors named "Tomonori Kato"

45 Publications

Lateral Cutaneous Nerve Entrapment Syndrome (LACNES).

Am J Med 2021 May 1. Epub 2021 May 1.

Department of General Medicine, Chiba University Hospital, Japan.

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http://dx.doi.org/10.1016/j.amjmed.2021.03.035DOI Listing
May 2021

A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin.

Ann Hematol 2021 Mar 11;100(3):743-752. Epub 2021 Jan 11.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 10/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 10/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 10/L and platelets ≥ 50 × 10/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 10/L and platelets ≥ 50 × 10/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.
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http://dx.doi.org/10.1007/s00277-020-04365-zDOI Listing
March 2021

Xiphodynia.

Am J Med 2021 03 28;134(3):e215-e216. Epub 2020 Sep 28.

Department of General Medicine, Chiba University Hospital, Japan.

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http://dx.doi.org/10.1016/j.amjmed.2020.08.033DOI Listing
March 2021

Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome.

Bone Marrow Transplant 2020 07 16;55(7):1399-1409. Epub 2020 Mar 16.

Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.

A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.
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http://dx.doi.org/10.1038/s41409-020-0859-8DOI Listing
July 2020

Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome.

Biol Blood Marrow Transplant 2020 01 20;26(1):139-144. Epub 2019 Sep 20.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P < .001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained.
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http://dx.doi.org/10.1016/j.bbmt.2019.09.021DOI Listing
January 2020

Oncological and renal outcomes of segmental ureterectomy vs. radical nephroureterectomy for upper tract urothelial carcinoma.

Oncol Lett 2018 Nov 19;16(5):6861-6867. Epub 2018 Sep 19.

Division of Urology, Niigata Rosai Hospital, Japan Organization of Occupational Health and Safety, Joetsu, Niigata 942-8502, Japan.

Segmental ureterectomy (SU) represents a promising alternative for the treatment of upper tract urothelial carcinomas (UTUCs) as it is a less invasive procedure and guarantees the preservation of renal units. The present study evaluated oncological outcomes and renal functions following SU when compared with radical nephroureterectomy (RNU). A total of 26 patients with UTUCs who underwent SU (n=12) or RNU (n=14) were retrospectively evaluated. SU was performed in patients with clinically unifocal disease. In the SU group, the following surgeries were carried out: 7 direct ureterocystoneostomy, 1 reimplantation on psoas hitch bladder, 1 reimplantation on Boari flap bladder, 2 ureteral end-to-end anastomosis and 1 subtotal ureterectomy. In the SU group, tumors were low grade urothelial carcinoma (UC) in 6 patients, high grade UC in 5 patients and high grade UC with squamous cell differentiation in 1 patient, as well as ≤pT1 in 5, ≥pT2 in 6 and pTis in 1 patient; 'p' refers to the pathological state. The 5-year overall, cancer-specific, recurrence free and metastasis free survival in the SU group were 77.8, 87.5, 34.4 and 80.8%, respectively, which all exhibited no significant differences when compared with those of the RNU group. With regard to renal function, postoperative estimated glomerular filtration rates were preserved in the SU group. The present study demonstrated that SU does not result in poorer cancer control when compared with RNU. Thus, SU is an acceptable alternative to RNU in selected cases, as it is less invasive and preserves renal functions.
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http://dx.doi.org/10.3892/ol.2018.9463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202487PMC
November 2018

PSA response following the 'steroid switch' in patients with castration-resistant prostate cancer treated with abiraterone: A case report.

Oncol Lett 2018 Oct 17;16(4):5383-5388. Epub 2018 Aug 17.

Department of Urology, Teikyo University Chiba Medical Center, Ichihara, Chiba 299-0111, Japan.

A 69-year-old man presented initially with back pain and incomplete bilateral lower limb paralysis. The level of prostate-specific antigen (PSA) in the patient was elevated to 167.0 ng/ml, and multiple bone metastases were detected. Thoracic laminectomy was performed in an emergency due to spinal decompression. Subsequently, the patient was diagnosed with prostate cancer from an examination of resected bone specimens. Combined androgen blockade with degarelix and bicalutamide was initiated in October 2013. Consequently, the serum PSA level decreased to <1.0 ng/ml, but thereafter gradually increased. Subsequent bicalutamide withdrawal response was not observed, and switch of anti-androgen therapy to flutamide also resulted in a poor response. Then, abiraterone (1,000 mg daily) in combination with prednisolone (10 mg daily) was initiated when the level of PSA increased to 35.9 ng/ml in June 2015. The level of PSA decreased to the lowest point of 4 ng/ml; however, PSA level increased again to 21.7 ng/ml in April 2016. Consequently, a 'steroid switch' was attempted. Abiraterone therapy was continued, but concomitant corticosteroid was switched from prednisone to dexamethasone (1.0 mg per day). Fortunately, serum PSA level decreased promptly to the lowest point of 0.6 ng/ml. In the present case report, a review of recent literature was presented and potential explanations of the mechanism underlying the 'steroid switch' were described. Pharmacokinetic differences between dexamethasone and prednisolone may partially explain why the 'steroid switch' occurs. Other mechanisms may include the activation of the glucocorticoid receptor, mineralocorticoid receptor and/or mutant androgen receptor. Corticosteroids accelerate a number of transcription factors, cellular growth factors and cytokines, which may also be potential mechanisms. The 'steroid switch' at PSA progression might be a feasible option for therapy, which may delay the development of the disease. Although the underlying mechanisms require further study, clinicians should pay attention to this phenomenon.
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http://dx.doi.org/10.3892/ol.2018.9321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144877PMC
October 2018

Abiraterone acetate withdrawal syndrome: Speculations on the underlying mechanisms.

Oncol Lett 2018 Feb 14;15(2):2669-2672. Epub 2017 Dec 14.

Division of Urology, Kuki General Hospital (Formerly Satte General Hospital), Saitama 346-8530, Japan.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.
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http://dx.doi.org/10.3892/ol.2017.7628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777279PMC
February 2018

Disseminated Cutaneous Infection of Mycobacterium colombiense in a Patient with Myelodysplastic Syndrome.

Intern Med 2018 Feb 1;57(3):423-427. Epub 2017 Nov 1.

Department of Hematology and Oncology, Anjo Kosei Hospital, Japan.

Mycobacterium colombiense (M. colombiense) is a member of the Mycobacterium avium complex (MAC). To our knowledge, this is the third case report of an M. colombiense infection. An 80-year-old man, immunocompromised by myelodysplastic syndrome (MDS), developed a skin rash with exfoliation and eruption on his face and scalp. Mycobacteria were detected in pus samples. Broad-range polymerase chain reaction (PCR) revealed the mycobacteria to be M. colombiense. The lesions resolved after daily administration of rifampicin, ethambutol, and clarithromycin. In conclusion, broad-range PCR identified this rare mycobacterium, allowing for the administration of appropriate combination antibiotic therapy.
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http://dx.doi.org/10.2169/internalmedicine.7890-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827328PMC
February 2018

Prospective observational study on the first 51 cases of peripheral blood stem cell transplantation from unrelated donors in Japan.

Int J Hematol 2018 Feb 13;107(2):211-221. Epub 2017 Oct 13.

Department of Hematology, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya, 453-8511, Japan.

The Japan Marrow Donor Program (JMDP) has facilitated unrelated peripheral blood stem cell transplantation (URPBSCT) since 2010. We conducted a prospective multicenter observational study to evaluate the feasibility of such transplantation. Between 2011 and 2014, 51 patients underwent URPBSCT from 8/8 allele-matched donors for hematological malignancies. The median age of the patients was 50 years; 21 had high-risk disease. Myeloablative conditioning regimens were used in 31 patients, and tacrolimus based graft-versus-host disease (GVHD) prophylaxis was used for all patients. The cumulative rate of engraftment was 96%. With a median follow-up period of 610 days for survivors, 100-day and 1-year overall survival rates were 86 and 59%, respectively. The cumulative incidence of non-relapse mortality and relapse at 1 year were 14 and 35%, respectively. The incidence of grade II to IV acute GVHD at 100 days and extensive type of chronic GVHD at 1 year were 25 and 32%, respectively. The probability of overall survival was comparable with that of bone marrow transplantation from HLA matched-unrelated donors in Japan, although the incidence of chronic GVHD was higher. Further follow-up with more patients is clearly warranted to establish the optimal use of URPBSCT together with the approaches of minimizing chronic GVHD.
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http://dx.doi.org/10.1007/s12185-017-2341-yDOI Listing
February 2018

The Efficacy of an Oral Elemental Diet in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Intern Med 2016;55(24):3561-3569. Epub 2016 Dec 15.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

Objective Conditioning regimens for hematopoietic stem cell transplantation (HSCT) are well known to cause severe gastrointestinal toxicities that often disturb the oral intake of the patients followed by poor nutrition and life-threatening infection. An oral elemental diet (ED) is an easily consumed and assimilated form of liquid nutrients mainly composed of amino acids. It alleviates the digestive loading from the intestine and is mainly used for enteral nutritional support in patients with Crohn's disease. We herein report, for the first time, the efficacy of ED for patients undergoing HSCT. Methods We evaluated the efficacy of ED in a prospective cohort study. The primary endpoint for this study was the hospitalization period. The secondary endpoint was the occurrence of oral mucositis, nausea, diarrhea and fever. Patients A total of 73 patients were consecutively enrolled between March 2011 and March 2013. Twenty-three patients underwent autologous HSCT and 50 patients underwent allogeneic HSCT. The first 21 patients did not receive ED (non-ED group; NEG) while in the successive 52 patients (ED group; EG), oral ED was started before conditioning and was continued until 28 days after transplantation. Results The patient characteristics were similar between the two groups. The mean duration of ED administration for EG was 28.7 days (range, 3-37 days), and the mean total-dose of ED administration was 1904 g (range, 240-2,960 g). The median hospitalization period was significantly shorter in EG compared to NEG, (34 days vs. 50 days; p=0.007). Grade 3-4 oral mucositis occurred less in EG than NEG (25% vs. 48%; p=0.06). Conclusion Oral ED may promote an early mucosal recovery and thereby shorten the duration of hospitalization.
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http://dx.doi.org/10.2169/internalmedicine.55.7310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283954PMC
April 2017

Trousseau's syndrome caused by bladder cancer producing granulocyte colony-stimulating factor and parathyroid hormone-related protein: A case report.

Oncol Lett 2016 Nov 20;12(5):4214-4218. Epub 2016 Sep 20.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.

The present study reports a rare case of bladder cancer that caused Trousseau's syndrome, a malignancy-associated hypercoagulative state leading to venous or arterial thrombosis. A 38-year-old Japanese female patient experienced a sudden onset of visual field defects and lower limb weakness. Cerebral magnetic resonance imaging revealed multi-regional hypointense areas compatible with acute cerebral infarction. Despite the repeated administration of anticoagulant treatment with heparin, the condition could not be adequately controlled and thromboembolic events occasionally recurred. Several tumor markers, including carbohydrate antigen 19-9, cancer antigen 125, carcinoembryonic antigen, cytokeratin 19 fragment and squamous cell carcinoma antigen levels, were elevated. Consequently, computed tomography scans were performed, which revealed a massive bladder tumor with multiple bone and lymph node metastases. The patient also exhibited other paraneoplastic disorders, including leukocytosis due to granulocyte colony-stimulating factor (G-CSF) production, and hypercalcemia due to parathyroid hormone-related protein (PTHrP) production. Transurethral resection of the bladder tumor was performed, and the tumor was pathologically confirmed as urothelial cell carcinoma. Immunohistochemical testing revealed positive staining for G-CSF and PTHrP. Despite undergoing gemcitabine/cisplatin-based systemic chemotherapy, the disease developed rapidly and the patient succumbed to the disease within 3 months of initial symptoms. The present case indicates that occult visceral malignancy should be considered in patients with unexplained thromboembolism.
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http://dx.doi.org/10.3892/ol.2016.5152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104261PMC
November 2016

A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

Int J Hematol 2017 Jan 30;105(1):79-86. Epub 2016 Sep 30.

Department of Hematology, Fujita Health University, Toyoake, Japan.

Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.
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http://dx.doi.org/10.1007/s12185-016-2095-yDOI Listing
January 2017

Analysis of repeated 24-core saturation prostate biopsy: Inverse association between asymptomatic histological inflammation and prostate cancer detection.

Oncol Lett 2016 Aug 9;12(2):1132-1138. Epub 2016 Jun 9.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.

Saturation prostate biopsy protocols have been developed to improve the prostate cancer (PCa) detection rate, particularly in the setting of repeat biopsies. The present study attempted to clarify the association between PCa detection and various risk factors in repeat saturation biopsies. A retrospective analysis was conducted on 78 Japanese patients for whom findings had caused suspicion of PCa despite previous negative prostate biopsies, and who consecutively underwent a 24-core transperineal repeat biopsy at Toyama University Hospital (Toyama, Japan). PCa was confirmed histologically in 16 of the 78 patients (20.5%). A univariate analysis revealed that the prostate-specific antigen (PSA) level at repeat biopsy was higher (P<0.01), the fPSA/tPSA ratio was lower (P=0.04), the total prostate volume was smaller (P=0.01) and the PSA density was higher (P<0.01) in PCa patients than in patients with benign prostatic disease (BPD). Histological inflammation was more frequently observed in BPD patients than in PCa patients (P<0.01). A multivariate analysis revealed that histological inflammation was the only independent predictor of the presence of a malignant lesion on repeat biopsy (odds ratio, 0.027; P=0.01). It must be considered that inflammation may cause a PSA increase in some patients with a negative initial biopsy, leading to unnecessary repeat biopsy.
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http://dx.doi.org/10.3892/ol.2016.4693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950658PMC
August 2016

[Antiandrogen withdrawal syndrome].

Nihon Rinsho 2016 May;74 Suppl 3:584-8

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May 2016

Retraction-Related Acute Liver Failure after Urological Laparoscopic Surgery.

Curr Urol 2014 Oct 20;7(4):199-203. Epub 2014 Aug 20.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

Liver retraction is necessary for optimal exposure during laparoscopic right renal surgery. We described a patient who developed fulminant liver failure as a result of liver retractor-induced excessive ischemic changes in the right lobe of the liver. A 37-year-old male underwent a right side laparoscopic pyeloplasty for ureteropelvic junction obstruction. At the beginning of the operation, a small snake retractor was placed through a 5-mm port under direct vision. The liver was lifted in the appropriate direction to optimize exposure by using the laparoscope holder. The operation was prolonged. However, we achieved significant improvements in the efficiency of liver retraction using the holder. On the first postoperative day, the patient's serum levels of GOT, GPT and LDH had remarkably increased. A computerized tomogram confirmed the presence of excessive ischemic changes of the right lobe of the liver. Our method which used a laparoscope holder device for liver retraction maintained a better surgical field. However, neglecting to make minor adjustments to the positioning of the retractor can cause significant pressure on the liver parenchyma in a single area. As surgical procedures increase in complexity, the surgeon should keep these potential side effects in mind and shift the retraction point at regular intervals. In this report, we discussed various types of retractor-related liver injuries and their management, and highlighted the importance of intermittent release of retraction during prolonged surgery.
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http://dx.doi.org/10.1159/000365676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483302PMC
October 2014

Analysis of Japanese Patients Treated with or without Long-Term Epirubicin Plus Ara-C Intravesical Instillation Therapy for Low-Grade Superficial Bladder Cancer.

ScientificWorldJournal 2015 21;2015:325305. Epub 2015 May 21.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.

The high incidence of tumor recurrence following transurethral resection (TUR) represents a major problem encountered in the management of bladder cancer. This study examined the efficacy of intravesical chemotherapy in superficial bladder cancer. We retrospectively analyzed 90 Japanese cases with low-grade superficial transitional cell carcinoma (stage T1, grades 1 and 2) who were rendered tumor-free by TURBT (TUR of bladder tumor) and who thereafter were treated with or without intravesical chemotherapy. Among them, instillation was terminated in 2 patients due to adverse effects (severe but reversible chemical cystitis). Remaining 88 patients were divided into 2 groups according to therapy: the TURBT-only group (n = 46), defined as patients treated with TURBT alone, and the Instillation group (n = 42), defined as patients treated with weekly intravesical instillation therapies using epirubicin plus Ara-C. Recurrence-free rate was significantly higher in the Instillation group than in the TURBT-only group (p = 0.02, HR = 0.457). The 5-year recurrence-free rate was 58.5% for the Instillation group and 38.6% for the TURBT-only group. Our instillation schedule represents the most intensive regimen among previously reported therapies and resulted in a 54.3% decrease in incidence of tumor recurrence. We believe that the results of this study could provide useful information on management of bladder cancer.
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http://dx.doi.org/10.1155/2015/325305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458547PMC
July 2016

Minimally Invasive Endourological Techniques may Provide a Novel Method for Relieving Urinary Obstruction due to Ureterosciatic Herniation.

Case Rep Nephrol Dial 2015 Jan-Apr;5(1):13-9. Epub 2014 Aug 15.

Department of Urology, Tokyo Kosei Nenkin Hospital, Tokyo, Japan.

Ureterosciatic herniation, the protrusion of the hernia sac through the sciatic foramen, is an extremely rare cause of ureteral obstruction. We describe a case revealed by severe left back pain in a 72-year-old female. She was referred to our hospital for urological assessment of left hydronephrosis observed by ultrasonography. Intravenous ureterography (IVU) showed findings compatible with a left sciatic ureter, a dilated ureter with a fixed kinking, which is known as the 'curlicue' sign. We decided to attempt recovery of the herniated ureter using a retrograde approach. Ureteral stent placement was performed to decompress the dilated upper urinary tract. The ureterosciatic hernia was relieved with the passage of a flexible guide wire and a double-pigtail stent. Three months after ureteral stenting, she refused continuing to have an indwelling stent and the stent was removed. Thereafter, IVU revealed recurrent ureterosciatic hernia; however, there was no hydroureter or hydronephrosis. The patient is currently being under observation for 6 years after stenting and continues to be without hydronephrosis or symptoms. Placement of an internal stent possibly provides the rigidity to the ureter, thereby reducing the hernia and urinary obstruction. In the previous reports, most symptomatic patients have been treated surgically, with conservative therapy reserved for asymptomatic patients. For the patient who is elderly or a poor surgical candidate, retrograde stenting may provide safe reduction and efficacious treatment. This endourological approach provides a minimally invasive means for the management of urinary obstruction caused by ureterosciatic herniation.
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http://dx.doi.org/10.1159/000366154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294447PMC
April 2015

Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.

Ann Hematol 2015 Jul 15;94(7):1139-48. Epub 2015 Feb 15.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.
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http://dx.doi.org/10.1007/s00277-015-2312-4DOI Listing
July 2015

Clinical factors associated with sperm DNA fragmentation in male patients with infertility.

ScientificWorldJournal 2014 4;2014:868303. Epub 2014 Aug 4.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.

Objective: The clinical factors associated with sperm DNA fragmentation (SDF) were investigated in male patients with infertility.

Materials And Methods: Fifty-four ejaculates from infertile Japanese males were used. Thirty-three and twenty-one were from the patients with varicoceles and idiopathic causes of infertility, respectively. We performed blood tests, including the serum sex hormone levels, and conventional and computer-assisted semen analyses. The sperm nuclear vacuolization (SNV) was evaluated using a high-magnification microscope. The SDF was evaluated using the sperm chromatin dispersion test (SCDt) to determine the SDF index (SDFI). The SDFI was compared with semen parameters and other clinical variables, including lifestyle factors.

Results: The SDFI was 41.3 ± 22.2% (mean ± standard deviation) and did not depend on the cause of infertility. Chronic alcohol use increased the SDFI to 49.6 ± 23.3% compared with 33.9 ± 18.0% in nondrinkers. The SDFI was related to adverse conventional semen parameters and sperm motion characteristics and correlated with the serum FSH level. The SNV showed a tendency to increase with the SDFI. The multivariate analysis revealed that the sperm progressive motility and chronic alcohol use were significant predictors of the SDF.

Conclusion: The SCDt should be offered to chronic alcohol users and those with decreased sperm progressive motility.
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http://dx.doi.org/10.1155/2014/868303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137616PMC
October 2015

Sperm nuclear vacuoles in relation to acrosome reactions and sperm motility.

ScientificWorldJournal 2014 3;2014:178970. Epub 2014 Jul 3.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.

We investigated sperm nuclear vacuolation in relation to acrosome reactions and the maintenance of sperm motility. Thirty male patients who visited our Male Infertility Clinic were enrolled. These patients underwent conventional semen analyses, Acrobeads tests, and high-magnification observation of the sperm head to evaluate the degree of nuclear vacuolation on the Acrobeads test scoring after 24 hours of incubation. The presence of acrosome reactions was evaluated using the Acrobeads test. The spermatozoa were classified into three groups: (I) those bound to MH61-beads, (II) motile spermatozoa that did not bind to MH61-beads, and (III) immotile spermatozoa that did not bind to MH61-beads. The percentage of spermatozoa with large nuclear vacuoles (%LNV) was compared between the three groups. The degree of sperm nuclear vacuolation was evaluated in 17,992 ejaculated spermatozoa. The mean %LNVs were 2.4% in group I, 5.8% in group II, and 9.8% in group III. These values were significantly different from each other (P < 0.001, paired t-test). There were no correlations between the %LNV values and the Acrobeads scores. In conclusion, the degree of sperm nuclear vacuolation was significantly lower in the acrosome-reacted spermatozoa and spermatozoa with maintained motility, and higher in the immotile spermatozoa that did not bind to MH61-beads.
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http://dx.doi.org/10.1155/2014/178970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109670PMC
April 2015

Upfront autologous stem-cell transplantation with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) in patients with newly diagnosed primary central nervous system lymphoma.

Int J Hematol 2014 Aug 20;100(2):152-8. Epub 2014 Jun 20.

Department of Hematology and Oncology, Anjo Kosei Hospital, Higashi-Hirokute 28 Anjo-Chou, Anjo, Aichi, Japan,

Treatment of primary central nervous system lymphoma (PCNSL) improved in recent years. However, the high neurotoxicity and low survival rates associated with this condition remain unresolved. We report 13 consecutive patients with PCNSL for whom upfront melphalan, cyclophosphamide, etoposide, and dexamethasone (known as LEED) followed by autologous stem-cell transplantation (ASCT) was planned at the Anjo Kosei Hospital. All patients were pathologically diagnosed with diffuse large B-cell lymphoma and were negative for human immunodeficiency virus. All patients were to receive three cycles of high-dose methotrexate-based induction chemotherapy, two cycles of high-dose AraC-based chemotherapy, and LEED followed by ASCT. All 13 patients achieved a partial response, and the 3-year overall survival (OS) rate was 76.2 %. Seven of the 13 patients were alive at the last follow-up, without any adverse events, including neurotoxicity. Six of the 13 (46.2 %) patients underwent ASCT and the 3-year OS rate was 80.0 %. Although this study included only a limited number of patients, these preliminary signs of efficacy and tolerability merit further consideration. To make further improvements in survival, the rate of patients undergoing ASCT should be increased. Other prospective studies involving greater numbers of patients are required to confirm these findings.
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http://dx.doi.org/10.1007/s12185-014-1608-9DOI Listing
August 2014

Laparoscopic resection of retroperitoneal neural tumors.

Curr Urol 2013 Aug 28;7(1):40-4. Epub 2013 Jul 28.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

Purpose: Retroperitoneal neural tumor (RNT) is rarely excised laparoscopically, and the laparoscopic management of RNT remains controversial. We herein report 4 cases of laparoscopic excision of RNT that resulted in diverse clinical outcomes.

Patients And Methods: Between August 2005 and January 2011, we performed laparoscopic excision of RNT in 4 patients. The mean tumor size was 4.5 cm. The mean operative time was 297 minutes and the mean amount of blood loss was 55 ml. The surgeries were uneventful, with no operative complications or evidence of intra-abdominal bleeding. However, 2 patients required reoperation for delayed hemorrhage and urinoma formation, respectively.

Results: The postoperative pathological diagnoses were schwannoma in 3 patients and ganglioneuroblastoma in 1 patient. All patients were well with no signs of peripheral neuropathy or radiculopathy, and CT and/or (18)F-FDG PET/CT performed during follow-up indicated no evidence of disease.

Conclusions: Obtaining extensive preoperative knowledge of the source neural and vascular anatomy of the tumor is important for the surgical planning of laparoscopic resection of RNT. When a great deal of care is taken to divide the tumor and the source nerves and vital vessels, safe execution of RNT can be achieved for minimal postoperative mortality and morbidity.
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http://dx.doi.org/10.1159/000343553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3783273PMC
August 2013

Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

PLoS One 2014 7;9(5):e96252. Epub 2014 May 7.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096252PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012982PMC
January 2015

Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation.

Cell Immunol 2014 Mar-Apr;288(1-2):53-9. Epub 2014 Mar 11.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.

The effect of programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific T cells has not been thoroughly examined. We evaluated the involvement of exhausted CMV-specific T cells in persistent CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT). CMV-specific CD8+ T cells obtained from an HLA-A∗24:02-positive patient, who failed to eliminate CMV for more than 1 year after HSCT, responded poorly to CMV pp65 peptide and showed high PD-1 expression. Sera from patients with persistent CMV infection showed a significantly higher IL-6 level than those from patients with temporary CMV infection after allogeneic HSCT and healthy donors. CD33+ adherent cells produced IL-6, and regulated PD-1 expression and growth of CMV-specific CD8+ T cells through cell-to-cell contact. Although further investigation is required to clarify the association between IL-6 level and CMV infection in more patients, IL-6 might be a useful biomarker of persistent CMV infection after allogeneic HSCT.
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http://dx.doi.org/10.1016/j.cellimm.2014.02.007DOI Listing
May 2014

Primary melanoma of the urinary bladder identified by urine cytology: a rare case report.

Diagn Cytopathol 2014 Dec 14;42(12):1091-5. Epub 2014 Feb 14.

Laboratory of Pathology, Toyama University Hospital, Toyama, Japan.

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http://dx.doi.org/10.1002/dc.23074DOI Listing
December 2014

Application of a new technique, spiral tissue microarrays constructed using needle biopsy specimens, to prostate cancer research.

Int J Oncol 2014 Jan 13;44(1):195-202. Epub 2013 Nov 13.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

Tissue microarrays were constructed using prostate needle biopsy specimens obtained from 58 patients who underwent radical prostatectomy for localized or locally advanced prostate cancer (PC). We used the spiral array (SA) technique, a novel approach for tissue array construction in a spiral form, which has advantages over small needle biopsy specimens. Roll-shaped tissue pieces produced by slicing a prostate biopsy tissue block and trimming the cancer segment were used to obtain a tissue array block. Cancer segments measuring >3 mm were incorporated into the tissue arrays. Cancer fragments (n=253) were obtained from formalin-fixed, paraffin-embedded needle biopsy specimens. The median number of cancer fragments per patient was four (1-8, min-max). On SA, the median number of confirmed cancer fragments per patient was four (1-7) and 224 cancer fragments (88.5%) were confirmed histologically. Each core of reeled tissue contained at least one cancer fragment. The expressions of multiple prognostic molecular markers for PC (Ki-67, p53 and bcl-2) were immunohistochemically measured using the SA. The Ki-67 and bcl-2 expressions were significantly associated with the Gleason score (GS). A univariate analysis identified Ki-67, bcl-2 and GS as significant predictors of cancer-specific survival, p53 and bcl-2 as significant predictors of overall survival and Ki-67, adjuvant androgen deprivation and GS as significant predictors of biochemical progression. In a multivariate analysis, p53 was independently associated with overall survival, while adjuvant androgen deprivation and GS were associated with biochemical progression. These results indicate that SA has potential as a new tool for translational research on PC.
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http://dx.doi.org/10.3892/ijo.2013.2173DOI Listing
January 2014

Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy.

Mol Immunol 2013 Dec 1;56(4):399-405. Epub 2013 Aug 1.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Research Fellow of Japan Society for the Promotion of Science, Japan.

Subgroup B adenovirus serotype 11 (Ad11) occasionally causes fatal infections in immunocompromised patients. The present study describes a novel Ad11 epitope presented by HLA-A*24:02 that could be used for adoptive immunotherapy. Ten synthetic Ad11 hexon protein-derived nonamer peptides that bound to HLA-A*24:02 were selected by a computer algorithm and MHC stabilization assay. Stimulation of peripheral blood mononuclear cells from HLA-A*24:02+ donors with each of these synthetic peptides induced peptide-specific CD8(+) T-cells for three peptides. Testing the reactivity of these peptide-specific CD8(+) T-cells against various target cells confirmed that peptide TYFNLGNKF is naturally processed in Ad11-infected cells and is presented by HLA-A*24:02. Emergence of TYFNLGNKF-specific CD8(+) T-cells coincided with the clearance of adenoviruses in a patient with Ad11 disease. Importantly, TYFNLGNKF-specific CD8(+) T-cells were suggested to be not serotype cross-reactive. The novel HLA-A*24:02-restricted Ad11 epitope could be used for anti-Ad11 adoptive immunotherapy and to monitor immunity to Ad11 using MHC tetramers.
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http://dx.doi.org/10.1016/j.molimm.2013.05.232DOI Listing
December 2013

Observation of spermatozoa by a high-magnification microscope.

Reprod Med Biol 2014 01 20;13(1):21-28. Epub 2013 Jul 20.

Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research University of Toyama 2630 Sugitani Toyama Toyama Japan.

Semen analyses are the primary tool for evaluating male infertility, as semen parameters are useful for predicting potential fertility. In the field of assisted reproductive technology (ART), the single best motile spermatozoon should be selected, especially when performing intracytoplasmic sperm injection (ICSI). In this context, the motile sperm organelle morphology examination (MSOME) was developed as a method of assessing the detailed morphology of motile spermatozoa in real time at a magnification of up to 6,300× on a video system. The use of ICSI with MSOME-selected sperm is called intracytoplasmic morphologically selected sperm injection (IMSI). IMSI improves the outcomes of ICSI. MSOME can be also applied to evaluate male infertility. Among MSOME parameters, the presence of sperm nuclear vacuoles is the most important finding. Large sperm nuclear vacuoles (LNV) are related not only to poor ART outcomes, but also to poor semen quality and sperm DNA damage, such as DNA fragmentation and chromatin condensation failure. It has been suggested that sperm head vacuoles are produced at earlier stages of sperm maturation. It is possible that the number of LNV can be decreased by surgical or medical treatment for male infertility. Therefore, the level of LNV has the potential to be used as an alternative parameter of semen quality and a new tool for evaluating the therapeutic effects of treatment in male patients with infertility.
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http://dx.doi.org/10.1007/s12522-013-0164-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892975PMC
January 2014

Micafungin for empirical antifungal therapy in patients with febrile neutropenia: multicenter phase 2 study.

Int J Hematol 2013 Aug 16;98(2):231-6. Epub 2013 Jul 16.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Empirical antifungal therapy is the current standard of care for patients with febrile neutropenia unresponsive to broad-spectrum antimicrobials. Although a number of antifungal agents are currently available, the need remains for effective but less toxic alternatives for this indication. We therefore conducted a phase 2 study of micafungin for 80 patients with hematologic diseases who were suffering from persistent or recurrent fever after at least 96 h of antibacterial therapy. The patients were treated with micafungin at a fixed dose of 150 mg/day. Of the 78 evaluable patients, 54 (69 %) achieved defervescence by the time of neutrophil recovery, and 56 (72 %) completed the treatment in accordance with the provision of the protocol. Four patients developed invasive fungal infection, nine changed antifungal therapy because of lack of efficacy, and three discontinued micafungin because of drug-related adverse events. Based on the composite end point taking account of these, the overall treatment success rate was 60 %, with the lower limit of a 90 % confidence interval (50.3 %) exceeding the predefined threshold success rate (50 %). These findings show the efficacy and safety of micafungin for empirical antifungal therapy in patients with persistent or recurrent febrile neutropenia, warranting further investigation of this drug in a phase 3 study.
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http://dx.doi.org/10.1007/s12185-013-1396-7DOI Listing
August 2013