Publications by authors named "Tomoyuki Otsuka"

42 Publications

Safety and efficacy of using cereal food (Frugra®) to improve blood pressure and bowel health in patients undergoing chronic hemodialysis: A pilot study.

J Pharmacol Sci 2021 Sep 18;147(1):132-137. Epub 2021 Jun 18.

Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Hypertension and constipation are major hemodialysis complications. Salt restriction is one of the most important nonpharmacological interventions in managing hypertension. In patients undergoing hemodialysis, nonpharmacological strategies to manage constipation are extremely difficult to develop owing to the presence of excess dietary potassium and fluids. Frugra®, which is a cereal food that has a low salt content of 0.5 g per serving, may help reduce salt intake. Additionally, Frugra is rich in dietary fiber, thereby beneficial for such patients. In this study, we evaluated the safety and efficacy of Frugra in patients undergoing hemodialysis, focusing mainly on blood pressure and bowel health by changing the usual breakfast meal to Frugra for 8 weeks. We enrolled 11 patients undergoing hemodialysis. Despite the absence of changes in the patients' dry weight levels, their systolic blood pressure levels decreased from 155.5 ± 20.9 mmHg to 137.9 ± 10.3 mmHg after 2 months (P < 0.05). All participants reported improvements in bowel movement, and the levels of indoxyl sulfate, a representative gut-derived uremic toxin, were decreased from 49.3 μg/ml to 33.4 μg/ml. Furthermore, adverse events including electrolyte abnormalities were not observed. Therefore, Frugra may be useful to manage the health of patients undergoing hemodialysis.
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http://dx.doi.org/10.1016/j.jphs.2021.06.007DOI Listing
September 2021

EML4-ALK fusion variant.3 and co-occurrent PIK3CA E542K mutation exhibiting primary resistance to three generations of ALK inhibitors.

Cancer Genet 2021 Aug 28;256-257:131-135. Epub 2021 May 28.

Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.

The ALK inhibitors are promising therapeutic agents against lung cancer harboring ALK fusion genes and are currently under development up to the third generation. However, its therapeutic effects are reported to be affected by differences in ALK variants and co-occurrent mutations. Materials and Methods; We experienced an autopsy case of an ALK-positive lung cancer patient who showed primary resistance to three generations of ALK inhibitors. The poor survival time of the case was 14 months. To reveal the mechanism of primary resistance to three generations of ALK inhibitors, we performed next generation sequencing for 12 specimes obtained from an autopsy with covering whole exons of 53 significantly mutated, lung cancer-associated genes and amplicon-based target RNA sequenceing for the ALK fusion gene. The NGS analysis revealed a rare variant.3 of ALK fusion, in which 30 bp of base was inserted at the end of ALK intron.19 and was associated with EML exon.6 [E6_ins30A20] and a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. Structural analysis of the fusion protein ALK [E6_ins30A20] showed no interferance with the binding of ALK inhibitors to the kinase domain. The NGS analysis of primary and metastatic lesions obtained from an autopsy revealed a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. The constitutive activation of PI3K-Akt signal by PIK3CA E542K mutation occurred downstream of ALK signaling pathway, could lead to primary resistance to ALK inhibitors in all generations.
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http://dx.doi.org/10.1016/j.cancergen.2021.05.010DOI Listing
August 2021

Gallbladder neuroendocrine carcinoma: An important differential diagnosis of gallbladder adenocarcinoma.

JGH Open 2021 Jun 10;5(6):717-719. Epub 2021 May 10.

Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute Osaka Japan.

Gallbladder neuroendocrine carcinomas (NECs) are a rare but important differential diagnosis of gallbladder cancer. This case report highlights the importance of pathological diagnosis and the efficiency of endoscopic ultrasound-guided fine-needle aspiration. Pathological diagnosis should be attempted because the treatment of gallbladder NEC differs from that of gallbladder adenocarcinoma, especially in unresectable cases.
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http://dx.doi.org/10.1002/jgh3.12556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171154PMC
June 2021

Prognostic Impact of Cancer Activity on Clinically Relevant Bleeding Events After Percutaneous Coronary Intervention.

J Med Invest 2021 ;68(1.2):29-37

Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan.

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods. J. Med. Invest. 68 : 29-37, February, 2021.
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http://dx.doi.org/10.2152/jmi.68.29DOI Listing
January 2021

Multicentre cohort study of the impact of percutaneous coronary intervention on patients with concurrent cancer and ischaemic heart disease.

BMC Cardiovasc Disord 2021 Apr 13;21(1):177. Epub 2021 Apr 13.

Cancer Control Centre, Osaka International Cancer Institute, Osaka, Japan.

Background: The incidence of concurrent cancer and ischaemic heart disease (IHD) is increasing; however, the long-term patient prognoses remain unclear.

Methods: Five-year all-cause mortality data pertaining to patients in the Osaka Cancer Registry, who were diagnosed with colorectal, lung, prostate, and gastric cancers between 2010 and 2015, were retrieved and analysed together with linked patient administrative data. Patient characteristics (cancer type, stage, and treatment; coronary risk factors; medications; and time from cancer diagnosis to index admission for percutaneous coronary intervention [PCI] or IHD diagnosis) were adjusted for propensity score matching. Three groups were identified: patients who underwent PCI within 3 years of cancer diagnosis (n = 564, PCI + group), patients diagnosed with IHD within 3 years of cancer diagnosis who did not undergo PCI (n = 3058, PCI-/IHD + group), and patients without IHD (n = 27,392, PCI-/IHD- group). Kaplan-Meier analysis was used for comparisons.

Results: After propensity score matching, the PCI + group had better prognosis (n = 489 in both groups, hazard ratio 0.64, 95% confidence interval 0.51-0.81, P < 0.001) than the PCI-/IHD + group. PCI + patients (n = 282) had significantly higher mortality than those without IHD (n = 280 in each group, hazard ratio 2.88, 95% confidence interval 1.90-4.38, P < 0.001).

Conclusions: PCI might improve the long-term prognosis in cancer patients with IHD. However, these patients could have significantly worse long-term prognosis than cancer patients without IHD. Since the present study has some limitations, further research will be needed on this important topic in cardio-oncology.
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http://dx.doi.org/10.1186/s12872-021-01968-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045293PMC
April 2021

Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study.

Mol Clin Oncol 2021 Apr 8;14(4):65. Epub 2021 Feb 8.

Department of Medical Oncology, Osaka International Cancer Institute, Osaka Prefectural Hospital Organization, Osaka 541-8567, Japan.

The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.
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http://dx.doi.org/10.3892/mco.2021.2227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890436PMC
April 2021

A phase II study of the safety of olanzapine for oxaliplatin based chemotherapy in coloraectal patients.

Sci Rep 2021 Feb 25;11(1):4547. Epub 2021 Feb 25.

Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, Osaka, 541-8567, Japan.

Olanzapine has exhibited efficacy as an antiemetic agent when used with 5-HT receptor antagonists, dexamethasone, and NK receptor antagonists for patients receiving highly emetogenic chemotherapy. In addition, several studies have reported the efficacy or safety of olanzapine in patients receiving moderately emetogenic chemotherapy, including carboplatin, irinotecan, and oxaliplatin. However, no reports of olanzapine use have focused on patients receiving oxaliplatin-based chemotherapy. Therefore, we analyzed the safety of antiemetic therapy using olanzapine, palonosetron, aprepitant, and dexamethasone in colorectal cancer patients undergoing oxaliplatin-based chemotherapy. This study was a prospective phase II single-institution study of 40 patients (median age 60 years, 23 patients were male). The primary endpoint was the incidence of adverse events, and the exploratory endpoints were the rate of chemotherapy-induced nausea and vomiting. Almost all patients (90%) had a performance status of 0. All patients received the scheduled antiemetic therapy. The most common adverse event was somnolence (n = 7 patients, 17.5%). All adverse events were grade 1. Thirty-six patients were included in the exploratory analysis of efficacy. No patients experienced vomiting during the first 120 h after chemotherapy, and complete response and complete control were both 86.1%. The rate of total control was 55.6% during the same time period. Olanzapine use with 5-HT receptor antagonists, dexamethasone, and NK receptor antagonists was safe for colorectal cancer patients receiving oxaliplatin-based chemotherapy.
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http://dx.doi.org/10.1038/s41598-021-84225-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907185PMC
February 2021

Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease.

Sci Rep 2020 10 19;10(1):17647. Epub 2020 Oct 19.

Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Prevalence of sarcopenia is high in patients with chronic kidney disease (CKD), especially in those with dialysis. Various pathological conditions related to CKD, such as chronic inflammation, insulin resistance, and endothelial dysfunction, are thought to be associated with the development and progression of sarcopenia. Advanced glycation end products (AGE), one of the representative uremic toxins, have been shown to contribute to various CKD-associated complications. This study investigated the role of AGE in frailty and sarcopenia in patients and animals with CKD, respectively. In patients undergoing dialysis, serum AGE levels were significantly increased according to the frailty status and inversely associated with physical performance and activity. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD.
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http://dx.doi.org/10.1038/s41598-020-74673-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573579PMC
October 2020

Association of adipocytokines with peritoneal function.

Perit Dial Int 2021 01 17;41(1):79-85. Epub 2020 Jan 17.

Department of Nephrology, Graduate School of Medicine, 26367Nippon Medical School, Tokyo, Japan.

Background: Preservation of peritoneal function is crucial for the continuation of peritoneal dialysis (PD). A previous study suggested that blood cholesterol is involved in the preservation of peritoneal function; therefore, we determined whether adipocytokines can predict peritoneal function preservation.

Methods: Eighty patients were enrolled. Serum adiponectin, leptin, apelin, various blood components, and estimated glomerular filtration rate (eGFR) (mL/min/m) were measured. In addition, the duration of PD, presence or absence of peritonitis and diabetes mellitus, body mass index, urine output, peritoneal /, renal /, weekly /, peritoneal creatinine clearance rate (CCr), renal CCr, weekly CCr, use or nonuse of statin products, dialysate volume, glucose exposure, and use or nonuse of icodextrin dialysate were assessed. Peritoneal equilibration tests were performed at 6-month intervals, and dialysate-to-plasma [D/P] ratio and glucose uptake ratio [D/D] were measured. Associations of the baseline values and their percent changes with various adipocytokines and test items were evaluated.

Results: Multiple regression analyses identified adiponectin ( = 0.0392, = 0.0348) as a significant predictive factor of D/P and D/D ratios. eGFR was identified as a significant predictive factor ( = 0.015) of percent change in the D/P ratio. Apelin ( = 0.0484), high-density lipoprotein cholesterol ( = 0.0066), dialysate volume ( = 0.0223), and urine output ( = 0.0020) were identified as factors affecting the duration of PD.

Conclusions: Adipocytokines are a predictive factor of peritoneal function and the duration of PD in patients undergoing PD.
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http://dx.doi.org/10.1177/0896860819896133DOI Listing
January 2021

A case of female Fabry disease revealed by renal biopsy.

CEN Case Rep 2020 02 21;9(1):24-29. Epub 2019 Sep 21.

Department of Nephrology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Fabry disease (FD) is an X-linked inherited glycosphingolipid metabolism disorder, therefore, heterozygous female FD patients display highly variable clinical symptoms, disease severity, and pathological findings. This makes it very challenging to diagnosing female patients with FD. A 69-year-old Japanese female was introduced to the nephrologist for the evaluation of proteinuria. A renal biopsy was performed. Although the light microscopic examinations revealed that most of the glomeruli showed minor glomerular abnormalities, however, vacuolation was apparently found in the tubular epithelial cells. Immunofluorescence staining for globotriaosylceramide was positively detected in some podocytes and distal tubular epithelial cells. In addition, myelin-like structure (zebra body) was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, biochemical and genetic analysis confirmed the diagnosis of female FD. Enzyme replacement therapy was performed in conjunction with renin-angiotensin aldosterone system inhibitors and beta-blockers. The patient's family members received the analysis, and the same DNA missense mutation was detected in the patient's grandson. The enzyme replacement therapy was introduced to the grandson. The present case showed that renal biopsy can contribute towards a correct diagnosis for FD. Particularly, in female FD patients, careful examination of pathological changes is essential, for example, vacuolation of any type of renal cells may be a clue for the diagnosis.
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http://dx.doi.org/10.1007/s13730-019-00420-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990169PMC
February 2020

Aldehyde dehydrogenase 2 genotype in tolerability of alcohol contained in paclitaxel in Japanese breast cancer patients.

Breast Cancer 2019 Mar 22;26(2):229-234. Epub 2018 Oct 22.

Department of Clinical Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.

Background: Paclitaxel (PTX) is an essential anticancer drug used to treat breast cancer. Because it contains alcohol as a solvent, it is contraindicated in many Japanese breast cancer patients when they are suspected of alcohol intolerance. Aldehyde dehydrogenase 2 (ALDH2) is one of several enzymes that catalyzes dehydrogenation of aldehydes, and plays an important role in ethanol metabolism. Deficiency of this isozyme is believed to be responsible for facial flushing and other unpleasant symptoms following ethanol intake. In this study, we examined the safety of PTX for patients with the ALDH2 GA genotype.

Methods: We performed ALDH2 genotyping on 25 patients with various cancers who were suspected to be intolerant to alcohol based on an interview using a simple question. Ten patients with the ALDH2 GA genotype, including 5 breast cancer patients, underwent chemotherapy containing PTX up to 100 mg/m (range 80-100 mg/m), and were questioned about 16 alcohol-related symptoms at 11 timepoints to evaluate sensitivity to alcohol.

Results: All patients completed the first course of planned chemotherapy with either no or grade 1 alcohol-related symptoms.

Conclusions: Our study suggests that PTX up to 100 mg/m can be used safely for patients with the ALDH2 GA genotype. To confirm the necessity of a genotyping test for ALDH2, further studies evaluating alcohol sensitivity in response to PTX among patients with the ALDH2 AA genotype are required.
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http://dx.doi.org/10.1007/s12282-018-0918-9DOI Listing
March 2019

Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients.

JCI Insight 2018 10 4;3(19). Epub 2018 Oct 4.

Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.

Background: The PD-1-blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events.

Methods: To define the duration of binding and residual efficacy of nivolumab after discontinuation, we developed a simplified strategy for T cell monitoring and used it to analyze T cells from peripheral blood from 11 non-small cell lung cancer patients previously treated with nivolumab. To determine the suitability of our method for other applications, we compared transcriptome profiles between nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell monitoring in 2 nivolumab-treated patients who developed progressive lung tumors during long-term follow-up.

Results: Prolonged nivolumab binding was detected more than 20 weeks after the last infusion, regardless of the total number of nivolumab infusions (2-15 doses) or type of subsequent treatment, in 9 of the 11 cases in which long-term monitoring was possible. Ki-67 positivity, a proliferation marker, in T cells decreased in patients with progressive disease. Transcriptome profiling identified the signals regulating activation of nivolumab-bound T cells, which may contribute to nivolumab resistance. In 2 patients who restarted nivolumab, T cell proliferation markers exhibited the opposite trend and correlated with clinical response.

Conclusions: Although only a few samples were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T cells might help determine residual efficacy under various types of concurrent or subsequent treatment.

Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000024623.

Funding: This work was supported by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282, and JP15K09220), Japan Agency for Medical Research and Development (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for Evolutional Science and Technology (JPMJCR16G2).
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http://dx.doi.org/10.1172/jci.insight.59125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237460PMC
October 2018

Current Practice and Outcomes of Peritoneal Dialysis in the Nippon Medical School Musashi Kosugi Hospital.

J Nippon Med Sch 2018 ;85(2):102-109

Department of Nephrology, Graduate School of Medicine, Nippon Medical School.

Introduction: Various innovations for preventing complications and improving a patient's quality of life have been implemented for peritoneal dialysis (PD), which was established in Japan approximately 35 years ago and introduced at our hospital in 1999. Herein, we investigate the outcomes of patients undergoing PD to identify approaches for improving their long-term prognosis.

Methods: This retrospective study included 114 patients who underwent PD between September 1999 and August 2017 and included various parameters such as patient survival rate, technical survival rate, cause (s) of PD withdrawal, incidence of peritonitis, dialysis duration, and change in residual renal function (RRF). Furthermore, factors associated with PD withdrawal and duration, as well as risk factors for peritonitis, were examined.

Results: Mean (± standard deviation) PD duration was 35.62 (±29.88) months in all patients and 37.16 (±34.09) months in 58 patients who withdrew from treatment. Five-year continuance and survival rates were 40.41% and 55.74%, respectively (p=0.0061). However, in patients aged ≥65 years, the continuance and survival rates were not significantly different (p=0.1250). Furthermore, the continuance and survival rates in diabetic patients were not significantly different from those of non-diabetic patients (p=0.1334 and 0.7140, respectively). Comparison of changes in RRF in young and elderly patients revealed that it was not significantly sustained in elderly patients (p=0.0259). The Cox proportional hazards model revealed that age (p=0.0455) and total cholesterol levels (p=0.0494) were independent risk factors for PD withdrawal, and multiple regression analysis showed that the presence of peritonitis (p=0.0063) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.0087) were significant factors for PD duration. Peritonitis incidence was 0.077 times per patient per year, and multivariate analysis identified PD duration (p=0.0009) and LDL-C levels (p=0.0054) as independent risk factors for peritonitis.

Conclusion: The findings of this study revealed that assessment of the nutritional status of the patient and prevention of peritonitis are important for continuation of PD. PD is a safe treatment option that can maintain the quality of life in elderly patients. In a rapidly aging society, the need for PD-based medical care is expected to increase.
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http://dx.doi.org/10.1272/jnms.2018_85-16DOI Listing
August 2018

Phase II trial of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for untreated non-squamous non-small-cell lung cancer.

Cancer Chemother Pharmacol 2018 07 4;82(1):111-117. Epub 2018 May 4.

Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.

Purpose: We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods: Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m, days 1 and 8) plus pemetrexed (500 mg/m, day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity. The primary endpoint was the 1-year survival rate. The secondary endpoints were progression-free survival (PFS), overall survival (OS), response in induction phase, and safety.

Results: From February 2012 to September 2014, 53 assessable patients were enrolled in this study. Thirty-eight (71.7%) patients completed induction therapy, while 35 (66.0%) received maintenance therapy. The 1-year survival rate was 67.7%. The median PFS and OS were 5.3 and 18.6 months, respectively. The response rate and disease control rate (DCR) during the induction phase were 37.7 and 86.8%, respectively. Eight patients (15.1%) discontinued the therapy due to adverse events (AEs) during the induction phase, but both hematological and non-hematological AEs were infrequent.

Conclusions: Treatment with induction chemotherapy of pemetrexed plus split-dose cisplatin showed a promising 1-year survival rate, DCR, and transition rate into maintenance phase. This regimen is feasible and well-tolerated. A phase III study comparing this regimen with conventional tri-weekly regimen is warranted.
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http://dx.doi.org/10.1007/s00280-018-3598-4DOI Listing
July 2018

Quantitative pulmonary blood flow measurement using O-HO PET with and without tissue fraction correction: a comparison study.

EJNMMI Res 2017 Dec 22;7(1):102. Epub 2017 Dec 22.

Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita city, Osaka, Japan.

Background: Physiological measures per lung parenchyma, rather than per lung volume, sometimes reflect the disease status. PET images of the lung, which are usually expressed per lung volume, could confound the interpretation of the disease status, especially in cases with a prominent heterogeneity in aeration. The aim of the present study was to develop a method for measuring pulmonary blood flow (PBF) with aeration correction using O-HO PET and to compare the results with those obtained using a conventional method. We obtained the voxel-based tissue fraction (TF) derived from density images converted from transmission images obtained using an external Cs point source. Quantitative PBF values with and without the TF were calculated using O-HO PET to examine contralateral lung tissue in 9 patients with unilateral lung cancer. The heterogeneity in PBF before and after TF correction was then evaluated and compared. As a measure of PBF heterogeneity, we used the skewness and kurtosis of the PBF distribution.

Results: The mean PBF of contralateral lung was 1.4 ± 0.3 mL/min per mL of lung. The TF-corrected PBF was 5.0 ± 0.6 mL/min per mL of lung parenchyma. After TF correction, the skewness and kurtosis of the PBF decreased significantly.

Conclusions: The present PBF calculation method using TF correction demonstrated that the normal PBF increased significantly and the PBF distribution became uniform. The proposed TF correction method is a promising technique to account for variations in density when interpreting PBF in PET studies.
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http://dx.doi.org/10.1186/s13550-017-0350-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741573PMC
December 2017

Catalytic enantioselective aza-Diels-Alder reactions of unactivated acyclic 1,3-dienes with aryl-, alkenyl-, and alkyl-substituted imines.

Chem Commun (Camb) 2017 Aug;53(64):8996-8999

Department of Applied Chemistry, Osaka City University, Sumiyoshiku, Sugimotocho, Sugimoto, Osaka 558-8585, Japan.

A catalytic enantioselective aza-Diels-Alder reaction of unactivated acyclic dienes with aryl-, alkenyl-, and alkyl-substituted imines is described. With 5-10 mol% loadings of a new Brønsted acid catalyst, the aza-Diels-Alder reaction of unactivated acyclic dienes proceeded to give the corresponding aza-Diels-Alder adducts in high yields (up to 98%) with excellent enantioselectivity (up to 98% ee). Preliminary DFT calculations suggest that the reaction proceeds through a chiral ion pair intermediate.
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http://dx.doi.org/10.1039/c7cc03010jDOI Listing
August 2017

Evaluation of Natriuretic Peptide in Non-small Cell Lung Cancer Patients Treated with Bevacizumab Together with Carboplatin-Paclitaxel: A Prospective Study.

Anticancer Res 2017 07;37(7):3505-3512

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan

Aim: To identify predictive markers for efficacy of combination bevacizumab and carboplatin-paclitaxel treatment in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Patients And Methods: Twenty patients received carboplatin (area under the concentration-time curve (AUC) 6 mg/ml×min) and paclitaxel (200 mg/m) with bevacizumab (15 mg/kg) on day 1 of a 21-day cycle. After four cycles of induction therapy, patients received bevacizumab maintenance therapy until disease progression or unacceptable toxicity occurred. Plasma and serum samples (baseline, day 8 and before cycle 2) were analyzed for natriuretic peptide content.

Results: Plasma brain natriuretic peptide (BNP) levels were significantly decreased at day 8 (20.1±4.0 pg/ml vs. 9.1±1.8 pg/ml, p=0.0002). Patients whose plasma BNP level was reduced to <50% of the baseline at day 8 had a longer progression-free survival (PFS) than those with a less decrease (9.73 versus 2.63 months, p=0.00013). In multivariate Cox analysis, decrease of plasma BNP concentration was associated with a longer PFS (p=0.0022).

Conclusion: Decrease of plasma BNP concentration correlated with PFS after a treatment of combination bevacizumab plus carboplatin-paclitaxel.
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http://dx.doi.org/10.21873/anticanres.11718DOI Listing
July 2017

Trastuzumab emtansine suppresses the growth of HER2-positive small-cell lung cancer in preclinical models.

Biochem Biophys Res Commun 2017 07 17;488(4):596-602. Epub 2017 May 17.

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; AMED-CREST, Suita, Osaka, Japan.

Overcoming chemoresistance is essential for achieving better prognoses in SCLC. Previously, we reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated ADCC. However, irinotecan-resistant SCLC cells, such as SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we examined the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC. Treatment with T-DM1 significantly suppressed the growth of SBC-3/SN-38 xenografts in mice compared with trastuzumab (P < 0.05). Histological analysis of xenografts was performed to evaluate the therapeutic effect on apoptosis, proliferation and tumor vasculature. T-DM1 monotherapy induced apoptosis in SBC-3/SN-38 xenografts to a greater extent than trastuzumab monotherapy with the apoptotic index of 3.71 ± 1.56% vs. 0.60 ± 0.32% (P < 0.05), and also inhibited the proliferation of tumor cells compared with trastuzumab with the proliferative index of 74.30 ± 5.54% vs. 80.12 ± 4.81% (P < 0.05). On the other hand, no significant difference in micro vessel density was observed between the treatment groups. In vivo imaging using fluorescence-labeled T-DM1 showed that intravenously administered T-DM1 was rapidly delivered to xenografts and continued to accumulate for several days in a HER2-selective fashion. From these findings, delivery of the cytotoxic agent DM1 into cells via HER2-mediated internalization is expected to exert antitumor effect in such ADCC-lacking SCLC cells. Collectively, T-DM1 will be a promising option for overcoming trastuzumab-resistance in HER2-upregulated SCLC.
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http://dx.doi.org/10.1016/j.bbrc.2017.05.090DOI Listing
July 2017

Classification of idiopathic interstitial pneumonias using anti-myxovirus resistance-protein 1 autoantibody.

Sci Rep 2017 02 23;7:43201. Epub 2017 Feb 23.

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.

Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis. We identified disease-specific autoantibodies and enriched KEGG pathways unique to each disease, and demonstrated that IPF and INSIP are serologically distinct. Furthermore, we discovered a new INSIP-specific autoantibody, anti-myxovirus resistance-1 (MX1) autoantibody. Patients positive for anti-MX1 autoantibody constituted 17.5% of all cases of chronic fibrosing IIPs. Notably, patients rarely simultaneously carried the anti-MX1 autoantibody and the anti-aminoacyl-transfer RNA synthetase autoantibody, which is common in chronic fibrosing IIPs. Because MX1 is one of the most important interferon-inducible anti-viral genes, we have not only identified a new diagnostic autoantibody of INSIP but also obtained new insight into the pathology of INSIP, which may be associated with viral infection and autoimmunity.
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http://dx.doi.org/10.1038/srep43201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322336PMC
February 2017

Rapid intracranial response to osimertinib, without radiotherapy, in nonsmall cell lung cancer patients harboring the EGFR T790M mutation: Two Case Reports.

Medicine (Baltimore) 2017 Feb;96(6):e6087

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Japan.

Rationale: Most of nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) activating mutations eventually acquire resistance to the first EGFR-tyrosine kinase inhibitors (TKIs) therapy after varying periods of treatment. Of note, approximately one-third of those patients develop brain metastases, which deteriorate their quality of life and survival. The effect of systemic chemotherapy on brain metastases after acquisition of EGFR-TKI resistance is limited, and thus far, whole-brain radiation therapy, which may cause the harmful effect on neurocognitive functions, has been the only established therapeutic option for especially symptomatic brain metastases. Osimertinib is a third-generation oral, potent, and irreversible EGFR-TKI. It can bind to EGFRs with high affinity even when the EGFR T790M mutation exists in addition to the sensitizing mutations. Its clinical efficacy for NSCLC patients harboring the T790M mutation has already been shown; however, the evidence of osimertinib on brain metastases has not been documented well, especially in terms of the appropriate timing for treatment and its response evaluation.

Patient Concerns, Diagnoses, And Interventions: We experienced 2 NSCLC patients with the EGFR T790M mutation; a 67-year-old woman with symptomatic multiple brain metastases administered osimertinib as seventh-line chemotherapy, and a 76-year old man with an asymptomatic single brain metastasis administered osimertinib as fifth-line chemotherapy.

Outcomes: These patients showed great response to osimertinib within 2 weeks without radiation therapy.

Lessons: These are the first reports to reveal the rapid response of the brain metastases to osimertinib within 2 weeks. These cases suggest the possibility that preemptive administration of osimertinib may help patients to postpone or avoid radiation exposures. In addition, rapid reassessment of the effect of osimertinib on brain metastases could prevent patients from being too late to receive essential radiotherapy.
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http://dx.doi.org/10.1097/MD.0000000000006087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313025PMC
February 2017

Successful treatment with gefitinib after Stevens-Johnson syndrome associated with afatinib therapy in a patient with adenocarcinoma of the lung.

Int Cancer Conf J 2017 Jan 5;6(1):38-41. Epub 2016 Nov 5.

1Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 Japan.

We report a case of a 65-year-old woman with stage IV lung adenocarcinoma who experienced Stevens-Johnson syndrome (SJS) during afatinib therapy. The patient received afatinib as the first-line therapy after the confirmation of harboring an exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene. The patient presented with multiple erythematous papules mainly on the body trunk and thigh 32 days after afatinib administration. Subsequently, diffuse erosions of oral mucosa and purpuric macules with flat atypical targets emerged. Skin biopsy specimen showed the histology compatible with epidermal necrosis and the patient was diagnosed as having SJS. The symptoms of SJS were recovered by systemic steroid and immunoglobulin treatment. Gefitinib was administered as the third-line therapy after the second-line therapy with carboplatin plus pemetrexed had failed. Tumor shrinkage was obtained shortly and has been maintained without the recurrence of SJS. Rechallenge of tyrosine kinase inhibitor by gefitinib could be an alternative treatment option in patients who experienced SJS by afatinib.
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http://dx.doi.org/10.1007/s13691-016-0269-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498331PMC
January 2017

A Case of Cryoglobulinemic Membranoproliferative Glomerulonephritis Induced by Hepatitis C Virus.

J Nippon Med Sch 2015 ;82(4):193-201

Department of Nephrology, Nippon Medical School Musashi Kosugi Hospital.

A 61-year-old man with bilateral purpura of the lower limbs and subsequent edema, was hospitalization after renal dysfunction developed. The presence of hepatitis C virus (HCV) RNA and cryoglobulin and the finding of membranoproliferative glomerulonephritis on renal biopsy led to a diagnosis of HCV-related glomerulonephritis due to cryoglobulinemia. Because of the pre-existence of nephrotic syndrome and the continuously increasing serum level of creatinine, treatment with cryofiltration, interferon, and steroids was started. After 5 cryofiltration sessions, the cryocrit level had decreased to 1% and the levels of serum creatinine and proteinuria had also decreased. However, 3 weeks after the start of treatment, nephrotic syndrome developed again and was accompanied by lower-extremity mononeuropathy and renal dysfunction. Thereafter, the patient showed disorientation, an affective disorder, and delirium, and his condition gradually deteriorated. Radiological examination of the head and examination of the cerebrospinal fluid showed no abnormalities. Despite the withdrawal of the interferon therapy and the reduction of the steroid dose, the patient's conditions remained unchanged, and the level of consciousness deteriorated. Although cryofiltration had beneficial effects and plasma exchange was continuously performed, the patient died on the 74th hospital day. Because of the significant changes due to ventilatory support and hemorrhage associated with disseminated intravascular coagulation, the autopsy findings did not allow us to definitively determine whether the symptoms had been caused by the HCV-related membranoproliferative glomerulonephritis or the interferon therapy or both. We have reported this case to provide insight into whether interferon therapy should be administered for HCV-related membranoproliferative glomerulonephritis with marked neurological symptoms due to cryoglobulinemia.
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http://dx.doi.org/10.1272/jnms.82.193DOI Listing
April 2016

Evaluation of Bone Metastasis Using Serial Measurements of Serum N-Telopeptides of Type I Collagen in Patients with Lung Cancer: A Prospective Study.

Anticancer Res 2015 Jul;35(7):3987-93

Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.

Background/aim: The bone resorption biomarker cross-linked N-Telopeptides of type I collagen (NTx) has been shown to aid in the diagnosis of metastatic bone disease from lung cancer (MBDLC). Patients with MBDLC are often treated with zoledronic acid (ZA). ZA reduces the levels of NTx and also lowers the risk of skeletal adverse events in patients with MBDLC.

Patients And Methods: Patients with MBDLC at initial diagnosis were included in the study. NTx was measured in serum (sNTx) once a month using the OSTEOMARKTM sNTx assay. MBDLC was assessed by monthly physical examinations and bone scintigraphy every 3 months for 12 months.

Results: Twenty patients were enrolled between June and December 2010. The sNTx concentration at baseline was 19.8 ± 5.8 nmol bone collagen equivalents (nmol BCE)/l. In the 16 patients receiving ZA, the level of sNTx significantly decreased after the first month of treatment (baseline vs. 1 month of treatment: 21.3 ± 5.5 vs. 13.6 ± 2.7 nmol BCE/l; p<0.01). During the follow-up period, 13 of the patients treated with ZA experienced worsening of bone metastasis. There were statistically significant differences in the levels of sNTx at baseline (20.3 ± 4.8 nmol BCE/l), at the lowest levels after administration of ZA (11.8 ± 2.9 nmol BCE/l vs. baseline; p<0.001), and at the time of measurable disease progression (14.1 ± 4.6 nM BCE/l vs. baseline; p<0.05).

Conclusion: Serial measurements of sNTx in patients with MBDLC treated with ZA may effectively predict disease progression.
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July 2015

Effectiveness of Tyrosine Kinase Inhibitors in Japanese Patients with Non-small Cell Lung Cancer Harboring Minor Epidermal Growth Factor Receptor Mutations: Results from a Multicenter Retrospective Study (HANSHIN Oncology Group 0212).

Anticancer Res 2015 Jul;35(7):3885-91

Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.

Aim: Non-small cell lung cancer (NSCLC) with minor mutations in the epidermal growth factor receptor (EGFR) gene, except for the common 15 base-pair deletions in exon 19 and the L858R mutation in exon 21, is rare, and only few data exist on this patient population. The aim of the present study was to describe the clinical characteristics and to clarify the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in patients with NSCLC harboring minor mutations of the EGFR gene.

Patients And Methods: This was a multicenter, retrospective study that analyzed specimens from patients with NSCLC who had minor EGFR gene mutations and were treated with EGFR-TKIs between June 2002 and March 2012.

Results: Out of 56 patients with minor mutations of the EGFR gene, 44 were treated with either gefitinib or erlotinib. Mutation sites were G719X in exon 18 (n=35), L861Q in exon 21 (n=11), and G874S in exon 21 (n=1). Three patients had both the G719S and the L861Q mutation. The response rate to TKI treatment was 29.5%, and the disease control rate was 63.6%. The median progression-free survival (PFS) was 6.7 months [95% confidence interval (CI)=2.06-8.66 months]. The median PFS was 7.2 months (95% CI=4.23-12.3 months) in 32 patients who received first- or second-line treatment with EGFR-TKIs, whereas the median PFS was 1.57 months (95% CI=0.73-3.8 months) in 12 patients treated with EGFR-TKIs as a third-line or later treatment. In multivariate Cox analysis, erlotinib therapy was associated with a longer PFS than gefitinib (p=0.025).

Conclusion: Patients with NSCLC harboring minor mutations of the EGFR gene exhibited a modest response to EGFR-TKI treatment. Treatment with first-generation EGFR-TKIs, in particular erlotinib, may be considered a first- or second-line option for patients with NSCLC with minor EGFR mutations.
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July 2015

Nuclear survivin expression in small cell lung cancer.

Anticancer Res 2015 May;35(5):2935-9

Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Osaka, Japan.

Background/aim: Little evidence exists regarding a relationship between survivin expression and prognosis in small cell lung cancer (SCLC). We investigated the relationship between survivin expression, clinical characteristics and prognosis in SCLC patients.

Materials And Methods: We retrospectively reviewed medical records of study patients and analyzed their tumor sections using nuclear survivin labeling index (LI).

Results: A significant correlation between nuclear survivin LI and clinical stage was found (p=0.012). In multivariate analysis, a significant association was found between survival and clinical stage (hazard ratio (HR)=2.09; 95 % confidence interval (CI)=1.08-4.31; p=0.027) but not between survival and nuclear survivin LI (HR=0.96; 95 % CI=0.91-1.02; p=0.2).

Conclusion: We did not find any positive relationship between nuclear survivin expression and survival in SCLC patients. Conversely, we found a positive relationship between clinical stage and nuclear survivin LI, which is considered to be useful in deciding treatment strategies.
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May 2015

Comparison of pain and efficacy of darbepoetin alfa and epoetin Beta pegol treatment in patients receiving peritoneal dialysis.

J Nippon Med Sch 2015 ;82(1):21-6

Department of Nephrology, Nippon Medical School Musashi Kosugi Hospital.

Background: Sustained erythropoiesis-stimulating agents (ESAs) have recently been identified as the standard therapeutic agent for anemia in patients undergoing peritoneal dialysis (PD). However, few reports have compared pain between various types of sustained ESAs or between administration routes. Furthermore, the change ratio of the dose of sustained ESAs reportedly ranges from 0.8 to 1.3. In the present study, to compare darbepoetin alfa and epoetin beta pegol (a continuous erythropoietin receptor activator [CERA]), we examined the dolorific differences between administration routes and the effect on anemia by using a chjange ratio of 0.8 with darbepoetin alfa in patients with renal anemia undergoing PD.

Subjects And Method: We randomly assigned 20 patients with stable hemoglobin levels undergoing PD to either a darbepoetin alfa therapy group or a CERA therapy group. Based on a previous report, the change ratio of the CERA group from CERA to darbepoetin alfa therapy was assumed to be 0.8, and therapy was crossed-over to darbepoetin alfa again 2 months later. The dolorific evaluation (pain measurement) used both a face scale and a visual analogue scale. We compared the agents as well as administration routes with respect to pain. We also measured variables related to anemia and iron metabolism.

Results: The change ratio of the CERA group at the start of the study was 0.821. On resumption of darbepoetin alfa therapy 2 months later, the doses of darbepoetin alfa increased. The darbepoetin alfa group showed a stronger tendency for pain, although the difference was not significant. In contrast, subcutaneous administration in the CERA group showed significant pain just after injection. The CERA group, however, showed a significant decrease in hemoglobin levels after 2 months of treatment (p=0.0489). No significant change was found in the hematocrit or the reticulocyte count. There were no significant differences in iron metabolism, as shown by serum iron levels and total iron-binding capacity, in either group. However, serum ferritin levels showed a tendency to decrease in the darbepoetin alfa group.

Conclusion: No significant difference in pain was found between darbepoetin alfa and CERA therapies, but a significant difference in pain was noted between administration routes, just after injection, in the CERA group. The results also suggest that a change ratio of 0.8 from darbepoetin alfa to CERA is low for managing anemia.
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http://dx.doi.org/10.1272/jnms.82.21DOI Listing
March 2016

Favorable response to trastuzumab plus irinotecan combination therapy in two patients with HER2-positive relapsed small-cell lung cancer.

Lung Cancer 2015 Mar 10;87(3):321-5. Epub 2015 Jan 10.

Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan; Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.

Small-cell lung cancer (SCLC) easily recurs with multidrug resistance phenotype. However, standard therapeutic strategies for relapsed-SCLC remain unestablished. Human epidermal growth factor receptor 2 (HER2) expression correlates with poor prognosis in extensive disease-SCLC. We have reported previously that HER2 expression is upregulated when HER2-positive SCLC cells acquire chemoresistance, and also demonstrated that trastuzumab exerts significant antitumor activity toward HER2-upregulated chemoresistant SCLC, mainly via antibody-dependent cell-mediated cytotoxicity mechanism. Based on these preclinical data, we treated two patients with HER2-positive SCLC by combination of trastuzumab (6 mg/kg, day 1) and irinotecan (80 mg/m(2), days 1 and 8) every 21 days as the third-line chemotherapy following two prior regimens, first-line carboplatin plus etoposide and second-line amrubicin. One patient achieved partial response after the first cycle and received 6 cycles in total without disease progression for 4.5 months. The other also received 4 cycles and kept stable disease for 3.5 months. This treatment can be continued safely at an outpatient clinic without any severe adverse event. In conclusion, trastuzumab plus irinotecan chemotherapy is promising and feasible against HER2-positive relapsed SCLC. Further clinical studies are encouraged to confirm the antitumor efficacy of trastuzumab in SCLC.
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http://dx.doi.org/10.1016/j.lungcan.2015.01.003DOI Listing
March 2015

A case of neuromyelitis optica spectrum disorder with early successful induction of double filtration plasmapheresis.

Ther Apher Dial 2014 Jun;18(3):317-8

Department of Nephrology, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan.

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http://dx.doi.org/10.1111/1744-9987.12216DOI Listing
June 2014

Clinical benefit of the change of dialysate calcium concentration from 3.0 to 2.75 mEq/L.

Ther Apher Dial 2014 Apr;18(2):181-4

Division of Nephrology, Department of Internal Medicine, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan.

Because active vitamin D preparations and calcimimetics have been widely used to treat secondary hyperparathyroidism, maintenance of acceptable serum calcium and phosphate levels is important. A 2.75 mEq/L dialysate calcium product, which may bring the calcium balance closer to 0, has recently been launched, and we had an opportunity to examine its possible benefits. We performed a 6-month retrospective review after switching from 3.0 mEq/L to 2.75 mEq/L calcium dialysate in 85 outpatients undergoing chronic hemodialysis. We evaluated blood biochemical parameters, including predialysis and postdialysis serum calcium and phosphate levels, predialysis intact parathyroid hormone (iPTH) levels; dialysis dose (Kt/V); and doses of concomitant active vitamin D preparations, calcimimetics, phosphate binder, and erythropoiesis-stimulating agents. Postdialysis calcium levels were significantly lower and predialysis corrected calcium levels significantly decreased. The change in calcium levels before and after dialysis was smaller after switching of the dialysate than before. iPTH levels significantly increased 1 month after switching of the dialysate. No remarkable changes were observed in phosphate levels or Kt/V. The dose of alfacalcidol, one of the concomitant drugs, somewhat increased, and no remarkable changes in dosage were observed for other concomitant drugs. These results were favorable in terms of calcium balance. However, there may be limitations in interpreting the results, but the resultant calcium levels suggest that switching to 2.75 mEq/L calcium dialysate may improve the control of calcium levels. In addition, it is hoped that the treatment choice of secondary hyperparathyroidism is extended.
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http://dx.doi.org/10.1111/1744-9987.12099DOI Listing
April 2014
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