Publications by authors named "Masanori Nishikawa"

55 Publications

Efficacy and safety of carboplatin and pemetrexed followed by maintenance with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer: A single-arm, open-label, multicenter, phase II study.

Asia Pac J Clin Oncol 2021 Feb 10. Epub 2021 Feb 10.

Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Purpose: Carboplatin plus pemetrexed followed by maintenance pemetrexed is expected to be well-tolerated by the elderly. This multicenter, prospective study examined the efficacy and tolerability of the regimen in elderly patients with previously untreated advanced non-squamous non-small cell lung cancer.

Methods: The primary endpoint was the 1-year survival rate, with secondary endpoints of response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse event rate. Efficacy was compared between patients with performance status (PS) 0 and 1.

Results: Forty-one patients were enrolled between March 2011 and April 2016. Median age was 76.0 years. The 1-year survival rate was 73% (95% confidence interval (CI), 56-84%). RR was 44%, DCR was 81%, median PFS was 7.2 months (95%CI, 3.98-9.20 months), and median OS was 17.4 months (95%CI, 13.60-22.83 months). Twenty-one patients (51%) transitioned to maintenance therapy. Toxicities of grade ≥ 3 during the induction phase included anemia (37%), thrombocytopenia (29%), neutropenia (22%), appetite loss (15%), nausea (10%), bacterial pneumonia (7%), febrile neutropenia (5%), and interstitial pneumonia (2%). Treatment was discontinued in two patients with interstitial pneumonia, but no deaths were encountered. During the maintenance phase, one patient needed dose reductions due to phlegmon. No significant difference in efficacy was seen between PS 0 and PS 1.

Conclusion: Carboplatin and pemetrexed followed by maintenance pemetrexed for non-squamous non-small cell lung cancer in elderly patients appear effective and tolerable.
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http://dx.doi.org/10.1111/ajco.13488DOI Listing
February 2021

Ultrasound findings for spontaneous regression of omphalomesenteric remnant after birth.

J Clin Ultrasound 2020 Dec 1. Epub 2020 Dec 1.

Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.

We report a rare case of spontaneous regression of omphalomesenteric remnant after birth. Unlike previously reported cases, no surgery was required. The omphalomesenteric duct sometimes persists at birth. Its regression after birth, however, is extremely rare. A neonate passed a bloody stool 3 minutes after birth. Meckel's scan detected slight technetium-99 m uptake around the umbilicus. Sonographic examination detected a luminal structure connected to the small bowel, which gradually regressed, however, and was no longer visible by the 52nd day after birth. Careful follow-up is required after occurrence of bloody stool and intestinal obstruction from Meckel's diverticulum.
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http://dx.doi.org/10.1002/jcu.22957DOI Listing
December 2020

Survey of the current status of subclinical coronavirus disease 2019 (COVID-19).

J Infect Chemother 2020 Dec 6;26(12):1294-1300. Epub 2020 Sep 6.

Kanagawa Physicians Association, Japan.

Objectives: We investigated relationships between subclinical COVID-19 (coronavirus disease 2019) and background factors.

Methods: We determined SARS-CoV-2 antibody (IgG) prevalence in 1603 patients, doctors, and nurses in 65 medical institutions in Kanagawa Prefecture, Japan and investigated their background factors. Antibodies (IgG) against SARS-CoV-2 were analyzed by Immunochromatographic test.

Results: The 39 subjects (2.4%) were found to be IgG antibody-positive: 29 in the patient group (2.9%), 10 in the doctor/nurse group (2.0%), and 0 in the control group. After adjustment for age, sex, and the antibody prevalence in the control group, antibody prevalence was 2.7% in the patient group and 2.1% in the doctor/nurse group. There was no significant difference between the antibody-positive subjects and the antibody-negative subjects in any background factors investigated including overseas travel, contact with overseas travelers, presence/absence of infected individuals in the living area, use of trains 5 times a week or more, BCG vaccination, and use of ACE inhibitor and ARB.

Conclusions: Antibody prevalence in the present survey at medical institution is higher than that in Tokyo and in Osaka measured by the government suggesting that subclinical infections are occurring more frequently than expected. No background factor that influenced antibody-positive status due to subclinical infection was identified.
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http://dx.doi.org/10.1016/j.jiac.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474902PMC
December 2020

Epilepsy in patients with advanced Fukuyama congenital muscular dystrophy.

Brain Dev 2021 Jan 25;43(1):106-110. Epub 2020 Jul 25.

Department of Pediatric Neurology, Osaka Women's and Children's Hospital, Japan.

Background: Recent advances in respiratory management have improved survival for patients with Fukuyama congenital muscular dystrophy (FCMD), characterized by congenital muscular dystrophy and brain malformation. Previous studies reported that more than half of patients exhibit seizures in childhood. However, little is known about epilepsy after childhood.

Methods: To elucidate the long-term clinical course of epilepsy, we retrospectively reviewed all medical records in nine patients (6 males, mean age 20.7 years) with FCMD diagnosed between 1981 and 2019.

Results: The follow-up periods ranged from 6 to 30 years (mean 18.4 years). A total of 75 EEG recordings were available from nine patients. In some patients, EEGs were normal during early childhood but tended to show paroxysmal discharges with age. Overall, epileptic seizures were observed in six patients. Except for one presenting with afebrile seizure at one year of age, the remaining five patients developed epilepsy between 13 and 22 years of age. The most common seizure type was focal impaired awareness seizure. After adolescence, four patients exhibited status epilepticus. Their convulsive movements of the seizures became less prominent with progression of the disease. At the last evaluation, most patients (5/6) had uncontrolled seizures.

Conclusions: Despite presence of distinct brain malformation, epileptic seizures may develop after childhood in FCMD patients. Our experience suggests that clinicians should be careful not to overlook epileptic seizures, especially in advanced-stage patients who had profound muscle weakness.
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http://dx.doi.org/10.1016/j.braindev.2020.06.017DOI Listing
January 2021

Prenatally diagnosed congenital hemangioma with elevated middle cerebral artery peak systolic velocity mimicking the Kasabach-Merritt phenomenon: A case report.

J Obstet Gynaecol Res 2019 Dec 9;45(12):2456-2460. Epub 2019 Sep 9.

Department of Maternal Fetal Medicine, Osaka Women's and Children's Hospital, Osaka, Japan.

Congenital hemangioma is a rare vascular tumor that develops prenatally, and a large congenital hemangioma may be accompanied by the Kasabach-Merritt phenomenon. We present a case of prenatally diagnosed fetal congenital hemangioma through ultrasound and maternal anti-Jr(a) antibody alloimmunization with elevated middle cerebral artery peak systolic velocity. To investigate fetal anemia and hemostatic condition, we performed percutaneous umbilical blood sampling, which revealed no symptom of either Kasabach-Merritt phenomenon or sensitization to anti-Jr(a) antibody. Consequently, pregnancy could be continued without further intervention. After birth, congenital hemangioma was found on the infant's left thigh, and Kasabach-Merritt phenomenon was not shown. Percutaneous umbilical blood sampling could provide precise information prenatally in case of congenital hemangioma with maternal alloimmunization.
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http://dx.doi.org/10.1111/jog.14121DOI Listing
December 2019

Multicenter study of zoledronic acid administration in non-small-cell lung cancer patients with bone metastasis: Thoracic Oncology Research Group (TORG) 1017.

Mol Clin Oncol 2019 Oct 23;11(4):349-353. Epub 2019 Jul 23.

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Kanagawa 240-8555, Japan.

Skeletal-related events (SREs) may occur at the time of first diagnosis in 20-30% of lung cancer patients with bone metastases. Several clinical trials have shown that zoledronic acid (ZA) is effective for decreasing SREs. The main objective of the present study was to discuss clinical data of ZA and compare the frequency of SREs with previous reports. All patients with non-small-cell lung cancer (NSCLC) with metastatic bone disease who were administered ZA at least twice between January 2008 and December 2009 were eligible for inclusion in the study. In total, 198 consecutive patients were identified. The median duration of ZA administration was 106 days [95% confidence interval (CI), 92-133 days], and the median number of ZA administrations was 4 (range, 2-41). The median time to first SRE in patients who experienced SRE following ZA treatment was 202 days (95% CI, 156-264 days). Among the 78 patients who had already experienced SRE prior to ZA treatment, 35 (45%) experienced SRE subsequently after starting ZA treatment. On the other hand, among the 120 patients without a history of SRE before starting ZA treatment, 42 (35%) experienced SRE after the start of ZA administration (P=0.16). No osteonecrosis of the jaw (ONJ) was reported in any of the patients. The present study revealed that ZA had a certain level of efficacy regardless of the presence or absence of prior SREs. However, the duration of ZA therapy was short in this study; further accumulation of data on the long-term prognosis and incidence rates of ONJ and other late complications of ZA therapy seems to be particularly important.
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http://dx.doi.org/10.3892/mco.2019.1903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713944PMC
October 2019

Asthma control and quality of life in a real-life setting: a cross-sectional study of adult asthma patients in Japan (ACQUIRE-2).

J Asthma 2019 Sep 25;56(9):1016-1025. Epub 2018 Sep 25.

e Airway Institute in Sendai , Sendai , Japan.

: The level of asthma control in adult asthma patients receiving treatment in clinical practice from allergy and/or respiratory specialists in Japan remains unclear. We conducted the ACQUIRE-2 study (NCT02640742) to evaluate level of asthma control, asthma symptoms, health-related quality of life (HR-QoL), and reliever medication use in this setting. : This observational study was undertaken between December 2015 and June 2016 in 58 medical institutions across Japan. We enrolled outpatients aged ≥20 years diagnosed with asthma for ≥1 year who were being managed by specialists. Criteria to evaluate the level of asthma control were based on modified definitions of the Asthma Prevention and Management Guideline 2015, Japan (JGL 2015) and Global Initiative for Asthma (GINA) 2012. Asthma symptoms, HR-QoL, and reliever medication use were also evaluated. : Of 1250 enrolled patients, 1175 were analyzed, 62.9% of whom were women. Mean (± standard deviation) age and duration of asthma were 59.7 ± 14.5 years and 16.9 ± 14.0 years, respectively. Using JGL 2015-based criteria, 24.4%, 69.2%, and 6.5% of patients had well-controlled, insufficiently-controlled, and poorly-controlled asthma, respectively. Using GINA-based criteria, 35.1%, 49.8%, and 15.1% of patients had controlled, partly controlled, and uncontrolled asthma, respectively. Daytime and nighttime asthma symptoms were experienced by 51.5% and 44.9% of patients, respectively. The mean MiniAQLQ score was 5.8 ± 1.0 (7-point scale). : Asthma was not well-controlled in the majority of patients in this study. To achieve better asthma control, improvements in symptom monitoring and management may be required.
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http://dx.doi.org/10.1080/02770903.2018.1514628DOI Listing
September 2019

Phase II study of bevacizumab, cisplatin, and docetaxel plus maintenance bevacizumab as first-line treatment for patients with advanced non-squamous non-small-cell lung cancer combined with exploratory analysis of circulating endothelial cells: Thoracic Oncology Research Group (TORG)1016.

BMC Cancer 2018 03 2;18(1):241. Epub 2018 Mar 2.

Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Background: Preclinical studies have demonstrated that docetaxel and bevacizumab may act synergistically by decreasing endothelial cell proliferation and preventing circulating endothelial progenitor mobilization. The objective of this study was to assess the efficacy and safety of a combination therapy of bevacizumab, cisplatin, and docetaxel in chemotherapy-naive Japanese patients with advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods: Eligible patients were chemotherapy-naive and had advanced/recurrent non-squamous NSCLC. The patients received 4 cycles of docetaxel (60 mg/m), cisplatin (80 mg/m), and bevacizumab (15 mg/kg) once every 3 weeks, followed by bevacizumab as maintenance therapy, every 3 weeks until disease progression or attainment of unacceptable toxicity level. The primary endpoint was objective response rate (ORR). The numbers of circulating endothelial cells (CEC) were also estimated on days 1 and 8 of the first cycle for the exploratory analysis of efficacy prediction.

Results: A total of 47 patients were enrolled from October 2010 to April 2012. Bevacizumab as maintenance therapy was administered to 41 patients (87.2%), and the median number of total treatment cycles was 9 (range: 1-36). ORR, median progression-free survival (PFS), and median overall survival of the patients were 74.5%, 9.0 months, and 27.5 months, respectively. The most common grade 3/4 adverse event was neutropenia (95.7%), followed by leukopenia (59.6%) and hypertension (46.8%). PFS was longer in patients with ≥10 count increase in CECs than that in patients with < 10 count increase in CECs (respective median PFS of 11.0 months versus 6.90 months) although the difference was not statistically significant (p = 0.074).

Conclusions: A combination therapy of bevacizumab, cisplatin, and docetaxel, followed by bevacizumab as maintenance was highly effective in patients with non-squamous NSCLC despite the high incidence of grade 3/4 neutropenia. The increase in CEC count between days 1 and 8 may predict the efficacy of our bevacizumab-contained treatment regimen.

Trial Registration: UMIN Clinical Trial Registry; UMIN000004368 . Registered date; October 11, 2010 (Retrospectively registered).
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http://dx.doi.org/10.1186/s12885-018-4150-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833040PMC
March 2018

A Soup Service for Advanced Digestive Cancer Patients with Severe Anorexia in Palliative Care.

J Palliat Med 2018 03 27;21(3):380-382. Epub 2017 Nov 27.

3 Department of Nutrition, Kyoto Second Red Cross Hospital , Kyoto, Japan .

Background/aims: The palliative care team (PCT), nutrition support team (NST), and department of nutrition in our hospital developed a special soup service for patients with terminal cancer. We evaluated the usefulness of this soup service for improving the mood in patients with advanced digestive cancer with severe anorexia.

Material And Methods: We retrospectively reviewed the clinical data of 18 patients with advanced cancer originating in digestive organs who received soup service at our institution between 2015 and 2016. Members of the PCT, NST, and a licensed cook visited the bedside of each patient and served them a cup of soup twice a week.

Results: Fifteen patients (83%) were able to taste the soup with no adverse events, and 11 (73%) of them enjoyed the taste of the soup. In the five patients who died in our hospital during the service, the time between their last soup intake and death ranged from two to seven days (median three days).

Conclusion: Even terminally ill patients suffering from advanced digestive cancer with severe anorexia were able to enjoy the taste of the soup served to them. The establishment of special meal service, such as this soup service, may not only relieve their stress but also support the strength of living and help improve their spiritual quality of life.
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http://dx.doi.org/10.1089/jpm.2017.0369DOI Listing
March 2018

A de novo microdeletion in a patient with inner ear abnormalities suggests that the 10q26.13 region contains the responsible gene.

Hum Genome Var 2016 19;3:16008. Epub 2016 May 19.

Tokyo Women's Medical University Institute for Integrated Medical Sciences , Tokyo, Japan.

Microdeletions in the 10q26.1 region are related to intellectual disability, growth delay, microcephaly, distinctive craniofacial features, cardiac defects, genital abnormalities and inner ear abnormalities. The genes responsible for inner ear abnormalities have been narrowed to fibroblast growth factor receptor 2 gene (FGFR2), H6 family homeobox 2 gene (HMX2) and H6 family homeobox 3 gene (HMX3). An additional patient with distinctive craniofacial features, congenital deafness and balance dysfunctions showed a de novo microdeletion of 10q26.11q26.13, indicating the existence of a gene responsible for inner ear abnormalities in this region.
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http://dx.doi.org/10.1038/hgv.2016.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871931PMC
June 2016

Problems of elderly patients on inhalation therapy: Difference in problem recognition between patients and medical professionals.

Allergol Int 2016 Oct 5;65(4):444-449. Epub 2016 May 5.

Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan.

Background: There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals.

Methods: A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed.

Results: According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy.

Conclusions: Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.
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http://dx.doi.org/10.1016/j.alit.2016.04.002DOI Listing
October 2016

Can neoadjuvant chemotherapy reduce the surgical risks for localized neuroblastoma patients with image-defined risk factors at the time of diagnosis?

Pediatr Surg Int 2016 Mar 13;32(3):209-14. Epub 2016 Jan 13.

Pediatric Surgery, Graduate School of Medicine, Osaka University, 1-1 Yamadaoka, Suita, 565-0871, Osaka, Japan.

Purpose: To date, no detailed study of the changes in the image-defined risk factors (IDRFs) after neoadjuvant chemotherapy has been performed. The aim of this study was to investigate the effect of chemotherapy on IDRFs for stage L2 neuroblastomas.

Methods: Fifteen stage L2 patients treated by neoadjuvant chemotherapy were selected. Changes after chemotherapy in the number of positive IDRFs, tumor size and major surgical complications were evaluated.

Results: All IDRFs disappeared after chemotherapy in four patients (group A) and a reduction in the number of IDRFs, but not disappearance, after chemotherapy was observed in five patients (group B). No change in the number of IDRFs after chemotherapy was observed in six patients (group C). All tumors in groups A shrunk to <20 % of the pretreatment volume. Major surgical complications were observed in one of two, two of three and three of five patients who underwent tumor excision in groups A, B and C, respectively.

Conclusions: Only 27 % of the tumors with IDRFs became negative for IDRFs after chemotherapy. For negative IDRFs, tumors should shrink to <20 % of the volume at the time of diagnosis. Stage L2 tumors may have a potential risk for surgery even after neoadjuvant chemotherapy.
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http://dx.doi.org/10.1007/s00383-016-3858-5DOI Listing
March 2016

Can Image-Defined Risk Factors Predict Surgical Complications in Localized Neuroblastoma?

Eur J Pediatr Surg 2016 Feb 3;26(1):117-22. Epub 2015 Nov 3.

Department of Paediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Introduction: Image-defined risk factors (IDRFs) have been propounded for predicting the surgical risks associated with localized neuroblastoma (NB) since 2009. In 2011, a new guideline (NG) for assessing IDRFs was published. According to the NG, the situation in which "the tumor is only in contact with renal vessels," should be considered to be "IDRF-present." Previously, this situation was diagnosed as "IDRF absent." In this study, we evaluated the IDRFs in localized NB patients to clarify the predictive capability of IDRFs for surgical complications, as well as the usefulness of the NG. Materials and

Methods: A total of 107 localized patients with NB were included in this study. The enhanced computed tomography and magnetic resonance images from the time of their diagnoses were evaluated by a single radiologist. We also analyzed the association of clinical factors, including the IDRFs (before and after applying the NG), with surgical complications.

Results: Of the 107 patients, 33 and 74 patients were diagnosed as IDRF-present (OP group), and IDRF-absent (ON group) before the NG, respectively. According to the NG, there were 76 and 31 patients who were classified as IDRF-present (NP group) and IDRF absent (NN group), respectively. Thus, 43 (40%) patients in the ON group were reassigned to the NP group after the NG. Surgical complications were observed in 17 of 82 patients who underwent surgical resection. Of the patients who underwent secondary operations, surgical complication rates were 55% in the OP group and 44% in the NP group. According to a univariate analysis, non-INSS 1, IDRFs before and after the NG and secondary operations were significantly associated with surgical complications. In a multivariate analysis, non-INSS 1 status and IDRFs after the NG were significantly associated with surgical complications.
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http://dx.doi.org/10.1055/s-0035-1566100DOI Listing
February 2016

Feasibility of Cancer Immunotherapy with WT1 Peptide Vaccination for Solid and Hematological Malignancies in Children.

Pediatr Blood Cancer 2016 Feb 15;63(2):234-41. Epub 2015 Oct 15.

Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.

Background: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies.

Methods: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times.

Results: Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission.

Conclusions: WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.
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http://dx.doi.org/10.1002/pbc.25792DOI Listing
February 2016

Congenital optic tract hypoplasia.

J AAPOS 2015 Aug 27;19(4):383-5. Epub 2015 Jul 27.

Paediatric Ophthalmology, Institute of Child Health, University College London.

We report a case of isolated unilateral optic tract hypoplasia, described only twice previously. Bilateral optic disk hypoplasia was seen ophthalmoscopically and visual field studies showed an incongruous right homonymous hemianopia. Magnetic resonance imaging showed bilateral hypoplasia of both optic nerves and the left optic tract. Spectral domain optical coherence tomography mapping correlated well with the visual field studies.
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http://dx.doi.org/10.1016/j.jaapos.2015.03.018DOI Listing
August 2015

A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911.

Eur J Cancer 2015 Sep 11;51(14):1904-10. Epub 2015 Jul 11.

Thoracic Oncology Research Group, Kanagawa, Japan.

Background: Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene.

Methods: Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d.

Results: Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes.

Conclusion: The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
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http://dx.doi.org/10.1016/j.ejca.2015.06.120DOI Listing
September 2015

Perinatal factors associated with long-term respiratory sequelae in extremely low birthweight infants.

Arch Dis Child Fetal Neonatal Ed 2015 Jul 17;100(4):F314-9. Epub 2015 Mar 17.

Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan.

Objective: To assess lung function at 8 years old in extremely low birthweight (ELBW) survivors and to identify perinatal determinants associated with impaired lung function.

Design: Retrospective cohort study.

Setting: Level III neonatal intensive care unit.

Patients: ELBW survivors born in 1990-2004 with available spirometry at 8 years old were studied. Children were excluded if they had a Wechsler Intelligence Scale for Children Third Edition full IQ <70.

Main Outcome Measures: Multivariate logistic regression analysis was used to identify perinatal determinants associated with airway obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <80%) at school age and the predictive power of potential determinants. Potential risk factors and predictors assessed in this study were gestational age, birth weight, small for gestational age, sex, chorioamnionitis, premature rupture of membranes, antenatal steroids, surfactant administration, respiratory distress syndrome, postnatal steroids, severe bronchopulmonary dysplasia and bubbly/cystic appearances of the lungs by X-ray during the neonatal period.

Results: Of 656 ELBW survivors, 301 (45.9%) had attended a school-age follow-up at 8 years old. A total of 201 eligible children completed the lung function test. Bubbly/cystic appearance of the lungs (OR 4.84, 95% CI 1.26 to 18.70) was associated with a low FEV1/FVC ratio. Children with bubbly/cystic appearance had characteristics of immaturity and intrauterine inflammation.

Conclusions: Within a cohort of ELBW infants, a bubbly/cystic appearance of the lungs in the neonatal period was the strongest determinant of a low FEV1/FVC ratio at school age.
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http://dx.doi.org/10.1136/archdischild-2014-306931DOI Listing
July 2015

Association of p62/SQSTM1 excess and oral carcinogenesis.

PLoS One 2013 24;8(9):e74398. Epub 2013 Sep 24.

Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan ; Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.

p62/SQSTM1 (sequestosome1) has never been evaluated in oral epithelium. In order to clarify the role of p62/SQSTM1 in carcinogenesis in oral epithelium, both p62/SQSTM1 and Nrf2 were immunohistochemically evaluated in 54 carcinomas and 14 low grade dysplasias. p62/SQSTM1 knockdowns were also designed in oral cancer cells, and we analyzed the Nrf2 pathway, GSH contents and ROS accumulation. The association between p62/SQSTM1 excess and prognosis was addressed in a clinical cohort of oral carcinoma cases. p62/SQSTM1 excess was more obvious in carcinomas, but Nrf2 was abundant in almost all samples of the oral epithelium. In oral carcinoma cells, p62/SQSTM1 knockdown did not affect the Nrf2-Keap1 pathway but did significantly reduce GSH content with subsequent ROS accumulation, and caused cell growth inhibition in the irradiated condition. Finally, p62/SQSTM1 excess was associated with poor prognosis in a clinical cohort. In oral epithelial carcinogenesis, p62/SQSTM1 excess played a role in GSH induction rather than Nrf2 accumulation, and may cause resistance to cytotoxic stresses such as radiation or chemotherapy. Immunohistochemical evaluation of p62/SQSTM1 may be a potential significant marker to identify early carcinogenesis, chemo-radiotherapeutic resistance or poor prognosis of oral squamous cell carcinomas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074398PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782476PMC
July 2014

[Series: Emergency medical care physicians are needed; thoracentesis and tube thoracostomy].

Nihon Naika Gakkai Zasshi 2013 May;102(5):1243-7

Department of Emergency and Critical Care Medicine, Tokyo Medical University, Japan.

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http://dx.doi.org/10.2169/naika.102.1243DOI Listing
May 2013

Effectiveness of the new injection program 'saline test injection mode' for use power injector in pediatric contrast CT.

Australas Phys Eng Sci Med 2013 Sep;36(3):347-54

Department of Radiology, Osaka Medical Center and Research Institute for Maternal and Child Health, 840, Murodocho, Izumi, Osaka 594-1101, Japan.

To improve the safety of the use of a power injector for pediatric contrast CT, we newly developed a saline test injection mode for a power injector and investigated its usefulness. We used an injection route and investigated the relationship of the injection pressure to the injection rate of saline and the contrast medium. From this relationship, we investigated it was possible to estimate the change of pressure injection of contrast medium from the pressure change of saline injection. The correlation between the saline test injection pressure and the contrast medium injection pressure was investigated in 64 clinical cases. The detection rate of side effects from the saline test injection was investigated in 473 patients. Regarding the correlation between the injection rate and pressure for both saline and contrast, the pressure rose as the rate increased. The contrast medium injection pressure could be estimated from the correlation observed with saline. The clinical data were obtained had a relationship similar to that with phantom data. The detection rate of side effects from the saline test injection was 4.4% in the clinical cases. In these cases, examinations were completed by re-establishing an injection route or administering hypnotics. Our results suggest that contrast medium pressure can be estimated from a saline test injection, thus aiding in prediction of the risk of injection abnormality. Reactions to injections could be observed in the present study, facilitating the prevention of examination failure. Countermeasures can be taken against the cause of the reaction, and the examination can be performed after confirming the absence of a reaction to injection. Therefore, a saline test injection may be useful in pediatric contrast CT.
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http://dx.doi.org/10.1007/s13246-013-0207-zDOI Listing
September 2013

[Series: Knowledge of emergency required for internist; management of anaphylaxis].

Nihon Naika Gakkai Zasshi 2012 Dec;101(12):3570-6

Department of Respiratory Medicine, Fujisawa City Hospital, Japan.

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http://dx.doi.org/10.2169/naika.101.3570DOI Listing
December 2012

The impact of a negative history of smoking on survival in patients with non-small cell lung cancer detected with clinic-based screening programs.

Intern Med 2012 15;51(22):3115-8. Epub 2012 Nov 15.

Department of Respiratory Medicine, Fujisawa City Hospital, Japan.

Objective: The aim of this study was to determine the epidemiological characteristics of never-smoking patients with non-small cell lung cancer (NSCLC) detected with clinic-based screening programs, focusing on clinical risk factors and survival.

Methods: The medical records of NSCLC patients (n=285) diagnosed at Fujisawa City Hospital between April 2000 and December 2010 with lesions that were originally detected with clinic-based screening programs in Fujisawa City were reviewed to identify the clinicopathological variables and survival outcomes.

Results: Of the 285 NSCLC patients, 95 (33.3%) were never-smokers. A comparison between the never-smoking and ever-smoking patients revealed that the never-smokers included a significantly greater proportion of women and patients with adenocarcinoma (86.3% vs. 12.6%: p<0.001 or 94.7% vs. 55.8%: p<0.001, respectively). The overall survival rate of the never-smoking patients was significantly superior to that of the ever-smokers (p=0.004). In addition to smoking status, factors found to be significantly associated with the overall survival rate in univariate analyses were gender, stage, histology and first line treatment. A multivariate analysis revealed smoking status to be an independent prognostic factor in addition to stage and first line treatment.

Conclusion: The differences in the clinicopathological factors and survival outcomes between never-smoking and ever-smoking patients with NSCLC detected with clinic-based screening programs suggest that persuading people to never start smoking is important.
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http://dx.doi.org/10.2169/internalmedicine.51.8284DOI Listing
May 2013

Long-term survivor with pulmonary veno-occlusive disease.

Circulation 2012 Mar;125(12):e503-6

Division of Cardiology, Fujisawa City Hospital, Kanagawa, 2-6-1 Fujisawa, Kanagawa, Japan.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.111.088450DOI Listing
March 2012

[Knowledge of emergency required for internist: acute respiratory failure].

Nihon Naika Gakkai Zasshi 2011 Jul;100(7):2000-5

Department of Respiratory Medicine, Fujisawa City Hospital, Japan.

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http://dx.doi.org/10.2169/naika.100.2000DOI Listing
July 2011

Multiplex polymerase chain reaction for six herpesviruses after hematopoietic stem cell transplantation.

Pediatr Int 2011 Dec;53(6):1010-7

Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.

Background: Herpesviruses cause life-threatening diseases after hematopoietic stem cell transplantation (HSCT). It is necessary that viral diseases are identified early and safely diagnosed. The purpose of this study was to evaluate the efficacy of multiplex polymerase chain reaction (PCR) for qualitative detection of the six herpesviruses simultaneously: herpes simplex virus type 1 and type 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus (EBV) and human herpesvirus 6B.

Methods: Multiplex PCR was applied to patients with various clinical manifestations including central nervous system, cutaneous and mucosal complications after allogeneic HSCT, and the data were retrospectively analyzed.

Results: Patients positive for cytomegalovirus in peripheral blood by multiplex PCR might need pre-emptive treatment, but a positive result for EBV had no specific correlation with EBV-associated post-transplant lymphoproliferative disease, and positive result for human herpesvirus 6B failed to show any clinical significance. The multiplex PCR was safe and helpful to diagnose viral diseases of local regions, for example, the central nervous system, skin and mucosa.

Conclusions: It may be worthwhile to survey the six herpesviruses with multiplex PCR after HSCT.
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http://dx.doi.org/10.1111/j.1442-200X.2011.03437.xDOI Listing
December 2011

[Series: Knowledge of emergency required for internist; management of asthma exacerbations].

Nihon Naika Gakkai Zasshi 2011 Jun;100(6):1683-91

Department of Respiratory Medicine, Fujisawa City Hospital, Japan.

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http://dx.doi.org/10.2169/naika.100.1683DOI Listing
June 2011

Extending the phenotype of lethal skeletal dysplasia type al Gazali.

Am J Med Genet A 2011 Jun 12;155A(6):1404-8. Epub 2011 May 12.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

In this study, we describe the clinical and radiological phenotype of two patients with a rare skeletal dysplasia type al Gazali. The phenotype is characterized by brachycephaly, flat face, hypertelorism, low-set ears, hypertrichosis, hypoplastic thorax, as well as short extremities with brachydactyly. Further characteristics are severe fetal hydrops, radiologic signs of increased bone density and short, poorly modeled tubular bones with wide diaphysis and smooth, rounded metaphyses. Cortical bones as well as vertebral endplates are thick and the skull is sclerotic with prominent parietal bones and a large anterior fontanel. Our cases suggest that skeletal dysplasia type al Gazali is a lethal condition and provide further evidence that it is inherited in an autosomal recessive manner. Both morphological and radiological features of these patients are very similar, which together with the previous report may indicate the presence of a new clinical entity in the group of skeletal dysplasias with increased bone density and metaphyseal and diaphyseal involvement. Surprisingly, histological analysis of the bone tissue and the growth plate shows completely normal structure, which suggests that the skeletal dysplasia type al Gazali is a systemic disorder resulting in increased bone density and restricted growth of the skeleton.
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http://dx.doi.org/10.1002/ajmg.a.33990DOI Listing
June 2011

Histological examination of the relationship between respiratory disorders and repetitive microaspiration using a rat gastro-duodenal contents reflux model.

Exp Anim 2011 ;60(2):141-50

Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

Microaspiration due to gastroesophageal reflux (GER) has been suggested as a factor contributing to the development and exacerbation of several respiratory disorders. To explore the relationship between GER and respiratory disorders, we histologically examined the bilateral lungs of a rat gastroduodenal contents reflux model, which was previously used to investigate the histogenesis of Barrett's esophagus and esophageal carcinoma. GER was surgically induced in male Wistar rats. The bilateral lungs of the reflux rats were examined with hematoxylin and eosin (HE), PAS-Alcian blue, and Azan staining at 10 and 20 weeks after surgery. Immunohistochemical staining of CD68 and α-SMA was also performed. Aspiration pneumonia with severe peribronchiolar neutrophilic and lymphocytic infiltrates, goblet cell hyperplasia, prominence of blood vessels, and increased thickness of the smooth muscle layer were detected. Bronchiolitis obliterans (BO)-like lesions comprising granulation tissue with macrophages, spindle cells, and multinucleated giant cells in the lumen of respiratory bronchioles were observed in the bilateral lungs of the reflux animals. These findings suggest that the severe inflammation and the BO-like lesions may play a role in exacerbation of the forced expiratory volume in 1 second (FEV 1) in human cases. In conclusion, we speculate that repetitive microaspiration due to GER may contribute to the exacerbation of various respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD), and the development of BO syndrome following lung transplantation. The reflux model is a good tool for examining the causal relationships between GER and respiratory disorders.
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http://dx.doi.org/10.1538/expanim.60.141DOI Listing
August 2011

Dexamethasone-induced up-regulation of two-pore domain K+ channel genes, TASK-1 and TWIK-2, in cultured human periodontal ligament fibroblasts.

In Vitro Cell Dev Biol Anim 2011 Apr 27;47(4):273-9. Epub 2011 Feb 27.

Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

Two-pore domain K(+) channels are widely expressed in many types of cells, and have various important functions, especially maintaining the resting membrane potential. In the previous report, we have confirmed the presence of several kinds of two-pore domain K(+) channels in the periodontal ligament (PDL) fibroblasts. It is well known that dexamethasone (Dex) regulates the functions of various kinds of ion channels. In this work, we investigate if Dex affects the gene expressions of the two-pore domain K(+) channels in the PDL fibroblasts. We also examined the effects of other steroid hormones on the K(+) channels gene expression. The mRNA levels of two-pore domain K(+) channels in human PDL fibroblasts were examined in the presence or absence of Dex by RT-PCR. The effects of other steroid hormones (aldosterone, estrogen, 1α,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], and retinoic acid) were also examined. Dex significantly induced the expression of TASK-1 and TWIK-2 in mRNA levels in both a dose- and a time-dependent manner. The stimulatory effects of Dex were completely abolished by a glucocorticoid receptor antagonist. 1,25-(OH)(2)D(3) also increased the TASK-1 mRNA levels but had no effect on TWIK-2 expression. Dex, one of the potent glucocorticoid, probably have a protective role against external stimuli by maintaining the membrane potential of PDL fibroblasts through the up-regulation of TASK-1 and TWIK-2 K(+) channels.
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http://dx.doi.org/10.1007/s11626-011-9388-5DOI Listing
April 2011