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Keiko Higuchi - Top 30 Publications

Association Between Laryngopharyngeal Reflux and Radiation-induced Mucositis in Head and Neck Cancer.

We investigated whether laryngopharyngeal reflux (LPR) is a risk factor for radiation-induced mucositis.

Successful treatment of radiation-induced mucositis with proton pump inhibitor administration: A report of two laryngeal cancer cases.

Presently, the relationship between laryngopharyngeal reflux (LPR) and radiation-induced mucositis has not been fully explored. In the present study, we report 2 cases of laryngeal cancer in which radiation-induced mucositis ameliorated after proton pump inhibitor (PPI) administration. Case 1 was diagnosed with T1aN0M0 right glottis carcinoma and was treated with radiation therapy. Grade 3 mucositis occurred after administration of 46Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of radiation therapy. Case 2 was diagnosed with T2N0M0 supraglottic cancer and was treated with concurrent chemoradiation therapy. Grade 3 mucositis occurred after administration of 44Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of chemoradiation therapy. In both cases, a remarkable therapeutic effect of PPI was observed in the perilaryngeal areas including the epiglottic vallecula, arytenoid, and postcricoid area. In both cases, LPR involvement was suspected before the onset of radiation therapy. The two cases presented here, indicated a causal relationship between LPR and radiation-induced mucositis. In cases of severe mucositis in the perilaryngeal area in patients with LPR prior to radiation therapy, PPI administration may be an effective therapeutic option.

Effects of GOLD-Adherent Prescribing on COPD Symptom Burden, Exacerbations, and Health Care Utilization in a Real-World Setting.

Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines recommend specific drug therapy protocols for chronic obstructive pulmonary disease (COPD) patients based on symptoms and exacerbation risk. This study used electronic health records (EHRs) to assess the effect of adherence and nonadherence to GOLD prescribing guidelines on COPD symptom burden, exacerbations, and health care resource utilization (HCRU) during the 180 days following index treatment start. Included patients had COPD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 490.xx, 491.xx, 492.xx, 496.xx), a valid GOLD stage within the study period (January 1, 2007 to December 31, 2012), and were 40 to 90 years of age at first GOLD staging (GOLD date). Adherence or nonadherence to GOLD-defined prescribing was based on COPD medication prescribed within 180 days on either side of the GOLD date. Of 4234 patients included in the analysis, approximately 36% were prescribed GOLD-adherent pharmacotherapy. Prevalence of all COPD-related symptoms during the 180 days following index treatment start were significantly reduced in the GOLD-adherent (n=1531) versus the GOLD-nonadherent group (n=2703). GOLD-adherent prescribing was associated with significant reductions in proportions of patients with all-cause hospitalizations and emergency department (ED) visits (unadjusted odds ratios [ORs], 0.69 and 0.63, respectively), as well as respiratory-specific ED visits (unadjusted OR, 0.65), compared with GOLD-nonadherent prescribing. In analyses that divided patients receiving GOLD-nonadherent treatment into undertreated and overtreated patients, undertreatment was associated with significant increases in many COPD symptoms, and both undertreatment and overtreatment were associated with increases in some HCRU endpoints. GOLD-adherent prescribing delivers moderate benefits with respect to COPD symptoms and HCRU.

Inhaled aztreonam lysine versus inhaled tobramycin in cystic fibrosis. An economic evaluation.

Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin.

Economic Burden of COPD in the Presence of Comorbidities.

The morbidity and mortality associated with COPD exacts a considerable economic burden. Comorbidities in COPD are associated with poor health outcomes and increased costs. Our objective was to assess the impact of comorbidities on COPD-associated costs in a large administrative claims dataset.

Clinical and economic outcomes in a real-world population of patients with elevated triglyceride levels.

This study investigated real-world treatment patterns, healthcare utilization, and costs of hypertriglyceridemia in a large commercially insured United States population.

Prognosis was not deteriorated by multiple primary cancers in esophageal cancer patients treated by radiotherapy.

Esophageal cancer patients are often associated with multiple primary cancers (MPC). The aim of this study is to evaluate the effect of MPC on prognosis in esophageal cancer patients treated by radiotherapy. Between 2001 and 2008, esophageal cancer patients treated by definitive radiotherapy at Gunma Cancer Center were retrospectively reviewed. Exclusion criteria were preoperative or postoperative radiotherapy, palliative radiotherapy, follow-up of <6 months, radiation dose of <50 Gy and no information on MPC. We analyzed 167 esophageal cancer patients and 56 (33.5%) were associated with MPC. Gastric cancer was the most frequent tumor (38.2%), followed by head and neck cancer (26.5%). Median follow-up time was 31.5 months (range 6.1-87.3 months). Patients with MPC included more stage I/II esophageal cancer than those without MPC (66.1% vs. 36.9%, P < 0.01). The 5-year overall survival rate for esophageal cancer with MPC was relatively better than those without MPC (46.1% vs. 26.7%), although the difference did not reach statistical significance in univariate analysis (P = 0.09). Stage I/II esophageal cancer patients had a significantly better overall survival than stage III/IV patients (P < 0.01). Among esophageal cancer patients with MPC, there was no difference in overall survival between antecedent and synchronous cancer (P = 0.59). Our study indicated that the prognosis of esophageal cancer patients treated by radiotherapy was primarily determined by the clinical stage itself, but not the presence of MPC.

Stereocontrolled synthesis of an indole moiety of sespendole and stereochemical assignment of the side chain.

Two possible diastereomers of the indole moiety of sespendole were synthesized from 3-hydroxy-4-nitrobenzaldehyde in a highly stereoselective manner. Comparison of (1)H and (13)C NMR spectra of the two synthetic materials with those sespendole leads us to propose that the relative stereochemistry of the epoxyalcohol is syn.

Health care utilization & costs for cystic fibrosis patients with pulmonary infections.

To examine patterns of health care utilization and costs among cystic fibrosis (CF) patients with pulmonary infections.

Comparison of chemoradiotherapy with radiotherapy alone in patients with esophageal adenocarcinoma.

Despite the wide use of definitive chemoradiotherapy (CRT) for locally advanced esophageal adenocarcinoma, there is little evidence that CRT improves the survival of patients with esophageal adenocarcinoma compared with radiotherapy (RT) alone. Therefore, we retrospectively evaluated the outcome of patients with esophageal adenocarcinoma treated by CRT and RT alone. Patients were treated at the Gunma Prefectural Cancer Center (Ota, Japan) and the Gunma University Hospital (Maebashi, Japan). Patients provided written informed consent before treatment. Patients with distant metastases were excluded. CRT consisting of RT, nedaplatin, and 5-fluorouracil has been performed since 2002 when patients have adequate bone marrow, liver, and renal function. Between November 1993 and April 2006, 8 patients were treated by CRT and 12 were RT alone. The median follow-up period of surviving patients was 19 months. CRT group had a significantly higher complete response rate than those RT alone group (87% vs. 33%, P = 0.05). Of all patients, 2-year overall survival rate was 41% and the median survival time was 18 months. The 2-year overall survival of patients treated by CRT was 58%, significantly better than 24% of those with RT alone (P = 0.02). CRT can improve outcomes of patients with esophageal adenocarcinoma compared with RT alone.

Comparison of recombinant protein expression in a baculovirus system in insect cells (Sf9) and silkworm.

Using a hybrid baculovirus system, we compared the expression of 45 recombinant proteins from six categories using two models: silkworm (larvae and pupae) and an Sf9 cell line. A total of 45 proteins were successfully expressed; preparation of hybrid baculovirus was unsuccessful for one protein, and two proteins were not expressed. A similar pattern of expression was seen in both silkworm and Sf9 cells, with double and multiple bands found in immunoblotting of the precipitate of both hosts. Degraded proteins were seen only in the silkworm system (particularly in the larvae). Production was more efficient in silkworms; a single silkworm produced about 70 times more protein than 10(6) Sf9 cells in 2 ml of culture medium.

Dose-volume histogram parameters and clinical factors associated with pleural effusion after chemoradiotherapy in esophageal cancer patients.

To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT).

Hypothalamic neuronal histamine signaling in the estrogen deficiency-induced obesity.

Menopause is one of the triggers that induce obesity. Estradiol (E2), corticotropin-releasing hormone (CRH), and hypothalamic neuronal histamine are anorexigenic substances within the hypothalamus. This study examined the interactions among E2, CRH, and histamine during the regulation of feeding behavior and obesity in rodents. Food intake was measured in rats after the treatment of E2, alpha-fluoromethyl histidine, a specific suicide inhibitor of histidine decarboxylase that depletes hypothalamic neuronal histamine, or CRH antagonist. We measured food intake and body weight in wild-type mice or mice with targeted disruption of the histamine receptors (H1-R) knockout (H1KO mice). Furthermore, we investigated CRH content and histamine turnover in the hypothalamus after the E2 treatment or ovariectomy (OVX). We used immunohistochemical staining for estrogen receptors (ERs) in the histamine neurons. The E2-induced suppression of feeding was partially attenuated in rats pre-treated with alpha-fluoromethyl histidine or CRH antagonist and in H1KO mice. E2 treatment increased CRH content and histamine turnover in the hypothalamus. OVX increased food intake and body weight, and decreased CRH content and histamine turnover in the hypothalamus. In addition, E2 replacement reversed the OVX-induced changes in food intake and body weight in wild-type mice but not in H1KO mice. Immunohistochemical analysis revealed ERs were expressed on histamine neurons and western blotting analysis and pre-absorption study confirmed the specificity of ER antiserum we used. These results indicate that CRH and hypothalamic neuronal histamine mediate the suppressive effects of E2 on feeding behavior and body weight.

Histopathological variation of primary mucosa-associated lymphoid tissue lymphoma of the oral cavity.

Primary mucosa-associated lymphoid tissue (MALT) type lymphoma arising in the oral cavity is rare. We examined histopathologic, immunohistological and genotypic findings of seven cases of intraoral MALT lymphoma using formalin-fixed paraffin-embedded tissues. Histologically, two variants have been delineated. (i) In four cases of minor salivary gland type, the lymphoid follicles were surrounded by centrocyte-like (CCL) cells with occasional follicular colonization. The CCL cells invaded the residual salivary gland duct resulting in a lymphoepithelial lesion. CCL cells frequently showed plasmacytic differentiation. (ii) In three cases of follicular growth type, the lesion was characterized by follicular growth pattern resulting from prominent follicular colonization. CCL cells showed minimal plasma cell differentiation. There was no residual epithelial component detected even by cytokeratin immunostaining. There were no Epstein-Barr virus-encoded small RNA-positive cells detected by in situ hybridization. API2-MALT1 fusion transcript does not appear to be associated with either histological variant of primary intraoral MALT lymphoma.

Implementing health information technology to improve the process of health care delivery: a case study.

Integration of health information is critical to the provision of effective, quality care in today's fragmented health care system. The increasing prevalence of chronic conditions and the demand for a comprehensive understanding of patient health on the part of providers are driving the need for the integration of health information through electronic health information systems. Two distinct health information systems currently utilized in the health care field include electronic medical records (EMR) and chronic disease management systems (CDMS). The integration of these systems is likely to enable the efficient management of health information and improve the quality of health care as it would provide real-time patient information in a coordinated manner. The lack of real-time information may result in delayed treatment, uninformed decisions, inefficient resource use, and medical errors. Despite their importance and widespread support, these systems have slow provider adoption rates. Our understanding of how health information technology may be used to improve health care is limited by the relative paucity of research on the adoption, integration, and implementation of these 2 types of systems. This paper documents the use of an EMR at Marshfield Clinic, a multidisciplinary group practice in the United States. We review the concomitant use of an EMR for clinical data capture and the implementation of a proprietary CDMS, InformaCare, for care management of chronic diseases. These 2 systems allow providers to deliver health care using evidence-based guidelines that meet the Institute of Medicine's aim of providing safe, efficient, patient-centered, and timely care.

A multicenter phase II study of local radiation therapy for stage IEA mucosa-associated lymphoid tissue lymphomas: a preliminary report from the Japan Radiation Oncology Group (JAROG).

The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial.

Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice.

Apelin, the endogenous ligand of the APJ receptor, has been identified in a variety of tissues, including stomach, heart, skeletal muscle, and white adipose tissue. We sought to clarify the effects of apelin on body adiposity and the expression of uncoupling proteins (UCPs) in C57BL/6 mice. Treatment with ip apelin at a dose of 0.1 mumol/kg.d for 14 d decreased the weight of white adipose tissue and serum levels of insulin and triglycerides, compared with controls, without influencing food intake. Apelin treatment also decreased body adiposity and serum levels of insulin and triglycerides in obese mice fed a high-fat diet. Apelin increased the serum adiponectin level and decreased that of leptin. Additionally, apelin treatment increased mRNA expression of UCP1, a marker of peripheral energy expenditure, in brown adipose tissue (BAT) and of UCP3, a regulator of fatty acid export, in skeletal muscle. In addition, immunoblot bands and relative densities of UCP1 content in BAT were also higher in the apelin group than controls. Furthermore, apelin treatment increased body temperature and O(2) consumption and decreased the respiratory quotient. In conclusion, apelin appears to regulate adiposity and lipid metabolism in both lean and obese mice. In addition, apelin regulates insulin resistance by influencing the circulating adiponectin level, the expression of BAT UCP1, and energy expenditure in mice.

Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus.

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.

Initial experience with the quality assurance program of radiation therapy on behalf of Japan Radiation Oncology Group (JAROG).

We evaluated the efficacy of our quality assurance (QA) program of radiation therapy (RT) in a prospective phase II study. This is the first description of the experience of the Japan Radiation Oncology Group (JAROG) with this program.

Multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects of a population of more than 5,000.

Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study.

Reactive lymphoid hyperplasia with giant follicles associated with post-therapeutic state of hematological malignancies: a report of six cases.

Radiation therapy alone for stage I (UICC T1N0M0) squamous cell carcinoma of the esophagus: indications for surgery or combined chemoradiotherapy.

The aim of this study was to clarify the efficacy and limitations of radiation therapy (RT) for superficial esophageal carcinoma, and to explore the indications for more aggressive therapy, such as combined chemo-radiotherapy.

Frequency and characteristics of isolated para-aortic lymph node recurrence in patients with uterine cervical carcinoma in Japan: a multi-institutional study.

In most cases of uterine cervical carcinoma recurrence, the first site of distant metastasis or recurrence is reported to be the para-aortic region. Some reports have demonstrated that, in cases of isolated para-aortic lymph node recurrence treated by radiation therapy, patients survived for a long period, which suggests that isolated para-aortic lymph node recurrence in uterine cervical carcinoma is a regional disease rather than systemic disease. Determining the predictive characteristics of isolated para-aortic lymph node recurrence in patients at the time of the initial treatment for primary uterine cervical carcinoma is important, so we conducted the current multi-institutional study.

Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases.

We conducted clinicopathologic and immunohistochemical analyses of the prevalence of Epstein-Barr virus (EBV) among 24 patients with malignant lymphoma complicating systemic rheumatic diseases. (SRD) These 24 patients included 17 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 2 with systemic sclerosis (SS), and 2 with dermatomyositis (DM). There were 2 men and 22 women ranging in age from 30 to 86 years (mean: 64 years). The interval between the onset of rheumatic disease and that of malignant lymphomas ranged from 3 months to 35 years (mean: 142 months). The use of immunosuppressive drugs before the onset of malignant lymphoma was recorded in 15 patients. Among them, 5 patients received methotrexate (MTX) therapy. Malignant lymphomas were found at extranodal sites in 9 patients, and the disease was in the advanced stage in 17 patients. Histologic and immunohistochemical studies demonstrated that 18 cases (75%) were B-cell lymphoma (RA=12, SLE=2, SS=2, DM=2), 3 (12.5%) were peripheral T-cell lymphoma (RA=3), and 3 (12.5%) were classical Hodgkin lymphoma (RA=2, SLE=1). As in previous reports, there was an increased frequency of diffuse large B-cell lymphoma (50%) in the present series. Moreover, a majority of the diffuse large B-cell lymphomas exhibited activated B-cell phenotype. EBV-encoded small RNAs (Epstein-Barr early region [EBER]-) and/or LMP-1+tumor cells were identified in only 3 cases of classical Hodgkin lymphomas. Our findings suggested EBV-associated lymphoma comprised only a small fraction of all non-Hodgkin's lymphomas in the general SRD patient population.

The role of radiotherapy for thymic carcinoma.

The aim of this study is to evaluate retrospectively the role of radiotherapy for thymic carcinoma.

MR imaging of mucinous carcinoma of the breast.

We examined retrospectively the MR imaging findings in eight patients with mucinous carcinoma of the breast to better describe the imaging characteristics of this disease.

Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging.

Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis.