PubMed | Tokushima Prefectural Central Hospital, Kumamoto University, Chugoku Central Hospital, NHO Nishigunma Hospital and 10 more.
Type: Journal Article | Journal: Annals of hematology | Year: 2016
Bortezomib is one of the most widely used novel drugs for the treatment of multiple myeloma (MM). However, twice-weekly intravenous administration is associated with innegligible adverse events and treatment discontinuation. We therefore evaluated the long-term efficacy and feasibility of reduced frequency treatment with intravenous bortezomib in elderly patients with relapsed and/or refractory MM. A total of 47 bortezomib-nave patients (median age 75years) received bortezomib (1.3mg/m(2), intravenously) and dexamethasone (20mg) on days 1, 8, and 15 of every 4-week cycle. Twenty-six patients completed the planned 8cycles. Best responses were stringent complete response (sCR) in 5 patients, very good partial response (VGPR) in 3, PR in 15, stable disease (SD) in 18, and disease progression (PD) in 6, respectively. Median progression-free and overall survivals were 9.6 and 35.1months, respectively. After progression, 11 patients were retreated with bortezomib-based regimens and another 24 patients with immunomodulatory drugs. Multivariate analysis revealed that ISS 3, t(4;14), and <4 therapy cycles were significantly poor prognostic factors and that subsequent therapy with bortezomib-based regimens was a favorable factor for extended OS. The common adverse events were diarrhea, constipation, and peripheral neuropathy with no grade 4 toxicity. In conclusion, reduced frequency treatment with intravenous bortezomib+dexamethasone is an effective option for elderly patients with MM.
PubMed | National Hospital Organization Hokkaido Cancer Center, University of Pennsylvania, National Hospital Organization Shikoku Cancer Center, Chugoku Central Hospital and 8 more.
Type: Journal Article | Journal: American journal of hematology | Year: 2016
Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed.
Tokunaga T.,Nagoya University |
Shimada K.,Nagoya University |
Yamamoto K.,Aichi Cancer Center |
Chihara D.,Aichi Cancer Center |
And 16 more authors.
Blood | Year: 2012
Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted. © 2012 by The American Society of Hematology.
Three-Arm Randomized Trial of Sodium Alginate for Preventing Radiation-Induced Esophagitis in Locally Advanced Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy: The OLCSG1401 Study Protocol
PubMed | Okayama University of Science, Red Cross, National Hospital Organization Shikoku Cancer Center, Chugoku Central Hospital and 7 more.
Type: | Journal: Clinical lung cancer | Year: 2016
Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, this intensive therapy often causes severe esophagitis, which could deteriorate a patients quality of life (QOL), leading to poor treatment compliance. Sodium alginate, approved in Japan for gastritis, is sufficiently highly viscous to remain in the esophageal mucosa, providing a protective effect in the esophagus. To investigate whether this compound has a preventive effect against severe esophagitis in patients receiving concurrent CRT, we plan a 3-arm randomized trial of sodium alginate with 2 different schedules versus water. The primary endpoint is set as the proportion of patients with grade 3 esophagitis using the Common Terminology Criteria for Adverse Events, version 4.0. With stratification by institute, performance status, and percentage of the esophageal volume receiving >35 Gy, the patients will be randomly assigned to 1 of the following groups: sodium alginate initiated concomitantly with CRT (group A), sodium alginate initiated soon after the development of extremely mild esophagitis during CRT (group B), or water administered throughout CRT (group C). Assuming that the proportion of grade 3 esophagitis would be 8% in groups A and B and 27% in group C, the required sample size would be 200 patients, with 70% power and 5% . The secondary endpoints include QOL, the frequency of additional prescriptions of analgesics, treatment response, and survival. The results of the present study will clarify whether sodium alginate can prevent esophagitis in patients with LA-NSCLC undergoing CRT.
PubMed | Okayama University of Science, Himeji Medical Center and Chugoku Central Hospital
Type: | Journal: Modern rheumatology | Year: 2016
To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD.Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development.Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p=0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3mg/w, p=0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein-Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p=0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy.Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.
PubMed | Red Cross, Shimonoseki City Hospital, National Hospital Organization Shikoku Cancer Center, Chugoku Central Hospital and 8 more.
Type: Journal Article | Journal: Clinical lung cancer | Year: 2016
Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory non-small-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with non-small-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided of 0.05, of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK
PubMed | Red Cross, Ehime Prefectural Central Hospital, Chugoku Central Hospital, Iwakuni Medical Center and 4 more.
Type: Journal Article | Journal: Cancer chemotherapy and pharmacology | Year: 2016
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now key agents in treating EGFR-mutant non-small cell lung cancer (NSCLC). The efficacy of gefitinib or erlotinib monotherapy can be predicted by the development of a skin rash. However, it has not been fully evaluated if this is the case with afatinib monotherapy.We retrospectively studied 49 consecutive patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. The relationship of several toxicities with tumor response was examined.Grade 2, or more severe, common adverse events (AEs) included skin rash in 17 patients (35%), diarrhea in 19 (39%) and mucositis in 15 (31%). Of these, the number of patients who developed Grade 2 AEs during the first week after the initiation of afatinib therapy was: five patients had skin rash (10%), 12 patients had diarrhea (25%) and four patients had mucositis (8%). As for an objective response, 21 (43%) of the 49 had a partial response. Associating the AEs with the antitumor effect, those who had a Grade 2 skin rash within the first week tended to have a greater tumor response compared with those without a rash (80 vs. 39%; p=0.077).Our small study demonstrated that the early development of a skin rash might be associated with the response to afatinib monotherapy.
Ohki T.,Chugoku Central Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013
The autonomy Laparo-angle needle holder is a flexible device which has several articulating parts facilitating some traditionally difficult way of suture passage. This device is often used for laparoscopic surgery, and there have been few reports for video-assisted thoracic surgery (VATS). We used this device for complete VATS lobectomy and segmentectomy, and it enables us to suture a bronchus with the optimal direction even in the deep surgical field on complete VATS lobectomy and segmentectomy. Although some training may be needed to freely manipulate this device, it can be useful for minimallyinvasive video-assisted thoracic surgery.
Sakamoto K.,Chugoku Central Hospital
Rinsho byori. The Japanese journal of clinical pathology | Year: 2011
Smoking is the riskiest factor for impairment of pulmonary function. Recent researches have indicated that abdominal obesity is also associated with the impairment. 'Lung age' is a novel index to evaluate respiratory function, and it is calculated from the data of the height, sex, and forced expiratory volume in 1-second. Using 'lung age' as an index, we studied on the relationship of 'lung age' to smoking, waist circumference, BMI, or metabolic syndrome. The study population included 1,681 persons who visited our Medical Checkup Office, and the population consisted of smoker group (n = 279) and non-smoker group (n = 1,402). In both men and women, 'lung age' was significantly higher in the smoker group than in non-smoker group (p < 0.05). In addition, the smoker group and non-smoker group were classified by waist circumference, BMI, and the presence of metabolic syndrome, respectively. As a result, 'lung age' of smoker with abdominal obesity group, smoker with obesity group, and smoker with metabolic syndrome group were significantly high. Furthermore, in multivariate linear regression analysis, we examined relation between 'lung age' and the following factors including gender, smoking, waist circumference, BMI and metabolic syndrome. There was closely related to 'lung age' in order of gender, smoking, metabolic syndrome, and waist circumference. Both smoking and abdominal obesity should be significant risk factors in increasing 'lung age'.
PubMed | Chugoku Central Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2016
Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.