Sadahiro S.,Tokai University |
Tsuchiya T.,Sendai City Medical Center |
Sasaki K.,Otaru Ekisaikai Hospital |
Kondo K.,National Hospital Organization |
And 12 more authors.
Annals of Oncology | Year: 2015
Background: While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer. Patients and methods: Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety. Result: A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group. Conclusion: Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Yokouchi M.,Keio University |
Yokouchi M.,Nerima General Hospital |
Kubo A.,Keio University |
Kawasaki H.,Keio University |
And 5 more authors.
Journal of Dermatological Science | Year: 2015
Background: The tight junction (TJ) barrier is located in the granular layer of the epidermis. Filaggrin deficiency predisposes patients to atopic dermatitis (AD) by impairing stratum corneum (SC) barrier function. Altered TJ barrier function has been observed in the skin of patients with AD; however, it remains unclear whether TJ function is influenced by filaggrin deficiency directly or secondarily via skin inflammation. Objective: To investigate the in vivo effects of filaggrin deficiency and skin inflammation on epidermal TJ function. Methods: Morphological changes in the TJ were investigated in filaggrin knockout mice and mice with hapten-induced dermatitis using en face visualization of epidermal sheets, and functional changes in the TJ were assessed with an in vivo permeation assay using tracers of various sizes. Results: In filaggrin knockout mice, there was no apparent change in the honeycomb morphology of the TJ, TJ component mRNA expression, or TJ barrier function in neonates and adults, indicating that filaggrin-deficiency had no direct effects on the TJ. By contrast, in mice with hapten-induced dermatitis, the mRNA expression of TJ components was decreased markedly and the TJ barrier function was size-dependently impaired: the TJ leaked small tracers (<5. kDa), but not large tracers (>30. kDa). Conclusion: Filaggrin deficiency did not affect the epidermal TJ barrier directly, but once dermatitis occurred, the skin inflammation induced TJ dysfunction. Since TJ dysfunction induces the SC barrier impairment, skin inflammation will enhance skin permeability to external antigens and result in a vicious cycle of barrier dysfunction and skin inflammation. © 2014 Japanese Society for Investigative Dermatology.
PubMed | Red Cross, Aomori Prefectural Central Hospital, Nerima General Hospital, Kumamoto University and 12 more.
Type: Clinical Trial, Phase III | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2015
While adjuvant chemotherapy is preferable for high-risk colon cancer, treatment duration is controversial. Oral uracil and tegafur (UFT)/leucovorin (LV) is widely used as a standard adjuvant chemotherapy for colon cancer in Japan. We conducted a phase III trial to investigate the optimal duration of adjuvant chemotherapy for stage IIB/III colon cancer.Patients with curatively resected stage IIB/III colon cancer were eligible for enrollment in this trial. Patients were registered within 6 weeks after surgery and were randomly assigned to receive UFT/LV for 28 of 35 days for 6 months in the control group or for 5 consecutive days per week for 18 months in the study group. The primary end point was the disease-free survival (DFS), and the secondary end points were overall survival (OS) and safety.A total of 1071 patients were registered from 233 centers. A statistically significant difference in DFS was not observed between the study group and the control group; the 5-year DFS was 69% in the study group and 69% in the control group. The 5-year OS was 85% in the study group and 85% in the control group.Eighteen-month treatment with UFT/LV did not improve DFS or OS compared with 6-month UFT/LV treatment in patients with stage IIB/III colon cancer. The important finding from this study is that not 18 months but 6 months of treatment is enough for postoperative UFT/LV for stage IIB/III colon cancer.UMIN-CTR C000000245.
PubMed | Red Cross, Juntendo University, National Hospital Organization, Kansai Medical University and 16 more.
Type: Comparative Study | Journal: Clinical colorectal cancer | Year: 2015
The usefulness of adjuvant chemotherapy for stage II colon cancer has not been established. Meanwhile, the presence of stage II colon cancer with high-risk factors for recurrence has been reported. To our knowledge, no prospective study of adjuvant chemotherapy for stage II colon cancer with high-risk factors has been implemented to date.This study is a prospective nonrandomized controlled study based on patients selection of treatment option, including randomized therapeutic decision-making, to evaluate the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) with leucovorin (LV) for stage II colon cancer with high-risk factors for recurrence, compared with surgery alone. Five courses of UFT/LV therapy will be given as follows: UFT (300 mg/m(2)/d) with LV (75 mg/d) will be orally administered in 3 doses per day. Treatment will be received daily for 28 days, followed by a 7-day rest or will be received daily for 5 days, followed by a 2-day rest. For both regimens, 1 course will last 5 weeks, and 5 courses will be given. The primary end point is disease-free survival. A propensity score matching will be conducted based on 7 variables that represent risk factors to minimize selection bias in a comparison between the nonrandomized arms. For this nonrandomized comparison, a target sample size is set at 1200 (400 and 800 patients for the surgery alone and UFT/LV groups, respectively) and 1720 patients will be enrolled. In this study we aim to evaluate the therapeutic usefulness of adjuvant chemotherapy with UFT/LV for stage II colorectal cancer with risk factors for recurrence.
Watanabe G.,Tohoku University |
Ishida T.,Tohoku University |
Furuta A.,Red Cross |
Takahashi S.,Tohoku University |
And 5 more authors.
American Journal of Surgical Pathology | Year: 2015
It is difficult to predict the TP53 status by p53 immunohistochemistry (IHC). We aimed to improve the accuracy of p53 IHC with p53-regulated proteins for predicting the TP53 mutation status. TP53 mutations were detected in 19 of 38 breast cancer patients (50%). Five of 7 cases of protein-truncating mutation of TP53 were completely negative for p53 IHC, whereas 11 of 12 cases of TP53 point mutation were strongly positive for p53 IHC. Therefore, to avoid false negatives, we extracted p53-dependent universally downregulated genes using microarray analysis from 38 breast cancer patients and 2 p53-inducible cell lines. From 9 commonly repressed genes, we evaluated 3 genes, baculoviral IAP repeat-containing 5 (BIRC5), polo-like kinase 1 (PLK1), and BUB1 mitotic checkpoint serine/threonine kinase (BUB1), which were previously identified as p53-dependent repressed genes. PLK1≥Allred total score (TS) 5 showed the highest correlation with TP53 mutation. To decrease false positivity, we evaluated p21 IHC. Although strong staining of p21 was observed in 4 cases (10.5%), all 4 were wild-type TP53. Thus, p53 mutation-like (p53mt-like) IHC was identified by p53 TS7,8 with PLK1≥TS 5 and p21 TS≤6. p53 mt-like IHC correlated with TP53 mutation (predictive value=0.94). In other 157 breast cancer cases, p53 mt-like was an independent prognostic marker in multivariate analysis and a strong prognostic factor. Stratification with p53 mt-like IHC identified patients with a poorer prognosis. In conclusion, we identified reliable IHC conditions to predict the TP53 status of breast cancer patients. © Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Umezu T.,Nerima General Hospital |
Ashitani K.,Nerima General Hospital |
Toda T.,Nerima General Hospital |
Yanagawa T.,Nerima General Hospital
BMC Research Notes | Year: 2013
Background: Thyroid storm is a serious condition of thyrotoxicosis. Hyperthyroidism often presents with thrombotic events, especially at cerebral sites; however, the possible association between a lower extremity deep vein thrombosis (LEDVT) and thyroid storm has not been previously reported. We encountered a patient who developed thyroid storm, associated with rhabdomyolysis, followed by LEDVT and a small silent pulmonary embolism (PE). The case is discussed with references to the pertinent literature. Case presentation. A 50-year-old woman with no past medical history was referred to our hospital because of severe diarrhea, muscle weakness in her lower limbs (manual muscle testing: MMT 3), and disturbances of consciousness. She was diagnosed as having Graves' disease based on the presence of struma, exophthalmos, and hyperthyroidism with TSH receptor antibody positivity; we further determined that the patient was experiencing thyroid storm based on the results of the Burch-Wartofsky scoring system and a Japanese diagnostic criteria. Treatment with steroids, iodine potassium, methimazole, and propranolol was initiated. Severe watery diarrhea continued, and the laboratory data revealed hypokalemia (2.0 meq/L). On day 14, a blood analysis showed a sudden elevation in her creatinine kinase (CK) level, leading to a diagnosis of rhabdomyolysis. Thereafter, the muscle weakness in her lower limbs advanced to a degree of MMT 1. Seven days after the diagnosis of rhabdomyolysis, pitting edema began to appear in bilateral lower extremities. Contrast-enhanced CT scans revealed a LEDVT involving the left common iliac vein, bilateral femoral veins, and left popliteal vein. Furthermore, a small PE was identified. Hyperthyroidism often presents with thrombotic events, especially at cerebral sites, but few reports of PE or LEDVT have been made. Conclusion: This case suggests that the occurrence of thyroid storm may be associated with a risk of LEDVT and/or PE. We suggest that DVT preventive measures are undertaken, and that a lower limb venous echo or contrast-enhanced CT examination would be considered if LEDVT is suspected. © 2013 Umezu et al.; licensee BioMed Central Ltd.
Yamanoi K.,Keio University |
Kondoh Y.,Nerima General Hospital |
Fujii T.,Nerima General Hospital |
Kurihara N.,Nerima General Hospital |
And 2 more authors.
Pathology International | Year: 2010
Few cases of gastric carcinoma with infiltrating multi-nucleated giant cells (MGCs) have been reported, and giant cells infiltrating the gastric carcinoma were previously described as osteoclast-like giant cells (OGCs). However, hepatoid adenocarcinomas have never been reported previously, and the present case is extremely rare. A 100-year-old Japanese man with gastralgia was found to have a mass in his gastric body. Histological examination showed a poorly differentiated adenocarcinoma with infiltration of MGCs. Vascular and lymphatic invasion were noted but there were no metastases. Almost all the tumor comprised cells with hepatoid-like features. The MGCs proliferated, with infiltration of lymphoid cells. A few MGCs contained mucous material in their cytoplasm, indicating these were foreign-body giant cells. Immunohistochemically, the hepatoid-like components were positive for AFP, and staining with polyclonal antibodies against carcinoembryonic antigen (CEA) showed the canalicular pattern. We concluded that this component was hepatoid adenocarcinoma. The MGCs were positive for CD68, and surrounding infiltrating lymphoid cells were diffusely positive for CD3. Infiltration of MGCs in gastric cancer may represent a cellular immune response against gastric cancer invasion. Further studies are required to elucidate the etiology of MGCs in gastric cancer. © 2010 The Authors. Pathology International © 2010 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
Hamaguchi T.,National Cancer Center Hospital |
Shirao K.,Oita University |
Moriya Y.,The Surgical Center |
Yoshida S.,Aomori Prefectural Central Hospital |
And 2 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011
Objective: In the latter 1990s, adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan. We conducted two independent randomized controlled trials in patients with Stage III colon and rectal cancer. Methods: Patients were randomly assigned to receive surgery alone or surgery followed by treatment with UFT (400 mg/m 2/day), given for five consecutive days per week for 1 year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS). Results: A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. The patients' characteristics were similar between the UFT group and the Surgery-alone group. There was no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the Surgery-alone group. The only grade 4 toxicity in the UFT group was diarrhea, occurring in one patient with colon cancer and one patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.89). © 2010 Springer-Verlag.
Arakaki K.,University of Ryukyus |
Chinen K.,Nerima General Hospital |
Kamiya M.,SRL Inc |
Tanabe Y.,University of Ryukyus |
And 5 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2014
Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.
PubMed | Nerima General Hospital
Type: Case Reports | Journal: The Tokai journal of experimental and clinical medicine | Year: 2011
We herein report the case of a bladder tumor in an 85-year-old man who had been engaged in phenacetin abuse. He had been taking phenacetin owing to migraine headaches since he was 45 year of age. His total intake of phenacetin was approximately 7.3 to 11.5 kg over a period of years. He visited the Department of Urology in our hospital due to gross hematuria and pain on urination. IVP and a pelvic CT scan revealed a tumor mass on the right lateral wall of the urinary bladder. TUR-BT was performed. A histopathological examination of the resected specimen was diagnosed as urotherial carcinoma, grade 23, pT2N0M0. To our acknowledge, only 24 cases of urotherial tumors owing to phenacetin abuse have been previously reported in the Japanese literature, making this the 25 th such case to be reported in Japan.