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Karube K.,Aichi Cancer Center Research Institute | Nakagawa M.,Aichi Cancer Center Research Institute | Tsuzuki S.,Aichi Cancer Center Research Institute | Takeuchi I.,Nagoya Institute of Technology | And 10 more authors.
Blood | Year: 2011

Oligo-array comparative genomic hybridization (CGH) and gene-expression profiling of natural killer (NK) - cell neoplasms were used in an effort to delineate the molecular pathogenesis involved. Oligoarray CGH identified two 6q21 regions that were most frequently deleted (14 of 39 or 36%). One of these regions included POPDC3, PREP, PRDM1, ATG5, and AIM1, whereas the other included LACE1 and FOXO3. All genes located in these regions, except for POPDC3 and AIM1, were down-regulated in neoplastic samples, as determined by gene-expression analysis, and were therefore considered to be candidate tumor-suppressor genes. A20 and HACE1, the well-known tumor-suppressor genes located on 6q21-23, were included as candidate genes because they also demonstrated frequent genomic deletions and down-regulated expression. The Tet-Off NK cell line NKL was subsequently established for functional analyses. Seven candidate genes were transduced into Tet-Off NKL and forced re-expression was induced. Re-expression of FOXO3 and PRDM1 suppressed NKL proliferation, but this was not the case after re-expression of the other genes. This effect was confirmed using another NK cell line, SNK10. Furthermore, genomic analyses detected nonsense mutations of PRDM1 that led to functional inactivation in one cell line and one clinical sample. PRDM1 and FOXO3 are considered to play an important role in the pathogenesis of NK-cell neoplasms. © 2011 by The American Society of Hematology.


Mano Y.,Kyushu University | Shirabe K.,Kyushu University | Yamashita Y.-I.,Red Cross | Harimoto N.,Iizuka Hospital | And 7 more authors.
Annals of Surgery | Year: 2013

OBJECTIVE:: To clarify the prognostic value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND:: Although a high NLR has been reported to be a predictor of poor survival in patients with various cancers, it has not been extensively examined in patients with HCC. METHODS:: This retrospective study enrolled 958 patients who underwent hepatectomy without preoperative therapy for HCC from 1996 to 2009. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. To determine the mechanism of NLR elevation, immunohistological examination using CD163 staining was performed in 150 patients. RESULTS:: Univariate and multivariate analyses showed that NLR was an independent prognostic factor in overall and recurrence-free survival. The best cutoff of NLR was 2.81, and 238 of 958 patients (24.8%) had NLR of more than 2.81. The 5-year survival rate after hepatectomy was 72.9% in patients with NLR less than 2.81 and 51.5% in those with NLR 2.81 or more (P < 0.0001). CD163-positive cell counts were significantly higher in tumors in the group with NLR 2.81 or more than in the group with NLR less than 2.81 (P = 0.0004). CONCLUSIONS:: Our results show that NLR is an independent predictor of survival after hepatectomy in patients with HCC. Accumulation of tumor-associated macrophages in the tumor is associated with a high NLR. Copyright © 2013 Lippincott Williams & Wilkins.


Kodate M.,Iizuka Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2010

We report a 70-year-old man who suffered from right anterior chest wall tumor. Physical examination revealed an elastic hard mass at the right 4th rib measured 6 cm in diameter. Chest X-ray and computed tomography (CT) revealed enhanced mass and destruction of the 4th rib. As needle aspiration cytology did not define the diagnosis, we performed a chest wall resection and reconstruction. Histological diagnosis of the tumor was plasmacytoma (IgG lambda type). Five months after the operation, the tumor recurred at the right anterior chest wall. Radiotherapy was performed with dose of 50 Gy. Fourteen months after the operation, the tumor recurred at the lower sternum, and the chemotherapy was performed using ranimustine, vincristine, melpharan and dexamethasone. He is doing well 2 years and 9 months after surgery without signs of progressive disease or conversion to myeloma


Yamada T.,Iizuka Hospital | Natori Y.,Iizuka Hospital
Journal of Stroke and Cerebrovascular Diseases | Year: 2013

Background: Diagnosis has a major impact on the outcome of subarachnoid hemorrhage (SAH). We studied patients with SAH who were admitted to our hospital in an effort to identify ways to prevent misdiagnosis. Methods: A total of 494 patients with SAH were admitted to the Department of Neurosurgery from 2003 through 2010. Misdiagnosis occurred in 30 patients (6.1%). We studied the symptoms and the types of misdiagnoses in these 30 patients. Results: Misdiagnosis occurred 37 times in the 30 patients (6 patients were given more than 1 misdiagnosis). There were 3 types of misdiagnoses. Type 1 cases were misdiagnosed as a common cold, type 2 cases were misdiagnosed as circulatory organ disease, and type 3 cases were misdiagnosed as digestive organ disease. Conclusions: Type 1 cases were mild, and diagnosis required detailed medical history analyses. Type 2 cases were severe and were diagnosed based on electrocardiographic and echocardiographic changes characteristic of SAH. Symptoms of type 3 cases included vomiting, and diagnosis required recognition of meningeal irritation syndrome and detailed medical history analyses. © 2013 by National Stroke Association.


Takahashi Y.,Iizuka Hospital
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society | Year: 2011

Erlotinib is a potent drug used for treating epidermal growth factor receptor (EGFR) mutation positive lung cancer. In this study, we report a case of erlotinib induced cutaneous vasculitis. The patient was a 69-year-old woman with a history of left lower lobe resection for lung cancer. Two years after the resection, she had metastasis in the adrenal glands for which we initiated erlotinib therapy at a dose of 150 mg/day. The patient developed multiple purpurae with a partially necrotic region on both lower thighs at 8 weeks after initiating therapy. The skin biopsy results revealed cutaneous vasculitis. We stopped erlotinib therapy after this diagnosis because of this adverse effect as well as because it exacerbated the cancer. The patient's skin manifestation disappeared 2 weeks after stopping therapy, with no recurrence of any symptoms of systemic vasculitis. We reviewed the literature on drug-induced vasculitis due to oral EGFR inhibitors and found 13 such cases. In most cases, the symptoms appeared 1-2 months after initiating therapy. In all the cases, the symptoms resolved within 2-6 weeks after stopping drug therapy. Erlotinib-induced cutaneous vasculitis is rare but may cause fatal systemic vasculitis. Therefore, the skin of patients who are undergoing erlotinib therapy should be carefully examined at regular intervals during the course of therapy for drug-induced adverse effects.


Sakamoto K.,University of Tsukuba | Sakamoto K.,Iizuka Hospital | Ueno T.,University of Tsukuba | Kobayashi N.,University of Tsukuba | And 5 more authors.
American Journal of Physiology - Renal Physiology | Year: 2014

Focal segmental glomerulosclerosis (FSGS) is a podocyte disease. Among the various histologies of FSGS, active epithelial changes, hyperplasia, as typically seen in the collapsing variant, indicates disease progression. Using a podocyte specific injury model of FSGS carrying a genetic podocyte tag combined with double immunostaining by different sets of podocytes and parietal epithelial cell (PEC) markers [nestin/Pax8, Wilms' tumor-1 (WT1)/claudin1, and podocalyxin/Pax2], we investigated the direction of epithelial phenotypic transition and its role in FSGS. FSGS mice showed progressive proteinuria and renal dysfunction often accompanied by epithelial hyperplasia, wherein 5-bromo-4-chloro-3-indoyl β-D-galactoside (X-gal)-positive podocyte-tagged cells were markedly decreased. The average numbers of double positive cells in all sets of markers were significantly increased in the FSGS mice compared with the controls. In addition, the average numbers of double-positive cells for X-gal/Pax8, nestin/Pax8 and podocalyxin/Pax2 staining in the FSGS mice were comparable, whereas those of WT1/claudin1 were significantly increased. When we divided glomeruli from FSGS mice into those with FSGS lesions and those without, double-positive cells tended to be more closely associated with glomeruli without FSGS lesions compared with those with FSGS lesions. Moreover, the majority of double-positive cells appeared to be isolated and very rarely associated with FSGS lesions (1/1,997 glomeruli). This study is the first to show the incidence and localization of epithelial cells with phenotypical changes in FSGS using a genetic tag. The results suggest that the major direction of epithelial phenotypic transition in cellular FSGS is from podocytes to PECs and that these cells were less represented in the active lesions of FSGS. © 2014 the American Physiological Society.


Ando K.,Juntendo University | Sekiya M.,Juntendo University | Tobino K.,Iizuka Hospital | Takahashi K.,Juntendo University
Lung | Year: 2013

Purpose: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, as current reports of its clinical features show. To determine CPFE's physiologic and radiologic features, we conducted quantitative assessment of computed tomography scans to compare with those of chronic obstructive pulmonary disease (COPD). Methods: In 23 patients with CPFE and 42 patients with COPD, we measured the extent of emphysema (LAA %), parenchymal density, and total cross-sectional areas of pulmonary vessels smaller than 5 mm2 (%CSA <5) and 5-10 mm2 (%CSA 5-10). Results: For CPFE, airflow was better, but diffusing capacity for carbon monoxide (DLCO) was worse than for COPD, whereas LAA % was similar for both groups. The %CSA <5 was greater but %CSA5-10 was less in CPFE than COPD. COPD involved a negative correlation between DLCO and LAA % at all lung sites; those factors correlated for CPFE only in the upper lobe (r = -0.535). In contrast, CPFE had a negative correlation between DLCO and parenchymal density in lower lobes (r = -0.453), but COPD showed no correlation in any such sections. In CPFE, no correlation was apparent between LAA in upper lobes and parenchymal density in lower lobes. The annual rate of FVC decline (-169.26 ml/year) in CPFE patients correlated with parenchymal density (r = -0.714). Conclusions: In CPFE, fibrosis and emphysema apparently existed independently, but both correlate with and likely contribute to the disproportionate reduction in gas exchange. Our study also suggested that pulmonary fibrotic changes may be more important contributors than emphysema for disease progression. © 2013 Springer Science+Business Media New York.


Natori Y.,Iizuka Hospital
Japan Medical Association Journal | Year: 2011

Revisions to the Organ Transplant Act have made it possible for the organs of a brain-dead patient to be donated for transplantation with the permission of the patient's family only, even if the patient's desires regarding donation have not been set out in writing, in all brain-death cases unless the patient has expressly indicated that they do not wish to be an organ donor. However, there has fundamentally been no change in the "legal determination of brain death"; the main changes to the Act are those related to the broadening of the age range for organ donor eligibility. Under these revisions, age divisions have also been set at ages 6 and 18 as well as the original 15, and the criteria and conditions for organ donor eligibility in each age group have become more complicated. Under the original Act, in cases where there is damage to a patient's eardrum, vestibular reflex was deemed to be impossible to perform and a legal determination of brain death was not made. However, under these revisions, regardless of the patient's age, it is now possible to perform tests to ascertain brain death using sterile physiological saline. In fact, from a medical standpoint the legal determination of brain death has a limited range of discretion, and since some matters such as the order in which tests are performed may be trivial medically, they may hold significant meaning legally and is required utmost care.


Kozo N.,Iizuka Hospital
Asian Cardiovascular and Thoracic Annals | Year: 2010

Fibrin glues are widely used for various pulmonary operations, but commercially produced glues are made of heterogeneous fibrinogen that has infection risks. We used autologous cryoprecipitate and evaluated its clinical value as a fibrin sealant instead of the commercially available glue. One hundred patients who underwent thoracoscopic bullectomy for primary spontaneous pneumothorax were studied. The apical visceral pleura was covered with an absorbable mesh and a fibrin glue. Autologous cryoprecipitate glue was used in 30 patients (group A), and commercially produced fibrinogen was used in 70 (group B). The mean duration of postoperative chest drainage was 1.9 days in group A and 1.5 days in group B. The cumulative 2-year postoperative recurrence rate was 3.4% in group A and 6.5% in group B. There were no differences in clinical results after surgery for primary spontaneous pneumothorax, using either autologous cryoprecipitate or commercially produced fibrinogen. The production autologous cryoprecipitate was easy and low-cost. We propose that autologous cryoprecipitates be used in operations for primary spontaneous pneumothorax. © SAGE Publications 2009.


Clinical evaluation of micrometastases in the lymph nodes of lung cancer patients is not currently recommended in guidelines because of several different results concerning their prevalence and prognostic implications. However, a recent large, prospective, multicenter clinical study has shown a significant prognostic impact of micrometasteses in the lymph nodes of patients with resectable lung cancer; therefore, the clinical significance of micrometastases as predictive markers of recurrence and prognosis has begun to be clarified. From the viewpoint of surgery for lung cancer, sentinel node navigation surgery, segmentectomy, and individualized therapies such as adjuvant chemotherapy are expected to be developed. In the near future, standardization and improvement of the efficiency of diagnostic procedures will be necessary in common clinical practice. Recently, minimal residual cancer cell research, such as circulating tumor cells in the peripheral blood and disseminated tumor cells in the bone marrow, has made good progress. As research in this field continues, it is expected that the mechanism of metastasis and novel therapeutic strategies targeting minimal residual cancer cells will become better understood.

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