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Morimoto T.,Kyoto University | Sakuma M.,Kyoto University | Matsui K.,Yamaguchi University | Kuramoto N.,Kyoto University | And 6 more authors.
Journal of General Internal Medicine | Year: 2011

BACKGROUND: The epidemiology of adverse drug events (ADEs) and medication errors has received little evaluation outside the U.S. and Europe, and extrapolating from these data might not be valid, especially regarding selecting and prioritizing solutions. OBJECTIVE: To assess the incidence and preventability of ADEs and medication errors in Japan. DESIGN: The Japan Adverse Drug Events (JADE) study was a prospective cohort study. PATIENTS: A cohort of 3,459 adults admitted to a stratified random sample of seven medical and eight surgical wards and three intensive care units in three tertiary care hospitals over 6 months. MAIN MEASURES: We measured ADE and medication error rates from daily reviews of charts, laboratories, incident reports, and prescription queries by on-site reviewers; presence of a signal was considered an incident. Two independent physicians reviewed incidents to determine whether they were ADEs or medication errors and to assess severity and preventability. KEY RESULTS: We identified 1,010 ADEs and 514 medication errors (incidence: 17.0 and 8.7 per 1,000 patient-days, respectively) during the study period. Among ADEs, 1.6%, 4.9% and 33% were fatal, life-threatening and serious, respectively. Among ADEs, 14% were preventable. The rate per admission was 29 per 100 admissions, higher than in U.S. studies because associated with of the long length of hospital stay in Japan (mean, 17 days). CONCLUSIONS: The epidemiology and nature of ADEs and medication errors in Japan were similar to other countries, although more frequent per admission. Solutions that worked in these countries might thus improve medication safety in Japan, as could shortening hospital length of stay. © 2010 Society of General Internal Medicine.


PubMed | Harasanshin Hospital, National Hospital Organization Fukuoka Higashi Medical Center, National Hospital Organization Beppu Medical Center, Fukuoka City Hospital and 7 more.
Type: Journal Article | Journal: Scandinavian journal of gastroenterology | Year: 2016

Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications.One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated.Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate.Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.


PubMed | University of Washington, You no mori clinic, Fujita Health University Hospital, Keio University and 4 more.
Type: Journal Article | Journal: BMC health services research | Year: 2017

Physician-led home visit care with medical teams (Zaitaku care) has been developed on a national scale to support those who wish to stay at home at the end of life, and promote a system of community-based integrated care in Japan. Medical care at the end of life can be expensive, and is an urgent socioeconomic issue for aging societies. However medical costs of physician-led home visits care have not been well studied. We compared the medical costs of Zaitaku care and hospital care at the end of life in a rapidly aging community in a rural area in Japan.A cross-sectional study was performed to compare the total medical costs during patients final days of life (30days or less) between Zaitaku care and hospital care from September 2012 to August 2013 in Fukuoka Prefecture, Japan.Thirty four patients died at home under Zaitaku care, and 72 patients died in the hospital during this period. The average daily cost of care during the last 30days did not differ significantly between the two groups. Although Zaitaku care costs were higher than hospital care costs in the short-term (10days, Zaitaku care $371.2 vs. Hospital care $202.0, p=0.492), medical costs for Zaitaku care in the long-term care (30days) were less than that of hospital care ($155.8 vs. $187.4, p=0.055).Medical costs of Zaitaku care were less compared with hospital care if incorporated early for long term care, but it was high if incorporated late for short term care. For long term care, medical costs for Zaitaku care was 16.7% less than for hospitalization at the end of life. This physician-led home visit care model should be an available option for patients who wish to die at home, and may be beneficial financially over time.


Koshikawa N.,Tokyo Medical University | Mizushima H.,Osaka University | Minegishi T.,Tokyo Medical University | Eguchi F.,Aso Iizuka Hospital | And 5 more authors.
Cancer Science | Year: 2011

Increased expression of heparin-binding EGF-like growth factor (HB-EGF) and membrane-type matrix metalloproteinase-1 (MT1-MMP) is frequently associated with various types of malignant tumor. HB EGF-like growth factor has been reported to promote the malignant progression of ovarian carcinoma. Based on this finding, inhibition of HB-EGF activity with CRM197 is now under phase I clinical evaluation. On the other hand, MT1-MMP expressed in ovarian carcinoma cells is thought to promote invasion and growth of tumor cells by degrading the extracellular matrix. However, we recently demonstrated that co-expression of MT1-MMP and HB-EGF in gastric carcinoma cells leads to cleavage of HB-EGF within its N-terminal heparin-binding region, converting it into a potent heparin-independent growth factor. In this study, we evaluated the importance of regulation of HB-EGF by MT1-MMP in clinical samples of ovarian carcinoma. We detected co-expression of HB-EGF and MT1-MMP in clear cell ovarian carcinoma tissues, particularly at the invasion front and in tumor cells that had disseminated into the ascites, whereas HB-EGF alone was expressed in non-invasive borderline ovarian tumor tissue. Furthermore, a soluble HB-EGF fragment that corresponds to that processed by MT1-MMP was detected in malignant ascites obtained from patients with metastatic ovarian carcinoma. Ovarian carcinoma cells that express MT1-MMP and HB-EGF exhibited enhanced cell growth in a 3D-collagen matrix and anchorage-independent growth in suspension. These results indicate that MT1-MMP co-expressed with HB-EGF in ovarian carcinoma cells potentiates the activity of HB-EGF to promote invasive tumor growth and spreading in vivo. © 2010 Japanese Cancer Association.


Yamada Y.,Kyushu University | Kohashi K.,Kyushu University | Fushimi F.,Aso Iizuka Hospital | Takahashi Y.,Kyushu University | And 6 more authors.
Cancer | Year: 2014

BACKGROUND Solitary fibrous tumors (SFTs) are soft tissue tumors of intermediate malignancy that rarely metastasize. Although unresectable SFTs are reported to have a poor prognosis, to the authors' knowledge there is currently no effective therapy. Molecular target therapy is a promising approach for patients with unresectable tumors, but knowledge of the molecular biology of SFTs is currently insufficient to support such therapy. The current study investigated the activation of receptor tyrosine kinases (RTKs) and the Akt-mammalian target of rapamycin (Akt-mTOR) pathway in SFTs as therapeutic targets. METHODS The phosphorylation statuses of Akt-mTOR pathway proteins (p-Akt, p-mTOR, phosphorylated 4E-binding protein [p-4EBP1], and phosphorylated S6 ribosomal protein [p-S6RP]) and RTKs (phosphorylated platelet-derived growth factor receptor-α [p-PDGFRα], p-PDGFRβ, p-c-met, and phosphorylated insulin-like growth factor-1 receptor-β [p-IGF-1Rβ]) were assessed by immunohistochemistry in 66 samples of SFTs, and the data were compared with clinicopathological and histopathological findings. The expression of phosphorylated proteins was assessed by Western blot analysis in 6 frozen samples. RESULTS The immunohistochemical results were as follows: p-Akt, 56.0% (nuclear and cytoplasmic staining); p-mTOR, 69.6% (nuclear and cytoplasmic staining); p-4EBP1, 80.3% (nuclear and cytoplasmic staining); p-S6RP, 69.6% (cytoplasmic staining); p-PDGFRα, 39.0% (cytoplasmic staining); p-PDGFRβ, 52.0% (cytoplasmic staining); p-c-met, 37.8% (nuclear staining) and 19.6% (cytoplasmic staining); and p-IGF-1Rβ, 16.6% (nuclear staining). Phosphorylation of the Akt-mTOR pathway proteins was correlated with one another except for p-Akt with S6RP. p-PDGFRβ and p-IGF-1Rβ were correlated with p-Akt. Moreover, significant relationships were noted between disease-free survival or overall survival and the presence of hypoglycemia, necrosis, cystic and myxoid degeneration, and atypical findings. CONCLUSIONS The Akt/mTOR pathway was activated in approximately 50% of the cases of SFTs and was associated with RTKs, which were phosphorylated at different rates. Thus, the Akt-mTOR pathway may be involved in the tumorigenesis of SFTs. Cancer 2014;120:864-876. © 2013 American Cancer Society. The results of the current study demonstrated that the following were candidate prognostic factors for solitary fibrous tumors: activation of the Akt-mammalian target of rapamycin (Akt/mTOR) pathway, the existence of paracrine-autocrine system-associated phosphorylation of the receptor tyrosine kinases (RTKs), and some histological features. The RTKs and the Akt/mTOR pathway have the potential to be therapeutic targets. © 2013 American Cancer Society.


Shirabe K.,Aso Iizuka Hospital | Shirabe K.,Kyushu University | Kajiyama K.,Aso Iizuka Hospital | Harimoto N.,Aso Iizuka Hospital | And 3 more authors.
World Journal of Surgery | Year: 2010

Background: Massive bleeding during hepatectomy is a risk for mortality and morbidity. We examined the risk factors for massive bleeding and their correlations with outcomes. Methods: The study was a retrospective case series. Among 353 consecutively hepatectomized patients, the mean estimated blood loss (EBL) was 825 ml. Ten patients (2.8%) experienced EBL of between 3000 and 5000 ml. Five patients (1.4%) experienced massive EBL defined as more than 5000 ml, and all five patients had undergone right major hepatectomy (RMH) for primary liver cancer (PLC). All the patients with PLC who underwent RMH were divided into two groups: group I with EBL ≤ 5000 ml (n = 19) and group II with EBL > 5000 ml (n = 5). Perioperative factors regarding massive bleeding and operative mortality and morbidity were compared between the two groups. Results: Among the ten patients who experienced EBL of between 3000 and 5000 ml, three had partial hepatectomy of no more than subsegmentectomy of the paracaval portion of the caudate lobe and three had central bisegmentectomy. The mean tumor size was 7.9 ± 4.7 cm in group I and 15.1 ± 2.2 cm in group II (P = 0 .0034). Tumor compression of the inferior vena cava (IVC) on CT scans was observed in all patients in group II, but in no patients in group I (P < 0.0001). Four of five patients in group II received surgery through an anterior approach. The liver-hanging maneuver (LHM) was applied in 14 of 19 patients (74%) in group I but could not be applied in group II (P = 0.0059). No postoperative and in-hospital mortalities occurred in group II and there were no significant differences in the incidence of mortality and morbidity between the groups. Conclusions: RMH for large PLCs, tumor compression of the IVC, and an anterior approach without the LHM are risks for massive bleeding during hepatectomy. Preparation of rapid infusion devices in these cases is necessary to avoid prolonged hypotension. © 2010 Société Internationale de Chirurgie.


Kikkawa Y.,Kyushu University | Natori Y.,Aso Iizuka Hospital | Sasaki T.,Kyushu University
Neurologia Medico-Chirurgica | Year: 2012

A 42-year-old male presented with a rare case of delayed aneurysmal formation of the intracranial ophthalmic artery after closed head injury manifesting as subarachnoid hemorrhage. Initial magnetic resonance angiography revealed no aneurysmal formation, but angiography 7 days after the injury demonstrated an intracranial ophthalmic artery aneurysm. Follow-up computed tomography angiography demonstrated enlargement of the aneurysm. The aneurysm was successfully treated by surgical resection. Histological examination revealed that the aneurysm was a pseudoaneurysm. Traumatic intracranial aneurysm (TICA) is rare and usually occurs in the peripheral arteries of the cerebral circulation or the basal portion of the internal carotid artery. The present case shows that failure to demonstrate an aneurysm on the initial angiography in the acute stage does not exclude the presence of traumatic aneurysm. This case clearly shows the time course of development of a TICA of the ophthalmic artery after closed head injury.


Abe T.,Aso Iizuka Hospital | Nagaie T.,Aso Iizuka Hospital | Miyazaki M.,Aso Iizuka Hospital | Ochi M.,Aso Iizuka Hospital | And 2 more authors.
Clinical and Experimental Gastroenterology | Year: 2013

Purpose: Laparoscopic appendectomy (LA) for acute appendicitis has several advantages over open appendectomy (OA). In cases of complicated appendicitis, LA is converted to OA at a constant rate, though converting appendectomy (CA) has several disadvantages. We retrospectively determined preoperative risk factors for failure of LA and subsequent conversion to OA. Methods: Consecutive cases of preoperative computed tomography (CT) and attempted LA were retrieved from our hospital database and grouped by procedure (LA versus CA). Patients with negative appendectomies (n = 28), opened appendectomy (n = 210), delayed interval appendectomy (n = 3), or who were,14 years of age were excluded. Results: Average patient age, preoperative C-reactive protein (CRP) level, and diffuse peritonitis were significantly different between the groups. CT inflammation and occurrence of complicated appendicitis were significantly higher in CA than LA. Conversion to OA was mostly because of dense adhesions, diffuse peritonitis, and difficulties in excision of the appendix due to perforation or severe inflammation from surgical point of view. Postoperative complications were significantly lower in LA than CA, although the rate of intraoperative abscess was not different. Conclusion: Most patients with acute appendicitis can be successfully treated with LA. We identified the following significant risk factors of CA: CT inflammation grade 4 or 5; complicated appendicitis; higher preoperative CRP level; and diffuse peritonitis. © 2013 Abe et al, publisher and licensee Dove Medical Press Ltd.


Oya M.,Aso Iizuka Hospital | Akahoshi K.,Aso Iizuka Hospital | Toyomasu T.,Aso Iizuka Hospital
Gastric Cancer | Year: 2012

We report a rare case of adenocarcinoma arising in a gastric partial diverticulum in the upper portion of the stomach. The lesion had been followed up for approximately 14 years as a gastric submucosal tumor. However, a recent regular check-up revealed mucous material with some neoplastic tissue discharged from the top of the lesion. A surgically resected specimen showed a well-demarcated submucosal lesion identical to a pseudodiverticulum carrying a distinctive intramucosal minimally invasive adenocarcinoma in part, with surrounding nonneoplastic but hyperplastic mucosal components. Intestinal phenotype, along with gastric foveolar, pyloric gland-type phenotypes, and neoplastic cells with neuroendocrine differentiation, were also identified in the adenocarcinoma. Chronic and persistent irritation within the diverticulum was postulated to be implicated in the carcinogenesis of the lesion, which carried no definite Helicobacter pylori microorganisms. We believe it is crucial not to overlook carcinoma in a diverticulum presenting as a long-standing submucosal tumor. © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2011.


Ueno T.,University of Tsukuba | Ueno T.,Aso Iizuka Hospital | Takeda K.,Aso Iizuka Hospital | Nagata M.,University of Tsukuba
Nephrology Dialysis Transplantation | Year: 2012

Background. Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. Methods. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Results. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. Conclusion. Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis. © 2011 The Author.

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