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Tajiri N.,Social Insurance Tagawa Hospital | Shimajiri S.,University of Occupational and Environmental Health Japan
Hepatology Research | Year: 2011

A 50-year-old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9mg/dL and 32μg/dL, respectively. The 24-h urinary copper excretion was 331.8μg/day. Kayser-Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4μg/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory-Denk bodies. Many of the p62-expressing cells were positive for 4-Hydroxy-2-nonenal (HNE). Few Ki-67-positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper-loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease. © 2011 The Japan Society of Hepatology.


PubMed | Red Cross, Sasebo City General Hospital, Nakagami Hospital, Omuta City Hospital and 6 more.
Type: Clinical Trial, Phase II | Journal: International journal of clinical oncology | Year: 2016

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.


PubMed | Kumamoto University, Social Insurance Tagawa Hospital, Nakagami Hospital, Kyushu University and 4 more.
Type: Journal Article | Journal: International journal of clinical oncology | Year: 2016

This study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients.This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age 20 years; Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m(2) oxaliplatin on day 1 plus 1,000 mg/m(2) capecitabine b.i.d. on days 1-14) every 3 weeks. The primary endpoint was confirmed objective response rate.The study included 47 patients (male/female 30/17; median age 69 years; age range 38-81 years with 10 patients 75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0-67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8-12.3) and 34.6 months (95 % CI 19.9-not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed.First-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients.UMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E.


Shitara K.,Aichi Cancer Center Hospital | Morita S.,Yokohama City University | Fujitani K.,The Surgical Center | Kadowaki S.,Saitama Cancer Center Hospital | And 13 more authors.
Gastric Cancer | Year: 2012

Background It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy. Methods We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy. Results In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1 months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4 months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8 months, and the median overall survival (OS) was 12.2 months. Compared with patients with an RFI of\6 months (n = 25), patients with an RFI of C6 months (n = 27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2 months, respectively), and longer overall survival (7.3 vs. 16.6 months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6 months was still significantly associated with PFS and OS. Conclusions S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of C6 months. © 2011 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.


Kawaguchi T.,Social Insurance Tagawa Hospital | Miyajima I.,Kurume University | Maekawa R.,Social Insurance Tagawa Hospital | Yano H.,Kurume University | Torimura T.,Kurume University
Journal of Japanese Society of Gastroenterology | Year: 2015

A 55-year-old man presented with general malaise in May 2012. On reviewing his clinical records in 1989, we found that he had a hepatocellular carcinoma (HCC) in the left lobe, for which he had undergone left lobectomy in November 1989. However, there was no record of any follow-up examination from 1996 to 2011. Computed tomography in May 2012 revealed a right adrenal gland tumor measuring 8.5 × 6.5cm, which we treated by right adrenalectomy. Postoperative pathological examination showed this to be a metastasis of poorly differentiated HCC. To the best of our knowledge, no previous study has reported HCC recurrence such a long duration after HCC resection.


Okabe Y.,Kurume University | Kaji R.,Kurume University | Ishida Y.,Kurume University | Noda T.,Nagata Hospital | And 3 more authors.
Digestive Endoscopy | Year: 2010

In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater. © 2010 Japan Gastroenterological Endoscopy Society.


Mitsuyama K.,Kurume University | Niwa M.,Toagosei Co. | Masuda J.,Kurume University | Yamasaki H.,Kurume University | And 17 more authors.
Journal of Gastroenterology | Year: 2014

Background: Various noninvasive tests have been studied to screen for patients with Crohn's disease (CD), and were found to have limited accuracy and sensitivity, particularly in Asian populations. The aim of our study was to explore the possible diagnostic utility of antibodies to the CD peptide (ACP) in patients with CD. Methods: In a multicenter study using enzyme-linked immunosorbent assay, serum ACP levels were determined in 196 patients with CD, 210 with ulcerative colitis, 98 with other intestinal diseases, 132 with other inflammatory diseases, and 183 healthy controls. and then examined for correlation to clinical variables. The diagnostic utility of ACP was evaluated by receiver operating characteristics analysis and compared with anti-Saccharomyces cerevisiae antibodies (ASCA). Results: ACP levels were significantly elevated in the CD patients, but not in the other groups that included UC, other intestinal diseases, other inflammatory diseases and the healthy controls. Among these other groups, ACP levels were not significantly different. In the CD patients, ACP had a higher sensitivity and specificity (63.3 and 91.0 %, respectively) than ASCA (47.4 and 90.4 %). ACP levels were negatively associated with disease duration, but not with CDAI, disease location, or medical treatment. Conclusions: ACP, a newly proposed serologic marker, was significantly associated with CD and was highly diagnostic. Further investigation is needed across multiple populations of patients and ethnic groups, and more importantly, in prospective studies. © 2013 Springer.

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