University of Technology of Compiègne, France
University of Technology of Compiègne, France

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Saito M.,Sapporo Medical University | Yamashita K.,Sapporo Medical University | Arimura Y.,Sapporo Medical University | Kaneto H.,Muroran City General Hospital | And 16 more authors.
Acta Oncologica | Year: 2016

Background: Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer. Methods: We performed a prospective multicenter trial (SHERLOCK trial) involving patients with allstage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated. Results: Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0 ng/ml (median 10.3), correlated with tissue HER2 status (p=0.003). At a cut-off level of 28.0 ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2. Conclusions: Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer. © 2016 Taylor & Francis.


PubMed | Teine Keijinkai Hospital, Obihiro Kyokai Hospital, Sapporo Satozuka Hospital, Sapporo Medical University and 12 more.
Type: Journal Article | Journal: Acta oncologica (Stockholm, Sweden) | Year: 2016

Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity of gastric cancer can be an obstacle to accurate HER2 assessment. Serum HER2, concentrations of the HER2 extracellular domain shed into the bloodstream, has a potential to compensate HER2 immunohistochemistry (IHC) but has not been scrutinized in gastric cancer. This study sought to explore the clinical utility of serum HER2 in gastric cancer.We performed a prospective multicenter trial (SHERLOCK trial) involving patients with all-stage gastric or gastro-esophageal junction cancer. Serum HER2 was measured using direct chemiluminescence while tissue HER2 status was determined using IHC and fluorescent in situ hybridization. For stage IV cases, concordance between local and central laboratories in tissue HER2 assessment was also evaluated.Of 224 patients enrolled, both tissue HER2 status and serum HER2 levels were successfully determined in 212 patients and 21% (45/212) were tissue HER2-positive. Serum HER2 levels, ranged from 4.5 to 148.0ng/ml (median 10.3), correlated with tissue HER2 status (p=0.003). At a cut-off level of 28.0ng/ml determined by receiver operating characteristics analysis, sensitivity, specificity, positive and negative predictive values of serum HER2 were 22.6%, 100%, 100% and 82.3%, respectively. All nine cases with elevated serum HER2 were tissue HER2-positive stage IV cases. Among 61 stage IV cases, the agreement rate for IHC scoring between the local and the central laboratories was 82% and tissue HER2 judgment was conflicting in five (8.2%) cases. Of these five cases, four were confirmed as false-negative and two of these four patients demonstrated elevated serum HER2.Serum HER2 levels correlated with tissue HER2 status in gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be a useful adjunct tool to detect tissue HER2 false-negative gastric cancer.


Sugino S.,Sapporo Medical University | Sugino S.,Otaru Municipal Hospital | Sugino S.,Pennsylvania State University | Hayase T.,Sapporo Medical University | And 9 more authors.
Experimental Brain Research | Year: 2014

Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the μ-opioid receptor gene (OPRM1) might be associated with individual differences in opioid sensitivity, as well as with the incidence and severity of postoperative nausea and vomiting (PONV). The goal of the present study was to determine, in a cohort of Japanese surgical patients, genotypes and haplotypes of several SNPs in the OPRM1 gene, and their association with PONV during the early (first 24 h) postoperative period. We examined the incidence and severity of PONV, during the first 24 h after surgery, in 85 Japanese patients receiving intravenous patient-controlled analgesia fentanyl analgesia for postoperative pain control. Eight tag SNPs of the OPRM1 gene (rs1799971, A/G; rs510769, G/A; rs4870266, G/A; rs3798683, G/A; rs1323042, A/C; rs609623, C/T; rs9397685, A/G; and rs644261, C/G) were selected based on their minor allele frequency (>10 %) and linkage disequilibrium strength (<80 %), and genotyped for haplotype analysis and determination of associations with PONV. Only one out of eight investigated SNPs, rs9397685, in the intronic part of the OPRM1 gene was associated with differences in the occurrence and severity of PONV. We also found four common haplotypes with a frequency of >10 % in the investigated patients, including GGGAACAC (33 %), AGGGACAC (19 %), GGGAACGC (12 %), and AGAGACAC (10 %). The severity of PONV in carriers of the GGGAACGC haplotype was significantly lower than in the carriers of the other haplotypes (P < 0.05). One intronic SNP, rs9397685, and haplotypes constructed from eight SNPs within the OPRM1 gene locus might be involved in the severity of PONV associated with general anesthesia and opioid administration. This novel finding, if validated and verified in larger and additional ethnic cohorts, might contribute to better knowledge of the contribution of the OPRM1 gene to PONV. © 2014 Springer-Verlag.


Isosaka M.,Otaru Municipal Hospital | Adachi T.,Otaru Municipal Hospital | Iida T.,Otaru Municipal Hospital | Mitsuhashi K.,Otaru Municipal Hospital | And 5 more authors.
Journal of Japanese Society of Gastroenterology | Year: 2014

A 60-year-old woman underwent upper gastrointestinal endoscopy for an abnormality identified during routine examination. The lower gastric corpus showed a type 0-I elevated lesion with a faded mucosa and an area of converging mucosal folds in contact with the lesion. Biopsy indicated the former to be a high-grade adenoma and the latter to be a mucosa-associated lymphoid tissue (MALT) lymphoma. At the same time, Helicobacter pylori infection was diagnosed. Eradication therapy was administered to manage the MALT lymphoma ; this resulted in improvement after 3 months. Endoscopic submucosal dissection was performed for the elevated lesion, and subsequent histopathology showed contact between the MALT lymphoma and gastric cancer. Therefore, the patient was diagnosed with a collision tumor. Concurrent cancers are increasingly reported and should be considered during examination.


Aral K.,Otaru Municipal Hospital | Aral K.,Hakodate Goryoukaku Hospital | Imai A.,Otaru Municipal Hospital | Ikeda T.,Hakodate Goryoukaku Hospital
Japanese Journal of Plastic Surgery | Year: 2015

Ectopic hamartomatous thymomas that are extremely rare benign tumors of the lower neck and suprasternal region are most common in middleaged men. Histologically, this tumor is characterized by an admixture of spindle cells, epithelial cells, and mature adipose cells. Its histogenesis is still controversial. The results of fine-needle aspiration biopsy in conjunction with characteristic clinical findings may contribute to correctly diagnosing this tumor. Although it is difficult to distinguish hamartomatous thymomas from malignant lesions such as sarcomas, the correct diagnosis of this tumor is important because it follows a benign clinical course and surgical excision is an adequate therapy. We report the case of an ectopic hamartomatous thymoma in the right subclavicular region of a 63-year-old man, for which fine needle aspiration biopsy was preoperatively performed. This article also includes a review of the literature regarding this tumor.


Gadolinium ethoxybenzyl diethylenetriamine pantaacetic acid (Gd-EOB-DTPA) is incorporated into liver cells, and liver parenchyma show hyperintensity due to the T1 shortening effect. The T1 value of liver parenchyma in the hepatocyte phase changes from the pre-contrast phase. However, in patients with liver dysfunction, the difference of T1 value is generally small. In examination of hepatic disease, the optimal flip angle should be selected according to the patient's state. The definition of hepatic dysfunction based on biochemical data is diverse. Therefore, if the image findings can estimate liver dysfunction, the operator will select the optimal flip angle. Hence, we defined the criteria of liver dysfunction based on the image data; one or more of the following abnormalities-irregular liver surface, splenomegaly, and expansion of portal trunk. In classification by imaging data, we compared the T1 value of liver parenchyma in the hepatocyte phase, and found that the T1 value was significantly different between normal and cirrhotic liver. Then, in a phantom study simulating normal and cirrhotic liver, we set the optimal flip angle (FA)-21 degrees for the normal liver state, and 18 degrees for the LC state. In Gd-EOB-DTPA-enhanced study, the operator can select the optimal FA for each patient according to the image findings.


PubMed | Otaru Municipal Hospital
Type: Case Reports | Journal: Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology | Year: 2014

A 60-year-old woman underwent upper gastrointestinal endoscopy for an abnormality identified during routine examination. The lower gastric corpus showed a type 0-I elevated lesion with a faded mucosa and an area of converging mucosal folds in contact with the lesion. Biopsy indicated the former to be a high-grade adenoma and the latter to be a mucosa-associated lymphoid tissue (MALT) lymphoma. At the same time, Helicobacter pylori infection was diagnosed. Eradication therapy was administered to manage the MALT lymphoma; this resulted in improvement after 3 months. Endoscopic submucosal dissection was performed for the elevated lesion, and subsequent histopathology showed contact between the MALT lymphoma and gastric cancer. Therefore, the patient was diagnosed with a collision tumor. Concurrent cancers are increasingly reported and should be considered during examination.


Gadolinium ethoxybenzyl diethylenetriamine pantaacetic acid (Gd-EOB-DTPA) is incorporated into liver cells, and liver parenchyma show hyperintensity due to the T1 shortening effect. The T1 value of liver parenchyma in the hepatocyte phase changes from the pre-contrast phase. However, in patients with liver dysfunction, the difference of T1 value is generally small. In examination of hepatic disease, the optimal flip angle should be selected according to the patients state. The definition of hepatic dysfunction based on biochemical data is diverse. Therefore, if the image findings can estimate liver dysfunction, the operator will select the optimal flip angle. Hence, we defined the criteria of liver dysfunction based on the image data; one or more of the following abnormalities-irregular liver surface, splenomegaly, and expansion of portal trunk. In classification by imaging data, we compared the T1 value of liver parenchyma in the hepatocyte phase, and found that the T1 value was significantly different between normal and cirrhotic liver. Then, in a phantom study simulating normal and cirrhotic liver, we set the optimal flip angle (FA)-21 degrees for the normal liver state, and 18 degrees for the LC state. In Gd-EOB-DTPA-enhanced study, the operator can select the optimal FA for each patient according to the image findings.


PubMed | Otaru Municipal Hospital
Type: Case Reports | Journal: Masui. The Japanese journal of anesthesiology | Year: 2010

A 60-year-old man with angina was scheduled for total gastrectomy, splenectomy, and cholecystectomy. Bare-metal stents were implanted into his left anterior descending coronary artery four weeks before the operation. Aspirin and clopidogrel were administered until one week before the operation and then injection of to 15,000 units of heparin per day was given. Anesthesia was maintained with sevoflurane, remifentanil and fentanyl. At 330 minutes after starting the operation, 2-mm ST segment elevation was observed and it recovered immediately. After the operation, new 9-mm ST segment elevation in leads V2-V6 was observed. Emergent cardiac catheterization showed occlusion of the coronary artery with in-stent thrombosis. An additional stent was implanted and 10,000 units of heparin per day was injected. After five days, new stent thrombosis occurred and an additional stent was implanted. Administration of aspirin, clopidogrel and cilostazol was started immediately. Anesthesiologists should pay attention to the kind of coronary stent, consider the timing of the operation, and continue administration of aspirin.


PubMed | Otaru Municipal Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2012

S-1 and capecitabine are orally administered fluoropyridines reported to be effective in the treatment of advanced gastric cancer(AGC). In fact, both S-1/CDDP and capecitabine/CDDP are considered to be the standard first-line treatments for AGC.However, no information concerning on the activity of capecitabine in S-1-pretreated patients with AGC has been reported. Here, we present a case of recurrent gastric cancer that showed a partial response resulting in 6 months of progres-sion-free survival, thanks to capecitabine/CDDP after the failure of multiple anticancer drugs such as S-1/CDDP. S -1 and capecitabine may exhibit cross-resistance because they both have the same final active metabolite: 5-fluorouracil(5-FU). Dihydropyrimidine dehydrogenase(DPD)is the rate-limiting enzyme in the degradation of 5-FU, and S-1 contains the inhibitor of DPD. Thus, S-1, but not capecitabine, is active against tumors with high DPD expression. On the other hand, capecitabine is activated to 5-FU by thymidine phosphorylase(TP)within the tumor tissue and is more effective against tumors with high TP expression. The present case suggests that S-1 and capecitabine do not always exhibit cross-resistance, and that capecitabine may be effective in S-1-pretreated patients with AGC.

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