Itami, Japan
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Kato M.,Osaka University | Nishida T.,Osaka University | Yamamoto K.,Toyonaka Municipal Hospital | Hayashi S.,Toyonaka Municipal Hospital | And 15 more authors.
Gut | Year: 2013

Background: After endoscopic submucosal dissection (ESD) of early gastric cancer (EGC), patients are at high risk for synchronous or metachronous multiple gastric cancers. Objective: To elucidate the time at which multiple cancers develop and to determine whether scheduled endoscopic surveillance might control their development. Design: A multicentre retrospective cohort study from 12 hospitals was conducted. Patients with EGC who underwent ESD with en bloc margin-negative curative resection were included. Synchronous cancer was classified as concomitant cancer or missed cancer. The cumulative incidence of metachronous cancers and overall survival rate were calculated using the Kaplan-Meier method. Results: From April 1999 to December 2010, 1258 patients met the inclusion criteria. Synchronous or metachronous multiple cancers were detected in 175 patients (13.9%) during a mean of 26.8 months. Among the 110 synchronous cancers, 21 were missed at the time of the initial ESD. Many of the missed lesions existed in the upper third of the stomach and the miss rate was associated with the endoscopist's inexperience (<500 oesophagogastroduodenoscopy cases). The cumulative incidence of metachronous cancers increased linearly and the mean annual incidence rate was 3.5%. The incidence rate did not differ between patients with or without Helicobacter pylori eradication. Four lesions (0.32%) were detected as massively invading cancers during the follow-up. Conclusions: Nineteen per cent of synchronous cancers were not detected until the initial ESD. The incidence rate of metachronous cancer after ESD was constant. Scheduled endoscopic surveillance showed that almost all recurrent lesions were treatable by endoscopic resection.


Miyashiro I.,Japan National Cardiovascular Center Research Institute | Hiratsuka M.,Itami City Hospital | Sasako M.,Hyogo College of Medicine | Sano T.,Cancer Institute Hospital of Japanese Foundation for Cancer Research | And 5 more authors.
Gastric Cancer | Year: 2014

Background: To evaluate the feasibility and accuracy of diagnosis using sentinel node (SN) biopsy in T1 gastric cancer, a multicenter trial was conducted by the Japan Clinical Oncology Group (JCOG). Methods: Sentinel node biopsy with indocyanine green (ICG) was performed in patients with T1 gastric cancer. Green-stained nodes (GNs), representing SNs, were removed first, and gastrectomy with lymphadenectomy was then performed. GNs in one plane (with the largest dimension) were histologically examined intraoperatively by frozen section with hematoxylin and eosin (H&E) stain. All harvested lymph nodes (GNs and non-GNs) were histologically examined by paraffin section after surgery. The primary endpoint was to determine the proportion of false negatives, which was defined as the number of patients with negative GNs by frozen section divided by those with positive GNs and/or positive non-GNs by paraffin section. The sample size was set at 1,550, based on the expected and threshold value as 5 and 10 % in the proportion of false negatives. Results: Accrual was suspended when 440 patients were enrolled because the proportion of false negatives was high. In the primary analysis, the proportion of false negatives was 46 % (13/28) after a learning period with 5 patients for each institution. Seven of 13 patients had nodal metastases outside the lymphatic basin. False negatives remained at 14 % (4/28) even by examining additional sections of GNs by paraffin section. Conclusions: The proportion of false negatives was much higher than expected. Intraoperative histological examination using only one plane is not an appropriate method for clinical application of SN biopsy in gastric cancer surgery. © 2013 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.


Miyashiro I.,Japan National Cardiovascular Center Research Institute | Hiratsuka M.,Itami City Hospital | Kishi K.,Japan National Cardiovascular Center Research Institute | Takachi K.,The Mutual | And 4 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Reliable indicators that can intraoperatively determine the absence of nodal metastasis are in great demand to avoid unnecessary lymphadenectomy. However, little has been reported about the intraoperative diagnostic performance of sentinel node (SN) biopsy. Methods: Sentinel node biopsy by subserosal or submucosal injection of indocyanine green (ICG) was performed in 241 patients with American Joint Committee on Cancer tumor, node, metastasis staging system, 7th edition, clinical T1 (n = 190) and T2 (n = 51) gastric cancer by two experienced surgeons. All nodes that stained green (green node, GN), representing SNs, were excised before gastrectomy and were sliced into 2-mm sections for intraoperative histological examinations with hematoxylin and eosin staining. The sliced GNs were also examined simultaneously by imprint cytology. Results: The GNs were detectable in 240 patients (3.8 ± 2.4 nodes per patient; range 1-17 nodes; median 3 nodes), and the success rate of detection was 99.6 % (240 of 241). Of 240 patients with a successful detection, 29 were found to have lymph node (LN) metastases; 16 were diagnosed with LN metastases in both GNs and non-GNs, 12 in GNs alone, and 1 in non-GNs alone. The false-negative rate based on the SN concept was 3.4 % (1 of 29). However, two patients with cT1 gastric cancer were diagnosed as intraoperative GN negative but were later confirmed as GN positive by histological examinations of paraffin sections. As an intraoperative diagnosis, the false-negative rate was 10.3 % (3 of 29). Conclusions: Sentinel node biopsy using ICG could be performed intraoperatively within reasonable limits under certain conditions, such as multiplanes for detection, combination use of imprint cytology, and open surgery by experienced surgeons. © 2012 Society of Surgical Oncology.


Fushimi R.,Osaka University | Takashina M.,Osaka University | Yoshikawa H.,Osaka University | Kobayashi H.,University of Tokyo | And 3 more authors.
American Journal of Infection Control | Year: 2013

Background: This study evaluated 3 potential indicators of gastrointestinal endoscope cleanliness: adenosine triphosphate (ATP), microbiological load, and protein. Methods: Before and after cleaning, ATP and microbiological load were determined from swabs of exterior surfaces and rinses of interior suction/accessory channels. Similarly, before and after cleaning, residual protein was determined from rinses of interior suction/accessory channels. Results: Before cleaning, ATP values were 10,417 relative light units (RLU) from the exterior endoscope surface and 30,281 RLU from the suction/accessory channel rinsates. After cleaning, these ATP values were decreased to 82 RLUs and 104 RLUs, a statistically significant difference. A similar trend was observed with microbiological load, but the change in residual protein from before cleaning to after cleaning was not significant. ATP values reliably reflected microbiological colony counts. Conclusions: ATP measurement can provide a reliable, rapid and practical assessment of endoscope cleanliness for routine monitoring in the clinical setting. Copyright © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.


PubMed | Osaka Rosai Hospital, Central Institute for Experimental Animals, Osaka University, Itami City Hospital and 8 more.
Type: | Journal: Scientific reports | Year: 2017

Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients. Next, to consider the involvement of a trace amount of pre-existing variants below the detection limit, we analysed human hepatocyte chimeric mice infected with DAA-nave patient serum. L31V-Y93H variants emerged after treatment with ledipasvir (LDV)/GS-558093 (nucleotide NS5B inhibitor) and decreased under the detection limit, but these variants were dissimilar to the L31V-Y93H variants reappearing after ASV/DCV re-treatment. Finally, to develop an infection derived from a single HCV clone, we intrahepatically injected full-genome HCV RNA (engineered based on the wild-type genotype 1b sequence) into chimeric mice. A new Y93H mutation actually occurred in this model after LDV monotherapy failure. In conclusion, post-treatment RASs appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy.


Murayama Y.,Itami City Hospital | Oritani K.,Osaka University | Tsutsui S.,Itami City Hospital
World Journal of Gastroenterology | Year: 2015

There are 33 human tetraspanin proteins, emerging as key players in malignancy, the immune system, fertilization, cellular signaling, adhesion, morphology, motility, proliferation, and tumor invasion. CD9, a member of the tetraspanin family, associates with and influences a variety of cell-surface molecules. Through these interactions, CD9 modifies multiple cellular events, including adhesion, migration, proliferation, and survival. CD9 is therefore considered to play a role in several stages during cancer development. Reduced CD9 expression is generally related to venous vessel invasion and metastasis as well as poor prognosis. We found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative, proapoptotic, and antiangiogenic effects, strongly indicating that CD9 is a possible therapeutic target in patients with gastric cancer. Here, we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer, which still shows poor prognosis. © 2015 Baishideng Publishing Group Inc. All rights reserved.


Nakai T.,Itami City Hospital | Nakamura T.,Itami City Hospital | Onishi A.,Itami City Hospital | Hashimoto K.,Itami City Hospital
Journal of Orthopaedics | Year: 2013

Background: Measures for pain management after total hip arthroplasty (THA) are important for early improvement in the quality of life after operation and early postoperative rehabilitation. We investigated the analgesic effect of locally injected drugs around the total hip prosthesis. Methods: 54 patients undergoing THA were randomized either to receive a periarticular intraoperative injection of a 30-ml mixture containing morphine hydrochloride 10 mg, 0.5% bupivacaine 20 ml, epinephrine 0.3 mg, and saline 8.7 ml or to receive no injection. The perioperative analgesic regimen was standardized. The evaluation items included assessment of pain using a 100-point visual analog scale (VAS) after the patients awoke on the day of the operation and on postoperative day 1, the dose of diclofenac sodium suppository, the number of days for acquiring assisted ambulation with a walking cane, and side effects. Results: The VAS score on the day of the operation was significantly low in the injection group. No cardiac or central nervous system toxicity was observed. Conclusions: Intraoperative periarticular injection with multimodal drugs can significantly reduce pain on the day of the operation, with no apparent risks, following THA. © 2013 Professor PK Surendran Memorial Education Foundation Publishing Services by Reed Elsevier India Pvt. Ltd. All rights reserved.


PubMed | Itami City Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2016

A 60-year-old man underwent total gastrectomy with Japanese D2 lymph node dissection for advanced gastric cancer. The resected specimen was diagnosed as well-differentiated tubular carcinoma, pT3, pN1, cM0, and the final stage was considered as B. During adjuvant chemotherapy with S-1 (120 mg/day, administered for 4 weeks and then stopped for 2 weeks), multiple liver metastases were detected by contrast-enhanced CT images 6 months after the operation. Eight courses of XP therapy (capecitabine 1,600 mg/m2/day: day 1-14, cisplatin 70 mg/m2/day: day 1, then stopped until days 15-21) were administered in consideration of the recurrence during adjuvant chemotherapy with S-1, resulting in a partial response. Adverse events such as grade 1-2 abdominal pain, general fatigue, and the resultant deterioration of ADL led to discontinuation of chemotherapy. The residual liver metastasis was treated with RFA therapy, causing it to disappear completely. Serum CEA level was 5.5 ng/mL postoperatively, elevated to 13.9 ng/mL at the time of recurrence and 2.4 ng/mL after XP and RFA therapy. He is doing well without any recurrence 2 years and 6 months later.


PubMed | Itami City Hospital
Type: Case Reports | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2016

We encountered a case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy for a long time. A pancreaticoduodenectomy was successfully performed on an 80- year-old man. Multiple liver metastases developed 6 months postoperatively. Microscopically, the primary lesion was diagnosed as adenosquamous carcinoma with anaplastic carcinoma component, and the final diagnosis was considered to be Stage disease. S-1monotherapy (80 mg/day, administered for 4 weeks and then stopped for 2-weeks) was effective. A partial response was noted after 3 months, and 9 months after the initial administration of S-1, a complete response was achieved, which persisted for more than 12 months, according to contrast-enhanced CT evaluations.Serum CEA and CA19-9 levels, which became slightly elevated at the time of liver metastasis development, normalized promptly and remained within normal limits. Adverse effects of chemotherapy of more than grade 2 severity were not apparent, and the patient tolerated the 11th course of S-1 administration, consistently. A standard therapeutic strategy and its outcomes in cases of pancreatic cancer recurrence are not clearly outlined in the Japanese Guideline for the Treatment of Pancreatic Cancer. A case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy is reported in this paper.


PubMed | Itami City Hospital
Type: Journal Article | Journal: Gan to kagaku ryoho. Cancer & chemotherapy | Year: 2017

A 73-year-old woman was diagnosed with gall bladder cancer by contrast enhanced CT images.The tumor was detected at the fundus of the gall bladder and enhanced heterogeneously.She underwent radical cholecystectomy including Japanese D2 lymph node dissection for gall bladder cancer.After 4 courses of oral S-1(80mg/m2 administered for 4 weeks and then stopped for 2 weeks)as adjuvant chemotherapy, a liver metastasis at segment 5 appeared 11 months postoperatively.It showed a ring enhanced tumor on contrast enhanced CT images.FDG accumulated in a similar lesion on PET-CT images.The patient successfully underwent partial hepatectomy of segment 5 of the liver.However, another liver metastasis at segment 7 appeared 5 months after the second operation, but it was resected successfully.The primary lesion and both liver metastases showed similar microscopic appearances.Seven courses of gemcitabine therapy(gemcitabine 1,000mg/m2 once every week for 3 weeks and then stopped for 1 week)were administered as adjuvant chemotherapy.She is now doing well without any sign of recurrence 2 years after the initial operation and 14 months after the secondary liver resection.

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