Arimura Y.,Keiyukai Sapporo Hospital |
Masao H.,Sapporo Medical University |
Okahara S.,Keiyukai Sapporo Hospital |
Tanuma T.,Keiyukai Sapporo Hospital |
And 4 more authors.
Gastrointestinal Endoscopy | Year: 2010
Background: Endoscopic submucosal dissection (ESD) was originally developed in Japan for en bloc resection of gastric neoplasms. Objective: To clarify whether the novel ESD procedure is feasible and gives results that justify the pursuit of integrated minimally invasive procedures aimed at curing early squamous cell carcinoma of the esophagus (SCCE). Design: Retrospective cohort study. Setting: A single-institution trial by experienced endoscopists. Patients: This study involved 300 consecutively enrolled patients with SCCE (Tumor, Nodes, Metastasis classification T1, N0) who underwent either EMR (n = 184) or ESD (n = 116) from March 1994 to July 2007. Intervention: The patients underwent endoscopic resection and then were followed by periodic endoscopy for 8 to 174 months (mean 65 months). Main Outcome Measurements: Resectability, cure rates, complications, disease-free survival of the two groups, and risk factors for local recurrence were explored. Results: En bloc resection and the local recurrence rate were significantly better in the ESD group (P = .0009 and .065, respectively). The frequency of perforation was not significantly different between the two groups (P = .68). Four independent risk factors for local recurrence were identified by the Cox regression model: EMR, deep cancer invasion, upper esophagus location, and family history of esophageal cancer. Radical cure is mostly obtained by successful endoscopic retreatment of local recurrence after previous endoscopic resection. Disease-free survival was significantly better with ESD. Limitations: The study's retrospective nature prevents definitive conclusions. Conclusions: We provide evidence that ESD gives a higher cure rate and is safer than conventional endoscopic resection when applied to early SCCE. ESD warrants prospective comparative studies with conventional endoscopic resection. Copyright © 2010 by the American Society for Gastrointestinal Endoscopy.
Kurokawa Y.,Osaka University |
Sugimoto N.,Japan National Cardiovascular Center Research Institute |
Miwa H.,Hyogo College of Medicine |
Tsuda M.,Hyogo Cancer Center |
And 10 more authors.
British Journal of Cancer | Year: 2014
Background: S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC. Methods: Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m-2) intravenously on day 1, and trastuzumab (course 1, 8 mg kg-1; course 2 onward, 6 mg kg -1) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events. Results: A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%). Conclusions: Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC. © 2014 Cancer Research UK.
Yoshii S.,Keiyukai Sapporo Hospital |
Yoshii S.,Nippon Telegraph and Telephone |
Nojima M.,Sapporo Medical University |
Nojima M.,Tokyo Medical University |
And 9 more authors.
Clinical Gastroenterology and Hepatology | Year: 2014
Background & Aims: More information is needed on the long-term outcomes of patients who undergo endoscopic resection of colorectal tumors. We evaluated recurrence of colorectal cancer (CRC) after endoscopic resection or a combination of endoscopic research and surgery for T1 colorectal tumors. Methods: We conducted a retrospective study of 389 patients with T1 CRC treated by endoscopic resection from January 1989 to December 2008 in Sapporo, Japan. We compared outcomes between patients who underwent subsequent surgery (ER+ SURG, n= 205) and those who did not (ER only, n= 184) and statistically adjusted baseline differences between the groups according to the propensity scores. Results: There was almost no risk of cancer recurrence among patients without indications for surgery recommended by the Japanese Society for Cancer of the Colon and Rectum (these indications include tumors with vertical margins, deep submucosal invasion, lymphatic or venous invasion, poor differentiation, or high-grade budding). Among patients with indications for surgery, the cumulative risks of recurrence (CRRs) were 3.7% in the ER+ SURG group and 20.1% in the ER only group (P= .001). However, the patients with only deep submucosal invasion had a low CRR, even without surgery (2.3% in the ER+ SURG group and 3.4% in the ER only groups, P=.867). In contrast, patients with indications for surgery other than deep submucosal invasion (high-risk patients) had much better outcomes when they also underwent surgery (CRRs: 5.8% in the ER+ SURG group vs 58.0% in the ER only group, P < .001). Conclusions: On the basis of a retrospective study of patients who underwent endoscopic resection for T1 CRC, those with tumors with only submucosal invasion are at low risk for cancer recurrence. However, patients with other high-risk tumor features have greater risks for cancer recurrence and benefit from subsequent surgery. © 2014 AGA Institute.
PubMed | Red Cross, National Hospital Organization Hokkaido Cancer Center, Fukushima Medical University, Obihiro Kosei Hospital and 10 more.
Type: | Journal: Oncotarget | Year: 2017
The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-RII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-RII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-RII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-RII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.
Niinuma T.,Sapporo Medical University |
Suzuki H.,Sapporo Medical University |
Nojima M.,Sapporo Medical University |
Nosho K.,Sapporo Medical University |
And 22 more authors.
Cancer Research | Year: 2012
Large intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXCand HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference-mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs. ©2012 AACR.
Takahashi H.,Keiyukai Daini Hospital |
Arimura Y.,Sapporo Medical University |
Okahara S.,Keiyukai Daini Hospital |
Kodaira J.,Keiyukai Daini Hospital |
And 4 more authors.
BMC Gastroenterology | Year: 2015
Background: Esophageal stenosis following endoscopic submucosal dissection (ESD) is a serious adverse event that makes subsequent management more difficult. Methods: This parallel, randomized, controlled, open-label study was designed to examine whether local steroid injection is an effective prophylactic treatment for esophageal stenoses following extensive ESD. This single center trial was conducted at the Keiyukai Hospital, a tertiary care center for gastrointestinal disease in Japan [University Hospital Medical Network Clinical Trial Registry (UMIN-CTR) on 15 September 2011 (UMIN000006327)]. Thirty-two patients with mucosal defects involving ≥75% of the esophageal circumference were randomized to receive a single dose of triamcinolone acetonide injections (n = 16) or be treated conventionally (n = 16). The primary outcome was the frequency of stricture requiring endoscopic dilatation; the surrogate primary endpoint was the number of dilatation sessions needed. Secondary outcomes included adverse event rates, the minimum diameter of the stenotic area and the duration of the course of dilatation treatments. Results: The frequency of stricture was not significantly different between the groups because of insufficient statistical power, but the number of dilatation sessions required was significantly less in the steroid group (6.1 sessions [95% confidence interval, CI 2.8-9.4] versus 12.5 [95% CI 7.1-17.9] sessions in the control group; P = 0.04). The perforation rate was similar in both groups. The minimum diameter of stenotic lumens was significantly greater in the treatment group than controls (11.0 mm versus 7.1 mm, respectively; P = 0.01). The perforation rate was not significantly different between the groups (1.0% versus 0.5% in the treatment and control group, respectively). Steroid injection was effective in cases of mucosal defects encompassing the entire esophageal circumference. Conclusions: Prophylactic endoscopic steroid injection appears to be a safe means of relieving the severity of esophageal stenoses following extensive ESD. © 2015 Takahashi et al.; licensee BioMed Central.
Koinuma J.,University of Tokyo |
Koinuma J.,Hokkaido University |
Akiyama H.,Saitama Cancer Center |
Fujita M.,Keiyukai Sapporo Hospital |
And 6 more authors.
Cancer Science | Year: 2012
To identify potential molecular targets for diagnosis, treatment and/or prevention of lung and esophageal carcinomas, we screened for genes that were overexpressed in tumors through gene expression analyses of 120 lung cancers and 19 esophageal squamous-cell carcinomas using a cDNA microarray consisting of 27 648 cDNA or expressed sequence tags. In this process, we identified a gene, Opa interacting protein 5 (OIP5), to be highly transactivated in the majority of lung and esophageal cancers. Immunohistochemical staining using 336 archived non-small cell lung cancers and 305 esophageal squamous-cell carcinomas specimens demonstrated that OIP5 expression was significantly associated with poor prognosis of lung and esophageal cancer patients (P = 0.0053 and 0.0168, respectively), and multivariate analysis confirmed its independent prognostic value for non-small cell lung cancers (P = 0.0112). Suppression of OIP5 expression with siRNA effectively suppressed the growth of cancer cells, whereas the exogenous expression of OIP5 enhanced the growth of cancer cells. In addition, OIP5 protein is likely to be stabilized through its interaction with Raf1. OIP5 is a promising target for developing new prognostic biomarkers and anti-cancer drugs. © 2011 Japanese Cancer Association.
Sasaki Y.,Sapporo Medical University |
Negishi H.,Sapporo Medical University |
Idogawa M.,Sapporo Medical University |
Yokota I.,Sapporo Medical University |
And 8 more authors.
Cancer Research | Year: 2011
Hepatoma-derived growth factor (HDGF) is a secreted heparin-binding growth factor that has been implicated in cancer development and progression. Here, we report that HDGF is a critical target for transcriptional repression by the tumor suppressor p53. Endogenous HDGF expression was decreased in cancer cells with introduction of wild-type p53, which also downregulated HDGF expression after DNA damage. In support of the likelihood that HDGF is a critical driver of cancer cell growth, addition of neutralizing HDGF antibodies to culture media was sufficient to block cell growth, migration, and invasion. Similarly, these effects were elicited by conditioned culture medium from p53-expressing cells, and they could be reversed by the addition of recombinant human HDGF. Interestingly, we found that HDGF was overexpressed also in primary gastric, breast, and lung cancer tissues harboring mutant p53 genes. Mechanistic investigations revealed that p53 repressed HDGF transcription by altering HDAC-dependent chromatin remodeling. Taken together, our results reveal a new pathway in which loss of p53 function contributes to the aggressive pathobiological potential of human cancers by elevating HDGF expression. ©2011 AACR.
Takahashi H.,Keiyukai Sapporo Hospital |
Arimura Y.,Sapporo Medical University |
Okahara S.,Keiyukai Sapporo Hospital |
Uchida S.,Keiyukai Sapporo Hospital |
And 4 more authors.
Endoscopy | Year: 2011
Background and study aims: Growing evidence suggests that esophageal stricture frequently develops after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in early esophageal cancer patients, with an incidence proportional to the greater extent of mucosal defects resulting from improved EMR/ESD techniques. There seems to be a potential risk of perforation during bougienage in such patients. Patients and methods: 648 stricture dilations for 78 lesions in 76 patients were consecutively included. The outcomes after combined use of Maloney and Savary wire-guided bougienage for esophageal strictures after EMR/ESD were analyzed in a single-institute retrospective case series study. The perforation rate was determined and risk factors for perforation were identified. Results: Patients underwent a median of 5.0 dilation procedures performed over a median 3.0 months for post-EMR/ESD strictures. Initial dilation was done a median 14 days following endoscopic resection. Perforations developed in seven patients (7/648 dilation procedures, 1.1 %), all in the lower esophagus, and bleeding occurred in one patient (0.1 % dilations). Two independent risk factors for development of perforation during dilation therapy for post-EMR/ESD stricture were identified: multiple dilations (odds ratio [OR] 1.2; P = 0.012), and lower site of stricture (OR 12.8; P = 0.043). Dysphagia was ameliorated by the dilations, and no patient required surgery. Conclusions: A specific emerging risk of perforation in dilation therapy for post-EMR/ESD strictures was identified. Carefully planned treatment is necessary in patients with severe post-EMR/ESD strictures especially strictures requiring multiple dilations or located in the lower esophagus. © Georg Thieme Verlag KG Stuttgart - New York.
Itoh K.,Keiyukai Sapporo Hospital
Japanese Journal of Clinical Radiology | Year: 2010
Scintigraphy is useful in the evaluation of acute renal failure and individual renal function. Morphological assessment of the kidney is alternative to US, CT and MRI rather than scintigraphy. On the other hand, blood sample methods are simple and accurate in the evaluation of global renal function. Renal function is represented as GFR which is estimatd from serum creatinine, age and sex in a routine study. Blood sample methods must be expected to serve as a precise examination of GFR in CKD.