Kuniya Tanaka

Yokohama City University, Yokohama, Kanagawa, Japan

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Publications (184)346.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CEA-positive tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS + NAC; FGS only; and FGS + NAC. An anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with a pancreatic cancer PDOX 24 h before surgery. The PDOX was clearly labeled with fluorophore-conjugated anti-CEA antibody. Only one out of 8 mice had local recurrence in the FGS only group and zero out of 8 mice had local recurrence in the FGS + NAC which was significantly lower than BLS only or BLS + NAC mice, where local disease recurred in 6 out of 8 mice in each treatment group (p = 0.041 and p = 0.007, respectively). NAC did not significantly reduce recurrence rates when combined with either FGS or BLS. These results indicate that FGS can significantly reduce local recurrence compared to BLS in pancreatic cancer resistant to NAC. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
    Pancreatology 03/2015; DOI:10.1016/j.pan.2015.02.008 · 2.50 Impact Factor
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    ABSTRACT: Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.
    PLoS ONE 02/2015; 10(2):e0117417. DOI:10.1371/journal.pone.0117417 · 3.53 Impact Factor
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    ABSTRACT: We compared clinical outcomes of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) against those of classical 2-stage hepatectomy in treating metastatic liver disease. Short-term outcomes, serial changes in volume of the future liver remnant (FLR), functional FLR volume, and tumor growth activity during the treatment period, were compared between our first 11 consecutive patients treated with ALPPS and 54 patients treated with classical 2-stage hepatectomy. Mortality in the ALPPS group (9%) tended to be higher than in the classical 2-stage group (2%, P = 0.341). The FLR hypertrophy ratio (FLR volume after vs. before the procedure) 1 week after the first operation in the ALPPS group (1.54 ± 0.18) exceeded that in the classical 2-stage group (1.19 ± 0.29, P = 0.005), being similar to the ratio at 3 weeks after the first procedure in the classical 2-stage group (1.40 ± 0.43). However, functional volume of the FLR in the ALPPS group 1 week after the first procedure (52.1%) tended to be smaller than that in the classical group 3 weeks after the first procedure (59.2%). ALPPS should be used with extreme caution, giving special attention to postoperative complications and grade of functional liver regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European Journal of Surgical Oncology 02/2015; DOI:10.1016/j.ejso.2015.01.031 · 2.89 Impact Factor
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    ABSTRACT: Soft-tissue sarcomas are a group of rare mesenchymal carcinomas that include approximately 50 histological types, and account for 1% of all adult cancer cases. The yearly incidence of soft-tissue sarcomas in the USA is approximately 11,280 cases, with an overall mortality of 3,900 deaths per year. In this study, we established a patient-derived orthotopic xenograft (PDOX) from a patient with a soft-tissue sarcoma of the retroperitoneum in nude mice and compared it to a subcutaneous patient-derived model of the same tumor for histology. In the PDOX model, a bulky tumor grew in the left retroperitoneum in the same manner as the patient's tumor. Upon histological examination, the majority of the PDOX tissue section comprised sarcomatous high-grade spindle cells of varying sizes, similar to the original patient tumor. In contrast, the majority of the subcutaneously-implanted tumor comprised round to oval cells. These results indicate that the PDOX recapitulated the histology of the original tumor more than the subcutaneous model. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 02/2015; 35(2):697-701. · 1.87 Impact Factor
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    ABSTRACT: Background Although intraoperative peritoneal lavage is often performed routinely with the aim of reducing peritoneal contamination, little evidence of lavage benefits in elective liver resection without bile duct resection is available. We addressed the issue with a randomized clinical trial.Methods We prospectively and randomly assigned consecutive patients undergoing liver resection to a lavage group or a non-lavage group. Peritoneal lavage was performed at the end of operation for patients in the lavage group. The primary endpoint was the rate of surgical site infection.ResultsNinety-six patients were assigned to the lavage group and 97 to the non-lavage group. When superficial/deep incisional infection and organ/space infection were considered together, no significant difference in surgical site infection rate was evident between lavage (21.9%) and non-lavage groups (13.4%, P = 0.135). However, organ/space infection was significantly more frequent in the lavage group (16.7%) than the non-lavage group (7.2%, P = 0.048). Peritoneal lavage was identified as a risk factor for organ/space infection by multivariate analysis (relative risk, 2.977; confidence interval, 1.094 to 8.100; P = 0.033).Conclusion Intraoperative peritoneal lavage does not reduce overall incidence of surgical site infection and may increase risk of organ/space infection.
    01/2015; DOI:10.1002/jhbp.222
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    ABSTRACT: Although a 'liver-first' approach recently has been advocated in treating synchronous colorectal metastases, little is known about how results compare with those of the classical approach among patients with similar grades of liver metastases. Propensity-score matching was used to select study subjects. Oncologic outcomes were compared between 10 consecutive patients with unresectable advanced and aggressive synchronous colorectal liver metastases treated with the reverse strategy and 30 comparable classically treated patients. Numbers of recurrence sites and recurrent tumors irrespective of recurrence sites were greater in the reverse group then the classic group (p = 0.003 and p = 0.015, respectively). Rates of freedom from recurrence in the remaining liver and of freedom from disease also were poorer in the reverse group than in the classical group (p = 0.009 and p = 0.043, respectively). Among patients treated with 2-stage hepatectomy, frequency of microvascular invasion surrounding macroscopic metastases at second resection was higher in the reverse group than in the classical group (p = 0.011). Reverse approaches may be feasible in treating synchronous liver metastases, but that strategy should be limited to patients with less liver tumor burden. © 2015 S. Karger AG, Basel.
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    ABSTRACT: The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.
    PLoS ONE 12/2014; 9(12):e114310. DOI:10.1371/journal.pone.0114310 · 3.53 Impact Factor
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    ABSTRACT: Recombinant human soluble thrombomodulin (rTM) protects against disseminated intravascular coagulopathy by inhibiting coagulation, inflammation, and apoptosis. This study tests the hypothesis that rTM is hepatoprotective after extensive hepatectomy (Hx) and investigates the mechanisms underlying this effect. Experiment 1: rats (15 per group) were injected with rTM (1.0 or 2.0 mg/kg) or saline just before 95% Hx and their 7-d survival assessed. Experiment 2: rats were assigned to either a treated (2.0 mg/kg rTM just before Hx) or control group (n = 5 per group). Five rats per group were euthanized immediately after surgery, and at 1, 3, 6, 12, and 24 h postoperatively; serum and liver remnant samples were collected for biochemical and histologic analysis, as well as reverse-transcription polymerase chain reaction and Western blotting. All saline-injected rats died within 52 h of Hx, whereas injection of 2.0 mg/kg rTM prolonged survival (P = 0.003). rTM increased the number of Ki67-positive cells and reduced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. The number of myeloperoxidase-positive cells and the expression of high-mobility group box 1 protein did not differ. Reverse-transcription polymerase chain reaction revealed that rTM significantly enhanced protease-activated receptor-1 and sphingosine kinase 1 messenger RNA expression and significantly reduced plasminogen activator inhibitor-1 and Bax messenger RNA expression. Immunohistochemistry and Western blotting demonstrated that protease-activated receptor-1 expression 24 h after Hx was significantly higher in rTM-treated than in control rats. rTM may improve survival after extensive Hx by inhibiting apoptosis and promoting liver regeneration. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Surgical Research 11/2014; DOI:10.1016/j.jss.2014.10.048 · 2.12 Impact Factor
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    ABSTRACT: The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.
    Oncotarget 10/2014; · 6.63 Impact Factor
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    ABSTRACT: A survival benefit is generally considered unobtainable following incomplete hepatic resection in patients with colorectal liver metastases. However, this question should be readdressed considering recent chemotherapy, often combining a monoclonal antibody directed against colorectal cancer with various classic and improved strategies. We examined whether a survival benefit could be obtained from maximal reduction surgery for colorectal liver metastases.
    Anticancer research 10/2014; 34(10):5547-54. · 1.87 Impact Factor
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    ABSTRACT: The tumor-infiltrating lymphocyte (TIL) count in several types of cancer, including colorectal cancer and colorectal liver metastases (CRLM), reportedly predicts survival following resection; however, the prognostic significance of the TIL counts remains controversial. In total, 162 patients who underwent potentially curative resection for CRLM from 1992 to 2010 were immunohistochemically analyzed retrospectively. CD4, CD8, and FoxP3 were examined as markers for helper T cells, cytotoxic T cells, and regulatory T cells (Tregs), respectively. The correlation between patients' TIL composition and long-term outcome was investigated. The median follow-up time was 46.6 months for all patients and 46.8 months for survivors. Cancer-specific survival (CSS) at 1, 3, and 5 years was 93.2, 65.6, and 51.0 %, respectively. The 5-year disease-free survival and CSS among patients with high infiltration of peritumoral Tregs was 44.2 and 74.8 %, respectively, while those of patients with low infiltration of peritumoral Tregs was 18.9 and 40.3 %, respectively (p < 0.01 for both). Multivariate analyses indicated that synchronous liver metastases, hypoalbuminemia, and low peritumoral Treg infiltration were significant predictors of unfavorable CSS. Low peritumoral Treg infiltration proved to be a significant predictor of unfavorable CSS in patients undergoing resection for CRLM.
    Annals of Surgical Oncology 08/2014; 22(1). DOI:10.1245/s10434-014-3974-1 · 3.94 Impact Factor
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    ABSTRACT: We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naïve. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naïve-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naïve in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.
    PLoS ONE 08/2014; 9(8):e103382. DOI:10.1371/journal.pone.0103382 · 3.53 Impact Factor
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    ABSTRACT: Recent advances in multidetector computed tomography (MDCT) offer several benefits for management of perihilar tumors. Resection planning for perihilar cholangiocarcinoma should consider two factors: safety and curability. Recognition of individual anatomic variations is particularly important for avoiding intraoperative injury. In particular, hepatic arterial variations often restrict resection procedures. Extent of both longitudinal and vertical invasion by biliary tumors can be estimated from multiplanar reconstruction (MPR) images. Longitudinal extent of resection can be planned based on two anatomic landmarks, the U point and the P point, readily identifiable in preoperative 3-dimensional (3D) images and by intraoperative inspection. Concerning vertical invasion, when direct vascular invasion is suspected from a finding of attachment of tumor and vessels such as portal veins and/or hepatic arteries without a thin low-density plane of separation shown by MPR, these vessels should be resected en bloc with the tumor. Surgical team members can plan and simulate details of vascular resection and reconstruction using 3D images. Reduced operative morbidity and increased R0 resection rates are expected because of better planning of procedures. These techniques soon may increase long-term survival for patients with perihilar cholangiocarcinoma.
    08/2014; 21(8). DOI:10.1002/jhbp.75
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    ABSTRACT: A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1 combined with gemcitabine was conducted. But one year later, a recurrent tumor was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial response, and after 9 courses, a radiological complete response was achieved. We could then perform total pancreatotectomy and resection of the metastatic liver tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be consid- ered.
    Gan to kagaku ryoho. Cancer & chemotherapy 07/2014; 41(7):901-4.
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    ABSTRACT: The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on a pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purposes of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.
    Journal of Cellular Biochemistry 07/2014; 115(7). DOI:10.1002/jcb.24769 · 3.37 Impact Factor
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    ABSTRACT: The aim of this study is to determine if ultraviolet light (UVC) irradiation in combination with fluorescence-guided surgery (FGS) can eradicate metastatic human pancreatic cancer in orthotopic nude-mouse models. Two weeks after orthotopic implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3 treatment groups; BLS-only (n = 8) or FGS (n = 8) or FGS-UVC (n = 8). The residual tumors were resected using a hand-held portable imaging system under fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical resection bed was irradiated with 2700 J/m2 UVC (254 nm) in the mice treated with FGS-UVC. The average residual tumor area after FGS (n = 16) was significantly smaller than after BLS only (n = 24) (0.135±0.137 mm2 and 3.338±2.929 mm2, respectively; p = 0.007). The BLS treated mice had significantly reduced survival compared to FGS- and FGS-UVC-treated mice for both relapse-free survival (RFS) (p<0.001 and p<0.001, respectively) and overall survival (OS) (p<0.001 and p<0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to FGS-only treated mice (p = 0.008 and p = 0.025, respectively); with RFS lasting at least 150 days indicating the animals were cured. The results of the present study suggest that UVC irradiation in combination with FGS has clinical potential to increase survival.
    PLoS ONE 06/2014; 9(6):e99977. DOI:10.1371/journal.pone.0099977 · 3.53 Impact Factor
  • Kuniya Tanaka, Itaru Endo
    Annals of Surgery 05/2014; DOI:10.1097/SLA.0000000000000665 · 7.19 Impact Factor
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    ABSTRACT: Background and Aim: The aim of the present study was to evaluate the efficacy of liver resection for multinodular hepatocellular carcinoma (MNHCC). A total of 399 patients who underwent R0 resection for HCC from 1992 to 2011 were subjected to analysis. Out of these 399 patients, 107 patients had multinodular HCC, while 292 had a single tumor. The 3- and 5-year overall survival rates of patients with MNHCC were 62.0% and 38.1% respectively. By a multivariate analysis of the survival of the 107 patients after liver resection for MNHCC, it was shown that the presence of four or more tumors and a lower serum albumin level were unfavorable prognostic factors for long-term survival. With respect to the patients with four or more HCCs, portal vein invasion was an independent unfavorable prognostic factor for long-term survival. However, in patients with four or more HCCs without portal vein invasion, overall survival rates of those with preoperative serum albumin level >4.0 mg/dl and a platelet count >10(5)/mm(3) were significantly higher than those of patients with albumin <4.0mg/dl or platelet count <10(5)/mm(3) (p=0.049). Liver resection can provide a survival benefit, even for patients with multiple HCCs. Even if patients have four or more tumors without portal vein invasion and with well-preserved liver function, resection for HCC may be the treatment of choice.
    Anticancer research 05/2014; 34(5):2421-6. · 1.87 Impact Factor
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    ABSTRACT: The optimal cut-off value of the number of colorectal liver metastases (CRLM) to predict prognosis after hepatic resection remains unclear. This study was conducted to determine a suitable cut-off value. A total of 727 hepatectomized patients with CRLM were evaluated. We proposed the following optimal cut-off values: first, a small P-value for the log-rank test with no overlapping of the 95% confidence interval (CI) for median survival time using the Kaplan-Meier method and the hazard ratio (HR) using the Cox proportional hazards model and, second, the maximum HR value for accurate separation. For disease-free survival analysis, of the three group separations, A2 (1, 2-4, and ≥5) showed a small P-value and the largest HR, whereas two group separations, B2, B3 and B4 showed similarly small P-values, but B4 (1-4, ≥5) indicated the largest HR. Regarding the overall survival analysis, of the three group separations, A2 showed the smallest P-value, whereas the two group separations, B4 showed similarly small P-values, with the largest HR. Tumor number separation in patients with CRLM after hepatic resection should be performed using the A2 (1, 2-4, and ≥5) or B4 (1-4 and ≥5) classifications.
    03/2014; 21(3). DOI:10.1002/jhbp.58
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    ABSTRACT: The prognostic factors for patients with colorectal cancer liver metastasis (L-Mets) have not been fully described. Resected specimens were obtained surgically from 1998 to 2008 at our university hospital. We investigated whether the status of two primary lesion cancer stem biomarkers, CD44 and CD133, were maintained in L-Mets and whether these markers were L-Mets prognostic factors. To investigate the CD133 and CD44 status, proliferation, invasiveness, and chemoresistance were examined immunohistochemically by using MIB-1, E-cadherin, and ABC-G2. The CD44-positive rate in primary lesions and L-Mets was 41.4 and 58.7 %, respectively. There was no correlation of CD44 expression between primary lesions and L-Mets (r = 0.250, p = 0.071). The CD133-positive rate in primary lesions and L-Mets was 53.6 and 44.6 %, respectively. There was no correlation of CD133 expression between primary lesions and L-Mets (r = 0.219, p = 0.135). In the CD133-negative group, the MIB-1 index was significantly higher than in the CD133-positive group (61.6 vs. 46.3 %, p = 0.003), and E-cadherin expression was significantly lower in the CD133-negative group compared with the CD133-positive group (29.3 vs. 46.8 %, p = 0.001). Absence of CD133 expression in L-Mets correlated with poor overall survival (p = 0.006), and multivariate regression analysis showed that it was an independent marker for poor survival (hazard ratio 0.320, p = 0.0016). The absence of CD133 expression in L-Mets was an independent marker and a poor prognostic factor, possibly because of increased proliferation and invasiveness.
    Annals of Surgical Oncology 02/2014; 21(6). DOI:10.1245/s10434-014-3549-1 · 3.94 Impact Factor

Publication Stats

2k Citations
346.67 Total Impact Points

Institutions

  • 1996–2015
    • Yokohama City University
      • Department of Medicine
      Yokohama, Kanagawa, Japan
  • 2014
    • Teikyo University
      • Department of Surgery
      Edo, Tōkyō, Japan
  • 2013
    • King Hussein Cancer Center
      `Ammān, Amman, Jordan