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Okazaki, Japan

Nagino M.,Nagoya University | Ebata T.,Nagoya University | Yokoyama Y.,Nagoya University | Igami T.,Nagoya University | And 3 more authors.
Annals of Surgery

Objective: To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progressmade in surgical treatment of this disease. Background: Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed. Methods: Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinomawere treated, ofwhom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed. Results: The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator. Conclusions: Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed. Copyright © 2013 by Lippincott Williams and Wilkins. Source

Yatabe Y.,Aichi Cancer Center
Cancer and Metastasis Reviews

Considerable knowledge has accumulated about mutations of the epidermal growth factor receptor (EGFR)-tyrosine kinase domain since these were first identified in 2004. Patients with nonsmall cell lung cancer with this mutation show dramatic clinical responses to treatment with EGFR-tyrosine kinase inhibitors, whose effectiveness has been established recently in large clinical trials. Most of the mechanisms responsible for resistance to treatment, which most responders experience eventually, have been elucidated, and methods to overcome resistance have been developed. In addition to the clinical benefit, understanding EGFR mutations sheds new light on the molecular and pathological aspects of this adenocarcinoma subset, which include frequent development in nonsmokers or females, and particular clusters within the molecular classification in lung cancer. In contrast to the involvement of EGFR mutations in the early stage of lung adenocarcinoma development, EGFR amplification is superimposed on the progression to invasive cancer. In this review, I summarize the clinicopathological characteristics of EGFR mutations in lung cancer. I also provide an overview of the current understanding of the lung adenocarcinoma subset harboring EGFR mutations with special reference to the molecular classification of lung cancer and the novel concept of the "terminal respiratory unit." © 2010 Springer Science+Business Media, LLC. Source

Kerr K.M.,Royal Infirmary | Tsao M.-S.,University of Toronto | Nicholson A.G.,Royal Brompton and Harefield Hospitals NHS Foundation Trust | Yatabe Y.,Aichi Cancer Center | And 2 more authors.
Journal of Thoracic Oncology

Therapeutic antibodies to programmed death receptor 1 (PD-1) and its ligand PD-L1 show promising clinical results. Anti-PD-L1 immunohistochemistry (IHC) may be a biomarker to select patients more likely to respond to these treatments. However, the development of at least four different therapeutics, each with a different anti-PD-L1 IHC assay, has raised concerns among pathologists and oncologists alike. This article reviews existing data on the IHC biomarker aspects of studies using these drugs in non-small-cell lung cancer (NSCLC) and considers the challenges ahead, should these drug/IHC assay combinations reach routine practice. For each the known biomarker assays in development, there is a different monoclonal IHC antibody clone, produced by one of two diagnostics companies. Each test requires proprietary staining platforms and uses different definitions of a "positive" test for PD-L1 expression, on tumor cells and, in one test, also on tumor infiltrating immune cells. There are still considerable gaps in our knowledge of the technical aspects of these tests, and of the biological implications and associations of PD-L1 expression in NSCLC, considering heterogeneity of expression, dynamic changes in expression, and prognostic implications among other factors. The International Association for the Study of Lung Cancer Pathology Committee raises the prospect of trying not only to harmonize and standardize testing for PD-L1 by IHC, at least at a technical level, but also, ideally, as a predictive marker, to facilitate availability of this test and a promising treatment for patients with NSCLC. © 2015 by the International Association for the Study of Lung Cancer. Source

Aoba T.,Nagoya University | Ebata T.,Nagoya University | Yokoyama Y.,Nagoya University | Igami T.,Nagoya University | And 4 more authors.
Annals of Surgery

OBJECTIVE: To analyze lymph node status in resected perihilar cholangiocarcinoma, to clarify which index (ie, location, number, or ratio of involved nodes) is better for staging, and to determine the minimum requirements for node examination. BACKGROUND: In the TNM classification for perihilar cholangiocarcinoma, the number or ratio of involved nodes is not considered for nodal staging. The minimum requirement for histologic examination of lymph nodes is arbitrary. METHODS: This study involved 320 patients with perihilar cholangiocarcinoma who underwent resection from January 2000 to December 2009 at Nagoya University Hospital. The relationship between lymph node status and patient survival was retrospectively analyzed. RESULTS: Total lymph node counts (TLNCs), ie, the number of lymph nodes examined histologically, averaged 12.9 ± 8.3 (range: 1-59). Lymph node metastasis was found in 146 (45.6%) patients and was an independent, powerful prognostic factor. The survival rates were not significantly different between patients with regional node metastasis alone and those with distant node metastasis (19.2% vs 11.5% at 5 years, P = 0.058). The survival for patients with multiple node metastases was significantly worse than that for patients with single metastasis (12.1% vs 27.6% at 5 years, P = 0.002), regardless of the presence or absence of distant lymph node metastasis. The survival for patients with lymph node ratios (LNRs) of 0.2 or less was significantly better than that for patients with LNRs greater than 0.2 (21.4% vs 13.5% at 5 years, P = 0.032). Upon multivariate analysis of the 146 patients with lymph node metastasis, the number of involved nodes (single vs multiple) was identified as an independent prognostic factor (RR of 1.61, P = 0.045), whereas the locations (regional alone vs distant) and ratios (LNR ≤ 0.2 vs LNR > 0.2) of involved nodes were not. When the 148 pN0-R0 patients were divided into 3 groups (ie, those with TLNC ≥ 8, with TLNC = 5, 6, or 7, and with TLNC ≤ 4), survivals were identical between the first and second groups, whereas they were largely different between the former two and the third. CONCLUSIONS: Lymph node metastasis is a powerful, independent prognostic factor in perihilar cholangiocarcinoma and is better classified based not on location but on the number of involved nodes. To adequately assess nodal status, histologic examination of 5 or more nodes is recommended. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Deoliveira M.L.,University of Zurich | Schulick R.D.,Johns Hopkins Hospital | Nimura Y.,Aichi Cancer Center | Rosen C.,Mayo Medical School | And 3 more authors.

Perihilar cholangiocarcinoma is one of the most challenging diseases with poor overall survival. The major problem for anyone trying to convincingly compare studies among centers or over time is the lack of a reliable staging system. The most commonly used system is the Bismuth-Corlette classification of bile duct involvement, which, however, does not include crucial information such as vascular encasement and distant metastases. Other systems are rarely used because they do not provide several key pieces of information guiding therapy. Therefore, we have designed a new system reporting the size of the tumor, the extent of the disease in the biliary system, the involvement of the hepatic artery and portal vein, the involvement of lymph nodes, distant metastases, and the volume of the putative remnant liver after resection. The aim of this system is the standardization of the reporting of perihilar cholangiocarcinoma so that relevant information regarding resectability, indications for liver transplantation, and prognosis can be provided. With this tool, we have created a new registry enabling every center to prospectively enter data on their patients with hilar cholangiocarcinoma. The availability of such standardized and multicenter data will enable us to identify the critical criteria guiding therapy. © 2011 American Association for the Study of Liver Diseases. Source

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