記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background. Tumor reduction by present-day prehepatectomy chemotherapy can render initially unresectable disease resectable. However, little is known about whether effects on liver metastases with radiologically defined "attachment to or invasion of" major intrahepatic vessels differ between chemotherapy regimens with or without monoclonal antibodies. We compared histologically the relationships between liver tumors and major intrahepatic vessels after chemotherapy according to regimens used to treat colorectal liver metastasis.
Methods. In 38 patients who underwent chemotherapy and hepatectomy with pretreatment images showing metastases attached to or invading major intrahepatic vessels, 62 metastases showed attachment to or invasion of 88 vessels. After resection, attachment, invasion, and separation were determined histopathologically in resected specimens.
Results. Thirteen patients received cytotoxic drug combinations alone, whereas 25 were treated with regimens including a monoclonal antibody (bevacizumab in 15 and cetuximab in 10). By imaging, 16% (5/32) of vessels in patients receiving cytotoxic drugs alone, 23% (8/35) of vessels in-those also receiving bevacizumab, and 48% (10/21) of vessels in those also receiving cetuximab showed detachment after chemotherapy (P =.015 for cetuximab versus cytotoxic and P =.039 for cetuximab versus bevacizumab). Excluding 8 vessels not evaluated histologically, 23 of 31 vessels in the cytotoxic group remained attached or invaded, as did 16 of 29 in the bevacizumab group and 8 of 20 vessels in the cetuximab group (P =.05 versus cytotoxic).
Conclusion. Prehepatectomy chemotherapy regimens including monoclonal antibodies, particularly anti-epidermal growth factor receptor antibodies, eradicated attachment or invasion between vessels and metastases more frequently. Individualized strategies for prehepatectomy chemotherapy based on intrahepatic location of metastases may offer advantages according to proximity of the metastases to the major intrahepatic vessels.

DOI： 10.1016/j.surg.2013.12.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Breast cancer patients who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) usually have a favourable prognosis. We report on a patient with early metastases to the brain after achieving pCR. The primary tumour was 7.0 cm in diameter with axillary lymph node metastases, hormone receptor-negative, human epidermal growth factor receptor-2-positive (3+), and histological grade 2 with 60% of cells positive for Ki-67. The patient underwent NAC followed by surgery, and achieved pCR. Five months after surgery, during adjuvant treatment with trastuzumab, she developed headache and dizziness. Brain imaging revealed multiple metastatic brain tumours. She received whole-brain radiotherapy followed by lapatinib and capecitabine therapy. At 7 months after surgery, she remains alive with a persistent mild headache. Physicians should be aware of the possibility of early brain metastases, and consider new treatment strategies to prevent brain metastases in high-risk patients who achieve pCR.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.

DOI： 10.1007/s10549-012-2398-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pin.12028

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PIONEER BIOSCIENCE PUBL CO  

Breast cancer is the most common type of cancer in women. However, it is very rarely manifested as hematologic disorders. A 35-year-old woman was admitted because of disseminated intravascular coagulation. Examinations revealed the presence of breast cancer in her left breast; therefore, paclitaxel was administered weekly. Although disseminated intravascular coagulation was controlled, pulmonary dysfunction due to lymphangitis carcinomatosa suddenly occurred 10 weeks after treatment. Pulmonary dysfunction was effectively treated with epirubicin and cyclophosphamide. Twenty-three weeks after treatment, the patient developed liver dysfunction accompanied with jaundice due to progressive metastatic lesions in the liver; liver dysfunction improved after the administration of vinorelbine. Subsequently, because of the recurrence of pulmonary dysfunction, rechallenge with epirubicin and cyclophosphamide was performed and was effective; however, this therapy was discontinued because of its adverse effects. She expired of liver failure 33 weeks after the occurrence of disseminated intravascular coagulation. Metastatic tumors in the bone marrow, lung, and liver showed different sensitivities to different anti-cancer agents. We report a case of breast cancer manifested by hematologic disorders which was treated by a sequential chemotherapy.

DOI： 10.3978/j.issn.2072-1439.2012.10.17

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: The purpose of our study was to investigate prognostic significance of lymph-node micrometastasis in gallbladder carcinoma. Methodology: In total, 1,094 lymph nodes from 41 patients who had undergone radical resection with lymph-node dissection, including para-aortic lymph nodes were stained with hematoxylin and eosin (H&E) and immunostained with anti-cytolceratin 7/8 antibody. Micrometastasis in each lymph node was defined as tumor cells that were detectable only by immunohistochemical evaluation and were not detected by H&E staining. Results: Metastases were detected in 163 lymph nodes (24.9%) by H&E staining. Micrometastases were found in 25 of the remaining lymph nodes (2.3%). Among 24 patients with lymph-node metastasis based on the H&E staining, 12 had micrometastases. Of the 17 patients in whom lymph-node metastasis was not detected by the H&E staining, one was found to have micrometastasis. Micrometastasis correlated significantly with lymph node metastasis on H&E staining and pN (Tumor-Node-Metastasis 5th ed.). On multivariate analysis of data from 17 node-positive patients who underwent curative resection, micrometastasis and microscopic venous invasion were significant prognostic factors. Conclusions: Our findings suggest that micrometastasis might be traces of scatter of cancer cells to the whole body rather than an event in an initial stage of the metastasis.

DOI： 10.5754/hge10010

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：COGNIZANT COMMUNICATION CORP  

Breast cancer is not a single entity. This study therefore aimed to identify differences in the impacts of anticancer agents and predictive factors between different breast cancer subtypes. A total of 234 patients with luminal (n = 109), luminal-HER2 (L-H, n = 29), HER-2 (n = 35), or triple negative (TN, n = 61) breast cancer subtypes were treated with standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane. Pathological response and prognosis were examined in each subtype. Expression levels of estrogen and progesterone receptors, HER-2, nuclear grade, MIB-1, p53, topoisomerase II alpha (topoII alpha), cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGER) were examined in association with quasipathological complete response (QpCR). QpCR rates were 9.1% (10/109) in luminal, 45% (13/29) in L-H, 37% (13/35) in HER2, and 54.1% (33/61) in TN. Non-QpCR patients showed significantly poorer 3-year disease-free survival than QpCR patients in TN, but not in patients with other subtypes. No factors were associated with QpCR in luminal patients. Patients with higher nuclear grade were more likely to achieve QpCR in L-H. The proliferative markers MIB-1 and topolla had opposite impacts on pathological response in HER-2 and TN. The QpCR rate was significantly higher in TN lacking CK5/6 and/or EGFR expression, defined as nonbasal subtype, compared with basal subtype (p = 0.049). Cytotoxic anticancer agents were associated with different responses in different breast cancer subtypes. Identifying basal-type cancer and further subdivision of nonbasal types is important for treating TN patients.

DOI： 10.3727/096504012X13473664562565

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