Changing trends in the risk factors for second primary malignancies after autologous stem cell transplantation for multiple myeloma before and after the introduction of proteasome inhibitors and immunomodulatory drugs

The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously

Strategy for the accurate preoperative evaluation of the number of metastatic axillary lymph nodes in breast cancer

Summary: Background: After the ACOSOG Z0011 trial, it became important to evaluate the number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of this paper is to confirm whether the number of metastases can be accurately diagnosed by preoperative computed tomography (CT), ultrasound sonography (US), and US-guided fine-needle aspiration cytology (FNAC). Methods: We retrospectively analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer patients. Metastasis was suspected based on the following findings: LNs with a long-axis diameter of ≥10 mm or a short-axis diameter of ≥5 mm on CT, and LNs with the absence of a fatty hilum, focal cortical thickness or a cortical thickness ≥2 mm on US. We also examined the results of FNAC making a rapid bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic based on the US findings. Results: On CT, all cases with ≥3 LNs with a long-axis diameter of ≥10 mm and a short-axis diameter of ≥5 mm had metastasis. However, there was no relationship between the number of detected LNs and the number of metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs with cortical thickness ≥6 mm had metastasis. The accuracy of bedside-FNAC for suspicious LNs was 100%. Conclusions: Although we can pick up LNs that are likely to have metastasis on CT/US, it was impossible to accurately predict the number of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately predict the number of metastases. Keywords: Bedside fine-needle aspiration cytology, Computed tomography, Lymph node metastasis, Rapid diagnosis, Ultrasound sonograph

乳癌の進展における不完全な上皮 : 間葉移行現象とその分子機構

application/pdfテネイシン-C(TNC)は乳癌をはじめとする固形腫瘍の浸潤部位で高発現し、特に小型の癌巣を形成する乳癌浸潤部には高頻度にTNCが発現していた。乳癌細胞株MCF7をTNCで処理すると、上皮間葉移行様変化が誘導され、更にTGF-β1を加えるとそれが増強されることを見出した。この変化に関与するインテグリン(ITG)の探索を行い、ITGαvβ6とαvβ1が関与することを明らかにできた。また、ITGと複合体を形成するFAK/SRCのシグナル伝達系の活性化が関与していた。さらに、免疫組織化学によりこれらのレセプターのヒト乳癌組織での発現が確認できた。High expression of tenascin-C(TNC) has been demonstrated in invasive fronts of various cancers including breast cancer. We found the more extensive expression in invading areas of the small cancer nests. TNC treatment in vitro induced epithelia mesenchymal transition(EMT)-like change of breast cancer cells MCF7, that was enhanced by additional transforming growth factor-beta1. We also showed the contribution of alphαvbeta6 and alphαvbeta1 integrins to this phenotypic change. Activation of FAK and SRC forming integrin adhesion complex was associated with EMT change. Immunohistochemistry of the integrins showed their expression in human breast cancer tissues.平成21~23年度科学研究費補助金(基盤研究(C))研究成果報告書2159036