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Introduction Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. Patients and Methods We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. Results Among hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node–positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II. Conclusion In hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.

Background In hormone receptor (HR)-positive / human epidermal growth factor receptor 2 (HER2)-negative breast cancers, high Ki-67 predicts poor prognosis. Recently, it has been reported that among breast cancers with high Ki-67, low Ki-67 after short-term preoperative hormone therapy (post Ki-67) might predict favorable prognosis compared to high post Ki-67 (SABCS 2017). However, the differences in gene expression profiling of breast cancers between high and low post Ki-67 among high Ki-67 before treatment are unclear. Therefore, this study aimed to clarify genetic differences in two groups and to explore novel therapeutic targets for the poor prognostic group after the treatment. Methods Seventy-seven patients with primary HR-positive / HER2-negative breast cancer who received an aromatase inhibitor for 2 weeks [NCBI Gene Expression Omnibus repository GSE80077:19 cases, GSE20181:58 cases] were enrolled in this study. Forty-five patients with high pre Ki-67 among them were stratified into two groups, high (H→H) and low (H→L) post Ki-67 after short-term preoperative hormone therapy. We compared gene expression profiling in two groups about the followings. 1) 3 genes (ESR1, PGR and ERBB2) related to classical clinical treatment strategy of breast cancer, immune- and inflammatory-related genes 2) 178 pathways (gene set analysis) 3) 41 genes that are targeted by FDA-approved drugs or have been investigated with clinical trials as molecular target agents for various malignant tumors including breast cancer Results 1) TNF that is inflammatory-related gene were significantly overexpressed in H→L group (P=0.021). However, 3 genes related to clinical treatment of breast cancer and immune-related genes expression had no significant difference between two groups. 2) 5 gene sets (Tryptophan metabolism, Propanoate metabolism, beta-Alanine metabolism, SNARE interactions in vesicular transport and Nucleotide excision repair) were significantly upregulated in H→L group. (P ≤ 0.005) 3) 5 targeted genes (PARP, BRCA2, FLT4, CDK6 and PDCD1LG2) were significantly overexpressed in H→H group (P ≤ 0.05). Conclusions There were different gene expression and biological processes in two groups stratified by post-Ki67. In the future, it is necessary to seek new therapeutic strategies for poor prognostic group with high post-Ki67 in considerations of these differences. Citation Format: Yukiko Kajiwara, Takayuki Iwamoto, Yusuke Otani, Miwa Fujihara, Yoko Suzuki, Minami Hatono, Takahiro Tsukioki, Kengo Kawada, Mariko Kochi, Hirokuni Ikeda, Tadahiko Shien, Naruto Taira, Hiroyoshi Doihara. Gene expression profiling of breast cancers between high and low Ki-67 after short-term preoperative hormone therapy among hormone receptor-positive / human epidermal growth factor receptor 2-negative breast cancers with high Ki-67 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-04.

Background: Patient reported outcomes (PROs) have been increasingly important in breast cancer treatment. The questionnaires to evaluate PROs require high response compliance, simplicity, and friendliness. Recently, the communication with Emojis has become friendliness because of the development of social networking services and electronic devices. Therefore, we developed the Emoji scale, a novel indicator to evaluate PROs. Furthermore, two-step validation pilot studies were planned to examine the reliability of the Emoji scale for breast cancer patients at a single center. Pilot 1(Step 1) Aims: To evaluate the content validity (the primary endpoint), concurrent validity and test retest reliability of the Emoji scales (secondary endpoints). Eligibility criteria: (1) Patients with stage 0-III breast cancer. (2) Patients who have been over 1 year since the end of the initial treatment such as surgery, chemotherapy, and radiation therapy or (3) hormone receptor positive patients who have been over 1 year from the start of the endocrine therapy. (4) Patients aged >20 years who understand Japanese. Methods: The participants will complete the PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) and Emoji scale questionnaires regarding 18 cancer related symptoms twice. First, both questionnaires will be completed in a consulting room while the staff will track the time required for completion of each questionnaire. Thereafter, the patients will be asked if there are any difficult or confused items. Second, both questionnaires will be completed again at home 7 days later. The number of planned participants is 100. Statistical analyses: Content validity will be evaluated by categorizing the comments from participants, and the nature of problems will be determined. The correlation coefficient between the PRO-CTCAE and Emoji scale scores will evaluate the concurrent validity. For the test-retest reliability, the kappa statistic between each scale at different time will be used. We will compare the time required for completion with using the t-test. Pilot 2(Step2) Aims: To evaluate the responsiveness (the primary endpoint), the effect size, the concurrent validity and comparison of the average score between participants with high and low Performance Status. (the secondary endpoints). Eligibility criteria: (1) Patients with stage 0-IV breast cancer who are scheduled to start chemotherapy or endocrine therapy. (2) Patients aged >20 years who understand Japanese. Methods: The participants will complete both the PRO-CTCAE and Emoji scales before they start a new breast cancer treatment (T1). Those will comprise chemotherapy (Cohort A: anthracycline based regimens, Cohort B: docetaxel based regimens, Cohort C: paclitaxel based regimens, Cohort E: eribulin based regimens, and Cohort F: capecitabine/S1 based regimens) or endocrine therapy (Cohort D: tamoxifen/aromatase inhibitor). After several weeks, the participants will complete the same questionnaires again (T2). This time interval will depend on the therapy, and some participants will be complete once again the questionnaires (T3) a few weeks after T2. The number of planned participants is 30 in each cohort. Statistical analyses: Responsiveness will be evaluated by the correlation coefficient between the change from the baseline to second or third score of each scale. The effect size of the Emoji scale will be determined by the difference between the average score of the second or third and that of the baseline divided by the standard deviation of the baseline score. The correlation coefficient for each scale at each time will evaluate the concurrent validity at each time. A comparison of the average scores between PS will be performed using the t-test. Citation Format: Yoko Suzuki, Naruto Taira, Yukiko Kajiwara, Mariko Kochi, Takayuki Iwamoto, Hirokuni Ikeda, Tadahiko Shien, Hiroyoshi Doihara, Yuichiro Kikawa, Yukari Uemura. Validation study of the Emoji scale in evaluating patient reported outcomes for breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-19-01.

Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. In previous case–control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

Background: Overall survival (OS) is the established endpoint to evaluate the effects of drug treatment in comparative clinical trials of metastatic breast cancer. But assessing OS requires long follow-up periods and large sample size, which raise costs and create long delays in the drug approval process. Progression-free survival (PFS) or time to progression (TTP) is considered as a surrogate for OS and is often used as an alternative to OS. In some cancers the two endpoints are highly correlated, but in others they are not. Furthermore, the effect of breast cancer (BC) subtypes on the surrogacy of PFS/TTP for OS has not been completely defined. Method: A systematic literature review of randomized control trials was conducted to identify studies that reported both the hazard ratio (HR) of PFS/TTP and OS for BC subtypes {i.e. estrogen receptor (ER) positive, HER2 positive, and triple negative (TN)}. The correlation between the HR of PFS/TTP and OS was evaluated using weighted Spearman's rank correlation. Results: A total of 49 trials (34 phase III trials and 15 phase II trials) were selected for analysis. Among these trials, there were 8 comparison trials between one chemotherapy and another chemotherapy regimen, 18 comparison trials between chemotherapy and chemotherapy plus molecularly-targeted therapy, 9 comparison trials between one endocrine therapy and another endocrine therapy, and 5 comparison trials between endocrine therapy and endocrine therapy plus molecularly-targeted therapy. There were 17 trials reporting the HR of PFS/TTP and OS for ER positive, 16 trials for HER2 positive, and 9 trials for TN BC. Weighted Spearman's rank correlation revealed that coefficient between the HR of PFS/TTP and OS was 0.721(p Conclusion: There was a strong correlation between the HR of PFS/TTP and OS for ER positive BC, and a weak correlation between the HR of PFS/TTP and OS for HER2 positive and TN BC. The validity of using PFS/TTP as an OS surrogate marker was shown for metastatic BC, especially for ER positive BC. Citation Format: Tsukioki T, Taira N, Sakamaki K, Suzuki Y, Kajiwara Y, Hatono M, Takahashi Y, Kawata K, Kochi M, Iwamoto T, Ikeda H, Shien T, Doihara H. Progression-free survival or time to progression in comparative clinical trials of metastatic breast cancer as a potential surrogate for overall survival: A systematic review of 49 trials focusing on breast cancer subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-19.

Background : Isoflavones are phytoestrogens that may be effective in preventing osteoporosis, reducing cardiovascular events, and improving menopausal symptoms such as hot flash due to their estrogen-like actions. Isoflavones are currently used as a supplement for improving symptoms of menopause. Epidemiological studies have shown that ingestion of soy products may also reduce the risk of breast cancer, and antitumor effects on hormone receptor (HR)-positive breast cancer cells have been shown in vitro for equol, an isoflavone metabolite. Equol binds to estrogen receptors (ERα, β) and is thought to antagonize ERα-estradiol binding in the presence of estradiol. Since equol shows an antiestrogenic effect, similar to that of the hormonal agent tamoxifen, it is thought that equol acts as a selective estrogen receptor modulator (SERM), but the mechanism is still unclear. In this study, we evaluated the antitumor effects of equol alone and in combination with existing therapeutic agents in HR-positive breast cancer cells, and examined the mechanism of these effects. Methods : The antitumor effects of equol alone and in combination with hormone drugs (4-hydroxytamoxifen (Tam), fulvestrant (Ful)) and chemotherapeutic agents (paclitaxel (Ptx), doxorubicin (Dox)) were examined using a MTS assay. Combination indexes (CIs) were determined in HR-positive MCF-7, T-47D, and ZR-75-1 cell lines. The mechanisms of the drug effects were evaluated by Western blot for assessment of changes in chemoresistance factors at the protein level. Results : In MCF-7, T-47D and ZR-75-1 cells, there was a concentration-dependent antitumor effect of equol and of the other hormonal agents. CIs showed an antagonistic effect of equol with Tam and a synergistic effect with Ful in all cell lines. Equol also had an antagonistic effect with the two chemotherapeutic agents, with the strongest antagonism occurring at a low dose of equol. Western blot showed that ER, PgR, Cyclin D1 and Bcl-2 were upregulated via ER at a low concentration of equol, similarly to the effect of 17-β-estradiol (E2), and ER, PgR, Cyclin D1 and Bcl-2 were downregulated at a high concentration, similarly to the effect of Tam. In addition, ER, PgR and cyclin D1 were downregulated with the combination of equol and Tam, while the expression of Bcl-2, a chemoresistance factor, increased. Conclusion : These results suggest that equol has a concentration-dependent antitumor effect in HR-positive breast cancer cell lines and may antagonize the effect of existing therapeutic agents (hormone drugs and chemotherapeutic agents). In particular, it was considered that in combination of equol and Tam, the apoptosis inducing action of each drug was attenuated and antagonistic effect was shown. Citation Format: Hatono M, Ikeda H, Taira N, Suzuki Y, Kajiwara Y, Kawata K, Takahashi Y, Tsukioki T, Kochi M, Iwamoto T, Shien T, Doihara H. Effects of a soy isoflavone in breast cancer treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-06.

Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non‐small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide‐3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR‐TKI‐resistant NSCLC cell lines. The results showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed in several resistant cell lines, which caused the resistance to single‐agent treatment with either inhibitor alone. Meanwhile, the combined therapy successfully regulated the compensatory activation of the key intracellular signals and synergistically inhibited the cell growth of those cells in vitro and in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy proved effective included (MET) mesenchymal‐epithelial transition factor amplification, induction of epithelial‐to‐mesenchymal transition (EMT) and EGFR T790M mutation. In further analysis, the combination therapy induced the phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis cascade. Additionally, long‐term treatment with the combination therapy induced the conversion from EMT to mesenchymal‐to‐epithelial transition in the resistant cell line harboring EMT features, restoring the sensitivity to EGFR‐TKI. In conclusion, our results indicate that the combined therapy using MEK and PI3K inhibitors is a potent therapeutic strategy for NSCLC with the acquired resistance to EGFR‐TKIs.

Purpose Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. Method We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen. Result There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08). Conclusion Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.

Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines. We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect. Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells. We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.

Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. A multicenter case–control study was performed in 530 patients and 1043 controls. Breast density was classified as C1–C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34–2.70]; C1 vs. C4 2.85 [95% CI 1.10–7.16]). This correlation was also significant in patients in the third BMI quartile (22.3–24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38–42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17–3.15]; C1 vs. C4 11.89 [95% CI 1.56–245.17]). Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

A70 's male was diagnosed with advanced papillary thyroid carcinoma and underwent total thyroidectomy with left lymph node dissection(T4a, N1b, M0, stage IV A). Six years after the surgery, subclavicular and mediastinal lymph node recurrence was observed. Radioiodine therapy was not successful for those lesions. Lymph node dissection was performed via the cervical and transsternal approaches. One year after the second surgery, cervical and mediastinal lymph node recurrence was again observed. We removed the cervical lymph nodes via the cervical approach. One month after cervical dissection, we removed the mediastinal lymph nodes via video-assisted thoracoscopic surgery(VATS). The lymph nodes were relatively easily dissected by VATS under excellent surgical views. Repeat mediastinal dissection via median sternotomy could be associated with significant complications. VATS is expected to reduce the risk of reoperation and enhance surgical outcomes.

A49 -year-old woman presented with a 3.5 cm mass in her right breast. Mammography revealed a lobular mass with poorly defined margins and no microcalcification. Ultrasonography showed a hypoechoic mass with an irregular margin. The tumor was diagnosed as breast carcinoma using a core needle biopsy. The patient underwent a modified radical mastectomy with sentinel lymph node biopsy, and received adjuvant chemotherapy. The tumor consisted of 2 types of carcinoma. The center of the tumor was solid-tubular carcinoma, and the periphery was acinic cell carcinoma(ACC). Histopathologically, the neoplastic cells of the periphery were characterized by widespread acinic cell-like differentiation with a eosinophilic granular or clear cytoplasm, resembling acinic cells of the parotid gland(t3, f[+], ly0, v0, n0, stage II B). Immunohistochemically, the specimens tested positive for salivary gland amylase, and negative for collagen type IV , ER, PgR, and HER2. We administered UFT as adjuvant chemotherapy. Eight months after surgery, local recurrence was observed. ACC of the breast is rare, and has been reported to have a good prognosis. Further investigations are needed to elucidate its true histogenesis the appropriate treatment.

We report a case of minimal thyroid carcinoma diagnosed by a solitary pulmonary metastasis. A 70's man visited a medical practitioner because of chest discomfort, and there was an abnormality on the chest X-ray. Chest computed tomography(CT) showed a nodule in the right middle lobe of the lung. Positron emission tomography with 18-fluorodeoxyglucose(FDG)-PET revealed increased FDG uptake in that tumor, but did not reveal any other lesion. The tumor was clinically suspected to be a carcinoid tumor, primary lung cancer, metastatic lung cancer, or a benign tumor. Right middle lobe lobectomy was performed, and the tumor was diagnosed as a metastasis from a thyroid papillary carcinoma by pathological diagnosis during surgery. After surgery, we found a tumor in the left lobe of the thyroid by CT and US. Because the patient did not desire 131I therapy, he underwent a left hemithyroidectomy and neck dissection. There was a papillary carcinoma 1.0 cm in the thyroid gland and there were 3 cervical lymph node metastases. There has been no recurrence for 11 years after surgery.

Spontaneous rupture of the esophagus, which is also known as Boerhaave’s syndrome, is a rare life-threatening condition that requires urgent surgical management. The optimal treatment involves surgical repair of the esophageal defect, which is usually accomplished via laparotomy, thoracotomy, or both, and mediastinal debridement. Here, we report a case of spontaneous rupture of the esophagus that was treated with suturing repair and drain insertion using a hand-assisted laparoscopic approach.

Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of 18F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images.

Background: The treatment for metastatic breast cancer (MBC) is usually systemic therapy decided by the hormone and HER2 status of primary breast cancer lesion. There are some reports about the discrepancy in hormone and HER2 status between primary and metastatic lesion in these days. We have reported previously that the expression of ALDH-1 which considered the pathological markers of breast cancer stem cell in axillary lymph node matastases is a significant predictor of poor outcome in primary breast cancer patients (Figure 1). We evaluated the role of surgery in the diagnosis and treatment of a solitary pulmonary nodule (SPN) in breast cancer patients and demonstrated the significance of analyzing the immunopathological features in metastatic breast cancer lesion. Methods: Between 1990 and 2006, 17 patients (PM) with SPN which were diagnosed breast cancer metastases underwent complete pulmonary resection and 36 MBC patients (AP) underwent autopsy after breast cancer related death in our hospitals. We retrospectively analyzed clinicopathological features and the expression of ER, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions. Results: The median age of PM patients was 53 (range 30-80). All PM patients had not other metastases and had undergone curative breast cancer operation. The pulmonary operation were partial pulmonary resection in 15(88%) and lobectomy in 2 (12%) patients. The median disease free survival (DFS) was 63 months (range 9-175). Median overall survival (OS) was 181 months and the median OS after pulmonary operation was 48 months. The median DFS and OS of AP patients were 21 and 43 months. All AP patients had multiple visceral metastases. We compared the immunohistlogical status between primary and metastatic lesion and evaluated the colletation with these status in metastatic lesion and prognosis in all patients. Conclusion: Pulmonary resection was effective to diagnose and the OS after resection was relatively long in PM patients. We report the value of the expression of ER, HER2, Ki67 and ALDH-1 in distant metastatic lesions. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-20.

患者は57歳女性．2000年12月に肺癌に対し，胸腔鏡補助下右S3区域切除施行．病理診断は高分化型腺癌，Stage IAであった．術後4年目の胸部X線，CTにて右上葉に5×5cmの腫瘤陰影を認めた．右肺癌再発を疑い胸腔鏡下手術を行った．右上葉に臓側胸膜の引きつれを伴う弾性硬の腫瘤を認めた．術中迅速病理検査では悪性所見は得られなかったが，肉眼所見では悪性が強く疑われたため，右上中葉切除を行った．切除標本肉眼的所見では腫瘤は5.5×5.0cm，割面は白色，周囲との境界は明瞭で，内部に黄緑色の膿汁の貯留を認めた．切除標本の軟X線写真にて，病変部の辺縁にほぼ一致して前回手術時のステープルラインを認めた．病理組織学的検査では肉芽腫形成を認めた．膿汁の培養からMycobacterium aviumが検出された．以上から自験例を肺癌術後のステープルラインに発生した非定型抗酸菌症を伴う肺肉芽腫と判断した．

66歳, 男性. 40年前に急性虫垂炎にて手術を受けた. 糖尿病のために10年前からインスリンを使用していた. 約半年前から間欠的な腹痛が頻回にあるため, 近医で胃カメラなどを受けたがはっきりした原因は不明であった. 1カ月前, 同様の腹痛が出現し, 救急外来を受診した. 臨床症状と画像所見より小腸イレウスと診断され緊急入院となった. 入院後, 絶食と補液にて速やかに症状は改善した. 明らかな原因は不明だが, 診断もかねて腹腔鏡手術を施行した. 臍上部よりカメラポートを挿入. 5mmのワーキングポート右側腹部より2箇所挿入し, 腹腔内を観察したところ, Treitz靱帯より約40cmの空腸に漿膜浸潤を伴う全周性の小腸癌を認めた. 4cmの小開腹を行い, 小腸部分切除を施行した. 今回, 原因不明のイレウスの診断と治療に対し腹腔鏡が有用であったので報告する.

膵十二指腸動脈瘤(以下, PDAA)は近年のinterventional radiologyの発達に伴い報告例も増えてきつつある. 破裂後に診断されることが多く, 破裂した場合, 出血部位はさまざまで, 消化管, 後腹膜, 腹腔内などである. しかし, 総胆管への穿破は報告が少なく, 極めてまれといえる症例を経験した. 症例は56歳の男性で, 大酒家で慢性膵炎の既往があった. 急性胆嚢炎にて入院し, 保存的治療後, 腹腔鏡下胆嚢摘出術を行った. 術後, 膵炎が増悪し, 保存的治療にて軽快していたが, 8日目に突然吐血した. 緊急内視鏡検査で, 十二指腸乳頭部からの出血を認め, 腹部CTでは総胆管に出血を思わせる像を認めた. ただちに腹部血管造影検査を行ったところ, 後上膵十二指腸動脈に仮性動脈瘤と造影剤の血管外漏出を認めた. マイクロコイルを用いた塞栓術が可能で, 止血に成功した. 総胆管に穿破した例は極めて少なく, 文献的考察を加えて報告する.

An 85-year-old man complaining of vague abdominal discomfort was admitted to our hospital. A pulsatile 8 × 7-cm mass in the right upper abdomen was noticed on clinical examination. Computed tomography of the abdomen showed a huge arterial aneurysm in the right gastroepiploic artery, and the left gastroepiploic artery was meandering and expanding. An image diagnosis of gastroepiploic arterial aneurysm (GEAA) was made. Because of the huge size of the aneurysm and the predicted high risk of perforation, surgical intervention was planned. The aneurysm was identified in the greater curve and was found to adhere firmly to the transverse colon. Partial resection of the stomach, aneurysmectomy and partial resection of the transverse colon were performed. Clinically, splanchnic arterial aneurysms are rare. Among them, GEAA is especially rare. We report a rare case of a huge GEAA that was treated successfully by surgery.

A 58-year-old man presented with paralysis and pain in the left leg, and a mass was found in his thigh. Because of the growth of the mass and the worsening of his symptoms, the patient visited our hospital. Multidetector computed tomography revealed a large deep femoral arterial (DFA) aneurysm. Surgical intervention was planned because of the large size of the aneurysm, the high risk of perforation and the worsening symptoms. Aneurysmectomy and revascularization of the distal DFA with an artificial blood vessel graft were performed. DFA aneurysms are extremely rare. These aneurysms have a high rate of rupture, and surgery plays an important role in their treatment. However, standard methods have not yet been established because of their rarity of DFA aneurysm. We describe a case of DFA aneurysm in a patient who was successfully treated with aneurysmectomy and revascularization with an artificial blood vessel graft.

症例は84歳,女性.腹部膨満感を主訴に当院内科を受診,腸閉塞症の診断にて緊急入院した.腹部超音波, CTにて肝臓に大小多数の腫瘍性病変と盲腸に腫瘤像を認め,盲腸癌による腸閉塞症および多発性肝転移を疑った.全身状態を考慮し,消化管の通過障害を改善することを目的として回盲部切除術を行った.切除標本の病理組織学的所見では,核異型・核分裂像に富む多角形の腫瘍細胞が胞巣状・充実性に浸潤増殖し,腫瘍細胞の索状の配列,ロゼット様構造も多数認められた.さらにGrimelius染色,神経内分泌マーカーによる免疫染色にて陽性反応を認め,自験例を盲腸内分泌細胞癌と診断した.大腸内分泌細胞癌は,急速に発育して早期から脈管侵襲と転移をきたす予後不良の高悪性度癌である.発生経路についても不明な点が多く,現在でも,治療法は確立されていない.

症例は48歳 (1996年当時), 女性. 11歳時に肺結核の罹患歴がある. 約15年前から検診時に右中肺野に異常陰影を指摘されていたが放置していた. 1996年初め頃から咳および黄色の喀痰を認めるようになり, 9月当院内科を受診し胸部CTにて肺アスペルギルス症を疑われた. 喀痰培養では一般細菌, 真菌, 抗酸菌はすべて陰性, また血清抗アスペルギルス抗体, β-Dグルカンは陰性であった. 気管支ファイバーおよびCTガイド下生検でも有意の所見は得られなかった. 術前に確定診断を得られなかったが, 肺真菌症を強く疑い右S6区域切除術を行った. 病理組織所見では壊死組織の周囲に菌糸を認め, その菌糸はGrocott染色陽性でアスペルギルスより太く, 隔壁を有さず直角に分枝する特徴から肺ムコール症と診断した. 現在, 術後約8年を経過しているが再発を認めず健在である.

症例は54歳,男性.アルコール性肝硬変のため当院通院中,大量の腹水の貯留と臍ヘルニアを認めていた.突然の腹痛が出現し,同時に臍部から大量の腹水漏出を認めたため,救急搬入された.来院時,臍ヘルニア頂部に径1cm大の皮膚潰瘍と同部からの腹水の漏出を確認した.全身状態は安定していた.臍ヘルニア破裂と診断し,同日緊急手術を行った.臍を中心として紡錘状に皮膚切開を行い,臍および臍部の余剰皮膚とともにヘルニア嚢切除を行った.ヘルニア門を縫合閉鎖したのち,腹直筋前鞘の上にプローリンメッシュ™を縫合固定し,手術を終了した.術後,一時的に炎症反応の上昇を認めたが,重篤な合併症はなく経過した.成人臍ヘルニアは本邦では比較的稀な疾患であり,さらに破裂をきたした症例は散見されるのみである.

症例は83歳,女性.嘔気を主訴に当院内科を受診,腸閉塞症の診断で同日緊急入院した.入院時腹部CTを施行したが左大腿骨人工骨頭置換術後であり,人工骨頭によるアーチファクトのため骨盤底の評価は困難であった.腹部超音波検査にて左大腿部,大腿動静脈の背側に嵌頓した小腸とヘルニア門を確認し,左閉鎖孔ヘルニア嵌頓と診断,緊急開腹手術を行った.開腹すると左閉鎖孔に回腸がRichter型に嵌頓していた.嵌頓腸管を引き出すと虚血性変化を認めたため,小腸部分切除を行い,ヘルニア門は腹膜縫合により閉鎖した.閉鎖孔ヘルニアは痩せた高齢の多産の女性に好発する比較的稀な疾患であり,その診断には超音波検査は有用である.自験例のような腹腔内やその周囲に人工物を留置しており腹部CTによる評価が困難な症例では超音波検査は確定診断において非常に有用であった.

今回われわれは, 肝前性門脈圧亢進症に伴う気管支静脈瘤の一例を経験したので若干の文献的考察を加えて報告する.症例は60歳男性, 繰り返す喀血と右肺巨大腫瘤の精査のため当科紹介となった.胸部X線・CT・MRIにて右胸腔に21×11cmの巨大な腫瘤を認め, 画像所見・臨床経過から慢性膿胸と診断した.胸腹部造影CT・MRIで胸部食道から胃噴門部にかけて著明に発達した側副血行を認め, また肝門部での門脈狭窄と肝外門脈の拡張も認めた.胃食道内視鏡では下部食道から胃噴門部にかけて全周性の食道静脈瘤を, 気管支内視鏡では気管下部から両側主気管支にかけて膜様部を中心とした非拍動情生・暗赤色・薄壁の血管拡張所見を認めた.以上の所見から, 肝門部門脈狭窄による肝前性門脈圧亢進症に伴った気管支静脈瘤と診断した.繰り返す喀血は静脈瘤からの出血と考えられた.

腸管嚢腫様気腫症は,確定診断が出来れば重篤な臨床症状がない限り,保存的治療が可能な疾患である.今回われわれは,消化管穿孔として開腹術を行った腸管嚢腫様気腫症の1例を経験したので報告する.症例は80歳,女性.右下腹部痛を主訴に当院内科を受診した.胸部・腹部X線写真では異常所見を認めなかった.腹部CT,超音波検査にて,肝表面に腹腔内遊離ガス像と,盲腸から上行結腸にかけて腸管壁の肥厚を認めた.以上から,結腸憩室穿孔または虫垂穿孔による腹膜炎を疑い,緊急開腹手術を行った.消化管に明らかな穿孔部は認めなかったが,回腸末端から約90cm口側の回腸漿膜下および腸間膜に,多数の気腫性変化と散在する粘膜下腫瘍様の硬結を触知した.手術は約25cmの回腸を切除した.病理組織学的検査では,粘膜下層に嚢胞状病変を認め,腸管嚢胞様気腫症と診断した.術後経過は良好で,現在,術後約8カ月を経過したが,再発は認めていない.

幽門狭窄で発症した胃迷入膵原発腺癌の1例を報告する. 症例は58歳の女性で, 約1か月前からの食後頻回の嘔吐を主訴に当院来院した. 胃内視鏡検査では幽門輪の全周性の狭窄を認めたが粘膜生検では悪性所見は認めなかった. また, 超音波内視鏡検査でも胃壁層構造は保たれており腫瘍像は認めなかった. 症状の改善を目的に2度のバルーン拡張術を行ったが, 狭窄症状が軽快しなかったため開腹術を行った. 幽門部粘膜の術中迅速病理検査では悪性所見を認めなかったため, 幽門輪切除術のみを行った. 病理組織学的検査では, 粘膜筋板から漿膜にかけて浸潤性に増殖する腺癌を認め, その近傍に異所性膵組織および上皮に異型を伴う膵導管が存在していたことより, 胃迷入膵原発の腺癌と診断した. 後日胃幽門側追加切除術, リンパ節郭清 (D2) を行ったところ, No.5にリンパ節転移を認めた. 総合所見はpT2, pN1, sH0, sP0, cM0, fStage IIであった.

症例は76歳の女性. 肺癌 (高分化腺癌, IB期) の手術既往がある. 開腹歴はない. 腹痛, 嘔吐を主訴に腸閉塞症の診断で入院し, 保存的に一時改善したが腸閉塞が再発したため手術を行った. 回腸末端から約150cmの回腸壁が瘢痕状に狭窄しており同部の小腸を切除した. 切除標本では腸間膜反対側に径20×15mmの粘膜下腫瘍を認めた. 病理組織学的所見では, 粘膜下層から漿膜の脂肪組織にかけて多数の膵組織を認め, ランゲルハンス島, 腺房細胞, 膵導管を有しておりHeinrich I型迷入膵と診断した. 迷入膵は胃, 十二指腸など上部消化管に好発し, 回腸迷入膵は比較的まれである. 自験例は, 開腹歴のない減圧処置に抵抗性の腸閉塞であり, さらに肺癌の小腸転移の可能性も考慮する必要があり, 示唆に富む症例であった.

症例は56歳の女性. 夕食に鰯の酢の物を摂取したが, 翌朝心窩部痛および嘔吐が出現したため来院した. 当初は急性胃腸炎との診断にて保存的治療を行ったが, 翌日の腹部US, CTにて空腸に同心円状の層状構造をみとめ腸重積症と診断し緊急手術を行った. 手術所見では, トライツ靱帯から約10cmの空腸に順行性に腸重積症を認めた. 用手的に整復を行ったが, 腸管の浮腫が高度であったため約30cmの空腸を切除した. 切除標本では口側端に発赤した浮腫状の粘膜を認めたのみであったが, 病理組織学的検査で粘膜下層に虫体の迷入と著明な好酸球の浸潤を認め小腸アニサキス症と診断した. 腸アニサキス症はまれではあるが腸重積症も引き起こすことがあることも念頭に置き, 詳細な病歴の聴取, 検査成績, 画像診断など総合的に判断し診療に当たることが重要であると思われた.

症例は51歳,女性.心窩部のつかえ感および疼痛を主訴に来院した.胸部X線写真では縦隔内に消化管ガス像を認め,上部消化管透視では,臓器軸性に捻転した全胃がいわゆるupside down stomachの像を呈し左横隔膜上に脱出していた.臓器軸性胃軸捻転症を伴った食道裂孔ヘルニアと診断し開腹術を行った.ヘルニア内容は全胃,大網,横行結腸であり腹腔内への還納は容易であった.食道裂孔は約6×4.5cmと開大していた.手術はヘルニア嚢を結紮切除した後に食道裂孔を縫縮し,さらにNissen法によるfun-doplicationを加えた.胃軸捻転症は新生児,幼児に好発し成人発症例は少ない.本症例のように胃軸捻転症を伴い全胃が脱出した成人食道裂孔ヘルニアは稀な症例と思われ報告する.

症例は42歳，女性．右腋窩腫瘤を自覚し，近医を受診した．右腋窩に3.8cm大，右乳房DC領に1.2×1.2cmの腫瘤を認めた．穿刺吸引細胞診にて，悪性の疑いと診断され，当科紹介受診となった．乳癌および腋窩リンパ節転移も否定できないため手術施行した．右腋窩腫瘤および右乳腺腫瘤を摘出し，それぞれ術中迅速病理に提出，その結果悪性所見は認めなかった．本症例のように腋窩腫瘤と同側の乳腺に腫瘤認める場合には，特に慎重に診療にあたり過剰診断・過剰手術にならないように注意するべきであると思われた．

Background: Malignant pericardial effusion caused by carcinomatous pericarditis is a complication of advanced malignancy. Breast cancer is the second most important cause of malignant pericardial effusion. Malignant pericardial effusion is the end stage of breast cancer, and the prognosis is very poor. Pericardial effusion may cause cardiac tamponade and sudden death if it is not controlled properly. There is a debate on which is the best method to control pericardial effusion. Case Report: We describe the clinical course of a 55-year-old woman with recurrent breast cancer, pericardial effusion, and cardiac tamponade caused by carcinomatous pericarditis. Thoracoscopic pericardial window was performed to control the pericardial effusion. The patient survived for about 5 years after being diagnosed with pericardial metastases. Conclusion: The observed long-term survival in such a patient with the development of pericardial effusions and cardiac tamponade caused by carcinomatous pericarditis attributable to breast cancer is rare. Thoracoscopic pericardial window was effective in controlling the pericardial effusion.

A 37-year-old woman noticed a right anterior chest mass and pain. The mass had been rapidly growing and she visited our hospital. The mass was hard and 8 × 7 cm in size. It was detected in the upper inner quadrant of her anterior chest wall. A computed tomography (CT) examination and magnetic resonance imaging (MRI) of the chest revealed a large heterogeneously enhanced mass arising from the right chest wall with lytic destruction of the rib and coarse calcification. An image diagnosis of osteogenic sarcoma originating from a rib was made. She underwent surgical excision of the tumor and chest wall reconstruction. Microscopic examination of the resected tumor showed multiple neoplastic cells accompanied by osteoid formation within the tumor. The tumor was diagnosed as high-grade malignant osteosarcoma of the rib. Primary osteosarcoma commonly originates in the long bone in children and adolescents, but it occurs very rarely in the ribs in adults. Surgical resection plays an important role in the treatment for this disease. We report a case of primary osteosarcoma that originated in the rib of a young woman and was treated successfully by surgery.

Background Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer. Methods From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS). Results Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037). Conclusion Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes.

Patients with estrogen receptor (ER)-positive breast cancers have a better prognosis than those with ER-negative breast cancers, but often have low sensitivity to chemotherapy and a limited survival benefit. We have previously shown a combination effect of taxanes and fulvestrant and suggested that this treatment may be useful for ER-positive breast cancer. In this study, we evaluated the effects of combinations of hormone drugs and chemotherapeutic agents. In vitro, the effects of combinations of five chemotherapeutic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) and three hormone drugs (fulvestrant, tamoxifen, and 4-hydroxytamoxifen) were examined in ER-positive breast cancer cell lines using CalcuSyn software. Changes in chemoresistant factors such as Bcl2, multidrug resistance-associated protein 1, and microtubule-associated protein tau were also examined after exposure of the cells to hormone drugs. In vivo, tumor sizes in mice were evaluated after treatment with docetaxel or doxorubicin alone, fulvestrant alone, and combinations of these agents. Combination treatment with fulvestrant and all five chemotherapeutic agents in vitro showed synergistic effects. In contrast, tamoxifen showed an antagonistic effect with all the chemotherapeutic agents. 4-Hydroxytamoxifen showed an antagonistic effect with doxorubicin and 5-fluorouracil, but a synergistic effect with taxanes and vinorelbine. Regarding chemoresistant factors, Bcl2 and microtubule-associated protein tau were downregulated by fulvestrant. In vivo, a combination of fulvestrant and docetaxel had a synergistic effect on tumor growth, but fulvestrant and doxorubicin did not show this effect. In conclusion, fulvestrant showed good compatibility with all the evaluated chemotherapeutic agents, and especially with docetaxel, in vitro and in vivo.

Introduction Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT. Methods The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes. Results mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-β-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect. Conclusions Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.

Background UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. Methods We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Results Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. Conclusion The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.

Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer.

Background In patients with early breast cancer, sentinel lymph node biopsy (SLNB) has been emerging as a new standard of care. The use of SLNB with a blue dye is convenient and safe, but it requires a high level of technical skill. Recently, an instrument that can provide fluorescence imaging of lymphatic flow has been introduced. In the present study, we analyzed breast lymphatic pathways and discussed its potential as a modality to complement the use of SLNB with a blue dye. Methods Thirty-seven consecutive patients with breast cancer were examined. To obtain fluorescence imaging, an invisible near-infrared fluorescence imaging system was used. After indocyanine green was subdermally injected in the subareolar site and at two sites around the tumor, the subcutaneous lymphatic drainage pathway (LDP) was observed. Results In 27 (72.9%) of the patients, the number of LDP from the periareolar area was one or two. In 21(63.6%) of 33 patients with subdermal injection around the tumor, no LDP was observed from the peritumoral area. Lymphatic connection between the peritumoral area and the periareolar area was observed very frequently (91.7%). In 26 (70.3%) of the patients, multiple routes joined together and only one route was ultimately directed to the axilla. Significant correlation was seen between body mass index (BMI) and the transit time to the axilla after injection (p = 0.0038). Additionally, a significant correlation was seen between the number of LPD from the periareolar area and the distance between detected SLNs and the fluorescence line-disappearing point (p = 0.034). Conclusions This instrument can provide some important information, and can be an available and reliable navigator for SLNB with a blue dye.

Intrapulmonary aberrant needles are rare in clinical practice. We report the successful removal of intrapulmonary aberrant needle. A 59-year-old man, though he was asymptomatic, was referred to our department after an abnormal shadow had been detected on a chest X-ray. Chest X-ray and chest computed tomography (CT) showed a foreign body suspected to be a metal artifact in the left upper lobe. It was diagnosed as an intrapulmonary aberrant needle and an operation under video-assisted thoracoscopic surgery was performed. Using perioperative fluoroscopy, we could confirm the location of the needle and remove it successfully. An intrapulmonary aberrant needle should be removed surgically, even if the patient is asymptomatic, due to the development of lung abscess or pyothorax and the risk containing harmful matter to health.