PURPOSE: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. MATERIALS AND METHODS: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and beta-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. RESULTS: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and beta-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. CONCLUSION: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and beta-catenin. Future research is needed on a larger data set or with other molecular biomarkers.
Antibodies ; beta Catenin ; Bile Ducts, Extrahepatic ; Biomarkers ; Chemoradiotherapy ; Cytoplasm ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 9 ; Medical Records ; Proto-Oncogene Proteins c-akt ; Retrospective Studies

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.
Adult ; Aldehyde Dehydrogenase ; Apoptosis ; Astrocytes ; Brain Neoplasms ; Caspase 3 ; Cell Cycle ; Cell Survival ; Disulfiram ; DNA Damage ; Flow Cytometry ; Glioblastoma ; Humans ; In Vitro Techniques ; Methylation ; Prognosis ; Radiation Tolerance ; Radiotherapy

PURPOSE: The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer. MATERIALS AND METHODS: Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed. RESULTS: After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance. CONCLUSION: Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.
Adenocarcinoma, Mucinous ; Chemoradiotherapy ; Humans ; Magnetic Resonance Imaging ; Mucins ; Pathology ; Rectal Neoplasms ; Treatment Outcome

Introduction  The demographic composition of the ethnic Korean population in Japan (often referred to as zainichi) shows a declining birthrate. However, zainichi who live in zainichi Korean communities have more children than zainichi living in predominantly Japanese communities. Social capital (SC) can increase societal efficiency by promoting cooperative behavior within communities. This study clarified the family formation and SC that supports childcare for zainichi mothers living in zainichi Korean communities.Methods  We conducted semi-structured interviews with 10 zainichi mothers living in zainichi Korean communities in Japan. We qualitatively and descriptively analyzed the family formation and SC that support childcare in this population. The Ethical Committee of Osaka Prefecture University approved this study and the participants gave their written informed consent.Results  We extracted three categories and 12 subcategories for “thoughts on current family formation” and four categories and 11 subcategories for “SC supporting childcare.” Zainichi mothers living in Korean communities “think consciously about marriage” and “think positively about having multiple children and family formation,” but they have “concerns about childbearing and child-rearing.” “People who support childcare practically and mentally” and “childcare services” were also identified as important factors. Although zainichi mothers felt dissatisfied with “support that they wanted to use but found difficult to use,” they considered childcare support as human and physical SC. As an additional resource, they felt that “the zainichi community fosters security and bonding,” and thus promotes SC for child-rearing.Discussion  Networks with common norms, values, and understanding facilitated cooperation among zainichi mothers. “The zainichi community, which fosters security and bonding,” may support family formation through engendering a positive perception of child-rearing.

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy, Segmental* ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Time-to-Treatment

Objectives  High gestational weight gain (GWG) is associated with perinatal risks to mother and child. Research shows that non-Japanese Asian women have higher GWG than Japanese women. However, no studies have compared GWG in these two populations using GWG recommendations in accordance with Japanese and Institute of Medicine (IOM) guidelines. The study aim was to compare GWG in non-Japanese Asian and Japanese pregnant women.Methods  This was a retrospective observational study. All participants were aged ≥20 years and gave birth between September 2019 and the end of October 2020 at one perinatal medical center in Japan. Medical record data were analyzed for 170 non-Japanese Asian and 316 Japanese pregnant women. We used t-tests and chi-square tests to examine differences in age, parity, smoking status, antenatal checkups, pre-pregnancy body mass index, and GWG. Logistic regression analysis was used to estimate odds ratios (95% confidence intervals) for above- and below-recommended GWG by non-Japanese Asian and Japanese status. We also analyzed differences in delivery type, abnormal blood loss, and birth size according to GWG.Results  After adjustment for confounding factors, the multivariable-adjusted OR and 95% CI for GWG above the Japanese guidelines recommendations was 1.86 (1.23-2.81) and that for GWG above IOM guidelines recommendations was 2.46 (1.45-4.16) for non-Japanese Asian women, as compared with Japanese women. Conversely, the multivariable-adjusted OR and 95% CI for GWG below Japanese guidelines recommendations was 1.55 (1.03-2.32) and that for GWG below IOM guidelines recommendations was 1.87 (1.26-2.76) for Japanese women, compared with non-Japanese Asian women. Conclusion  Because Japanese women tend to be below recommended GWG and non-Japanese Asian women tend to be above recommended GWG, midwives need to provide careful guidance to reduce perinatal risks.