Natsumi Yamashita

Impact of perioperative peripheral blood values on postoperative complications after esophageal surgery

PurposePrediction of the postoperative course of esophagectomy is an important part of the strict perioperative management of patients undergoing surgery for esophageal cancer.MethodsTo evaluate their clinical importance, peripheral blood values, including white blood cell count (WBC), lymphocyte count, and the levels of total protein, transferrin, factor XIII, D-dimer, fibrin, and fibrinogen degradation products (FDP) were measured before and after esophagectomy for esophageal cancer in 24 patients.ResultsThe preoperative WBC and the pre- and postoperative lymphocyte count were decreased remarkably in patients who received preoperative chemoradiotherapy. The values of perioperative serum transferrin were significantly lower in patients with postoperative pneumonia than in those without. The activity of plasma factor XIII was suppressed on postoperative day (POD) 7 in patients with pneumonia and on POD 14 in patients with leakage.ConclusionsThese results suggest that patients who receive preoperative chemoradiotherapy are potentially immunosuppressed, the preoperative serum transferrin level is a possible predictive marker of postoperative pneumonia, and suppression of factor XIII activity is related to anastomotic insufficiency.

A comprehensive analysis of immunohistochemical studies in intrahepatic cholangiocarcinoma using the survival tree model.

Objective: Various immunohistochemical studies have been performed regarding intrahepatic cholangiocarcinoma (ICC), including the cell cycle-related proteins (p27, cyclin D1, 14-3-3σ, p53, cyclin B1 and Ki-67), the proto-oncogenes (c-erbB-2 and c-Met), the extracellular matrix proteins (tenascin and laminin) and others (β-catenin, epidermal growth factor receptor, osteopontin, aquaporin 1, MUC5AC and fascin). Nevertheless, none of these have been proven to be a predictive power of the prognosis with high specificity and sensitivity for ICC. Methods: Sixty-one patients with ICC were selected and ICC specimens were immunohistochemically stained with the above 16 markers, as previously reported. Results: The immunoreactivity of osteopontin, tenascin and Ki-67 divided the patients with ICC into 4 subgroups by the survival tree model. There was a significant relationship between the location of the tumor, TNM classification, histological differentiation, tumor size, lymphatic permeation, perineural invasion, lymph node metastasis, intrahepatic metastasis and viral infection among the 4 subgroups. In addition, there was a significant difference in survival among the 4 subgroups. Conclusion: In this study, the subgrouping by the survival tree model might be helpful for predicting the patients’ prognosis in ICC.

Impact of Human T Cell Leukemia Virus Type 1 in Living Donor Liver Transplantation

Human T cell leukemia virus type 1 (HTLV‐1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV‐1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV‐1 status in living donor liver transplantation (LDLT). Twenty‐six of 329 (7.9%) HTLV‐1 carriers underwent primary LDLT. One recipient negative for HTLV‐1 before LDLT received a graft from an HTLV‐1 positive donor. Eight donors were HTLV‐1 positive. Twenty‐seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV‐1 positive donors and two from negative donors. The 1‐, 3‐ and 5‐year HTLV‐1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV‐1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development.

Significance of metacognitive skills in laparoscopic surgery assessed by essential task simulation

Abstract Background: Metacognition is the knowledge about ones own methods of perceiving, remembering, thinking, and acting. This study determined the significance of metacognitive skills in laparoscopic surgery with the aim of applying the findings in a laparoscopic surgery training program. Material and methods: Eighteen medical students with no experience in laparoscopic surgery (novice group) and eight expert surgeons who had each performed >100 laparoscopic surgeries (expert group) were enrolled. The examinees in each group performed an evaluation task using a virtual reality simulator and answered questions about the task. Results: The longest performance times, longest path lengths, and most frequent tissue damage occurred at 135° in the novice group and at 180° in the expert group. The greatest recognition of task difficulties, impatience, and irritation occurred at 135° in the novice group and at 180° in the expert group. There were statistically significant correlation coefficients between the instrument path length and task difficulty (metacognition) at 135° (R = 0.74, p = 0.03) and 180° (R = 0.79, p = 0.02) in the expert group, but there were no significant correlations in the novice group. Conclusion: We elucidated the significance of metacognitive skills in laparoscopic surgery. A training program should include recognition feedback systems.

Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis

Several studies have suggested an association between post‐transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living‐donor liver transplantation (LDLT).

A Change-Point Regression Approach for Efficacy Evaluation of Dietary Supplements

In clinical trials for dietary supplements and functional foods, the study population tends to be a mixture of healthy subjects and those who are not so healthy but are not definitely diseased (called “borderline subjects”). For such heterogeneous populations, the t-test and ANCOVA method often fail to provide the desired treatment efficacy. We propose an alternative approach for the efficacy evaluation of dietary supplements and functional foods based on a change-point linear regression model. The model does not require the assumption of a constant treatment effect and provides clinically interpretable results. By employing the AIC-based profile likelihood method, inferences can be made easily using standard statistical software. The proposed method was applied to the Garcinia study data, and the merit of the method was demonstrated by comparing it with traditional methods.

Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan

The natural history of human T‐cell leukemia virus type 1 (HTLV‐1), which causes adult T‐cell leukemia (ATL) or HTLV‐1 associated myelopathy, after liver transplantation is unclear.

Abstract P2-05-12: Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in invasive breast cancer

Background: E-cadherin and vimentin are now regarded as major and conventional canonical markers of epithelial-mesenchymal transition (EMT). It is commonly assumed E-cadherin is uniformly lost during the process of EMT. We previously reported that the elevated expression of vimentin contributes to the aggressive phenotype in invasive breast cancer. On the other hand, the role of E-cadherin in breast cancer biology might be unclear and more complex. Although, cell cohesion during breast cancer invasion is often overlooked, accumulating evidences indicate breast tumor cells are typically cohesive and often display membrane-localized E-cadherin in both the primary tumor and distant metastases, termed collective invasion. Multiple mechanisms have emerged to address how epithelial breast tumors invade. Aims: The aim of this study is to reveal the clinical importance of the expression of E-cadherin and vimentin in breast cancer. Methods: The E-cadherin and vimentin protein expression were evaluated by immunohistochemistry (IHC) in 177 invasive breast cancer samples. Among these, E-cadherin and vimentin expression were evaluated in the set of primary breast cancer and metastatic lymph nodes in 65 cases. Results: The positive vimentin expression was highly correlated with poor disease-free survival (DFS) and overall survival (OS) (p=0.019 and p=0.0044), however, the E-cadherin expression alone did not correlate with prognosis. Interestingly, Both E-cadherin and vimentin positive tumor had the worst DFS and OS among all breast cancer (p=0.03 and p=0.0089). Vimentin expression was highly correlated between primary tumors and metastatic lymph nodes. However, E-cadherin expression levels were significantly elevated in metastatic lymph nodes (p=0.0017), Co-expression of E-cadherin and vimentin in the metastatic lymph nodes also showed worst DFS and OS (p=0.12 and p=0.027). Conclusions: Co-expression of E-cadherin and vimentin seems to be associated with the most aggressive phenotype and poorest prognosis in breast cancer, and positive E-cadherin expression may not always play roles for tumor suppression. Citation Format: Yamashita N, Tokunaga E, Inoue Y, Tanaka K, Ueo H, Saeki H, Oki E, Maehara Y. Epithelial paradox; clinical significance of co-expression of E-cadherin and vimentin in invasive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-12.

Evaluation of the HER2 and Hormone Receptor Status in Metastatic Breast Cancer Using Cell Blocks: A Multi-Institutional Study

Objective: We explore the problems associated with the cell block (CB) method for receptor analysis in breast cancer metastases and propose a method for reporting the results. Study Design: Nine institutions used the CB method for the analysis of hormone receptors (HRs) and HER2 (human epidermal growth factor receptor 2) protein in cytological specimens of breast cancer metastases in routine practice. The stained slides were independently evaluated by 8 pathologists. Dual in situ hybridization assay was performed in cases of discordant results for HER2 protein. Based on the results, we propose a method for receptor scoring in the CB method. Results: Of 61 specimens, 57 contained tumor cells. Two or more pathologists disagreed on the results for the estrogen receptor, progesterone receptor, and HER2 protein in 3 (5.3%), 13 (22.8%), and 19 (33.3%) cases, respectively. The discrepant results for the HRs were attributed to the presence of a few positive cells or faintly stained cells. The high interobserver discordance rate for HER2 protein was explained by interobserver differences in the scoring criteria. Conclusion: The use of categorical scoring into positive and negative is recommended for evaluating the HR expressions. Use of strict criteria for HER2 protein 2+ and 3+ cases is recommended, as HER2-positive cases should not be missed.

Abstract P5-13-05: The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy

Background. The estrogen receptor (ER)/ GATA3/ Forkhead box A1 (FOXA1) network is necessary for the ERα functional signature specific to luminal type breast cancers. High expression of FOXA1 indicates a good prognosis in ER-positive breast cancer. However, little is known about the association between the expression of FOXA1 and GATA3, and the efficacy of neoadjuvant endocrine therapy (NAE). This study investigated their predictive potential for NAE and the changes of their expression after NAE. Methods. The expression of ER, progesterone receptor (PgR), Ki67, FOXA1, and GATA3 were analyzed by immunohistochemistry in 66 patients with hormone receptor-positive/ human epidermal growth factor receptor 2 (HER2)-negative breast cancer who had been treated with NAE between March 2003 and December 2012 at Kyushu University Hospital, National Kyushu Cancer Center, and Sagara Hospital. The association between the expression of biological marker and the efficacy of NAE, and their expression changes after NAE were evaluated. Results. The median age of the patients was 60 years (range, 30–84 years). Pre- and post-menopausal patients were 24 (36.4%) and 42 (63.6%). Endocrine agents that were administered are as follows: aromatase inhibitors (AIs) for 42 patients (63.6%), luteinizing hormone-releasing hormone (LHRH) agonist plus AI for 10 patients (15.2%), LHRH agonist plus tamoxifen for 13 patients (19.7%). NAE yielded a partial response (PR) in 21 patients (31.8%) and stable disease (SD) in 45 patients (68.2%). Breast conserving surgery was performed in 56 patients (84.8%) and mastectomy was performed in 10 patients (15.2%). Preoperative Endocrine Prognostic Index (PEPI) score was 0 in 10 patients (15.2%) and 1 or greater (score 1 ≤) in 56 patients (84.8%). Pre-treatment FOXA1 expression was positively correlated with GATA3 (P = 0.0003) and PgR (P = 0.0138). Post-treatment Ki67 expression was significantly lower in tumors, which achieved PR compared with those with SD (P = 0.0007). The expression of PgR, Ki67, and FOXA1 was significantly lower in post-treatment tumors compared with those in pre-treatment samples (p 20%, the expression of Ki67 and FOXA1 were significantly lower in post-treatment tumors (P Conclusions. FOXA1 expression correlated with PgR expression, and was reduced significantly after NAE. These results suggest that blocking the effect of estrogen might reduce FOXA1 expression. Citation Format: Tanaka K, Tokunaga E, Inoue Y, Ueo H, Yamashita N, Sagara Y, Ohi Y, Taguchi K, Ohno S, Okano S, Kitao H, Oki E, Oda Y, Maehara Y. The relationship between the expression of FOXA1 and GATA3 and the efficacy of neoadjuvant endocrine therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-05.