Yasuhiro Okumura

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies.

A Lymph Node Staging System for Gastric Cancer: A Hybrid Type Based on Topographic and Numeric Systems

Although changing a lymph node staging system from an anatomically based system to a numerically based system in gastric cancer offers better prognostic performance, several problems can arise: it does not offer information on the anatomical extent of disease and cannot represent the extent of lymph node dissection. The purpose of this study was to discover an alternative lymph node staging system for gastric cancer. Data from 6025 patients who underwent gastrectomy for primary gastric cancer between January 2000 and December 2010 were reviewed. The lymph node groups were reclassified into lesser-curvature, greater-curvature, and extra-perigastric groups. Presence of any metastatic lymph node in one group was considered positive. Lymph node groups were further stratified into four (new N0–new N3) according to the number of positive lymph node groups. Survival outcomes with this new N staging were compared with those of the current TNM system. For validation, two centers in Japan (large center, n = 3443; medium center, n = 560) were invited. Even among the same pN stages, the more advanced new N stage showed worse prognosis, indicating that the anatomical extent of metastatic lymph nodes is important. The prognostic performance of the new staging system was as good as that of the current TNM system for overall advanced gastric cancer as well as lymph node—positive gastric cancer (Harrell C-index was 0.799, 0.726, and 0.703 in current TNM and 0.799, 0.727, and 0.703 in new TNM stage). Validation sets supported these outcomes. The new N staging system demonstrated prognostic performance equal to that of the current TNM system and could thus be used as an alternative.

A two-stage operation for thoracic esophageal cancer: esophagectomy and subsequent reconstruction by a free jejunal flap

When the stomach is unavailable for esophageal reconstruction due to previous gastrectomy or synchronous gastric cancer, a pedicled jejunum or colon, with or without vascular supercharge, has been the alternative. However, these reconstructions are not free from severe complications, such as necrosis. We have introduced a new surgical technique for delayed esophageal reconstruction using a free jejunal flap. We used this technique in 11 patients. Four weeks after subtotal esophagectomy, reconstruction using free jejunal flaps was performed. A free jejunum was placed at the pre-sternum, and the internal thoracic artery and vein were usually used as the recipient vessels. There were no cases of flap necrosis and no hospital deaths. Anastomotic leakage occurred in two cases. Both leakages were cured by conservative treatment. Delayed esophageal reconstruction using a free jejunal flap can be considered to be a safe procedure when the stomach is unavailable as an esophageal substitute.

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

Background Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases. Methods The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens. Results Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC. Conclusions The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.

Evaluation of 18F-FDG uptake for detecting lymph node metastasis of gastric cancer: a prospective pilot study for one-to-one comparison of radiation dose and pathological findings.

BackgroundGastric cancer exhibits various degrees of fluorine F-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT). We evaluated the relationship between 18F-FDG uptake and the presence/absence of metastasis in individual lymph nodes (LN) on a one-to-one basis.MethodsWe analyzed 21 patients with gastric cancer. We injected 18F-FDG intravenously in the morning, and gastrectomy with LN dissection was performed in the afternoon of the same day. Radiation doses were measured at each LN using a well-type counter, and we then compared 18F-FDG uptake, the shortest diameter, and pathological examination results for each LN.ResultsIn our study, 906 LNs were analyzed, including 115 metastatic LNs. Metastatic LNs showed significantly higher 18F-FDG uptake (P < 0.0001), and were significantly enlarged (P < 0.0001). The receiver operating characteristics (ROC) curve had a larger area under the curve (0.71) for 18F-FDG uptake than for the shortest LN diameter (0.60). Considering histology, the ROC curve for intestinal type adenocarcinoma had a larger area under the curve than that for diffuse type (0.75 vs 0.61).ConclusionsF-FDG uptake is potentially a more useful variable than LN diameter for discriminating between LN with and without metastasis, especially in intestinal type gastric cancer cases.

Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab

Objective: The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer. Method: Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing. Results: The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs. Conclusion: LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

Mediastinoscopic view of the bronchial arteries in a series of surgical cases evaluated with three-dimensional computed tomography

BackgroundWe have routinely performed three-dimensional computed tomography (3-D CT) prior to video-assisted transmediastinal esophagectomy to evaluate the small arteries in the mediastinal operative field. This evaluation would be helpful in performing mediastinoscopic esophagectomy.MethodsThirty-one patients who underwent transmediastinal esophagectomy with preoperative evaluations by 3-D CT were the study subject. The bronchial arteries depicted by the 3-D CT were classified by their origin and laterality. In 18 of the 31 cases, the surgical video was available and the identification rate in the video was reviewed for each of the categorized bronchial arteries.ResultsThe detection rates of each classified artery were as follows (abbreviations, detection rate); the intercostal-bronchial trunk (IBT, 22/31), the direct left bronchial artery (LBA, 17/31), the common trunk of bronchial arteries (CTB, 7/31), the direct right bronchial artery (RBA, 2/31), and the ectopic arteries (16/31). The ectopic arteries arose from the aortic arch (11 cases), the right subclavian artery (6 cases) or the left subclavian artery (1 case). The identification rates of IBT, LBA, CTB, RBA and any of the ectopic arteries in the video review were 12/13, 4/8, 3/4, 1/1 and 2/10, respectively.ConclusionsPreoperative 3-D CT was a highly sensitive evaluation for the bronchial arteries encountered during transmediastinal esophagectomy. Orthotopic arteries except for LBA were frequently identified at the predicted sites. Although RBA and CTB were present infrequently, they often flowed into regional nodes at the bilateral bronchi or the tracheal bifurcation and, therefore, should be preoperatively evaluated.

A feasibility study of portable compton camera for metastatic lymph node detection

We are developing a portable Compton camera to be placed inside the human body for local inspection of metabolic functions of metastatic lymph node in gastric cancer. Before fabricating the portable Compton camera, Radioactivity measurement of metastatic and non-metastatic lymph nodes with an injection of FDG was conducted at the University of Tokyo Hospital. The detector that used to measure the radioactivity is composed of a 5mm × 5mm × 5mm GAGG scintillation crystal [2], a Hamamatsu Si-APD, an ASIC and a FPGA and size of the read-out board is 13 × 80 mm. The maximum radioactivity of FDG was about 7kBq. A Monte Carlo simulation result of the portable Compton camera shows that 7kBq phantoms can be imaged within 2 minutes.