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Background Vascular endothelial growth factor (VEGF) is a key player in angiogenesis, and bevacizumab, a humanized monoclonal antibody against VEGF-A, is already utilized in daily clinical practice coupled with chemotherapy for locally advanced and metastatic breast cancers (ABC). Although the impact of bevacizumab plus paclitaxel therapy on PFS was prominent, no OS benefit has been demonstrated so far. Identification of a robust biomarker for bevacizumab therapy in terms of benefit on OS is a critical issue. Since VEGF modulates various functions of cancer immunity, direct inhibition of VEGF, in addition to vascular normalization by bevacizumab may lead to improvement of immune microenvironment, resulting in favorable prognosis in patients. On the basis of this aspect, predictive efficacy of peripheral immune related parameters were investigated in patients treated with bevacizumab plus paclitaxel. Method A total of 182 patients with locally advanced and metastatic breast cancers treated with bevacizumab plus paclitaxel were retrospectively recruited from three institutes. We measured neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in the peripheral blood taken at baseline (the same day just before start of 1st treatment). Bevacizumab 10 mg/kg on days 1 and 15 and paclitaxel 80 or 90 mg/m2 on day 1, 8, and 15 of each 28-day cycle were administered intravenously. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0mg/dL, respectively and baseline values of these factors were measured. Results We divided the patients into NLR-high (n=101) and -low (n=81); CRP-high (n=62) and -low (n=89). The progression-free survival (PFS) of patients with NLR-low was significantly longer than that of patients with NLR-high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.31-0.70; p=0.0002). In addition, OS of patients with NLR-low was significantly better than those with -high (22.2 vs. 13.5 months; HR, 0.55; 95% CI, 0.38-0.80; p=0.0017). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with -high (HR, 0.42; 95% CI, 0.27-0.66; p Citation Format: Hiromi Ozawa, Yoshimasa Miyagawa, Ayako Yanai, Takehiro Yanagawa, Jyunichi Inatome, Chiyomi Egawa, Arisa Nishimukai, Kaori Takamoto, Takashi Morimoto, Atsushi Sata, Reiko Fukui, Ayako Bun, Tomoko Higuchi, Yukie Fujimoto, Michiko Imamura, Yasuo Miyoshi. Baseline neutrophil-to-lymphocyte ratio and C-reactive protein predict efficacy of bevacizumab plus paclitaxel therapy for locally advanced or metastatic breast cancer [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 P3-08-49.

The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic breast cancers. A total of 179 patients treated with bevacizumab plus paclitaxel were recruited from three institutes in the test cohort. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0 mg/dL, respectively, and baseline values of these factors were measured. The PFS of patients with NLR-low was significantly longer than that of patients with -high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.48, 95% confidence interval (95% CI), 0.31–0.73; p = 0.0004). OS of patients with NLR-low was significantly better than those with-high (22.2 vs. 13.5 months; HR, 0.57, 95% CI, 0.39–0.83; p = 0.0032). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with patients with -high (HR, 0.44, 95% CI, 0.28–0.68; p = 0.0001 and HR, 0.39, 95% CI, 0.26–0.61, p < 0.0001, respectively). In the validation cohort from two institutes (n = 57), similar significant improvements in PFS and OS were confirmed for patients with NLR-low (p = 0.0344 and p = 0.0233, respectively) and CRP-low groups (p < 0.0001 and p = 0.0001, respectively). Low levels of NLR and CRP at baseline were significantly associated with improved prognosis in patients treated with bevacizumab plus paclitaxel.

Under the Economic Partnership Agreements(EPA)with Indonesia and the Philippines, about 1,000 foreign care workers have entered Japan since 2008. They have started working in hospitals and nursing care facilities all over Japan,practicing intercultural care. This paper examines the phenomenon of intercultural care in Japan with a focus on the issues involving the EPA. It first gives an overview of the current state of intercultural care in Japan. Then it describes problems related to the EPA as a framework for accepting foreign care workers in Japan and discusses the issues involving language, culture,and communication in the field of intercultural care.

症例は35歳，女性．主訴は左乳房に有痛性の腫瘤を自覚し受診となる．触診，超音波検査，マンモグラフィー，CT，MRIより乳癌を強く疑い，切除生検を施行した結果，病理組織診にて肉芽腫性乳腺炎と診断された．また，肉芽腫性乳腺炎を発症して1カ月後に両側下腿に有痛性の紅斑が出現がみられ皮膚生検を施行し結節性紅斑と診断された．病変は経過観察のみで自然に軽快した．肉芽腫性乳腺炎は稀な乳腺良性疾患であり，臨床症状や画像診断では乳癌との鑑別が困難である．今回われわれは肉芽腫性乳腺炎に結節性紅斑を併存し自然軽快した稀な症例を経験した．文献的考察を加えて報告する．

The accuracy of one-step nucleic acid amplification (OSNA) for the detection of lymph node (LN) metastasis in breast cancer patients has been well established. This study aimed to evaluate its accuracy for patients treated with neoadjuvant chemotherapy (NAC). For this study, 300 LNs, 115 sentinel lymph nodes (SLNs), and 185 non-SLNs from 88 breast cancer patients treated with NAC were examined by means of histology (hematoxylin and eosin staining and pancytokeratin immunostaining) and OSNA. The diagnostic accuracy, sensitivity, and specificity of OSNA were respectively 92.3, 88.5, and 93.3 % for all LNs, and the corresponding values were 87.8, 75.0, and 91.2 % for SLNs and 95.1, 97.3, and 94.6 % for non-SLNs. The diagnostic accuracy of OSNA was significantly lower for SLNs than for non-SLNs (P = 0.021), which was attributable to the low sensitivity for detection of micrometastases (micromets) due to lower CK19 mRNA expression detected by in situ hybridization (ISH) in SLN micromets than in non-SLN micromets. For primary breast tumors, CK19 mRNA expression showed a significant reduction after NAC (P = 0.040). The diagnostic accuracy of OSNA for NAC-treated patients is similar to that for NAC-nontreated patients, but its accuracy is significantly lower for SLNs than for non-SLNs. The findings obtained with CK19 mRNA ISH suggest that most SLN micromets cannot be detected by OSNA due to the reduced expression of CK19 mRNA induced by NAC.

CASE 1: A 61-year-old man having advanced gastric cancer was presented with massive hematemesis. We could not control bleeding by gastrointestinal endoscopic hemostatic therapy, so we performed a transcatheter arterial embolization (TAE). We performed embolization on the left gastric artery. CASE 2: A 58-year-old man having advanced gastric cancer was presented with hematemesis. We could not control bleeding by gastrointestinal endoscopic procedure, so we conducted TAE. We performed embolization on the left gastric artery and right gastric artery. In both cases, hemostasis was achieved by TAE, and effectively controlled the bleeding from advanced gastric cancer.

A 41-year-old man who had non-small cell lung cancer invading his right 3rd, 4th and 5th ribs with hilum lymph node swelling(cT3N1M0, cStage III A), received chemoradiation therapy, cisplatin(CDDP)/docetaxel, and 2 Gy/Fr of irradiation prior to surgery. But the therapy was discontinued due to interstitial pneumonitis on day 24, during 28 Gy of radiation. At that time, a PET-CT scan revealed the accumulation of FDG in the primary tumor, hilar lymph node, and one of the ipsilateral axillar lymph nodes, in which cancer cell presence was proven by aspiration needle cytology. We organized a radical operation even though the node status was classified to cStage IV, because ipsilateral axillary lymph nodes may be regarded as regional nodes for tumors invading the chest wall. Right upper lobectomy and chest wall resection were performed, and the ipsilateral hilar, mediastinal, and axillary lymphnode were dissected. Pathological findings showed no active cancer cell in the primary lesion and hilar lymph nodes(Ef. 3), but obvious metastasis in one of the axillary lymph nodes(pT0N0M1b, pStage IV). The patient received adjuvant chemotherapy(CDDP/vinorelbine), and is alive and tumor-free 10months after the resection.

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

A 75-year-old female presented with appetite and weight loss and epigastralgia. CT revealed a primary gallbladder carcinoma Stage IVb with multiple hepatic metastases. Gastrofiberscopy revealed an invasion to duodenal and bleeding from the tumor. For her poor performance status, it seems to be too difficult to undergo a general chemotherapy. So after gastrojejunostomy, transarterial embolization (TAE) was performed. She underwent 2 times TAE. There was a notable reduction in tumor size. But pulmonary metastases were found in bilateral lung. She died after 8 months. TAE may be useful for advanced gallbladder carcinoma with tumor vascularity.

We analyzed a treatment outcome and the effect of systemic chemotherapy for patient with unresectable gallbladder carcinoma. Sixteen patients were investigated. Gemcitabine (GEM) was administrated for fifteen patients as the first-line chemotherapy. S-1 was administrated for ten patients as the second-line chemotherapy. The response rate and tumor control rate of the first-line GEM were 14.3% and 78.6%, respectively. The median progression free time of the first-line GEM was 6.0 months. The response rate and tumor control rate of the second-line S-1 were respectively 20.0% and 30.0%. The median progression free time of the second-line S-1 was 1.8 months. The median survival time of all cases was 14.9 months. The outcome of systemic chemotherapy for patients with unresectable gallbladder carcinoma in our hospital was feasible compared with past reports.

Primary liver cancer with lymph node metastasis was recognized as poor prognosis. We herein report a case of post operative lymph node recurrence treated with UFT. A 74-year-old man with a huge mass lesion in the right liver with para Aortic lymph node metastasis admitted our hospital in April 2007. Extended right lobe hepatectomy and lymph node dissection were performed in May. A histological examination of the resected specimen showed a combined hepatocellular-cholangiocarcinoma with three lymph node metastasis. Computed tomography(CT)revealed intra hepatic metastasis (S3) and right adrenal grand metastasis 5 months after surgery. Transarterial embolization (TAE) and right adrenalectomy were performed for each metastasis. CT revealed a lymph node metastasis at the right side of infra vena cava 1 year after surgery. He was treated by oral administration of UFT (200 mg/day). The AFP and PIVKA-II value gradually decreased after administration of UFT. The size of lymph node metastasis became small confirmed by CT. But the AFP and PIVKA-II value increased 1 year and 7 months after surgery. TAE was performed against lymph node metastasis 1 year and 9 months after surgery. This case suggests UFT is useful for suppressing the growth of the lymph node metastasis.

A 64-year-old man was admitted to general practitioner because of dyschezia. He was diagnosed with lower rectal cancer by colonoscopy and referred to our hospital for therapy. At first, in spite of multiple liver metastases, we tried a resection of primary lesion in order to control of breeding, dyschezia and pain. However, we had to give up the resection, so we made sigmoid colostomy only. One month after the operation, a combination chemo-radiotherapy using S-1 was performed for controlling of local symptom. S-1 (120 mg/day) was administered on days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19, 21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the tumor was remarkably reduced and the reduction was judged as partial response. Moreover after 6 courses of FOLFIRI, the reduction was judged as complete response. Local control therapy (S-1+chemo-radiation) plus systemic therapy (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.