Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

[The Long Term Result of Rhomboid Flap Reconstruction for Locally Advanced Breast Cancer].

In patients undergoing mastectomy for locally advanced breast cancer, surgical skin flap reconstruction is sometimes required in order to cover large skin defects. Generally, we reconstruct by using latissimus dorsi or rectus abdominis when the direct closure is difficult. These constructions are difficult and have various complications. Our facility started rhomboid flap reconstruction after mastectomy. We report the result of rhomboid flap reconstruction. Five patients were performed rhomboid flap reconstruction. Three of 5 patients were cutaneous invasion, 1 patient was skin metastasis after mastectomy, and the other patient was Paget's disease. Regarding post operative complications, there were 2 cases of surgical site infection, 2 cases of skin necrosis and 1 case of seroma. The median length of postoperative hospital stay was 9 days. Median follow-up period was 381 days(221-508 days). Only 1 patient progressed. The median progression-free survival was 332 days(221-508 days). Rhomboid flap reconstruction is effective way for the improvement of the QOL of the patients with advanced breast cancer because the long term result was not bad and we can repair large skin defect easily.

Relationship between serum lipid levels and the immune microenvironment in breast cancer patients: a retrospective study.

BACKGROUND: Therapeutic agents for dyslipidaemia, in particular statins, have been recently reported to suppress growth and metastasis of breast cancer. However, the predictive value of lipid control in breast cancer patients has not been discussed sufficiently. In addition, though immunometabolism is a relatively novel approach for tumour immunotherapy, the relationship between lipid metabolism and immune status has not been well documented. We therefore investigated the effects of lipid metabolism on antitumour immune response and cancer prognosis. METHODS: Except for patients with ductal carcinoma in situ, 938 patients treated with curative surgery were examined. The correlation between treatment for dyslipidaemia or serum lipid levels and clinicopathological features, including the prognosis, was evaluated retrospectively. Also, we stratified these results by intrinsic subtype of breast cancer, menopause, and type of therapeutic agents for dyslipidaemia. Moreover, neutrophil- to-lymphocyte ratio (NLR) and tumour-infiltrating lymphocytes (TILs) were used as indicators of systemic and local immune status, respectively. RESULTS: Of 194 patients treated for dyslipidaemia, recurrence-free survival (RFS) and overall survival (OS) did not differ significantly between users of drugs for dyslipidaemia and non-users (p = 0.775 and p = 0.304, log-rank, respectively). Among postmenopausal, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients treated for dyslipidaemia, the good serum lipid control group had significantly better RFS (p = 0.014, log-rank), lower postoperative NLR (p = 0.012), and higher TILs in resected tissues (p = 0.024) than the poor control group. Multivariate analysis showed that postoperative serum lipid levels were a risk factor for recurrence (hazard ratio = 4.722, 95% confidence interval 1.006-22.161, p = 0.049). CONCLUSIONS: Good control of serum lipid metabolism may improve the tumour immune microenvironment and prognosis in postmenopausal HR-positive/HER2-negative breast cancer patients.

Differences in tumor-infiltrating lymphocyte density and prognostic factors for breast cancer by patient age.

BACKGROUND: Lymphocytes that surround cancer participate in tumor-related immune responses and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs index the tumor microenvironment and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TIL density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of preoperative chemotherapy (POC) in BC patients who were aged either less than 45 years or more than 60 years. METHODS: We retrospectively examined the data of 356 breast cancer patients who underwent POC, including 75 patients aged ≤ 45 years and 116 patients aged > 60 years. Using pre-treatment needle biopsy specimens, TIL density was compared for each age group by Student's t-test. After analyzing different factors that affect TIL density, prognostic factors were also examined. RESULTS: Older patients with triple-negative BC had significantly lower TIL density than younger patients, while in human epidermal growth factor receptor 2 (HER2)-enriched BC, TIL density was significantly higher in the younger age group than that in the older age group. In addition, younger patients with HER2-rich breast cancer showed significantly higher complete pathological response rates than older patients with HER2-rich BC. In addition, significant differences in overall survival were observed among these patients with triple-negative BC. CONCLUSIONS: Our study suggests that younger BC patients possess significantly higher TIL density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

[A Case of Liver Abscess during Treatment for Abemaciclib-Induced Interstitial Lung Disease].

The patient was a 64-year-old woman. The patient was operated for left breast cancer(pT2N0M0, stage ⅡA, Luminal A). Eight years after surgery, CT findings revealed lung metastasis in the S8 and S9 areas of the left lung. The patient was treated with a combination of abemaciclib and letrozole, which resulted in a partial response(PR). One year after treatment, the lung metastases remained small, but multiple interstitial shadows appeared in both lower lung fields. The patient was diagnosed with drug-induced interstitial lung disease(Grade 1), and abemaciclib withdrawal and steroid therapy were initiated. After 3 months of treatment with prednisolone at 30 mg/day, the interstitial shadows tended to improve on CT, but a liver abscess was found in the S8 area of the right lobe of the liver. Prednisolone was tapered and abemaciclib was resumed at a dose of 200 mg/day, resulting in scarring of the lung injury and resolution of the liver abscess. The patient's PR was maintained for 18 months after relapse. We report a case of liver abscess during treatment of abemaciclib-induced interstitial lung disease.

Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy.

PURPOSE: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors' immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. METHODS: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient's height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. RESULTS: The median BMI was 21.9 kg/m2 (range, 14.3-38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031). CONCLUSIONS: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-positive breast cancer.

BACKGROUND: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2- breast cancer. METHODS: In stages I-II of HR+/HER2- breast cancer patients who underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy), forty-two patients relapsed after surgery. TILs were evaluated using needle biopsy specimens for the diagnosis of breast cancer. Morphological assessment was conducted using conventional hematoxylin and eosin staining. RESULTS: Six patients had no TILs density. In them, local recurrence was significantly less (p = 0.022), while distant metastases were significantly more (p = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2- breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis (p = 0.015, odds ratio [OR] = 0.127), although not as independent factors (p = 0.285, OR = 0.144). CONCLUSIONS: Our findings indicate that TILs may predict distant metastatic recurrence in stages I-II of HR+/HER2- breast cancer in patients who do not undergo chemotherapy.

Prediction of survival after eribulin chemotherapy for breast cancer by absolute lymphocyte counts and progression types.

BACKGROUND: In the Response Evaluation Criteria for Solid Tumors (RECIST) diagnostic criteria, the concepts of progression by preexisting disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the "PPL" form indicates invasion, and the "PNM" form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte count (ALC) is an indicator of the host's immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy. METHODS: From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1500/µl, based on previous studies. RESULTS: The PPL group (71 patients, 80.7%) had significantly longer progression-free survival (PFS) (p = 0.022, log-rank) and overall survival (OS) (p < 0.001, log-rank) than the PNM group (17 patients, 19.3%). In the 51 patients with ALC < 1500/µl, the PPL group had a significantly better prognosis than the PNM group (PFS: p = 0.035, OS: p < 0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC ≥ 1500/µl, the PPL group had a better OS compared with the PNM group (p = 0.055, log-rank), but there was no significant difference in PFS between the two groups (p = 0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and "high-ALC and PPL" were factors for a good prognosis (p < 0.001, HR = 0.321; p = 0.036, HR = 0.290). CONCLUSIONS: The progression form of PNM had a worse prognosis than PPL in patients treated with eribulin. In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC ≥ 1500/µl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker "high-ALC (ALC ≥ 1500/µl) and PPL" was particularly useful as a prognostic marker following eribulin chemotherapy.

[A Case of Synchronous Double Cancer including Borderline Resectable Pancreatic Body Cancer and Breast Carcinoma with Osseous/Cartilaginous Differentiation Treated with Neoadjuvant Chemotherapy and Radical Resection].

A 78-year-old woman with a left breast cancer was examined at our institute. Ultrasonography showed 48 mm sized mass at zone C of the left breast, and left axillary lymph node swelling. Pathological examination of core needle biopsy revealed invasive ductal carcinoma and lymph node metastasis. In addition, contrast computed tomography showed 30 mm sized an hypovascular mass at pancreatic body involved the portal vein. Endoscopic ultrasound guided fine needle aspiration biopsy of the pancreas revealed adenocarcinoma. The diagnosis was synchronous double cancer including borderline resectable pancreatic body cancer and left breast cancer, and she received neoadjuvant chemotherapy consisting of gemcitabine and nab-paclitaxel. The effect of neoadjuvant chemotherapy was judged to be stable disease for breast cancer, partial response for pancreatic cancer. Then, she underwent pancreatosplenectomy with portal vein and gastroduodenal artery resection and reconstruction, left mastectomy and axillary lymph node dissection. Pathologic examination of the excised specimen revealed the diagnosis of breast cancer with osseous/cartilaginous differentiation and pancreatic moderately differentiated adenocarcinoma. She was treated with fluorouracil, epirubicin, and cyclophosphamide as adjuvant therapy, and there has been no recurrence.

[A Case of Adenoid Cystic Carcinoma of the Breast].

Primary adenoid cystic carcinoma(ACC)of the breast is a rare type of breast cancer. A 53-year-old woman with a right breast mass was examined at our institute. Ultrasonography showed 12.5×10.3×8.4 mm sized an ill-defined hypoechoic mass at zone C of the right breast. Pathological examination of core needle biopsy revealed atypical cells with solid and cribriform growth pattern. Computed tomography did not reveal lymph node metastases or distant metastases. The preoperative diagnosis was Stage ⅠA(cT1cN0M0, ER/PgR/HER2=-/-/1+)invasive ductal carcinoma or ACC. Surgery consisted of breast-conserving surgery and sentinel node biopsy. Pathological examination of the excised specimen revealed a so- called adenoid cystic pattern, so the final diagnosis was Stage ⅠA(pT1cN0M0, ER/PgR/HER2=-/-/1+)ACC. After 1 year of observation without adjuvant treatment, there has been no recurrence.

[Experience with BD EleVationTM in Vacuum-Assisted Biopsy].

For qualitative diagnosis of breast mass, core needle biopsy(CNB)and fine-needle aspiration biopsy cytology(FNAC)are widely used. Overseas, vacuum-assisted biopsy(VAB)is often the first choice for qualitative diagnosis, and its proper use has become a clinical issue. In addition, with the progress of diagnostic imaging in recent years, the chances of finding micro-lesions such as ductal carcinoma in situ(DCIS)are increasing. Since a sufficient amount of tissue sample is required for these diagnoses and abundant biopsy materials are required, tissue biopsy by VAB may be desirable. The advantage of tissue biopsy with VAB is that accurate definitive diagnosis is possible by collecting a sufficient amount of tissue to obtain pretreatment tissue information. On the other hand, there is concern that patient stress may occur, such as hematoma formation after puncture and invasion by a thick puncture needle. It is lightweight and has an ergonomic design that provides stable grip. New technological innovations in this device may contribute to the reduction of patient stress, and are expected to be used in the future. We outline the experience of using BD EleVationTM in breast suction tissue biopsy at our institution.

The effect of smoking on biological change of recurrent breast cancer.

BACKGROUND: The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence. METHODS: This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined. RESULTS: When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p = 0.024). CONCLUSIONS: Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

Factors predictive of invasive ductal carcinoma in cases preoperatively diagnosed as ductal carcinoma in situ.

BACKGROUND: Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy. METHODS: In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15-3 (CA15-3). The platelet-lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (< 160.0) groups. RESULTS: Invasion was found more frequently after surgery in pathologically high-grade cases than in pathologically not-high-grade cases (p = 0.015). The median PLR was 138.9 and 48 patients (40.7%) were classified into the high PLR group. The high PLR group was significantly more likely to have invasion detected by the postoperative pathology than the low PLR group (p = 0.018). In multivariate analysis of factors predictive of invasion in postoperative pathology, a high PLR (p = 0.006, odds ratio [OR] = 3.526) and biopsy method (VAB vs. CNB, p = 0.001, OR = 0.201) was an independent risk factor. CONCLUSIONS: The PLR may be a predictor of invasion in the postoperative pathology for patients diagnosed with DCIS by preoperative biopsy.

Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment.

BACKGROUND: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. METHODS: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. RESULTS: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. CONCLUSIONS: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer.

BACKGROUND: Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer. METHODS: We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted. RESULTS: For SLN biopsy (SLNB), a median of 2 (range, 1-8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p < 0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p = 0.017, lymphatic invasion; p = 0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p = 0.008, odds ratio [OR] = 2.522) and TILs (p < 0.001, OR = 0.137) as independent factors. CONCLUSIONS: Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.

Effects of low-dose remifentanil infusion on analgesic or antiemetic requirement during brain function mapping: A retrospective cohort study.

BACKGROUND: Pain and discomfort during the awake phase in awake craniotomy should be relieved to facilitate brain mapping. Although some anaesthesiologists use low-dose (0.01-0.05 µg/kg/min) remifentanil infusion to provide analgesia during this phase, its efficacy and side effects have never been evaluated. Therefore, this study primarily aimed to investigate the effects of low-dose remifentanil infusion on the need for antiemetic treatment during brain mapping and secondarily aimed to determine its effects on the need for additional analgesic treatment. METHODS: This retrospective study included 218 patients who underwent awake craniotomy at our centre from 2008 to 2018. The relationship between low-dose remifentanil infusion during the awake phase and the requirement for analgesic or antiemetic treatment was examined. A multivariable competing risk regression analysis was performed to adjust for patient and operative variables. RESULTS: Sixty-six patients (30.3%) received low-dose (median rate: 0.01 µg/kg/min) remifentanil infusion during the awake phase. Forty-nine patients (22.5%) received an antiemetic and 99 (45.4%) received additional analgesic treatment. The difference in additional analgesic treatment was not significant between patients who received low-dose remifentanil infusion and those who did not (adjusted hazard ratio: 1.13; 95% confidence interval: 0.75-1.70; P = .570); however, the use of antiemetics significantly increased in patients who received remifentanil (adjusted hazard ratio: 1.78; 95% confidence interval: 1.01-3.15; P = .047). CONCLUSION: Low-dose remifentanil infusion during the awake phase in awake craniotomy significantly increased the need for antiemetics but did not decrease the need for additional analgesic treatment.

[Clinical Significance of Inflammatory Markers in Recombinant Human-Soluble Thrombomodulin Therapy for DIC in Solid Tumors].

BACKGROUND: The peripheral blood neutrophil-lymphocyte ratio(NLR), platelet-lymphocyte ratio(PLR), and lymphocyte- monocyte ratio(LMR)of cancer patients have been proposed as indicators of systemic inflammatory response. Recombinant human-soluble thrombomodulin(rTM)has also been reported its efficacy in DIC associated with solid tumors. In this study, we investigated the clinical significance of inflammatory markers in rTM therapy for DIC associated with solid tumors. PATIENTS AND METHOD: A retrospective study of 63 patients with solid tumors with DIC was performed. We examined the correlation between NLR, LMR, PLR and DIC withdrawal rate and 28-day survival rate. RESULTS: The DIC withdrawal rate was not correlated in LMR(p=0.655), and significantly higher in low NLR and low PLR cases(p=0.037, p=0.024). Furthermore, 28-day survival rate was not correlated in LMR(p=0.632), and significantly higher in low NLR and low PLR cases(p= 0.046, p=0.014). CONCLUSIONS: It was suggested that NLR and PLR may be useful as predictive markers of DIC withdrawal rate and 28-day survival rate in rTM therapy for DIC associated with solid tumors.

[Effectiveness of Atezolizumab Combination Therapy for PD-L1(SP142)Positive Lung and Breast Double Cancer-A Case Report].

The anti-PD-L1 antibody atezolizumab has become the standard of immunochemotherapy with the results of the international phase Ⅲ trials in lung cancer and breast cancer. We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer. A 56-years-old woman. She noticed a lump in her right breast and visited a nearby doctor, who referred her to our hospital for close examination and treatment. Ultrasonography revealed about 5 cm mass on the right mammary gland and axillary lymph nodes swelling. Core-needle biopsy was confirmed invasive ductal carcinoma( ER negative, PgR negative, HER2 negative, Ki-67 high expression). CT findings showed right mammary mass, right axillary lymph nodes swelling, liver mass, and lung tumor with mediastinal lymph nodes swelling. Therefore, a bronchoscopic biopsy was performed and a diagnosis of primary lung cancer was obtained. Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage ⅢA/B or ⅣA/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage ⅢB or Ⅳ triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.

[A Case of Cervical Metastasis from Breast Cancer].

A 59-year-old female was performed a left mastectomy with axillary lymph node dissection. Final diagnosis of the surgical specimen was left breast cancer pT2N1M0, Stage ⅡB, Luminal type. She was treated with adjuvant endocrine therapy, however, chest wall recurrence was identified at 1 year and 3 months after surgery, and curative resection of this tumor and radiotherapy were performed. Nine months later, she was admitted to the hospital for cervical pain and dyspnea, and magnetic resonance imaging showed bone metastasis in cervical vertebra which compressed spinal cord. Although cervical fusion therapy was performed, she died 39 days later. Metastasis spinal cord compression in breast cancer patients may result in irreversible spinal cord injury if treatment is delayed. Rapid diagnosis and systemic treatment for oncologic emergency are significant.

[A Case in Which Re-Administration of Pertuzumab/Trastuzumab with Eribulin Therapy Was Useful for Recurrent HER2 Breast Cancer].

Pertuzumab plus trastuzumab plus docetaxel regimen is the first choice for the initial treatment of HER2-positive recurrent breast cancer. However, docetaxel causes many adverse events. A 48-year-old woman was admitted to our hospital for a left breast tumor and was diagnosed with left breast cancer(T1N0M0, Stage Ⅰ, Luminal A). We performed a breast-conserving surgery and sentinel lymph node biopsy, followed by irradiation of the remaining parts of the mammary gland and adjuvant therapy with tamoxifen. Three and a half years after the first surgery, she underwent local resection due to chest wall recurrence of breast cancer. The recurrent tumor was HER2-positive, and we administered fluorouracil, epirubicin, cyclophosphamide( FEC)and paclitaxel plus trastuzumab. Liver metastases were confirmed on completion of cycle 11 of trastuzumab administration, and the regimen was changed to pertuzumab plus trastuzumab plus docetaxel. A partial response was seen following this regimen. The next line of treatment was the administration of 5 cycles of T-DM1, which resulted in stabilizing the disease. The liver metastases progressed, and the regimen was changed to pertuzumab plus trastuzumab plus eribulin. Partial response was seen following this regimen for liver metastases without serious adverse events(20 cycles).