[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 Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3 and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC). PATIENTS AND METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry. RESULTS: The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p=0.038) and HER2-enriched breast cancer (HER2BC) (p=0.021), while the total number of pathological complete response (pCR) patients was greater (p<0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p<0.001 and p=0.02, respectively). Moreover, on multivariate analysis low-LAG-3 expression status was an independent predictor of favorable prognosis (TNBC: p=0.014, HR=8.124; HER2BC: p=0.048, HR=10.400). CONCLUSION: Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

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.

Pathological Complete Response following Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma with Mammary Paget's Disease: A Case Report.

Mammary Paget's disease is a rare malignancy. Mastectomy or breast-conserving surgery has been considered as the standard treatment, while there have been few reports of neoadjuvant chemotherapy (NAC). A 53-year-old woman with erythema and skin ulceration of the left breast was admitted to our institution. Breast examinations revealed left invasive ductal carcinoma (cT1bN0M0, cStage I), and a punch biopsy of the left mammary erythema indicated Paget's disease (cTisN0M0, cStage0). The patient received NAC because of multiple lesions. Consequently, the breast tumor clinically disappeared, and the erythema improved. These outcomes made it easier to perform surgery (left mastectomy and sentinel node biopsy). Histopathological examination revealed no residual cancer cells in either the mammary gland or breast skin, and no metastasis was found in the sentinel lymph node. Therefore, NAC may be a useful treatment for mammary Paget's 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.

Injection-Molded Coamorphous Tablets: Analysis of Intermolecular Interaction and Crystallization Propensity.

The processing steps involved in converting from a powder to a tablet entail numerous operations in a which the coamorphous system is recrystallized and dissociated easily. This research focused on (i) a single-step preparation of a coamorphous tablet during injection molding (IM) from the bulk powder, and (ii) a mechanistic characterization of the coamorphous formulation. We selected several organic acids [citric acid, succinic acid, tartaric acid, and malic acid] in an effort to compound with basic loratadine (a poorly water-soluble drug). Loratadine-acids coamorphous tablets were produced via an IM process, and the dissolution was more enhanced than in the pure loratadine amorphous. The interaction was analyzed by FT-IR and terahertz spectroscopies. Each tablet was stored at 40 °C/75%RH, and then XRD patterns were acquired at the desired timepoints. In summary, loratadine exhibited ionic interaction with each acid, and the physical stability of the coamorphous tablet was in proportion to the loratadine-acids interaction strength. Terahertz spectra detected the molecular mobility, which plays an important role in the crystallization propensity of a coamorphous system. This understanding offers a framework for robust coamorphous tablet formulation using the IM methodology.

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.

Breast Angiosarcoma with a Preoperative Diagnosis of Late Recurrence of Breast Cancer: A Case Report.

Angiosarcoma is a malignant mesenchymal tumor characterized by the presence of vascular endothelial cells. Although rare, angiosarcoma developing in the mammary glands has a poor prognosis. We report a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer. A 78-year-old woman noticed a tumor in her right breast and visited our hospital. The patient had undergone breast-conserving surgery and axillary lymph node dissection from the right breast 12 years before the visit. The tumor was diagnosed as T4bN0M0, stage IIIB. Anastrozole was administered as postoperative adjuvant therapy for 5 years; the patient also received 50-Gy whole-breast radiation therapy after surgery. Physical examination during her visit revealed an elevated lesion with blue purpura around the nipple in the right breast. We performed breast ultrasound and detected a well-defined 19.6 × 16.4 × 10.7 mm hypoechoic tumor in the left subareolar area. The patient underwent core needle biopsy (CNB). Based on the CNB specimen findings, she was suspected to experience late local recurrence after surgery. Therefore, she underwent total mastectomy after breast-conserving surgery. A dark-red tumor sized 18 × 12 mm was found in a specimen from the nipple. The pathological diagnosis of the specimen revealed short spindle-shaped tumor cells with strong nuclear pleomorphism and a significant interstitial fibrosis. Immunohistochemistry using D2-40 and CD31 antibodies showed irregular luminal proliferation at the anastomosis, infiltration into the surrounding tissue, and massive necrosis, thereby leading to the diagnosis of breast angiosarcoma. We have reported a case of breast angiosarcoma with a preoperative diagnosis of late recurrence of breast cancer.

[A Case of a Malignant Phyllodes Tumor in the Breast with Lymph Node Metastasis].

A 52-year-old woman experienced right breast pain and detected a mammary tumor 6 months ago. She then noticed rapid enlargement of the tumor, which was suspected to be a borderline malignant phyllodes tumor. The tumor size was approximately 15 cm and presented with skin congestion but without infiltration. The tumor showed internal heterogeneous echo and rich blood flow signals on breast ultrasonography. Ultrasonography also showed swelling of the axillary lymph node. Lymph node cytology revealed the presence of atypical cells in the lymph node, and CT scan showed lymph node metastasis in the right axilla and no distant metastases. We performed mastectomy with lymph node sampling. Pathological examination of the specimens confirmed a malignant phyllodes tumor and a metastatic lymph node. One month later, a subcutaneous mass and multiple pulmonary nodules were identified on a chest CT scan. Chest wall irradiation(45 Gy)and chemotherapy were performed, but the number of pulmonary nodules, pleural effusion, and size of the subcutaneous mass continued to increase. Although she underwent another chemotherapeutic treatment, she died 5 months after the surgery. Thus, we report a case of a malignant phyllodes tumor with an extremely rare lymph node metastasis, which rapidly progressed even though multimodal therapy was performed.

[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.

Treatment of anaplastic thyroid cancer with tyrosine kinase inhibitors targeted on the tumor vasculature: initial experience in clinical practice.

Anaplastic thyroid cancer (ATC) is a rarely occurring refractory disease. While recent clinical trials have demonstrated the efficacy of tyrosine kinase inhibitor (TKI) therapy for ATC, evidence is scarce in clinical practice. In this study, we reviewed our initial experiences with TKI treatment in ATC patients with the aim of revealing the efficacy and safety of the same in clinical practice. We retrospectively reviewed our experiences with TKI treatment use in ATC patients diagnosed at our institute from 2014 to 2019. Changes in the patients' neutrophil-to-lymphocyte ratio (NLR) by TKI therapy introduction as well as their clinical factors to indicate the efficacy were examined. Seven patients showed no indication for TKI treatment, while 13 (65%) received treatment. The median duration of TKI treatment was 1.9 months. All patients died, and the overall survival period from diagnosis was 4.7 (95% confidence interval: 2.0-11.5) months. Adverse events ≥Grade 3 were observed commonly (92.3%), and resulted in the termination of TKI treatment in six cases (46.1%). Existence of multiple unfavorable characteristics (higher Prognostic Index) was associated with poor survival. The NLR decreased after the introduction of TKIs and increased again when treatment failed. The response rate to TKI among the ATC patients were approximately 30% in practice. Although the duration of the response was short, several patients demonstrated long survival durations when TKI treatment was provided after successful multidisciplinary treatment to control local disease. Decreases in high NLR values during treatment may suggest the continued effect of TKIs.

[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.

[A Case of Metastatic Invasive Lobular Carcinoma of the Breast Initially Presenting with Periorbital Swelling].

The patient was 54 years old, female. She was aware of gradually worsening right peri-eyelid swelling 2 years before the first presentation to our dermatology department. She underwent biopsy of eyelid skin 2 times. Nevertheless, definitive diagnosis was not obtained. Two months after the initial examination, right anterior thoracic swelling appeared, and right axillary, right subclavian, and interpectoral lymphadenopathy were detected. She was referred to our department for diagnosing metastatic breast cancer. Ultrasonography showed hypoechoic lesion with distortion(largest lesion>2 cm)in right breast, which was suspected to be a breast cancer. The results of breast core needle biopsy, the third time's eyelid skin biopsy and additional imaging studies confirmed T2N3M1, Stage Ⅳ right mammary invasive lobular carcinoma with metastasis to the eyelid skin, right axillary lymph nodes, right subclavian lymph nodes and the subcutaneous tissue of the right back. Immunohistochemical studies showed ER-positive, PgR-negative, HER2-negative, and low Ki-67 expression. Endocrine therapy with letrozole was initiated, which maintained stable disease without compromising the quality of life.

[A Case of Dermatitis Caused by Metronidazole Gel That Needed to Be Differentiated from Breast Cancer Skin Metastasis].

Seventy years old woman noticed a mass in her right breast before 3 years. Since she had ulcer bleeding, she visited our hospital. In physical findings, a hemorrhagic about 8 cm mass with an ulcer was found in the upper right breast. Breast ultrasonography revealed a large tumor of approximately 8 cm in the right A area, and needle biopsy revealed invasive ductal carcinoma(ER positive, PgR positive, HER2 positive, Ki-67 low expression). Right axillary lymph node metastasis was confirmed, but no clear distant metastasis was observed. Pretreatment diagnosis was right breast cancer, cT4bN1M0, Stage ⅢB, Luminal HER. Chemotherapy was started with pertuzumab, trastuzumab, and docetaxel, and the tumor was reduced after 6 cycles. Due to side effects, the drug was changed to a molecular targeted drug only and the treatment was continued. However, redness was observed in the entire right breast, and breast cancer skin metastasis was suspected. Since the dermatitis caused by metronidazole gel was also distinguished, the redness was improved when the application was stopped. When confirmed by a patch test, a reaction to metronidazole gel was observed, leading to the diagnosis of dermatitis caused by metronidazole gel.

[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).

Adenoid Cystic Carcinoma of the Breast: A Case Report.

Adenoid cystic carcinomas (ACCs) are malignant tumors that most often occur in the salivary glands and bronchi, with occurrence in the breast being rare. ACCs of the breast reportedly give rise to few lymph node metastases or distant metastases and have a favorable prognosis. A 56-year-old woman with a left breast mass identified by mammographic screening was examined at our institute. Breast ultrasound revealed a sharply marginated, hypoechoic mass 12.7 × 9.4 × 8.7 mm in size in the upper outer quadrant of the left breast, and a vacuum-assisted biopsy (VAB) was performed at the mass site. Pathological examination of the VAB specimen revealed atypical cells with a cribriform growth pattern, and mucosal fluid surrounding tumor nests and within tumor ducts. The area around the tumor nests and inside of tumor ducts were also positively stained with alcian blue. These findings, we reached a pathological diagnosis of ACC. The preoperative diagnosis was stage I (cT1N0M0) triple-negative left breast cancer. Surgery consisted of breast-conserving surgery and sentinel node biopsy. The excised specimen was a 15.0 × 12.1 × 9.7 mm mass with a greyish white cut surface. Pathological examination of the excised specimen revealed a so-called adenoid cystic pattern. Results from immunohistochemical staining were identical to those from a VAB specimen, as they were estrogen receptor-negative, progesterone receptors-negative, and human epidermal growth factor receptor 2-negative, with low Ki67 expression. The final diagnosis, given the above findings, was left breast cancer (ACC) pT1N0M0 stage I triple-negative subtype.

Sorafenib inhibits vascular endothelial cell proliferation stimulated by anaplastic thyroid cancer cells regardless of BRAF mutation status.

Anaplastic thyroid cancer (ATC) is a rare refractory disease, frequently associated with BRAF mutations and aberrant vascular endothelial growth factor (VEGF) secretion. The antitumor effects of sorafenib were evaluated, and its mechanisms of action were investigated. Four human ATC cell lines were used: OCUT­4, which possesses a BRAF mutation; OCUT­6 and ACT­1, which carry NRAS mutations; and OCUT­2, which possesses mutations in BRAF and PI3KCA. The viability of Sorafenib was evaluated by MTT assay. In order to examine the inhibitory effect of Sorafenib on intracellular signal transduction, expression of mitogen­activated protein kinase kinase was examined by western blotting. In addition, cell cycle analysis was performed using flow cytometry. The inhibitory effects of sorafenib on the growth of ATC cells and human umbilical vein endothelial cells (HUVECs) stimulated with conditioned media from ATC cells were examined. Sorafenib inhibited the viability of OCUT­4 more effectively than other ATC cell lines; these effects may have been mediated cytostatically by suppressing mitogen­activated protein kinase kinase phosphorylation. Conversely, similar suppression was not observed in OCUT­6 cells, which possess an NRAS mutation. The four cell lines secreted different quantities of VEGF, and the proliferation of HUVECs was differentially stimulated by their conditioned media. Both anti­VEGF antibody and sorafenib prevented this stimulation of proliferation. In conclusion, sorafenib more effectively inhibited RAF­generated growth signals in ATC cells compared with signals generated by its upstream gene, RAS. ATC cells stimulated the growth of HUVECs via humoral factors, including VEGF; this effect was clearly inhibited by sorafenib. The present findings highlighted the potential of sorafenib for the treatment of ATC and provided insight into its mechanism of action.

Continuous intraoperative neuromonitoring for thyroid cancer surgery: A prospective study.

OBJECTIVE: We evaluated the utility of continuous intraoperative neuromonitoring (CIONM) during surgery for thyroid cancer (TC) in an educational university hospital. STUDY DESIGN: Prospective observational study. METHODS: During the period April 2016 to March 2017, 43 patients who underwent standardized surgery with CIONM were prospectively included: 5 men and 38 women, 24-87 years old (median 52 years); 23 lobectomies and 20 total thyroidectomies with node dissection were conducted. Thirty-six operations were performed by a supervising surgeon, and seven were performed by trainees. RESULTS: Temporal vocal cord paresis (VCP) was identified in 9 of 63 nerves at risk (14.3%) by postoperative laryngoscopy. VCP was not related to clinical factors including the surgeon's experience or the severe nerve stress demonstrated by CIONM. A significant relation only between VCP and loss of signal (LOS) was demonstrated (P = .002). The recovery of VCP was rapid (<1 month) in patients with global injury even when LOS was demonstrated, but was prolonged in patients demonstrating obvious segmental nerve injury and LOS. CONCLUSION: The present standard protocol of CIONM was useful to some extent to protect prolonged VCP, but not enough to detect every nerve stress causing VCP during TC surgery. On the other hand, CIONM is a promising method that could contribute surgical education at training hospitals enabling the instant confirmation of the procedure safely. LEVELS OF EVIDENCE: 3b.