[Three Cases of Locally Advanced Breast Cancer with Skin Invasion Treated with Cadexomer Iodine for Local Control].

Advanced breast cancer with skin invasion are relatively often accompanied by bleeding, effusion, malodor, and pain, which reduce the quality of life(QOL)of the patients and their families. Therefore, local symptom control is as important as surgical treatment and chemotherapy. We control these symptoms by using cadexomer iodine, cadexomer iondine is expensive, but relatively easy for family to use and keep patients' QOL.

A comparative study of unpasteurized and pasteurized frozen whole hen eggs using size-exclusion chromatography and small-angle X-ray scattering.

Hen eggs are rich in proteins and are an important source of protein for humans. Pasteurized frozen whole hen eggs are widely used in cooking and confectionery and can be stored for long periods. However, processed eggs differ from raw eggs in properties such as viscosity, foaming ability, and thermal aggregation. To develop pasteurized frozen whole egg products with properties similar to those of unpasteurized whole eggs, it is necessary to establish a method that can differentiate between the two egg types with respect to the structures of their proteins. In this study, size-exclusion chromatography (SEC) and SEC coupled with small-angle X-ray scattering (SEC-SAXS) were successfully used to differentiate between the proteins in unpasteurized and pasteurized frozen whole eggs. We found that proteins in the plasma fraction of egg yolk, especially apovitellenins I and II, formed large aggregates in the pasteurized eggs, indicating that their structures are sensitive to temperature changes during pasteurization, freezing, and thawing. The results suggest that SEC and SEC-SAXS can be used to differentiate between unpasteurized and pasteurized frozen whole eggs. Additionally, they may be useful in determining molecular sizes and shapes of multiple components in various complex biological systems such as whole eggs.

Immune checkpoint inhibitor-induced refractory polyarthritis rapidly improved by sarilumab and monitoring with joint ultrasonography: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography. PATIENT CONCERNS: A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion. DIAGNOSES: We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis). INTERVENTIONS: After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab. OUTCOMES: Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy. LESSONS: Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.

[Adjuvant Capecitabine for Residual Disease after Standard Neoadjuvant Chemotherapy Among Patients with Triple-Negative Breast Cancer].

CREATE-X trial demonstrated the effectiveness of additional capecitabine therapy in prolonging disease-free survival among patients who are HER2 negative, especially those with triple-negative breast cancer who had residual invasive disease after standard neoadjuvant chemotherapy. We investigated our data regarding adjuvant capecitabine for residual disease. Ten patients were enrolled, and the average age of the patients was 54.2 years. All patients completed 8 courses of treatment; all adverse events were Grade 2 or lower. Five-year disease-free survival rate was 70.0% in an average observation period of 40.9 months. Three patients recurred within 2 years, and all patients had brain metastasis. In the CREATE-X trial, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group; our results were same as those of CREATE-X. Brain metastasis may be detected by the early phase of enhanced brain MRI.

Effect of adjuvant chemotherapy in patients with ER + /HER2- breast cancer, assessed by propensity score matching: significance of nuclear grade and nodal status.

BACKGROUND: Survival benefits of chemotherapy (CT) differ among patients with estrogen receptor-positive (ER +) breast cancer. This study investigated the survival benefits of CT for ER + and human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients by propensity score matching (PSM). METHODS: Patients with stages I-IIIER + /HER2- BC were enrolled in this study. The primary endpoints were 5-year recurrence-free survival (RFS) and overall survival (OS) in the non-CT and CT groups of the selected population matched by PS. The PS was analyzed by a logistic regression model with factors those influence provided indication of chemotherapy [tumor size, nuclear grade (NG), progesterone receptor, and nodal status]. RESULTS: This study enrolled 895 patients between 2000 and 2015. The median follow-up period was 5.7 years. Overall, the 5-year RFS was 94.3% and 90.1% in the non-CT and CT-treated groups, respectively (p = 0.106). The 5-year OS was 97.5% in the non-CT group and 95.6% in the CT group (p = 0.047). Using PSM, 236 patients were selected. After matching, both the 5-year RFS and the 5-year OS were higher in the CT group than in the non-CT group (96.8% vs. 82.7%, p = 0.003 and 100% vs. 91.9%, p < 0.001, respectively). Particularly in the case of the node negative/NG3 and 1-3 node positive/NG2 patients after PSM, the 5-year RFS was significantly higher in the CT group than in the non-CT group (p = 0.041 and p = 0.006, respectively). CONCLUSION: After PSM, CT significantly improved both the RFS and OS of ER + / HER2- BC patients, especially for node negative/NG3 and 1-3 node positive/NG2 patients.

Quantitative analysis of the relationship between structure and antioxidant activity of tripeptides.

Peptides from enzymatic hydrolysates of food proteins exhibit significant antioxidant activity. Several studies have attempted to determine the factors contributing to the antioxidant activity of peptides; however, the physicochemical properties and factors essential for the antioxidant activity of peptides are still unclear. In this study, in order to clarify the factors important for peptide antioxidant activity based on the properties of component amino acids, 55 tripeptides were synthesized from 20 natural amino acids and their antioxidant activity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay system. The tripeptides were divided into two data sets: a training set comprising 50 compounds and a validated set comprising five compounds. The structure-activity relationship of the training set was then analyzed using classical quantitative structure-activity relationship (QSAR) analysis. The study findings demonstrate that the presence of a cysteine residue at any position, an aromatic amino acid at the C-terminus, higher hydrophobicity of the N-terminal residue, and smaller HOMO-LUMO energy gap of the middle residue can significantly enhance the antioxidant activity. The activities of the five validated compounds were predicted using the constructed QSAR model, and a good correlation between measured and predicted activities was observed. The information obtained from the QSAR model could be useful for effective production of antioxidant peptides from food proteins such as egg white proteins.

Breast-conserving surgery without radiation in elderly women with early breast cancer.

BACKGROUND AND OBJECTIVES: Irradiation after breast-conserving surgery (BCS) decreases the incidence of ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, daily radiation treatments are burdensome to elderly patients, whose risk of IBTR is relatively low. Since 2001, we have offered BCS without radiation to patients meeting our selection criteria. This study assessed the prognosis of the patients who chose this option. METHODS: Between 2001 and 2014, 203 patients met the selection criteria: aged ≥60 years; pathologically node-negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. Among these patients, 84 and 119 underwent BCS with or without radiation, respectively. IBTR, overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated. RESULTS: The median follow-up duration was 6.2 years. There were no significant differences in tumor size or the number of patients with adjuvant therapy between the groups. The 5-year IBTR rates were 0.9% and 1.6% in the non-irradiated and irradiated groups, respectively (p = 0.308). The 5-year OS rates were 94.1% and 98.7% (p = 0.391). Similarly, the 5-year BCSS rates were 97.2% and 98.7% (p = 0.812). CONCLUSION: It is suggested that the omission of irradiation could be an option for elderly breast cancer patients who satisfy our criteria.

[Ethinyl Estradiol Therapy for Postmenopausal Women with Heavily Pre-Treated Endocrine-Responsive Metastatic Breast Cancer].

Ethinyl estradiol(EE2)therapy has been reported to be an effective endocrine therapy for postmenopausal hormone receptor-positive advanced breast cancer, especially in the supposed acquired resistance state. The current study retrospectively investigated the efficacy and safety of EE2 therapy in postmenopausal women with hormone receptor-positive advanced breast cancer who had previously undergone multiple endocrine therapies. Twelve patients were enrolled; median lines of endocrine therapies were seven before EE2. Median PFS was 4.8 months and median overall survival was 10.0 months. Grade 3 adverse event comprised of anorexia in only one patient. EE2 therapy may be considered effective and safe in hormone receptor-positive advanced breast cancer even in late-stage endocrine therapy.

A Patient with Nivolumab-related Fulminant Type 1 Diabetes Mellitus whose Serum C-peptide Level Was Preserved at the Initial Detection of Hyperglycemia.

A 77-year-old-man with renal cell carcinoma who was undergoing nivolumab treatment visited our department due to hyperglycemia; his plasma glucose level was 379 mg/dL. Although his serum C-peptide immunoreactivity (CPR) level was preserved (5.92 ng/mL), we suspected an onset of fulminant type 1 diabetes mellitus (FT1DM) and immediately started insulin therapy. His CPR levels gradually decreased and were depleted within 1 week. We later discovered that the patient's casual CPR level had been abnormally high (11.78 ng/mL) 2 weeks before his admission. Hence, the possibility of FT1DM in hyperglycemic patients undergoing nivolumab treatment should not be excluded, even with a preserved CPR level.

Eggshell membrane protein can be absorbed and utilised in the bodies of rats.

OBJECTIVE: Eggshell membranes, the thin film lining the insides of eggshells, are constituted mostly from protein (eggshell membrane protein, ESM-P). The digestibility and dietary net protein utility of ESM-P are not known. ESM-P functions as a barrier to prevent foreign matter from reaching the egg white and yolk, so it would be expected not to decompose easily by digestion when ingested. We therefore prepared a hydrolysate of the membrane (ESM-H). In this study, we assessed the digestibility and net protein utility of ESM-P and ESM-H in rats. RESULTS: The digestibility of ESM-P and ESM-H were 87.0% and 94.8%, respectively, significantly lower than that of casein (98.5%). The net protein utility values were 84.7% and 84.6%, respectively, significantly higher than that of casein (75.1%). Digestibility was significantly higher for ESM-H than for ESM-P, but there was no significant difference in net protein utility between ESM-P and ESM-H. These results demonstrated that more than 80% of ESM-P or ESM-H is absorbed and utilised in the bodies of rats.

[A Case of Breast Carcinoma with Cartilaginous Differentiation and Distant Metastasis with Complete Response to Post-Operative Chemotherapy].

We report a case of breast cancer with cartilaginous differentiation that responded well to chemotherapy, which completely eliminated distant metastasis. A 63-year-old woman visited our hospital complaining of a large hemorrhagic mass measuring 15 cm in diameter with ulceration of the left breast. Palpation revealed swelling of the left axillary and right supraclavicular (SC)lymph nodes, suggesting breast cancer metastasis. A CT scan revealed metastasis in the right lung measuring 2.5 cm in size. She underwent a total mastectomy with axillary dissection. The pathological findings were as follows; breast carcinoma with cartilaginous differentiation accompanied by a single lymph node metastasi(s 1/21)and skin involvement, ly0, v0, ER(-), PgR(-), HER2 0, Ki-67 80%. Four courses of AC therapy were administered as postoperative chemotherapy, which resulted in a decrease in the size of the SC lymph node to 1 cm. Subsequently, 12 courses of weekly paclitaxel yielded a complete response of the lung and SC lymph node metastasis. Oral administration of S-1 after paclitaxel therapy resulted in no recur- rence for 16 months after the operation.

Long-term effect of exemestane therapy on bone mineral density supported by bisphosphonates: Results of 5-year adjuvant treatment in postmenopausal women with early-stage breast cancer.

PURPOSE: Unlike anastrozole, the effect of long-term exemestane (EXE) therapy on bone mineral density (BMD) is still unknown. We assessed changes in BMD from baseline to 5 years of EXE treatment. METHODS: Postmenopausal women with endocrine-responsive breast cancer receiving EXE as adjuvant therapy were enrolled in this study. EXE was administered for 5 years. The BMD of the lumbar spine (LS) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry at baseline and after 6 months and 1, 2, 3, 4, 5 and 6 years. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis with a T-score of -2.5 or lower. RESULTS: Eighty-one patients were enrolled in the study between 2005 and 2010. The median follow-up period was 54.9 months. Forty-two patients were administered Bis. Overall, the BMD of the LS increased by 7.3% from baseline and that of the FN increased by 3.4% with 5 years of EXE treatment. At the sixth year (i.e. 1 year after the treatment), BMD of the LS increased by 7.2% and that of the FN increased by 5.7%. Furthermore, the BMD of the FN increased by 12.0% in patients treated upfront with Bis and by 1.2% in those not treated with Bis (P = 0.0262). Fractures developed in nine patients (11.1%) and seven (8.6%) had fragility fractures. CONCLUSION: Oral Bis improves BMD of the FN in patients with osteoporosis. Five-year EXE treatment with proper addition of Bis helps maintain the BMD of the LS and FN at the sixth year.

[HER2-Positive Breast Cancer with Severe Infusion Reaction to Pertuzumab plus Trastuzumab-A Case Report].

A 64-year-old woman detected a tumor in her left breast in July 2015, and the tumor became exposed and ulcerated in January 2016. Subsequently, the tumor began to bleed, and the patient was admitted to our hospital on an emergency basis in March 2016. A CT scan revealed the presence of a giant tumor in the left breast, accompanied by chest wall infiltration, left axillary lymph node metastasis, and multiple liver and bone metastases. Following needle biopsy, the specimen was diagnosed as Luminal-HER2-type invasive ductal carcinoma, and pertuzumab plus trastuzumab plus docetaxel was administered. Upon administration of 2/3 of the pertuzumab, the patient developed chills. Therefore, the administration rate was reduced; however, the patient experienced palpitations, nausea, tachycardia, and decreased blood pressure at the end of the administration. Pertuzumab was temporarily discontinued, a replenisher was infused, and the symptoms improved within approximately 20 minutes. However, the patient again experienced chills, tachycardia, and decreased blood pressure immediately after reinitiating trastuzumab administration and complained of strong pain at the tumor site. Continuation of chemotherapy was deemed dangerous, and administration was discontinued. It has been reported that infusion reactions to trastuzumab are associated with clinical stage. In this case, the symptoms of the infusion reaction were severe because of the large tumor volume. It is necessary to consider administration of premedication and the administration time of anti-HER2 drugs in cases with high tumor burden such as the current case.

[Bevacizumab plus Paclitaxel Therapy Was Effective for Metastatic Breast Cancer with Dysphagia Due to Mediastinal Lymph Node Metastasis-A Case Report].

A 69-year-old woman noticed a tumor of the right breast, and presented to our hospital with dysphagia. A tumor of size 10 cm exposed to the skin and swollen axillary lymph node were observed. She was diagnosed with invasive ductal carcinoma, luminal-B by core-needle biopsy. CT scan revealed primary breast cancer with lung, bone, and lymph node metastasis. Endoscopic and fluoroscopic findings of the esophagus showed severe stenosis by extrinsic compression. In order to improve the quality of life(QOL)immediately, bevacizumab plus paclitaxel therapy was initiated. After the first course, the dysphagia improved, and she was able to take normal meals after 2 courses of treatment. Primary tumor and metastatic lesions had remarkably shrunk on CT scan. After 4 courses of treatment, we changed to endocrine therapy and continued outcome treatment. Bevacizumab was effective for immediate improvement of QOL in such as an oncologic emergent case of metastatic breast cancer.

Self-assembled nanogel of cholesterol-bearing xyloglucan as a drug delivery nanocarrier.

Xyloglucan (XG) is a multibranched polysaccharide consisting of a main chain ß-1,4-glucan with xylose and galactose side chains. In this study, cholesterol-bearing XG (CHXG) was synthesized by the reaction of XG with cholesteryl N-(6-isocyanatohexyl) carbamate. The CHXG molecules self-assembled in water to form nanogels consisting of about 100 molecules of XG, and were characterized using light scattering and transmission electron microscopy. The number of cholesteryl groups per physical cross-linking site was estimated using a fluorescence quenching method. The resulting CHXG nanogels could be complexed with molecules of low molecular weight, such as iodine and paclitaxel, making the nanogels useful as drug carriers. The CHXG nanogels could also be specifically internalized by hepatocytes via the galactose receptors on their cell surface. CHXG self-assembled nanogels may be suitable as novel drug nanocarriers with galactose-specific targetability.

[Treatment Out Come of Eribulin in Patients with Advanced or Metastatic Breast Cancer Who Resistant to Anthracycline and Taxane].

PATIENTS AND METHODS: This retrospective observational study contains advanced or metastatic breast cancer female patients who pretreated with anthracycline and/or taxane received eribulin(ERI)mesylate. The primary endpoint was the progressionfree survival(PFS)and secondary endopoints were objective response rate(ORR), clinical benefit rate(CBR), overall survival (OS), and post-progression survival(PPS). RESULTS: A total of 32 patients underwent chemotherapy cycles(median 3; range 1-9 cycles). The ORR was 15.6% and the CBR was 31.3%. The median PFS, OS and PPS were 2.9 months, 8.5 months, 5.6 months respectively. The OS, PPS for relative dose intensity(RDI)<85% and RDI≥85% were 7.2 months, 3.4 months and 14.5 months, 11.4 months, respectively(p=0.005, 0.004). In multivariate analysis for OS and PPS, the visceral disease, total dose of ERI and RDI correlated with OS and PPS. The most frequent treatment-related Grade 3/4 adverse events was neutropenia( 56%). No Grade 3 and 4 peripheral sensory neuropathy was occurred. CONCLUSIONS: ERI exhibited efficacy and tolera- bility in patients with heavily pretreated A/MBC. The total dose and RDI of ERI would induce favorable effect for prognosis.

[Ethinylestradiol Following Everolimus plus Exemestane Was Effective in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer - A Case Report].

A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin.Then, estrogen therapy with ethinylestradiol( EE2)was started in December 2013.T he pleural effusion disappeared and the liver metastases were reduced.After 11 months of progression-free survival(PFS), regrowth of the liver metastases was seen.Thus, everolimus plus exemestane was administered, and approximately 8 months of PFS was obtained.Therefore, both EE2 and everolimus are effective therapy even for heavily pretreated metastatic breast cancer.