The effect of exercise and educational programs for breast cancer patients on the development of breast cancer-related lymphoedema: secondary endpoint from a randomized controlled trial in the Setouchi Breast Project-10.

BACKGROUND: Although the association between higher physical activity and preventive effect on breast-cancer-related lymphoedema (BCRL) has been reported, it is unclear what intervention is optimal. We aimed to investigate the effect of exercise and educational programs on BCRL development. METHODS: This study was a secondary endpoint analysis from a prospective randomized controlled trial. We enrolled patients with stage 0-III breast cancer from March 2016 to March 2020 and randomly assigned them to the control (n = 111), education (n = 115), or exercise (n = 104) group. As secondary endpoint, we assessed the incidence of and preventive effect on BCRL at 12 months post-intervention. RESULTS: There were no significant differences in the incidence of BCRL at 12 months post-intervention between the exercise and control groups (9.8% and 10.8%, P = 0.83) and the education and control groups (11.6% and 10.8%, P = 1.00). There were no significant differences in time to BCRL onset from the day of surgery between the exercise and control groups (event rate at 12 months: 20.7% and 17.2%, log-rank, P = 0.54) and the education and control groups (18.8% and 17.2%, log-rank, P = 0.57). The multivariable analyses indicated that axillary dissection and obesity significantly increased the risk of BCRL [hazard ratio (HR): 2.36, 95% confidence interval (CI) 1.52-3.67 and HR: 1.68, 95% CI 1.07-2.63, respectively]. CONCLUSIONS: The intervention did not decrease the risk of BCRL, and axillary dissection and obesity were the risk factors of BCRL. TRIAL REGISTRATION NUMBER: UMIN000020595 at UMIN Clinical Trial Registry.

Pilot trial of an electronic patient-reported outcome monitoring system in patients with metastatic breast cancer undergoing chemotherapy.

BACKGROUND: Electronic patient-reported outcomes monitoring (ePROM) is a useful communication tool for patients and healthcare providers in cancer chemotherapy. In this study, we examined the feasibility of our newly developed ePROM system, which we refer to as "Hibilog". METHODS: An ePROM app was developed by extracting 18 items from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptom monitoring was conducted every two weeks for patients with metastatic breast cancer undergoing chemotherapy. The primary outcome was the response rate to the ePROM system. The secondary outcomes were response time, item missing rate, and distribution of responses for each symptom. RESULTS: A total of 71 cases (mean age 52.6 years) were analyzed. Performance status was 0 in 76% of the cases and 1 or higher in 24%. First-line treatment was being administered in 30% of cases, second-line treatment in 17%, and third-line or higher treatment in 53%. The response rate to the ePROM system from registration to week 40 remained high at around 80%, indicating good compliance. The average response time was 5.5 min and the missing rate for each item was below 0.4%. Among 1,093 responses, the top 3 symptoms causing interference with daily life were Fatigue (63%), Numbness and tingling (48%), and General pain (46%). CONCLUSION: Our developed ePROM system was able to capture symptoms accurately in patients with metastatic breast cancer undergoing chemotherapy while maintaining a high response compliance.

Long-Term Physical Activity and Body Composition After Exercise and Educational Programs for Breast Cancer: A Randomized Controlled Trial From the Setouchi Breast Project-10.

BACKGROUND: It is unclear what interventions can sustain long-term higher physical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. METHODS: This was a prospective randomized controlled trial for patients with stage 0 to III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents (METs)/week at 1 year after registration. RESULTS: From March 16, 2016, to March 15, 2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = .492) and between the education and control groups (62% and 53%, P = .126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = .0083), BMI (P = .0034), and body fat percentage (P = .0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = .0038) compared to control group. CONCLUSION: Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival.

[A Case of Giant Phyllodes Tumor Treated with Breast Reconstruction].

A 62-year-old woman was diagnosed with right breast tumor 2 years ago, which she refused to undergo surgery. The patient experienced a rapid enlargement of the mass over the past 1 month, and visited hospital. The patient was diagnosed with a borderline phyllodes tumor by needle biopsy. Her right breast was occupied by an 18 cm mass. We conducted tumor resection and immediate reconstruction with DIEAP flap. The pathological diagnosis was a malignant phyllodes tumor, and the postoperative radiation to the chest wall was performed. During a year and a half follow up, she has no recurrence and highly satisfied with the reconstructed breast. Phyllodes tumors may recur locally regardless of whether they are benign or malignant, and we need strict follow-up.

[A Case Report of Multiple Endocrine Neoplasia Type 2A(MEN2A)Diagnosed with Medullary Thyroid Carcinoma].

We experienced a case of multiple endocrine neoplasia type 2A(MEN2A)diagnosed with medullary thyroid carcinoma. The patient was a 50s woman who was referred for a thyroid nodule detected in the right lobe during a carotid ultrasound examination. After undergoing a hemithyroidectomy, it was determined that the tumor was medullary carcinoma. RET gene test was performed, confirming a mutation at codon768, leading to the diagnosis of MEN2A. A completion thyroidectomy was performed to remove the remaining thyroid tissue. Postoperatively, the patient is undergoing systemic surveillance.

[A Case of HER2-Positive Metastatic Breast Cancer Achieved a Complete Response to Paclitaxel and Trastuzumab in Combination with Pertuzumab in Fifth Therapy].

We report a case of HER2-positive metastatic breast cancer achieved a complete response(CR)to paclitaxel(PTX) and trastuzumab(HER) in combination with pertuzumab(PER) in 5th therapy. A 69-year-old woman was diagnosed left breast cancer and underwent mastectomy and sentinel lymph node biopsy in January 2011. Pathological examination revealed an invasive ductal carcinoma that was ER 0%, PgR 0%, HER2(3+), Ki-67 67% and node negative. Two years after the operation, she found multiple lung metastases in both lungs. She was administered drug treatment as HER2-positive metastatic breast cancer, but multiple lung metastases got worse after 4th treatment. Weekly PTX, trastuzumab and pertuzumab were administered as 5th therapy. After 2 months, lung metastases diminished significantly. After 44 courses of drug treatment, positron emission tomography computed tomography(PET-CT)scan revealed CR. She wanted to cease treatment, so she continues to get CT scan every half a year and the CR has been maintained.

[Clinical Practice of the Efficiency and Safety of Palbociclib in Patients with Metastatic Breast Cancer].

We aimed to examine the effects of palbociclib and neutropenia in patients with metastatic breast cancer(MBC). From December 2017 to December 2019, 18 patients with estrogen receptor(ER)-positive, human epidermal growth factor receptor 2(HER2)-negative MBC were treated with palbociclib for at least 1 cycle. The most common adverse event(AE) was neutropenia, which occurred in 83% of all cases. With cessation and dose reduction, none of the patients had Grade 4 neutropenia. Palbociclib used in the first- or second-line treatment of MBC showed a higher efficacy than when used as the third-line treatment, which was observed as a longer duration to stay on treatment and higher efficacy.

[A Case of the Locally Advanced Breast Cancer with Serious Comorbidities Obtained a Good Local Control].

A 66-years-old woman was referred to our hospital with the chief complaint of a huge exposed left breast mass, associated massive exudates, bleedingand foul-smelling discharge. Invasive ductal carcinoma was diagnosed by core needle biopsy. The computed tomography showed left axillary lymph node metastases and no distant metastasis. Her performance status(PS) was Grade 3. She had serious comorbidities such as non-alcoholic steatohepatitis and liver cirrhosis, renal dysfunction. DMpC therapy and Mohs paste therapy were started since her overall status was improved. The huge left breast tumor and left axillary lymph node metastases were reduced remarkably. Total mastectomy and axillary lymph node dissection and free skin grafting was perfomed, and PS was improved to Grade 0, She received DMpC therapy for 4 months postoperatively, and radiotherapy at left chest wall and supraclavicular fossa.

Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1ß in macrophages.

BACKGROUND: Type I interferons (IFNs), including IFN-alpha (IFNA) and IFN-beta (IFNB), have anti-inflammatory properties and are used to treat patients with autoimmune and inflammatory disorders. However, little is known of the role of IFN-tau (IFNT), a type I IFN produced by ruminant animals for inflammation. Because IFNB has recently been shown to inhibit nucleotide-binding oligomerization domain-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome activation and subsequent secretion of the potent inflammatory cytokine interleukin (IL)-1ß, we examined the effects of ruminant IFNT on NLRP3 inflammasome-mediated IL-1ß secretion in human THP-1 macrophages. METHODS AND RESULTS: IFNT dose-dependently inhibited IL-1ß secretion induced by nano-silica, a well-known activators of NLRP3 inflammasomes, in human macrophages primed with lipopolysaccharide (LPS, TLR4 agonist) and Pam3CSK4 (TLR1/2 agonist). IFNT also suppressed phagocytosis of nano-silica and reactive oxygen species (ROS) generation. Western blot analysis showed that IFNT inhibited both pro-IL-1ß and mature IL-1ß. In addition, real-time RT-PCR analysis showed that IFNT suppressed IL-1ß mRNA expression induced by LPS and Pam3CSK4. Although nano-silica particles did not induce IL-10 secretion, IFNT induced IL-10 secretion in a dose-dependent manner. Furthermore, IFNT-suppressed IL-1ß secretion was restored by anti-IL-10 neutralizing antibody. CONCLUSIONS: Ruminant IFNT inhibits NLRP3 inflammasome-driven IL-1ß secretion in human macrophages via multiple pathways, including the uptake of nano-silica particles, generation of ROS, and IL-10-mediated inhibition of pro-IL-1ß induction. It may be a therapeutic alternative to IFNA and IFNB.

Pitavastatin reduces elevated IL-18 levels in Japanese subjects with hypercholesterolemia: sub-analysis of Kansai investigation of statin for hyperlipidemic intervention in metabolism and endocrinology (KISHIMEN).

AIM: Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study. METHODS: The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r = 0.259, p = 0.0181); however, percent changes in these levels were not significantly correlated. CONCLUSION: Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects.

Effects of pitavastatin on lipid profiles and high-sensitivity CRP in Japanese subjects with hypercholesterolemia: Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN) investigatars.

AIM: The effect of pitavastatin on high-sensitivity C-reactive protein (hs-CRP) has not been reported, yet, in humans. We, therefore, investigated the effects of pitavastatin on lipid profiles and hs-CRP in Japanese subjects with hypercholesterolemia. METHODS: The subjects were 178 Japanese with hypercholesterolemia, including 103 (58%) with type 2 diabetes. Pitavastatin (12 mg/day) was administered for 12 months. Serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG) and hs-CRP levels were measured for 12 months. RESULTS: Serum LDL-C and RLP-C levels were significantly decreased by 30.3% and 22.8%, respectively. Serum TG levels were decreased by 15.9% in subjects with basal TG levels above 150 mg/dl. Serum HDL-C levels were significantly increased. The administration of pitavastatin reduced serum hs-CRP levels by 34.8%. No serious adverse events were observed, including changes in glycosylated hemoglobin levels of diabetic patients. CONCLUSION: These results suggest that pitavastatin significantly improves lipid profiles and reduces proinflammatory responses, without adverse effects, in Japanese subjects with hypercholesterolemia, including those with diabetes mellitus.

Pericardial reconstruction using a pedicle flap of the diaphragmatic central tendon.

A 46-year-old woman was referred to our hospital for further evaluation of an abnormal shadow on a chest X-ray. Chest computed tomography and magnetic resonance imaging revealed a lobulated tumor arising from the left lower lobe. At operation, the tumor tissue was found to have invaded the lingula and pericardium, involving the left phrenic nerve. Resection of the left lower lobe, lingula and pericardium including the phrenic nerve was performed for extended pulmonary malignancy. A pedicle flap of the diaphragmatic central tendon was used as a pericardial patch for pericardial reconstruction with satisfactory results. The patient's postoperative course was uneventful. The postoperative histological diagnosis was pulmonary adenocarcinoma with sarcomatous elements [pT3N2M0]. At present, 43 months after the operation, the patient is receiving chemotherapy after having undergone cyberknife radiotherapy for brain metastasis of the tumor. The use of a pedicle diaphragmatic flap was effective in repairing a pericardial defect after extensive resection of pulmonary malignancy.

Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus.

Most T lymphocytes are generated within the thymus. It is unclear, however, how newly generated T cells relocate out of the thymus to the circulation. The present study shows that a CC chemokine CCL19 attracts mature T cells out of the fetal thymus organ culture. Another CC chemokine CCL21, which shares CCR7 with CCL19 but has a unique C-terminal extension containing positively charged amino acids, failed to show involvement in thymic emigration. Neonatal appearance of circulating T cells was defective in CCL19-neutralized mice as well as in CCR7-deficient mice but not in CCL21-neutralized mice. In the thymus, CCL19 is predominantly localized in the medulla including endothelial venules. These results indicate a CCL19- and CCR7-dependent pathway of thymic emigration, which represents a major pathway of neonatal T cell export.