Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) was initially used for locally advanced or inoperable breast cancers. Its extension to early disease has facilitated breast-conserving surgery (BCS). This study investigated the use of NAC in patients registered with the Hong Kong Breast Cancer Registry (HKBCR); it also assessed NAC effectiveness according to rates of pathological complete response (pCR) and BCS. METHODS: Records were retrieved from the HKBCR regarding 13 435 women who had been diagnosed with invasive breast cancer during the period of 2006 to 2017, including 1084 patients who received NAC. RESULTS: The proportion of patients treated with NAC nearly doubled from 5.6% in 2006-2011 to 10.3% in 2012-2017. The increase was most pronounced among patients with stage II or III disease. In terms of biological subtype, substantial increases in the receipt of NAC were evident among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) tumours. The best rates of pCR were observed in patients with HER2-positive (non-luminal) [46.0%] tumours, followed by patients with luminal B (HER2-positive) [29.4%] and triple-negative (29.3%) tumours. After NAC, the rate of BCS was 53.9% in patients with clinical stage IIA disease, compared with 38.2% in patients with pathological stage IIA disease who did not receive NAC. CONCLUSION: The use of NAC in Hong Kong increased from 2006 to 2017. The findings regarding rates of pCR and BCS indicate that NAC is an effective treatment; it should be considered in patients with stage ≥II disease, as well as patients with HER2- positive (non-luminal) or triple-negative breast cancers.

Seasonal variation of patulous Eustachian tube diagnoses using climatic and national health insurance data.

OBJECTIVES: This study aimed to analyse if there were any associations between patulous Eustachian tube occurrence and climatic factors and seasonality. METHODS: The correlation between the monthly average number of patients diagnosed with patulous Eustachian tube and climatic factors in Seoul, Korea, from January 2010 to December 2016, was statistically analysed using national data sets. RESULTS: The relative risk for patulous Eustachian tube occurrence according to season was significantly higher in summer and autumn, and lower in winter than in spring (relative risk (95 per cent confidence interval): 1.334 (1.267-1.404), 1.219 (1.157-1.285) and 0.889 (0.840-0.941) for summer, autumn and winter, respectively). Temperature, atmospheric pressure and relative humidity had a moderate positive (r = 0.648), negative (r = -0.601) and positive (r = 0.492) correlation with the number of patulous Eustachian tube cases, respectively. CONCLUSION: The number of patulous Eustachian tube cases was highest in summer and increased in proportion to changes in temperature and humidity, which could be due to physiological changes caused by climatic factors or diet trends.

Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly.

The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. INTRODUCTION: It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. METHODS: Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. RESULTS: Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48-1.80) and 1.42 (95% CI, 1.28-1.58); two, 1.75 (95% CI, 1.47-2.08) and 2.03 (95% CI, 1.69-2.43); three or more, 2.46(95% CI, 1.92-3.15) and 1.92 (95% CI, 1.34-2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80-3.44) or vertebral (HR, 1.40; 95% CI, 1.03-1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86-4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12-3.22). CONCLUSION: The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

Changes in the Ratio of T Helper 1 to T Helper 2 Signature Cytokines in Patients Undergoing Living Donor Liver Transplantation Surgery: A Prospective Controlled Study.

BACKGROUND: The balance between T helper 1 (Th1) and T helper 2 (Th2) signature cytokines plays a critical role in the immune response. The aim of this study was to evaluate the Th1 to Th2 cytokine ratio in healthy persons and patients with cirrhotic hepatitis and to investigate changes in the Th1 to Th2 cytokine ratio during living donor liver transplantation (LDLT) surgery. METHODS: Eighty patients were allocated to each of the donor and recipient groups. In the recipient group, signature cytokines-interferon gamma (IFN-γ) and tumor necrosis factor α (TNF-α) as Th1 and interleukin 6 (IL-6) and interleukin 10 (IL-10) as Th2-were quantified after induction of anesthesia (baseline, stage 1), 60 minutes after the start of the anhepatic phase (stage 2), and 60 minutes after reperfusion (stage 3). In the donor group, cytokine levels were analyzed only at stage 1. The Th1/Th2 cytokine ratios at baseline and over time during surgery in the recipient group were evaluated. RESULTS: At stage 1, the recipient group exhibited higher levels of all cytokines than the donor group. However, the IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios of the groups were comparable. The levels of all cytokines, except IFN-γ, increased during LDLT. The IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios declined significantly during LDLT. CONCLUSIONS: The preoperative Th1/Th2 cytokine ratios were similar in healthy persons and patients with cirrhotic hepatitis. During LDLT surgery, Th2 activity was enhanced, as indicated by a shift in the Th1/Th2 cytokine ratio toward Th2.

C-reactive protein binds to integrin α2 and Fcγ receptor I, leading to breast cell adhesion and breast cancer progression.

C-reactive protein (CRP) is an acute phase protein synthesized upon the inflammatory responses, associated with breast cancer. The process of tumor cell invasion and metastasis involves the adherence of cells to the extracellular matrix via integrin as a receptor for matrix molecules. The present study investigated the role of CRP in the adhesive phenotype of breast cells and the underlying mechanisms. Here, we first showed that CRP induces adhesion of MCF10A human breast epithelial cells through the activation of integrin α2 signaling. Expression of integrin α2 was induced by CRP in which transcription factors c-fos and SP1 may be involved. Binding of CRP with integrin α2 leads to the activation of focal adhesion kinase (FAK), paxillin and ERKs. CRP also binds to an Fcγ receptor Fcγ receptor I (FcγRI), and induces activation of paxillin, FAK and ERKs. Integrin α2 and FAK have crucial roles in the adhesive and invasive phenotypes as well as MMP-9 upregulation induced by CRP in MCF10A cells. Treatment with an inflammatory lipid sphingosine-1-phosphate induced CRP, which may be secreted and exert an autocrine effect by binding to FcγRI and integrin α2. Involvement of CRP in adhesion, invasion, anchorage-independent growth and upregulation of integrin α2, paxillin and FAK was observed in MDA-MB-231 triple-negative human breast cancer (TNBC) cells. Using an in vivo invasion model and an orthotopic mouse tumor model with MDA-MB-231 cells, we showed that CRP has an important role in intravasation and tumor growth in vivo, demonstrating the in vivo relevance of our in vitro results. The present study elucidates a critical molecular basis between CRP, integrin α2 and FcγRI pathways in MCF10A breast cells and MDA-MB-231 TNBC cells, thereby providing useful information on CRP-induced aggressiveness of breast cells in the inflammatory microenvironment.

Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease. Choi DK, Jung SB, Park BH, Jeong BC, Seo SI, Jeon SS, Lee HM, Choi HY, Jeon HG.J Urol. 2015 Oct;194(4):910-5. [Epub 2015 Apr 28]. doi: 10.1016/j.juro.2015.04.093.

PURPOSE: We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. MATERIALS AND METHODS: We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease-glomerular filtration rate 90ml/min/1.73m2 or greater (230, 42.4%), chronic kidney disease stage II-glomerular filtration rate 60 to less than 90ml/min/1.73m2 (227, 41.8%), and chronic kidney disease stage III-glomerular filtration rate 30 to less than 60ml/min/1.73m2 (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. RESULTS: Among all patients (mean age = 56.0y) mean preoperative glomerular filtration rate, functional renal volume, and glomerular filtration rate/functional renal volume were 83.2ml/min/1.73m2, 340.6cm3, and 0.25ml/min/1.73m2/cm3, respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs. stage II 26.5% vs. stage III 12.8%, P<0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs. stage II 17.3% vs. stage III 16.5%, P = 0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs. stage II 20.1% vs. stage III 45.9%, P<0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (P = 0.012), diabetes mellitus (P = 0.023), hypertension (P = 0.015), and chronic kidney disease stage (P<0.001). CONCLUSIONS: Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration.

A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

BACKGROUND AND OBJECTIVE: Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. MATERIAL AND METHODS: Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. RESULTS: Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone. CONCLUSION: This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction.