Biomarkers changes after neoadjuvant chemotherapy in breast cancer: A seven-year single institution experience

The adoption of neoadjuvant chemotherapy (NACT) for breast cancer (BC) is increasing. The need to repeat the biomarkers on a residual tumor after NACT is still a matter of debate. We verified estrogen receptors (ER), progesterone receptors (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) status changes impact in a retrospective monocentric series of 265 BCs undergoing NACT. All biomarkers changed with an overall tendency toward a reduced expression. Changes in PR and Ki67 were statistically significant (p = 0.001). Ki67 changed in 114/265 (43.0%) cases, PR in 44/265 (16.6%), ER in 31/265 (11.7%) and HER2 in 26/265 (9.8%). Overall, intrinsic subtype changed in 72/265 (27.2%) cases after NACT, and 10/265 (3.8%) cases switched to a different adjuvant therapy accordingly. Luminal subtypes changed most frequently (66/175; 31.7%) but with less impact on therapy (5/175; 2.8%). Only 3 of 58 triple-negative BCs (5.2%) changed their intrinsic subtype, but all of them switched treatment. No correlation was found between intrinsic subtype changes and clinicopathological features. To conclude, biomarkers changes with prognostic implications occurred in all BC intrinsic subtypes, albeit they impacted therapy mostly in HER2 negative and/or hormone receptors negative BCs. Biomarkers retesting after NACT is important to improve both tailored adjuvant therapies and prognostication of patients

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Neoadjuvant therapy for resectable pancreatic adenocarcinoma: An interim report of a prospective randomized study

Background: We compare neoadjuvant chemoradiation therapy plus surgery versus surgery alone in patients with resectable pancreatic adenocarcinoma (RPA) in a prospective, controlled, randomized study. The primary end-point was to evaluate the R0 resection rate in the two groups and secondary was safety/efficacy of neoadjuvant therapy, postoperative mortality, morbidity, lymph node-ratio and pTNM stage. Methods: Patients with RPA were randomized to receive either neoadjuvant therapy plus surgery (group A) or surgery alone (group B). In group A, patients received gemcitabine (1,000 mg/m2) on days 1,8 every 21, followed by radiation therapy (45 Gy plus boost of 9 Gy) plus gemcitabine 50 mg/m2 biweekly, for 6 weeks. A CT scan restaging was performed before surgery. Results: From March 2007 we enrolled 19 consecutive patients (9 male and 8 female). Seventeen among the eligible patients 7 (41%) were randomized in group A and 10 (59%) in group B. After neoadjuvant therapy one patient (14.3%) had a progression of disease, 4 had stable disease (57.2%) and 2 (28.5%) had partial response. Consequently 6 patients in group A, underwent surgery (85.7%) and 4 of these (66.6%) experienced a successful resection. In group B surgical resection was performed in 9 patients (90%). R0 resection rate was 75% (3/4) in group A and 30% (2/9) in group B without statistically significant difference (p = 0.217). Regarding to safety myelotoxicity (57.1%), asthenia, weight loss (28.5%) and gastrointestinal toxicity (57.1%) were reported in group A patients. Overall postoperative mortality was 1 (11.1%) without significantly difference in the two groups (p = 1.000); overall postoperative morbidity was 0% in group A and 44.4% in group B (p = 0.093). There was no difference regarding pTNM stage (p = 0.364). Mean total number of lymph node removed with surgical specimen was similar in the two group (A: 29.5 vs. B: 27, p = 0.636). Mean number of lymph node metastasis was lesser in group A (p = 0.035). Conclusions: Despite the small number of patients, preliminary data suggest that neoadjuvant chemoradiation therapy plus surgery increases the R0 resection rate, reduces the lymph nodes ratio and allows a better postoperative cours

The Protease Inhibitor Gabexate Mesylate Reduces Invasiveness and Angiogenesis in Pancreatic Cancer Cell Lines, Enhancing Gemcitabine Action

Context Pancreatic cancer cells produce various proteases involved in invasion, angiogenesis and metastatic spread. Gabexate mesylate (GM), a serine protease inhibitor, may reduce invasive capabilities and enhance chemotherapy effects. Objective To evaluate the effect of treatment with GM and gemcitabine (GEM), alone or combined. Materials and methods Studies have been performed on cancer cell lines PANC-1, SW1990 and endothelial cell EA.hy926. Treatment consisted of GM (50-100 \ub5M for 24 h), alone or followed by GEM (250 \ub5M for 24 h). Aspects studied included: cell viability (MTT assay), cell invasiveness and migration (Boyden chambers chemoinvasion and chemotaxis assay), angiogenesis (endothelial tube formation assay) and VEGF levels (ELISA) in EA.hy926 cell, MMP-2 and MMP-9 activity (gelatin zymography). Results Cell viability: this parameter decreased by 40% with GM alone only in EA.hy926 cells (P&lt;0.05). Cell invasiveness: GM alone inhibited SW1990 and EA.hy926 cell line invasiveness by about 75% (P&lt;0.001). GM and GEM reduced invasiveness of PANC-1 and SW1990 cells by 55-65%. Angiogenesis and VEGF: inhibition of angiogenesis (from 60 to 90%) was observed in EA.hy926 cells incubated with the supernatant of PANC-1 and SW1990 cells treated with GM, alone or followed by GEM. Similar result was found for VEGF levels, strongly decreased in all cell lines treated with GM, alone or followed by GEM (P&lt;0.001). The inhibitory effect of GM on PANC-1 and SW1990 was superior to bevacizumab (P&lt;0.05). MMP-9 and MMP-2 activity: MMP-9 and MMP-2 activities were decreased by 40% after combined treatment (GM and GEM) in both PANC-1 and SW1990 cells. In EA.hy926 cells GM alone was more effective than the combination in inhibiting MMP-2 (P&lt;0.001). Conclusion These in vitro data indicate that GM can effectively inhibit pancreatic cancer cell invasiveness and angiogenesis, also enhancing the effect of gemcitabine