Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an emerging pathogen in dogs and has been found in Europe, Asia and North America. To date most studies are one-point prevalence ...studies and therefore little is known about the dynamics of MRSP in dogs and their surrounding. In this longitudinal study MRSP colonization in dogs and the transmission of MRSP to humans, contact animals and the environment was investigated. Sixteen dogs with a recent clinical MRSP infection were included. The index dogs, contact animals, owners and environments were sampled once a month for six months. Samples taken from the nose, perineum and infection site (if present) of the index cases and contact animals, and the nares of the owners were cultured using pre-enrichment. Index cases were found positive for prolonged periods of time, in two cases during all six samplings. In five of the 12 households that were sampled during six months, the index case was intermittently found MRSP-positive. Contact animals and the environment were also found MRSP-positive, most often in combination with a MRSP-positive index dog. In four households positive environmental samples were found while no animals or humans were MRSP-positive, indicating survival of MRSP in the environment for prolonged periods of time. Genotyping revealed that generally similar or indistinguishable MRSP isolates were found in patients, contact animals and environmental samples within the same household. Within two households, however, genetically distinct MRSP isolates were found. These results show that veterinarians should stay alert with (former) MRSP patients, even after repeated MRSP-negative cultures or after the disappearance of the clinical infection. There is a considerable risk of transmission of MRSP to animals in close contact with MRSP patients. Humans were rarely MRSP-positive and never tested MRSP-positive more than once suggesting occasional contamination or rapid elimination of colonization of the owners.
The insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance. This study aims to elucidate whether ...variation in the IGF-1 pathway is predictive for pathologic response in early HER2 negative breast cancer (BC) patients, taking part in the phase III NEOZOTAC trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy with or without zoledronic acid.
Formalin-fixed paraffin-embedded tissue samples of pre-chemotherapy biopsies and operation specimens were collected for analysis of IGF-1 receptor (IGF-1R) expression (n = 216) and for analysis of 8 candidate single nucleotide polymorphisms (SNPs) in genes of the IGF-1 pathway (n = 184) using OpenArray® RealTime PCR. Associations with patient and tumor characteristics and chemotherapy response according to Miller and Payne pathologic response were performed using chi-square and regression analysis.
During chemotherapy, a significant number of tumors (47.2 %) showed a decrease in IGF-1R expression, while in a small number of tumors an upregulation was seen (15.1 %). IGF-1R expression before treatment was not associated with pathological response, however, absence of IGF-1R expression after treatment was associated with a better response in multivariate analysis (P = 0.006) and patients with a decrease in expression during treatment showed a better response to chemotherapy as well (P = 0.020). Moreover, the variant T allele of 3129G > T in IGF1R (rs2016347) was associated with a better pathological response in multivariate analysis (P = 0.032).
Absent or diminished expression of IGF-1R after neoadjuvant chemotherapy was associated with a better pathological response. Additionally, we found a SNP (rs2016347) in IGF1R as a potential predictive marker for chemotherapy efficacy in BC patients treated with TAC.
ClinicalTrials.gov NCT01099436 . Registered April 6, 2010.
Methicillin-resistant Staphylococcus pseudintermedius (MRSP), which is often multidrug resistant (MDR), has recently emerged as a threat to canine health worldwide. Knowledge of the temporal ...distribution of specific MRSP lineages, their antimicrobial resistance phenotypes, and their association with clinical conditions may help us to understand the emergence and spread of MRSP in dogs. The aim of this study was to determine the yearly proportions of MRSP lineages and their antimicrobial-resistant phenotypes in the Netherlands and to examine possible associations with clinical conditions. MRSP was first isolated from a canine specimen submitted for diagnostics to the Faculty of Veterinary Medicine of Utrecht University in 2004. The annual cumulative incidence of MRSP among S. pseudintermedius increased from 0.9% in 2004 to 7% in 2013. MRSP was significantly associated with pyoderma and, to a lesser extent, with wound infections and otitis externa. Multilocus sequence typing (MLST) of 478 MRSP isolates yielded 39 sequence types (ST) belonging to 4 clonal complexes (CC) and 15 singletons. CC71 was the dominant lineage that emerged since 2004, and CC258, CC45, and several unlinked isolates became more frequent during the following years. All but two strains conferred an MDR phenotype, but strains belonging to CC258 or singletons were less resistant. In conclusion, our study showed that MDR CC71 emerged as the dominant lineage from 2004 and onward and that less-resistant lineages were partly replacing CC71.
•A patient communication aid could facilitate shared decision making (SDM).•The supportive function of the aid depends on timing and individual patients’ needs.•It is important to raise awareness of ...the presence of a choice in SDM aids.•And it is challenging to find a balance between full information and sensitivity.
To learn how to configure a patient communication aid (PCA) to facilitate shared decision-making (SDM) about treatment for advanced cancer.
The PCA consists of education about SDM, a question prompt list, and values clarification methods. Study 1. A first version was presented to 13 patients, 8 relatives and 14 bereaved relatives in interviews. Study 2. A second version was used by 18 patients in a pilot study. Patients and oncologists were interviewed, patients were surveyed, and consultations were audio-recorded.
Respondents reported that the aid facilitated patient control over information, raised choice awareness and promoted elaboration. Risks were identified, most importantly that the aid might upset patients. Also, some respondents reported that the PCA did not, or would not support decision making because they felt sufficiently competent, did not perceive a role for themselves, or did not perceive that the decision required elaboration.
Opinions on the usefulness of the PCA varied. It was challenging to raise awareness about the presence of a choice, and to find a balance between comprehensive information and sensitivity.
A future study should demonstrate whether the PCA can improve SDM, and whether this effect is stronger when oncologists receive training.
Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar ...clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent evidence has shown that the ratio between CA19-9 and bilirubin levels supports diagnostic distinction of benign or malignant hepatopancreaticobiliary diseases. Here, we investigate the diagnostic value of this ratio in PDAC, dCCA and benign diseases of the periampullary region in a novel fashion. To address this aim, we enrolled 265 patients with hepatopancreaticobiliary diseases and constructed four logistic regression models on a subset of patients (
= 232) based on CA19-9, bilirubin and the ratio of both values: CA19-9/(bilirubin
). Non-linearity was investigated using restricted cubic splines and a final model, the 'Model Ratio', based on these three variables was fitted using multivariable fractional polynomials. The performance of this model was consistently superior in terms of discrimination and calibration compared to models based on CA19-9 combined with bilirubin and CA19-9 or bilirubin alone. The 'Model Ratio' accurately distinguished between malignant and benign disease (AUC 95% CI, 0.91 0.86-0.95), PDAC and benign disease (AUC 0.91 0.87-0.96) and PDAC and dCCA (AUC 0.83 0.74-0.92) which was confirmed by internal validation using 1000 bootstrap replicates. These findings provide a foundation to improve minimally-invasive diagnostic procedures, ultimately ameliorating effective therapy for PDAC and dCCA.
Background
Minimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This ...study identified diagnostic plasma proteins based on proteomics of tumor secretome.
Materials and Methods
Secretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19‐9 (CA19‐9) were validated by enzyme‐linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power.
Results
In tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin‐2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p < .001, AUC = 0.844). Combined expression of THBS2 and CA19‐9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early‐ and late‐stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19‐9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin.
Conclusion
Our proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19‐9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD.
Implications for Practice
The combined plasma expression of thrombospondin‐2 and carbohydrate antigen 19‐9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.
This article identifies diagnostic plasma proteins to distinguish patients with pancreatic ductal adenocarcinoma and distal cholangiocarcinoma from benign disease and health donors and evaluates these new markers for additive value with CA19‐9 at different disease stages.
Background
Quality of life in cancer patients might be affected by chemotherapy-induced toxicity. Especially in patients with pancreatic ductal adenocarcinoma (PDAC), with a short life expectancy, ...fear of poor quality of life is often a reason for both patients and medical oncologists to refrain from further treatment. In this study, we investigated quality of life (QoL), pain, sleep, and activity levels in locally advanced pancreatic cancer (LAPC) patients after FOLFIRINOX treatment.
Methods
A total of 41 LAPC patients with stable disease or partial response were included after completion of at least four cycles of FOLFIRINOX. QoL was measured with the EORTC QLQ-C30 and NRS pain scores. Patients completed the Richards-Campbell Sleep Questionnaire (RCSQ) for five consecutive nights and wore a GENEActiv tri-axial accelerometer (Actiwatch) for 7 days, registering sleep duration, efficiency, and activity.
Results
Mean EORTC QLQ-C30 score for global health status was 78.3 (± 17.3), higher than reference values for cancer patients (
P
< 0.001) and general population (
P
= 0.045). LAPC patients reported few disease-related symptoms. Two patients (5%) reported pain scores > 3. Mean sleep duration was 8 h/night (± 1.2 h) and sleep efficiency 70% (± 9%) with high patient-reported quality of sleep (mean RCSQ score 72.0 ± 11.4). Mean duration of moderate-vigorous activity was 37 min/week (± 103 min/week).
Conclusions
QoL is very good in most LAPC patients with disease control after FOLFIRINOX, measured with validated questionnaires and Actiwatch registration. The fear of clinical deterioration after FOLFIRINOX is not substantiated by this study and should not be a reason to refrain from treatment.
Trial registration
Dutch trial register NL7578.
According to the Trastuzumab for Gastric Cancer (ToGA) study, trastuzumab plus cisplatin and capecitabine/5‐fluorouracil (5‐FU) is standard first‐line treatment for human epidermal growth factor ...receptor 2 (HER2)‐positive advanced oesophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab‐based cytotoxic backbone regimens compared to the standard ToGA regimen using meta‐analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first‐line trastuzumab‐based regimens for HER2‐positive oesophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in situ hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab‐based regimens to the ToGA regimen. Hazard ratios (HRs) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan‐Meier curves. Incidence counts and toxicity sample‐sizes were extracted for adverse events and compared using single‐arm proportion meta‐analysis in R. Fifteen studies (N = 557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5‐FU (median OS = 20.7 months) versus ToGA (16.0 months, HR = 0.75, 95% CI = 0.59–0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S‐1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand‐foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S‐1 can substitute capecitabine or 5‐FU when specific toxicities are encountered.
What's new?
Standard treatment for oesophagogastric cancers that are positive for human epidermal growth factor receptor 2 (HER2) consists of trastuzumab plus cisplatin and capecitabine or 5‐fluorouracil (5‐FU). Cisplatin‐containing doublet regimens, however, are known be more toxic and less effective than regimens without cisplatin. In this meta‐analysis, alternative trastuzumab‐based therapies were compared to the standard cisplatin‐containing regimen in the treatment of HER2‐positive metastatic oesophagogastric adenocarcinomas. The substitution of cisplatin with oxaliplatin was associated with increased survival and reduced toxicity. Hand–foot syndrome was reduced, without a compromise in efficacy, by replacing capecitabine with 5‐FU or the oral fluoropyrimidine S‐1.
: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to ...determine the optimal adjuvant regimen for gastric cancer treated with curative intent.
: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs).
: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies,
= 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies,
= 10,761) and 14 for DFS (30 studies,
= 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38⁻0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58⁻1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28⁻0.80).
: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.
Introduction:
Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 ...(hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines.
Methods:
Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays.
Results:
Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found.
Discussion:
These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy.
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