From Barrett's esophagus to adenocarcinoma and metastasis

The first description of islets of ectopic gastric mucosa in the esophagus was by Schmidt in 1805. One century later, in 1906, Tileston described peptic ulcerations in columnar epithe

Image analysis of palm oil crystallisation as observed by hot stage microscopy

An image processing algorithm previously used to analyse the crystallisation of a pure fat (tripalmitin) has been applied to the crystallisation of a multicomponent natural fat (palm oil). In contrast to tripalmitin, which produced circular crystals with a constant growth rate, palm oil produced speckled crystals caused by the inclusion of entrapped liquid, and growth rates gradually decreased with time. This can be explained by the depletion of crystallisable material in the liquid phase, whereas direct impingement of crystals (the basis of the Avrami equation) was less common. A theoretical analysis combining this depletion with assuming that the growth rate is proportional to the supersaturation of a crystallisable pseudo-component predicted a tanh function variation of radius with time. This was generally able to provide good fits to the growth curves. It was found that growth rate was a relatively mild function of temperature but also varied from crystal to crystal and even between different sides of the same crystal, which may be due to variations in composition within the liquid phase. Nucleation rates were confirmed to vary approximately exponentially with decreasing temperature, resulting in much greater numbers of crystals and a smaller final average crystal size at lower temperatures

Increased PXR and Suppressed T-Cell Signaling Are Associated With Malignant Degeneration of Barrett's Esophagus

Background and Aims: Barrett's esophagus (BE) is the precursor lesion for esophageal adenocarcinoma (EAC). To detect EAC in early stage, patients with BE undergo endoscopic surveillance. Surveillance cohorts largely consist of nondysplastic BE (NDBE) patients with a low annual progression risk (&lt;0.5%). Predictive biomarkers for malignant progression of NDBE could improve efficacy of surveillance. Biomarker research has mostly focused on aberrant protein expression on BE epithelial cells. Moreover, insight in cell signaling driving malignant transformation is unknown. This study uses a data-driven approach to analyze tumor-stroma interaction in NDBE which progressed to high-grade dysplasia or EAC. Methods: In this case-control study, we performed RNA sequencing analysis on index NDBE biopsies from 6 patients who, during long-term follow-up, progressed and 7 who did not progress to high-grade dysplasia/EAC. For control samples, squamous and duodenum tissues from BE patients were analyzed. For validation, we used quantitative PCR. Results: Significant differences in BE transcriptomic profiles between progressors and nonprogressors were found by principal component and differential expression analyses. Ingenuity pathway analysis indicated that 8 cell signaling pathways were significantly upregulated in the progressors, and 14 pathways were significantly downregulated. The most interesting finding was the upregulation of the xenobiotic metabolism pregnane X receptor signaling pathway in the progressor cohort, while of the downregulated pathways in progressors, several were related to the immune system. Conclusion: These novel transcriptomic insights are fundamental for developing (chemo-)preventive therapies. These could be therapies, which protect against toxins, including biles, responsible for pregnane X receptor activation or which enhance protective immune mechanisms. The identified RNA markers are promising biomarkers for improving risk stratification in surveillance programs.</p

Characterisation of high 1,3-distearoyl-2-oleoyl-sn-glycerol content stearins produced by acidolysis of high oleic sunflower oil with stearic and palmitic acids

Nine different stearin fractions with 1,3-distearoyl-2-oleoyl-sn-glycerol (StOSt) contents ranging from 69–84% were obtained via fractionation from fats produced by acidolysis of high oleic sunflower oil (HOSO) with various mixtures of stearic (either 95 or 98% pure) and palmitic acids (98% pure). Samples were further treated with silica to reduce the oxidised glyceride and DAG content. Isothermal crystallisation at 20°C showed a single main peak, but evidence of crystallisation during the initial DSC transient was also apparent for high StOSt content samples. This was confirmed as the α form by stop-and-return DSC and XRD. The main crystallisation event was generally faster (including a shorter induction time) for samples with higher StOSt levels (lower POSt levels). Silica treatment generally accelerated transformations to higher polymorphs (γ, β′ and β). Raman microscopy experiments showed that crystallisation of the β-form was achieved after 7 days storage at 20°C but only in the silica treated stearin samples. This is consistent with higher solid fat content (SFC) values that were obtained with silica treated samples, which also increased with higher levels of StOSt. The results suggest that such stearins could potentially replace shea stearin in cocoa butter equivalents (CBE) formulations

Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens

Simple Summary: Esophageal adenocarcinoma (EAC) is one of the two major subtypes of esophageal cancer. In early disease stage, many EAC patients are asymptomatic. Most patients will present with late-stage disease in case of dysphagia and/or weight loss. Patients who undergo treatment with curative intent, have 5-year survival rates rarely exceeding 30%. Currently, curative treatment consists of chemo- and radiotherapy combined with surgical resection. Despite differences between tumors at the molecular level, all patients receive similar treatment, which results in heterogeneous therapeutic response. The aim of this review is to discuss the current research on molecular characteristics in EAC, which may predict tumor response. Moreover, we also discuss the rationale and research on adjusted regimens for EAC with for instance chemoradiotherapy and surveillance instead of (immediate) surgical resection. In future, these findings will lead to more personalized treatment approaches for EAC.Esophageal cancers confer a major health challenge and are highly aggressive malignancies with poor prognosis. Esophageal adenocarcinoma (EAC) is one of the two major histopathological subtypes of esophageal cancer. Despite advances in treatment modalities, the prognosis of patients with EAC remains poor, with a 5-year survival rate that rarely exceeds 30% in patients treated with curative intent. Chemoradiotherapy followed by resection is the treatment of choice for EAC patients, which are deemed to be curable. Current patient stratification and treatments are based on outcomes from clinical trials. Unfortunately, the molecular heterogeneity of EAC which determines the chemo- and radiosensitivity of these cancers are not taken into account. A more personalized approach in the treatment of EAC could improve patient outcomes. This review aims at summarizing literature on translational and clinical research in the field of EAC which could be of importance to develop personalized approaches. As suggested by the TCGA, expression data features molecular classifications by different platforms, including miRNA, genomic mutations and reverse-phase protein arrays. Here, we summarize literature on transcriptomic, data-driven approaches to identify distinct subtypes of EAC associated with molecular features. These novel classifications may determine the responsiveness to chemo(radio)therapy and help to identify novel molecular targets within cell signaling pathways. Moreover, we discuss the current clinical research efforts on tailored treatment regimens for patients with EAC taking into account the heterogeneous response to chemoradiotherapy. We summarize the evidence regarding active surveillance instead of immediate surgical resection after application of neoadjuvant chemo(radio)therapy in EAC. We consider that in future patients with complete response to chemo(radio)therapy, predicted by (transcriptomic) biomarkers, might benefit most from this approach. Finally, challenges to overcome for current findings to be implemented in clinical practice and move the field forward are being discussed.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Low Level of Her-2 Locus Amplification by Fluorescent In Situ Hybridization Does Not Correlate with Her-2 Protein Overexpression by Immunohistochemistry in Barrett's Esophagus

An accurate evaluation of the Her-2 status has important prognostic and therapeutic implications in many carcinomas. The aim of the study was to correlate Her-2 locus (17q11.2) amplification and chromosome 17 gains as assessed by fluorescent in situ hybridization (FISH) with Her-2 protein overexpression by immunohistochemistry (IHC) in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). We analyzed 34 patients with Her-2 amplification and/or chromosome 17gains using FISH on brush cytology specimens. Seven patients (21%) showed high Her-2 locus amplification (Her-2: Cep17 ≥ 5 : 1), 5 (15%) showed low Her-2 locus amplification (Her-2: Cep17 ≥ 2 < 5 : 1), and 22 (65%) displayed gains of chromosome 17 only. Further, we confirmed Her-2 amplification on corresponding biopsies that were taken at the same occasion as the cytologybrushings. Then, we compared the FISH results with IHC data obtained from the corresponding biopsies and showed that low level of Her-2 amplification does not correlate with Her-2 protein overexpression (score +3/+2; P = 1), in contrast to the high amplification level (P = .001). Thus, in our population of BE and EAC patients, low level of Her-2 amplification does not result in detectable level of Her-2 protein as assessed by IHC

Prognostic factors in renal-cell carcinoma: Immunohistochemical detection of p53 protein versus clinico-pathological parameters

Immunoreactivity forp53 protein was assessed in 100 cases of primary renal-cell carcinoma (RCC). The results were correlated with clinical survival data (follow-up 24 to 84 months: mean: 39 months) and with clinico-pathological parameters, including nuclear grade, tumour stage, cell type, tumour architecture and tumour diameter. In all, 32% of the tumours were p53-positive; there was no difference in survival between p53-positive and -negative cases. Similarly, p53 expression did not correlate with any of the clinico-pathological parameters mentioned. Nuclear grade (grade 1 + 2 vs. grade 3 + 4) had a striking impact on prognosis and so, to a lesser extent, did tumour stage and the occurrence of a spindle-cell component. The immunohistochemical detection of p53 in RCC is not of prognostic value. The estimation of nuclear grade, however is a major predictor of prognosis

Ethnic disparities in tuberculosis incidence and related factors among indigenous and other communities in ethnically diverse Suriname

Background: In Suriname, a country home to many ethnic groups, a high incidence of tuberculosis (TB) has been found among Indigenous Trio Amerindians. However, whether wider ethnic disparities in TB incidence and its associated risk factors (e.g., diabetes mellitus and HIV) exist in Suriname, is not known. We sought to investigate disparities in TB incidence and its risk factors on ethnicity in Suriname, as this could give way to targeted TB intervention programs. Methods: Anonymized patient data from 2011 to 2015 was extracted from the National TB Registry and analyzed. Differences in the five-year incidence rates of TB for the six largest ethnic groups-Creole, Hindustani, Indigenous, Javanese, Maroon, and Mixed-were assessed using a chi-square goodness-of-fit test, and TB patient differences regarding ethnicity were evaluated for selected factors using a multinomial logistic regression with Creole patients as reference. Results: 662 Patients were eligible for analyses with the following ethnic makeup: Creole (36.4%), Hindustani (15.6%), Indigenous (8.6%), Javanese (10.6%), Maroon (15.1%), and Mixed ethnicity (13.7%). Differences in five-year incidence rates for TB were significant, chi(2)(5, N = 662) = 244.42, p Conclusions: Our study has demonstrated that ethnic disparities in tuberculosis incidence exist in Suriname and that they are associated with specific, known risk factors such as HIV (especially for Creole people). For Indigenous people, risk factors may include diminished access to health care facilities and low socioeconomic status. However, direct data on these factors was unavailable. These findings call for targeted national intervention programs-with special attention given to the vulnerabilities of susceptible ethnic groups-and improved data collection