Acetato de lanreotida e acetato de octreotida de liberação prolongada para o tratamento de pacientes com sintomas associados a tumores endócrinos gastroenteropancreáticos funcionais / Lanreotide acetate and extended-release octreotide acetate for the treatment of patients with symptoms associated with functional gastroenteropancreatic endocrine tumors

INTRODUÇÃO: Os tumores neuroendócrinos (TNE) são neoplasias, com origem mais comum no trato gastrointestinal, que podem cursar com liberação de hormônios associado a sintomas, levando a síndrome carcinoide, com incidência anual estimada em 0,25/1.000.000 na Europa (ano de 2008). As manifestações clínicas mais comuns incluem diarreia secretória e rubor súbito, mas a diarreia é considerada mais debilitante com potencial risco de morte. Quando o tratamento curativo com ressecção completa não é viável pela presença de doença metastática, o tratamento é direcionado para o controle dos sintomas da síndrome carcinoide e os análogos da somatostatina (octreotida ou lanreotida) são considerados terapia de primeira linha na SC. PERGUNTAS DE PESQUISA: O acetato de octreotida de liberação prolongada (octreotida LAR) e o acetato de lanreotida de liberação prolongada (lanreotida LP) são eficazes, seguros e custo-efetivos para o tratamento dos sintomas relacionados à SC associados ao TNE gastroenteropancreático funcional em pacientes adultos? EVIDÊNCIAS CLÍNICAS: Foram selecionados três ensaios clínico

Clinicopathologic characterization and assessment of prognostic factors for intraabdominal solitary fibrous tumors involving the gastrointestinal tract and liver.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms with a potential to metastasize in 10-30% of cases. Several risk models have been designed to predict tumor behavior at the pleura and extrapleural sites. Intrabdominal SFTs primarily involving the gastrointestinal tract (SFTGI) and liver (SFTL) are rare. We analyzed a series of SFTGI and SFTL to describe the clinicopathologic features and evaluate prognostic factors. The cohort included 33 males and 25 females, with a median age of 58.5 years and a mean tumor size of 15.6 cm. Patients with SFTL were predominantly older females compared to patients with SFTGI. By univariate analysis, high mitotic count (> 4/10 HPF), tumor size, tumor necrosis, and nuclear pleomorphism were associated with both disease-specific survival (DSS) and metastasis-free survival (MFS) (p < 0.05). Tumor location (SFTL vs. SFTGI) also predicted MFS (p = 0.026). Only very high mitotic count (> 9/10 HPF) predicted local recurrence-free survival (LFS, p = 0.001). Further analysis showed that all adverse histologic parameters (necrosis, hypercellularity, pleomorphism) correlated with high mitotic grade (> 4/10 HPF) (p < 0.05). On multivariate analysis, only mitosis predicted DSS (p = 0.023), MFS (p = 0.01), and LFS (p = 0.017). Validation of the 3 risk models (mDemicco, Salas, Pasquali) showed variable associations with DSS, MFS, and LFS, while a simplied 3-tiered risk model based on mitosis (0-4, 5-9, > 9/10 HPF) performed well in predicting all risks. Our results suggest that prognostication of SFTs is mainly associated with mitotic activity, supporting the use of mitosis (> 4 and/or > 9/10 HPF) for tumor grading and risk stratification at specific locations.

Noninvasive Assessment of Acute Graft-Versus-Host Disease of the Gastrointestinal Tract After Allogeneic Hemopoietic Stem Cell Transplantation Using 18F-FDG PET.

Acute graft-versus-host disease of the gastrointestinal tract (acute GIT-GVHD) often complicates allogeneic hemopoietic stem cell transplantation (AHSCT). 18F-FDG PET/CT is known to detect active inflammation and may be a useful noninvasive test for acute GIT-GVHD. The objective of this study was to evaluate the diagnostic utility of 18F-FDG PET/CT to noninvasively assess patients with clinically suspected acute GIT-GVHD. Fifty-one AHSCT patients with clinically suspected acute GIT-GVHD prospectively underwent 18F-FDG PET/CT scanning followed by upper and lower GIT endoscopy within 7 d. Endoscopic biopsies of 4 upper GIT and 4 colonic segments were obtained for histology to compare with corresponding quantitative segmental 18F-FDG PET/CT SUVmax Receiver-operating-characteristic curve (ROC) analysis was performed to determine predictive capacity of 18F-FDG PET/CT SUVmax for acute GIT-GVHD. A separate qualitative visual 18F-FDG PET/CT analysis was also performed for comparison. Results: Twenty-three of 51 (45.1%) patients had biopsy-confirmed acute GIT-GVHD, with 19 of 23 (82.6%) having upper GIT and 22 of 22 (100%) colonic involvement. One of 23 patients did not undergo a colonoscopy. GVHD involved the entire colon contiguously in 21 of 22 patients. For quantitative analysis, histology from 4 upper GIT and 4 colonic segments were compared with 18F-FDG PET/CT SUVmax Colonic segments positive for GVHD had a higher SUVmax (4.1 [95% CI, 3.6-4.5]) than did normal colonic segments (2.3 [1.9-2.7], P = 0.006). No difference was demonstrated in upper GIT segments. Quantitative 18F-FDG PET/CT yielded a 69% sensitivity, 57% specificity, 73% negative predictive value, and 59% positive predictive value for the detection of GVHD compared with 70%, 76%, 76%, and 68%, respectively, for qualitative analysis. Conclusion: 18F-FDG PET is a useful noninvasive diagnostic test for acute GIT-GVHD, which when present always involves the colon and usually in its entirety, suggesting colonic biopsy obtained by sigmoidoscopy is adequate for histologic confirmation when acute GIT-GVHD is suspected. Of note, 18F-FDG PET cannot distinguish acute GIT-GVHD from non-GVHD inflammatory changes in the colon.

Endoscopic ultrasound fine needle biopsy was not more cost-effective than fine-needle aspiration with rapid on-site evaluation in gastrointestinal lesions diagnosis.

BACKGROUND AND AIM: Cost-effectiveness comparison between endoscopic ultrasound (EUS)-guided acquisition techniques by fine-needle aspiration (FNA) and fine needle biopsy (FNB) in gastrointestinal lesions is still scarce. EUS-FNB has been shown to be more cost-effective than EUS-FNA, however, when adding rapid on-site evaluation (ROSE) to EUS-FNA, it is unclear whether EUS-FNB remains more cost-effective. Our aim was to assess cost-efficacy of EUS-FNB as compared to EUS-FNA with ROSE in gastrointestinal lesions. METHOD: All patients who underwent EUS-FNA with ROSE or EUS-FNB at Galilee Medical Center were retrospectively reviewed. Cost-effectiveness analysis was based on the additional EUS sessions needed and on the average cost expenditure to achieve one final pathological diagnosis. RESULTS: Seventy-four cases were included in the final analysis. Of them, 21 patients (28.4%) were in the EUS-FNB group (group A), as compared to 53 patients (71.6%) who underwent EUS-FNA with ROSE (group B). Additional EUS sessions needed to achieve one final pathological diagnosis were needed in 14.3% of group A patients vs 9.4% in group B patients (P = .5). and, the average cost for achieving one final pathological diagnosis was similar in both groups (1226 ± 369$ for group A vs 1158 ± 309.6.7$ for group B, P = .2). Notably, even after analyzing pancreatic and non-pancreatic gastrointestinal lesions separately, there was no cost benefit of EUS-FNB over EUS-FNA with ROSE. CONCLUSIONS: Cost-effectiveness analysis was not different between EUS-FNB vs EUS-FNA with ROSE. Thus, the preference of one modality over the other should be based on availability and local expertise.

An assessment of potential biomarkers of environment enteropathy and its association with age and microbial infections among children in Bangladesh.

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.

Assessment of a 4-Week Starch- and Sucrose-Reduced Diet and Its Effects on Gastrointestinal Symptoms and Inflammatory Parameters among Patients with Irritable Bowel Syndrome.

Dietary advice constitutes a treatment strategy for irritable bowel syndrome (IBS). We aimed to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal symptoms in IBS patients, in relation to dietary intake and systemic inflammatory parameters. IBS patients (n = 105) were randomized to a 4-week SSRD intervention (n = 80) receiving written and verbal dietary advice focused on starch and sucrose reduction and increased intake of protein, fat and dairy, or control group (n = 25; habitual diet). At baseline and 4 weeks, blood was sampled, and participants filled out IBS-SSS, VAS-IBS, and Rome IV questionnaires and dietary registrations. C-reactive protein and cytokines TNF-α, IFN-γ, IL-6, IL-8, IL-10, and IL-18 were analyzed from plasma. At 4 weeks, the intervention group displayed lower total IBS-SSS, 'abdominal pain', 'bloating/flatulence' and 'intestinal symptoms´ influence on daily life' scores (p ≤ 0.001 for all) compared to controls, and a 74%, responder rate (RR = ΔTotal IBS-SSS ≥ -50; RRcontrols = 24%). Median values of sucrose (5.4 vs. 20 g), disaccharides (16 vs. 28 g), starch (22 vs. 82 g) and carbohydrates (88 vs. 182 g) were lower for the intervention group compared to controls (p ≤ 0.002 for all), and energy percentages (E%) of protein (21 vs. 17 E%, p = 0.006) and fat (47 vs. 38 E%, p = 0.002) were higher. Sugar-, starch- and carbohydrate-reductions correlated weakly-moderately with total IBS-SSS decrease for all participants. Inflammatory parameters were unaffected. IBS patients display high compliance to the SSRD, with improved gastrointestinal symptoms but unaltered inflammatory parameters. In conclusion, the SSRD constitutes a promising dietary treatment for IBS, but needs to be further researched and compared to established dietary treatments before it could be used in a clinical setting.

Establishment of a Novel Oral Murine Model of Ricin Intoxication and Efficacy Assessment of Ovine Ricin Antitoxins.

Ricin, produced from the castor beans of Ricinus communis, is a cytotoxin that exerts its action by inactivating ribosomes and causing cell death. Accidental (e.g., ingestion of castor beans) and/or intentional (e.g., suicide) exposure to ricin through the oral route is an area of concern from a public health perspective and no current licensed medical interventions exist to protect from the action of the toxin. Therefore, we examined the oral toxicity of ricin in Balb/C mice and developed a robust food deprivation model of ricin oral intoxication that has enabled the assessment of potential antitoxin treatments. A lethal oral dose was identified and mice were found to succumb to the toxin within 48 h of exposure. We then examined whether a despeciated ovine F(ab')2 antibody fragment, that had previously been demonstrated to protect mice from exposure to aerosolised ricin, could also protect against oral intoxication. Mice were challenged orally with an LD99 of ricin, and 89 and 44% of mice exposed to this otherwise lethal exposure survived after receiving either the parent anti-ricin IgG or F(ab')2, respectively. Combined with our previous work, these results further highlight the benefit of ovine-derived polyclonal antibody antitoxin in providing post-exposure protection against ricin intoxication.

Diagnostic disagreement between clinical standard histopathological- and retrospective assessment of histopathology-based gastrointestinal graft-versus-host disease in children.

BACKGROUND: No previous paediatric study has evaluated the frequency of diagnostic disagreement between clinical standard histopathological assessment (CSHA) and retrospective, independent, histopathological assessment (RIHA) of gastrointestinal Graft-Versus-Host Disease (GI-GVHD) METHODS: In a retrospective cohort study, based on gastrointestinal biopsies collected from allogeneic HSCT-treated children (<18 years) with symptom-based GI-GVHD, we evaluated; disagreement of histopathology-based GI-GVHD diagnosis in CSHA vs RIHA, and potential clinical consequences of differences between the assessments. The CSHA-based diagnoses were retrieved from histopathology reports. The RIHA was performed by one pathologist, blinded to the CSHA outcomes and based on the minimal criteria for histopathology-based GI-GVHD diagnosis by the NIH 2014. RESULTS: Seventy children with 92 endoscopic occasions (including 22 re-endoscopies) were enrolled. GI-GVHD was observed in 73% (67/92) of the endoscopies in the RIHA and in 54% (50/92) in the CSHA (P = .014). The RIHA confirmed 94% (47/50) with GI-GVHD and 52% (22/42) with non-GI-GVHD diagnoses, established in the CSHA. Disagreement, that is endoscopic occasions with GI-GVHD solely detected in RIHA or detection of GI-GVHD in CSHA but not in RIHA, was observed in 20/42 (48%) and 3/50 (6%), respectively (McNemar's test, P = .0008). The risk of a subsequent re-endoscopy was higher in endoscopic occasions with GI-GVHD detected in RIHA but not in CSHA vs if non-GI-GVHD were detected in both readings (P = .005). CONCLUSION: Our results suggest that in children with symptom-based GI-GVHD without histopathological confirmation in CSHA, a second, NIH 2014 based histopathological assessment should be considered before performing a re-endoscopy.

Cost and logistics implications of a nationwide survey of schistosomiasis and other intestinal helminthiases in Sudan: Key activities and cost components.

It is vital to share details of concrete experiences of conducting a nationwide disease survey. By doing so, the global health community could adapt previous experiences to expand geographic mapping programs, eventually contributing to the development of disease control and elimination strategies. A nationwide survey of schistosomiasis and intestinal helminthiases was conducted from December 2016 to March 2017 in Sudan. We aimed to describe details of the key activities and cost components required for the nationwide survey. We investigated which activities were necessary to prepare and conduct a nationwide survey of schistosomiasis and intestinal helminthiases, and the types and amounts of transportation, personnel, survey equipment, and consumables that were required. In addition, we estimated financial and economic costs from the perspectives of the donor and the Ministry of Health. Cash expenditures incurred to implement the survey were defined as financial costs. For economic costs, we considered the true value for society as a whole, and this category therefore accounted for the costs of all goods and services used for the project, including those that were not sold in the market and therefore had no market price (e.g., time spent by head teachers and teachers). We organized costs into capital and recurrent items. We ran one-way sensitivity and probabilistic analyses using Monte-Carlo methods with 10,000 draws to examine the robustness of the primary analysis results. A total of USD 1,465,902 and USD 1,516,238 was incurred for the financial and economic costs, respectively. The key cost drivers of the nationwide survey were personnel and transportation, for both financial and economic costs. Personnel and transportation accounted for around 64% and 18% of financial costs, respectively. If a government finds a way to mobilize existing government officials with no additional payments using the health system already in place, the cost of a nationwide survey could be remarkably reduced.

Systemic lupus erythematosus gastrointestinal involvement: a computed tomography-based assessment.

Systemic lupus erythematosus (SLE) gastrointestinal (GI) complication is characterized by multi-segment and multi-compartment involvement. The aim of this study is to develop a computed tomography (CT) image-based system for disease evaluation. SLE patients with GI involvement from two independent cohorts were retrospectively included. Baseline abdominal CT scan with intravenous and oral contrast was obtained from each individual. A CT scoring system incorporating the extent of GI tract involvement and intestinal wall thickness, along with extra-GI compartment involvement, was developed and validated. The outcome measurement was the time to GI functional recovery, defined as the time to tolerable per os (PO) intake ≥50% of ideal calories (PO50). A total of 54 and 37 patients with SLE GI involvement were enrolled in the derivation and validation cohorts, respectively. The CT scores for SLE GI involvement were positively correlated with patients' time to PO50 (r = 0.57, p < 0.0001, derivation cohort; r = 0.42, p = 0.0093, validation cohort). Patients with a CT score ≤ 3 had a shorter time to PO50 (median time of 0 day) in pooled cohort, whereas those with a CT score > 3 incurred a significantly prolonged recovery with a median time to PO50 of 13 days (p < 0.0001). The CT-based scoring system may facilitate more accurate assessment and individualized management of SLE patients with GI involvement.

Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review.

Endoscopic resection (ER) allows optimal staging with potential cure of early-stage luminal malignancies while maintaining organ preservation. ER and surgery are non-competing but complementary therapeutic options. In addition, histological examination of ER specimens can either confirm or refine the pre-procedure diagnosis. ER is used for the treatment of Barrett's related early carcinomas and dysplasias, early-esophageal squamous cell carcinomas and dysplasias, early gastric carcinomas and dysplasia, as well as low-risk submucosal invasive carcinomas (LR-SMIC) and, large laterally spreading adenomas of the colon. For invasive lesions, histological risk factors predict risk of lymph node metastasis and residual disease at the ER site. Important pathological risk factors predictive of lymph node metastasis are depth of tumor invasion, poor differentiation, and lymphovascular invasion. Complete resection with negative margins is critical to avoid local recurrences. For non-invasive lesions, complete resection is curative. Therefore, a systematic approach for handling and assessing ER specimens is recommended to evaluate all above key prognostic features appropriately. Correct handling starts with pinning the specimen before fixation, meticulous macroscopic assessment with orientation of appropriate margins, systematic sectioning, and microscopic assessment of the entire specimen. Microscopic examination should be thorough for accurate assessment of all pathological risk factors and margin assessment. Site-specific issues such as duplication of muscularis mucosa of the esophagus, challenges of assessing ampullectomy specimens and site-specific differences of staging of early carcinomas throughout the gastrointestinal tract (GI) tract should be given special consideration. Finally, a standard, comprehensive pathology report that allows optimal staging with potential cure of early-stage malignancies or better stratification and guidance for additional treatment should be provided.

Pharmacokinetic/pharmacodynamic assessment of a novel, pharmaceutical lipid-aspirin complex: results of a randomized, crossover, bioequivalence study.

Aspirin (acetylsalicylic acid, ASA) can lead to gastrointestinal mucosal injury through disruption of its protective phospholipid bilayer. A liquid formulation of a novel pharmaceutical lipid-aspirin complex (PL-ASA) was designed to prevent this disruption. We sought to determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of PL-ASA compared with immediate release aspirin (IR-ASA). In this active-control crossover study, 32 healthy volunteers were randomized to receive 1 of 2 dose levels (a single dose of 325 mg or 650 mg) of either PL-ASA or IR-ASA. After a 2-week washout period between treatment assignments, subjects received a single dose of the alternative treatment, at the same dose level. The primary objectives of the study were to assess, for PL-ASA and IR-ASA at 325 mg and 650 mg dose levels, PK and PD bioequivalence, and safety, over a 24-h period after administration of both drugs. PK parameters were similar for PL-ASA and IR-ASA, and met FDA-criteria for bioequivalence. Regarding PD, both drugs also showed Cmin TxB2 values below 3.1 ng/mL (cut-off associated with decreased cardiovascular events) and > 99% inhibition of serum TxB2 ( ≥ 95% inhibition represents the cut-off for aspirin responders) along with similar results in several secondary PK/PD parameters. There were no serious adverse events or changes from baseline in vital signs or laboratory values in either of the 2 treatment groups. PL-ASA's novel liquid formulation has similar PK and PD performance compared with IR-ASA, supporting functional and clinical equivalence. These data coupled with the improved gastric safety of PL-ASA suggest that this novel formulation may exhibit an improved benefit-risk profile, warranting evaluation in future trials.Clinical trial registration: http://www.clinicaltrials.gov . Unique Identifier: NCT04008979.

Prognosis assessment in metastatic gastrointestinal stromal tumors treated with tyrosine kinase inhibitors based on CT-texture analysis.

PURPOSE: Identification of prognostic CT-textural features in patients with gastrointestinal stromal tumors undergoing tyrosine kinase inhibitor (TKI) therapy. METHODS AND MATERIALS: We identified 25 GIST patients (mean age, 70.58 ± 9.7 years; range, 41.25-84.08 years; 20 males, 5 females) with a total of 123 scans, each examined with a standardized CT protocol between 1/2014-7/2018. 92 texture features, based on pyradiomics library, were extracted and correlated to response categories; evaluated with help of modified Choi criteria. All patients underwent therapy with imatinib in the first line and different tyrosine kinase inhibitors after disease progression. KIT and PDGFR-mutations were registered in all patients as well as the number of previous treatment regimens, patient's age as well as gender and the presence of contrast enhancement (vitality) in tumor. The lesion with the largest diameter was chosen and contoured using the spherical VOI tool. Inter-rater testing was performed by a second experienced radiologist. Regression and AUC analysis was performed. RESULTS: Ten variables could be confirmed to be significantly associated with disease progression. Of them, four textural parameters were significantly positively associated with disease progression and negatively with progression free survival (Glcm Id [grey-level co-occurrence matrix inverse difference], p = 0.012, HR 3.83; 95% CI 1.697-8.611, Glcm Idn [grey-level co-occurrence matrix inverse difference normalized], p = 0.045, HR 2.06, 95% CI 1.015-4.185, Glrlm [grey-level run length matrix] normalized, p = 0.005, HR 3.181; 95% CI 1.418-7.138 and Ngtdm [neighboring grey-tone difference matrix] coarseness, p < 0.001, HR 3.156, 95% CI 1.554-6.411). Single variables were shown to be significantly inferior to the combination of all variables. After 6 months, 90% of patients with 0-1 risk factors (group 1), 64.4% with 2-3 risk variables and 38.1% of patients presenting > 3 structural risk variables showed stable disease. Gclm Id, Gclm Idn and Glrlm non-uniformity were associated with the number of previous treatments, Glrlm non-uniformity also with tumor vitality (enhancement), whereas Gclm Idn and Ngtdm coarseness were associated with the number of tumor mutations. CONCLUSION: Some of the CT-textural features correlate with disease progression and the progressive free survival as well as with the number of gene mutations and the number of treatment regimens the patients were exposed to as well as with the tumor enhancement. All these features reflect tumor homogeneity.

Usefulness of Strain Elastography, ARFI Imaging, and Point Shear Wave Elastography for the Assessment of Crohn Disease Strictures.

OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of strain elastography, acoustic radiation force impulse (ARFI) imaging and point shear wave elastography (p-SWE) for assessment of the predominant types of intestinal stenosis in Crohn disease. METHODS: Twenty-five patients were enrolled in this study, among whom 25 suspicious stenoses in 25 intestinal segments were studied using gray scale ultrasonography. All 3 elastography methods were performed, and all patients underwent endoscopy within 24 hours with pathologic biopsy. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), Youden index, and area under the receiver operating characteristic curve (AUROC) were calculated. Pathologic findings were regarded as the gold standard. RESULTS: For SE, the optimal cutoff value was a score of 4 or greater (sensitivity, 75%; specificity, 66.7%; accuracy, 68%; PPV, 30%; NPV, 93.3%; AUROC, 0.708; however, P > .05). The results of ARFI imaging were similar: the optimal cutoff value was a score of 4 or greater (sensitivity, 50%; specificity, 81%; accuracy, 76%; PPV, 33.3%; NPV, 89.4%; AUROC, 0.669; P < .05). However, for p-SWE, the optimal cutoff value was reached when the shear wave velocity exceeded 2.73 m/s (sensitivity, 75%; specificity, 100%; accuracy, 96%; PPV, 100%; NPV, 95.5%; AUROC, 0.833; P < .05). CONCLUSIONS: p-SWE had the best performance for evaluating and differentiating intestinal stenosis in Crohn disease, while neither SE nor ARFI imaging achieved satisfactory outcomes for evaluating inflammatory stenosis and fibrotic stenosis of Crohn disease.

Insecticide activity of Curcuma longa (leaves) essential oil and its major compound α-phellandrene against Lucilia cuprina larvae (Diptera: Calliphoridae): Histological and ultrastructural biomarkers assessment.

Lucilia cuprina, known as the Australian blowfly, is of high medico-sanitary and veterinary importance due to its ability to induce myiasis. Synthetic products are the most frequent form of fly control, but their indiscriminate use has selected for resistant populations and accounted for high levels of residues in animal products. This study aimed to assess the effect of essential oil from leaves of Curcuma longa (CLLEO), and its major compound α-phellandrene against L. cuprina L3. An additional goal was to determine the morphological alterations in target organs/tissues through ultrastructural assessment (SEM) and light microscopy, as well as macroscopic damage to cuticle induced by CLLEO. Groups of 20 L3 were placed on filter paper impregnated with increasing concentrations of CLLEO (0.15 to 2.86 µL/cm2) and α-phellandrene (0.29 to 1.47 µL/cm2). Efficacy was determined by quantifying L3 mortality 6, 24 and 48 h after contact with CLLEO and by measuring the structural damage to L3. CLLEO and α-phellandrene inhibited adult emergence by 96.22 and 100%, respectively. Macroscopic cuticle damage, appeared as diffuse pigment and darkening of larval body, was caused by both extracts. The SEM revealed dryness on the cuticle surface, distortion of the sensorial structures and general degeneration in treated L3. Furthermore, alterations in target organs (digestive tract, fat body and brain) were noticed and shall be used as biomarkers in future attempts to elucidate the mechanism of action of these compounds. The vacuolar degeneration and pyknotic profiles observed in the brain tissue of treated larvae with both extracts and the decreased motility within <6 h after treatment leads us to suggest a neurotoxic activity of the products. This work demonstrates the potential use of CLLEO and α-phellandrene as bioinsecticides to be used against L. cuprina, representing an ecofriendly alternative for myiasis control in humans and animals.

Defining outcomes following congenital diaphragmatic hernia using standardised clinical assessment and management plan (SCAMP) methodology within the CDH EURO consortium.

Treatment modalities for neonates born with congenital diaphragmatic hernia (CDH) have greatly improved in recent times with a concomitant increase in survival. In 2008, CDH EURO consortium, a collaboration of a large volume of CDH centers in Western Europe, was established with a goal to standardize management and facilitate multicenter research. However, limited knowledge on long-term outcomes restricts the identification of optimal care pathways for CDH survivors in adolescence and adulthood. This review aimed to evaluate the current practice of long-term follow-up within the CDH EURO consortium centers, and to review the literature on long-term outcomes published from 2000 onward. Apart from having disease-specific morbidities, children with CDH are at risk for impaired neurodevelopmental problems and failure of educational attainments which may affect participation in society and the quality of life in later years. Thus, there is every reason to offer them long-term multidisciplinary follow-up programs. We discuss a proposed collaborative project using standardized clinical assessment and management plan (SCAMP) methodology to obtain uniform and standardized follow-up of CDH patients at an international level.

High-dose acute exposure of paraquat induces injuries of swim bladder, gastrointestinal tract and liver via neutrophil-mediated ROS in zebrafish and their relevance for human health risk assessment.

The exact toxicological mechanisms of paraquat (PQ) poisoning are not entirely clear, especially on the high-level acute exposure. To assess the health risk of PQ, especially to suicidal individuals, accidental ingestion eaters, occupational groups, and special multitude, firstly we explored the acute toxic effect and the possible mechanisms of high-level exposure of PQ using zebrafish. The mainly target organs of PQ were swim bladder which is the homolog of the mammalian lung, followed by gastrointestinal tract and liver. Morphological malformations which were further defined by histopathologic examination include smaller size, fibrosis and inflammatory cell invasion for swim bladder; irregularly arranged or dissolved epithelial folds, loss of villous architecture, and ecclasis of mucosal cells in a smaller lumen for gastrointestinal tract; as well as smaller size, degeneration, fibrous proliferation, atrophy for liver. In addition, PQ enhanced leukocyte recruitment (neutrophil migrated first, followed by macrophage) into swim bladder and induced ROS which can be scavenged by glutathione. Moreover, qRT-PCR results showed that PQ increased the expression level of genes involved in the inflammatory response, such as L-1ß, IL-6, IL-8, TNF-α, TNF-ß, IFN-1, TGF-ß, and NF-kB. For the first time, our results demonstrated that acute exposure of PQ induced pulmonary toxicity which was followed by gastrointestinal and hepatic toxicity via neutrophil-mediated ROS in zebrafish. In summary, these findings generated here will contribute to our better understanding of characteristics of PQ acute poisoning and can provide valuable information on better PQ poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.

Differentiating breast carcinoma with signet ring features from gastrointestinal signet ring carcinoma: assessment of immunohistochemical markers.

Signet ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with Signet ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing Signet ring features were reviewed. Non-mammary and non-gastrointestinal tumors with this morphology were included for comparison. Estrogen receptor (ER), progesterone receptor (PR), E-cadherin, CK7, CK20, GCDFP-15, mammaglobin, CDX2, GATA-3, and HepPar-1 immunohistochemistry was performed. Expression patterns were compared between breast and gastrointestinal tumors as well as lobular breast and gastric tumors. Ninety-three cases were identified: 33 breast carcinomas including 13 lobular, 50 gastrointestinal tumors including 23 gastric, and 10 from other sites. ER (sensitivity=81.8%, specificity=100%, positive predictive value (PPV)=100%, negative predictive value (NPV)=89.3%) and GATA-3 (sensitivity=100%, specificity=98%, PPV=96.8%, NPV=100%) expression were associated with breast origin. CK20 (sensitivity=66.7%, specificity=93.3%, PPV=94.1%, NPV=63.6%) and CDX2 (sensitivity=72%, specificity=100%, PPV=100%, NPV=68.9%) demonstrated the strongest discriminatory value for gastrointestinal origin. These markers exhibited similar discriminatory characteristics when comparing lobular and gastric signet ring carcinomas. In a limited trial on metastatic breast and gastric cases, these markers successfully discriminated between breast and gastric primary sites in 15 of 16 cases. ER and GATA-3 are most supportive of mammary origin and constitute an effective panel for distinguishing primary breast from primary gastrointestinal Signet ring tumors when combined with CK20 and CDX2 immunohistochemistry.

Toxicity assessment of ZnO-decorated Au nanoparticles in the Mediterranean clam Ruditapes decussatus.

The synthesis of hybrid nanomaterials has greatly increased in recent years due to their special physical and chemical properties. However, information regarding the environmental toxicity associated with these chemicals is limited, in particular in the aquatic environment. In the present study, an experiment was performed in which the marine bivalve (Ruditapes decussatus) was exposed for 14days to 2 concentrations of zinc oxide-decorated Au nanoparticles (Au-ZnONPs: Au-ZnONP50=50µg/L; Au-ZnONP100=100µg/L). The stability and resistance of Au-ZnONPs in the natural seawater were assessed by combining transmission electron microscopy and dynamic light scattering. Inductively coupled plasma-atomic emission spectroscopy revealed uptake of these nanoparticles within clams and their ability to induce metallic deregulation. The results obtained indicate that Au-ZnONPs induce biochemical and histological alterations within either the digestive gland or gill tissues at high concentration. This was deduced from the significant increase in H2O2 level, superoxide dismutase and catalase activities and malondialdehyde content. Furthermore, the toxicity of Au-ZnO nanoparticles was linked with the increase of intracellular iron and calcium levels in both tissues. Histological alterations in gill and digestive gland were more pronounced with Au-ZnONP100 and this is likely related to oxidative mechanisms. Gill and digestive gland are differentially sensitive to Au-ZnONPs if the exposure concentration is higher than 50µg/L. In conclusion, the parameters considered here could constitute reliable biomarkers for evaluation of hybrid nanoparticles toxicity in environmental model organisms. In addition, based on the results obtained, gill and digestive gland of R. decussatus could be proposed as models to detect harmful effects of hybrid nanoparticles.

Evaluation of the Relationships Between Computed Tomography Features, Pathological Findings, and Prognostic Risk Assessment in Gastrointestinal Stromal Tumors.

OBJECTIVES: The aim of this study was to correlate computed tomography (CT) findings with pathology in gastrointestinal stromal tumors (GISTs). METHODS: A retrospective evaluation of CT images of 44 patients with GISTs was performed. Computed tomography findings analyzed were location, size, margins, degree and pattern of contrast enhancement, angiogenesis, necrosis, signs of invasion, peritoneal effusion, peritoneal implants, surface ulceration, and calcifications.Associations between CT features and mitotic rate, Miettinen classes of risk, lesions size, and among CT features were investigated. χ Test and Fisher test were performed. RESULTS: Mitotic rate was associated with margins (P = 0.016) and with adjacent organ invasion (P = 0.043). Pattern of contrast enhancement (P = 0.002), angiogenesis (P = 0.006), necrosis (P = 0.006), invasion of adjacent organs (P = 0.011), and margins (P = 0.006) were associated with classes of risk. Several associations (P < 0.05) between lesion size and CT features and among all the investigated CT features were found. CONCLUSIONS: Computed tomography features could reflect GIST biology being associated with the mitotic rate and with classes of risk.