Immunohistochemical/histochemical double staining method in the study of columnar metaplasia of the oesophagus

Intestinal metaplasia in Barrett\u2019s oesopha- gus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotyp- ic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metapla- sia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the his- tochemical features in cells that shows an aber- rant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53, both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These find- ings suggest that some immunophenotypic changes are present in CLO and they can pre- cede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition charac- terized by any extention of columnar epitheli- um. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology

Functionalized carbon nanostructures versus drug resistance: Promising scenarios in cancer treatment

Carbon nanostructures (CN) are emerging valuable materials for the assembly of highly engineered multifunctional nanovehicles for cancer therapy, in particular for counteracting the insurgence of multi-drug resistance (MDR). In this regard, carbon nanotubes (CNT), graphene oxide (GO), and fullerenes (F) have been proposed as promising materials due to their superior physical, chemical, and biological features. The possibility to easily modify their surface, conferring tailored properties, allows different CN derivatives to be synthesized. Although many studies have explored this topic, a comprehensive review evaluating the beneficial use of functionalized CNT vs G or F is still missing. Within this paper, the most relevant examples of CN-based nanosystems proposed for MDR reversal are reviewed, taking into consideration the functionalization routes, as well as the biological mechanisms involved and the possible toxicity concerns. The main aim is to understand which functional CN represents the most promising strategy to be further investigated for overcoming MDR in cancer

Alginate bioconjugate and graphene oxide in multifunctional hydrogels for versatile biomedical applications

In this work, we combined electrically-conductive graphene oxide and a sodium alginatecaffeic acid conjugate, acting as a functional element, in an acrylate hydrogel network to obtain multifunctional materials designed to perform multiple tasks in biomedical research. The hybrid material was found to be well tolerated by human fibroblast lung cells (MRC-5) (viability higher than 94%) and able to modify its swelling properties upon application of an external electric field. Release experiments performed using lysozyme as the model drug, showed a pH and electro-responsive behavior, with higher release amounts and rated in physiological vs. acidic pH. Finally, the retainment of the antioxidant properties of caffeic acid upon conjugation and polymerization processes (Trolox equivalent antioxidant capacity values of 1.77 and 1.48, respectively) was used to quench the effect of hydrogen peroxide in a hydrogel-assisted lysozyme crystallization procedure

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

none16noGenetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/ normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/ metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.openCabibi D.; Caruso S.; Bazan V.; Castiglia M.; Bronte G.; Ingrao S.; Fanale D.; Cangemi A.; Calo V.; Listi A.; Incorvaia L.; Galvano A.; Pantuso G.; Fiorentino E.; Castorina S.; Russo A.Cabibi, D.; Caruso, S.; Bazan, V.; Castiglia, M.; Bronte, G.; Ingrao, S.; Fanale, D.; Cangemi, A.; Calo, V.; Listi, A.; Incorvaia, L.; Galvano, A.; Pantuso, G.; Fiorentino, E.; Castorina, S.; Russo, A

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p < 0.001). Notably, among 18 relapsed patients with 557 and/or 558 deletion or deletion/insertion, 14 patients (77.8%) harbored deletions simultaneously involving 557 and 558 codons, while only 4 patients (22.2%) harbored deletions involving only 1 of the 557/558 codons. Thus, when 557 or 558 deletions occurred separately, the tumor showed a prognostic behavior similar to the GIST carrying deletions outside the 557/558 position. Remarkably, patients with GISTs stratified as intermediate risk, but carrying the 557/558 deletion, showed a similar outcome to the high-risk patients with tumors harboring deletions in codons other than 557/558, or duplication/insertion/SNV. Conclusion: Our data support the inclusion of the PV type and codon location in routine risk prediction models, and suggest that intermediate-risk patients whose GISTs harbor 557/558 deletions may also need to be treated with adjuvant imatinib like the high-risk patients

Numerical modeling of the thermal contact in metal forming processes

Heat flow across the interface of solid bodies in contact is an important aspect in several engineering applications. This work presents a finite element model for the analysis of thermal contact, which takes into account the effect of contact pressure and gap dimension in the heat flow across the interface between two bodies. Additionally, the frictional heat generation is also addressed, which is dictated by the contact forces predicted by the mechanical problem. The frictional contact problem and thermal problem are formulated in the frame of the finite element method. A new law is proposed to define the interfacial heat transfer coefficient (IHTC) as a function of the contact pressure and gap distance, enabling a smooth transition between two contact status (gap and contact). The staggered scheme used as coupling strategy to solve the thermomechanical problem is briefly presented. Four numerical examples are presented to validate the finite element model and highlight the importance of the proposed law on the predicted temperature.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under the project PTDC/EMS-TEC/1805/2012 and by FEDER funds through the program COMPETE Programa Operacional Factores de Competitividade, under the project CENTRO-07-0224- FEDER-002001 (MT4MOBI). The second author is also grateful to the FCT for the postdoctoral grant SFRH/BPD/101334/2014. The authors would like to thank Prof. A. Andrade-Campos for helpful contributions on the development of the finite element code presented in this work.info:eu-repo/semantics/publishedVersio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Comentarios sobre algunas herramientas utilizadas en la resolución de problemas no-lineales de mecánica del continuo

In this paper we try to put in the simple mathematical level of tensor calculus developments of differential manifold analysis that allow to formulate in a systematic way the solution of nonlinear Continuum Mechanics problem

CLINICAL ROLE OF GASLESS LAPAROSCOPIC ADRENALECTOMY

BACKGROUND: Several studies have demonstrated that the pneumoperitoneum (PNP) may have several hemodynamic, metabolic, neurologic, and humoral effects; in a limited number of patients, these effects represent a contraindication to the use of the PNP in the presence of glaucoma, cardiovascular insufficiency, advanced chronic obstructive bronchitis, and neurologic disease. PATIENTS AND METHODS: Between May 2002 and July 2008, we performed 9 laparoscopic gasless adrenalectomies in 8 patients (5 male and 3 female): 4 left, 3 right, and 1 bilateral, treated in 2 different operations. Mean age was 54.8 years (range: 34 to 76 y). Preoperative diagnosis was Cushing in 5 cases, pheochromocytoma in 1 case, incidentaloma in 1 case, and Conn in 2 cases. Postoperative histologic findings were cortical adenoma in 6 cases, pheochromocytoma in 1 case, and cortical hyperplasia in 2 cases. Contraindication to PNP were vascular endocranicanic malformation, acute glaucoma, history of vascular cerebral accident and hypertensive retinopathy, and recent neurosurgical intervention. We performed laparoscopic adrenalectomy in lateral flank position, using the LaparoTenser, an abdominal wall retractor, with 2 curved needles (Aghi Pluriplan) placed in the subcutaneous tissue of the anterolateral abdominal wall that allows low-pressure PNP offering a better view without negative effects of intra-abdominal pressure. RESULTS: The mean operative time was 73 minutes (range: 45 to 120 min): left average 71.2 minutes, right average 75.0 minutes. The mean postoperative hospital stay was 3.38 days (range: 3 to 5 d). There was no conversion to open surgery. There were no intraoperative or postoperative complications. All patients are alive and there were no recurrences. CONCLUSIONS: The gasless technique is a valid alternative to PNP when patients present a contraindication to the PNP, as it makes it possible to avoid the risks of intra-abdominal pressure and to conserve the advantages of a mini-invasive access