Exactitud diagnóstica en el cáncer de esófago localizado. Estudio observacional retrospectivo.

OBJECTIVE: To assess the accuracy of the diagnostic tests for a correct clinical tumor staging in localized esophageal cancer (EC). METHOD: Retrospective observational study of patients who underwent esophagectomy for cancer in a referral hospital between January 2003 and September 2019. Those patients who received neoadjuvant treatment were excluded in order to avoid bias from downstaging effects. The preoperative stage was compared with the pathological stage of the surgical specimen. Computed tomography (CT) , endoscopic ultrasound (EUS) and positron emission tomography (PET) were evaluated. The pT stage was correlated with the tumor length described in the esophagram (EG). RESULTS: Among the 63 patients included, the clinical staging was correct in 16 (global accuracy 25.4%), it was overstaged in 21 (33.2%) and understaged in 26 (41.3%). For cT staging, the accuracy of EUS was higher than that of CT (46.6% and 34.9%, respectively), specially for early stages. EG tumor length correlated with pT stage (p < 0.05). For cN staging, PET had the highest sensitivity (50.0%) and negative predictive value (75.0%). CONCLUSIONS: Despite the multiple diagnostic tools used, the global accuracy of clinical staging in localized EC is still a challenge. The lack of a test that stands out significantly from the others reinforces the need to use them in a complementary way.

OBJETIVO: Evaluar la exactitud diagnóstica para el estadiaje clínico del cáncer de esófago (CE) localizado. MÉTODO: Estudio observacional retrospectivo de los pacientes esofagectomizados por CE en un hospital de referencia entre enero de 2003 y septiembre de 2019. Se excluyeron aquellos que recibieron neoadyuvancia para evitar sesgos de infraestadiaje. Se comparó el estadio preoperatorio con el estadio patológico de la pieza quirúrgica. Se evaluaron la tomografía computarizada (TC), la ecoendoscopia (EUS) y la tomografía por emisión de positrones (PET). El estadio pT se correlacionó con la longitud tumoral descrita en el esofagograma (EG). RESULTADOS: De los 63 pacientes incluidos, el estadiaje clínico fue correcto en 16 (exactitud 25.4%), con sobreestadiaje en 21 (33.2%) e infraestadiaje en 26 (41.3%). Para el estadiaje cT, la EUS fue superior a la TC (exactitud 46.6% y 34.9%, respectivamente), en especial para estadios precoces. La longitud tumoral del EG se correlacionó con el estadio pT (p < 0.05). Para el estadiaje cN, la PET tuvo la mayor sensibilidad (50.0%) y el mayor valor predictivo negativo (75.0%). CONCLUSIONES: A pesar de las múltiples herramientas diagnósticas empleadas, la exactitud diagnóstica en el CE localizado es limitada. La ausencia de una prueba que destaque de manera significativa refuerza la necesidad de emplearlas de forma complementaria.

Diagnóstico inesperado en paciente con sospecha de GIST: infiltración gástrica por mieloma múltiple.

El mieloma múltiple se caracteriza por la proliferación neoplásica medular de células plasmáticas productoras de inmunoglobulina monoclonal. Un porcentaje pequeño de pacientes presenta compromiso extramedular en forma de plasmocitoma, siendo la localización más habitual las vías respiratorias altas. La afectación gastrointestinal es rara y la clínica asociada dependerá de la localización, la extensión y el mecanismo de infiltración. La afectación gástrica en forma de tumoración tiene un aspecto y una sintomatología similares a los de otras lesiones, por lo que es necesario realizar un diagnóstico histológico para un adecuado tratamiento. A continuación se presenta el caso de un mieloma múltiple con afectación gástrica.Multiple myeloma is characterized by medullary neoplastic proliferation of plasma cells producing monoclonal immunoglobulin. A small percentage of patients have extramedullary involvement in form of plasmacytoma, the most common location being the upper respiratory tract. Gastrointestinal involvement is rare and the associated symptoms will depend on the location, extent and mechanism of infiltration. Gastric involvement presents an appearance and symptoms similar to other lesions, so a histological diagnosis is necessary for proper treatment. This article presents the case of multiple myeloma with gastric involvement.

Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats.

Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100µg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney-injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL-1ß and TNF-α, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection.

Comparative antioxidant capacities of quercetin and butylated hydroxyanisole in cholesterol-modified erythrocytes damaged by tert-butylhydroperoxide.

Phenolic compounds are potent antioxidants that scavenge reactive oxygen species (ROS), protecting the cells against oxidative damage. Their antioxidant capacities are governed by their structural features and the nature and physical state of the cell membrane. Our study compares the protective effects of butylated hydroxyanisole (BHA) and quercetin against the cellular injury induced by oxidative stress, and the influence of membrane cholesterol contents in their antioxidant capacities, analyzing the structural changes and cellular stability of native and cholesterol-modified erythrocytes exposed to tert-butylhydroperoxide in presence of each antioxidant. The data provide clear evidence that BHA affords better protection than quercetin against ROS generation, lipid peroxidation and lipid and GSH losses in oxidized erythrocytes. However, cellular integrity and stability are better protected by quercetin owing to the hemolytic effect of BHA. Both antioxidants suppress the alterations in membrane fluidity with similar efficiency, reducing methemoglobin formation in all oxidized erythrocytes. Membrane cholesterol depletion decreases the protection against the oxidative damage provided by both antioxidants. This lower preservation may be due to low antioxidant contents, a lower antioxidant capacity, or even to an increased oxidative damage in this membrane type as a consequence of environment modifications after cholesterol depletion.

Evaluation of nitazoxanide for the treatment of disseminated cystic echinococcosis: report of five cases and literature review.

We aimed to evaluate the effectiveness of nitazoxanide in disseminated cystic echinococcosis (DCE) that failed to respond to surgical and antiparasitic therapy. We report on seven patients (five of them with bony involvement): two cases from the literature and five patients who were included in a compassionate trial of nitazoxanide therapy in our hospital. Median follow-up time until nitazoxanide therapy was 12 years and all patients had received prior medical treatment and extensive surgery. Nitazoxanide (500 mg/12 h) in combination with albendazole, with/without praziquantel, was administered for 3-24 months. Three patients improved: one with muscle involvement (clinico-radiological response), one with lung involvement (radiological response), and another with soft tissue and bony involvement (clinico-radiological response of soft tissue cysts). There was one discontinuation after 15 days of starting therapy. Nitazoxanide combination therapy could have a role in the treatment of DCE when there is no bony involvement. Long-term safety profile seems to be favorable.

Alterations in erythrocyte membrane protein composition in advanced non-small cell lung cancer.

Cancer can be associated with hematological complications related to red blood cell (RBC) function, whose physiological roles have now been expanded since it is now known that RBC are also signalling cells. The aim of this study was to explore the alterations occurring in the protein composition of RBC in advanced non-small cell lung cancer (NSCLC). Blood samples from 21 patients with advanced (stages III-IV) NSCLC (16 squamous cell carcinomas and 5 adenocarcinomas), and from 21 healthy volunteers were used. Samples from 6 randomly selected patients and 6 controls were used for the screening of erythrocyte ghost alterations by Differential Scanning Calorimetry (DSC). Samples from 15 patients and 15 controls, different from those used in the DSC measurements, were randomly selected for analysis of the expression of glycophorin (GP) species, band 3, and glycoproteins by SDS-PAGE and Western blotting or lectin enzyme immunoassays. Additionally, 5 patients with chronic obstructive pulmonary disease (COPD) were used as a control group representative of a benign inflammatory disease. Blood samples from the COPD patients were used to analyze the expression of GPs, band 3 and syaloglycoproteins. We observed the following in NSCLC: (a) changes in GP expression levels, mainly decreases in the GPA and GPC monomers, and in the GPAB dimers; (b) a decrease in the band 3 protein level, and (c) alterations in the expression of different sialoglycoproteins. RBC from the COPD patients also showed protein abnormalities, some of them, especially at the level of band 3 and the syaloglycoproteins, being similar to those in NSCLC.

Membrane cholesterol contents influence the protective effects of quercetin and rutin in erythrocytes damaged by oxidative stress.

Flavonoids are potent scavengers of reactive oxygen species (ROS) that effectively prevent erythrocyte oxidation. Their antioxidant activities are governed by their structural characteristics and their ability to interact with and penetrate lipid bilayers. In order to gain a better understanding of the relationship between cholesterol contents and the antioxidant effectiveness of flavonoids against oxidative damage induced by ROS in cells, here we analyzed the integrity and structural stability of cholesterol-modified (enriched or depleted) and control erythrocytes exposed to tert-butyl hydroperoxide in the presence of quercetin or rutin. In control and cholesterol-enriched erythrocytes, quercetin provided greater protection against lipid peroxidation, ROS formation, and it preserved better cellular integrity than rutin. Both antioxidants suppressed the alterations in membrane fluidity and lipid losses with similar efficiency, reducing hemoglobin oxidation by 30% and GSH losses by 60% in the above-mentioned erythrocytes. Cholesterol depletion reduced the efficiency of the antioxidant power of both flavonoids against oxidative damage induced in the erythrocyte membrane, while a stronger degree of protection of GSH and hemoglobin contents was observed, mainly in the presence of rutin. These findings suggest a preferential incorporation of the antioxidants into the membranes from erythrocytes with normal and high cholesterol contents, whereas they would mainly be located in the cytoplasm of cholesterol-depleted erythrocytes.

Structural characteristics of a lipid peroxidation product, trans-2-nonenal, that favour inhibition of membrane-associated phosphotyrosine phosphatase activity.

Protein-tyrosine phosphatases (PTPs) are very susceptible to oxidation by reactive oxygen species (ROS), which induce the oxidation of catalytic cysteines, thereby inactivating these PTPs. PTPs are also inactivated by treatment with different aldehydes (such as trans-2-nonenal), produced after tissue damage by ROS. However, the molecular mechanisms behind such aldehyde-due inactivation remain unknown. Using commercially available compounds, we examined the structural characteristics of trans-2-nonenal that allow the inhibition of platelet membrane-associated PTP activity, as well as how these compounds affect the dynamics of SH-, CO- and NH2- protein groups on the membranes. PTP was effectively inhibited by physiological amounts of trans-2-nonenal (1-10 microM). Incubation with trans-2-nonene (10 microM) also decreased PTP activity, although to a lower extent. Treatment with nonyl aldehyde almost eliminated PTP inhibition. Decreases in protein thiols were visible after trans-2-nonenal and trans-2-nonene treatments. Both the latter compounds also increased protein carbonyls (although trans-2-nonenal was more effective) and decreased protein amino groups to an equal extent. Collectively, our data indicate that alpha,beta unsaturation (and not a double bond in another position) is the most important structural determinant for PTP inhibition, the alkenal with 9-carbon atoms being the most effective in eliciting such inhibition. The data allow us to predict the modification of sulfhydryls and/or the formation of addition products with lysyl or histidyl residues, and hence the kind of specific antibodies that it would be necessary to generate in order to test such modifications directly.