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Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P = .027), BRCA1 (P < .001), and BRCA2 (P < .001); ATR with BRCA1 (P = .007), and ATM (P = .001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P = .010) and death (1.664 vs 0.929, P = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P = .032), and no significant correlation for the other markers. Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.

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INTRODUCTION: The advantages of single-stage treatment of cholecystocholedocholithiasis are well established, but the conditions for carrying out treatment on an outpatient basis require a review of concepts and practices of medical corporations. OBJECTIVE: To evaluate the practice of treating cholecystocholedocholithiasis by laparoendoscopy on an outpatient basis with cost analysis. METHOD: A retrospective study was conducted on patients with cholecystocholedocholithiasis treated by combined laparoscopic cholecystectomy and endoscopic choledocholithotomy from January 2015 to January 2019. After collecting data from physical and digital medical records, the patients were divided into two groups-AR (n = 42)-ambulatory regimen and HR (n = 28)-hospitalization regimen-which were compared in terms of demographic, clinical and treatment variables and their results, as well as in terms of costs. RESULTS: The mean age of the AR group was lower than that of the HR group and the physical status of the AR patients was better when assessed according to the American Society of Anesthesiologists (ASA) (p = 0.01). There was no difference between groups regarding the risk of choledocholithiasis (p = 0.99). For the AR group, the length of stay was shorter: 11.29 h × 65.21 h (p = 0.02), as was the incidence of postoperative complications assessed by applying the Clavien-Dindo classification: 3 (7.1%) × 11 (39.2%) (p < 0.01). The total mean costs were higher for the HR group (USD 2489.93) than the AR group (USD 1650.98) (p = 0.02). CONCLUSION: Outpatient treatment of cholecystocholedocholithiasis by laparoendoscopy is safe and viable for most cases, has a lower cost and can support the reorientation of training and practice of hepatobiliary surgeons.

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Roux-en-Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation ß-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered a single oral dose of 25-mg racemic carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-carvedilol were 2- to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach Cmax of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the ß-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.

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Since the incidence of gastric adenocarcinoma (GA) is high in populations living at high altitudes, we evaluated the influence of altitude on the expression of HIF-1 and survival of Ecuadorian GA patients. METHOD: 155 GA cases were studied: 56 from coastal (GAC) and 99 from mountainous regions (GAM), and 74 non-GA controls (25 coast and 49 mountain). The expression of HIF-1/HER2 was analyzed by immunohistochemistry. Analyses were performed using Fisher's exact and Breslow-Day tests for homogeneity and Kaplan-Meier curves and restricted median survival time ΔRMST. RESULTS: HIF-1 was overexpressed in normal/inflamed gastric mucosa, especially in mountainous non-GA patients (p = 0.001). There was no difference between GAC and GAM in terms of age/gender, HIF-1/HER2 expression, stage/tumor location. Median survival at 120 months was significantly higher among GAC, with a difference (ΔRMST) of 43.7 months (95% CI 29.5, 57.8) (p < 0.001) and those with positive HIF-1 expression: ΔRMST 26.6 months (95% CI 11.0, 42.1) (p < 0.001). Positive HIF-1 expression was associated with better GAM survival, with ΔRMST 33.6 months (95% CI 14.2, 52.9) (p < 0.001). CONCLUSION: Despite the limitations of this retrospective study, GA patients in the coastal region and those who expressed HIF-1 exhibited a better prognosis, but this factor was associated with better survival only in the mountain region.

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Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.

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Diagnosis and treatment of pancreatic ductal adenocarcinoma (PA) remains a challenge in clinical practice. The aim of this study was to assess the role of microRNAs (miRNAs-21, -23a, -100, -107, -181c, -210) in plasma and tissue as possible biomarkers in the diagnosis of PA. Samples of plasma (PAp-n = 13), pancreatic tumors (PAt-n = 18), peritumoral regions (PPT-n = 9) were collected from patients during the surgical procedure. The control group consisted of samples from patients submitted to pancreatic surgery for trauma or cadaveric organs (PC-n = 7) and healthy volunteers donated blood (PCp-n = 6). The expression profile of microRNAs was measured in all groups using RT-PCR, serum CA19-9 levels were determined in PA and PC. In tissue samples, there was a difference in the expression of miRNAs-21, -210 (p < 0.05) across the PAt, PC and PPT groups. The PAp showed overexpression of miRNAs-181c, -210 (p < 0.05) when compared to PCp. The combination of miRNAs-21, -210 tissue expression and serum CA19-9 showed 100% accuracy in the diagnosis of PA, as well as miR-181c expression in the plasma (PApxPCp). The expression of microRNAs in plasma proved to be a promising tool for a noninvasive detection test for PA, as well as further studies will evaluate the utility of microRNAs expression as biomarkers for prognostic and response to therapy in PA.

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OBJECTIVES: The benefits of using a fibrin sealant to reinforce the pancreaticojejunal anastomosis are still contentious, a fact that justifies the study of its effects on clinical outcomes and costs of pancreaticoduodenectomy. METHODS: Study of 62 consecutive patients submitted to pancreaticoduodenectomy, divided into two groups of 31 patients each: GWS = group with sealant and GWOS = group without sealant that were compared according to demographic, clinical, laboratory aspects, the incidence of postoperative pancreatic fistula (POPF), according to the definition of the International Study Group on Pancreatic Fistula, updated in 2016, and its postoperative complications categorized according to the Clavien classification, as well as hospital costs evaluated by the absorption costing method (with the exception of those related to medications). RESULTS: The groups were homogeneous and there were no significant differences in the postoperative clinical course or in the indicators of hospital care between them. Hard texture of pancreatic tissue was the only protective factor against the development of POPF (RR = 0.29 (95%CI:0,12-0,68); p = 0.005). Moreover, hospital costs were higher in GWS than in GWOS (p < 0.0001). CONCLUSIONS: The use of fibrin sealant to reinforce pancreaticojejunal anastomosis did not improve the clinical and healthcare outcomes and, in addition, increased hospital costs.

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BACKGROUND: Fine needle biopsy (FNB) histological samples by endoscopic ultrasound. It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. AIM: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. METHODS: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. RESULTS: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. CONCLUSIONS: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

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ABSTRACT Background: It is important to obtain representative histological samples of solid biliopancreatic lesions without a clear indication for resection. The role of new needles in such task is yet to be determined. Aim: To compare performance assessment between 20G double fine needle biopsy (FNB) and conventional 22G fine needle aspiration (FNA) needles for endoscopic ultrasound (EUS)-guided biopsy. Methods: This prospective study examined 20 patients who underwent the random puncture of solid pancreatic lesions with both needles and the analysis of tissue samples by a single pathologist. Results: The ProCore 20G FNB needle provided more adequate tissue samples (16 vs. 9, p=0.039) with better cellularity quantitative scores (11 vs. 5, p=0.002) and larger diameter of the histological sample (1.51±1.3 mm vs. 0.94±0.55 mm, p=0.032) than the 22G needle. The technical success, puncture difficulty, and sample bleeding were similar between groups. The sensitivity, specificity, and diagnostic accuracy were 88.9%, 100%, and 90% and 77.8%, 100%, and 78.9% for the 20G and 22G needles, respectively. Conclusions: The samples obtained with the ProCore 20G FNB showed better histological parameters; although there was no difference in the diagnostic performance between the two needles, these findings may improve pathologist performance.

RESUMO Racional: As lesões sólidas pancreáticas não ressecáveis cirurgicamente demandam boa amostragem tecidual para definição histológica e condução oncológica . O papel das novas agulhas de ecopunção no aprimoramento diagnóstico ainda necessita elucidação. Objetivo: Comparar as biópsias guiadas por ecoendoscoopia com a nova agulha 20G de bisel frontal duplo (FNB) com a agulha de aspiração fina 22G convencional. Métodos: Este estudo prospectivo avaliou 20 pacientes submetidos à punção de lesões pancreáticas sólidas com ambas agulhas e envolveu análise de amostras teciduais por um único patologista. Resultados: A agulha FNB 20G forneceu amostras de tecido mais adequadas (16 vs. 9, p=0,039) com melhores escores quantitativos de celularidade (11 vs. 5, p=0,002) e maior diâmetro máximo da amostra histológica (1,51±1,3 mm vs. 0,94±0,55 mm, p=0,032) que a agulha 22G. O sucesso técnico, dificuldade de punção e sangramento da amostra foram semelhantes entre os grupos. A sensibilidade, especificidade e acurácia diagnóstica foram 88,9%, 100% e 90% e 77,8%, 100% e 78,9% para as agulhas 20G e 22G, respectivamente. Conclusão: As amostras obtidas com a FNB 20G apresentaram melhores parâmetros histológicos, embora não tenha havido diferença no desempenho diagnóstico entre as duas agulhas.

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