DSpace Collection:https://hdl.handle.net/10171/189042024-03-29T13:13:54Z2024-03-29T13:13:54ZSmall bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groupshttps://hdl.handle.net/10171/678932023-11-27T06:05:39Z2020-01-01T00:00:00ZTitle: Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups
Abstract: The present evidence-based guidelines are focused on the
use of device-assisted enteroscopy in the management of
small-bowel diseases. A panel of experts selected by the
Spanish and Portuguese small bowel study groups reviewed
the available evidence focusing on the main indications of
this technique, its role in the management algorithm of each
indication and on its diagnostic and therapeutic yields. A set
of recommendations were issued accordingly.; Estas recomendações baseadas na evidência detalham o
uso da enteroscopia assistida por dispositivo no manejo
clínico das doenças do intestino delgado. Um conjunto de
Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta
técnica, o seu papel nos algoritmos de manejo de cada
indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores.2020-01-01T00:00:00ZRisk of cancer in family members of patients with lynch-like syndromehttps://hdl.handle.net/10171/678852023-11-27T06:05:46Z2020-01-01T00:00:00ZTitle: Risk of cancer in family members of patients with lynch-like syndrome
Abstract: Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC
patients develop mismatch repair deficiency without germline pathogenic mutation, known as
Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and
LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6,
and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of
pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients
diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were
calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients.
In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of
patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56–2.71),
which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67–4.90;
p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR
of LLS patients (SIR, 2.04; 95% CI, 1.44–2.80) but was lower than that among FDR of patients with
LS (SIR, 5.01, 95% CI, 4.26–5.84; p < 0.001). FDRs with LLS have an increased risk of developing
CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus,
their management should take into account this increased risk.2020-01-01T00:00:00ZUroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLDhttps://hdl.handle.net/10171/678262023-11-20T06:05:26Z2023-01-01T00:00:00ZTitle: Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD
Abstract: Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions.Results: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial & beta;-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced & beta;-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-& beta;1 stimulation.Conclusions: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.2023-01-01T00:00:00ZTherapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinomahttps://hdl.handle.net/10171/675422024-01-30T12:22:41Z2023-01-01T00:00:00ZTitle: Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma
Abstract: Background: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant
chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified
FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other
tumors, but scarce data is available in pancreatic cancer.
Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included
in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil
(5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated.
Results: By exploratory univariate analyses, a significantly longer progression-free survival was observed
for patients with either 5-FU area under the curve (AUC) above 28 mcg$h/mL or CPT-11 AUC values below
10 mcg$h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability
after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC 28 mcg$h/mL [HR ¼ 0.251, 95% CI 0.096e0.656; p ¼ 0.005]
and CPT-11 AUC <10 mcg$h/mL [HR ¼ 0.189, 95% CI 0.073e0.486, p ¼ 0.001].
Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might
improve survival outcomes in patients with pancreatic ductal adenocarcinoma.2023-01-01T00:00:00Z