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PURPOSE: Epidemiological evidence shows that physical activity, including continuous stimulus changes and appropriate exercise programs, improves brain degeneration in the hippocampus, prefrontal cortex (PFC), and anterior cingulate cortex (ACC). Therefore, we investigated the possible synergistic effects of physical activity and nutrition in controlling chronic fatigue and reducing oxidative stress in patients at risk for depression and suicide. METHODS: We systematically reviewed the literature on various systemic factors related to the effects of 1) suppressing oxidative stress and 2) improving depression through exercise and nutrition. To conduct this review, we searched the PubMed database for papers published until May 1, 2024, using the terms "physical activity OR exercise" and "fatigue" OR "anti-fatigue," "oxidative stress" and "depression" and "suicide." We then reviewed the resulting list of articles related to antioxidant mechanisms. RESULTS: Appropriate physical activity and natural product intake can substantially change whole-body homeostasis and provide a way to overcome the threat of depression and suicide by regulating metabolites, scavenging free radicals, and neurotransmitters. CONCLUSION: Suicide and depression prevention play crucial roles in improving patients' quality of life. Our review provides evidence supporting the idea that exercise and antioxidant nutrition diminish oxidative stress and fatigue by improving the degeneration of the hippocampus, PFC, and ACC.
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BACKGROUND: Owing to its strong acid inhibition, potassium-competitive acid blocker (P-CAB) based regimens for Helicobacter pylori (H. pylori) eradication are expected to offer clinical advantages over proton pump inhibitor (PPI) based regimens. This study aims to compare the efficacy and adverse effects of a 7-day and a 14-day P-CAB-based bismuth-containing quadruple regimen (PC-BMT) with those of a 14-day PPI-based bismuth-containing quadruple regimen (P-BMT) in patients with high clarithromycin resistance. METHODS: This randomized multicenter controlled clinical trial will be performed at five teaching hospitals in Korea. Patients with H. pylori infection who are naive to treatment will be randomized into one of three regimens: 7-day or 14-day PC-BMT (tegoprazan 50 mg BID, bismuth subcitrate 300 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or 14-day P-BMT. The eradication rate, treatment-related adverse events, and drug compliance will be evaluated and compared among the three groups. Antibiotic resistance testing by culture will be conducted during the trial, and these data will be used to interpret the results. A total of 366 patients will be randomized to receive 7-day PC-BMT (n = 122), 14-day PC-BMT (n = 122), or 14-day P-BMT (n = 122). The H. pylori eradication rates in the PC-BMT and P-BMT groups will be compared using intention-to-treat and per-protocol analyses. DISCUSSION: This study will demonstrate that the 7-day or 14-day PC-BMT is well tolerated and achieve similar eradication rates to those of 14-day P-BMT. Additionally, the 7-day PC-BMT will show fewer treatment-related adverse effects and higher drug compliance, owing to its reduced treatment duration. TRIAL REGISTRATION: Korean Clinical Research Information Service registry, KCT0007444. Registered on 28 June 2022, https://cris.nih.go.kr/cris/index/index.do .
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapêutico , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Bismuto/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Metronidazol/uso terapêutico , Estudos Multicêntricos como Assunto , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Projetos de PesquisaRESUMO
Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in patients undergoing Roux-en-Y (REY) reconstruction; although balloon-assisted enteroscopy is the first-line treatment, it is not always available considering equipment and expertise. We aimed to evaluate the feasibility of using a cap-assisted colonoscope as the primary approach for ERCP in REY reconstruction. We included 47 patients with REY who underwent ERCP using a cap-assisted colonoscope between January 2017 and February 2022. The primary outcome was intubation success for ERCP using a cap-assisted colonoscope during REY reconstruction. The secondary outcomes were cannulation success, procedure-related adverse events, and variables affecting successful intubation. Comparing side-to-side jejunojejunostomy (SS-JJ) and side-to-end jejunojejunostomy (SE-JJ) groups, the intubation success rate using a cap-assisted colonoscope in the SS-JJ group was higher than that in the SE-JJ group (34 of 38 (89.5%) vs. 1 of 9 (11.1%), p < 0.001). Successful intubation was achieved in 37 (97.4%) and 8 (88.9%) patients in the SS-JJ and SE-JJ groups, respectively, after applying the rescue technique using a balloon-assisted enteroscope for failed ERCP using only a colonoscope. No perforation occurred. Multivariable analysis showed that SS-JJ was a predictive factor for successful intubation (odds ratio [95% confidence interval] = 37.06 [3.91-925.56], p = 0.005). Usage of a cap-assisted colonoscope can be crucial for ERCP in patients undergoing REY reconstruction. Anatomically, SS-JJ can facilitate easy and accurate identification of the afferent limb and a highly successful ERCP using a cap-assisted colonoscope.
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BACKGROUND/AIMS: There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. METHODS: Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. RESULTS: A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. CONCLUSION: PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.
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Neoplasias da Mama , Neoplasias Gastrointestinais , Síndrome de Peutz-Jeghers , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Lactente , Pré-Escolar , Criança , Adolescente , Feminino , Síndrome de Peutz-Jeghers/epidemiologia , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/diagnóstico , Neoplasias Gastrointestinais/etiologia , Neoplasias Gastrointestinais/complicações , Risco , República da Coreia/epidemiologiaRESUMO
Background/Aims: Various endoscopic submucosal dissection (ESD) methods for gastric tumors have been tried. However, no studies have yet compared results according to the ESD method for gastric body tumors using a dual knife. The objective of this study was to compare outcomes of two ESD methods for gastric body tumors: the pocket-creation method and conventional method. Methods: Patients who underwent ESD for a gastric body tumor were retrospectively reviewed. Patients were divided into two groups according to the ESD method: the conventional method (group I) and pocket-creation method (group II). Characteristics of patients and tumors, hospitalization period, incidence of complications, resection margin status, incidence of surgical operation, procedure time, and laboratory findings were investigated. Results: Of the total of 100 patients, 52 belonged to group I and 48 to group II. All tumors were successfully resected en bloc. Resection margin involvement was found in six (11.5%) of group I and six (12.5%) of group II. Complications were observed in seven (13.5%; major complication five, minor two) of group I and eight (16.7%; major two, minor six) of group II. There were no significant differences in ESD outcomes such as hospitalization period, incidence of complications, resection margin status, incidence of surgical operation, procedure time, or inflammatory response after ESD between the two groups. Conclusions: Both methods are suitable for treating gastric body tumors with adequate treatment success rates and comparable complication rates.
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Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastroscopia/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Margens de Excisão , Mucosa Gástrica/cirurgia , Mucosa Gástrica/patologia , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Duodenal underwater endoscopic mucosal resection (UEMR) has been suggested as a feasible treatment option for superficial non-ampullary duodenal epithelial tumors (SNADETs). However, its efficacy and safety have not been fully established yet. Thus, the objective of this systematic review and meta-analysis was to determine the efficacy and safety of UEMR as compared with conventional endoscopic mucosal resection (CEMR) in the treatment of SNADETs. METHODS: We conducted a comprehensive literature search in PubMed, EMBASE, the Cochrane Library. Studies comparing CEMR and UEMR for the resection of SNADET were included. Outcomes included en-bloc and complete resection rates, adverse events, and procedure time. RESULTS: A total of six studies with 2454 lesions were included in the quantitative synthesis. En-bloc and complete resection rates were not significantly different between UEMR and CEMR (OR for en-bloc resection: 0.997 [95% CI 0.439-2.266]; OR for complete resection: 0.960 [95% CI 0.628-1.468]). There was no significant risk difference for perforation (risk difference: - 0.002; 95% CI - 0.009 to 0.005) or delayed bleeding (risk difference: - 0.001; 95% CI - 0.014 to 0.011). Procedure time was significantly shorter in the UEMR (standardized mean difference: - 1.294; 95% CI - 2.461 to - 0.127). The risk of recurrence was not significantly different between UEMR and CEMR (risk difference: 0.001; 95% CI - 0.041 to 0.044). CONCLUSION: Although our results did not show any superiority of UEMR over CEMR in the treatment of SNADETs, UEMR showed equivalent efficacy and safety as compared with CEMR and was associated with a shorter procedure time.
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Neoplasias Duodenais , Ressecção Endoscópica de Mucosa , Neoplasias Epiteliais e Glandulares , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Duodeno/cirurgia , Duodeno/patologia , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Neoplasias Epiteliais e Glandulares/etiologia , Neoplasias Epiteliais e Glandulares/patologia , Resultado do Tratamento , Mucosa Intestinal/cirurgia , Mucosa Intestinal/patologiaRESUMO
PURPOSE: Exercise helps modify the lipid profile in the body, partly through its impact on sterol regulatory element binding protein-1 (SREBP-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ). Individual differences in response to exercise and genetic variations may influence the response to PA. Therefore, this study explored Rosae multiflorae fructus (RMF) as a supplement candidate that improves exercise capacity and controls non-alcoholic fatty liver disease (NAFLD) by suppressing lipogenesis and controlling lipid peroxidation. METHODS: RMF is a natural herbal medicine used in Dongui Bogam. RMF has antioxidant, anti-inflammatory, and anti-allergic effects. However, the effects of RMF on NAFLD have not yet been investigated. In this study, we examined the effects of RMF in a mouse model of high-fat diet-induced NAFLD. Mouse livers were isolated and analyzed using H&E staining and immunohistochemistry. RESULTS: RMF downregulated lipid peroxidation markers, such as CYP2E1, in the livers of mice with high-fat diet-induced NAFLD. Additionally, the RMF significantly reduced the lipid accumulation-related protein expression of CD36, SREBP-1, and PPAR-γ. CONCLUSION: RMF exerts anti-lipid peroxidation and anti-lipogenic effects in a high-fat diet-induced NAFLD mouse model.
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BACKGROUND: Endoscopic submucosal dissection (ESD) can provide a high en bloc resection rate and has been widely applied as curative treatment for early colorectal cancer (ECC). However, surgical treatment is occasionally required, and reports on the long-term prognosis of ESD are insufficient. This study aimed to investigate the long-term outcomes of ECC removal by ESD, including local recurrence and metastasis. METHODS: This multicenter study was conducted retrospectively on 450 consecutive patients with ECC who were treated with ESD between November 2003 and December 2013. Clinical, pathological, and endoscopic data were collected to determine tumor depth, resection margin, lymphovascular invasion, and recurrence. RESULTS: The median follow-up period was 53.8 (12-138 months). The en bloc resection rate was 85.3% (384) and in intramucosal cancer being 84.1% and in superficial submucosal invasion (SM1) cancer being 89.8% (p = 0.158). The curative resection rate was 76.0% (n = 342), and there was no statistical difference between the two groups (77.3% vs. 71.4%, p = 0.231). The overall recurrence free survival rate (RFS) was 98.7% (444/450). In patients with curative resection, there was no statistically significant difference in RFS according to invasion depth (intramucosal: 99.3% vs. SM1: 97.1%, p = 0.248). CONCLUSIONS: Patients with curatively resected ECC treated with ESD showed favorable long-term outcomes. Curatively resected SM1 cancer has a RFS similar to that of intramucosal cancer.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
Double-balloon enteroscopy (DBE) has become one of the standard methods in the diagnosis and treatment of small bowel (SB) disease. However, previous studies for DBE have limitations due to heterogeneity of indications and operators. The aim was to investigate the indication, location of the lesion, diagnostic yield, and therapeutic yield of DBE based on long-term data from a single operator. A retrospective study was performed by reviewing medical records of subjects who had received DBE at our unit in the past 17 years. Overall diagnostic yield was 78.7% (210/267). The diagnostic yield for obscure gastrointestinal bleeding (OGIB) was 68.3% (84/123). The diagnostic yield for OGIB was significantly lower (p < 0.001) than that for other indications. Therapeutic yield was 24.7% (66/267). Complications occurred in 7 (2.6%). Crohn's disease, intestinal tuberculosis, nonsteroidal anti-inflammatory drug enteropathy, and diverticular lesions were mainly found in the ileum. Vascular lesions, non-specific inflammation, and neoplastic lesions were found more frequently in the jejunum. DBE is an excellent and safe endoscopic method for the diagnosis and treatment of SB lesions. DBE has a lower diagnostic rate for OGIB than for other indications. The location where a lesion is commonly found depends on the type of the lesion.
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Background/Aims: Clarithromycin resistance is a main factor for treatment failure in the context of Helicobacter pylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. We aimed to compare the efficacy and cost-effectiveness of 14-day bismuth-based quadruple therapy versus 14-day metronidazole-intensified triple therapy for clarithromycin-resistant H. pylori infection with genotypic resistance. Methods: This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Results: The overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy. Conclusions: Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Metronidazol , Resultado do TratamentoRESUMO
The fibroblast growth factor-4 receptor (FGFR4) is a member of receptor tyrosine kinase. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor has been shown to increase genetic susceptibility to cancers. However, its prognostic impact in cancer patients still remains controversial. Herein, we performed this meta-analysis to evaluate the clinicopathological and prognostic impacts of the FGFR4 Gly388Arg polymorphism in patients with cancer. We carried out a computerized extensive search using PubMed, Medline, and Ovid Medline databases up to July 2021. From 44 studies, 11,574 patients were included in the current meta-analysis. Regardless of the genetic models, there was no significant correlation of the FGFR4 Gly388Arg polymorphism with disease stage 3/4. In the homozygous model (Arg/Arg vs. Gly/Gly), the Arg/Arg genotype tended to show higher rate of lymph node metastasis compared with the Gly/Gly genotype (odds ratio = 1.21, 95% confidence interval (CI): 0.99-1.49, p = 0.06). Compared to patients with the Arg/Gly or Arg/Arg genotype, those with the Gly/Gly genotype had significantly better overall survival (hazard ratios (HR) = 1.19, 95% CI: 1.05-1.35, p = 0.006) and disease-free survival (HR = 1.25, 95% CI: 1.03-1.53, p = 0.02). In conclusion, this meta-analysis showed that the FGFR4 Gly388Arg polymorphism was significantly associated with worse prognosis in cancer patients. Our results suggest that this polymorphism may be a valuable genetic marker to identify patients at higher risk of recurrence or mortality.
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We conducted a systemic literature review of randomized controlled trials (RCTs) to identify phase III RCTs on salvage treatment of advanced gastric cancer (AGC) and performed a Bayesian network meta-analysis with random-effects model. The overall survival (OS) was the primary outcome of interest. A total of 20 randomized phase III trials were selected. For the second-line treatment, olaparib plus paclitaxel had the highest surface under the cumulative ranking curve value (90.5%), followed by paclitaxel plus ramucirumab (88.4%) and pembrolizumab (86.5%), indicating that these treatments could be the most effective regimens in terms of OS. Nivolumab, chemotherapy, and apatinib showed significant OS benefit compared with best supportive care for the third-line treatment. In conclusion, pembrolizumab may be the most preferable regimen as a second-line treatment for patients with PD-L1-expressing AGC, while paclitaxel-based combinations are recommended for PD-L1-negative AGC. Nivolumab might be the most preferable third-line treatment.
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Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Humanos , Metanálise em Rede , Nivolumabe/uso terapêutico , Paclitaxel , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Balloon-assisted enteroscopy (BAE) is an important diagnostic modality for ongoing obscure gastrointestinal bleeding (OGIB). However, it is difficult to determine the optimal insertion route. We retrospectively analyzed the records of patients with OGIB contained in a multicenter enteroscopy database of 1108 balloon-assisted enteroscopy (BAE) procedures (875 patients) to find out factors affecting BAE route selection in patients with OGIB. A total of 603 BAE procedures in 512 patients were investigated: there were 392 (65.0%) bidirectional and 211 (35.0%) unidirectional procedures. Overt OGIB was more frequent in the latter group (p = 0.024). Computed tomography (CT) was more frequently performed in the unidirectional group (p < 0.001). Capsule endoscopy and a small bowel barium study were performed more frequently in the bidirectional group (p < 0.001 and p = 0.039, respectively). Multivariate analysis showed that occult OGIB, capsule endoscopy and a small bowel barium study were independently associated with use of the bidirectional approach (p = 0.011, p = 0.013 and p = 0.046, respectively). Conversely, CT was associated with use of the unidirectional approach (p < 0.001). Conclusion: CT can aid the selection of an optimal insertion route in OGIB patients. However, capsule endoscopy and small bowel barium study are unhelpful.
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Unlike in normal cells, ursodeoxycholic acid (UDCA) causes apoptosis rather than protection in cancer cells. Aim of this study was to demonstrate whether UDCA actually inhibits proliferation and induces apoptosis in bile duct cancer cells; the effect of UDCA on the expression of COX-2, PI3K/AKT, ERK, and EGFR; how UDCA affects cancer cell invasiveness and metastasis, since these effects are not established in bile duct cancer cells. SNU-245 cells (human extrahepatic bile duct cancer cells) were cultured. MTT assays were performed to evaluate the effect of UDCA on the cell proliferation. A cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay were used to determine apoptosis. Western blot analysis measured expression levels of various proteins. The invasiveness of the cancer cells was evaluated by invasion assay. In cultured bile duct cancer cells, UDCA suppressed cell proliferation in bile duct cancer cells by inducing apoptosis and p53 activation, blocking deoxycholic acid (DCA)-induced activated EGFR-ERK signaling and COX-2, inhibiting DCA-induced activated PI3K-AKT signaling, and suppressing the invasiveness of bile duct cancer cells. In addition, a MEK inhibitor impaired UDCA-induced apoptosis in bile duct cancer cells. UDCA has antineoplastic and apoptotic effects in bile duct cancer cells. Thus, UDCA could be a chemopreventive agent in patients with a high risk of cancer, and/or a therapeutic option that enhances other chemotherapeutics.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/metabolismo , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Ácido Ursodesoxicólico/farmacologia , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ácido Desoxicólico/metabolismo , Receptores ErbB/metabolismo , Flavonoides/farmacologia , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidoresRESUMO
OBJECTIVES: Diagnosis of reflux esophagitis according to the Los Angeles classification minimal change (LA-M) has a low inter-observer agreement. We aimed to investigate whether the inter-observer agreement of reflux esophagitis was better when expert endoscopists read the endoscopic images, or when the linked color imaging (LCI) or blue laser imaging (BLI)-bright mode was used. In addition, whether the inclusion of LA-M in the definition of reflux esophagitis affected the consistency of the diagnosis was investigated. METHODS: During upper endoscopy, endoscopic images of the gastroesophageal junction were taken using white light imaging (WLI), BLI-bright, and LCI modes. Four expert endoscopists and four trainees reviewed the images to diagnose reflux esophagitis according to the modified LA classification. RESULTS: The kappa values for the inter-observer variability for the diagnosis of reflux esophagitis were poor to fair among the experts (κ = â0.22, 0.17, and 0.27 for WLI, BLI-bright, and LCI, respectively) and poor among the trainees (κ = â0.18, 0.08, and 0.14 for WLI, BLI-bright, and LCI). The inter-observer variabilities for the diagnosis of reflux esophagitis excluding LA-M were fair to moderate (κ = â0.42, 0.35, and 0.42 for WLI, BLI-bright, and LCI) among the expert endoscopists and moderate among the trainees (κ = 0.48, 0.43, and 0.51 for WLI, BLI-bright, and LCI). CONCLUSIONS: The inter-observer agreement for the diagnosis of reflux esophagitis was very low for both the expert endoscopists and the trainees, even using BLI-bright or LCI mode. However, when reflux esophagitis LA-M was excluded from the diagnosis of esophagitis, the degree of inter-observer agreement increased.
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Esofagite Péptica , Junção Esofagogástrica/diagnóstico por imagem , Esofagoscopia , Gastroscopia , Competência Clínica , Cor , Esofagite Péptica/diagnóstico por imagem , Esofagoscopia/educação , Esofagoscopia/normas , Gastroscopia/educação , Gastroscopia/normas , Humanos , Aumento da Imagem , Lasers , Luz , Variações Dependentes do ObservadorRESUMO
Backgrounds/Aims: PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods: MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results: Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions: Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.
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Atorvastatina/farmacologia , Colesterol , Colesterol 7-alfa-Hidroxilase/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , PPAR gama , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Receptores Citoplasmáticos e NuclearesRESUMO
BACKGROUND: Onartuzumab, a humanized monovalent monoclonal antibody to the MET protein, has been tested in various cancers. We conducted a meta-analysis of randomized phase II and III clinical trials to investigate the efficacy and safety of onartuzumab in solid cancers. METHODS: We searched PubMed, PMC, EMBASE, and the Cochrane library databases. We included randomized phase II or III trials that evaluated the additional benefits of onartuzumab in comparison with the standard treatments. Data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled and analyzed. RESULTS: From nine studies, a total of 2,138 patients were included in the meta-analysis. The addition of onartuzumab to the standard treatment resulted in no improvement of PFS (hazard ratio (HR) = 1.00 [95% confidence interval (CI), 0.90-1.11], P = 0.93) and OS (HR = 1.08 [95% CI, 0.94-1.23], P = 0.29). In the subgroup analysis with patients with non-small-cell lung cancer (NSCLC), onartuzumab was not associated with a significant improvement of OS (HR = 1.12 [95% CI, 0.93-1.34], P = 0.23) and PFS (HR = 1.05 [95% CI, 0.91-1.21], P = 0.52). With respect to AEs, onartuzumab increased the incidence of hypoalbuminemia (odds ratio (OR) = 14.8 [95% CI, 3.49-62.71], P < 0.001), peripheral edema (OR = 6.52 [95% CI, 3.60-11.81], P < 0.001), neutropenia (OR = 1.36 [95% CI, 1.03-1.79], P = 0.03), thrombocytopenia (OR = 1.98 [95% CI, 1.03-3.81], P = 0.04), and venous thrombotic events (OR = 3.05 [95% CI, 1.39-6.71], P = 0.006). CONCLUSION: This meta-analysis indicates that the addition of onartuzumab to the standard treatments had no definite survival benefit with increased severe toxicities in patients with solid cancer.
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Anticorpos Monoclonais/uso terapêutico , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Humanos , Neoplasias/patologia , Prognóstico , Proteínas Proto-Oncogênicas c-met/imunologia , Taxa de SobrevidaRESUMO
BACKGROUND: Currently, because the population is aging, use of medications has been increasing, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents. AIMS: This study aims to investigate whether NSAIDs can cause damage to the small bowel (SB) mucosa. METHODS: Endoscopic videos of subjects who had undergone capsule endoscopy (CE) were evaluated by three experts in order to identify SB injury. All medications taken within 2 weeks from the time of CE were investigated. Cases with a final diagnosis of intestinal tuberculosis, inflammatory bowel disease, Behcet's disease, Peutz-Jeghers syndrome, small bowel lymphoma, or Henoch-Schönlein purpura were excluded from the analysis. RESULTS: Among the 273 subjects, 125 (45.8%) had SB erosions or ulcers (erosion group) and the remaining 148 (54.2%) did not (no erosion group). SB erosions or ulcers were more common in females, patients aged > 60 years, and subjects taking NSAIDs (p = 0.048, 0.032, and < 0.001, respectively). No statistically significant differences were found between the two groups in the following variables: history of cancer and GI surgery, reasons for the test, comorbidities, and use of anticoagulants and antiplatelet agents. Multivariate analysis showed that use of NSAIDs [OR 4.191 (95% CI 1.858-9.458), p < 0.001] was an independent risk factor for SB erosions or ulcers. CONCLUSIONS: Use of NSAIDs is the only independent risk factor for SB injury identified in this study. Antithrombotic agents do not cause or exacerbate damage to the SB, according to our results. CLINICAL TRIAL REGISTRATION: KCT0004795.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Endoscopia por Cápsula , Enteropatias/induzido quimicamente , Enteropatias/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background/Aims: Although balloon-assisted enteroscopy (BAE) enables endoscopic visualization of small bowel (SB) involvement in Crohn's disease (CD), there is no data on the changes in outcomes over time. We therefore investigated the changes in BAE use on CD patients over different time periods in terms of its role and clinical outcomes. Methods: We used a multicenter enteroscopy database to identify CD patients with SB involvement who underwent BAE (131 procedures, 116 patients). We compared BAE-related factors and outcomes between the first period (70 procedures, 60 patients) and the second period (61 procedures, 56 patients). The specific cutoff point for dividing the two periods was 2007, when BAE guidelines were introduced. Results: Initial diagnosis of SB involvement in CD was the most common indication for BAE during each period (50.0% vs 31.1%, p=0.034). The largest change was in the number of BAE uses for stricture evaluation and/or treatment, which increased significantly in the latter period (2.9% vs 21.3%, p=0.002). The diagnostic yield in patients with suspected CD was 90.7% in the first period and 95.0% in the second (p=0.695). More endoscopic interventions were performed in the second period than in the first (5.1% vs 17.6%, p=0.041). Enteroscopic success rates were high throughout (100% in the first period vs 80.0% in the second period, p>0.999). In the first and second periods, therapeutic plans were adjusted in 62.7% and 61.4% of patients, respectively. Conclusions: The overall clinical indications, outcomes, and effectiveness of BAE were constant over time in CD patients with SB involvement, with the exception that the frequency of enteroscopic intervention increased remarkably.
Assuntos
Doença de Crohn , Laparoscopia , Enteroscopia de Balão , Constrição Patológica/etiologia , Humanos , Intestino Delgado/diagnóstico por imagemRESUMO
Background/Aims: The diagnosis of small bowel Crohn's disease with negative ileocolonoscopic findings has been challenging. Fecal calprotectin (FC) has been used to detect colonic inflammation, but its efficacy for detecting small bowel inflammation is less established. We performed an updated meta-analysis to evaluate the diagnostic accuracy of FC to detect active small bowel inflammation observed during capsule endoscopy. Methods: We conducted a systematic literature search for studies that evaluated the correlation between small bowel inflammation and FC in patients with suspected/established Crohn's disease. We calculated the pooled sensitivity, specificity, and diagnostic odds ratios (DORs) and constructed hierarchical summary receiver operating characteristic curves for FC cutoffs of 50, 100, and 200 µg/g. Results: Fourteen studies were eligible for the final analysis. The DORs of all FC cutoffs were significant. The highest DOR was observed at 100 µg/g (sensitivity, 0.73; specificity, 0.73; and DOR, 7.89) and was suggested as the optimal diagnostic cutoff. If we analyzed only studies that included patients with suspected Crohn's disease, the DOR was 8.96. If we analyzed only studies that included patients with a Lewis score ≥135 as a diagnostic criterion for active disease, the DOR was 10.90. Conclusions: FC has significant diagnostic accuracy for detecting small bowel inflammation, and an FC cutoff of 100 µg/g can be used as a tool to screen for small bowel Crohn's disease.