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BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.
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Biomarcadores de Tumor , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Femenino , Masculino , Pronóstico , China/epidemiología , Persona de Mediana Edad , Anciano , Inflamación , Aprendizaje Automático , Estudios de Cohortes , Estimación de Kaplan-Meier , Adulto , Estadificación de Neoplasias , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. METHODS: Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15 < 10), subgroup analysis, correlation analysis, and logistic regression. Lastly, we evaluated the somatic symptom severity (SSS) among FC patients subjected to various stressors. RESULTS: Notable disparities were observed between SOM + and SOM- groups in variety of physiological and psychological variables, including gender, stressful events, sleep disorders, reduced interest, GAD-7, PHQ-15, PHQ-9, PAC-QOL, anterior rectocele, KESS, and internal anal sphincter achalasia (IASA) (P < 0.05). Subgroup analysis affirmed consistent findings across mental symptoms. Correlation analyses revealed significant associations between SSS and KESS, anterior rectocele, GAD-7, PHQ-9, and PAC-QOL (P < 0.05). Logistic regression identified PHQ-9 (OR = 7.02, CI: 2.06-27.7, P = 0.003), GAD-7 (OR = 7.18, CI: 2.00-30.7, P = 0.004), and KESS (OR = 16.8, CI: 3.09-113, P = 0.002) as independent predictors of SSS. Elevated SSS scores were significantly associated with couple, parental, and work-related stressors (P < 0.05). CONCLUSION: A marked heterogeneity was observed between SOM + and SOM- patients of FC, with SOM + accompanied by more severe constipation, anxiety and depression symptoms. This finding underscores the importance of considering somatic symptoms in diagnosis and treatment of FC.
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Síntomas sin Explicación Médica , Calidad de Vida , Humanos , Calidad de Vida/psicología , Estudios Transversales , Rectocele , Encuestas y Cuestionarios , Pacientes Ambulatorios , Ansiedad/diagnóstico , Depresión/diagnóstico , Depresión/psicología , Estreñimiento/diagnósticoRESUMEN
OBJECTIVE: The current study used a composite outcome to investigate whether applying the ERAS protocol would enhance the recovery of patients undergoing laparoscopic total gastrectomy (LTG). EXPOSURES: Laparoscopic total gastrectomy and perioperative interventions were the exposure. An ERAS clinical pathway consisting of 14 items was implemented and assessed. Patients were divided into either ERAS-compliant or non-ERAS-compliant group according the adherence above 9/14 or not. MAIN OUTCOMES AND MEASURES: The primary study outcome was a composite outcome called 'optimal postoperative recovery' with the definition as below: discharge within 6 days with no sever complications and no unplanned re-operation or readmission within 30 days postoperatively. Univariate logistic regression analysis and multivariate logistic regression analysis were used to model optimal postoperative recovery and compliance, adjusting for patient-related and disease-related characteristics. RESULTS: A total of 252 patients were included in this retrospective study, 129 in the ERAS compliant group and 123 in the non-ERAS-compliant group. Of these, 79.07% of the patients in ERAS compliant group achieved optimal postoperative recovery, whereas 61.79% of patients in non-ERAS-compliant group did (P = 0.0026). The incidence of sever complications was lower in the ERAS-compliant group (1.55% vs. 6.5%, P = 0.0441). No patients in ERAS compliant group had unplanned re-operation, whereas 5.69% (7/123) of patients in non-ERAS-compliant group had (p = 0.006). The median length of the postoperative hospital stay was shorter in the in the ERAS compliant group (5.51 vs. 5.68 days, P = 0.01). Both logistic (OR 2.01, 95% CI 1.21-3.34) and stepwise regression (OR 2.07, 95% CI 1.25-3.41) analysis showed that high overall compliance with the ERAS protocol facilitated optimal recovery in such patients. In bivariate analysis of compliance for patients who had an optimal postoperative recovery, carbohydrate drinks (p = 0.0196), early oral feeding (P = 0.0043), early mobilization (P = 0.0340), and restrictive intravenous fluid administration (P < 0.0001) were significantly associated with optimal postoperative recovery. CONCLUSIONS AND RELEVANCE: Patients with higher ERAS compliance (almost 70% of the accomplishment) suffered less severe postoperative complications and were more likely to achieve optimal postoperative recovery.
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Recuperación Mejorada Después de la Cirugía , Laparoscopía , Humanos , Laparoscopía/métodos , Estudios Retrospectivos , Gastrectomía/métodos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Immunotherapeutic strategies aimed at enhancing tumor cell killing by tumor-specific T cells hold great potential for reducing tumor burden and prolonging survival of cancer patients. Although many potential tumor antigens have been described, identifying relevant targets when designing anti-cancer vaccines or targeted cell therapies remains a challenge. To identify novel, potentially immunogenic candidate tumor antigens, we performed integrated tumor transcriptomic, seromic, and proteomic analyses of high grade serous ovarian cancer (HGSC) patient tumor samples. We identified tumor neo-antigens and over-expressed antigens using whole exome and RNA sequencing and examined these in relation to patient-matched auto-antibody repertoires. Focusing on MHC class I epitopes recognized by CD8+ T cells, HLA-binding epitopes were identified or predicted from the highly expressed, mutated, or auto-antibody target antigen, or MHC-associated peptides (MAPs). Recognition of candidate antigenic peptides was assessed within the tumor-infiltrating T lymphocyte (TIL) population expanded from each patient. Known tumor-associated antigens (TAA) and cancer/testis antigens (CTA) were commonly found in the auto-antibody and MAP repertoires and CD8+ TILs recognizing epitopes from these antigens were detected, although neither expression level nor the presence of auto-antibodies correlated with TIL recognition. Auto-antibodies against tumor-mutated antigens were found in most patients, however, no TIL recognition of the highest predicted affinity neo-epitopes was detected. Using high expression level, auto-antibody recognition, and epitope prediction algorithms, we identified epitopes in 5 novel antigens (MOB1A, SOCS3, TUBB, PRKAR1A, CCDC6) recognized by HGSC patient TILs. Furthermore, selection of epitopes from the MAP repertoire identified 5 additional targets commonly recognized by multiple patient TILs. We find that the repertoire of TIL specificities includes recognition of highly expressed and immunogenic self-antigens that are processed and presented by tumors. These results indicate an ongoing autoimmune response against a range of self-antigens targeted by HGSC TILs.
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Linfocitos Infiltrantes de Tumor , Neoplasias Ováricas , Masculino , Humanos , Femenino , Epítopos/metabolismo , Linfocitos T CD8-positivos , Proteómica , Multiómica , Antígenos de Neoplasias , Péptidos , Autoantígenos , Epítopos de Linfocito TRESUMEN
Objective: Colon adenocarcinoma (COAD) is one of the leading causes of cancer death worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA. However, the posttranscriptional dysregulation of APA in COAD is poorly understood. Methods: We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA events were evaluated using PDUI values, and the prognostically significant APA events were screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune regulatory network based on APA regulatory genes was analyzed and established. Results: A total of 95 APA events were found to influence the COAD outcomes. Among them, 39 genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a COAD prognostic signature. The analysis results suggested that a high signature score was associated with poor prognosis and was significantly correlated with a variety of immune cells, including NK and Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory genes-APA genes-immune cells. Conclusion: Our study revealed that APA events in COAD may regulate tumor progression by influencing immune cells, which provides a new direction for exploring the influencing mechanism of the tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.
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Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared with adenocarcinomas (ACs). The lack of a systematic molecular overview of this disease has led to slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumors and adjacent tissues, including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate the cellular heterogeneity of the tissues. The proteomes of tissues were profiled by data-independent acquisition (DIA) mass spectrometry (MS). Based on the over 6000 proteins quantified, univariate analysis and pathway enrichment revealed that some proteins and pathways demonstrated differences between SRCC and ACs. Importantly, the upregulation of a majority of complement-related proteins was notable for SRCC but not for ACs. A hypothesis, based on the proteomics evidence, was proposed that the complement cascade was evoked in the SRCC microenvironment upon infiltration, and the SRCC cells survived the complement cytotoxicity by secreting endogenous negative regulators. Moreover, an attempt was made to establish appropriate cell models for gastric SRCC through proteomic comparison of the 15 gastric cell lines and gastric tumors. The predictions of a supervised classifier suggested that none of these gastric cell lines qualified to mimic SRCC. This study discovered that the complement cascade is activated at a higher level in gastric SRCC than in ACs.
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Carcinoma de Células en Anillo de Sello/metabolismo , Proteínas del Sistema Complemento/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Carcinoma de Células en Anillo de Sello/patología , Línea Celular Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteómica , Estómago/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.
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Trasplante de Riñón , Donadores Vivos , Humanos , Colesterol , Supervivencia de Injerto , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/etiología , Receptores de TrasplantesRESUMEN
OBJECTIVE: To examine outcomes of living-donor intestinal transplant (LDITx) recipients. BACKGROUND: LDITx is not routinely performed because of surgical risks to the donor and the potential inferior physiologic performance of the segmental graft. However, data on the effectiveness of LDITx are scarce. DESIGN: This retrospective cohort study included patients undergoing LDITx between May 1999 and December 2021 in intestinal transplant programs in 2 university-affiliated hospitals in China. RESULTS: Actuarial survival rates were 80%, 72.7%, 66.7% for patient and 72.4%, 63.6%, 60% for graft at 1, 3, and 5 years, respectively. Recipients with >3/6 HLA-matched grafts had superior patient and graft survival rates than those with ≤3/6 HLA-matched grafts ( P <0.05). There were 12 deaths among the recipients, with infection being the leading cause (41.7%), followed by rejection (33.3%), surgical complications (16.7%), and others (8.3%). There were 16 graft losses among the recipients, with acute cellular rejection being the predominant cause (37.5%), followed by infection (25%), technical failure (12.5%), chronic rejection (12.5%), and others (12.5%). With an average follow-up of 3.7 (range, 0.6-23) years, the rates of acute and chronic rejection were 35% and 5%, and the rate of cytomegalovirus disease and post-transplant lymphoproliferative disease were 5% and 2.5%, respectively. Of the 40 patients, 28 (70%) are currently alive and have achieved enteral autonomy. CONCLUSIONS: LDITx is a valuable treatment option for patients with end-stage intestinal failure. Improved immunosuppression, better HLA matching, and shorter cold ischemia times were associated with reduced rates of rejection, viral-mediated infection and improved graft survival.
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Trasplante de Riñón , Donadores Vivos , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Estudios RetrospectivosRESUMEN
TRAPPC11 has been implicated in membrane traffic and lipid-linked oligosaccharide synthesis, and mutations in TRAPPC11 result in neuromuscular and developmental phenotypes. Here, we show that TRAPPC11 has a role upstream of autophagosome formation during macroautophagy. Upon TRAPPC11 depletion, LC3-positive membranes accumulate prior to, and fail to be cleared during, starvation. A proximity biotinylation assay identified ATG2B and its binding partner WIPI4/WDR45 as TRAPPC11 interactors. TRAPPC11 depletion phenocopies that of ATG2 and WIPI4 and recruitment of both proteins to membranes is defective upon reduction of TRAPPC11. We find that a portion of TRAPPC11 and other TRAPP III proteins localize to isolation membranes. Fibroblasts from a patient with TRAPPC11 mutations failed to recruit ATG2B-WIPI4, suggesting that this interaction is physiologically relevant. Since ATG2B-WIPI4 is required for isolation membrane expansion, our study suggests that TRAPPC11 plays a role in this process. We propose a model whereby the TRAPP III complex participates in the formation and expansion of the isolation membrane at several steps.
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Autofagosomas/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Portadoras/metabolismo , Distrofia Muscular de Cinturas/genética , Proteínas de Transporte Vesicular/metabolismo , Autofagia , Células Cultivadas , Fibroblastos/metabolismo , Células HeLa , Humanos , Membranas Intracelulares/metabolismo , Mutación , Unión Proteica , Transporte de Proteínas , Proteínas de Transporte Vesicular/genéticaRESUMEN
BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China. METHODS: Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. RESULTS: Among mCRC patients (3878/8136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p < 0.001). The most common sequence from first- to second-line was from FOLFOX and other oxaliplatin-based regimens to FOLFIRI and other irinotecan-based regimens (286/1200, 24%). CONCLUSIONS: Our findings reflected a lack of consensus on the choice of third-line therapy and limited available options in China. It is evident o continue promoting early CRC diagnosis and to increase the accessibility of treatment options for mCRC patients. As the only nationwide large-scale study among CRC and mCRC patients before more biologics became available in China, our results can also be used as the baseline to assess treatment pattern changes before and after more third-line treatment were approved and covered into the National Health Insurance Plan in China between 2017 and 2018.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Registros Médicos/estadística & datos numéricos , Terapia Molecular Dirigida/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Camptotecina/administración & dosificación , Cetuximab/administración & dosificación , China/epidemiología , Neoplasias Colorrectales/epidemiología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán/administración & dosificación , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective: The morbidity and mortality of gastric cancer (GC) is high, but there are lack of the biomarkers for early diagnosis and progression of GC. We aimed to identify a novel biomarker for the growth and progression of GC.Methods: The Cancer Genome Atlas (TCGA) database including 352 eligible patients was used to screen candidate genes related to the prognosis of GC. A proteomics analysis of Chinese Human Proteome Sketches (CHPS) including 84 eligible sample tissues was conducted to further identify candidate biomarkers. A series of in vitro assays were performed to investigate the functions of candidate proteins in GC. Next, to verify whether the candidate oncogene was associated with gastric carcinogenesis, we screened its expression levels using samples from 200 patients with chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, or GC and healthy controls.Results: According to the analyses of the TCGA database and CHPS, we found that S100A9 may be associated with the prognosis of GC. The results of proliferation, wound-healing and invasion assays, immunohistochemistry (IHC) and western blot showed that high levels of S100A9 in tissues were significantly associated with GC aggressiveness and a poor prognosis (p < .05). Furthermore, we found that the expression of S100A9 increased gradually during the process of gastric carcinogenesis (p < .05). The diagnostic sensitivity and specificity of S100A9 as a biomarker for early GC were 61.4% and 81.3%, respectively.Conclusions: This study reveals that S100A9 may be a novel biomarker for the early diagnosis and prognosis of GC patients.
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Biomarcadores de Tumor/metabolismo , Calgranulina B/metabolismo , Neoplasias Gástricas/diagnóstico , Estómago/patología , Carcinogénesis , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/patología , Humanos , Inmunohistoquímica , Masculino , Metaplasia/diagnóstico , Metaplasia/patología , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
Hypoxia inducible factor-1α (HIF-1α) is a central molecule involved in mediating cellular processes. Alterations of HIF-1α and hypoxically regulated microRNAs (miRNAs) are correlated with patients' outcome in various cancers, indicating their crucial roles on cancer development. Recently, an increasing number of studies have revealed the intricate regulations between miRNAs and HIF-1α in modulating a wide variety of processes, including proliferation, metastasis, apoptosis, and drug resistance, etc. miRNAs are a class of small noncoding RNAs which function as negative regulators by directly targeting mRNAs. Evidence shows that miRNAs can be regulated by HIF-1α at transcriptional level. In turn, HIF-1α itself can be modulated by many miRNAs whose alterations have been implicated in tumorigenesis, thus forming a reciprocal regulation network. These findings add a new layer of complexity to our understanding of HIF-1α regulatory networks. Here, we will provide a comprehensive overview of the current advances about the bidirectional interactions between HIF-1α and miRNAs in human cancers. Besides, the review will summarize the roles of miRNAs/HIF-1α crosstalk according to various cellular processes. Finally, the potential values of miRNAs/HIF-1α loops in clinical applications are discussed.
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Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia , MicroARNs/metabolismo , Neoplasias/fisiopatología , Apoptosis , Ciclo Celular/fisiología , Humanos , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/fisiología , MicroARNs/genéticaRESUMEN
Objective. A Perioperative Safety Checklist (PSC) for gastric cancer (GC) was established to evaluate the effects of PSC on the clinical outcomes of GC. Methods. This single-center preliminary observational study conducted at a tertiary referral hospital included patients with GC who underwent surgery from January 1, 2016, to June 30, 2016, treated without PSC (allocated to the control group) and those who underwent surgery between January 1, 2017, and June 30, 2017, managed according to the PSC designated as the PSCGC (Perioperative Safety Checklist for Gastric Cancer) group. Results. Overall, 1072 cases were enrolled, 556 cases in PSCGC group and 526 cases in control group. After matching, there were 474 patients in each group. PSC intervention led to significant reductions of the incidence of postoperative intestinal fistula formation (P = .034), the incidence of unplanned secondary surgery (P = 0.039), and the total hospitalization expenses (P < .001). Total completion rate of all 14 checklists items was 79.1%. Intraoperative blood loss in the complete and partial implementation groups was significantly lower than the complete nonimplementation group (P = .002), whereas hospitalization cost showed an opposite trend, which was significantly higher in the incomplete nonimplementation group (P = .015). Conclusion. PSC implementation was associated with a decreased incidence of gastrointestinal fistula formation, unplanned secondary surgery, and hospitalization cost in patients with GC. However, it had no effect on the in-hospital mortality, the incidence of postoperative complications during hospitalization (ie, incision complications and lung infections), unplanned secondary admission, and the duration of postoperative hospital stay.
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Lista de Verificación , Gastrectomía , Atención Perioperativa/métodos , Complicaciones Posoperatorias , Neoplasias Gástricas/cirugía , Anciano , Femenino , Gastrectomía/efectos adversos , Gastrectomía/mortalidad , Humanos , Fístula Intestinal/epidemiología , Fístula Intestinal/prevención & control , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Reoperación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
BACKGROUND/OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat obesity, and involves removal of the gastric fundus where ghrelin is mainly produced. Ghrelin stimulates appetite and regulates food intake through its effect on the hypothalamus and hippocampus (HIPP). While ghrelin's role on the hypothalamus has been explored, little is known about its role on HIPP. We tested the hypothesis that LSG-induced reductions in ghrelin levels would be associated with changes in HIPP activity. SUBJECTS/METHODS: Brain activity was measured with amplitude of low-frequency fluctuations (ALFF) captured with resting-state functional magnetic resonance imaging (fMRI) in 30 obese participants, both before and after 1-month of LSG, and in 26 obese controls without surgery that were studied at baseline and 1-month later. A two-way analysis of variance (ANOVA) was performed to model the group and time effects on ALFF and resting-state functional connectivity. RESULTS: One-month post-LSG there were significant decreases in appetite, body mass index (BMI), fasting plasma ghrelin and leptin levels, anxiety, and ALFF in HIPP and ALFF increases in posterior cingulate cortex (PCC, PFWE < 0.05). Decreases in HIPP ALFF correlated positively with decreases in fasting ghrelin and anxiety, and increases in PCC ALFF correlated positively with decreases in anxiety. Seed-voxel correlation analysis showed stronger connectivity between HIPP and insula, and between PCC and dorsolateral prefrontal cortex (DLPFC) post-LSG. CONCLUSIONS: These findings suggest that ghrelin effects in HIPP modulate connectivity with the insula, which processes interoception and might be relevant to LSG-induced reductions in appetite/anxiety. Role of LSG in PCC and its enhanced connectivity with DLPFC in improving self-regulation following LSG requires further investigation.
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Cirugía Bariátrica , Ayuno/sangre , Ghrelina/sangre , Hipocampo/fisiopatología , Obesidad Mórbida/cirugía , Pérdida de Peso/fisiología , Adulto , Apetito/fisiología , Femenino , Encuestas Epidemiológicas , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Obesidad Mórbida/diagnóstico por imagen , Obesidad Mórbida/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide. Until now, the involved mechanisms during the development of ESCC are largely unknown. This study aims to explore the driven-genes and biological pathways in ESCC. METHODS: mRNA expression datasets of GSE29001, GSE20347, GSE100942, and GSE38129, containing 63 pairs of ESCC and non-tumor tissues data, were integrated and deeply analyzed. The bioinformatics approaches include identification of differentially expressed genes (DEGs) and hub genes, gene ontology (GO) terms analysis and biological pathway enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, and miRNA-gene network construction. Subsequently, GEPIA2 database and qPCR assay were utilized to validate the expression of hub genes. DGIdb database was performed to search the candidate drugs for ESCC. RESULTS: Finally, 120 upregulated and 26 downregulated DEGs were identified. The functional enrichment of DEGs in ESCC were mainly correlated with cell cycle, DNA replication, deleted in colorectal cancer (DCC) mediated attractive signaling pathway, and Netrin-1 signaling pathway. The PPI network was constructed using STRING software with 146 nodes and 2392 edges. The most significant three modules in PPI were filtered and analyzed. Totally ten genes were selected and considered as the hub genes and nuclear division cycle 80 (NDC80) was closely related to the survival of ESCC patients. DGIdb database predicted 33 small molecules as the possible drugs for treating ESCC. CONCLUSIONS: In summary, the data may provide new insights into ESCC pathogenesis and treatments. The candidate drugs may improve the efficiency of personalized therapy in future.
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BACKGROUND: To compare the surgical and long-term survival outcomes of laparoscopic and open total gastrectomy (OTG) for locally advanced gastric cancer (AGC). METHODS: We retrospectively evaluated 308 and 900 patients in pathological locally AGC who underwent laparoscopic total gastrectomy (LTG) or OTG between June 2008 and December 2014. We compared surgical and long-term outcomes between the two groups using propensity score matching method. RESULTS: The LTG group showed a longer operation time (261.42 vs. 171.00 min, P = 0.001), less blood loss (185.47 vs. 217.84 ml, P = 0.000), earlier time to first flatus (3.47 vs. 4.12 days, P = 0.000), earlier time to start liquid diet (3.76 vs. 4.27 days, P = 0.000), and shorter postoperative hospital stay (7.56 vs. 8.22 days, P = 0.007). The overall complication rate was 15.2% in the LTG group and 17.2% in the OTG (P = 0.503). No significant difference was observed in overall survival (OS) and disease-free survival (DFS) between LTG and OTG (60.5% vs. 57.1%, P = 0.337; 57.4% vs. 54.4%, P = 0.341). CONCLUSIONS: Compared to OTG, LTG provides surgical benefits and comparable survival outcomes for patients with locally AGC.
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Gastrectomía/métodos , Laparoscopía , Neoplasias Gástricas/cirugía , Anciano , Pérdida de Sangre Quirúrgica , Supervivencia sin Enfermedad , Femenino , Gastrectomía/efectos adversos , Tracto Gastrointestinal/fisiopatología , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Puntaje de Propensión , Recuperación de la Función , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Obese individuals exhibit brain alterations of resting-state functional connectivity (RSFC) integrity of resting-state networks (RSNs) related to food intake. Bariatric surgery is currently the most effective treatment for combating morbid obesity. How bariatric surgery influences neurocircuitry is mostly unknown. Functional connectivity density (FCD) mapping was employed to calculate local (lFCD)/global (gFCD) voxelwise connectivity metrics in 22 obese participants who underwent functional magnetic resonance imaging before and 1 month after sleeve gastrectomy (SG), and in 19 obese controls (Ctr) without surgery but tested twice (baseline and 1-month later). Two factor (group, time) repeated measures ANOVA was used to assess main and interaction effects in lFCD/gFCD; regions of interest were identified for subsequent seed to voxel connectivity analyses to assess resting-state functional connectivity and to examine association with weight loss. Bariatric surgery significantly decreased lFCD in VMPFC, posterior cingulate cortex (PCC)/precuneus, and dorsal anterior cingulate cortex (dACC)/dorsomedial prefrontal cortex (DMPFC) and decreased gFCD in VMPFC, right dorsolateral prefrontal cortex (DLPFC) and right insula (pFWE < .05). lFCD decreased in VMPFC and PCC/precuneus correlated with reduction in BMI after surgery. Seed to voxel connectivity analyses showed the VMPFC had stronger connectivity with left DLPFC and weaker connectivity with hippocampus/parahippocampus, and PCC/precuneus had stronger connectivity with right caudate and left DLPFC after surgery. Bariatric surgery significantly decreased FCD in regions involved in self-referential processing (VMPFC, DMPFC, dACC, and precuneus), and interoception (insula), and changes in VMPFC/precuneus were associated with reduction in BMI suggesting a role in improving control of eating behaviors following surgery.
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Cirugía Bariátrica , Corteza Cerebral/fisiopatología , Conectoma/métodos , Ego , Función Ejecutiva/fisiología , Red Nerviosa/fisiopatología , Obesidad Mórbida/fisiopatología , Obesidad Mórbida/cirugía , Adolescente , Adulto , Cirugía Bariátrica/métodos , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Obesidad Mórbida/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: There still remains controversy for the choice of resection extent for gastric cancer involving the middle-third of the stomach. The aim of this study was to compare the technical feasibility and long-term outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third advanced gastric cancer (AGC) and to determine which is the optimal surgical procedure. METHODS: For this study, clinical data for 379 patients who underwent LADG or LATG with D2 lymph node dissection between April 2005 and June 2014 were analyzed retrospectively. The short- and long-term outcomes were compared between the propensity score-matched groups. RESULTS: The LADG group had a significantly shorter operating time (212.74 vs. 241.79 min, P < 0.001), less estimated blood loss (114.38 vs. 181.51 ml, P = 0.000), shorter first flatus and postoperative hospital stay. Additionally, the total cost of hospitalization was significantly higher in the LATG group than LADG group (71187.58 vs. 65783.25 RMB, P = 0.000). There were no significant differences in postoperative complications rate between the LADG group and the LATG group. The 5-year overall survival (OS) rates were 64.4% in the LADG group and 61.0% in the LATG group (P = 0.548). The resection extent was not an independent prognostic factor for the OS. CONCLUSIONS: LADG with D2 nodal dissection is a feasible treatment strategy for middle-third AGC with better short-term outcomes and similar long-term survival rates compared with LATG. We recommended that DG should be the optimal surgical procedure for middle one-third AGC under the premise of negative proximal resection margin.
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Gastrectomía/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Complicaciones Posoperatorias/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Enhanced recovery after surgery (ERAS) protocols or laparoscopic technique has been applied in various surgical procedures. However, the clinical efficacy of combination of the two methods still remains unclear. Thus, our aim was to assess the role of ERAS protocols in laparoscopic abdominal surgery. METHODS: We performed a systematic literature search in various databases from January 1990 to October 2017. The results were analyzed according to predefined criteria. RESULTS: In the present meta-analysis, the outcomes of 34 comparative studies (15 randomized controlled studies and 19 non-randomized controlled studies) enrolling 3615 patients (1749 in the ERAS group and 1866 in the control group) were pooled. ERAS group was associated with shorter hospital stay (WMD - 2.37 days; 95% CI - 3.00 to - 1.73; P 0.000) and earlier time to first flatus (WMD - 0.63 days; 95% CI - 0.90 to - 0.36; P 0.000). Meanwhile, lower overall postoperative complication rate (OR 0.62; 95% CI 0.51-0.76; P 0.000) and less hospital cost (WMD 801.52 US dollar; 95% CI - 918.15 to - 684.89; P 0.000) were observed in ERAS group. Similar readmission rate (OR 0.73, 95% CI 0.52-1.03, P 0.070) and perioperative mortality (OR 1.33; 95% CI 0.53-3.34; P 0.549) were found between the two groups. CONCLUSIONS: ERAS protocol for laparoscopic abdominal surgery is safe and effective. ERAS combined with laparoscopic technique is associated with faster postoperative recovery without increasing readmission rate and perioperative mortality.
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Abdomen/cirugía , Laparoscopía , Cuidados Posoperatorios , Costos de Hospital , Humanos , Tiempo de Internación , Complicaciones PosoperatoriasRESUMEN
BACKGROUND & AIMS: The relationship between consumption of red and processed meat and pancreatic cancer risk is inconclusive. We conducted a systematic review and meta-analysis to analyze this relationship. METHODS: We performed a systematic search of PubMed, EMBASE, and the Web of Science to identify studies that examined associations between consumption of different kinds of meat with pancreatic cancer and were published through February 2016. By using data from these articles, we associated level of consumption with cancer risk and performed subgroup, meta-regression, and publication bias analyses. RESULTS: We collected and analyzed data from a total of 28 studies that involved 3,143,777 participants (11,325 consumers of red meat) and 2,904,866 participants (9955 consumers of processed meat). We observed statistically significant differences between consumers and non-consumers of these meats in case-control studies (red meat, P = .02; processed meat, P < .01) but not in cohort studies (red meat, P = .09; processed meat, P = .18). In cohort studies, a 100 g/day increase in red meat consumption was associated with significant increase in risk of pancreatic cancer (P = .01); a 50 g/day increase in processed meat consumption was not associated with significant increase in risk of pancreatic cancer (P = .90). In cohort studies, we observed associations in consumption of red meat by men and pancreatic cancer (P < .01) and consumption of processed meat by men and pancreatic cancer (P < .01) but no associations for women (red meat, P = .61; processed meat, P = .88). CONCLUSIONS: In a systematic review and meta-analysis, we found case-control but not cohort studies to associate consumption of red and processed meat with risk of pancreatic cancer. However, in cohort studies, consumption of red and processed meat appeared to increase risk of pancreatic cancer in men but not in women.