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1.
Gastroenterology ; 165(2): 402-413.e13, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36894035

RESUMEN

BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS: The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS: In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS: EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.


Asunto(s)
Gastritis Atrófica , Neoplasias Gástricas , Humanos , Biomarcadores de Tumor/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugía , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/genética , Antígeno CA-19-9 , Detección Precoz del Cáncer , Metaplasia
2.
Cell Biol Toxicol ; 40(1): 19, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38573528

RESUMEN

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) "reader" protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.


Asunto(s)
Neoplasias Gástricas , Humanos , Diferenciación Celular , Proteínas del Tejido Nervioso , Factores de Empalme de ARN
3.
Future Oncol ; 19(36): 2395-2403, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37990937

RESUMEN

At present, preoperative chemotherapy is the standard of care for the neoadjuvant treatment of potentially resectable gastric cancer (GC). However, because the efficacy and prognosis are not ideal, curative effects for this population are unsatisfactory. With the development of immune checkpoint inhibitors, the results of a few encouraging early trials of immunotherapeutic agents as neoadjuvant therapies for resectable GC have been reported. However, markers of the efficacy of immune checkpoint inhibitors remain unclear. This prospective single-center, single-arm observational study was designed to evaluate the efficacy of sintilimab plus the fluorouracil, leucovorin, oxaliplatin and docetaxel regimen as a neoadjuvant treatment for localized GC. More importantly, this work assesses multiple dimensions and include ctDNA, the immune microenvironment and intestinal microbiome to explore correlations between biomarkers and neoadjuvant therapeutic efficacy. Clinical trial registration: ChiCTR2200061629 (www.chictr.org.cn/index.aspx).


Asunto(s)
Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Docetaxel/uso terapéutico , Fluorouracilo/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Leucovorina/uso terapéutico , Terapia Neoadyuvante/métodos , Oxaliplatino/uso terapéutico , Estudios Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamiento farmacológico , Microambiente Tumoral
4.
Tumour Biol ; 39(6): 1010428317706207, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28656883

RESUMEN

Functions of microRNAs have been characterized in the embryologic, physiologic, and oncogenic processes, but the role of microRNAs in mediating tumor-specific organ metastasis was addressed only recently and still absent in gastric cancer peritoneal metastasis. Here, we used the microarray analysis to define the gastric cancer peritoneal metastasis-related microRNAs from highly peritoneal metastatic derivatives (GC-9811P cells) and the parental GC-9811 human gastric cancer cells. MiR-136 was found to be decreased in all peritoneal metastatic sublines when compared with that in the parental line. We further confirmed that miR-136 expression is frequently downregulated in gastric cancer peritoneal metastasis cells and tissues and its low expression is significantly associated with more peritoneal metastasis and worse prognosis. Moreover, restoring the expression of miR-136 could inhibit gastric cancer peritoneal metastasis in vitro and in vivo. Subsequent investigation characterized HOXC10 as a direct target of miR-136. In addition, knockdown of HOXC10 reduced GC-9811P cell migration and invasion, similar to the phenotype observed with miR-136 restoration in these cells, indicating that HOXC10 functions as a metastasis promoter in gastric cancer peritoneal metastasis. Upregulation of HOXC10 in parental GC-9811 cells resulted in a dramatic reduction of in vitro migration, invasion, and in vivo peritoneal metastasis. Furthermore, our results showed that ectopic expression of HOXC10 could reverse inhibition of metastasis by overexpressed miR-136 in GC-9811P cells. Our findings provide new insights into the role of miR-136 in the gastric cancer-specific peritoneal metastasis and implicate the potential application of miR-136 in gastric cancer peritoneal metastasis therapy.


Asunto(s)
Biomarcadores de Tumor/genética , Proteínas de Homeodominio/biosíntesis , MicroARNs/genética , Neoplasias Peritoneales/genética , Neoplasias Gástricas/genética , Animales , Biomarcadores de Tumor/biosíntesis , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Ratones , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/secundario , Peritoneo/patología , Regiones Promotoras Genéticas , Neoplasias Gástricas/patología , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Zhonghua Yi Xue Za Zhi ; 95(24): 1941-3, 2015 Jun 23.
Artículo en Zh | MEDLINE | ID: mdl-26710699

RESUMEN

OBJECTIVE: To discuss the variation of intestinal barrier and its clinical significance in patients with ulcerative colitis (UC). METHODS: Specimens were obtained from 200 patients of UC and 40 controls respectively from March 2010 to June 2013. UC samples were classified into three groups as mild (n = 68), moderate (n = 70) and severe (n = 62) according to Mayo classification. Immunohistochemistry was performed to examine the expression of occludin, ß-defensin and sIgA, which respectively reflect the changes of mechanical barrier, chemical barrier and immune barrier in intestinal tissue. The result and the clinical data were analyzed. RESULTS: Compared with controls, the expression of occludin and sIgA significantly decreased (28.53% ± 2.21% vs 44.28% ± 1.94%, 19.26% ± 1.09% vs 28.36% ± 2.36%, both P < 0.05), ß-defensin significantly increased (29.13% ± 1.75% vs 19.71% ± 1.83%, P < 0.05) in UC group. There was a significant difference of occludin levels among different active subgroups (P < 0.05), and the levels decreased significantly with the increase of UC classification (r = -0.753, P < 0.05). ß-defensin levels were significant differently among different active subgroups (P < 0.05), and the levels increased significantly with the increase of UC classification (r = 0.698, P < 0.05). There was no significant difference in the sIgA levels among the three stages (P > 0.05). In different gender, age and lesion site, there was no statistically significant difference in expression of three kinds of protein (all P > 0.05). CONCLUSION: UC patients exist intestinal barrier function injury, with the increase of UC classification, the damages of intestinal mechanical barrier and chemical barrier were more obvious.


Asunto(s)
Colitis Ulcerosa , Intestinos , Humanos , Inmunohistoquímica
6.
Adv Healthc Mater ; : e2400945, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38794820

RESUMEN

Unravelling the mechanisms for the immunosuppressive tumor microenvironment and developing corresponding therapeutic strategies are of great importance to improve the cancer immunotherapy. This study has revealed that there are abundant senescent cells accumulated in the colon cancer tissue, which contributes greatly to the immunosuppressive microenvironment. Oral delivery of Dasatinib and Quercetin (D+Q) eliminates the senescent cells with compromised efficiency due to the poor tumor penetration and short half-life. To improve the efficacy of senescent cell clearance, this work has developed an extracellular vesicle (EV) based senolytic strategy. The engineered senolytic EVs have anti-GPNMB (a senescent cell surface marker) displayed on the surface and D+Q loaded on the membrane. In a syngeneic mouse model, senolytic EVs efficiently and selectively eradicate the senescent cells and in turn unleashes the antitumor immunity. With the antitumor immunity boosted, cancer growth is inhibited and the survival is prolonged. In summary, this work has illuminated that senescent cells contribute to the immunosuppressive microenvironment in colon cancer and proposes a novel strategy to conquer the problem by EV-based senolytics.

8.
Front Nutr ; 10: 1043550, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37554699

RESUMEN

Objective: To study the value of Onodera's prognostic nutrition index (PNI) in patients with gastric neuroendocrine cancer (G-NEC). Methods: The clinical data on 148 cases of G-NEC presented between March 2010 and April 2022 were retrospectively analyzed. The relationship between the clinical characteristics of the patients and PNI was analyzed. Optimal PNI cutoff values for G-NEC prognosis prediction were calculated using the X-tile software. The survival curves were created using the Kaplan-Meier method. A Cox proportional hazards model was also established to identify independent prognostic factors that impact the prognosis of patients with G-NEC. Results: The median overall survival (OS) rate was 30 months (range 6-127 months), and the OS rates at 1, 3 and 5 years were 89.2, 71.6 and 68.2%, respectively. The mean PNI of the 148 patients before the operation was 49.5 ± 8.0. The mean PNI of patients with anemia (p < 0.001) and abnormal carcinoembryonic antigen (p = 0.039) was significantly lower than that of patients without such comorbidities. The mean PNI of patients with Stage III tumors (p < 0.001) and postoperative complications was significantly lower (p = 0.005). PNI optimal cutoff values were 50 (p < 0.001). Based on the cut-off value of the PNI, these patients were divided into a PNI-high group (PNI ≥ 50.0, n = 77) and a PNI-low group (PNI < 50.0, n = 71). The PNI-high group had a significantly better 5-years OS rate compared with the PNI-low group (76.6% vs. 59.2%, χ2 = 14.7, p < 0. 001). Multivariate analysis demonstrated that PNI and pathological stage were independent prognostic factors for patients with G-NEC. In the subgroup analysis, OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III of the disease. Conclusion: The PNI is a simple and useful marker for predicting long-term outcomes in G-NEC patients regardless of tumor stage. Based on our results, we suggest that PNI should be included in routine assessments of patients with G-NEC.

9.
Clin Res Hepatol Gastroenterol ; 47(1): 102050, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36375796

RESUMEN

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Glucosa , Radiofármacos
10.
JMIR Res Protoc ; 12: e48247, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37728978

RESUMEN

BACKGROUND: Commonly used noninvasive serological indicators serve as a step before endoscope diagnosis and help identify the high-risk gastric cancer (GC) population. However, they are associated with high false positives and high false negatives. Alternative noninvasive approaches, such as cancer-related features in cell-free DNA (cfDNA) fragments, have been gradually identified and play essential roles in early cancer detection. The integrated analysis of multiple cfDNA features has enhanced detection sensitivity compared to individual features. OBJECTIVE: This study aimed to develop and validate an assay based on assessing genomic-scale methylation and fragmentation profiles of plasma cfDNA for early cancer detection, thereby facilitating the early diagnosis of GC. The primary objective is to evaluate the overall specificity and sensitivity of the assay in predicting GC within the entire cohort, and subsequently within each clinical stage of GC. The secondary objective involved investigating the specificity and sensitivity of the assay in combination with possible serological indicators. METHODS: This is an observational case-control study. Blood samples will be prospectively collected before gastroscopy from 180 patients with GC and 180 nonmalignant control subjects (healthy or with benign gastric diseases). Cases and controls will be randomly divided into a training and a testing data set at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed by bisulfite-free low-depth whole methylome sequencing. A multidimensional model named Thorough Epigenetic Marker Integration Solution (THEMIS) will be constructed in the training data set. The model includes features such as the methylated fragment ratio, chromosomal aneuploidy of featured fragments, fragment size index, and fragment end motif. The performance of the model in distinguishing between patients with cancer and noncancer controls will then be evaluated in the testing data set. Furthermore, GC-related biomarkers, such as pepsinogen, gastrin-17, and Helicobacter pylori, will be measured for each patient, and their predictive accuracy will be assessed both independently and in combination with the THEMIS model. RESULTS: Recruitment began in November 2022 and will be ended in April 2024. As of August 2022,250 patients have been enrolled. The final data analysis is anticipated to be completed by September 2024. CONCLUSIONS: This is the first registered case-control study designed to investigate a stacked ensemble model integrating several cfDNA features generated from a bisulfite-free whole methylome sequencing assay. These features include methylation patterns, fragmentation profiles, and chromosomal copy number changes, with the aim of identifying the GC population. This study will determine whether multidimensional analysis of cfDNA will prove to be an effective strategy for distinguishing patients with GC from nonmalignant individuals within the Chinese population. We anticipate the THEMIS model will complement the standard-of-care screening and aid in identifying high-risk patients for further diagnosis. TRIAL REGISTRATION: ClinicalTrial.gov NCT05668910; https://www.clinicaltrials.gov/study/NCT05668910. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48247.

11.
Int J Surg ; 109(5): 1094-1104, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37222716

RESUMEN

BACKGROUND: The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS: In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS: Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION: Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.


Asunto(s)
ARN Largo no Codificante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Terapia Neoadyuvante , ARN Largo no Codificante/genética , Estudios de Cohortes , Supervivencia sin Enfermedad
12.
Front Oncol ; 12: 1042314, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36776381

RESUMEN

Objective: This study aimed to compare the feasibility and short-term clinical efficacy of triple-port laparoscopic distal gastrectomy (TPLDG) with five-port laparoscopic distal gastrectomy (FPLDG). Methods: From April 2020 to December 2021, this retrospective study included all consecutive patients (n = 21) who underwent TPLDG + D2 lymph node dissection, and randomly screened patients who underwent FPLDG + D2 lymph node dissection during this period (n = 30). Results: There were no significant differences in intraoperative (P > 0.05) and postoperative complication rate (P = 0.635) between the two groups. The changes in the first ambulation, flatus, water intake after surgery and postoperative hospitalization were also similar between the two groups (P > 0.05). However, time to abdominal drainage tube removal (1.62 ± 0.15 days vs. 2.00 ± 0.12 days, P = 0.046), NRS pain score on the first postoperative day (1.91 ± 0.15 days vs. 2.47 ± 0.12 days, P = 0.004) and hemameba level on the third postoperative day (7.89 ± 0.51 days vs. 10.52 ± 0.58 days, P = 0.002) were significantly lower in the TPLDG group compared to the FPLDG group. Conclusion: TPLDG is a safer, feasible, and short-term alternative to conventional LDG for distal gastric cancer.

13.
Front Endocrinol (Lausanne) ; 13: 947708, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36111294

RESUMEN

Background: This research aimed to build an m6A-associated lncRNA prognostic model of esophageal cancer that can be used to predict outcome in esophageal cancer patients. Methods: RNA sequencing transcriptome data and clinical information about patients with esophageal cancer were obtained according to TCGA. Twenty-four m6A-associated genes were selected based on previous studies. m6A-associated lncRNAs were determined through Pearson correlation analysis. Three m6A-associated lncRNA prognostic signatures were built through analysis of the training set using univariate, LASSO, and multivariate Cox regression. To validate the stabilization of the risk signature, Kaplan-Meier and ROC curve analyses were performed on the testing and complete sets. The prognoses of EC patients were predicted quantitatively by building a nomogram. GSEA was conducted to analyze the underlying signaling pathways and biological processes. To identify the underlying mechanisms through which the lncRNAs act, we constructed a PPI network and a ceRNA network and conducted GO and KEGG pathway analyses. EC samples were evaluated using the ESTIMATE algorithm to compute stromal, immune, and estimate scores. The ssGSEA algorithm was used to quantitatively infer immune cell infiltration and immune functions. The TIDE algorithm was performed to simulate immune evasion and predict the response to immunotherapy. Results: We identified and validated an m6A-associated lncRNA risk model in EC that could correctly and reliably predict the OS of EC patients. The ceRNA network, PPI network, and GO and KEGG pathway analyses confirmed and the underlying mechanisms and functions provided enlightenment regarding therapeutic strategies for EC. Immunotherapy responses were better in the low-risk subgroup, and PD-1 and CTLA4 checkpoint immunotherapy benefited the patients in the low-risk subgroup. Conclusions: We constructed a new m6A-related lncRNA prognostic risk model of EC, based on three m6A-related lncRNAs: LINC01612, AC025166.1 and AC016876.2, that can predict the prognoses of EC patients.


Asunto(s)
Neoplasias Esofágicas , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , ARN Largo no Codificante/genética , Enfermedades Raras/genética
14.
Front Nutr ; 9: 993896, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36082028

RESUMEN

Background: Total laparoscopic total gastrectomy (TLTG) for gastric cancer, especially with overlap esophagojejunostomy, has been verified that it has advantages of minimally invasion, less intraoperative bleeding, and faster recovery. Meanwhile, early oral feeding (EOF) after the operation has been demonstrated to significantly promote early rehabilitation in patients, particularly with distal gastrectomy. However, due to the limited application of TLTG, there is few related research proving whether it is credible or safe to adopt EOF after TLTG (overlap esophagojejunostomy). So, it is urgent to start a prospective, multicenter, randomized clinical trials to supply high level evidence. Methods/design: This study is a prospective, multicenter, randomized controlled trial with 200 patients (100 in each group). These eligible participants are randomly allocated into two different groups, including EOF group and delay oral feeding (DOF) group after TLTG (overlap esophagojejunostomy). Anastomotic leakage will be carefully observed and recorded as the primary endpoints; the period of the first defecation and exhaust, postoperative length of stay and hospitalization expenses will be recorded as secondary endpoints to ascertain the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy). Discussion: Recently, the adoption of TLTG was limited due to its difficult anastomotic procedure, especially in vivo esophagojejunostomy. With the innovation and improvement of operating techniques, overlap esophagojejunostomy with linear staplers simplified the anastomotic steps and reduced operational difficulties after TLTG. Meanwhile, EOF had received increasing attention from surgical clinicians as a nutrition part of enhanced recovery after surgery (ERAS), which had shown better results in patients after distal gastrectomy. Considering the above factors, we implemented EOF protocol to evaluate the feasibility and safety of adopting EOF after TLTG (overlap esophagojejunostomy), which provided additional evidence for the development of clinical nutrition guidelines. Clinical trial registration: [www.chictr.org.cn], identifier [ChiECRCT20200440 and ChiCTR2000040692].

15.
Life Sci ; 277: 119468, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33811901

RESUMEN

AIM: Small bowel transplantation (SBT) is the only therapy for end-stage short bowel syndrome. However, complicated pathological changes and an increased risk of postoperative infections in the perioperative period are major obstacles to patient survival, but the associated mechanisms remain unclear. METHODS: To explore perioperative alterations in the intestinal microbiota and their functional changes after SBT, 16S rRNA sequencing of ileostomy effluents and plasma analysis were performed pre-SBT and periodically post-SBT. RESULTS: The results suggested that the presence of Proteobacteria accelerated bacterial motility and chemotaxis during the first week in post-SBT recipients. Altered gut microbiota impaired intestinal barrier integrity and upregulated 16S rDNA, pathogen-associated molecular pattern (PAMP) and pattern-recognition molecule (PRM) levels in peripheral circulation. Importantly, the levels of neutrophils, monocytes, cytotoxic T lymphocytes, and natural killer cells and the expression of proinflammatory cytokines were increased in the peripheral blood and had potential roles in activating innate immune-mediated inflammatory injury after SBT. CONCLUSION: Together, our results suggest that altered microbiota and functional changes are probably related to innate immune-mediated inflammatory injury and graft survival after SBT, suggesting that the monitoring and regulation of intestinal microbiota are necessary for SBT patients.


Asunto(s)
Microbioma Gastrointestinal/inmunología , Intestino Delgado/microbiología , Intestino Delgado/trasplante , China , Citocinas/inmunología , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Supervivencia de Injerto/inmunología , Humanos , Inmunidad Innata/inmunología , Inflamación/inmunología , ARN Ribosómico 16S/genética
16.
Medicine (Baltimore) ; 100(20): e25793, 2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34011041

RESUMEN

ABSTRACT: Preoperative pulmonary function assessment is applied to select surgical candidates and predict the occurrence of postoperative complications. This present study enrolled 2323 colorectal cancer patients. Forced vital capacity (FVC) and maximal voluntary ventilation (MVV) were measured as predicted values. Associations between patient pulmonary function and both prognosis and postoperative complications was analyzed. The value of FVC and MVV optimal cutoff was 98.1 (P < .001) and 92.5 (P < .001), respectively. Low FVC and low MVV were associated with higher rates of postoperative fever (23.8% vs 13.9%, P < .001; 17.8% vs 13.3%, P = .049, respectively) and with higher rates of pneumonia (3.75% vs 1.73%, P = .002; 3.00% vs 1.71%, P = .009, respectively), pleural effusion (3.00% vs 1.57%, P = .033; 3.18% vs 1.42%, P = .006, respectively), and poor patient prognosis (5-year overall survival: 80.0% vs 90.3%, P < .001; 71.7% vs 91.9%, P < .001, respectively). In addition, low FVC was closely related to the higher rate of anastomosis leak (4.31% vs 2.29%, P = .013), low MVV was correlated with the higher rate of uroschesis (2.38% vs 0.65%, P < .001). In subgroup analyses, the predictive value of FVC and MVV in patients with different tumor stage was analyzed. Both low FVC and MVV were independent risk factors for poor prognosis in stage II and III, indicating that low FVC and MVV are predictive of poorer prognosis and higher risk of postoperative complications in colorectal cancer patients.


Asunto(s)
Colectomía/efectos adversos , Neoplasias Colorrectales/cirugía , Complicaciones Posoperatorias/epidemiología , Proctectomía/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Femenino , Fiebre/epidemiología , Fiebre/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Ventilación Voluntaria Máxima , Persona de Mediana Edad , Estadificación de Neoplasias , Derrame Pleural/epidemiología , Derrame Pleural/etiología , Neumonía/epidemiología , Neumonía/etiología , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Factores Sexuales , Capacidad Vital , Adulto Joven
17.
Medicine (Baltimore) ; 99(16): e19692, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32311946

RESUMEN

To evaluate the effect of the open abdomen (OA) and closed abdomen (CA) approaches for treating intestinal fistula with complicated intra-abdominal infection (IFWCIAI), and analyze the risk factors in OA treatment.IFWCIAI is associated with high mortality rates and healthcare costs, as well as longer postoperative hospital stay. However, OA treatment has also been linked with increased mortality and development of secondary intestinal fistula.A total of 195 IFWCIAI patients who were operated over a period of 7 years at our hospital were retrospectively analyzed. These patients were divided into the OA group (n = 112) and CA group (n = 83) accordingly, and the mortality rates, hospital costs, and hospital stay duration of both groups were compared. In addition, the risk factors in OA treatment were also analyzed.OA resulted in significantly lower mortality rates (9.8% vs 30.1%, P < .001) and hospital costs ($11721.40 ±â€Š$9368.86 vs $20365.36 ±â€Š$21789.06, P < .001) compared with the CA group. No incidences of secondary intestinal fistula was recorded and the duration of hospital stay was similar for both groups (P = .151). Delayed OA was an independent risk factor of death following OA treatment (hazard ratio [HR] = 1.316; 95% confidence interval [CI] = 1.068-1.623, P = .010), whereas early enteral nutrition (EN) exceeding 666.67 mL was a protective factor (HR = 0.996; 95% CI = 0.993-0.999, P = .018). In addition, Acinetobacter baumannii, Pseudomonas aeruginosa, and Candida albicans were the main pathogens responsible for the death of patients after OA treatment.OA decreased mortality rates and hospital costs of IFWCIAI patients, and did not lead to any secondary fistulas. Early OA and EN also reduced mortality rates.


Asunto(s)
Fístula del Sistema Digestivo/mortalidad , Fístula del Sistema Digestivo/cirugía , Infecciones Intraabdominales/mortalidad , Infecciones Intraabdominales/cirugía , Técnicas de Abdomen Abierto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fístula del Sistema Digestivo/complicaciones , Fístula del Sistema Digestivo/economía , Femenino , Costos de la Atención en Salud , Humanos , Infecciones Intraabdominales/complicaciones , Infecciones Intraabdominales/economía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Técnicas de Abdomen Abierto/economía , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
18.
Medicine (Baltimore) ; 98(47): e17837, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31764779

RESUMEN

INTRODUCTION: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare differential diagnosis for patients presenting with abdominal pain. Due to limited cases reported, surgical management strategies are poorly defined. PATIENT CONCERNS: A 54-year-old man presented to our emergency department with a 4-day history of epigastric pain combined with nausea and vomiting. The pain was dull, constant, and unbearable. It was accompanied by abdominal distention, but there was no radiating pain, chills, fever, or hematochezia. The patient did not have a history of abdominal surgeries, or tobacco or illicit drug use. DIAGNOSIS: A contrast-enhanced computerized tomography (CT) scan demonstrated an isolated and spontaneous superior mesenteric artery dissection with aneurysmal evolution of the false lumen, involving multiple side branches. The middle-lower jejunum and the whole ileum were extensively dilated, and the middle jejunum was ischemic with edema. INTERVENTIONS: Exploratory laparotomy and autologous small bowel transplantation. OUTCOMES: The patient was successfully treated using exploratory laparotomy and intestinal autotransplantation (IATx) without bowel resection and had a stable recovery without complications. CONCLUSION: For patients with severe mesenteric ischemia or those who fail to respond to initial conservative treatment, IATx may be a reasonable treatment strategy.


Asunto(s)
Disección Aórtica/cirugía , Intestino Delgado/trasplante , Arteria Mesentérica Superior/cirugía , Humanos , Masculino , Persona de Mediana Edad , Trasplante Autólogo , Procedimientos Quirúrgicos Vasculares/métodos
19.
J Cancer ; 10(26): 6584-6593, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31777587

RESUMEN

A positive association between the ABO blood types and survival has been suggested in several malignancies. However, little is known about the relationship between ABO blood group and survival in rectal cancer patients. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of a Chinese population in Northwest China region with curatively resected rectal cancer. We retrospectively analyzed 1613 consecutive patients who underwent curative surgery for rectal cancer between June, 2011 and December, 2016. The relationship between the ABO blood types and overall survival (OS) was analyzed. The median follow-up period of the 1613 rectal cancer patients was 69.6 months with 1427 alive. There was a significance difference of survival among ABO blood groups (P=0.007). The mean overall survival (OS) of the blood type B patients was 70.8 months, O was 64.3, whereas the mean OS of the AB and A blood type patients was significantly lower, 58.4 months and 59.7 months respectively (P=0.007, log-rank test). Compared with patients with A and AB blood types, patients with blood type B and O were more likely to have better survival(P=0.001). A blood groups were associated with significantly decreased overall survival in rectal cancer patients (hazard ratio = 1.263; 95% confidence interval = 0.776-2.054, P =0.010). In order to confirm our above results, we performed the same investigation in an independent cohort from another hospital of 505 Chinese patients and get the similar results. Our study showed that ABO blood group is associated with survival in Northwest Chinese patients with rectal cancer and the blood type B and O were favourable prognostic factors for patients with rectal cancer.

20.
Transplant Direct ; 4(8): e374, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30255134

RESUMEN

BACKGROUND: The availability of an identical twin donor that allows avoidance of complications related to graft rejection and immunosuppression represents an ideal treatment option for irreversible intestinal failure. METHODS AND RESULTS: We described a 45-year-old woman who lost most of her small bowel due to acute superior mesenteric thrombosis received a living-related small bowel transplant from her identical-twin sister. Monozygosity was established by buccal smear DNA amplification using short tandem repeat. A pretransplant panel-reactive antibody was 47.5% with several HLA antibodies in higher titers. The patient received a brief course of steroids without any additional immunosuppressive agents after transplantation. Her postoperative course was uneventful without an episode of rejection or infection. The preformed HLA antibodies steadily declined over time after transplantation. At a 5-year follow-up, the patient achieved full enteral autonomy from parenteral nutrition with a regular lifestyle. CONCLUSIONS: Identical-twin intestinal transplantation appears to provide the best outcomes by avoiding complications related to rejection and immunosuppression. We provide evidence that it may confer greater long-term immunological advantages even in a high-immunologic risk recipient.

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