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Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.
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Contenido Digestivo , Obstrucción Intestinal , Humanos , Femenino , Persona de Mediana Edad , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/cirugía , Necrosis/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Colorectal cancer (CRC) remains a significant global health concern, as characterized by its high mortality rate ranking second among all the leading causes of death. The liver serves as the primary site of CRC metastasis, and the occurrence of liver metastasis is a significant contributor to mortality among patients diagnosed with CRC. The survival rate of patients with colorectal liver metastasis has significantly increased with the advancement of comprehensive tumor therapy. However, radical surgery remains the key factor. Since there are frequently multiple liver metastases, which are prone to recurrence after surgery, it is crucial to preserve as much liver parenchyma as possible without affecting the prognosis. The issue of surgical margins plays a crucial role in this regard. In this review, we begin by examining the occurrence of positive surgical margins in liver metastases of patients diagnosed with CRC. We aim to define positive margins in hepatic surgery, examine the relationship between margins and prognosis and establish a foundation for future research in this field.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Márgenes de Escisión , Hepatectomía , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/patología , PronósticoRESUMEN
PURPOSE: To assess diagnostic performance and reproducibility of reduced bowel wall enhancement evaluated by quantitative methods using CT to identify bowel necrosis among closed-loop small bowel obstruction (CL-SBO) patients. METHODS: This retrospective single-center study included patients who diagnosed with CL-SBO caused by adhesion or internal hernia during January 2016 and May 2022. Patients were divided into necrotic group (n = 41) and non-necrotic group (n = 67) according to surgical exploration and postoperative pathology. Two doctors independently measured the attenuation of bowel wall and consensus was reached through panel discussion with a third gastrointestinal radiologist. Reduced bowel wall enhancement was assessed by four quantitative methods. Univariate analyses were used to evaluate the association between each method and bowel necrosis, and kappa/intraclass correlation coefficient values were used to assess interobserver agreement. Diagnostic performance parameters were calculated for each method. RESULTS: Reduced bowel wall enhancement in arterial phase (OR 8.98, P < 0.0001), reduced bowel wall enhancement in portal phase (OR 16.84, P < 0.001), adjusted reduced bowel wall enhancement in arterial phase (OR 29.48, P < 0.001), adjusted reduced bowel wall enhancement in portal phase (OR 145.69, P < 0.001) were significantly associated with bowel necrosis. Adjusted reduced bowel wall enhancement in portal phase had the best diagnostic performance (AUC: 0.92; Youden index: 0.84; specificity: 94.03 %) and interobserver agreement (kappa value of 0.59-0.73) to predict bowel necrosis. CONCLUSION: When assessing reduced bowel enhancement to predict bowel necrosis among CL-SBO patients, using unenhanced CT images and proximal dilated loop as standard references in portal phase is the most accurate quantitative method among those tested.
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Traumatismos Abdominales , Obstrucción Intestinal , Enfermedades Vasculares , Humanos , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Intestino Delgado/diagnóstico por imagen , Sensibilidad y Especificidad , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/cirugía , Enfermedades Vasculares/patología , Necrosis/diagnóstico por imagen , Necrosis/patología , Traumatismos Abdominales/complicacionesRESUMEN
Background and objective: Gastric cancer (GC) represents a major factor inducing global cancer-associated deaths, but specific biomarkers and therapeutic targets for GC are lacking at present. Therefore, the present work focused on developing an immune-related genetic signature at the single-cell level for categorizing GC cases and predicting patient prognostic outcome, immune status as well as treatment response. Methods: Single-cell RNA-sequencing (scRNA-seq) data were combined with bulk RNA-seq data in GC patients for subsequent analyses. Differences in overall survival (OS), genomic alterations, immune status, together with estimated immunotherapeutic outcomes were measured between different groups. Results: Nine cell types were identified by analyzing scRNA-seq data from GC patients, and marker genes of immune cells were also selected for subsequent analysis. In addition, an immune-related signature was established to predict OS while validating the prediction power for GC patients. Afterwards, a nomogram with high accuracy was constructed for improving our constructed signature's clinical utility. The low-risk group was featured by high tumor mutation burden (TMB), increased immune activation, and microsatellite instability-high (MSI-H), which were related to the prolonged OS and used in immunotherapy. By contrast, high-risk group was associated with microsatellite stability (MSS), low TMB and immunosuppression, which might be more suitable for targeted therapy. Meanwhile, the risk score generated by our signature was markedly related to the cancer stem cell (CSC) index. In addition, the immunotherapeutic response prediction accuracy of our signature was validated in an external dataset IMvigor210 cohort. Conclusion: A signature was constructed according to scRNA-seq data analysis. The signature-screened low- and high-risk patients had different prognoses, immune statuses and enriched functions and pathways. Such results shed more lights on immune status of GC, prognosis assessment, and development of efficient immunotherapeutic treatments.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/metabolismo , Pronóstico , Inestabilidad de Microsatélites , Inmunoterapia , ARN , Microambiente Tumoral/genéticaRESUMEN
Background: Hepatocellular carcinoma (HCC) refers to the malignant tumor associated with a high mortality rate. This work focused on identifying a robust tumor glycolysis-immune-related gene signature to facilitate the prognosis prediction of HCC cases. Methods: This work adopted t-SNE algorithms for predicting glycolysis status in accordance with The Cancer Genome Atlas (TCGA)-derived cohort transcriptome profiles. In addition, the Cox regression model was utilized together with LASSO to identify prognosis-related genes (PRGs). In addition, the results were externally validated with the International Cancer Genome Consortium (ICGC) cohort. Results: Accordingly, the glycolysis-immune-related gene signature, which consisted of seven genes, PSRC1, CHORDC1, KPNA2, CDCA8, G6PD, NEIL3, and EZH2, was constructed based on TCGA-HCC patients. Under a range of circumstances, low-risk patients had extended overall survival (OS) compared with high-risk patients. Additionally, the developed gene signature acted as the independent factor, which was significantly associated with clinical stage, grade, portal vein invasion, and intrahepatic vein invasion among HCC cases. In addition, as revealed by the receiver operating characteristic (ROC) curve, the model showed high efficiency. Moreover, the different glycolysis and immune statuses between the two groups were further revealed by functional analysis. Conclusion: Our as-constructed prognosis prediction model contributes to HCC risk stratification.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors of the human digestive system. Due to its insidious onset, many patients have already lost the opportunity for radical resection upon tumor diagnosis. In recent years, neoadjuvant treatment for patients with borderline resectable PDAC has been recommended by multiple guidelines to increase the resection rate of radical surgery and improve the postoperative survival. However, further developments are required to accurately assess the tumor response to neoadjuvant therapy and to select the population suitable for such treatment. Reductions in drug toxicity and the number of neoadjuvant cycles are also critical. At present, the clinical evaluation of neoadjuvant treatment is mainly based on several serological and imaging indicators; however, the unique characteristics of PDAC and the insufficient sensitivity and specificity of the markers render this system ineffective. The imaging evaluation system, magnetic resonance imaging (MRI), has its own unique imaging advantages compared with computed tomography (CT) and other imaging examinations. One key advantage is the ability to reflect the changes more rapidly in tumor tissue components, such as the degree of fibrosis, microvessel density, and tissue hypoxia. It can also perform multiparameter quantitative analysis of tumor tissue and changes, attributing to its increasingly important role in imaging evaluation, and potentially the evaluation of neoadjuvant treatment of pancreatic cancer, as several current articles have studied. At the same time, owing to the complexity of MRI and some of its limitations, its wider application is limited. Compared with CT imaging, few relevant studies have been conducted. In this review article, we will investigate and summarize the advantages, limitations, and future development of MRI in the evaluation of neoadjuvant treatment of PDAC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/terapia , Humanos , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Neoplasias PancreáticasRESUMEN
BACKGROUND: A novel procedure called shark mouth pancreaticojejunostomy (SMP) was developed, for the reconstruction of the pancreatic stump which has a theoretical advantage for anastomosis healing and wide applicability. METHODS: A comparative study of the patients who underwent SMP (SMP cohort) and those who underwent end-to-end dunking pancreaticojejunostomy (historic cohort) at Peking University Third Hospital was conducted. Each group was analyzed for the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) and morbidities. RESULTS: The clinicopathological data of 151 patients from the SMP cohort and 82 patients from the historic cohort were analyzed. In the SMP group, the rate of CR-POPF was 7.3% (11/151), which was significantly lower than the rate of CR-POPF in the historic group as 19.5% (16/82) (P = 0.005). The primary results were unaffected by sensitivity analyses based on several risk factors for CR-POPF. The rates of morbidities besides CR-POPF were 15.9% (24/151) in the SMP group and 17.1% (14/82) in the historic cohort (P = 0.194). The principal results were not changed by the propensity score matched (PSM) analysis. CONCLUSION: SMP is a safe and simple surgical procedure for the reconstruction of the pancreatic stump compared with end-to-end dunking pancreticojejunostomy.
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Pancreatoyeyunostomía , Tiburones , Animales , Humanos , Boca/cirugía , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/efectos adversos , Pancreatoyeyunostomía/efectos adversos , Pancreatoyeyunostomía/métodos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Introduction: The effect of liver margin on colorectal cancer liver metastases (CRLM) after hepatectomy has been controversial. In this study, we conducted a postoperative follow-up study of 205 patients with CRLM to clarify whether a positive margin is significant and to define the risk factors affecting CRLM survival. Methods: The data of 205 patients with CRLM who underwent surgical treatment at the Third Hospital of Peking University in the Department of General Surgery from January 2009 to December 2020 were retrospectively analyzed. The general data, surgical data and postoperative follow-up of the patients were statistically analyzed. Results: There were 130 cases (63.4%) of R0 resection and 75 cases (36.6%) of R1 resection. There were 136 males and 69 females, age 61 ± 11 years, and body mass index (BMI 24.5 ± 3.3â kg/m2). The overall survival rates at 1, 3, and 5 years for the entire cohort were 93.4%, 68.4%, and 45.5% in the R0 resection group vs. 93.2%, 53.7%, and 42% in the R1 resection group, respectively, which were not statistically significant (P = 0.520). The 1-, 3-, and 5-year disease-free survival rates of 63.2%, 33.3%, and 29.7% were significantly better in the R0 resection group than in the R1 resection group of 47.9%, 22.7%, and 17.7% (P = 0.016), respectively. After multivariable analysis, carbohydrate antigen 19-9 (CA19-9) > 39â U/ml (HR = 2.29, 95% CI: 1.39-3.79, P = 0.001), primary tumor perineural invasion (HR = 1.78, 95% CI: 1.01-3.13, P = 0.047), and BMI > 24â kg/m2 (HR = 1.75, 95% CI: 1.05-2.93, P = 0.033) were independently associated with poorer overall patient survival. The number of liver metastases >2 (HR = 1.65, 95% CI: 1.10-2.47, P = 0.016), the maximum diameter of metastases ≥50â mm (HR = 1.67, 95% CI: 1.06-2.64, P = 0.026), and vascular invasion of the primary tumor (HR = 1.65, 95% CI: 1.03-2.64, P = 0.038) were also independently associated with poorer disease-free survival. Conclusion: In patients undergoing hepatectomy for CRLM, the negative effect of the R1 margin should be downplayed, and although the disease-free survival of the R1 margin is shorter than that of the R0 margin, it has no impact on overall survival. To improve overall survival, extra attention should be given to the factors of preoperative BMI, preoperative CA19-9, and the presence of perineural invasion of the primary tumor.
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OBJECTIVES: The aims of this review were to determine whether positive peritoneal lavage cytology (CY+) precludes radical resection in pancreatic cancer and to propose prospections for future studies. METHODS: MEDLINE, Embase, and Cochrane Central were searched for related articles. Dichotomous variables and survival outcomes were analyzed with the estimation of odds ratio and hazards ratio (HR), respectively. RESULTS: A total of 4905 patients were included, of which 7.8% were CY+. Positive peritoneal lavage cytology was correlated with poor overall survival (univariate survival analysis [HR, 2.35; P < 0.00001]; multivariate analysis [HR, 1.62; P < 0.00001]), poor recurrence-free survival (univariate survival analysis [HR, 2.50; P < 0.00001]; multivariate analysis [HR, 1.84; P < 0.00001]), and higher initial peritoneal recurrence rate (odds ratio, 5.49; P < 0.00001). CONCLUSIONS: Although CY+ predicts poor prognosis and a higher risk of peritoneal metastasis after curative resection, it is not sufficient to preclude curative resection based on the current evidence, and high-quality trials should be conducted to assess the prognostic impact of operation among resectable CY+ patients. In addition, more sensitive and accurate methods to detect peritoneal exfoliated tumor cells and more effective comprehensive treatment for resectable CY+ pancreatic cancer patients are clearly warranted.
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Neoplasias Pancreáticas , Neoplasias Peritoneales , Humanos , Citología , Peritoneo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Lavado Peritoneal/métodos , Neoplasias Peritoneales/secundario , Pronóstico , Estudios Retrospectivos , Neoplasias PancreáticasAsunto(s)
Coristoma/diagnóstico por imagen , Hepatopatías/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Adulto , Coristoma/complicaciones , Coristoma/patología , Femenino , Humanos , Hepatopatías/complicaciones , Hepatopatías/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Páncreas/patología , Neoplasias Intraductales Pancreáticas/complicaciones , Neoplasias Intraductales Pancreáticas/patologíaRESUMEN
Objective To establish a nomogram for predicting the distant metastasis risk of pancreatic neuroendocrine tumors (pNETs) in elderly patients. Methods We extracted data of patients with diagnosis of pNETs at age ≥65 years old between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. All eligible patients were divided randomly into a training cohort and validation cohort. Uni- and multivariate logistic regression analyses were performed on the training cohort to identify independent factors for distant metastasis. A nomogram was developed based on the independent risk factors using rms packages of R software, and was validated internally by the training cohort and externally by the validation cohort using C-index and calibration curves. Results A total of 411 elderly patients were identified, of which 260 were assigned to training cohort and 151 to validation cohort. Univariate and multivariate logistic regression analyses indicated the tumor site (body/tail of pancreas: odds ratio [OR]=2.282; 95% confidence interval [CI]: 1.174 - 4.436, P<0.05), histological grade (poorly differentiated/undifferentiated: OR=2.600, 95% CI: 1.266-5.339, P<0.05), T stage (T2: OR=8.913, 95% CI: 1.985-40.010, P<0.05; T3: OR=11.830, 95% CI: 2.530-55.350, P<0.05; T4: OR=68.650, 95% CI: 8.020-587.600, P<0.05), and N stage (N1: OR=3.480, 95% CI: 1.807-6.703, P<0.05) were identified as independent risk factors for distant metastasis of pNETs in elderly. The nomogram exhibited good predicting accuracy, with a C-index of 0.809 (95% CI: 0.757 - 0.861) in internal validation and 0.795 (95% CI: 0.723 - 0.867) in external validation, respectively. The predicted distant metastasis rates were in satisfactory agreement with the observed values by the calibration curves. Conclusion The nomogram we established showed high discriminative ability and accuracy in evaluation of distant metastasis risk in elderly pNETs patients, and could provide a reference for individualized tumor evaluation and treatment decision in elderly pNETs patients.
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Nomogramas , Neoplasias Pancreáticas , Anciano , Humanos , Estadificación de Neoplasias , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: Surgical resection remains the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, a number of patients get disease recurred in a short time post-operation. Few studies have focused on the predictors of different recurrence patterns of PDAC. OBJECTIVE: To try to establish and verify a nomogram to predict recurrence free survival (RFS) in PDAC patients, and to distinguish the risk factors of local recurrence first and distant metastasis first via competing risk model. METHODS: Patients who underwent radical pancreatectomy for PDAC in our center from 2010 to 2018 were reviewed retrospectively. Kaplan-Meier methods and multivariate Cox regression analyses were used to identify the clinicopathological predictors of recurrence post-operation. And then, a nomogram was constructed and validated. Competing risk regression model was used to compare the predictors between local recurrence group and distant metastasis group. RESULTS: A total of 200 patients were included into the final analysis, and 153 patients got disease relapsed post-operation. CA19-9 level, vascular resection, tumor differentiation, lymph node ratio (LNR) and adjuvant chemotherapy were identified as independent risk factors for recurrence free survival (RFS) and incorporated into the nomogram. The C-index of the nomogram was 0.650. Competing risk model indicated that the status of lymph-node metastasis was significantly associated the patterns of first relapse. CONCLUSIONS: Nomogram and competing risk model were constructed to quantify the risk of recurrence following surgery for PDAC. Our findings may be useful for predicting RFS and recurrence pattern in clinical work.
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INTRODUCTION: Macrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases. METHODS: We identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, "key driver" mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed. RESULTS: We detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P < 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line. CONCLUSIONS: The nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.
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BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.
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COVID-19/complicaciones , Hepatopatías/virología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/mortalidad , COVID-19/fisiopatología , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hepatopatías/diagnóstico , Hepatopatías/mortalidad , Hepatopatías/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Tumor microenvironment (TME) exerts key roles in pancreatic ductal adenocarcinoma (PDAC) development. However, the factors regulating the cross-talk between PDAC cells and TME are largely unknown. In the present study, we identified a long noncoding RNA (lncRNA) KLHDC7B divergent transcript (KLHDC7B-DT), which was up-regulated in PDAC and correlated with poor survival of PDAC patients. Functional assays demonstrated that KLHDC7B-DT enhanced PDAC cell proliferation, migration, and invasion. Mechanistically, KLHDC7B-DT was found to directly bind IL-6 promoter, induce open chromatin structure at IL-6 promoter region, activate IL-6 transcription, and up-regulate IL-6 expression and secretion. The expression of KLHDC7B-DT was positively correlated with IL-6 in PDAC tissues. Via inducing IL-6 secretion, KLHDC7B-DT activated STAT3 signaling in PDAC cells in an autocrine manner. Furthermore, KLHDC7B-DT also activated STAT3 signaling in macrophages in a paracrine manner, which induced macrophage M2 polarization. KLHDC7B-DT overexpressed PDAC cells-primed macrophages promoted PDAC cell proliferation, migration, and invasion. Blocking IL-6/STAT3 signaling reversed the effects of KLHDC7B-DT on macrophage M2 polarization and PDAC cell proliferation, migration, and invasion. In conclusion, KLHDC7B-DT enhanced malignant behaviors of PDAC cells via IL-6-induced macrophage M2 polarization and IL-6-activated STAT3 signaling in PDAC cells. The cross-talk between PDAC cells and macrophages induced by KLHDC7B-DT represents potential therapeutic target for PDAC.
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Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Transducción de Señal/genética , Microambiente Tumoral , Macrófagos Asociados a Tumores/metabolismoRESUMEN
Objective To investigate the impact of prior non-pancreatic cancer on the survival outcomes of patients with localized pancreatic neuroendocrine tumors (PanNETs). Methods We reviewed the Surveillance, Epidemiology, and End Results database and selected patients with localized PanNETs diagnosed between 1973 and 2015. We divided the patients into two groups according to the presence or absence of prior non-pancreatic malignancy. Before and after propensity score matching, we compared the clinicopathological characteristics and studied the overall survival and cancer-specific survival. Results A total of 357 (12.9%) of 2778 patients with localized PanNETs had prior cancer. A total of 1211 cases with only a localized PanNET and 133 cases with a localized PanNET and prior cancer had complete data and met the inclusion criteria of the current study. Patients with prior cancer were associated with advanced age (>65 years, 57.9% prior cancer vs. 31.0% no prior cancer, P<0.001), later year of diagnosis (87.2% vs. 80.2%, P=0.049), a higher proportion of poorly differentiated/undifferentiated grade tumors (4.5% vs. 1.5%, P=0.025), and a higher proportion of no primary site surgery (19.5% vs. 10.4%, P=0.003). Prostate (29.32%), breast (18.05%), other genitourinary and retroperitoneal (16.54%), and gastrointestinal (12.78%) cancers were the most common prior cancer types. Most of the prior cancers (95.49%) were localized and regional, and only 4.51% of the prior cancers were distant. Patients with interval periods between the prior cancer and PanNET of ≤36 months, 36-60 months, 60-120 months, and >120 months accounted for 33.08%, 13.53%, 24.06%, and 29.32% of all cases with prior cancers, respectively. Univariate and multivariate Cox proportional hazards analyses were performed. The presence/absence of prior cancers did not impact survival outcomes of patients with localized PanNETs before and after propensity score matching (PSM). Further subgroups analysis showed that, patients with localized PanNETs and prior distant cancer had worse cancer-specific survival than patients with prior local/regional cancer or patients without prior cancer (P<0.001). No significant differences in cancer-specific survival were observed in terms of the different sites of the prior cancers and the different interval periods of prior cancers and PanNETs (P<0.05). Conclusions Patients with localized PanNETs and a history of prior cancer had survival outcomes that were comparable to those of patients with no history of prior cancer. Patients with localized PanNETs and prior cancer could be candidates for clinical trials if they satisfy all other conditions; aggressive and potentially curative therapies should be offered to these patients.
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Neoplasias Primarias Secundarias , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Anciano , Femenino , Humanos , Masculino , Análisis Multivariante , Tumores Neuroendocrinos/epidemiología , Neoplasias Pancreáticas/epidemiología , Puntaje de PropensiónRESUMEN
Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (Pâ<â.05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.
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Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/secundario , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Programa de VERF , Tasa de Supervivencia , Estados UnidosRESUMEN
OBJECTIVE: The aim of the study was to investigate the impact of a previous nonpancreatic malignancy on the survival outcomes in patients with a stage IV pancreatic neuroendocrine tumor (PanNET). METHODS: The Surveillance, Epidemiology, and End Results database was reviewed, and patients diagnosed with a stage IV PanNET between 2004 and 2015 were selected. Patients were divided into 2 groups according to the presence or absence of a previous nonpancreatic malignancy. Clinicopathological characteristics and survival outcomes were compared. RESULTS: A total of 1582 patients with stage IV PanNET were identified, of whom 116 (7.3%) had a prior malignancy. Prostate (33.62%), breast (17.24%), and gastrointestinal (12.07%) malignancies were the most common. Most prior malignancies (84.48%) were localized and regional. Patients with intervals of 36 months or less, 36 to 60 months, 60 to 120 months, and more than 120 months account for 25.86%, 14.66%, 31.03%, and 28.45% of all cases, respectively. Before and after propensity score matching, there was no significant difference detected regarding survival outcomes. CONCLUSIONS: Stage IV PanNET patients with a history of a prior cancer had comparable survival outcomes with patients without such history. These patients could be candidates for clinical trials if otherwise appropriate, and aggressive and potentially curative therapies should be offered.
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Neoplasias de la Mama/complicaciones , Neoplasias Gastrointestinales/complicaciones , Neoplasias Primarias Secundarias/patología , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Neoplasias de la Próstata/complicaciones , Adulto , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/complicaciones , Tumores Neuroendocrinos/complicaciones , Neoplasias Pancreáticas/complicaciones , Puntaje de PropensiónRESUMEN
As a rare malignant tumor, pancreatic neuroendocrine tumor (pNET) has very low incidence. However, most of the pNET patients would develop the distant metastasis, which significantly reduces patients' survival rate. Therefore, it is very important to construct a prognostic model of pNET patients with distant metastasis based on a large database to guide clinical application and treatment. The aim of this study is to establish nomograms for cancer-specific survival (CSS) and overall survival (OS) of patients with distant metastatic pNET based on the Surveillance, Epidemiology, and End Results (SEER) database.SEER were reviewed and the patients with pNET diagnosed between 1973 and 2015 were selected. After screening, a total of 624 cases were included in the study. Patients were randomly divided into a training cohort (nâ=â416) and a validation cohort (nâ=â208). Cox proportional hazard analysis revealed that age at diagnosis of ≥80 years, year of diagnosis, histological grade, and primary site surgery were independent factors both for CSS and OS. The nomograms indicated good accuracy in predicting 1-, 3-, and 5-year survival, with a C-index of 0.777 (95% confidence interval [CI], 0.743-0.811) for CSS and 0.772 (95% CI 0.738-0.806) for OS in training cohort. In the validation cohort, the C-index was 0.798 (95% CI 0.755-0.841) for CSS and 0.797 (95% CI 0.753-0.841) for OS. The calibration curves showed satisfactory consistency between predicted and actual survival.The study establishes excellent prognostic nomograms for CSS and OS for pNET patients with distant metastasis. They can be used to accurately predict survival rate, and provide useful information to physicians and patients.