Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
1.
Ann Surg ; 277(1): e61-e69, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091512

RESUMO

OBJECTIVE: To construct a prediction model for more precise evaluation of prognosis which will allow personalized treatment recommendations for adjuvant therapy in patients following resection of ESCC. BACKGROUND: Marked heterogeneity of patient prognosis and limited evidence regarding survival benefit of various adjuvant therapy regimens pose challenges in the clinical treatment of ESCC. METHODS: Based on comprehensive clinical data obtained from 4129 consecutive patients with resected ESCC in a high-risk region in China, we identified predictors for overall survival through a 2-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion. The model was internally validated using bootstrapping and externally validated in 1815 patients from a non-high-risk region in China. RESULTS: The final model incorporates 9 variables: age, sex, primary site, T stage, N stage, number of lymph nodes harvested, tumor size, adjuvant treatment, and hemoglobin level. A significant interaction was also observed between N stage and adjuvant treatment. N1+ stage patients were likely to benefit from addition of adjuvant therapy as opposed to surgery alone, but adjuvant therapy did not improve overall survival for N0 stage patients. The C -index of the model was 0.729 in the training cohort, 0.723 after bootstrapping, and 0.695 in the external validation cohort. This model outperformed the seventh edition American Joint Committee on Cancer staging system in prognostic prediction and risk stratification. CONCLUSIONS: The prediction model constructed in this study may facilitate precise prediction of survival and inform decision-making about adjuvant therapy according to N stage.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Esofagectomia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
2.
Ann Surg ; 277(4): e777-e784, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35129490

RESUMO

OBJECTIVE: To evaluate the long-term and short-term outcomes of MIE compared with OE in localized ESCC patients in real-world settings. BACKGROUND: MIE is an alternative to OE, despite the limited evidence regarding its effect on long-term survival. METHODS: We recruited 5822 consecutive patients with resectable ESCC in 2 typical high-volume centers in southern and northern China, 1453 of whom underwent MIE. Propensity score-based overlap weighted regression adjusted for multifaceted confounding factors was used to compare outcomes in the MIE and OE groups. RESULTS: Five-year OS was 62.7% in the MIE group and 57.7% in the OE group. The overlap weighted Cox regression showed slightly better OS in the MIE group (hazard ratio 0.93, 95% confidence interval: 0.82-1.06). Although duration of surgery was longer and treatment cost higher in the MIE group than in the OE group, the number of lymph nodes harvested was larger, the proportion of intraoperative blood transfusions lower, and postoperative complications less in the MIE group. 30-day (risk ratio [RR] 0.77, 0.381.55) and 90-day (RR 0.79, 0.46-1.35) mortality were lower in the MIE group versus the OE group, although not statistically significant. These findings were consistent across different analytic approaches and subgroups, notably in the subset of ESCC patients with large tumors. CONCLUSIONS: MIE can be performed safely with OS comparable to OE for patients with localized ESCC, indicating MIE may be recommended as the primary surgical approach for resectable ESCC in health facilities with requisite technical capacity.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Resultado do Tratamento , Esofagectomia/efeitos adversos , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Complicações Pós-Operatórias/etiologia
3.
J Pathol ; 258(1): 38-48, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35612571

RESUMO

Currently, surveillance for esophageal squamous cell carcinoma (ESCC) runs a risk of underestimation of early lesions which show absence of iodine staining, with no or only mild histologic changes. The development of molecular markers that indicate risk of progression is thus warranted. We performed whole-exome sequencing on biopsies from two sequential endoscopies of a single esophageal lesion and matching blood samples. There were 27 pairs of age-, gender-, pathologic stage-, and sampling interval-matched progressors and non-progressors identified in a prospective community-based ESCC screening trial. Putative molecular progression markers for ESCC were first evaluated by comparing somatic mutation, copy number alteration (CNA), and mutational signature information among progressors and non-progressors. These markers were then validated with another 24 pairs of matched progressors and non-progressors from the same population using gene alteration status identified by target sequencing and quantitative PCR. Progressors had more somatic mutation and CNA burden, as well as apolipoprotein B mRNA editing catalytic polypeptide-like and age-related signature weights compared with non-progressors. A gene score consisting of somatic NOTCH1 mutation and CDKN2A deletion is predictive of risk of progression in lesions which show absence of iodine staining under endoscopy but have no or only mild dysplasia. This gene score was also validated in an external cohort of matched progressors and non-progressors. Absence of NOTCH1 mutation and presence of CDKN2A deletion are markers of progression in squamous lesions of the esophagus. This gene score would be an ideal indicator for assisting the pathologist in the identification of high-risk individuals who could be potentially 'missed' or subject to a risk underestimation by histologic analysis, and might improve the performance of ESCC surveillance. © 2022 The Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Iodo , Carcinoma de Células Escamosas/patologia , Ensaios Clínicos como Assunto , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Humanos , Masculino , Mutação , Estudos Prospectivos , Receptor Notch1/genética
4.
J Gastroenterol Hepatol ; 38(3): 416-423, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36418206

RESUMO

BACKGROUND AND AIM: The impact of the presence of multiple Lugol-unstained lesions (LULs) in the esophagus on the risk of having severe dysplasia and above (SDA) lesions among asymptomatic individuals is unknown. METHODS: We collected demographic factors, behavioral variables, and features of LULs from 1073 participants who were biopsied at baseline endoscopic screening in a population-based screening trial, and these individuals were followed over a median time of 7 years. Outcome events were defined as SDA identified at screening, at reexamination, or during follow-up. "Multiple LULs" were defined as ≥ 2 LULs found in the entirety of the esophagus. Multivariable logistic regression models were fitted to assess the effect of "multiple LULs" on the cumulative risk of SDA. RESULTS: There were 147 SDA cases in the current study. After adjustment for potential risk factors and endoscopic features of LULs, the presence of "multiple LULs" slightly increased the cumulative risk of having SDA with no statistical significance (adjusted odds ratio [OR] = 1.26; 95% confidence interval [CI] [0.85, 1.88]). Further stratified analysis showed that this association was strong among subjects with small LULs (≤ 5 mm) (adjusted OR = 3.29; 95% CI [1.39, 7.79]). However, no such association was observed in subjects with larger LULs (adjusted OR = 0.99; 95% CI [0.63, 1.55], P interaction  = 0.022). CONCLUSIONS: The presence of "multiple small LULs (≤ 5 mm)" in chromoendoscopy indicates a higher cumulative risk of having SDA in the esophagus. We recommend biopsies be taken and surveillance be maintained at a more active level in individuals with relatively small but multiple LULs.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patologia , Esofagoscopia , Corantes , Fatores de Risco
5.
J Gastroenterol Hepatol ; 38(12): 2167-2173, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37726891

RESUMO

INTRODUCTION: This study aimed to evaluate the impact of Lugol-unstained lesion (LUL) location on the detection yield, which may help the endoscopist select targets for biopsy. METHODS: We enrolled 1064 subjects who had LULs at the baseline screening of a population-based randomized controlled trial. There were 1166 LULs with recorded location and pathologic diagnosis, and these were used for analysis. The detection rate of severe dysplasia and above (SDA) was calculated as the number of LULs identified as SDA divided by the number of LULs biopsied. Logistic regression with a generalized estimating equation was applied to evaluate the association between the location of a given LUL and the risk of the LUL being SDA. RESULTS: The detection rate of SDA for LULs located in the lower, middle, and upper esophagus increased from 5.9% and 10.9% to 16.7%. LUL location was significantly associated with having SDA (adjusted odds ratio (OR)upper vs. lower  = 2.88, 95% confidential interval (CI) = 1.48-5.60; adjusted ORmiddle vs. lower  = 1.63, 95% CI = 0.96-2.76), and the association was stronger in subgroups with a family history of esophageal squamous cell carcinoma (ESCC) (adjusted ORupper vs. lower  = 9.72, 95% CI = 2.57-36.69; adjusted ORmiddle vs. lower  = 3.76, 95% CI = 0.93-15.21). CONCLUSIONS: Our results suggest that more attention should be paid by endoscopists to LULs in the upper and middle esophagus, particularly for individuals with a family history of ESCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/diagnóstico
6.
BMC Med ; 20(1): 458, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434648

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood. METHODS: Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility. RESULTS: In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001). CONCLUSIONS: The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers.


Assuntos
Carcinoma Ductal Pancreático , DNA Tumoral Circulante , Neoplasias Pancreáticas , Humanos , DNA Tumoral Circulante/genética , Antígeno CA-19-9 , Metilação , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas
7.
Ann Surg Oncol ; 29(9): 5626-5633, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35181817

RESUMO

BACKGROUND: The aim was to systematically select blood markers routinely tested in clinical settings, which are independently associated with overall survival (OS) and are able to stratify prognosis of esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy. METHODS: We selected optimal blood markers for prognostic stratification from 60 candidates in a clinical cohort of 1819 consecutive patients with resectable ESCC in China. Selection was carried out using two-step multivariable Cox proportional hazards regression adjusted for multifaceted confounders. A composite index was developed by multiplying risk factors and dividing them by protective factors. RESULTS: With a median follow-up of 48.07 months, 641 deaths occurred in the 1819 patients and the 5-year OS was 56.30%. Two risk factors (mean corpuscular hemoglobin, fibrinogen) and a protective factor (albumin), all dichotomized and assigned values 1 and 2, were used to construct the composite index marker "MF-A". Three risk groups were created based on the MF-A score including low- (0.5), moderate- (1), and high-risk groups (2 and 4). Compared with patients in the low-risk group (1184/1778, 66.59%), those in the moderate- (488, 27.45%), and high-risk (106, 5.96%) groups were at elevated risk of death (adjusted HR: 1.32, 95% CI: 1.11-1.57; adjusted HR: 2.08, 95% CI: 1.56-2.75; Ptrend < 10-7). Within each TNM stage grouping, OS also trended to be significantly worse as the MF-A score increased. CONCLUSIONS: "MF-A" is a novel independent predictor which may be used to estimate and stratify prognosis for ESCC patients undergoing esophagectomy.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Albuminas , Índices de Eritrócitos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia , Fibrinogênio , Humanos , Prognóstico , Estudos Retrospectivos
8.
Gastrointest Endosc ; 93(5): 1065-1073.e3, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32950597

RESUMO

BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio6-10 mm vs ≤5 mm, 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio>10 mm vs ≤5 mm, 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.


Assuntos
Neoplasias Esofágicas , Lesões Pré-Cancerosas , China/epidemiologia , Corantes , Neoplasias Esofágicas/epidemiologia , Esofagoscopia , Humanos , Iodetos , Lesões Pré-Cancerosas/epidemiologia
9.
BMC Public Health ; 21(1): 2129, 2021 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-34801023

RESUMO

BACKGROUND: The association of early-life undernutrition and dyslipidemia found in previous studies may be confounded by the uncontrolled age difference between exposed and unexposed participants. The study aimed to investigate the association of early-life undernutrition and the risk of dyslipidemia in adulthood with good control of the age variable. METHODS: We took the Great Chinese Famine (1959-1961) as a natural experiment of severe undernutrition. This study was based on the baseline investigation of a population-based cohort in rural China. Undernutrition in early life was defined as being exposed to famine at younger than 3 years of age. Three approaches including Adjustment, Restriction, and Matching were applied to control the confounding effect of age. Logistic regression models were applied to evaluate the association between early-life famine and the presence of dyslipidemia. Stratified analysis by gender was also performed, and potential effect modification was tested by adding the interaction term of the famine exposure variable and gender into the model. RESULTS: Undernutrition in early life was associated with increased risk of borderline high and above (BHA) levels of total cholesterol (TC, ORAdjustment = 1.61; ORRestriction = 1.56; ORMatching = 1.87), triglycerides (TG, ORAdjustment = 1.33; ORRestriction = 1.30; ORMatching = 1.34), low-density lipoprotein cholesterol (LDL-C, ORAdjustment = 1.75; ORRestriction = 1.53; ORMatching = 1.77) and dyslipidemia (ORAdjustment = 1.52; ORRestriction = 1.45; ORMatching = 1.60), as well as high levels of TC, TG, LDL-C and dyslipidemia. An inverse association of undernutrition and risk of low high-density lipoprotein cholesterol (HDL-C) was found. Female participants with undernutrition experience had an increased risk of BHA TG and LDL-C (TG: ORAdjustment, female = 1.45; ORRestriction, female = 1.39; ORMatching, female = 1.51; LDL-C: ORAdjustment, female = 2.11; ORRestriction, female = 1.80; ORMatching, female = 2.15), but this association was not found in males. CONCLUSION: Early-life undernutrition increased the risk of TC, TG, LDL-C, and dyslipidemia. Gender would significantly modify this effect for TG and LDL-C. These results emphasize the importance of nutritional conditions in the early stages of life to long-term health consequences.


Assuntos
Dislipidemias , Desnutrição , Adulto , Pré-Escolar , China , LDL-Colesterol , Estudos de Coortes , Dislipidemias/epidemiologia , Fome Epidêmica , Feminino , Humanos , Masculino , Desnutrição/complicações , Desnutrição/epidemiologia , Prevalência , Fatores de Risco , Fatores Sexuais
10.
Chin J Cancer Res ; 33(6): 649-658, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35125809

RESUMO

OBJECTIVE: This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening. METHODS: A gastric cancer risk scoring system (GC-RSS) was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review. To assess the capability of this system for discrimination, risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers, and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve (AUC). To evaluate the performance of GC-RSS, the screening proportion, sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values. RESULTS: GC-RSS comprised nine predictors including advanced age, male gender, low body mass index (<18.5 kg/m2), family history of gastric cancer, cigarette smoking, consumption of alcohol, preference for salty food, irregularity of meals and consumption of preserved food. This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763, 0.706 and 0.696 in three validation sets. When subjects with risk scores ≥5 were evaluated with endoscopy, nearly 50% of these endoscopies could be saved with a detection rate of over 1.5 times achieved. When the cutoff was set at 8, only about 10% of subjects with the highest risk would be offered endoscopy, and detection rates for gastric cancer could be increased 2-4 fold compared to universal screening. CONCLUSIONS: An effective questionnaire-based GC-RSS was developed and validated. This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.

11.
Br J Cancer ; 122(6): 857-867, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31969677

RESUMO

BACKGROUND: About 25-37% of resectable pancreatic ductal adenocarcinoma (PDAC) had a great chance of early recurrence after radical resection, which is mainly due to preoperative micrometastasis. We herein demonstrated the profiles of ctDNA in resectable PDAC and use of ctDNA to identify patients with potential micrometastasis. METHODS: A total of 113 and 44 resectable PDACs were enrolled in discovery and validation cohorts, separately. A panel containing 50 genes was used to screen ctDNA by an NGS-based assessment with high specificity. RESULTS: In the discovery cohort, the overall detection rate was 38.05% (43/113). Among positive ctDNA, KRAS mutation had the highest detection rate (23.01%, 26/113), while the others were <5%. Survival analysis showed that plasma KRAS mutations, especially KRAS G12D mutation, had significant association with OS and RFS of resectable PDAC. Plasma KRAS G12D mutation showed a strong correlation with early distant metastasis. In the validation cohort, survival analysis showed similar association between plasma KRAS G12D mutation and poor outcomes. CONCLUSIONS: This study demonstrated that plasma KRAS mutations, especially KRAS G12D mutation, served as a useful predictive biomarker for prognosis of resectable PDAC. More importantly, due to high correlation with micrometastasis, preoperative detection of plasma KRAS G12D mutation helps in optimising surgical selection of resectable PDAC.


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , DNA Tumoral Circulante/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Período Pré-Operatório , Prognóstico , Estudos Prospectivos
12.
Clin Gastroenterol Hepatol ; 18(7): 1626-1635.e7, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31518715

RESUMO

BACKGROUND & AIMS: Chromoendoscopy with iodine staining is used to identify esophageal squamous dysplasia and esophageal squamous cell carcinomas (ESCCs)-absence of staining indicates suspicious regions of dysplasia. However, screening detects precancerous lesions (mild and moderate dysplasia) that do not require immediate treatment; it is a challenge to which lesions are at risk for progression. We investigated the association between absence of iodine staining at chromoendoscopy screening and lesion progression using 6 years of follow-up data from a population-based randomized controlled trial in China. We then constructed and validated a model to calculate risk of progression to severe dysplasia, carcinoma in situ, or ESCC. METHODS: We collected data from 1468 participants (45-69 years old) who were either negative for iodine staining at a baseline chromoendoscopy or found to have mild or moderate dysplasia in histologic analysis of biopsies in the Endoscopic Screening for Esophageal Cancer study in China, from January 2012 through September 2016; 788 of these participants were re-examined by endoscopy after a median interval of 4.2 years (development cohort). We investigated the association between absence of iodine staining and progression of esophageal lesions using Cox prediction models, considering corresponding baseline pathology findings and patient answers to a comprehensive questionnaire. Patients who did not receive a follow-up examination (n = 680) was used as the validation cohort; outcome events in these patients were identified by annual door to door active interviews or linkage with local electronic registry data. The primary outcome was incident esophageal severe dysplasia, carcinoma in situ, or ESCC. RESULTS: In the development cohort, 11 lesions that did not stain with iodine but were classified as not dysplastic in the histology analysis were found to be severe dysplasia, carcinoma in situ, or ESCC at the follow-up evaluation. These lesions accounted for 39.3% of all progressed lesions (n = 28). In the validation cohort, 6 patients with lesions did not stain with iodine but were classified as not dysplastic by histology had a later diagnosis of ESCC, determined from medical records; these patients accounted for 50.0% of all patients with lesion progression (n = 12) until the closing date of this study. We developed a model based on patient age, body mass index, pathology findings, and baseline iodine staining to calculate risk for severe dysplasia, carcinoma in situ, or ESCC. It identified patients for severe dysplasia, carcinoma in situ, or ESCC in the development set with an area under the curve of 0.868 (95% CI, 0.817-0.920) and in the validation set with an area under the curve of 0.850 (95% CI, 0.748-0.952). Almost no cases would be missed if subjects determined to be high or intermediate-high risk subjects by the model were included in surveillance. CONCLUSIONS: Absence of iodine staining at baseline chromoendoscopy identifies esophageal lesions at risk of progression with a high level of sensitivity. A model that combines results of iodine chromoendoscopy with other patient features identifies patients at risk of lesion progression with greater accuracy than histologic analysis of baseline biopsies.


Assuntos
Neoplasias Esofágicas , Iodo , Lesões Pré-Cancerosas , Idoso , China/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Esofagoscopia , Humanos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Estudos Prospectivos , Coloração e Rotulagem
13.
Gastrointest Endosc ; 91(6): 1253-1260.e3, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31911077

RESUMO

BACKGROUND AND AIMS: Prediction models for esophageal squamous cell carcinoma are not common, and no model targeting a clinical population has previously been developed and validated. We aimed to develop a prediction model for estimating the risk of high-grade esophageal lesions for application in clinical settings and to validate the performance of this model in an external population. METHODS: The model was developed based on the results of endoscopic evaluation of 5624 outpatients in one hospital in a high-risk region in northern China and was validated using 5765 outpatients who had undergone endoscopy in another hospital in a non-high-risk region in southern China. Predictors were selected with unconditional logistic regression analysis. The Akaike information criterion was used to determine the final structure of the model. Discrimination was estimated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed using a calibration plot with an intercept and slope. RESULTS: The final prediction model contained 5 variables, including age, smoking, body mass index, dysphagia, and retrosternal pain. This model generated an AUC of 0.871 (95% confidence interval, 0.842-0.946) in the development set, with an AUC of 0.862 after bootstrapping. The 5-variable model was superior to a single age model. In the validation population, the AUC was 0.843 (95% confidence interval, 0.793-0.894). This model successfully stratified the clinical population into 3 risk groups and showed high ability for identifying concentrated groups of cases. CONCLUSIONS: Our model for esophageal high-grade lesions has a high predictive value. It has the potential for application in clinical opportunistic screening to aid decision making for both health care professionals and individuals.


Assuntos
Neoplasias Esofágicas , China/epidemiologia , Detecção Precoce de Câncer , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago , Humanos , Programas de Rastreamento , Gradação de Tumores , Curva ROC , Medição de Risco
14.
Health Qual Life Outcomes ; 18(1): 228, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660494

RESUMO

BACKGROUND: This study aims to compare the performance of the recently developed Chinese (city) tariff of the EQ-5D-3L against the UK, US, Japanese and Korean tariffs in a general rural population in China. METHODS: From November 2015 to September 2016, 12,085 permanent residents aged 45-69 from 257 villages randomly selected from Hua County, Henan Province, China, were interviewed using EQ-5D-3L, and a one-on-one questionnaire investigation was used to collect data on factors associated with HRQOL. The health utility scores were calculated using the UK, US, Japanese, Korean and Chinese (city) tariffs. The agreement, known-groups validity and sensitivity of these five tariffs were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. RESULTS: The Korean tariff yielded the highest mean health utility score (0.963), followed by the Chinese (city) (0.948), US (0.943), UK (0.930) and Japanese (0.921) tariffs, but the differences in the scores of any two tariffs did not exceed the MCID. The Chinese (city) tariff showed higher ICC values (ICCs> 0.89, 95% CI:0.755-0.964) and narrower limits of agreement (0.099-0.167) than the Korean tariff [(ICCs> 0.71, 95% CI:0.451-0.955); (0.146-0.253)]. The Chinese (city) tariff had a higher relative efficiency and effect size statistics in 10 out of 11 variables as compared to the UK, US and Japanese tariffs. The Chinese (city) tariff (0.215) was associated with moderate mean absolute transition scores compared with the UK (0.342), US (0.230), Japanese (0.149) and Korean (0.189) tariffs for 1485 observed pairs of the EQ-5D-3L health states. CONCLUSIONS: Health utility scores derived from the five tariffs differed. The Chinese (city) tariff was the most suitable of these tariffs and was without obvious weakness. We recommend adopting the Chinese (city) tariff when applying EQ-5D-3L to assess quality of life among the elderly in China's agricultural region with socio-economic status similar to Hua County. Results of this study had provided a crucial basis for health surveys, health promotion projects, health intervention trials, and health economic evaluation taking HRQOL as a target in rural areas of China.


Assuntos
Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , Análise Custo-Benefício/estatística & dados numéricos , Inquéritos Epidemiológicos/normas , Qualidade de Vida/psicologia , População Rural/estatística & dados numéricos , Inquéritos e Questionários/normas , Idoso , China , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , República da Coreia , Fatores Socioeconômicos , Reino Unido , Estados Unidos
15.
Lipids Health Dis ; 19(1): 135, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532299

RESUMO

BACKGROUND: Heterogeneity should be carefully addressed to facilitate establishment of effective population-level blood lipid management. The primary aim of the study was to investigate gender heterogeneity in prevalence of dyslipidemia, including trends with age and associated factors in middle age rural Chinese. METHODS: This is a cross-sectional study based on a baseline investigation of a population-based randomized controlled trial in rural China, involving 26,378 permanent residents of age 45-69. The age-specific prevalence of dyslipidemia was estimated for men and women, and the trends of prevalence with age were compared. Logistic regression was used to explore the factors associated with prevalent risk of dyslipidemia. RESULTS: The overall prevalence of dyslipidemia was significantly higher in females than in males for borderline high and above (BHA) total cholesterol (TC ≥ 200 mg/dL), BHA triglycerides (TG ≥ 150 mg/dL) and BHA low-density lipoprotein cholesterol (LDL-C ≥ 130 mg/dL), but was lower for low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL) in females than the corresponding prevalence in males. The prevalence of borderline high and above TC, TG and LDL-C all rose with age in females, but was stable or even decreased with age in males. In contrast, graphic representation of the prevalence of low HDL-C showed no striking age related trend in both genders. Risk of dyslipidemia was associated predominantly with obesity in males, but was more predominantly associated with hypertension in females. CONCLUSION: Heterogeneity was found in comparing the prevalence of dyslipidemia in men and women, and gender heterogeneity was found in its trend with age and associated factors in middle aged rural Chinese. The effectiveness of population-level blood lipid management and CVD primary prevention programs in China is expected to be improved if gender heterogeneity is considered.


Assuntos
Dislipidemias/sangue , Hipertensão/sangue , Obesidade/sangue , Fatores Etários , Idoso , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/epidemiologia , Dislipidemias/patologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Lipídeos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/patologia , Fatores de Risco , População Rural , Caracteres Sexuais , Triglicerídeos/sangue
16.
Chin J Cancer Res ; 32(6): 742-754, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33446997

RESUMO

OBJECTIVE: We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk. METHODS: We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models. RESULTS: A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P<0.05 & false discovery rate-adjusted Q<0.10). A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI, 0.84-0.93). Cross-validation and sensitivity analysis, excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls, or restriction to screen-endoscopic-detected or clinically diagnosed case-control triads, or using only bacterial data measured at the baseline, yielded AUCs>0.84. CONCLUSIONS: The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

17.
Gut ; 68(2): 198-206, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29306867

RESUMO

OBJECTIVE: Description of the design and preliminary results of baseline recruitment and screening in the endoscopic screening for esophageal cancer in China (ESECC), the first randomised controlled trial (RCT) assessing efficacy and cost-effectiveness of endoscopic screening for esophageal squamous cell carcinoma (ESCC). DESIGN: ESECC trial is a cluster RCT, and 668 villages in rural Hua County, Henan Province, a high-incidence area of ESCC in China, were randomised into two arms at a ratio of 1:1. Screening arm participants were screened by Lugol chromoendoscopy; no screening was performed in the control arm. ESCC-specific and all-cause mortality, incidence of advanced ESCC and cost-effectiveness of screening will be evaluated in the next 10-year follow-up. Here, we report the performance of baseline recruitment and randomisation, prevalence of upper GI lesions and risk factors for ESCC. RESULTS: A total of 17 151 and 16 797 participants were enrolled in screening and control arms from January 2012 to September 2016. The truncated prevalence (aged 45-69 years) of oesophageal and overall upper GI high-grade lesions was 744.0/100 000 and 902.0/100 000. 69.9% of the 113 patients with high-grade oesophageal lesions were of early stage. Risk factors for severe oesophageal dysplasia and more severe lesions in this population included higher age, family history of ESCC, lower body mass index, eating rapidly and frequent ingestion of leftovers. CONCLUSION: This ESECC trial met the predesigned recruitment and randomisation requirements. Age, family history, undernutrition and unhealthy dietary habits increased the risk for high-grade oesophageal lesions in this high-risk population. TRAIL REGISTRATION NUMBER: NCT01688908; Pre-results.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Esofagoscopia/métodos , Idoso , Carcinoma de Células Escamosas/epidemiologia , China/epidemiologia , Detecção Precoce de Câncer , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , População Rural
18.
Carcinogenesis ; 40(12): 1445-1451, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31570939

RESUMO

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor-descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.


Assuntos
Transformação Celular Neoplásica/genética , Evolução Clonal/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Idoso , Progressão da Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteína Supressora de Tumor p53/genética
19.
Am J Epidemiol ; 188(4): 776-784, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608546

RESUMO

Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Endoscopia Gastrointestinal/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Adulto , Idoso , China/epidemiologia , Detecção Precoce de Câncer/métodos , Neoplasias Esofágicas/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
20.
Chin J Cancer Res ; 31(4): 699-706, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31564812

RESUMO

OBJECTIVE: To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China. METHODS: We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records (EMRs) as well as the New Rural Cooperative Medical Scheme (NCMS) claims records for cancer patients in Hua County People's Hospital (HCPH) and Anyang Cancer Hospital (ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value (PPV) were calculated taking the EMRs as the gold standard. RESULTS: The sensitivity of NCMS was 95.2% (93.8%-96.3%) and 92.0% (88.3%-94.8%) in ACH and HCPH, respectively. The PPV of the NCMS was 97.8% (96.7%-98.5%) in ACH and 89.0% (84.9%-92.3%) in HCPH. Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%, respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than non-common cancers were detected in HCPH and ACH separately (P<0.01). CONCLUSIONS: Identification of cancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA