Background
The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression ...grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.
Materials and Methods
This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.
Results
The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.
Conclusion
AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.
Implications for Practice
The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.
The aim of this large cohort study was to define the clinical significance of the AJCC/CAP tumor regression grading system for locally advanced rectal cancer, which could potentially be used to select the patients who would benefit from more intensive adjuvant chemotherapy as well as to protect patients from excessive treatment.
Despite evidence suggesting the utility of Epstein‐Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high‐risk regions, no validated NPC risk ...prediction model exists. We aimed to validate an EBV‐based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver‐operator‐characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross‐validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV‐based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93‐0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0‐92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9‐3.0%) to 12.5% (9.9‐15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255‐290) to 50 (41‐59). Combining the score with other risk factors (sex, first‐degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5‐year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high‐risk population. Adding nonviral risk factors did not improve NPC prediction.
What's new?
Evidence suggests that markers of Epstein‐Barr virus (EBV) infection are useful in screening for nasopharyngeal carcinoma (NPC). Few prospective studies, however, have validated the performance of EBV‐based risk scores for NPC. In this prospective validation study with data for more than 51 000 participants, EBV‐based risk score based on the combination of IgA antibodies against viral capsid antigen and EBV nuclear antigen 1 was found to be highly discriminating for NPC over follow‐up periods lasting five years. The findings indicate that EBV‐based scores could be valuable risk‐prediction tools for early NPC diagnosis, leading to improved clinical outcomes.
Background
The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by ...persistently reactivating EBV in long‐term based on a prospective cohort design.
Methods
A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE).
Results
With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE.
Conclusion
Smoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV.
Our study is a prospective design based on a NPC screening cohort in southern China. Our results provide the prospective evidence for the etiological relationship between smoking and NPC incidence in endemic areas, and first prospectively suggested smoking might increase NPC risk by persistently activating EBV.
Prospective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort ...study in southern China.
Based on an NPC screening cohort established in 2008-2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30-69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation.
During a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15-0.62) for the highest intake frequency and 0.29 (95% CI: 0.16-0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65-0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64-0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59-0.84) for VCA-IgA and 0.64 (95% CI: 0.54-0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals.
With inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas.
ObjectiveSeven recombinant viral capsid antigen-IgA (VCA-IgA) ELISA kits are widely used in China, but their diagnostic effects have not been evaluated. In this study, we evaluated whether the ...diagnostic effects of these kits are similar to those of the standard kit (EUROIMMUN, Lübeck, Germany).MethodsA diagnostic case–control trial was conducted with 200 cases of nasopharyngeal carcinoma (NPC) and 200 controls from NPC-endemic areas in southern China. The areas under the curve (AUCs), the sensitivities and the specificities of testing kits were compared with those of the standard kit. The test–retest reliability of each kit was determined by intraclass correlation coefficient (ICC). Their diagnostic accuracy in combination with Epstein-Barr virus nuclear antigen 1-IgA (EBNA1-IgA) was also evaluated in logistic models.ResultsThree testing kits—BB, HA and KSB—showed diagnostic accuracy equal to that of the standard kit, with good performance in the AUCs (0.926–0.945), and no significant differences in sensitivity were found between early-stage and advanced-stage NPCs. ICCs exceeded 0.8. Three logistic regression models were built, and the AUCs of these models (0.961–0.977) were better than those of the individual VCA-IgA kits. All new models had diagnostic accuracy equal to that of the standard kit. New cut-off values of these three kits and their corresponding combinations for researchers to replicate and use in NPC early detection and screening in the future were provided.ConclusionsThree recombinant VCA-IgA kits—BB,HA and KSB—had diagnostic effects equal to those of the standard kit, and, in combination with EBNA1-IgA in logistic regression models, can be used in future screening for NPC.
The advertising effect on consumers would be affected not only by the presentation of advertising messages but also by other factors. This study was based on the regulatory focus theory, mainly ...discussing the relationship among consumer goal orientation fits, the consumers' product knowledge and advertising effects. In this study, 285 valid questionnaires were obtained. The results of the study showed that it has a better advertising effect in terms of the attitude toward advertising, attitude toward the brand, and purchase intention when the consumer goal orientation is the promotion focus, and the messages on advertising have promotion benefits. Moreover, when the consumer goal orientation fits the benefits of the advertising messages, and the consumers' product knowledge is on the novice level, rather than expert level, consumers in the fit situation are more likely to have a better attitude toward advertising, attitude toward the brand and, purchase intention than in non-fit situations.
ObjectiveCommunity engagement practices in Indigenous health research are promoted as a means of decolonising research, but there is no comprehensive synthesis of approaches in the literature. Our ...aim was to assemble and qualitatively synthesise a comprehensive list of actionable recommendations to enhance community engagement practices with Indigenous peoples in Canada, the USA, Australia and New Zealand.DesignIntegrative review of the literature in medical (Medline, Cumulative Index to Nursing and Allied Health Literature and Embase) and Google and WHO databases (search cut-off date 21 July 2020).Article selectionStudies that contained details regarding Indigenous community engagement frameworks, principles or practices in the field of health were included, with exclusion of non-English publications. Two reviewers independently screened the articles in duplicate and reviewed full-text articles.AnalysisRecommendations for community engagement approaches were extracted and thematically synthesised through content analysis.ResultsA total of 63 studies were included in the review, with 1345 individual recommendations extracted. These were synthesised into a list of 37 recommendations for community engagement approaches in Indigenous health research, categorised by stage of research. In addition, activities applicable to all phases of research were identified: partnership and trust building and active reflection.ConclusionsWe provide a comprehensive list of recommendations for Indigenous community engagement approaches in health research. A limitation of this review is that it may not address all aspects applicable to specific Indigenous community settings and contexts. We encourage anyone who does research with Indigenous communities to reflect on their practices, encouraging changes in research processes that are strengths based.
Introduction
Haemophilic arthropathy is a serious complication of haemophilia often requiring surgical intervention. It is unclear whether advances in comprehensive care are associated with a ...reduction in orthopaedic interventions and peri‐procedural resource utilization.
Aim
To determine temporal patterns of orthopaedic interventions in persons with haemophilia (PWH), and evaluate changes in healthcare utilization and outcomes.
Methods
In this Canadian multicentre retrospective cohort study, adult PWH from Northern Alberta and British Columbia who underwent orthopaedic procedures (1990‐2018) were included. Temporal changes in the type of procedures, length of stay (LOS), factor utilization and outcomes were examined.
Results
: Sixty‐five patients (78% haemophilia A) underwent 102 surgeries at a median age of 46.3. Of the 46 severe PWH, 28 (61%) were on prophylaxis at time of surgery. The proportion of total knee arthroplasties (TKA) declined over time (56% 1990–1999, 51% 2000–2009, 27% 2010–2018), with a concomitant rise in ankle arthrodesis (0% 1990–1999, 18% 2000–2009, 27% 2010–2018). Over time, PWH underwent orthopaedic procedures at an older age (P = .02). There was a significant reduction in perioperative factor VIII utilization (P = .003) and median LOS (P < .0001). Major bleeds, prosthetic joint infections and thrombosis were not observed in the last decade.
Conclusion
In the last three decades, there was a decline in the proportion of TKA, likely reflecting the impact of widespread use of tertiary prophylaxis. However, ankle arthrodesis rates increased, suggesting that higher trough levels may be required to prevent ankle arthropathy. We observed a significant reduction in LOS and factor utilization, reflecting improvements in perioperative management.
Abstract
Background
Epstein–Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV ...seropositives within an NPC screening program in China.
Methods
The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals.
Results
By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%–99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%–68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%–14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%).
Conclusions
Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.
Obesity is a risk factor for gallbladder disease. The authors analyze the prevalence and clinicopathology of gallbladder disease among obese patients in Taiwan.
Prevalence and various clinical ...factors associated with cholelithiasis were studied in 199 patients who were undergoing bariatric surgery for obesity. Clinical data (gender, age, BMI and associated diseases), laboratory evaluation and immunoglobulin G antibodies against Helicobacter pylori were obtained from the patient records. The histopathologic findings of the gallbladder were also examined retrospectively. The degree of acute inflammation, chronic inflammation, cholesterolosis, cholesterol polyp and gastric metaplasia was determined and scored.
Of the patients, 91% (n=181) were females and 9% (n=18) were males, age 34.26 +/- 8.41 years, with mean BMI 35.28 +/- 6.11 kg/m2. The prevalence of cholelithiasis was 10.1%. Increased diastolic blood pressure and HBsAg carrier were the only significant factors associated with cholelithiasis. All obese patients in our study presented with variable degrees of chronic mononuclear cell infiltration in the gallbladder mucosa. Cholesterolosis was present in 100 patients (50.3%), followed by gastric metaplasia (27.1%), cholesterol polyp (16.1%) and acute inflammation (9.5%). Multivariate analysis showed an association between cholelithiasis and acute and chronic inflammation. The predictors of cholesterolosis were BMI, waist circumference and high-sensitivity C-reactive protein. The seroprevalence of H. pylori was 42.2%. Older age, abnormal liver function tests, calcium and HBsAg carrier were significantly different between H. pylori-seropositive and H. pylori-seronegative obese patients. However, we could rarely find H. pylori within the gallbladder mucosa.
Cholelithiasis in Asian obese patients is significantly associated with increased diastolic blood pressure and hepatitis B surface antigen carriers. Because chronic liver disease seems to be a risk factor for cholelithiasis in both non-obese and obese populations, prophylactic cholecystectomy can be considered in obese patients with HBsAg positivity. We did not find evidence that H. pylori has a role in the pathogenesis of gallbladder disease and gallstone by histologic and serologic examinations. Furthermore, mucosal abnormalities of acute and chronic inflammatory cell infiltration are common in obese patients, which related to cholelithiasis.
PDF
