Prevalence of incidental colorectal cancer and polyps in autopsies of different populations: a systematic review with meta-regression analysis.

The colorectal cancer (CRC) and polyps incidentally found in autopsies represent the lesions that have not actually caused problems throughout the lifetime and thus may not need to be removed during screening. This study aimed to investigate the prevalence of incidental CRC (iCRC) and polyps in autopsies of different populations. A systematic search was performed on 19 August 2022 to identify autopsy studies that provided data on prevalence of iCRC, adenomatous polyps, hyperplastic polyps, and/or all polyps combined. The prevalence was pooled with the random-effects model. Subgroup and multivariable meta-regression analyses were conducted to investigate the heterogeneity. Forty-three eligible studies including 59,656 autopsies were identified, with 94% conducted before 1990 when CRC screening was uncommon or not available. The pooled prevalence was 0.7% (95% confidence interval [CI], 0.3-1.2%) for iCRC, 18.4% (95% CI, 13.3-24.1%) for adenomatous polyps, 16.4% (95% CI, 8.7-25.9%) for hyperplastic polyps, 26.3% (95% CI, 15.4-38.8%) for all polyps combined, and 29.9% (95% CI, 14.8-47.6%) for iCRC plus polyps. The prevalence of iCRC was higher (1.2%) in white-predominant populations but lower (0.4%) after excluding low-quality studies. Multivariable analyses showed that the prevalence of polyps was higher in white-predominant populations and higher-quality studies, increased with age, and showed a downward trend from "before 1975" through "after 1985". In conclusion, the prevalence of iCRC in autopsies was not low, considering the average lifetime risk of CRC, while incidental polyps were common. Both varied greatly in different populations. These findings may have implications when weighing the benefits and harms of screening.

Forefoot Function after Hallux Valgus Surgery: A Systematic Review and Meta-Analysis on Plantar Load Measurement.

While hallux valgus (HV) surgeries are useful for correcting skeletal alignment problems, their effects on plantar load, which reflects forefoot functions, are less understood. The objective of this study is to conduct a systematic review and meta-analysis on the plantar load change after HV surgeries. A systematic search of Web of Science, Scopus, PubMed, CENTRAL, EMBASE, and CINAHL was performed. Studies that assessed the pre- and post-operative plantar pressure of HV patients undergoing surgeries and reported load-related parameters over the hallux, medial metatarsal, and/or central metatarsal regions were included. Studies were appraised by using the modified NIH quality assessment tool for before-after study. Studies suitable for meta-analysis were pooled with the random-effects model, using the standardized mean difference of the before-after parameters as an effect measure. Twenty-six studies containing 857 HV patients and 973 feet were included for the systematic review. Meta-analysis was conducted on 20 of them, and most studies did not favor HV surgeries. Overall, HV surgeries reduced the plantar load over the hallux region (SMD -0.71, 95% CI, -1.15 to -0.26), indicating that forefoot function worsened after surgeries. For the other five outcomes, the overall estimates were not statistically significant, indicating that surgeries did not improve them either. There was substantial heterogeneity among the studies, which in most cases could not be resolved by pre-planned subgroup analyses by surgical classification, year of publication, median age of patients, and length of follow-up. Sensitivity analysis removing lower-quality studies showed that the load integrals (impulse) over the central metatarsal region significantly increased (SMD 0.27, 95% CI, 0 to 0.53), indicating that surgeries increased the risk of transfer metatarsalgia. There is no solid evidence that HV surgeries could improve forefoot functions from a biomechanical point perspective. Currently available evidence even suggests that surgeries might reduce the plantar load over the hallux and adversely affect push-off function. The reasons behind and the effectiveness of alternative surgical methods warrant further investigation.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Association of positive and adverse childhood experiences with risky behaviours and mental health indicators among Chinese university students in Hong Kong: an exploratory study.

Background: Different childhood experiences may affect adult health differently. Objective: To explore the association of different types of positive childhood experiences(PCEs) and adverse childhood experiences (ACEs) with risky behaviours and mental health indicators, andhow PCEs and ACEs are associated with health outcomes in the context of each other. Method: This was an exploratory cross-sectional online survey including 332 university students in Hong Kong. ACEs (abuse and household challenges), PCEs (perceived safety, positive quality of life, and interpersonal support), risky behaviours (smoking, binge drinking, and sexual initiation), and mental health indicators(depression, anxiety, loneliness, self-rated health, multimorbidity, meaning in life, and life satisfaction)were measured. Results: The multivariable logistic regression analysis indicated cumulative effects of PCEs in lowered risks of depression, anxiety, loneliness, as well as better self-rated health, life satisfaction, and meaning in life (p < .05), after adjusting for ACEs. Results also indicated that ACEs had an increasing relationship with poorer mental health indicators, such as anxiety, loneliness, and life satisfaction (p < .05), after adjusting for PCEs. There was also an adverse association between having ≥4 ACEs with smoking and binge drinking. In addition, each type of PCE and ACE was significantly associated with one or more risky behaviours and mental health indicators. Stratified results showed that PCEs had stronger associations with mental health indicators in participants with fewer ACEs. Furthermore, ACEs had stronger associations with mental health indicators in participants with more PCEs than in those with fewer PCEs. Conclusions: In this study, PCE was proven to be an independent protective factor against poor mental health after accounting for ACE. ACE was also proven to be an independent risk factor for poor mental health and risky behaviours. These findings suggest a crucial need for the active promotion of PCEs and the prevention of child maltreatment. The results of subtypes and stratifications can be taken into consideration when developing targeted interventions in the future. HIGHLIGHTS: PCE is an independent protective factor against poor mental health after accounting for ACE. ACE is an independent risk factor for poor mental health and risky behaviours.PCEs and ACEs have different associations with health outcomes in the context of one another.

Antecedentes: Las diferentes experiencias de la infancia pueden afectar la salud de los adultos de manera diferente.Objetivo: Explorar la asociación de diferentes tipos de experiencias infantiles positivas (EIP) y experiencias infantiles adversas (EIA) con conductas de riesgo e indicadores de salud mental, y cómo las EIP y las EIA se asocian con resultados de salud en el contexto de cada uno.Método: Esta fue una encuesta transversal exploratoria en línea que incluyó a 332 estudiantes universitarios en Hong Kong. EIA (abuso y desafíos domésticos), EIP (seguridad percibida, calidad de vida positiva y apoyo interpersonal), comportamientos de riesgo (fumar, beber en exceso e iniciación sexual) e indicadores de salud mental (depresión, ansiedad, soledad, salud autoevaluada, multimorbilidad, sentido de la vida y satisfacción con la vida) fueron medidos.Resultados: El análisis de regresión logística multivariable indicó efectos acumulativos de EIP en disminuir el riesgo de depresión, ansiedad, soledad, así como mejor autoevaluación de la salud, satisfacción con la vida y sentido de la vida (p < 0,05), después de ajustar por EIA. Los resultados también indicaron que EIA tuvo una relación de incremento con indicadores de salud mental más deficientes, como ansiedad, soledad y satisfacción con la vida (p < 0,05), después de ajustar por EIP. También hubo una asociación adversa entre tener ≥4 EIA con fumar y beber en exceso. Además, cada tipo de EIP y EIA se asoció significativamente con uno o más comportamientos de riesgo e indicadores de salud mental. Los resultados estratificados mostraron que EIP tuvo asociaciones más fuertes con indicadores de salud mental en participantes con menos EIA. Además, EIA tuvo asociaciones más fuertes con indicadores de salud mental en participantes con más EIA que en aquellos con menos EIP.Conclusiones: En este estudio, se demostró que EIP es un factor protector independiente contra una pobre salud mental después de tomar en cuenta EIA. También se demostró que EIA es un factor de riesgo independiente para una pobre salud mental y comportamientos de riesgo. Estos hallazgos sugieren una necesidad crucial para la promoción activa de EIPs y la prevención del maltrato infantil. Los resultados de los subtipos y estratificaciones se pueden tener en cuenta al desarrollar intervenciones focalizadas en el futuro.

The role of body mass index in the association between dietary sodium intake and blood pressure: A mediation analysis with NHANES.

BACKGROUND AND AIMS: Recent research demonstrated that obesity and high dietary sodium intake, the two established risk factors for hypertension, were associated with each other. The objective was to investigate the potential indirect effect of sodium intake on blood pressure via body mass index (BMI). METHODS AND RESULTS: Using ten years data from US NHANES (2007-2016), the study included adult participants (>20 years old) who were not taking antihypertensive medications and without baseline diseases (n = 12,262). BMI was modelled as the mediator of sodium intake on systolic and diastolic blood pressure, adjusted for age, sex, socioeconomic status, smoking, drinking, physical activity, calorie intake, fluid intake and potassium intake. Mediation analysis was performed to evaluate total effect, direct effect and indirect effect via BMI. Subgroup analyses based on three age subgroups (20-40, 41-60 and ≥61 years old) were performed. The mean age was 39.29 (13.4) years and 53.1 (0.45) % were males. The mean BMI was 27.8 (6.20) kg/m2. Overall, 1 g/d increase in sodium intake was associated with an increased systolic blood pressure by 0.36 (95% confidence interval 0.14 to 0.58) mmHg, with a direct effect (0.14 (0.09-0.19)) and an indirect effect via BMI (0.23 (0.02-0.44)). The indirect effect was mainly observed in participants ≤60 years old. CONCLUSION: Sodium intake showed both direct effect and indirect effect (via BMI) on systolic blood pressure in US NHANES. The findings provide evidence for combining sodium restriction and weight reduction measures for prevention of hypertension. Cautions should be taken when generalizing the findings to other populations with lower average BMI.

Prognostic Models for Predicting Overall Survival in Patients with Primary Gastric Cancer: A Systematic Review.

BACKGROUND: This study was designed to review the methodology and reporting of gastric cancer prognostic models and identify potential problems in model development. METHODS: This systematic review was conducted following the CHARMS checklist. MEDLINE and EMBASE were searched. Information on patient characteristics, methodological details, and models' performance was extracted. Descriptive statistics was used to summarize the methodological and reporting quality. RESULTS: In total, 101 model developments and 32 external validations were included. The median (range) of training sample size, number of death, and number of final predictors were 360 (29 to 15320), 193 (14 to 9560), and 5 (2 to 53), respectively. Ninety-one models were developed from routine clinical data. Statistical assumptions were reported to be checked in only nine models. Most model developments (94/101) used complete-case analysis. Discrimination and calibration were not reported in 33 and 55 models, respectively. The majority of models (81/101) have never been externally validated. None of the models have been evaluated regarding clinical impact. CONCLUSIONS: Many prognostic models have been developed, but their usefulness in clinical practice remains uncertain due to methodological shortcomings, insufficient reporting, and lack of external validation and impact studies. IMPACT: Future research should improve methodological and reporting quality and emphasize more on external validation and impact assessment.

Influence of family income and medical insurance coverage on health-related quality of life and optimism in cancer patients at a Hong Kong private hospital: A cross-sectional study.

OBJECTIVE: Health-related quality of life (HRQL) and optimism are important health domains that express the physical, emotional, and psychological well-being of cancer patients. Previous studies have explored income and medical insurance coverage as predictors of their well-being with the aim to better understand their financial needs. The primary objective of this study was to examine the associations in the private health sector in Hong Kong. METHODS: The study was conducted cross-sectionally with a structured questionnaire in traditional Chinese. HRQL was assessed with the RAND 12-item Health Survey, and optimism was assessed with the Life Orientation Test. The two primary predictors were family income and medical insurance coverage. The associations were tested using logistic regression, controlling for other sociodemographic and clinical covariates. RESULTS: A total of 428 questionnaires were used in the regression model. After adjusting for other covariates, no significant association was observed with family income as the predictor. Medical insurance coverage was a significant and positive predictor of optimism with odds ratio of 2.30 and 95% confidence interval of 1.30 to 4.05 for the group with the most coverage with little to no coverage as the reference group. CONCLUSIONS: The significant association between medical insurance coverage and optimism might be an indication that the medical cost was a financial burden to many cancer patients in Hong Kong. In addition to their medical needs, cancer support organization and health care practitioners must be able to recognize and assist with the financial needs of the cancer patients.

Predictive role of skin rash in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib: a systematic review and meta-analysis.

PURPOSE: The survival benefit from gemcitabine plus erlotinib was on average marginal for advanced pancreatic cancer (APC) patients. Skin rash developed shortly after starting treatment seemed to be associated with better efficacy and might be used to assist clinical decision-making, but the results across studies were inconsistent. Thus, we conducted a systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, three Chinese databases, and the abstracts of important conferences were searched for eligible studies. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response. The random-effects model was used to pool results across studies if heterogeneity was substantial. Otherwise, the fixed-effect model was used. RESULTS: A total of 16 studies with 1,776 patients were included. Patients who developed skin rash during treatment had longer OS (8.9 vs 4.9 months, HR=0.57, 95% CI 0.50-0.64) and longer PFS (4.5 vs 2.4 months, HR=0.53, 95% CI 0.40-0.68) than those who did not. A dose- response relationship was also observed for both OS (HR=0.64 for grade-1 rash vs no rash and HR=0.46 for ≥grade-2 rash vs no rash) and PFS (HR=0.72 for grade-1 rash vs no rash and HR=0.43 for ≥grade-2 rash vs no rash). CONCLUSION: Skin rash was associated with better OS and PFS in APC patients treated with gemcitabine plus erlotinib. It might be used as a marker for efficacy to guide clinical decision-making toward a more precise and personalized treatment.

Comparison of direct sequencing and amplification refractory mutation system for detecting epidermal growth factor receptor mutation in non-small-cell lung cancer patients: a systematic review and meta-analysis.

BACKGROUND: Direct sequencing and amplification refractory mutation system (ARMS) are commonly used to detect epidermal growth factor receptor (EGFR) mutation status in patients with non-small-cell lung cancer to inform the decision-making on tyrosine kinase inhibitors treatment. This study aimed to systematically compare the two methods in terms of the rate of detected mutations and the association of detected mutations with clinical outcomes. MATERIAL AND METHODS: PubMed, EMBASE, China National Knowledge Infrastructure (in Chinese) and Wanfang database (in Chinese) were searched to identify relevant studies. Meta-analyses of EGFR mutation rates, rate differences, and the associations of EGFR mutations with clinical outcomes of tyrosine kinase inhibitors treatment were conducted. RESULTS: Eight hundred and sixty-six records were retrieved and 26 studies with 3282 patients were included. The pooled rate of mutations detected by ARMS (41%, 95% confidence interval (CI) 35% to 47%) was significantly higher than that by direct sequencing (28%, 95%CI 22% to 34%), with a weighted rate difference of 11% (95%CI 8% to 13%). There was a consistent trend that the associations between ARMS-detected mutations and clinical outcomes were stronger than those between direct-sequencing-detected mutations and clinical outcomes (pooled risk ratio for objective response: 5.18 vs. 2.25; hazard ratio for progression-free survival: 0.30 vs. 0.42; hazard ratio for overall survival: 0.46 vs. 0.54). CONCLUSIONS: More patients with EGFR mutations can be identified by ARMS than by direct sequencing, and those identified by ARMS seems to be able to benefit more from tyrosine kinase inhibitors than those identified by direct sequencing.

Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis.

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.

The patterns and timing of recurrence after curative resection for gastric cancer in China.

BACKGROUND: The recurrence of gastric cancer after curative resection had adverse effects on patients' survival. The treatment presence varied from different countries. The aims of this study were to understand the recurrence incidence, patterns, and timing and to explore the risk factors in China. METHODS: One thousand three hundred four patients who undergoing curative resection from more than 100 hospitals between January 1st 1986 and September 1st 2013, were surveyed in detail. Clinical pathological factors were examined as potential risk factors of each recurrence pattern using univariate and multivariate analyses. Recurrence timing was also analyzed based on disease-free survival. RESULTS: Among 1304 gastric cancer patients, 793 patients (60.8%) experienced recurrence and 554 patients (42.5%) experienced recurrence within 2 years after operation. The median disease-free survival was 29.00 months (interquartile range [IQR] 12.07, 147.23). Receiving operation in general hospitals was one of independent risk factors of local-regional recurrence (OR = 1.724, 95% CI 1.312 to 2.265) and distant metastasis (OR = 1.496, 95% CI 1.164 to 1.940). Patients would suffer lower risk of distant metastasis if they received no more than 3 cycles adjuvant chemotherapy (OR = 0.640, 95% CI 0.433 to 0.943). Adjuvant radiotherapy could reduce the risk of recurrence (OR 0.259, 95% CI 0.100 to 0.670), especially distant metastasis (OR = 0.260, 95% CI 0.083 to 0.816). CONCLUSIONS: More than 60% patients experienced recurrence after curative resection for gastric cancer, especially within 2 years after surgery. Risk factors were clarified between various recurrence patterns. Advanced gastric cancer and undergoing operation in general hospitals contributed to increased recurrence risk and worse survival. Enough number of lymph nodes harvest and standard D2 lymphadenectomy could reduce recurrence. Chinese patients would benefit from adjuvant chemotherapy and radiotherapy.

The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis.

OBJECTIVES: Estimate the epidermal growth factor receptor (EGFR) mutation prevalence in all non-small cell lung cancer (NSCLC) patients and patient subgroups. RESULTS: A total of 456 studies were included, reporting 30,466 patients with EGFR mutation among 115,815 NSCLC patients. The overall pooled prevalence for EGFR mutations was 32.3% (95% CI 30.9% to 33.7%), ranging from 38.4% (95% CI: 36.5% to 40.3%) in China to 14.1% (95% CI: 12.7% to 15.5%) in Europe. The pooled prevalence of EGFR mutation was higher in females (females vs. males: 43.7% vs. 24.0%; OR: 2.7, 95% CI: 2.5 to 2.9), non-smokers (non-smokers vs. past or current smokers: 49.3% vs. 21.5%; OR: 3.7, 95% CI: 3.4 to 4.0), and patients with adenocarcinoma (adenocarcinoma vs. non-adenocarcinoma: 38.0% vs. 11.7%; OR: 4.1, 95% CI: 3.6 to 4.8). MATERIALS AND METHODS: PubMed, EMBASE, and the Cochrane Library were searched to June 2013. Eligible studies reported EGFR mutation prevalence and the association with at least one of the following factors: gender, smoking status and histology. Random-effects models were used to pool EGFR mutation prevalence data. CONCLUSION: This study provides the exact prevalence of EGFR mutations in different countries and NSCLC patient subgroups.

The characteristics and prognostic value of signet ring cell histology in gastric cancer: A retrospective cohort study of 2199 consecutive patients.

Although signet ring cell cancer (SRCC) has long been regarded as an adverse prognostic factor of gastric cancer, the findings of existing studies on this issue are inconsistent. We conducted a retrospective cohort study of 2199 consecutive patients with gastric cancer treated in a tertiary cancer hospital in Beijing, China, 1994 to 2013. The characteristics of SRCC and non-SRCC were compared. The prognostic effects of SRCC and other important clinicopathological factors on overall survival were evaluated by both univariate and multivariate Cox regression analyses and expressed as hazard ratio (HR) with 95% confidence interval (CI). SRCC accounted for 16.1% of gastric cancer, increasing from 6% to 20% over the last 2 decades, and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. SRCC (HR: 1.387, 95% CI: 1.177-1.634), stage (HR: 1.752, 95% CI: 1.458-2.106), surgery (palliative resection: HR: 0.712, 95% CI: 0.590-0.859; curative resection: HR: 0.490, 95% CI: 0.380-0.633), performance status (HR: 1.849, 95% CI: 1.553-2.201), and age (HR: 1.070, 95% CI: 1.001-1.143) were independent prognostic factors for gastric cancer, whereas time period of diagnosis, sex, and tumor location were not statistically significantly associated with overall survival. Subgroup analyses showed that the prognostic value of SRCC did not vary much with age, sex, performance status, stage, and surgery and chemotherapy status. As compared with non-SRCC, SRCC accounted for increasingly more of gastric cancer and was associated with younger age, female sex, poor differentiation, diffuse type, and distal location. It was an independent prognostic factor associated with worse survival in gastric cancer.

The prognostic value of phosphatase and tensin homolog negativity in breast cancer: A systematic review and meta-analysis of 32 studies with 4393 patients.

The prognostic value of phosphatase and tensin homolog (PTEN) negativity in breast cancer has been evaluated by many studies but remains controversial. We conducted a meta-analysis to assess the association of PTEN negativity with overall survival and disease-free survival. Thirty-two studies with 4393 patients were identified. PTEN negativity was significantly associated with unfavorable overall survival in breast cancer (hazard ratio=1.89, 95% confidence interval 1.58-2.26), with low heterogeneity among the studies (I(2)=25%, P=0.160) and no evidence for publication bias. Meta-analysis of multivariate hazard ratios and sensitivity analyses did not materially change the results. The data on disease-free survival was heterogeneous (I(2)=61.9%, P<0.001), with a summary hazard ratio of 1.57 (95% confidence interval 1.31-1.89). The exact source of heterogeneity remains unclear. We thus concluded that PTEN negativity was significantly associated with unfavorable prognosis in terms of overall survival in breast cancer.

Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.

BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Network Meta-analysis.

A wide array of drugs are available for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), but the evidence for the comparative effectiveness is controversial.The objective of this study is to evaluate the comparative effectiveness and safety of monodrug therapies for BPH.Data sources are MEDLINE, EMBASE, and the Cochrane Library.We included randomized controlled trials that compared α-blockers, 5-alpha reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), phosphodiesterase-5 inhibitor (PDE5-Is), or placebo for the treatment of BPH.Comparative effectiveness and safety were pooled by both traditional meta-analysis and network meta-analysis. Summary effect size was calculated as mean difference (MD) and relative risk (RR), together with the 95% confidence intervals (CIs).This study included 58,548 participants from 124 trials in total. When compared with placebo, α-blockers, 5ARIs, and PDE5-Is reduced International Prostate Symptom Score (IPSS) by -1.35 to -3.67 points and increased peak urinary flow rate (PUF) by -0.02 to 1.95 mL/s, with doxazosin (IPSS: MD, -3.67[-4.33 to -3.02]; PUF: MD, 1.95[1.61 to 2.30]) and terazosin (IPSS: MD, -3.37 [-4.24 to -2.50]; PUF: MD, 1.21[0.74 to 1.66]) showing the greatest improvement. The improvement in the IPSS was comparable among tamsulosin, alfuzosin, naftopidil, silodosin, dutasteride, sildenafil, vardenafil, and tadalafil. The incidence of total adverse events and withdraws due to adverse events were generally comparable among various agents.In conclusion, α-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile.

Colorectal cancer: using blood samples and tumor tissue to detect K-ras mutations.

We performed a meta-analysis to assess whether blood can be substituted for tumor tissue in K-ras mutation testing. PubMed, EMBASE, MEDLINE, and BIOSIS databases were searched. Twenty-three studies including 1261 patients were included. The pooled overall sensitivity, specificity, and concordance rate were 0.69 (95% CI: 0.59-0.78), 0.96 (95% CI: 0.93-0.97), and 0.86 (95% CI: 0.82-0.89), respectively. Subgroup analysis indicated that plasma (sensitivity: 0.74; mutation rate: 0.34) exhibited superior sensitivity compared with serum (sensitivity: 0.45; mutation rate: 0.24). We conclude that blood is a suitable substitute for tumor tissue in K-ras mutation testing. K-ras mutation positivity in blood can be used to identify patients who should not receive EGFR monoclonal antibody therapy, but the absence of blood positivity does not necessarily imply negativity.

Blood as a Substitute for Tumor Tissue in Detecting EGFR Mutations for Guiding EGFR TKIs Treatment of Nonsmall Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC). We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens. Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used. This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48-6.70), PFS (HR: 0.72; 95% CI 0.64-0.80), and OS (HR: 0.71; 95% CI 0.50-0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma. Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases.

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%-93.9%) for KRAS, 96.8% (95% CI: 94.8%-98.0%) for BRAF, 93.9% (95% CI: 89.7%-96.5%) for PIK3CA and 71.7% (95% CI: 57.6%-82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%-12.4%) and 11.3% (95% CI: 8.0%-15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.

The prognostic value of phosphorylated Akt in breast cancer: a systematic review.

The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer has been investigated by many studies with inconsistent results. This systematic review was conducted to evaluate the association of pAkt overexpression with breast cancer prognosis in terms of overall survival and disease-free survival. Three electronic databases (PubMed, EMBASE and Chinese Biomedical Literature Database) were comprehensively searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) from different studies were combined using the random-effects model. In total, 33 studies with 9,836 patients were included for final analysis. The summary HR for overall survival and disease-free survival was 1.52 (95% CI: 1.29-1.78) and 1.28 (95% CI: 1.13-1.45), respectively, indicating higher risk of death and disease recurrence associated with pAkt overexpression. The results were robust in sensitivity analyses by omitting one study each time and by using the fixed-effects model instead. Subgroup and meta-regression analyses did not show that the prognostic effect of pAkt overexpression would change materially with such factors as population, status of hormone receptors, hormonal or trastuzumab treatment given, analyzing method (univariate versus multivariate) and methodological quality of the original studies. In conclusion, the available evidence suggests that pAkt overexpression is an adverse prognostic factor for breast cancer.