Involvement in treatment decision-making and self-reported efficacy among patients with advanced colorectal cancer: a nationwide multi-center cross-sectional study.

Introduction: This cross-sectional study evaluated the involvement of patients with advanced colorectal cancer (CRC) in treatment decision-making, assessed the treatment efficacy according to their self-reports, and investigated the influencing factors. Methods: Patients with advanced CRC were recruited from 19 hospitals from March 2020 to March 2021 by a multi-stage multi-level sampling method. A self-designed questionnaire was used to collect demographic and clinical characteristics, involvement of CRC patients in treatment decision-making, treatment methods, and self-reported efficacy. Univariate and unordered multinomial logistic regression analyses were used to evaluate the factors affecting the involvement in treatment decision-making and self-reported efficacy. Results: We enrolled 4533 patients with advanced CRC. The average age at diagnosis was 58.7 ± 11.8 years. For the treatment method, 32.4% of patients received surgery combined with chemotherapy, 13.1% of patients underwent surgery combined with chemotherapy and targeted therapy, and 9.7% of patients were treated with surgery alone. For treatment decision-making, 7.0% of patients were solely responsible for decision-making, 47.0% of patients shared treatment decision-making with family members, 19.0% of patients had family members solely responsible for treatment decision-making, and 27.0% of patients had their physicians solely responsible for treatment decision-making. Gender, age, education level, family income, marital status, treatment cost, hospital type, and treatment method were significantly associated with the involvement of patients in treatment decision-making. A total of 3824 patients submitted self-reported efficacy evaluations during treatment. The percentage of patients with good self-reported efficacy was 76.5% (for patients treated for the first time), 61.7% (for patients treated for the second time), and 43.2% (for patients treated after recurrence and metastasis), respectively. Occupation, education level, average annual family income, place of residence, time since cancer diagnosis, hospital type, clinical stage, targeted therapy, and involvement in treatment decision-making were the main influencing factors of self-reported efficacy of treatment. Discussion: Conclusively, CRC patients are not highly dominant in treatment decision-making and more likely to make treatment decisions with their family and doctors. Timely and effective communication between doctors and patients can bolster patient involvement in treatment decision-making.

Real-World Utilization, Barriers, and Factors Associated With the Targeted Treatment of Metastatic Colorectal Cancer Patients in China: A Multi-Center, Hospital-Based Survey Study.

Objectives: To explore the utilization, barriers, and factors associated with the targeted treatment of Chinese metastatic colorectal cancer (mCRC) patients. Methods: A total of 1,688 mCRC patients from 19 hospitals in 14 cities were enrolled from March 2020 to March 2021 using stratified, multistage cluster sampling. The use of targeted therapy and any barriers patients experienced were collected. Logistic regression analyses were conducted to identify the factors associated with initiating targeted treatment. Results: About 51.6% of the patients initiated targeted therapy, of whom 44.5%, 20.2%, and 35.2% started first-, second-, and third-line treatment, respectively. The most reported barriers were high medical costs and a lack of belief in the efficacy of targeted therapy. Patients treated in the general hospital, diagnosed at an older age, less educated, and who had a lower family income, no medical insurance, poor health-related quality of life, metastasis outside the liver/lung or systemic metastasis, a shorter duration of mCRC were less likely to initiate targeted therapy. Conclusion: Reduced medical costs and interventional education to improve public awareness could facilitate the use of targeted treatment for mCRC.

TD-Net: A Hybrid End-to-End Network for Automatic Liver Tumor Segmentation From CT Images.

Liver tumor segmentation plays an essential role in diagnosis and treatment of hepatocellular carcinoma or metastasis. However, accurate and automatic tumor segmentation remains a challenging task, owing to vague boundaries and large variations in shapes, sizes, and locations of liver tumors. In this paper, we propose a novel hybrid end-to-end network, called TD-Net, which incorporates Transformer and direction information into convolution network to segment liver tumor from CT images automatically. The proposed TD-Net is composed of a shared encoder, two decoding branches, four skip connections, and a direction guidance block. The shared encoder is utilized to extract multi-level feature information, and the two decoding branches are respectively designed to produce initial segmentation map and direction information. To preserve spatial information, four skip connections are used to concatenate each encoder layer and its corresponding decoder layer, and in the fourth skip connection a Transformer module is constructed to extract global context. Furthermore, a direction guidance block is well-designed to rectify feature maps to further improve segmentation accuracy. Extensive experiments conducted on public LiTS and 3DIRCADb datasets validate that the proposed TD-Net can effectively segment liver tumor from CT images in an end-to-end manner and its segmentation accuracy surpasses those of many existing methods.

Efficacy, safety, and immunogenicity of an Escherichia coli-produced Human Papillomavirus (16 and 18) L1 virus-like-particle vaccine: end-of-study analysis of a phase 3, double-blind, randomised, controlled trial.

BACKGROUND: This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up. METHODS: This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18-45 years, with intact cervix and 1-4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18-26 and 27-45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006. FINDINGS: Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2-100·0) against high-grade genital lesions (0 [0%] of 3310 participants in the vaccine group and 13 [0·4%] of 3302 participants in the control group) and 97·3% (89·9-99·7) against persistent infection (2 [0·1%] of 3262 participants in the vaccine group and 73 [2·2%] of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 [7·2%] of 3691 participants) and control groups (290 [7·9%] of 3681); none were considered related to vaccination. INTERPRETATION: The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.

Uncertainty-guided man-machine integrated patient-specific quality assurance.

PURPOSE: Providing the confidence level (Uncertainty) of prediction results and guiding patient-specific quality assurance (pQA) can enhance the safety of AI (Artificial intelligence)-based automatic pQA models. However, even state-of-the-art automatic pQA models can only predict the gamma passing rate (GPR) and cannot quantify the prediction uncertainty, limiting the safe clinical translation of these models. This study aims to develop an uncertainty-guided man-machine integrated pQA (UgMi-pQA) method to address this issue. METHODS: An uncertainty-aware dual-task deep learning (UDDL) model, combined with an interwoven training method and Monte Carlo dropout approximation Bayesian inference, to enable simultaneous output of the predicted GPR and corresponding total prediction uncertainty to guide pQA. 1541 pairs of field fluences and GPRs collected from 165 glioma, 50 lung (conventional fractionation), and 20 liver cases were separated for the UDDL model training, validation, calibration, and test in a ratio of 7:1:1:1, respectively. Furthermore, 413 pairs of fluences and GPRs collected from 12 breast, 10 cervix, 9 esophagus, 8 tongue, and 12 lung SBRT cases were gathered for the out-of-distribution (OOD) detection. RESULTS: Clinical accuracy of 100.0% was reached with only 61.7% of the workload. Samples with substantial prediction errors and failed samples with low label GPR (<95%) could be successfully screened out. The capability ranges of two different models were both successfully identified with the prediction uncertainty significantly larger for OOD samples than for in-distribution samples (p < 0.01). CONCLUSION: This study presents the first work on uncertainty quantification for deep learning automatic pQA tasks. The UgMi-pQA method can balance the efficiency and safety of the automatic pQA models and promote their clinical application.

Knowledge and awareness of colorectal cancer risk factors, screening, and associated factors in advanced colorectal cancer patients: a multicenter cross-sectional study in China.

Background: Colorectal cancer (CRC) is the 3rd most common malignancy globally, and its disease burden is increasing rapidly in China. But CRC patients' knowledge and awareness of CRC have not yet been examined, which could facilitate the identification of targeted population from public for intervention. Methods: A nationwide multicenter cross-sectional survey was conducted in 19 tertiary hospitals (10 cancer hospitals and 9 general hospitals) from March 2020 to March 2021 in China. During study period, all Stage III and IV CRC patients were invited to complete a semi-structured survey that had been designed to collect information about their socio-demographic characteristics, and knowledge and awareness of CRC risk factors and screening. A multivariate logistic regression model was used to identify factors associated with their knowledge and awareness. Results: In total, 4,589 advanced CRC patients were enrolled in this study, of whom, 46.2% were from tertiary cancer hospitals, and 59.5% were male. Patients had a mean age of 60.1±11.6 years. Before diagnosis, 65.1% of the patients had no related knowledge of the CRC risk factors, and 84.9% were unaware of the CRC screening-related information. Only 30.4% of patients had actively sought to acquire CRC-related knowledge before diagnosis. The 3 most common knowledge sources were relatives or friends who had been diagnosed with CRC (13.2%), popular science television/broadcast shows (12.9%), and community publicity and education (9.6%). Generally, knowledge and awareness were positively associated with better education level [odds ratios (ORs) ranged from 1.49 to 2.54, P<0.001], annual household income ranged from 50,000 Chinese Yuan (CNY) to 100,000 CNY (OR =1.32, P<0.001), being manual laborer (OR =1.25, P<0.001) and being white-collar worker (OR =1.47, P<0.001). Conclusions: Advanced CRC patients' knowledge and awareness of CRC were severely limited before diagnosis. Thus, those who had limited knowledge and awareness should has a priority for intervention.

Status and associated factors of cross-regional healthcare-seeking among patients with advanced colorectal cancer in China: a multicenter cross-sectional study.

Background: The imbalanced allocation of medical resources leads to the occurrence of cross-regional healthcare-seeking in China. Due to the low cure rate, advanced colorectal cancer (CRC) patients may seek cross-regional healthcare for high-level medical facilities. Investigating status of cross-regional healthcare-seeking and its associated factors among advanced CRC patients is important for policymakers to understand access to health services and improve the quality of oncology services. Methods: From March 2020 to March 2021, a cross­sectional, nation-wide, hospital-based, multi-center survey was conducted. Nineteen hospitals in seven regions were selected by multi-stage stratified sampling. All eligible CRC patients in the selected hospitals were invited to participate in the current study. The outcome variable, cross-regional healthcare-seeking, was defined as seeking health facilities outside the local administration policy of medical insurance. The demographics, clinical information, and medical treatment history of each eligible CRC patient in stage III or IV, were collected through the patients' self-reporting or medical records by trained interviewers. Univariate and multivariate logistic analyses were used to explore the associated factors of cross-regional healthcare-seeking. All statistical analyses were conducted using SAS 9.4. Results: A total of 4,589 individuals with advanced CRC were included. The average age of the patients was 60.1±11.6 years, and 59.5% were males. About 37.5% of the patients suffered from metastatic CRC at first diagnosis. Approximately 36.5% of the patients had sought cross-regional health care previously, and among them, 31.9% had encountered problems. The most common problems included complicated procedures (95.3%), unreimbursed expenses of outpatient service (71.0%), and reimbursement delay (59.4%). Logistic regression analysis showed that patients who completed undergraduate or above [odds ratio (OR) =1.40, 95% confidence interval (CI): 1.13-1.73], had an annual household income of more than 100,000 Chinse Yuan (CNY) (OR =1.46, 95% CI: 1.21-1.78), and had metastasis at diagnosis (OR =1.33, 95% CI: 1.18-1.51) were more likely to seek cross-regional health care. Conclusions: About one third of advanced CRC patients seek cross-regional health care, and 31.9% had encountered problems. There is a need to simplify procedures of reimbursement, optimize direct settlement system and referral mechanisms in order to improve the equality of health services.

Health-related quality of life in advanced colorectal cancer patients in China: a nationwide hospital-based survey.

Background: Colorectal cancer (CRC) is one of the most common cancers in China, and most CRC patients have already reached an advanced stage by the time of initial diagnosis. Due to the loss of health as a result of cancer, it has consequence on the treatment which may affect the psychophysical and social impairment of CRC patients. These indicators (psychophysical, function and social impairment) affect the health-related quality of life (HRQOL). There are limited studies that focus on advanced CRC patients in China. This study aimed to assess the HRQOL and its associated factors of advanced CRC patients in China. Methods: This was a cross-sectional, nationwide, hospital-based, and multi-center survey. According to the traditional administrative district definition, we selected 19 hospitals in 7 regions by multi-stage stratified sampling in China. For each eligible CRC patient with stage III or IV in the selected hospitals, socio-demographics, clinical information, and HRQOL were collected based on patients' self-reporting and/or medical records between March 2020 and March 2021. Patients completed the Functional Assessment of Cancer Therapy Colorectal (FACT-C) plus-traditional Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-9. Results: A total of 4,589 CRC patients (mean age 60.1 years, including 2,730 males and 1,859 females) were included. The total score of HRQOL in population was 128.2±24.70. There were significant differences in the overall score of HRQOL in gender, education level, occupation, region, disease type, and disease stage (P<0.05). The score of HRQOL was better in males, undergraduates and above, unemployed/laid-off, and southwestern and central China. Multivariate analysis showed that education level, occupation, location, number of hospitals visited and treatment methods, and gender were associated with utilities of CRC patients. Conclusions: The HRQOL is an important outcome measure for CRC patients. The HRQOL scores differed according to socio-demographic and clinical characteristics, and findings of these factors were associated with education level, occupation, region, number of visited and treatment methods, and gender.

The choice of medical facility and associated factors among Chinese advanced colorectal cancer patients: a cross-sectional multi-center study.

Background: Colorectal cancer (CRC) poses a significant public health burden worldwide. The investigation of the choice of medical facility among CRC patients is helpful for understanding access to health services and improving quality of oncology services to optimize health outcomes. However, there are limited studies on the topic. The objective of this study was to investigate the choice of medical facility and its associated factors among advanced CRC patients. Methods: This cross-sectional multi-center study included a total of 4,589 individuals with advanced CRC from 19 hospitals in 7 geographic regions in China. Participants were recruited by multi-stage stratified sampling. In the first stage, two cities in each geographic region were selected through simple random sampling. In the second stage, one tertiary cancer hospital and/or one general hospital were selected in each city. Data on medical experience and demographics were collected via a questionnaire during face-to-face interviews. Explanatory variables were selected based on the Andersen behavioral model. Multinomial logistic regression analyses were performed to explore the factors associated with the level of medical facility for the first treatment. Results: Hospitals at the prefecture level were the most common medical facility sought by advanced CRC patients for initial medical care (44.9%), the first definite diagnosis (46.3%), the first treatment (39.5%), and regular follow-up (38.9%). However, the first priority was changed to hospitals at the national level for the second treatment (38.0%) and after recurrence and metastasis (45.9%). Female {odds ratios (ORs) ranged from 1.31 [95% confidence interval (CI): 1.01-1.71] to 1.41 (95% CI: 1.07-1.87)} and relatively well-educated individuals [ORs ranged from 1.74 (95% CI: 1.20-2.53) to 7.26 (95% CI: 4.18-12.60)] preferred to seek higher-level health facilities. Individuals with metastatic CRC at diagnosis were more likely to visit hospitals in provincial capitals versus hospitals at the county level (OR =1.68, 95% CI: 1.27-2.22). Individuals with "good" health-related quality of life (HRQOL) (OR =0.63, 95% CI: 0.49-0.81) were less likely to seek hospitals at the prefecture level compared with hospitals at the county level. Conclusions: There is a need to improve the oncology services for CRC patients, including the optimization of referral reform policy and the promotion of quality of primary healthcare service. The results may provide evidence to fill the policy-implementation gap and potentially contribute to the improvement of the efficiency of the healthcare system.

Out-of-pocket medical expenditure and associated factors of advanced colorectal cancer in China: a multi-center cross-sectional study.

Background: Colorectal cancer (CRC) causes a substantial disease burden in China. Information on the medical expenditure of CRC patients is critical for decision-makers to allocate medical resources reasonably, however, relevant data is limited in China, especially advanced CRC. The aim of this survey was to quantify the out-of-pocket medical expenditure of advanced CRC and explore associated factors. Methods: A nation-wide, multi-center, cross-sectional survey was conducted from March 2020 to March 2021. Nineteen hospitals in seven geographical regions were selected by multi-stage stratified sampling. For each eligible CRC patient with stage III or IV disease in the selected hospitals, the socio-demographics, clinical information, and range of out-of-pocket medical expenditure data were collected based on patients' self-reporting or medical records. Multivariable logistic analysis was used to explore associated factors of medical expenditure. All statistical analyses were conducted using SAS 9.4. Results: The mean age of the 4,428 advanced CRC patients included was 59.5±11.6 years, 59.6% were male, and 80.1% of patients were in stage III or IV at the time of diagnosis. Besides, 57.2% of patients had an annual household income of less than 50,000 Chinese Yuan (CNY), 40.9% of patients had an out-of-pocket medical expenditure of 50,000-99,999 CNY. As for the affordability of medical expenditure, 33.2% could afford 50,000-99,999 CNY. Multivariate analysis showed that patients who were in the southern [odds ratio (OR): 1.63, 95% confidence interval (CI): 1.31-2.03] and southwestern (OR: 1.55, 95% CI: 1.25-1.93), were in stage III at the time of diagnosis (OR: 1.33, 95% CI: 1.13-1.57), visited three or more hospitals (OR: 1.26, 95% CI: 1.04-1.52), had sought cross-regional health care (OR: 1.60, 95% CI: 1.40-1.83), used genetic testing (OR: 1.26, 95% CI: 1.10-1.45) and targeted drugs (OR: 2.12, 95% CI: 1.79-2.51) had higher out-of-pocket medical expenditure. Conclusions: Patients with advanced CRC had a high out-of-pocket medical expenditure. It is necessary to strengthen the prevention and control of CRC to reduce the disease burden; also, it is critical to deepen the reform of the medical system, increase proportion of medical insurance reimbursement, and remove barriers to cross-regional health care.

Utilization of genetic biomarkers testing and its associated factors in advanced colorectal cancer patients in China: a nationwide multicenter clinical epidemiological study.

Background: Biomarkers are a key tool in early detection, prognostication, survival, and predicting treatment response of colorectal cancer (CRC). However, little is known about biomarker testing for CRC patients in real-life clinical practice in China. This study aimed to address the usage of biomarker testing and analyze factors related to its acceptance among Chinese patients with advanced CRC. Methods: A multicenter, cross-sectional, hospital-based clinical epidemiology study was conducted from March 2020 to March 2021. Nineteen hospitals were selected in seven geographical regions of China using stratified, multistage, nonrandomized cluster sampling. Data on demographics and clinical characteristics of each eligible CRC patient in stage III or IV diseases were recorded based on the patients' self-reporting and/or medical records. In addition, information on whether biomarker testing [RAS, BRAF, and microsatellite instability (MSI)] was performed, the results and timing for performing biomarker testing, and the reasons for refusing biomarker testing were also recorded. Univariate and multivariate logistic regression were conducted to explore the potential factors of biomarker testing. Results: A total of 4,526 patients were enrolled in the study, of whom 41.4%, 36.1%, and 28.2% underwent RAS, BRAF, and MSI testing, respectively. RAS, BRAF, and high-level MSI (MSI-high) mutation rates in Chinese patients with advanced CRC were 37.0%, 9.9%, and 8.1%, respectively. The logistic regression analysis revealed that the treating hospital, age at diagnosis, education, family income, tumor site, history of chemotherapy and radiotherapy, and metastases were dependent factors affecting the utilization of biomarker testing in advanced CRC in China (P<0.005). Conclusions: The biomarker testing rate, especially MSI testing, is less prevalent in clinical practice for patients with advanced CRC in China. Our findings may guide the formulation of biomarker testing of CRC strategies in China and other low-income countries.

Disease knowledge, medical experience, health-related quality of life and health-care costs among patients with advanced colorectal cancer in China: protocol for a nationwide multicentre survey.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in China. Most patients have developed advanced stage at diagnosis, leading to a low 5-year survival rate. To optimise prevention strategies, we planned a survey to evaluate the disease knowledge, medical experience and health-related quality of life (HRQOL) before and after the treatment of CRC, and healthcare costs among patients with advanced CRC in China. METHODS AND ANALYSIS: This is a nationwide, hospital-based, multicentre survey. Nineteen hospitals in seven cities were selected by multistage stratified sampling. Mainland China is divided into seven regions according to the traditional administrative district definition; two cities of each region were selected through simple random sampling, and then one tertiary cancer hospital and one general hospital were selected for each city. More than 4445 patients with CRC in the selected hospitals with stage III or IV will be enrolled in this study. The trained interviewers will collect information through patients' self-report and/or medical records, including demographics and medical history; knowledge about CRC high-risk factors, screening procedure and treatment methods; medical experience on CRC screening, diagnosis and treatment; HRQOL before and after CRC treatment; and costs of CRC. All data will be input by two independent staff and verified using Epidata V.3.1 software. Data validation plan will be made to guide data checking. All statistical analyses will be conducted using SAS V.9.4 and SPSS V.24.0 software. ETHICS AND DISSEMINATION: The study was approved by the ethics committees of Henan Cancer Hospital, the leading participant hospital. Findings of this study will be disseminated through peer-reviewed open-access journals and presented as posters and/or oral sections in national and international conferences. Results will also be popularised to the public via media or the internet.

Performance of low-dose computed tomography on lung cancer screening in high-risk populations: The experience over five screening rounds in Sichuan, China.

OBJECTIVE: To evaluate the performance of low-dose computed tomography (LDCT) on lung cancer screening in high-risk populations in Sichuan. METHODS: From April 2014 to July 2018, LDCT was performed annually on 3185 subjects aged 50-74 years who had smoked ≥ 20 pack-years (or subjects having quit smoking within 5 years). Information about all deaths and lung cancer diagnoses were obtained by active investigation, or passive matching to disease surveillance system. RESULTS: The screening population had a median age of 60 years. 62.4 % of which were current smokers and had smoked 30 pack-years. After participating in the baseline screening, the compliance rates of subjects consecutively completing one round, two rounds, three rounds, and four rounds of annual screening were 67.22 %, 52.84 %, 43.24 %, and 40.04 %, respectively. The positive rates in baseline and annual screening were 6.53 % and 5.79 %, respectively. During the 5 rounds, a total of 9522 person-times were screened by LDCT with a screening sensitivity of 89.13 % (95 % CI: 76.96-95.27), specificity of 94.36 % (95 % CI: 93.88-94.81), positive predictive value of 7.13 % (95 % CI: 5.30-9.53), and negative predictive value of 99.94 % (95 % CI: 99.87-99.98). There were no statistically significant performance differences between baseline and annual screening. The difference in the proportion of screen-detected stage I lung cancer between baseline screening and annual screening was not statistically significant, neither. CONCLUSION: The application of LDCT on lung cancer screening in high-risk populations shows favorable compliance and a high screening performance in the project area of Sichuan,China.

The Performance of Immunocytochemistry Staining as Triaging Tests for High-Risk HPV-Positive Women: A 24-Month Prospective Study.

It is urgent to develop an accurate approach to improve the predictive performance of hrHPV-based screening. The aim is to evaluate the performance of p16/Ki-67 and p16/MCM2 staining to triage high-risk human papillomavirus- (hrHPV-) positive women. Cervical specimens were collected from eligible women and tested for hrHPV genotyping, cytology, p16/Ki-67, and p16/MCM2 staining at baseline. Women were invited to participate in follow-up screening by cytology and hrHPV testing at 24 months. Positive women received colposcopy and biopsies. Histopathological diagnoses were the gold standard. 485 women came back for the follow-up screening. The positive rate of p16/Ki-67 was 20.2% and of p16/MCM2 was 27.2%. The positive rates of p16/Ki-67 ( P < 0.001) and p16/MCM2 (P=0.021) were increased by the severity of histopathology findings. Among hrHPV-positive women, the sensitivity, specificity, PPV, and NPV for p16/Ki-67 were 90.9%, 67.0%, 16.5%, and 99.0%, and for p16/MCM2 were 81.8%, 43.1%, 9.4%, and 97.1%. The sensitivity of cytology for triaging hrHPV-positive women were lower than p16/Ki-67 (P=0.012) and p16/MCM2 (P=0.065). The cocktail staining did not add sensitivity to p16/Ki-67 or p16/MCM2 staining alone (P > 0.05), however, cutting down the specificity of p16/Ki-67 staining alone with statistical significance (67.0% vs. 40.2%, P < 0.001). The risk of CIN2+ within 24 months for hrHPV-positive but triaging negative women at baseline was 0.5 (0.1-2.7), 0.7 (0.1-4.1), and 2.4 (1.1-5.0) for p16/Ki-67, p16/MCM2, and cytology, respectively. As an objective and accurate immunocytochemical staining, the p16/Ki-67 and p16/MCM2 dual staining performed better than cytology to triage positive hrHPV. On condition that high-quality cytology is unavailable, immunocytochemical staining by p16/Ki-67 or p16/MCM2 is an option for triaging hrHPV-positive women. The combination of p16/Ki-67 and p16/MCM2 could not improve the accuracy in detecting CIN2+.

Liver segmentation from abdominal CT volumes based on level set and sparse shape composition.

BACKGROUND AND OBJECTIVE: Liver segmentation from abdominal CT volumes is a primary step for computer-aided surgery and liver disease diagnosis. However, accurate liver segmentation remains a challenging task for intensity inhomogeneity and serious pathologies occurring in liver CT volume. This paper presents a novel framework for accurate liver segmentation from CT images. METHODS: Firstly, a novel level set integrated with intensity bias and position constraint is applied, and for normal liver, the generated liver regions are regarded as the final results. Then, for pathological liver, a sparse shape composition (SSC)-based method is presented to refine liver shapes, followed by an improved graph cut to further optimize segmentation results. The level set-based method is capable of overcoming intensity inhomogeneity in object regions, and the SSC- and graph cut-based strategy has outstanding power to address under-segmentation appearing in pathological livers. RESULTS: The experiments conducted on public databases SLIVER07 and 3Dircadb show that the proposed method can segment both healthy and pathological liver effectively. The segmentation performance in terms of mean ASD, RMSD, MSD, VOE and RVD on SLIVER07 are 0.9mm, 1.8mm, 19.4mm, 5.1% and 0.1%, respectively, and on 3Dircadb are 1.6mm, 3.1mm, 27.2mm, 9.2% and 0.5%, respectively, which outperforms many existing methods. CONCLUSIONS: The proposed method does not require complex training procedure on numerous liver samples, and has satisfying and robust segmentation performance on both normal and pathological liver in various shapes.

Impact of International Collaborative Training Programs on Medical Students' Research Ability.

International collaborative training programs for graduate students are widespread, but studies on their educational impact are limited. As an advanced cancer institute in China, Cancer Hospital Chinese Academy of Medical Science (CHCAMS) attaches great importance to international exchanges and cooperation within graduate education. The Department of Epidemiology of CHCAMS has been involved in several existing international training programs and has also launched a short-term training program in cooperation with foreign universities and institutes from 2008. Fogarty International Clinical Research Scholars and Fellows (FICRS-F) Program and the Fulbright-Fogarty Fellowship Program are the most typical examples of our practice in international cooperation on graduate education over these years. Our department has gained substantial experience in graduate-level international collaborative training, focused on cancer epidemiology. This paper is a brief introduction to the practice of different programs in our department and students' achievements during and after training. Moreover, we attempt to serve as a reference and help promote the training of graduate students pursuing careers in cancer research or global health by other universities or research institutes.

A retrospective analysis of the utility of endocervical curettage in screening population.

The performance of endocervical curettage (ECC) is a dispute in population screening programs. Data of 3,460 women referred to colposcopy examination and had completed pathological results in the Shanxi Province Cervical Cancer Screening Study I and II were reviewed. Among them, 0.6% and 2.7% women were identified as the histopathological confirmed high-grade squamous intraepithelial lesion or worse (HSIL+) by ECC alone or both ECC and quadrants biopsy respectively. Age, cytology, and colposcopy impression are the impact factors for the HSIL+ yield of ECC (P<0.05). The age-adjusted odds ratio for cytology and colposcopic impression were 5.283 (95%CI: 3.989-6.997) and 3.609 (95%CI: 2.910-4.476) respectively. In low-grade squamous intraepithelial lesion cytology and abnormal colposcopy, no additional HSIL+ was found by ECC. In low-grade squamous intraepithelial lesion cytology but normal colposcopy, the additional yield was 0.6%, 0.8% and 1.1% for the three age groups respectively. In high-grade squamous intraepithelial lesion or worse cytology, the additional HSIL+ yield by ECC ranged between 1.4% and 6.6%. We conclude that the performance of ECC increases with age, the severity of cytology, and colposcopic impression. For women 35 years and older, ECC should be performed if the cytological finding is high-grade or worse in cervical cancer screening program.

Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.

AIM: Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 inhibitor, HJ-PI01, by in silico analysis and experimental validation. METHODS: The protein-protein interaction (PPI) network, chemical synthesis, molecular docking, and molecular dynamics (MD) simulations were used to design and discover the new Pim-2 inhibitor HJ-PI01. The anti-tumor effects of HJ-PI01 were evaluated in human breast MDA-MB-231, MDA-MB-468, MDA-MB-436, MCF-7 cells in vitro and in MDA-MB-231 xenograft mice, which were treated with HJ-PI01 (40 mg·kg(-1)·d(-1), ig) with or without lienal polypeptide (50 mg·kg(-1)·d(-1), ip) for 10 d. The apoptosis/autophage-inducing mechanisms of HJ-PI01 were elucidated using Western blots, immunoblots, flow cytometry, transmission electron microscopy and fluorescence microscopy. RESULTS: Based on the PrePPI network, the potential partners interacting with Pim-2 in regulating apoptosis (160 protein pairs) and autophagy (47 protein pairs) were identified. Based on the structural characteristics of Pim-2, a total of 15 compounds (HJ-PI01 to HJ-P015) were synthesized, which showed moderate or remarkable anti-proliferative potency in the human breast cancer cell lines tested. The most effective compound HJ-PI01 exerted a robust inhibition on MDA-MB-231 cells compared with chlorpromazine and the pan-Pim inhibitor PI003. Molecular dynamics (MD) simulation revealed that HJ-PI01 had a good binding score with Pim-2. Moreover, HJ-PI01 (300 nmol/L) induced death receptor-dependent and mitochondrial apoptosis as well as autophagic death in MDA-MB-231 cells. In MDA-MB-231 xenograft mice, administration of HJ-PI01 remarkably inhibited the tumor growth and induced tumor cell apoptosis in vivo. Co-administration of HJ-PI01 with lienal polypeptide could improve the anti-tumor activity of HJ-PI01 and reduce its toxicity. CONCLUSION: The newly synthesized compound, HJ-PI01, can induce death receptor/mitochondrial apoptosis and autophagic cell death by targeting Pim-2 in human breast cancer cells in vitro and in vivo.

Liver vessel segmentation based on extreme learning machine.

Liver-vessel segmentation plays an important role in vessel structure analysis for liver surgical planning. This paper presents a liver-vessel segmentation method based on extreme learning machine (ELM). Firstly, an anisotropic filter is used to remove noise while preserving vessel boundaries from the original computer tomography (CT) images. Then, based on the knowledge of prior shapes and geometrical structures, three classical vessel filters including Sato, Frangi and offset medialness filters together with the strain energy filter are used to extract vessel structure features. Finally, the ELM is applied to segment liver vessels from background voxels. Experimental results show that the proposed method can effectively segment liver vessels from abdominal CT images, and achieves good accuracy, sensitivity and specificity.

Distribution of cervical intraepithelial neoplasia on the cervix in Chinese women: pooled analysis of 19 population based screening studies.

BACKGROUND: Controversy remains whether a pattern of cervical intraepithelial neoplasia exists on the cervix. Our study aims at determining if the prevalence of histologically proven lesions differs by cervical four-quadrant location or by 12 o'clock surface locations of diagnosis. METHODS: We conducted a retrospective, histopathological study of 19 different population based cervical cancer screening studies from 1999 to 2010 by Cancer Hospital of Chinese Academy of Medical Sciences. The Institutional Review Board for human research subjects at CHCAMS approved all of the studies. During the colposcopy procedure, participant received either 4-quadrant biopsy or directed biopsy with/without endocervical curettage. Data of all samples were stratified by the methods of sampling. Kruskal-Wallis test was used to determine overall distribution of normal/CIN1, CIN2 and CIN3+ on the cervix. RESULTS: In total, 53,088 cervical samples were included in distribution analysis. 66.9% samples were obtained by random biopsy, 16.1% were by directed biopsy, and 17.0% were by endocervical curettage. 95.9%of the biopsied samples were diagnosed as normal/CIN1, 2.0% were CIN2, and 2.1% were CIN3+. CIN2 and CIN3+ were most often found in quadrants 2 and 3 (χKW2=46.6540, p<0.0001) and at the 4- and 7-o'clock positions by directed biopsy (ORCIN2=2.572, 1.689, ORCIN3+=3.481, 1.678, respectively), and at the 5-, 6-, 7-, 9- and 12-o'clock positions by random biopsy. CIN3+ was least often found at the 11-o'clock position by directed biopsy (OR=0.608). CONCLUSIONS: Our results suggest a predisposition of specific locations on the cervix to CIN occurrence. Quadrants 2 and 3, especially the 4- and 7-o'clock positions should be preferentially targeted during biopsy. The decision for random biopsy should be reconsidered in future studies.