Expert Consensus on Acute Respiratory Failure in Critically Ill Cancer Patients (2023).

Objective This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients.Methods We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. Results The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. Conclusions The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes.

Methods for improving colorectal cancer annotation efficiency for artificial intelligence-observer training.

BACKGROUND: Missing occult cancer lesions accounts for the most diagnostic errors in retrospective radiology reviews as early cancer can be small or subtle, making the lesions difficult to detect. Second-observer is the most effective technique for reducing these events and can be economically implemented with the advent of artificial intelligence (AI). AIM: To achieve appropriate AI model training, a large annotated dataset is necessary to train the AI models. Our goal in this research is to compare two methods for decreasing the annotation time to establish ground truth: Skip-slice annotation and AI-initiated annotation. METHODS: We developed a 2D U-Net as an AI second observer for detecting colorectal cancer (CRC) and an ensemble of 5 differently initiated 2D U-Net for ensemble technique. Each model was trained with 51 cases of annotated CRC computed tomography of the abdomen and pelvis, tested with 7 cases, and validated with 20 cases from The Cancer Imaging Archive cases. The sensitivity, false positives per case, and estimated Dice coefficient were obtained for each method of training. We compared the two methods of annotations and the time reduction associated with the technique. The time differences were tested using Friedman's two-way analysis of variance. RESULTS: Sparse annotation significantly reduces the time for annotation particularly skipping 2 slices at a time (P < 0.001). Reduction of up to 2/3 of the annotation does not reduce AI model sensitivity or false positives per case. Although initializing human annotation with AI reduces the annotation time, the reduction is minimal, even when using an ensemble AI to decrease false positives. CONCLUSION: Our data support the sparse annotation technique as an efficient technique for reducing the time needed to establish the ground truth.

Consolidation chemotherapy with capecitabine after neoadjuvant chemoradiotherapy in high-risk patients with locally advanced rectal cancer: Propensity score study.

BACKGROUND: The effects of consolidation chemotherapy (CC) in neoadjuvant therapy in locally advanced rectal cancer (LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy (NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear. AIM: To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval. METHODS: We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm (cT3c-cT3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC (capecitabine 1000 mg/m2 twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching (PSM) and inverse probability of treatment weight (IPTW) were used to balance the differences between the two groups. The main outcome was the complete response (CR) rate. RESULTS: A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d (range, 37-168). The CR rate was 24.3% and 16.3% (P = 0.107) in the CC and non-CC groups' original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group (27.6% vs 16.2%, P = 0.045; 25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo (range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples (73.2% vs 71.9%, P = 0.913; 92.3% vs 86.7%, P = 0.294), PSM (73.2% vs 73.5%, P = 0.865; 92.5% vs 89.3%, P = 0.612), and IPTW (73.8% vs 72.1%, P = 0.913; 92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups (49.3% vs 53.5%, P = 0.492). CONCLUSION: One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in high-risk LARC but failed to improve the long-term outcomes.

Nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery.

BACKGROUND: There were few studies on the prognosis of tumor patients with sepsis after gastrointestinal surgery and there was no relevant nomogram for predicting the prognosis of these patients. AIM: To establish a nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery in the intensive care unit (ICU). METHODS: A total of 303 septic patients after gastrointestinal tumor surgery admitted to the ICU at Peking University Cancer Hospital from January 1, 2013 to December 31, 2020 were analysed retrospectively. The model for predicting the prognosis of septic patients was established by the R software package. RESULTS: The most common infection site of sepsis after gastrointestinal surgery in the ICU was abdominal infection. The 90-d all-cause mortality rate was 10.2% in our study group. In multiple analyses, we found that there were statistically significant differences in tumor type, septic shock, the number of lymphocytes after ICU admission, serum creatinine and total operation times among tumor patients with sepsis after gastrointestinal surgery (P < 0.05). These five variables could be used to establish a nomogram for predicting the prognosis of these septic patients. The nomogram was verified, and the initial C-index was 0.861. After 1000 internal validations of the model, the C-index was 0.876, and the discrimination was good. The correction curve indicated that the actual value was in good agreement with the predicted value. CONCLUSION: The nomogram based on these five factors (tumor type, septic shock, number of lymphocytes, serum creatinine, and total operation times) could accurately predict the prognosis of tumor patients with sepsis after gastrointestinal surgery.

Horizontal transmission might be a common route of hepatitis B virus exposure in highly endemic areas.

Hepatitis B virus (HBV) is a common viral pathogen that infects more than a third of the world's population; however, the transmission route remains to be further defined. The 18-year implementation of the free HBV vaccine for children has greatly changed the prevalence of HBV infection in China, which presents a unique real-world model for assessing the pattern of HBV transmission. Cross-sectional data of HBV seromarkers between July 2019 and April 2020 were collected from 53 371 individuals aged 1-60 years in four areas of North to South in Eastern China. Longitudinal data of HBV seromarkers between 2007 and 2020 were collected from 177 adults in an area of South China. The regional- and age-specific changes in HBV seromarkers were analyzed. Overall, positive rates of HBV surface antigen (HBsAg; from 3.44% to 15.1%) and antibody against HBV core antigen (anti-HBc; from 7.6% to 44.0%) significantly increased from North to South. Among persons aged ≤18 years, the positive rates of antibody against HBsAg (anti-HBs) and anti-HBc (+) remained at low levels in the North, while they were increasing among persons aged >12 years in the South, despite higher positive rates of anti-HBs (+). Among persons aged >18 years, the anti-HBs (+) rates remained relatively stable (~60%), while anti-HBc (+) rates increased significantly with age. Up to ~80% of the anti-HBs (+) adults in the South was anti-HBc (+) while it was 13.6% in the North. In the longitudinal cohort, the anti-HBc (+) rate among adults in the South increased by 14.2% during 10 years of follow-up. Horizontal transmission might be a common route in highly endemic areas, and may help to explain the high HBV exposure worldwide. The risk of horizontal transmission among children without seroprotective anti-HBs should be notified in highly endemic areas.

Improving the accuracy and consistency of clinical target volume delineation for rectal cancer by an education program.

BACKGROUND: Accurate target volume delineation is the premise for the implementation of precise radiotherapy. Inadequate target volume delineation may diminish tumor control or increase toxicity. Although several clinical target volume (CTV) delineation guidelines for rectal cancer have been published in recent years, significant interobserver variation (IOV) in CTV delineation still exists among radiation oncologists. However, proper education may serve as a bridge that connects complex guidelines with clinical practice. AIM: To examine whether an education program could improve the accuracy and consistency of preoperative radiotherapy CTV delineation for rectal cancer. METHODS: The study consisted of a baseline target volume delineation, a 150-min education intervention, and a follow-up evaluation. A 42-year-old man diagnosed with stage IIIC (T3N2bM0) rectal adenocarcinoma was selected for target volume delineation. CTVs obtained before and after the program were compared. Dice similarity coefficient (DSC), inclusiveness index (IncI), conformal index (CI), and relative volume difference [ΔV (%)] were analyzed to quantitatively evaluate the disparities between the participants' delineation and the standard CTV. Maximum volume ratio (MVR) and coefficient of variation (CV) were calculated to assess the IOV. Qualitative analysis included four common controversies in CTV delineation concerning the upper boundary of the target volume, external iliac area, groin area, and ischiorectal fossa. RESULTS: Of the 18 radiation oncologists from 10 provinces in China, 13 completed two sets of CTVs. In quantitative analysis, the average CTV volume decreased from 809.82 cm3 to 705.21 cm3 (P = 0.001) after the education program. Regarding the indices for geometric comparison, the mean DSC, IncI, and CI increased significantly, while ΔV (%) decreased remarkably, indicating improved agreement between participants' delineation and the standard CTV. Moreover, an 11.80% reduction in MVR and 18.19% reduction in CV were noted, demonstrating a smaller IOV in delineation after the education program. Regarding qualitative analysis, the greatest variations in baseline were observed at the external iliac area and ischiorectal fossa; 61.54% (8/13) and 53.85% (7/13) of the participants unnecessarily delineated the external iliac area and the ischiorectal fossa, respectively. However, the education program reduced these variations. CONCLUSION: Wide variations in CTV delineation for rectal cancer are present among radiation oncologists in mainland China. A well-structured education program could improve delineation accuracy and reduce IOVs.

Risk factors for failure of subclavian vein catheterization: a retrospective observational study.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze risk factors for failure of subclavian vein catheterization. METHODS: A retrospective analysis of 1562 patients who underwent subclavian vein puncture performed by the same experienced operator at Peking University Cancer Hospital from January 1, 2016 to January 1, 2019 was conducted. The success or failure of subclavian vein catheterization was registered in all cases. Various patient characteristics, including age, gender, body mass index (BMI), preoperative hemoglobin, preoperative hematocrit, preoperative mean corpuscular hemoglobin concentration (MCHC), preoperative albumin, preoperative serum creatinine, puncture needles from different manufacturers and previous history of subclavian vein catheterization were assessed via univariate and multivariate analyses. RESULTS: For the included patients, landmark-guided subclavian vein puncture was successful in 1476 cases and unsuccessful in 86 cases (success rate of 94.5%). Successful subclavian vein catheterization was achieved via right and left subclavian vein puncture in 1392 and 84 cases, respectively. In univariate analyses, age and preoperative hemoglobin were associated with failure of subclavian vein catheterization. In a multivariate analysis, aged more than 60 years was a risk factor while the central venous access with Certofix® was associated with an increased rate of success (p-values of 0.001 and 0.015, respectively). CONCLUSIONS: This study has demonstrated that patient aged more than 60 years was a risk factor for failure of subclavian vein catheterization while the central venous access with Certofix® was associated with an increased rate of success.

Development and validation of a GRGPI model for predicting the prognostic and treatment outcomes in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is among the most lethal and most prevalent malignant tumors. Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. Therefore, we aimed at identifying a glycolysis-related prognostic model for HNSCC and to analyze its relationship with tumor immune cell infiltrations. Methods: The mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), while glycolysis-related genes were obtained from the Molecular Signature Database (MSigDB). Bioinformatics analysis included Univariate cox and least absolute shrinkage and selection operator (LASSO) analyses to select optimal prognosis-related genes for constructing glycolysis-related gene prognostic index(GRGPI), as well as a nomogram for overall survival (OS) evaluation. GRGPI was validated using the Gene Expression Omnibus (GEO) database. A predictive nomogram was established based on the stepwise multivariate regression model. The immune status of GRGPI-defined subgroups was analyzed, and high and low immune groups were characterized. Prognostic effects of immune checkpoint inhibitor (ICI) treatment and chemotherapy were investigated by Tumor Immune Dysfunction and Exclusion (TIDE) scores and half inhibitory concentration (IC50) value. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to validate the model by analyzing the mRNA expression levels of the prognostic glycolysis-related genes in HNSCC tissues and adjacent non-tumorous tissues. Results: Five glycolysis-related genes were used to construct GRGPI. The GRGPI and the nomogram model exhibited robust validity in prognostic prediction. Clinical correlation analysis revealed positive correlations between the risk score used to construct the GRGPI model and the clinical stage. Immune checkpoint analysis revealed that the risk model was associated with immune checkpoint-related biomarkers. Immune microenvironment and immune status analysis exhibited a strong correlation between risk score and infiltrating immune cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis showed typical immune pathways. Furthermore, the GRGPIdel showed excellent predictive performance in ICI treatment and drug sensitivity analysis. RT-qPCR showed that compared with adjacent non-tumorous tissues, the expressions of five genes were significantly up-regulated in HNSCC tissues. Conclusion: The model we constructed can not only be used as an important indicator for predicting the prognosis of patients but also had an important guiding role for clinical treatment.

Arsenic concentration in peripheral blood is correlated with efficacy of a Traditional Chinese Medicine regimen containing realgar for the treatment of myelodysplastic syndrome.

OBJECTIVE: To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) and arsenic concentration in the peripheral blood of patients. METHODS: In this prospective study, a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019. Routine blood examination as well as liver and kidney function were monitored before and after treatment. The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment. The correlation between clinical effect and arsenic concentration was analyzed by Spearman's method. RESULTS: The treatment response rate was 54%. Two patients (4% ) achieved complete remission, 50% (25 of 50) showed hematologic improvement, and 23 patients had stable disease (23% ). No disease progression was observed. Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96 µg/L. Clinical efficacy was positively correlated with arsenic concentration (P < 0.05). The incidence of mild adverse reactions was 16%. CONCLUSION: A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.

Prognostic predictors in patients with sepsis after gastrointestinal tumor surgery: A retrospective study.

BACKGROUND: There have been different reports on mortality of sepsis; however, few focus on the prognosis of patients with sepsis after surgery. AIM: To study the clinical features and prognostic predictors in patients with sepsis after gastrointestinal tumor surgery in intensive care unit (ICU). METHODS: We retrospectively screened patients who underwent gastrointestinal tumor surgery at Peking University Cancer Hospital from January 2015 to December 2019. Among them, 181 patients who were diagnosed with sepsis in ICU were included in our study. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate adjusted analyses were performed to identify predictors of prognosis. RESULTS: The 90-d all-cause mortality rate was 11.1% in our study. Univariate analysis showed that body mass index (BMI), shock within 48 h after ICU admission, leukocyte count, lymphocyte to neutrophil ratio, international normalized ratio, creatinine, procalcitonin, lactic acid, oxygenation index, and sequential organ failure assessment (SOFA) score within 24 h after ICU admission might be all significantly associated with the prognosis of sepsis after gastrointestinal tumor surgery. In multiple analysis, we found that BMI ≤ 20 kg/m2, lactic acid after ICU admission, and SOFA score within 24 h after ICU admission might be independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. Compared with SOFA score, SOFA score combined with BMI and lactic acid might have higher predictive ability (area under the receiver operating characteristic curve, 0.859; 95% confidence interval, 0.789-0.929). CONCLUSION: Lactic acid and SOFA score within 24 h after ICU admission are independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery. SOFA score combined with BMI and lactic acid might have good predictive value.

Clinical analysis of patients with respiratory failure after esophageal cancer operation.

BACKGROUND: To explore the clinical profiles and outcomes of patients with acute respiratory failure (ARF) after esophagectomy. METHODS: We retrospectively analyzed cases of patients who had been diagnosed with ARF after esophagectomy and compared survivors with non-survivors to explore the risks that may affect their outcomes. RESULTS: In total, 62 patients were admitted to the intensive care unit (ICU) with ARF after esophagectomy between January 1, 2010, and December 31, 2017. Of these patients, 69.4% needed mechanical ventilation, with an average time on the ventilator of 304 hours (304.33±374.37 hours). The average length of stay in the ICU and in the hospital were 14 days (14.48±17.64 days) and 50 days (50.15±37.28 days), respectively. Mortality in the ICU and 90 days after the operation was 6.5% and 16.1%, respectively. Compared with the survivors, the 90-day post-operative non-survivors had a poorer N stage in the TNM classification system. The causes of ARF included anastomotic leakage, pneumonia, vocal cord paralysis, sputum plugging, pulmonary embolism (PE), and acute respiratory distress syndrome (ARDS). ARF induced by different factors occurred at different times and had different outcomes. The three most common reasons for mortality in the ICU were ARDS (33.33%), anastomotic leakage (11.76%), and pneumonia (10%). The three most common reasons for mortality in the 90-day post-operative period were pneumonia (40%), anastomotic leakage (23.53%), and ARDS and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) (33.33%). CONCLUSIONS: Anastomotic leakage, pneumonia, ARDS, and AECOPD were the main causes of death in ARF patients after esophagectomy. We found that the N stage in the TNM classification system may affect 90-day post-operative mortality in these patients.

Health economic evaluation of patients with sepsis after gastrointestinal tumor surgery-a cost consequences analysis in China.

BACKGROUND: The purpose of this study was to evaluate the health economics of patients with sepsis after gastrointestinal tumor operation in ICU. METHODS: This case-control study used 1:1 propensity-score (PS) matched method and patients were matched according to tumor type, age and gender. The study group was composed of 181 patients with sepsis after operation of gastrointestinal tumor in ICU, while the control group was composed of 181 patients without sepsis after operation of gastrointestinal tumor. The medical expenses and length of stay in the hospital of these patients were analyzed. RESULTS: The median of the total hospitalization cost for the study group was $26,038, which was 1.7 times of the control group (P<0.001). The costs of drugs, laboratory test, examination, treatment, operation, anesthesia, materials, ward and other costs in the study group were higher than those in the control group (P<0.001). The median length of stay in the hospital in the study group was 26 days, which were 12 days longer than that of the control group (P<0.001). However, there was no significant difference in daily average cost between the two groups (P=0.103). CONCLUSIONS: In ICU, patients with sepsis after operation of gastrointestinal tumor increased the cost of hospitalization and prolonged the length of stay in the hospital than those without sepsis.

The Influence of Venous Characteristics on Peripherally Inserted Central Catheter-Related Symptomatic Venous Thrombosis in Cancer Patients.

BACKGROUND: With increasing use, peripherally inserted central catheters (PICCs) are associated with the risk of venous thrombosis. Few studies have focused on the relationships between venous thrombosis and venous characteristics. This study aimed to identify effects of venous characteristics on symptomatic PICC-related venous thrombosis in cancer patients and explore the relationship between venous characteristics and blood flow velocity. METHODS: The data of patients who underwent placement of PICC were retrospectively studied between January 2015 and September 2017. Symptomatic PICC-related venous thrombosis was confirmed by ultrasound. Univariable, multivariable logistic regression analyses were performed to identify the risk factors associated with PICC-related venous thrombosis. In October 2017, 169 patients with PICCs were enrolled prospectively, and the relationships between blood flow velocity and venous characteristics were recorded and analyzed. RESULTS: A total of 2933 cancer patients were enrolled in this study; of these patients, 68 experienced symptomatic venous thrombosis. In the bivariate analysis, body mass index (BMI), history of venous thrombosis, triglycerides, tumor category, vessel diameter, vessel depth and arm circumference were associated with thrombosis. The multivariable analyses showed that arm circumference, vascular diameter, triglyceride level and tumor category were independent risk factors for thrombosis. Blood flow velocity was positively correlated with vessel depth and arm circumference but not with vessel diameter. CONCLUSION: Different venous characteristics can lead to different blood flow rates, which can affect the incidence of thrombosis. A vein depth of greater than 1.07cm or less than 0.57cm was associated with a higher incidence of PICC-related venous thrombosis, and the greater the arm circumference and vessel diameter, the greater the risk of venous thrombosis.

The risk factors on the prognosis of pulmonary embolism in tumor patients after the thoracic and abdominal surgery.

BACKGROUND: We studied the clinical profiles and the risk factors on the prognosis of tumor patients with pulmonary embolism (PE) after the thoracic and abdominal surgery. METHODS: We retrospectively screened patients who underwent the thoracic and abdominal surgery at the Peking University Cancer Hospital from January 1, 2007 to January 1, 2020. Among them, 115 patients who were diagnosed with PE were enrolled in our study. Cox regression was performed for multivariate adjusted factor analyses. RESULTS: The 90-day overall mortality rate was 11.3% in our study. Univariate analysis showed that gender, MPV, shock, oxygenation index and the APACHE II score within 24 hours after diagnosis of PE were statistically significant in the prognosis of PE after the thoracic and abdominal surgery. In multiple cox regression analysis, we found that patients with shock and the APACHE II score within 24 hours after diagnosis of PE were independent risk factors on the prognosis of PE after the thoracic and abdominal surgery (P values of 0.020 and 0.014, respectively). CONCLUSIONS: Shock and the APACHE II score within 24 hours after diagnosis of PE were independent risk factors on the prognosis of PE after the thoracic and abdominal surgery; however, the study power was limited.

Arsenic Disulfide Promoted Hypomethylation by Increasing DNA Methyltransferases Expression in Myelodysplastic Syndrome.

BACKGROUND: Previous studies have shown that DNA methylation plays a significant role in myelodysplastic syndrome (MDS). In addition to hypermethylation, aberrant hypomethylation can result in the transcriptional activation of oncogenes in cancer, including MDS. Therefore, drugs targeting DNA hypomethylation are needed for the treatment of MDS. This study aimed to investigate whether As2S2 promoted hypomethylation by increasing DNA methyltransferases (DNMTs) expression in MDS. PATIENTS AND METHODS: Ten bone marrow samples from MDS patients and 3 healthy donors were obtained for the examination of the DNA methylation with a Human Methylation 850K BeadChip. The mRNA expressions for the DNMTs in the ten MDS patients and 3 controls were compared by Q-PCR. Then, the MDS cell line SKM-1 was treated with As2S2. After 2 days of treatment, Human Methylation 850K BeadChip was applied to analyze the changes of gene methylation status in the cells. Q-PCR and Western blot were taken to test the changes of mRNA and protein expressions for DNMTs in SKM-1 cells after treatment. RESULTS: Five hundred ninety-two abnormally hypomethylated genes were found in MDS patients compared to those in controls by Human Methylation 850K. The mRNA expressions of DNMTs (DNMT1, DNMT3a and DNMT3b) in MDS patients were significantly lower than those in healthy individuals. The IC50 value of As2S2 for SKM-1 cells was 4.97 µmol/L.Treatment with As2S2 at 2 µmoL/L resulted in significant alterations in the methylation levels at 1718 sites in SKM-1 cells compared to those in the controls. Hypermethylation was observed in 1625 sites (94.58%), corresponding to 975 genes, compared to those in the controls. Finally, the expression levels of DNMTs (DNMT1, DNMT3a, and DNMT3b) significantly increased in SKM-1 cells treated with As2S2 at 2 µmoL/L and 4 µmoL/L. CONCLUSION: These data show a potential clinical application of As2S2 as an innovative hypermethylation agent in MDS.

Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation.

Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.

MRI-based radiomics model for preoperative prediction of 5-year survival in patients with hepatocellular carcinoma.

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

Arsenic-Containing Qinghuang Powder () is an Alternative Treatment for Elderly Acute Myeloid Leukemia Patients Refusing Low-Intensity Chemotherapy.

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION: QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder () in Patients with Myelodysplastic Syndrome.

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.