[Clinical pathway in Chinese county for lung cancer diagnosis and treatment (2023 edition)].

Lung cancer (LC) is the leading cause of death among patients with cancer both in worldwide and China. China accounts for 11.4% of the total number of cancer cases and 18.0% of the total number of cancer deaths in the world. Standardizing the diagnosis and treatment of LC is a key measure to improve the survival rate of LC patients and reduce the mortality rate. However, county hospitals generally face the problem of inaccessibility to advanced diagnostic and treatment technologies. Therefore, when developing quality control standards and clinical diagnosis and treatment specifications, it is necessary to combine the actual situation of county hospitals and formulate specific recommendations. The recommendations of treatment measures also need to consider the approval status of indications and whether it is included in the National Reimbursement Drug List (NRDL), to ensure the access to medicines. In order to solve the above problems, based on existing guidelines at home and abroad and the clinical work characteristics of county hospitals, the first clinical pathway in Chinese county for LC diagnosis and treatment (2023 edition) was compiled. This pathway elaborated on the imaging diagnosis, pathological diagnosis, molecular testing, and precision medicine based on histological-pathological types, tumor-node-metastasis (TNM) classification, and molecular classification, developed different diagnosis and treatment processes for different types of LC patients. Simultaneously, according to the actual work situation of county hospitals, the diagnosis and treatment recommendations in clinical scenarios are divided into basic strategies and optional strategies for elaboration. The basic strategies are the standards that county hospitals must meet, while the optional strategies provide more choices for hospitals, which are convenient for county doctors to put into clinical practice. All the recommended diagnostic and treatment plans strictly refer to existing guidelines and consensus, ensuring the scientificity.

[Two cases of pyridaben poisoning were successfully treated by blood purification].

Pyridaben is a broad-spectrum acaricide widely used in agriculture, accidental or self-administration of large doses of pyridaben can cause multiple organ failure in patients. Due to its damage to multiple organs and no specific antidote, the mortality rate is high. This paper reports two patients who took a large amount of pyridaben, developed severe metabolic acidosis, hyperlactatemia, toxic encephalopathy, and liver, kidney, heart and digestive tract damage. After timely gastric lavage, catharsis, organ support andblood purification treatment, the condition improved and discharged. It is expected to provide clinical ideas for the treatment of pyridaben poisoning.

Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC.

BACKGROUND: We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial. PATIENTS AND METHODS: This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. RESULTS: Of 793 patients, 345 (43.5%) had tTMB ≥175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB ≥175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/exome was not {OS: hazard ratio, 0.62 [95% confidence interval (CI) 0.48-0.80] and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS [hazard ratio (95% CI)] for pembrolizumab versus chemotherapy was observed regardless of STK11 [STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05)]; KEAP1 [KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99)], or KRAS [KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18)] mutation status. CONCLUSION: tTMB with a cut point of ≥175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score ≥1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status.

Prevalence and trend of gonorrhea in female sex workers and men having sex with men in China: a systematic review and meta-analysis.

OBJECTIVES: This systematic review was conducted to estimate the respective prevalence of gonorrhea among two high-risk populations in China and determine the epidemiological features of gonorrhea in them. STUDY DESIGN: Systematic review. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched to identify studies published between January 1, 1990, and October 31, 2022, with gonorrhea prevalence tested by polymerase chain reaction among female sex workers (FSWs) and men who have sex with men (MSM). Meta-regression and subgroup analyses were used to investigate potential factors of heterogeneity across studies. Trend analysis of prevalence was conducted by the Jonckheere-Terpstra method. RESULTS: We identified 88 prevalence data points from 49 studies in China, with 30,853 participants of FSWs and 5523 participants of MSM. Pooled prevalence of gonorrhea among FSWs and MSM were 6.9% (95% confidence interval: 4.6-9.7%) and 2.5% (95% confidence interval: 1.5-3.7%), respectively. The subgroup analyses showed there were period, regional, and specimen collection methods diversities among FSWs, and diversities of the regions and specimen collection anatomical sites were found among MSM, in which the prevalence of rectum and pharynx was significantly higher than the urethra. A decreasing trend in the prevalence of gonorrhea was seen among FSWs (z = -4.03) from 1999 to 2021, not found for MSM in China. CONCLUSION: The prevalence of gonorrhea is high in two high-risk groups in China, with extragenital infections requiring particular attention. The findings of this study will provide evidence to formulate national policy and guidance for gonorrhea prevention and control.

ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer.

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

PHGDH promotes the proliferation and differentiation of primary chicken myoblasts.

1. Chicken primary myoblasts (CPMs) are precursors that form muscle fibres. The proliferation and differentiation of CPMs is an essential stage in muscle development. Previous RNA-seq analysis showed that phosphoglycerate dehydrogenase (PHGDH) is a differentially expressed gene in chicken muscle tissue at different growth stages. Therefore, the following study explored the effect of PHGDH on the proliferation and differentiation of CPMs.2. The effect on the proliferation of CPMs by RT-qPCR, CCK-8, and EdU assays after the overexpression and knockdown of PHGDH was evaluated. RT-qPCR, western blotting, and indirect immunofluorescence were used to detect the effect of PHGDH on the differentiation of the CPMs. The expression was observed at different time points for differentiation induced by the CPMs.3. The results showed that PHGDH significantly promoted proliferation and differentiation in CPMs. The results showed that overexpression of PHGDH significantly upregulated CPM proliferation, while knockdown had the opposite effect. Marker genes showed that overexpression of PHGDH significantly upregulated the expression of P21, MYOG and MYOD genes, significantly downregulated the expression of the MSTN gene and promoted the expression of the MYHC protein. In contrast, PHGDH knockdown had the opposite effect.4. Desmin immunofluorescence analysis of myotube differentiation in primary myoblasts showed that overexpression of PHGDH significantly increased the area of myotube differentiation and promoted the proliferation and differentiation of myoblasts. Knockdown of PHGDH had the opposite effect.5. In summary, PHGDH was shown to play a positive role in regulating myoblast proliferation and differentiation. This provides a theoretical basis for further analysis of the regulatory mechanism of the PHGDH gene in chicken muscle development and for improving poultry production.

[Clinical application of LASEREO endoscopic system in early gastric cancer].

Objective: To evaluate the clinical application of LASEREO endoscopic system in early gastric cancer (EGC). Methods: A total of 68 patients diagnosed with EGC were retrospectively analyzed between August 2017 to December 2020 in Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine. There were 50 males and 18 females finally enrolled with a median age of 64 years. EGCs were analyzed from subjective and objective aspect, as well as from magnification and non-magnification status. Six endoscopists evaluated the visibility of the EGC (RSC) and calculated the color difference (ΔEC) between EGC and the surrounding mucosa in white light imaging (WLI), blue light imaging-bright (BLI-Bri) and linked color imaging (LCI) modes. In the case of magnification (×80), the visibility of the microstructures and microvessels (RSV) was analyzed and the color difference (ΔEV) between microvessels and non-vessels areas were calculated in WLI, BLI and LCI modes. The visibility was evaluated using visibility ranking scale(RS) and the color difference (ΔE) was calculated using L*a*b* color space. Results: In WLI, BLI-Bri, and LCI modes, the mean (±SD) RSC were 2.56±0.68, 2.63±0.59 and 3.17±0.50, and the mean(±SD) ΔEC were 15.71±5.58, 12.04±3.73, and 22.84±8.46, respectively, which in LCI were higher than those in WLI and BLI-Bri modes (P<0.001).Regarding the data evaluated by senior endoscopists, the RSC was higher in BLI-Bri than that in WLI mode (2.98±0.58 vs. 2.79±0.73, P<0.001), but as to those evaluated by junior endoscopists, there were no significant differences between the WLI and BLI-Bri modes(2.29±0.72 vs. 2.23±0.72,P =0.218).In magnifying endoscopy with WLI, BLI, and LCI modes, the mean(±SD) RSV were 2.95±0.28, 3.46±0.40, and 3.38±0.33, and the mean (±SD) ΔEV were 21.68±7.52, 44.29±10.94, and 45.38±14.29, respectively.The RSV and ΔEV in LCI and BLI were higher than that in WLI mode (P<0.001). Conclusions: LCI improves the visibility of EGC by increasing ΔEC, especially in junior endoscopists. Both BLI and LCI improve the visibility of microstructures and microvessels under magnification.

[The effect of human chorionic gonadotropin day serum progesterone level on the live birth rate of fresh embryo transfer with GnRH antagonist protocols].

Objective: To investigate the effect of human chorionic gonadotropin (HCG)day serum progesterone (P) level on the live birth rate (LBR) of fresh embryo transfer with GnRH antagonist protocols. Methods: Patients who underwent the first IVF/ICSI in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were included for analysis. The patients with normal ovarian response with GnRH antagonist protocols were included (n=765). The receiver operating characteristic curve (ROC) was used to select the optimal cut-off value of serum P on HCG day (0.83 µg/L), and the included cycles were divided into two groups: P<0.83 µg/L (n=444) and P≥0.83 µg/L (n=321). The primary outcome measure was LBR. Secondary outcome measures included clinical pregnancy rate (CPR) and early miscarriage rate. The difference of the above indexes between the two groups was compared. Multivariate logistic regression model was used to analyze the effect of serum P level on LBR in fresh embryo transfer cycles. Results: The maternal ages in P<0.83 µg/L group and P≥0.83 µg/L group were (32.40±5.49) years and (32.53±5.51) yeas, respectively. The paternal ages were (33.35±6.34) years and (33.43±6.38) years, respectively of which, the difference was not statistically significant (P>0.05). The CPR in the P<0.83 µg/L group was 45.9% (n=204), which was significantly higher than that in the P≥0.83 µg/L group (37.1%) (n=119) (P=0.014). There was no significant difference in the early miscarriage rate between the two groups [14.2% (n=29) vs 14.3% (n=17), P=0.986]. The LBR in the P<0.83 µg/L group was significantly higher than that in the P≥0.83 µg/L group [36.3% (n=161) vs 28.0% (n=90), P=0.017]. By multivariate logistic regression model analysis, the maternal age, type of embryo transferred, number of embryos transferred, endometrial thickness on HCG day and serum P level on HCG day were independent risk factors of LBR. The adjust OR(95%CI) were 0.91(0.88-0.94), 2.36(1.04-5.35), 1.84(1.14-2.95), 1.16(1.07-1.25)and 0.63(0.44-0.89), all P<0.05. Conclusion: When the GnRH antagonist protocol is applied in the normal ovarian response population, as the serum P on the HCG trigger day≥0.83 µg/L, the CPR and LBR of fresh embryo transfer are decreased.

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

BACKGROUND: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2; n = 300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. CONCLUSION: Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC. CLINICAL TRIAL IDENTIFIER: ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

[Clinicopathological and prognostic features of young onset patients with middle-low rectal cancer received neoadjuvant chemoradiotherapy].

Objective: To explore the clinicopathological and prognostic features of young onset patients with middle-low rectal cancer who received neoadjuvant chemoradiotherapy (NCRT). Methods: After NCRT, a total of 441 patients with primary middle-low rectal cancer treated with radical surgery at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from January 2004 to December 2016 were included. According to the age of disease onset, the patients were divided into the young group (51cases) and the middle-old group (390 cases), and the clinicopathological characteristics and survival of these patients were analyzed. Results: In the young group, 68.6% of patients received radical surgery within 7 weeks after NCRT, which was higher than 52.8% in the middle-old group (P=0.047). The stage ypTNM Ⅲ in the young group was 51.0%, higher than 34.1% in the middle-old group (P=0.027). The stage ypN+ in the young group was 51.0%, higher than 34.1% in the middle-old group (P=0.047), The incidence of disease progression in the young group was 39.2%, higher than 25.1% in the middle-old group (P=0.049). The incidence of distant metastasis in the young group was 35.3%, higher than 21.5% in the middle-old group(P=0.044). Most cases of disease progression occurred in the first 3 years after surgery for the young group, especially in the second year after surgery, the incidence of disease progression in the young group was 55.0%, higher than 26.5% in middle-old group (P=0.025). The 3-year and 5-year disease-free survival (DFS) rates for the young group were 63.7% and 58.2%, lower than 81.0% and 74.3% in the middle-old group (P=0.016), respectively. The 3-year and 5-year overall survival in the middle-old group (OS) rates for the young group were 85.4% and 69.2%, lower than 93.6% and 84.1% in the middle-old group (P=0.033), respectively. The multivariate analysis showed that, response of primary tumor (HR=4.804, 95% CI: 1.360-16.973) and total number of dissected lymph nodes (HR=4.336, 95% CI: 1.739-10.809) in the young group were independent prognostic factors related to DFS. The total dissected number of lymph nodes(HR=3.295, 95% CI: 1.076-10.091)was an independent prognostic factor related to OS. In the middle-old group, response of primary tumor (HR=2.626, 95% CI: 1.354-5.091), ypTNM stage (ypTNM Ⅲ: HR=5.837, 95% CI: 2.968-11.479) and tumor location distance from the anal verge (HR=0.500, 95% CI: 0.308-0.812) were independent prognostic factors related to DFS. Lymphovascular invasion (HR=0.500, 95% CI: 0.308-0.812) and ypTNM stage (ypTNM Ⅲ: HR=16.322, 95% CI: 5.049-52.771) were independent prognostic factors related to OS. Conclusions: Young onset rectal cancer patients are associated with shorter operation time interval, advanced pathological stage and poorer prognosis. More intensive adjuvant treatment and post-treatment surveillance should be conducted to young onset rectal cancer with NCRT.

[Long-term conditional disease-free survival for rectal cancer patients underwent neoadjuvant chemoradiotherapy].

Objective: To explore the application value of the conditional disease-free survival (cDFS) analysis in predicting prognosis of stage-specific rectal cancer patients underwent neoadjuvant chemoradiotherapy (nCRT). Methods: Clinicopathologic data of 436 patients with rectal cancer received nCRT and radical operation in Cancer Hospital, Chinese Academy of Medical Sciences between January 2004 and December 2016 were retrospectively reviewed. With reference to conditional probability, the 3-year cDFS of patients at different ypTNM stage after completion of nCRT was estimated using the Kaplan-Meier method. Results: There were 66 patients of ypTNM stage 0 (pathological complete response), 87 patients of ypTNM stage Ⅰ, 135 patients of ypTNM stage Ⅱ and 148 patients of ypTNM stage Ⅲ. The 3-year accumulated DFS of patients with ypTNM stage 0, ypTNM stage Ⅰ, ypTNM stage Ⅱ, and ypTNM stage Ⅲ were 97.0%, 93.1%, 85.2%, and 64.2%, respectively. On the condition of postoperactive disease-free survival for 1 year, 2 years, 3 years, 4 years, and 5 years, the corresponding 3-year cDFS of patients at ypTNM stage 0 were 97.0%, 95.5%, 96.9%, 98.4%, 100.0%, respectively. The corresponding 3-year cDFS of patients at ypTNM Ⅲ were 68.2%, 79.3%, 86.3%, 92.1%, 96.4%, respectively. The more advanced ypTNM staging resulted in the more improvement of 3-year cDFS being acquired. Conclusion: cDFS is a better method to reflect the dynamic changes of the prognosis of rectal cancer patients with nCRT in different ypTNM stage, and it is useful to guide the clinicians to assess the prognosis and propose appropriate surveillance.

[The risk factors for regional lymph node metastasis of mismatch repair deficient colorectal cancer].

Objective: To explore the risk factors for regional lymph node (RLN) metastasis in colorectal cancer patients with mismatch repair deficiency (dMMR). Methods: The data of 357 dMMR colorectal cancer patients who underwent surgery in National Cancer Center from January 2012 to December 2016 was retrospectively analyzed. Univariate and multivariate analysis were used to identify the risk factors for RLN metastasis. Results: Among the 357 patients, 204 were male and 153 were female, 61.6% (220/357) lesion located in right half colon, while the other 16.2% (58/357) located in rectum. Univariate analysis showed that tumor size, differentiation, lymphovascular invasion, tumor deposit, postoperative pathologic T stage (pT), the number of negative lymph nodes and the expression of the MSH6 protein were significantly associated with RLN metastasis (P<0.05). All of the patients with well differentiation tumors (15 patients) or staged pT1 (13 patients) had no RLN metastasis. Multivariate analysis showed that tumor differentiation (OR=2.582, 95%CI=1.567-4.274, P<0.001), pT (OR=3.778, 95%CI=1.448-12.960, P=0.015) and the expression of MSH6 protein (OR=2.188, 95%CI=1.159-4.401, P=0.021) were independent risk factors for RLN metastasis. Conclusions: The postoperative pT stage, tumor differentiation and the expression of MSH6 protein are independent risk factors for RLN metastasis of dMMR colorectal cancer. Preoperative assessment of these factors may further improve the accuracy of predicting the risk of RLN metastasis.

[Clinicopathological characteristics and prognostic analysis of patients with pathological complete response and near complete response after neoadjuvant treatment of rectal cancer].

Objective: To investigate the clinicopathological characteristics and prognosis of rectal cancer patients with pathological complete response and near complete response after neoadjuvant therapy. Methods: The clinicopathological data of patients who underwent neoadjuvant chemoradiotherapy plus radical surgery of rectal cancer in the Cancer Hospital of Chinese Academy of Medical Sciences from January 2004 to December 2016 were retrospectively collected. The clinicopathological characteristics and prognostic factor of patients with pathological complete response and near complete response were analyzed. Results: The clinical data of 142 patients were collected. There were 93 males and 49 females, aged from 24 to 81 years. The median disease-free survival was 53.9 months and the median overall survival was 55.0 months. Univariate analysis showed that the maximum diameter of scar or lesion, the status of lymph node metastasis and the distance between the lower edge of tumor and anal edge were associated with disease-free survival time; the maximum diameter of scar or lesion and the status of lymph node metastasis were associated with overall survival time. Multivariate Cox proportional hazards regression analysis showed that patients with scar or lesion diameter>3 cm (HR=4.406,95%CI:1.619-12.006), positive lymph node metastasis status (HR=4.102,95%CI:1.461-11.513) and tumor lower margin to anal margin distance ≤4 cm (HR=18.171,95%CI:2.357-140.073) had shorter disease-free survival time.The patients with scar or lesion diameter>3 cm (HR=8.573,95%CI:1.630-45.099) and lymph node metastasis status (HR=4.721, 95%CI:1.068-20.860) had shorter overall survival time. Conclusions: The overall prognosis of patients with pathological complete response or near complete response after neoadjuvant therapy for rectal cancer is better. The distance between the lower margin of the tumor and the anal edge, the status of lymph node metastasis and the maximum diameter of scars or lesion were the related factors affecting the prognosis of patients with rectal cancer.

Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis.

BACKGROUND: In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis. PATIENTS AND METHODS: Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum-pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points. RESULTS: A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum-pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum-pemetrexed had died. The hazard ratio (HR) for OS was 0.87 [95% confidence interval (CI) 0.67-1.12; P = 0.277]; the median OS was 26.8 months (95% CI 23.5-31.5) versus 22.5 months (95% CI 20.2-28.8) for osimertinib and platinum-pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18-1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16-0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum-pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum-pemetrexed arm. CONCLUSIONS: In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum-pemetrexed, which possibly reflects the high crossover rate of patients from platinum-pemetrexed to osimertinib. CLINICAL TRIALS NUMBER: ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.

Feasibility of using dynamic contrast-enhanced MRI for differentiating thymic carcinoma from thymic lymphoma based on semi-quantitative and quantitative models.

AIM: To evaluate the value of using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived parameters to differentiate thymic carcinoma and thymic lymphoma based on semi-quantitative and quantitative models. MATERIALS AND METHODS: Twenty-nine pathologically confirmed anterior mediastinum tumours in 29 patients were enrolled in this retrospective study, including 15 thymic carcinoma and 14 lymphoma patients. All the patients underwent pre-treatment mediastinum DCE-MRI. Both semi-quantitative and quantitative parameters were calculated and the volume transfer constant Ktrans, the flux rate constant between extravascular extracellular space and plasma kep, the extravascular extracellular volume fraction ve were obtained based on a modified Tofts model. DCE-MRI derived parameters were compared between thymic carcinoma and thymic lymphoma groups. RESULTS: Thymic carcinoma had significantly lower kep (p=0.040) and higher ve (p=0.018) than thymic lymphoma; however, there were no significant differences on Ktrans and semi-quantitative parameters between the two groups. ve had the highest area under the curve (cut-off value, 0.282; area under the curve, 0.748; sensitivity, 71.4%; specificity, 80%). The combination of kep and ve could increase the diagnostic performance significantly (area under the curve, 0.752; sensitivity, 57.1%; specificity, 93.3%). CONCLUSION: DCE-MRI derived parameters may have value in the differentiating thymic carcinoma and thymic lymphoma.

[The safety and efficacy of radical surgery after modified total neoadjuvant therapy for locally advanced rectal cancer].

Objective: To analyze the clinical-pathological data of patients with locally advanced rectal cancer who underwent modified total neoadjuvant therapy (TNT), and to evaluate the safety and efficacy of radical surgery after modified total neoadjuvant therapy. Methods: The clinical-pathological data of 30 locally advanced rectal cancer patients who underwent modified TNT (mTNT) followed by radical resection were retrospectively analyzed. The surgical procedure, postoperative complications, tumor regression grade, tumor downstaging and prognosis were analyzed. Results: The 30 patients included 24 males and 6 females with a median age of 55.5 years. All patients underwent radical surgery after neoadjuvant therapy, 14 patients received low anterior resection, 14 patients received abdominal perineal resection, and the other 2 patients received Hartmann procedure. All patients achieved R0 resection with a median operative time 220 minutes and the median intraoperative blood loss was 200 ml. The morbidity of postoperative complications was 20% (6/30), including dysuria in 2 patients, delayed healing of perineal incision in 2 patients, intestinal obstruction in 1 patient and pelvic hemorrhage in 1 patient. The median time to first flatus after surgery was 3 days and the median postoperative hospital stay was 8 days. Postoperative pathological results showed that 15 patients (50.0%) had severe tumor regression, including 4 patients (13.3%) achieved pathological complete response (pCR), 12 patients (40.0%) had moderate tumor regression, and 3 patients (10.0%) had minor tumor regression. Twenty patients had detailed pre-treatment clinical stage, and among those 20 patients, 15 patients (75.0%) and 13 patients (65.0%) achieved downstaging of tumor T stage and N stage, respectively. Only 2 patients appeared distant metastasis, and no patient had local recurrence. Conclusions: For locally advanced rectal cancer patients, mTNT doesn't increase the morbidity of postoperative complication and is a safe and effective treatment strategy with satisfactory short-term result.

[Special histopathological variants and potential diagnostic traps of classical follicular dendritic cell sarcoma].

Objective: To investigate the clinicopathological features, special morphologic variants and potential diagnostic traps of classical follicular dendritic cell sarcoma (FDCS). Methods: A total of 25 cases of classical FDCS diagnosed in the First Hospital Affiliated to Army Medical University from 2006 to 2018 were examined by hematoxylin-eosin staining, immunohistochemistry and in situ hybridization for Epstein-Barr virus-encoded mRNA (EBER). Meanwhile, the types and characteristics of the special variants of FDCS were summarized along with those reported in the literature. Results: The age of patients ranged from 23 to 77 years (mean 52 years), the male to female ratio was 1.5, and the maximum diameter of tumor was 1.5 to 20 cm (mean 7.4 cm). Twelve cases (48%) were misdiagnosed at the initial evaluation. Follow-up information was available for 17 patients, and the follow-up time was 5 to 96 months. The propotion of patients having recurrence, metastasis and mortality was 3/17, 5/17 and 2/17, respectively. Microscopically, besides the typical morphology, 10 cases of FDCS showed special histomorphologies and/or structures, including those mimicking lymphoepithelioma-like carcinoma, desmoplastic infiltrating carcinoma, classical Hodgkin's lymphoma (CHL), anaplastic large cell lymphoma (ALCL) and hemangiopericytoma. These morphologic variants were potential diagnostic pitfalls and warranted attention. Immunohistochemistry showed that more than two markers of follicular dendritic cells (such as CD21, CD23, CD35, etc.) were expressed in cases showing typical morphology and the special variants. All 25 cases were all negative for EBER by in situ hybridization. Conclusions: Classical FDCS is rare, besides the typical morphologic features, there are many special variants. In particular, these may be confused with lymphoepithelioma-like carcinoma in the nasopharynx, CHL or ALCL in the mediastinum/lymph node. Awareness of these variants is essential for accurate diagnosis.

[Circadian clock and non-alcoholic fatty liver disease].

The circadian clock is a generator of self-sustaining physiological and behavioral rhythms, which can be guided by external environmental factors, so as to synchronize biological behaviors with external environmental changes. The modern lifestyles make the human body incapable of synchronization to the external time with the circadian rhythm, and thus form a social jet lag. Non-alcoholic fatty liver disease (NAFLD) is a disorder closely related to metabolic abnormalities. The circadian clock is closely related to metabolic abnormalities and NAFLD and changes among them may be involved with feeding mode and ingredients, sleeping time, and intestinal flora. Molecules associated with the circadian clock are expected to become potential drugs for the treatment of NAFLD. This article mainly reviews the latest research progress of circadian clock and NAFLD.

[Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues].

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.