[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

[Therapeutic efficacy analysis of endoscopic combined with serological diagnosis strategy and endoscopic in G1 and G2 gastric neuroendocrine neoplasms].

Objective: To investigate the endoscopic combined serological diagnosis strategy for G1 and G2 gastric neuroendocrine neoplasms (G-NENs), and to evaluate the safety, short-term, and long-term efficacy of two endoscopic treatment procedures: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Methods: This study retrospectively analyzed the clinical data of 100 consecutive patients with G-NENs who were hospitalized at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2011 to October 2023. These patients underwent endoscopic treatment, and propensity score matching (PSM) was used to compare clinicopathological characteristics, as well as short-term and long-term efficacy of lesions in the EMR group and ESD group before and after treatment. Results: Among the 100 patients with G-NENs, the median age was 54 years old. Before surgery, 29 cases underwent endoscopic combined serological examination, and 24 of them (82.2%) had abnormally elevated plasma chromogranin A. The combined diagnostic strategy for autoimmune atrophic gastritis (AIG) achieved a diagnostic accuracy of 100%(22/22). A total of 235 G-NEN lesions were included, with 84 in the ESD group and 151 in the EMR group. The median size of the lesions in the ESD group (5.0 mm) was significantly larger than that in the EMR group (2.0 mm, P＜0.001). Additionally, the ESD group had significantly more lesions with pathological grade G2[23.8%(20/84) vs. 1.3%(2/151), P＜0.001], infiltration depth reaching the submucosal layer [78.6%(66/84) vs. 51.0%(77/151), P＜0.001], and more T2 stage compared to the EMR group[15.5%(13/84) vs. 0.7%(1/151), P＜0.001]. After PSM, 49 pairs of lesions were successfully matched between the two groups. Following PSM, there were no significant differences in the en bloc resection rate [100.0%(49/49) vs. 100.0%(49/49)], complete resection rate [93.9%(46/49) vs. 100.0%(49/49)], and complication rate [0(0/49) vs. 4.1%(2/49)] between the two groups. During the follow-up period, no recurrence or distant metastasis was observed in any of the lesions in both groups. Conclusions: The combination of endoscopy and serology diagnostic strategy has the potential to enhance the accuracy of diagnosing G1 and G2 stage G-NENs and their background mucosa. Endoscopic resection surgery (EMR, ESD) is a proven and safe treatment approach for G1 and G2 stage G-NENs.

[Clinical significance and research progress of quantitative hepatitis B virus core antibody measurement].

Hepatitis B virus core antibodies are specific antibodies produced after viral infection that appear early and last for a long time, and its levels in serum are measured by the double-antigen sandwich chemiluminescent microparticle immunoassay method, which has higher sensitivity and specificity, providing new clinical indicators for hepatitis B patients diagnosis, treatment, and drug withdrawal management. This article reviews the clinical significance and research progress of quantitative hepatitis B core antibody measurement and expounds on its research applications and prospects in clinical practice.

[Endoscopic hand-suturing combined with titanium clips for rectal defects closure after endoscopic submucosal dissection: a pilot study].

Objective: To explore the feasibility of endoscopic hand-suturing (EHS) for rectal defects closure after endoscopic submucosal dissection (ESD), and the clinical practicability of EHS combined with titanium clips. Methods: This is a prospective study performed by two experienced endoscopists from the Cancer Hospital, Chinese Academy of Medical Sciences who had received EHS training in sixporcine gastric ESD defects in vivo before the study. From December 2022 to February 2022, 20 patients with rectal mucosal lesions or submucosal diseases underwent ESD. Then EHS combined with titanium clips was adopted to close the rectal ESD defects. Specifically, we first sutured the defects as much as possible through EHS, then use titanium clips to fix the tail of the suture, and finally use additional titanium clips to close the residual parts of the defects that cannot be sutured. The main observational indicators were complete closure of the wound and delayed bleeding within one month after surgery. Results: In the 20 rectal cases, the size of defects ranged from 2.2 to 3.6 cm, with a median of 2.7 cm. All cases achieved complete closure without delayed bleeding, of which 12 (60.0%) were completely sutured with EHS and 8 (40.0%) required additional titanium clips to achieve complete closure after suturing. Conclusion: EHS technique is feasible and safe for rectum. EHS combined with titanium clips can also effectively close the rectal ESD defects, prevent postoperative delayed bleeding, and may be easier to be implemented in clinical practice.

[Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor].

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

[Risk factors for residual cancer or lymph node metastasis after endoscopic noncurable resection of early colorectal cancer].

Objective: Risk factors related to residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer were analyzed to predict the risk of residual cancer or lymph node metastasis, optimize the indications of radical surgical surgery, and avoid excessive additional surgical operations. Methods: Clinical data of 81 patients who received endoscopic treatment for early colorectal cancer in the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences from 2009 to 2019 and received additional radical surgical surgery after endoscopic resection with pathological indication of non-curative resection were collected to analyze the relationship between various factors and the risk of residual cancer or lymph node metastasis after endoscopic resection. Results: Of the 81 patients, 17 (21.0%) were positive for residual cancer or lymph node metastasis, while 64 (79.0%) were negative. Among 17 patients with residual cancer or positive lymph node metastasis, 3 patients had only residual cancer (2 patients with positive vertical cutting edge). 11 patients had only lymph node metastasis, and 3 patients had both residual cancer and lymph node metastasis. Lesion location, poorly differentiated cancer, depth of submucosal invasion ≥2 000 µm, venous invasion were associated with residual cancer or lymph node metastasis after endoscopic (P<0.05). Logistic multivariate regression analysis showed that poorly differentiated cancer (OR=5.513, 95% CI: 1.423, 21.352, P=0.013) was an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection of early colorectal cancer. Conclusions: For early colorectal cancer after endoscopic non-curable resection, residual cancer or lymph node metastasis is associated with poorly differentiated cancer, depth of submucosal invasion ≥2 000 µm, venous invasion and the lesions are located in the descending colon, transverse colon, ascending colon and cecum with the postoperative mucosal pathology result. For early colorectal cancer, poorly differentiated cancer is an independent risk factor for residual cancer or lymph node metastasis after endoscopic non-curative resection, which is suggested that radical surgery should be added after endoscopic treatment.

[Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion].

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

[The effective analysis of refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer treated by endoscopic radiotomy combined with local injection of triamcinolone acetonide].

Refractor esophageal stenosis after endoscopic submucosal dissection of early esophageal carcinoma is a difficult clinical problem. To verify the effect of endoscopic radial incision combined local triamcinolone injection to treat refractory esophageal stenosis, we retrospectively analyzed 7 patients diagnosed with refractory esophageal stricture after endoscopic mucosal dissection of early esophageal cancer in this study, of whom 4 male and 3 female patients, aged 50-76 years, with the mean age of 63 years. We performed the endoscopic radial incision in the thickness point of the scar stricture and injected the triamcinolone locally. The results showed it was safe and effective. The follow-up showed no esophageal stenosis occured and no adverse reaction such as hemorrhage, perforation, tumor-recurrence and triamcinolone-allergy occured.

[Efficacy of in-situ full-left/full-right split liver transplantation for adult recipients using the living donor liver transplantation technique:a single-center report of 25 cases].

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ2 test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.

[The clinical value of multi-target stool fecal immunochemical test-DNA in early screening and diagnosis for colorectal cancer].

Objective: To investigate the clinical diagnostic value of multi-target stool fecal immunochemical test-DNA (FIT-DNA) test in colorectal cancer (CRC) and advanced adenoma (AA). Methods: A total of 235 patients who were undergoing colonoscopy or colorectal cancer surgery in the Cancer Hospital, Chinese Academy of Medical Sciences from April 2021 to January 2022 were prospectively enrolled. There were 141 males and 94 females, with an average age of (55±13) years (22-86). The patients were divided into two groups, including 215 patients who were first diagnosed but not treated (86 cases of CRC, 12 cases of AA, 25 cases of non-advanced adenoma, 8 cases of hyperplastic or other polyps and 84 apparently healthy cases) and 20 patients in the intervention group (2 cases with a history of CRC surgery, 6 cases with a history of endoscopic surgery, 4 non-CRC patients with special diseases and 8 cases with a history of neoadjuvant chemoradiotherapy). Fresh stool samples were collected before intestinal preparation or surgery for FIT-DNA test using the matching kit for sample processing and nucleic acid purification. KRAS mutation and methylation of BMP3 and NDRG4 genes were detected by fluorescence probe method, and FIT method was employed to detect fecal occult blood. Colonoscopy or pathological biopsy results were used as the gold standard. And the screening and diagnostic efficacy of FIT-DNA test for colorectal cancer and advanced adenoma were evaluated by receiver operating curve (ROC). Results: The sensitivity of FIT-DNA test for early colorectal cancer and advanced adenoma was 7/7 and 8/12, respectively. And the negative predictive value was 98.1% (104/106) and 93.7% (104/111), respectively. The overall screening sensitivity for both early colorectal cancer and advanced adenoma was 15/19, and the negative predictive value was 96.3% (104/108). Besides, the area under the curves (AUCs) were 0.982 (95%CI: 0.960-1.000, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.841 (95%CI: 0.724-0.957, P<0.05), respectively. Moreover, the diagnostic sensitivity of FIT-DNA test was 98.8% (85/86) for colorectal cancer, 8/12 for advanced adenoma, and 94.9% (93/98) for both colorectal cancer and advanced adenoma, with a specificity of 88.9% (104/117). The AUCs were 0.968 (95%CI: 0.937-0.997, P<0.05), 0.758 (95%CI: 0.592-0.924, P<0.05) and 0.942 (95%CI: 0.905-0.979, P<0.05), respectively. After the inclusion of intervention group, the overall diagnostic sensitivity and specificity of FIT-DNA test was 91.6% (98/107) and 89.1% (114/128), respectively. Conclusion: FIT-DNA test has a high early screening and diagnostic efficacy for colorectal cancer.

[Effect and mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection].

Objective: To explore the role and specific mechanism of glucocorticoids in preventing stenosis after esophageal endoscopic submucosal dissection (ESD). Methods: Data of 81 patients [51 cases were male and 30 cases were female, aged (62.09±7.95) years] undergoing early esophageal cancer or precancerous lesions with a stripping range ≥3/4 circle hospitalized from January 2019 to February 2021 in Department of Gastroenterology, Zhongda Hospital, Southeast University. They were randomly divided into the control group (n=23), oral prednisone acetate group (n=28) and/or combined with local injection Triamcinolone acetonide group (n=30). Analysis the stenosis rates, endoscopic stent dilatation times, the scores of the Atkinson classification and QLQ-OES18 after 12 weeks. Also the expression of carbohydrate sulfotransferase15 (CHST15) mRNA, TGF-ß1 and Collagen-Ⅰ protein were compared by real-time PCR or immunohistochemistry. Results: The stenosis rates of the control group, oral prednisone acetate group and/or combined with local injection Triamcinolone acetonide group were 82.6% (19/23), 46.4% (13/28) and 20.0% (6/30) (P<0.001); endoscopic stent dilatation times [M (Q1,Q3)] in these three groups were 2 (1, 3), 0 (0, 0) and 0 (0, 0) (P<0.001). After ESD, the scores of the Atkinson classification and QLQ-OES18 in the three groups were lower than before (P<0.001); and the expression of CHST15 mRNA in the three groups were 4.31±0.13, 3.44±0.07 and 2.84±0.21 respectively (P<0.001). Compared with the control group, the expression of CHST15 mRNA in oral prednisone acetate group was down-regulated (P<0.001), and was the lowest in oral prednisone acetate combined with local injection Triamcinolone acetonide group (P<0.001). As CHST15 mRNA was down-regulated, the expression of TGF-ß1 and Collagen-I protein was also down-regulated (P<0.05). Conclusions: Oral prednisone alone or combined with local injection of triamcinolone acetonide both can prevent esophageal stenosis effectively. Oral combined with local injection of glucocorticoid is particularly more effective. Glucocorticoid can reduce the expression of CHST15 mRNA, thereby inhibiting the expression of TGF-ß1 and Collagen-I protein.

[Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure].

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

[Management strategies for chronic liver disease-related thrombocytopenia].

Chronic liver disease causes bleeding and coagulation system abnormalities through a variety of mechanisms. Thrombocytopenia is a common complication of chronic liver disease. Patients with chronic liver disease, especially liver cirrhosis, often face more invasive examinations or surgeries, which brings great challenges to clinical diagnosis and treatment. Traditional platelet transfusion is the main clinical intervention. With the approval of thrombopoietin receptor agonists, the current management standards for chronic liver disease-related thrombocytopenia may face changes. This article reviews the current main non-pharmacological and pharmacological interventions for chronic liver disease-related thrombocytopenia, and put forwards the corresponding clinical management improvement strategies based on the efficacy and limitations of these interventions.

[Analysis of risk factors for delayed bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm].

Objective: To determine the potential risk factors of delayed hemorrhage after endoscopic submucosal dissection (ESD) in patients with early gastric carcinomas or precancerous lesions. Methods: The clinical data of 637 patients with early gastric carcinomas (EGC) who treated with ESD in Department of Endoscopy at Cancer Hospital, Chinese Academy of Medical Sciences, from August 2013 to August 2019, were retrospectively analyzed. Univariate analysis and multivariate logistic analysis were conducted to evaluate the risk factors associated with delayed bleeding. Results: A total of 699 lesions in 637 patients, of which 696 lesions were resected enbloc, the curative resection rate was 92.1% (644/699). The pathological diagnosis after ESD showed that 46 cases were low-grade intraepithelial neoplasia, 71 were high-grade intraepithelial neoplasia, and 582 were cancer. Delayed bleeding occurred in 74 lesions, while other 625 lesions without postoperative bleeding. The incidence was 10.6%. Compared with the non-bleeding group, there were statistically significant differences in the maximum length of the lesion, the gross shape of the lesion, the control of intra operative bleeding, and the operation time in the delayed bleeding group (P<0.05). Multivariate logistic regression analysis showed that the maximum length of the lesion and the gross shape of the lesion were independent factors of delayed bleeding after ESD. Delayed bleeding was inclined to occur in patients with lesion size ≥3.0 cm (OR=1.958, 95% CI: 1.162-3.299) and the superficial and flat lesion (OR=10.598, 95% CI: 1.313-85.532) after ESD. Conclusions: The maximum length of the lesion and the gross shape of the lesion are independent impact factors of delayed bleeding occurring in patients with EGC and precancerous lesions after ESD. Patients with lesion size≥3 cm, or superficial flat lesion should be paid attention after ESD operation. It needs to take timely measures to prevent the very likely bleeding in order to ensure postoperative recovery and improve the quality of life for postoperative patients.

A Full Nesterov-Todd Step Infeasible Interior-point Method for Symmetric Optimization in the Wider Neighborhood of the Central Path.

In this paper, an improved Interior-Point Method (IPM) for solving symmetric optimization problems is presented. Symmetric optimization (SO) problems are linear optimization problems over symmetric cones. In particular, the method can be efficiently applied to an important instance of SO, a Controlled Tabular Adjustment (CTA) problem which is a method used for Statistical Disclosure Limitation (SDL) of tabular data. The presented method is a full Nesterov-Todd step infeasible IPM for SO. The algorithm converges to ε-approximate solution from any starting point whether feasible or infeasible. Each iteration consists of the feasibility step and several centering steps, however, the iterates are obtained in the wider neighborhood of the central path in comparison to the similar algorithms of this type which is the main improvement of the method. However, the currently best known iteration bound known for infeasible short-step methods is still achieved.

[Comparison of long-term outcomes between endoscopic submucosal dissection and surgical resection for early gastric cancer with undifferentiated histology].

Objective: Endoscopic submucosal dissection (ESD) of undifferentiated early gastric cancer (UD-EGC) remains controversial due to high positive rate of horizontal and vertical resection margins and the risk of lymph node metastasis. The purpose of this study was to compare long-term outcomes of patients with UD-EGC undergoing ESD versus surgery. Methods: This study was a retrospective cohort study. Inclusion criteria: (1) patients with early gastric cancer undergoing ESD or surgical resection; (2) histological types included poorly differentiated adenocarcinoma, poorly differentiated adenocarcima with signet ring cell carcinoma, and signet ring cell carcinoma; (3) no lymph node metastasis or distant metastasis was confirmed by preoperative CT and endoscopic ultrasonography. Exclusion criteria: (1) previous surgical treatment for gastric cancer; (2) synchronous tumors; (3) death with unknown cause; (4) additional surgical treatment was performed within 1 month after ESD. According to the above criteria, clinical data of patients with UD-EGC who received ESD or surgery treatment in Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2016 were collected. After further comparing the clinical outcomes between the two groups by 1:1 propensity score matching, 61 patients in the ESD group and 61 patients in the surgery group were finally included in this study. The disease-free and overall survivals were analyzed by Kaplan-Meier method. Results: All patients in the two groups completed operations successfully. In the ESD group, the median operation time was 46.3 (26.5, 102.3) minutes, 61 cases (100%) were en-bloc resection, and 57 cases (93.4%) were complete resection. Positive margin was found in 4 (6.6%) patients, of whom 2 were positive in horizontal margin and 2 were positive both in horizontal and vertical margins. In the surgery group, only 1 case had positive horizontal margin and no positive vertical margin was observed. There was no significant difference in the positive rate of margin between the two groups (P>0.05). Median follow-up time was 59.8 (3.0, 131.5) months. The follow-up rate of ESD group and surgery group was 82.0% (50/61) and 95.1% (58/61), respectively. The 5-year disease-free survival rate in ESD group and surgery group was 98.2% and 96.7%, respectively (P=0.641), and the 5-year overall survival rate was 98.2% and 96.6%, respectively (P=0.680). In the ESD group, 1 patient (1.6%) had lymph node recurrence, without local recurrence or distant metastasis. In the surgery group, 1 case (1.6%) had anastomotic recurrence and 1 (1.6%) had distant metastasis. Conclusion: ESD has a sinilar long-term efficacy to surgery in the treatment of UD-EGC.