Objective: To investigate the associations of macroscopic tumor regression patterns and distal resection margin (DRM) distance with local recurrence in patients with rectal cancer after neoadjuvant chemoradiotherapy (nCRT), and to provide evidence for surgical decision-making and intraoperative assessment of the distal resection extent. Methods: This single-center retrospective cohort study used data from the prospective MONT-R registry. A total of 410 patients with mid-to-low locally advanced rectal cancer who underwent nCRT followed by radical surgery at Peking Union Medical College Hospital between December 2017 and September 2022 were included. Of these, 276 patients were male (67.3%), and the median age was 60 years (interquartile range [IQR], 51-67 years). According to the gross appearance of postoperative specimens, tumors were classified as scar-like, ulcerative, or protruding mass-type patterns. Clinicopathological characteristics, DRM distance, and the incidence of inadequate DRM, defined as DRM ≤0.5 cm, were compared among groups. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were analyzed using the Kaplan-Meier method. Results: Of the 410 patients, 42 (10.2%) had scar-like tumors, 360 (87.8%) had ulcerative tumors, and 8 (2.0%) had protruding mass-type tumors. The lymph node metastasis rate differed significantly among groups (χ²=8.63, P=0.013), with no lymph node metastasis observed in the scar-like group, compared with 17.2% (62/360) in the ulcerative group and 1/8 in the protruding mass-type group. Pathological tumor diameter also differed significantly among groups (H=11.82, P=0.003) , with the mass-type showing the largest diameter [median (Q1, Q3): 2.9 (2.3, 4.0) cm], whereas no obvious difference was observed between the ulcerative type [2.0 (1.3, 2.5) cm] and the scar-like type [1.5 (1.2, 2.0) cm]. The distributions of ypT stage, perineural invasion, and lymphovascular invasion did not differ significantly among groups (all P>0.05). Only 4 patients had a positive circumferential resection margin; all of whom were in the ulcerative group. The proportions of CAP 0-1 tumor regression and pathological complete response were higher in the scar-type group than in the other groups, but the differences were not statistically significant (P=0.098 and P=0.081, respectively). The median DRM distances in the scar-type, ulcerative-type, and protruding mass-type groups were 1.15 (0.20, 2.00) cm, 1.70 (1.00, 2.75) cm, and 2.55 (1.38, 3.62) cm, respectively, with a significant difference among groups (H=9.67, P=0.008). The incidence of inadequate DRM was significantly higher in the scar-type group than in the ulcerative-type and protruding mass-type groups [38.1% (16/42) vs. 15.3% (55/360) vs. 1/8; χ²=13.67, P=0.001]. During a median follow-up of 51 months (IQR, 36-64 months), no significant differences were observed in DFS (P=0.947) or LRFS (P=0.175) among the three groups. Similarly, DFS (P=0.731) and LRFS (P=0.131) did not differ significantly between patients with inadequate and adequate distal resection margins. Conclusions: After nCRT for rectal cancer, patients with a scar-like macroscopic tumor regression pattern had a lower risk of lymph node metastasis and a shorter DRM. However, in the setting of standardized total mesorectal excision, a shorter DRM was not associated with adverse survival outcomes.

Objective: To analyze the characteristics of recurrence and metastasis as well as survival outcomes in patients with No.253 lymph node metastasis from sigmoid colon or rectal cancer, and patients with M1 colorectal cancer who underwent radical resection of metastatic lesions in the same period. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) Preoperative clinical staging indicated non-metastatic colorectal cancer; (2) Patients underwent standard radical surgery with D3 lymphadenectomy; (3) Postoperative pathology confirmed sigmoid colon adenocarcinoma or rectal adenocarcinoma, with definite status of No.253 lymph node metastasis; (4) No concurrent or prior other malignant tumors; (5) Complete clinical and follow-up data. Exclusion criteria: Patients who received preoperative neoadjuvant chemoradiotherapy, or underwent emergency surgery due to complications such as intestinal obstruction or perforation. Clinical and pathological data of 41 patients with sigmoid colon and rectal cancer who received radical resection with pathologically verified No.253 lymph node metastasis postoperatively between February 2016 and February 2018 were retrieved from the colorectal cancer database of the Department of General Surgery, Nanfang Hospital, Southern Medical University (No.253-positive group). Additionally, 71 patients with stage M1 colorectal cancer who had distant metastasis underwent radical resection of both primary and metastatic lesions and achieved postoperative no evidence of disease were enrolled as the stage M1 group. A 1∶1 propensity score matching (PSM) was performed between the No.253-positive group and the stage M1 group based on gender, age, tumor location, tumor diameter, pT stage, preoperative carcinoembryonic antigen level and postoperative adjuvant therapy. After PSM, 25 patients were included in each group. The 5-year disease-free survival (DFS) rate, 5-year overall survival (OS) rate, and characteristics of recurrence and metastasis were compared between the two groups. Results: After propensity score matching (PSM), there were no statistically significant differences in baseline characteristics between the No.253-positive group and the stage M1 group (all P>0.05, SMD<0.2). The overall 5-year DFS rate was 24.0% in the No.253-positive group versus 8.0% in the stage M1 group, with no significant difference (P=0.094). The overall 5-year OS rate was 32.0% and 16.0% for the two groups, respectively, and the difference was also not statistically significant (P=0.108). Stratified analysis by tumor location revealed no significant between-group differences in 5-year DFS and OS among patients with lower rectal cancer and upper rectal cancer (all P>0.05). For patients with sigmoid colon cancer, the No.253-positive group had a higher 5-year DFS rate than the stage M1 group (P=0.017), while no significant difference was observed in 5-year OS (P=0.581). Following PSM, recurrence or metastasis occurred in 76.0% (19/25) of patients in the No.253-positive group and 96.0% (24/25) in the stage M1 group. There were no significant differences in the patterns and anatomical distribution of recurrence and metastasis between the two groups (all P>0.05). However, the rate of multiple-site recurrence or metastasis was markedly higher in the stage M1 group (50.0%) than in the No.253-positive group (10.5%), and the difference reached statistical significance (P=0.009). The median time to recurrence or metastasis was 19 (2-58) months in the No.253-positive group and 17 (2-64) months in the stage M1 group, without a significant difference (U=215.5, P=0.767). Conclusions: Patients with No.253-positive sigmoid colon or rectal cancer showed overall survival outcomes similar to those of patients with synchronous M1 colorectal cancer who underwent curative-intent resection of metastatic lesions, but their recurrence and metastasis were relatively more limited in extent. No.253 lymph node metastasis may represent a high-risk state in the transition from regional lymphatic progression to systemic dissemination in sigmoid colon and rectal cancer, and its clinical significance may differ according to tumor location.

Objective: To analyze the application and clinical efficacy of the "three-step posterior approach" for preserving the vagus nerve in laparoscopic radical distal gastrectomy for gastric cancer. Methods: This was a retrospective cohort study. Clinical data of patients who underwent laparoscopic radical distal gastrectomy at the Department of Gastric Surgery, The First Affiliated Hospital of Nanjing Medical University from March 2020 to June 2023 were collected. Inclusion criteria included: age 18-75 years; pathological diagnosis of gastric adenocarcinoma; clinical stage cT1~2N0~1M0; and no history of gallstones. Patients with preoperative neoadjuvant chemotherapy, combined organ resection, or missing data were excluded. Patients were divided into a conventional laparoscopic radical distal gastrectomy (LDG) group and a laparoscopic vagus nerve-preserving distal gastrectomy (LVNPDG) group based on the surgical procedure. The preservation of the celiac branch of the vagus nerve was performed using the "three-step posterior approach". Step 1: First, lymph node dissection at No.11p was performed along the proximal splenic artery at the upper border of the pancreas. The left Toldt space was entered, Gerota fascia was exposed, and dissection was extended rightward along its surface to the left diaphragmatic crus. Step 2: Lymph nodes No.8 and No.12a were dissected, then retracted leftward to dissect No.9 lymph nodes. The adhesion between the right diaphragmatic crus and the left gastric mesentery was divided and connected to the left Toldt space, thereby completely mobilizing the left gastric mesentery from the posterior abdominal wall. Step 3: From the root of the left gastric artery, the left gastric mesentery was opened dorsally toward the diaphragm and incised distally to expose the left gastric artery. Using dissecting forceps, the left gastric mesentery was dissected toward the posterior trunk of the vagus nerve to identify, expose, and preserve the celiac branch running within it. Subsequently, dissection was extended along the celiac branch toward the cardia, and the posterior gastric branches of the vagus nerve to the posterior gastric wall were divided. Below the emergence of the hepatic branch from the anterior trunk of the vagus nerve, the hepatogastric ligament was incised to expose the right diaphragmatic crus, and a fixing suspension suture was placed while sparing the hepatic branch of the vagus nerve. A maximum ratio of 1∶3 propensity score matching (PSM) (caliper value 0.02) was performed using sex, age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, tumor size, differentiation, depth of invasion, lymph node metastasis, TNM stage, and anastomosis method as covariates. Perioperative indicators (operation time, blood loss, lymph node count, time to first flatus and diet, hospital stay), early postoperative complications, quality of life at 1 year postoperatively (constipation, diarrhea, flatulence, appetite, dumping syndrome), and nutritional status. Results: After PSM, 76 patients were included in the LVNPDG group, and 204 patients in the LDG group. There were no statistically significant differences in baseline characteristics between the two groups (all P> 0.05). The operation time in the LVNPDG group was longer than that in the LDG group [(183.2±35.8) minutes vs. (168.4±34.9) minutes, t=-3.136, P=0.002], but the time to first flatus was shorter in the LVNPDG group [(2.6±0.8) days vs. (2.9±0.7) days, t=2.748, P=0.007]. No statistically significant differences were observed between the two groups regarding intraoperative blood loss, the number of retrieved lymph nodes (total and per station), time to first liquid diet, or postoperative hospital stay (all P> 0.05). The incidence of early postoperative complications was 5.9% (12/204) in the LDG group and 7.9% (6/76) in the LVNPDG group, with no significant difference (χ²=0.113, P=0.736). Regarding quality of life and long-term complications at 1 year postoperatively, the incidence of diarrhea in the LVNPDG group was lower than in the LDG group [3.9% (3/76) vs. 13.2% (27/204), χ²=4.993, P=0.025], and the incidence of increased flatulence was also significantly lower [17.1% (13/76) vs. 33.3% (68/204), χ²=7.092, P=0.008]. Additionally, the incidence of gallstones in the LVNPDG group was 1.3% (1/76), which was significantly lower than the 8.8% (18/204) observed in the LDG group (χ²=4.934, P=0.026). There were no statistically significant differences between the two groups in terms of constipation, appetite loss, dumping syndrome, or changes in postoperative albumin levels (all P >0.05). Conclusions: The "three-step posterior approach" for preserving the vagus nerve in laparoscopic radical distal gastrectomy is technically safe and feasible, without increasing the risk of postoperative complications. Compared with traditional laparoscopic distal gastrectomy, this procedure effectively improves patients' postoperative quality of life.

Objective: To investigate the incidence of immune-related adverse events (irAEs) and corresponding perioperative outcomes among patients with colorectal cancer who received neoadjuvant immunotherapy and underwent curative radical resection. Methods: This was a retrospective, multicenter, real-world cohort study. A total of 452 patients with pathologically confirmed colorectal adenocarcinoma who completed neoadjuvant immunotherapy and curative radical surgery were enrolled from five tertiary hospitals between January 1, 2020 and December 31, 2024. The participating institutions included Beijing Friendship Hospital, Capital Medical University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; The Sixth Affiliated Hospital, Sun Yat-sen University; The First Affiliated Hospital of Nanchang University; and The Second Affiliated Hospital, Zhejiang University. The median age of the overall cohort was 58.5 years. In terms of clinical TNM staging, 86 patients (19.0%) were at stage Ⅱ and 366 (81.0%) were at stage Ⅲ. Based on MMR/MSI status, 116 patients (25.7%) were identified as deficient mismatch repair/high microsatellite instability (dMMR/MSI-H), and the remaining 336 (74.3%) as proficient mismatch repair/microsatellite stable (pMMR/MSS). Regarding treatment modalities, 92 patients (20.4%) received single-agent immune checkpoint inhibitor (ICI) therapy, 22 (4.9%) dual ICI combination therapy, 30 (6.6%) immunotherapy combined with chemotherapy, and 308 (68.1%) immunotherapy combined with chemoradiotherapy. All irAEs were graded in accordance with the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), and grade ≥3 irAEs were defined as severe irAEs. The primary outcomes were the overall incidence and organ-specific distribution of irAEs. Secondary outcomes covered irAE risks stratified by treatment regimens and MMR/MSI status, overall pathological complete response (pCR) rate, as well as perioperative clinical outcomes. Temporal trend analysis was conducted after logical validation of the initial onset time of irAEs. Results: The overall incidence of all-grade irAEs reached 24.6% (111/452), including 73 cases (16.2%) of grade 1, 24 (5.3%) of grade 2, 7 (1.5%) of grade 3, 5(1.1%) of grade 4 and 2 (0.4%) of grade 5. Severe irAEs (grade ≥3) occurred in 14 patients, accounting for 3.1% of the total cohort. A total of 157 irAE episodes were documented, among which single-organ involvement was observed in 65 patients (58.6%) and multi-organ involvement in 46 patients (41.4%). The most frequently affected organ systems were skin and mucous membranes (40 episodes, 25.5%), endocrine and thyroid system (36 episodes, 22.9%), hematopoietic system (34 episodes, 21.7%), hepatobiliary system (21 episodes, 13.4%), and gastrointestinal tract (9 episodes, 5.7%). Other involved systems comprised musculoskeletal system (6 episodes, 3.8%), urinary and renal system (6 episodes, 3.8%), cardiovascular system (4 episodes, 2.5%), and general systemic reactions (1 episode, 0.6%). One fatal grade 5 event consisting of fulminant myocarditis complicated with malignant arrhythmia and liver failure was recorded. Stratified by treatment strategy, the incidence of all-grade irAEs was 23.9% (22/92) for single-agent ICI, 27.3% (6/22) for dual ICI combination, 23.3% (7/30) for immunochemotherapy and 24.7% (76/308) for immunochemoradiotherapy; the corresponding incidence of severe irAEs was 3.3%, 4.5%, 3.3%, and 2.9%, respectively. Univariate and multivariate regression analyses confirmed that MMR/MSI status was the only independent risk factor for irAE occurrence (OR=2.626,95%CI:1.566-4.402,P<0.001). Validated complete onset time data were available for 85 patients, who were included in the temporal analysis, with 110 irAE episodes including 14 severe events identified. Approximately 58.8% (50/85) of irAEs emerged within 84 days after the first ICI administration, and 52.9% (45/85) developed one month after treatment cessation, including two grade 5 fatal events: severe myelosuppression/overlap syndrome following immunochemoradiotherapy, and fulminant myocarditis accompanied by malignant arrhythmia and liver failure after immunochemotherapy. The median time to first irAE onset was 61 (35-100) days. Among 14 severe irAEs, 9 events occurred after immunochemoradiotherapy, 3 after single-agent ICI therapy, 1 after dual ICI combination, and 1 after immuneochemotherapy. Apart from the 2 fatal cases, the other 11 severe irAEs were effectively alleviated via drug discontinuation, glucocorticoid intervention and/or supportive treatment, whereas one case of immune-related enteritis progressed into a chronic condition. No surgical delay of 14 days or longer attributed to irAEs was noted in the entire cohort. The median length of hospital stay was 14 (12-18) days in patients with irAEs versus 13 (11-16) days in those without irAEs, with no significant intergroup difference (Z=1.80, P=0.072). The postoperative complication rates were 18.9% (21/111) and 18.5% (63/341) in the irAEs and non-irAEs groups, respectively, showing no statistical discrepancy (χ²=0.01, P>0.999). The overall pCR rate of all enrolled patients was 49.8% (225/452). Conclusions: IrAEs, which are mostly mild-to-moderate and manifest as multi-organ involvement, are not rare during neoadjuvant immunotherapy for colorectal cancer. Skin, endocrine and hematopoietic systems are the predominantly affected sites, and the majority of irAEs are clinically manageable. Although severe irAEs remain uncommon, they are featured with delayed onset and life-threatening potential; in particular, cardiovascular toxicities such as fulminant myocarditis warrant close clinical vigilance. The onset of irAEs is not confined to the conventional neoadjuvant treatment period, hence sustained safety monitoring is required throughout the perioperative phase and even after treatment completion.

Neoadjuvant therapy has become the standard of care for locally advanced esophageal cancer; however, a subset of patients still faces the dilemma of treatment failure, characterized by clinical progression or failure to achieve R0 resection. The predominant recurrence patterns are distant metastasis and locoregional recurrence. This failure is a multidimensional consequence of patient characteristics, treatment modalities, and hospital volume. To address this clinical challenge, this article systematically explores individualized breakthrough strategies. The first is the perioperative "intensification and salvage" strategy, encompassing the re-evaluation of salvage surgery at high-volume centers, the intensification and conversion of systemic therapies (e.g., novel agents like bispecific ADCs), the individualized application of precision radiotherapy, and the standardized intervention of postoperative adjuvant immunotherapy (e.g., PD-1 inhibitors). The second strategy is molecular residual disease (MRD)-guided precision adjuvant therapy, utilizing liquid biopsy technologies such as ctDNA to implement an adaptive management model-intensifying treatment for MRD-positive patients while de-escalating or observing for MRD-negative ones. In the future, the clinical management of esophageal cancer will shift from passive "post-failure salvage" to proactive "whole-process prediction and adaptive management," aiming to further optimize treatment pathways and improve patient prognosis.

Objective: To investigate the diagnostic value of plasma circulating tumor DNA (ctDNA) methylation of glutathione S-transferase P1 (GSTP1) and secreted frizzled-related protein 2 (SFRP2) for early hepatocellular carcinoma (HCC), and to evaluate a multimodal model integrating smoking history, nodule size, alpha-fetoprotein (AFP), and protein induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ). Methods: This single-center retrospective case-control study enrolled 180 patients with HCC or liver cirrhosis at the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2023 to December 2024, with patients with cirrhosis serving as disease controls. The training set included 63 HCC patients and 63 cirrhosis patients, and the validation set included 26 HCC patients and 28 cirrhosis patients. Baseline clinical data, tumor biomarkers, liver function parameters, coagulation indices, imaging characteristics, and plasma ctDNA GSTP1/SFRP2 methylation levels detected by methylation-specific quantitative PCR (MS-qPCR) were collected. Logistic regression was used to identify independent risk factors and construct a multimodal diagnostic model. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, confusion matrix analysis, and decision curve analysis (DCA). Result: GSTP1 methylation was higher in the HCC group than in the cirrhosis group [0.87 (0.75, 0.97) vs. 0.76 (0.54, 0.86); U=-3.842, P<0.001], and SFRP2 methylation was also higher [0.83 (0.70, 0.94) vs. 0.71 (0.60, 0.83); U=-3.423, P<0.001]. Multivariate logistic regression identified smoking history (OR=18.84, 95%CI: 2.82-126.10), nodule diameter (OR=33.40, 95%CI: 2.50-446.58), AFP (OR=40.03, 95%CI: 7.39-216.95), PIVKA-Ⅱ (OR=6.18, 95%CI: 1.34-28.39), and GSTP1/SFRP2 methylation (OR=1.50/2.54) as independent risk factors for HCC. The multimodal model achieved AUCs of 0.962 and 0.955 in the training and validation sets, respectively, with positive predictive accuracies of 0.891 and 0.868, outperforming single-factor diagnostic methods. In conclusion, GSTP1 and SFRP2 methylation levels were significantly higher in the HCC group than in the cirrhosis group, and both were independent risk factors for HCC, indicating potential for early diagnosis. The multimodal model integrating ctDNA methylation and clinicoradiological indicators achieved AUCs of 0.962 and 0.955 in the training and validation sets, with positive predictive accuracies of 0.891 and 0.868, respectively. Conclusion: DCA showed greater net benefit than any single indicator, suggesting that this model could improve diagnostic performance for early HCC and provide a new strategy for liver cancer screening.

Objective: To assess the disease burden of esophageal cancer attributable to smoking in China and globally from 1990 to 2021 and to explore the causal association between smoking and esophageal cancer. Methods: Data on smoking-attributable esophageal cancer deaths and disability-adjusted life years (DALYs) in China and globally from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression models were used to analyze temporal trends in the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR). The lifetime smoking index from the UK Biobank was used as the exposure, and summary-level data for esophageal cancer from a genome-wide association study (GWAS) were used as the outcome. Mendelian randomization (MR) analysis was performed to investigate the causal relationship between smoking and esophageal cancer. Cochran's Q test was applied to assess heterogeneity among instrumental variables (IVs); MR-Egger regression and MR-PRESSO were used to evaluate horizontal pleiotropy of IVs; and leave-one-out analysis together with funnel plots were conducted to examine the stability of the results. Results: From 1990 to 2021, the absolute numbers of smoking-attributable esophageal cancer deaths and DALYs increased in both China and globally, whereas the ASMR and ASDR decreased significantly. Joinpoint analysis showed that the declines in ASMR and ASDR in China (AAPC:-1.49% and -1.87%, respectively) were faster than the corresponding global declines (-1.23% and -1.57%). The decrease was significantly more rapid in females than in males (all P<0.001). MR analysis confirmed a causal association between smoking and esophageal cancer (OR=1.004, 95%CI: 1.002-1.006, P<0.001). Cochran's Q test indicated no heterogeneity (P>0.05), and MR-Egger regression and MR-PRESSO showed no evidence of horizontal pleiotropy among the IVs (all P>0.05). Leave-one-out analysis and funnel plots demonstrated the robustness of the causal estimate. Conclusion: The disease burden of esophageal cancer attributable to smoking remains substantial in both China and globally, with declining trends in age-standardized rates; notably, the decline in China has outpaced the global average. Smoking is a causal risk factor for esophageal cancer, and males represent a high-risk group.

Objective: To explore the prognostic impact of hypomethylating agents (HMA) versus hydroxyurea plus best supportive care (HU/BSC) in patients with intermediate-and high-risk chronic myelomonocytic leukemia (CMML), and to analyze the patterns of clonal evolution and dynamic changes of inflammatory cytokines in patients with disease progression before and after HMA treatment. Methods: A total of 63 patients diagnosed with intermediate-and high-risk CMML admitted to the Department of Hematology, the Second Hospital of Tianjin Medical University between October 20 2017 and May 8 2025 were retrospectively enrolled. All patients were followed up every 3 months via outpatient and inpatient visits after discharge, with the last follow-up conducted on February 28, 2026. According to treatment regimens, the patients were divided into HMA group (n=31) and HU/BSC group (n=32). Treatment response, disease progression and survival outcomes were compared between the 2 groups. The Kaplan-Meier method was used to plot the survival curves of overall survival (OS) and progression-free survival (PFS). Bone marrow DNA was collected from patients with disease progression before and after treatment with HMA (n=20) and HU/BSC (n=13). Next-generation sequencing was used to detect 325 mutated genes related to hematological malignancies, and the clonal evolution of gene mutations in patients receiving the 2 treatment regimens before and after disease progression was investigated. Bone marrow supernatant specimens were collected from patients with disease progression treated with HMAs (n=8) and HU/BSC (n=8), and enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of 21 inflammatory cytokines including IL-6 and IFN-γ. The differences in inflammatory cytokine expression before and after disease progression were compared. Results: The median follow-up duration for all patients [M(Q₁,Q₃)] was 21 (10, 40) months. The median OS was 22.0 months (95%CI: 11.8-32.2) in the HMA group and 36.0 months (95%CI: 23.6-48.4) in the HU/BSC group, with no statistically significant difference between groups (P=0.208). The median PFS was 18.0 months (95%CI: 10.8-25.2) and 26.0 months (95%CI: 19.9-21.1) respectively, and the difference was also not statistically significant (P=0.108). Among patients with disease progression after HMA treatment, newly acquired mutations were predominantly enriched in RAS pathway genes, accounting for 25% (5/20). Clonal expansion of SF3B1, TP53 and RUNX1 was observed, and the mutational burden of each gene accounted for 10% (2/20). Compared with baseline levels, the concentrations of TNF-α [113.6 (104.1, 147.1) pg/ml vs 25.7 (20.2, 41.3) pg/ml, P<0.001] and IL-8 [77.5 (54.6, 115.8) pg/ml vs 7.0 (2.6, 9.2) pg/ml, P=0.003] were significantly increased after disease progression, while the level of IFN-γ [341.5 (221.2, 460.7) pg/ml vs 732.7 (389.0, 852.4) pg/ml, P=0.013] was markedly decreased. Conclusions: Compared with HU/BSC regimen, HMA failed to significantly improve OS and PFS in patients with intermediate-and high-risk CMML. Disease progression after HMA treatment may be closely associated with newly emerging mutations in the RAS pathway, clonal expansion of pre-existing mutations such as TP53, as well as the upregulation of TNF-α and IL-8 and downregulation of IFN-γ.

Objective: To analyze the clinical and genetic characteristics of pheochromocytoma and paraganglioma (PPGL), as well as genotype-phenotype correlations in children and adolescents. Methods: A retrospective analysis was performed on clinical data and germline genetic testing results of 93 pediatric and adolescent patients (age≤18 years) diagnosed with PPGL at Peking Union Medical College Hospital between January 2010 and February 2025. According to germline variant results, enrolled patients were divided into four subgroups(6 cases with variants of uncertain pathogenic significance or benign variants and 3 cases with incomplete genetic testing were excluded. A total of 84 cases were included for analysis): SDHB-mutant group(carring pathogenic or likely pathogenic SDHB variants,n=41), VHL group (carring pathogenic or likely pathogenic VHL variants, n=9), other-gene variant group (carrying pathogenic or likely pathogenic variants in alternative genes,n=8), and wild-type group (no definite pathogenic variants detected, n=26). Clinical manifestations, germline mutation spectrum, long-term prognosis, and genotype-related phenotypic discrepancies were statistically compared across groups. Results: Among the 93 patients, 54 were male and 39 were female; the mean onset age was (13.7±3.7) years, with the follow-up duration of 2.5 (1.0, 7.0) years. Follow-up was terminated in February 2026. Tumor classification included 56 paragangliomas, 34 pheochromocytomas, and 3 composite tumors with both lesions. Eighty-four patients received surgical resection. Ki-67 index≥5% was confirmed in 54% (27/50) of available pathological specimens. Postoperative tumor recurrence occurred in 21 cases, distant metastasis developed in 36 cases, and 12 patients presented with concurrent recurrence and metastasis. Germline pathogenic or likely pathogenic variants were identified in 64 patients (68.8%, 64/93), among which definite pathogenic/likely pathogenic mutations accounted for 58 cases (62.4%, 58/93): 41 with SDHB variants, 9 with VHL variants, and 8 with rare alternative-gene variants (2 cases each for SDHD and RET, 1 case apiece for SDHA, SDHC, MAX, and FH). In the SDHB-mutant group, paraganglioma accounted for 85.4% (35/41), all tumors were solitary (100.0%, 41/41), and metastatic rate reached 53.7% (22/41). In the VHL-mutant group, pheochromocytoma constituted 66.7% (6/9), multifocal lesions were seen in 77.8% (7/9), and metastatic rate was only 11.1% (1/9). Conclusions: PPGL in children and adolescents presents a strong hereditary predisposition; SDHB and VHL germline variants lead to distinctly divergent clinical phenotypes. SDHB mutations are characterized by solitary paragangliomas with high metastatic risk, whereas VHL mutations are associated with multiple pheochromocytomas featuring low metastatic risk.

Globally, especially in the Asia-Pacific region, chronic hepatitis B infection has led to an undesirable escalating morbidity and mortality with acute-on chronic liver failure, end-staged liver cirrhosis and hepatocellular carcinoma. This has happened despite the past four-decades of major scientific advances made in screening methods, vaccination strategies, highly effective low-cost anti-viral therapies and surveillance strategies for early detection of hepatocellular carcinoma. To address this health threat, APASL has formed a Viral Elimination Taskforce to unite key opinion leaders from its member countries and regions. The ongoing shifts in hepatitis B epidemiology, socioeconomic changes, and advancements in technology are taken into consideration. With the conjoint efforts of all the members of the APASL Viral Elimination Taskforce, these clinical practice guidelines have been formulated aiming to facilitate healthcare professionals, policy makers and patients in making practical and cost-effective management decisions for chronic hepatitis B infection. Altogether, it provides recommendations in thirteen major areas related to screening, vaccination, treatment and HCC surveillance. The implementation of these clinical practice guidelines represents major APASL effort toward elimination of the disease burden due to chronic hepatitis B infection in Asia-Pacific region.