Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

Objective     To explore the causes of conversion to thoracotomy in patients with minimally invasive esophagectomy (MIE) in a surgical team, and to obtain a deeper understanding of the timing of conversion in MIE. Methods     The clinical data of patients who underwent MIE between September 9, 2011 and February 12, 2022 by a single surgical team in the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. The main influencing factors and perioperative mortality of patients who converted to thoracotomy in this group were analyzed. Results     In the cohort of 791 consecutive patients with MIE, there were 520 males and 271 females, including 29 patients of multiple esophageal cancer, 156 patients of upper thoracic cancer, 524 patients of middle thoracic cancer, and 82 patients of lower thoracic cancer. And 46 patients were converted to thoracotomy for different causes. The main causes for thoracotomy were advanced stage tumor (26 patients), anesthesia-related factors (5 patients), extensive thoracic adhesions (6 patients), and accidental injury of important structures (8 patients). There was a statistical difference in the distribution of tumor locations between patients who converted to thoracotomy and the MIE patients (P<0.05). The proportion of multiple and upper thoracic cancer in patients who converted to thoracotomy was higher than that in the MIE patients, while the proportion of lower thoracic cancer was lower than that in the MIE patients. The perioperative mortality of the thoracotomy patients was not significantly different from that of the MIE patients (P=1.000). Conclusion     In MIE, advanced-stage tumor, anesthesia-related factors,extensive thoracic adhesions, and accidental injury of important structures are the main causes of conversion to thoracotomy. The rate varies at different tumor locations. Intraoperative conversion to thoracotomy does not affect the perioperative mortality of MIE.

Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023.

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

BACKGROUND: Video assisted thoracic surgery (VATS) is the main surgical method for lung cancer. The aim of this study was to analyze the reasons for conversion to thoracotomy in 83 cases among 1,350 consecutive cases who underwent video-assisted thoracic surgery (VATS) lobectomy by a single surgical team, in order to achieve a deeper understanding of the rules and the opportunity for conversion to thoracotomy in VATS lobectomy under normal conditions. METHODS: The clinical data of 1,350 patients who underwent VATS lobectomy between September 21, 2009 and June 1, 2020, by a single surgical team in the Fifth Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. There were 773 males and 577 females, aged 8-87 years, with a median age of 61.3 years, including 83 cases of benign diseases, 38 cases of lung metastases, and 1,229 cases of primary lung cancer. The cases with stage I, II and IIIa were 676, 323 and 230, respectively. The cases of left upper, left lower, right upper, right middle, right lower, right middle and upper and right middle and lower lobectomy were 301 (22.30%), 231 (17.11%), 378 (28.00%), 119 (8.81%), 262 (19.41%), 16 (1.19%) and 43 (3.19%), respectively. RESULTS: In the cohort of 1,350 consecutive patients with VATS lobectomy, 83 patients (6.15%) were converted to thoracotomy for different reasons. The conversion rate of benign lesions was significantly higher than that of malignant tumors (P<0.05). The conversion rate in stage IIIa was significantly higher than that in stage I and II (P<0.05). The conversion rate of combined lobectomy was significantly higher than that of single lobectomy (P=0.001). The conversion rate of left upper lobectomy was significantly higher than that of other single lobectomy (P<0.001). The conversion rate of right middle lobectomy was significantly lower than that of other single lobectomy (P=0.049). The main reasons for conversion were vascular injury (38.55%), lymph node interference (26.51%) and dense adhesion in thoracic cavity (16.87%). In the conversion group, the total operation time was (236.99±66.50) min and the total blood loss was (395.85±306.38) mL. The operation time in patients converted to thoracotomy due to lymph node interference was (322.50±22.68) min, which was significantly longer than that in the other groups (P<0.05). The intraoperative blood loss in patients converted to thoracotomy due to vascular injury was (560.94±361.84) mL, which was significantly higher than that in the other groups (P<0.05). With the increase in surgical experience, the number of vascular injuries gradually decreased at the early stage, mid-stage and late stage (P=0.045). CONCLUSIONS In VATS lobectomy, benign lung lesions and more advanced malignant tumors led to more surgical difficulties and higher conversion rate. The conversion rate was different in different lobectomy sites, with the highest in left upper lobectomy, and the lowest in right middle lobectomy. Vascular injury, lymph node interference and dense adhesion were the main reasons for conversion to thoracotomy, which led to prolonged operation time and increased blood loss. With the increasing number of surgical cases, the rate of conversion to thoracotomy in VATS lobectomy continues to decline, which may be mainly due to the more advanced treatment of pulmonary vessels.

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.

Objective:To investigate the contamination status of SARS-CoV-2 in imported frozen seafood from a Russia cargo ship in Qingdao and to analyze the risk factors for infection in local stevedores.Methods:The method of "two-stage, full coverage and mixed sampling" was used to collect the seafood packaging samples for the nucleic acid detection of SARS-CoV-2 by real-time fluorescent quantitative RT-PCR. A unified questionnaire was designed to investigate 71 stevedores in two shifts through telephone interview. The stevedores were divided into two groups, with 23 in the shit with two infections was group A and 48 in the shift without infection was group B. Software Epi Info7.2 was used to identify the risk factors for SARS-CoV-2 infections in the stevedores.Results:In the frozen seafood from a Russia cargo ship, the total positive rate of SARS-CoV-2 nucleic acid in the frozen seafood was 11.53% (106/919). The positive rate of SARS-CoV-2 nucleic acid in the frozen seafood unloaded by group A (14.29%,70/490) was significantly higher than that in the frozen seafood unloaded by group B (8.39%,36/429)( χ2=7.79, P=0.01) and the viral loads detected in the frozen seafood unloaded by group A were higher than those detected in the frozen seafood unloaded by group B. The scores of personal protection and behaviors in the stevedores in group A were significantly lower than those in group B ( P<0.05), and toilet use, smoking and improper hand washing before meals were the risk factors for the infection. Conclusions:The imported frozen seafood was contaminated by SARS-CoV-2 and the contamination distribution was uneven. Supervision and management of personal occupational protection and behaviors of workers engaged in imported frozen food transportation should be strengthened. It is suggested that a closed-loop monitoring and management system for the whole process of "fishing-transport- loading/unloading" should be established by marine fishery authority.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.