Literature analysis of ADR after the listing of apatinib / 中国药房

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Clinical effects and pathological characteristics of gastric tumors of fundic gland type treated with endoscopic submucosal dissection / 中华消化内镜杂志

To evaluate the clinical effects and pathological characteristics of gastric tumors of fundic gland type treated with endoscopic submucosal dissection (ESD), data of 7 patients who treated by ESD and whose postoperative pathology indicated gastric adenocarcinoma of fundic gland type or gastric oxyntic gland adenoma in Endoscopic Center of Beijing Chao-Yang Hospital of Capital Medical University from August 2018 to June 2022 were collected. The clinical characteristics, surgical complications, preoperative and postoperative pathological data and follow-up data were evaluated. The lesions of the 7 patients were all located at gastric fundus, and were treated by ESD successfully. No bleeding, perforation or other complications occurred during and after the operation. Postoperative pathology showed that tumor cells originated from deep mucosa with an invasive growth pattern. Most of tumor surfaces were covered with normal concave epithelium. Tumors infiltrated into submucosa in 4 patients, and submucosa infiltration depth was more than 500 μm (550 μm) in 1 patient. Immunohistochemistry showed that MUC-6 was diffusely positive, indicating that the tumor originated from the main cell source. The expressions of MUC-2, MUC-5AC, CDX-2, CD10, and CgA were negative in all cases. With the mean follow-up time of 21 months, the ulcer healed well after the operation, with no recurrence. Gastric tumors of fundic gland type have relatively unique biological characteristics, and ESD is the preferred treatment. In addition, the histological characteristics can be used to differentiate from other gastric tumors by immunohistochemistry.

Study on the inhibitory effect of UBE2T on radiosensitivity of lung adenocarcinoma / 中华放射肿瘤学杂志

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Functional gastrointestinal reconstruction strategies after laparoscopic proximal gastrectomy / 中华消化外科杂志

The incidence of adenocarcinoma of esophagogastric junction is gradually increa-sing. The metastasis of the distal lymph node of upper gastric cancer with tumor diameter <4 cm is rare, and proximal gastrectomy can meet the requirements of radical treatment. Reflux esophagitis, food stasis, anastomotic stenosis, and poor nutrient absorption are important factors affecting the quality of life of patients undergoing proximal gastrectomy. With the continuous promotion of laparoscopic radical gastrectomy, laparoscopic proximal gastrectomy with lymph node dissection has been standardized. However, the method of digestive tract reconstruction has not yet reached standardization consensus, and anti-reflux has become a hot spot in clinical attention in recent years. Through interpositioned jejunum reconstruction to achieve anti-reflux effect, or retaining or rebuilding the anti-flow structure of esophageal residual gastric anastomosis include a variety of additional anti-reflux surgery, which have their own different advantages and disadvan-tages. The authors introduce in detail a variety of mainstream anti-reflux surgery, and its modified program, with the aim of providing reference for colleagues and maximizing the benefits of patients.

Research progress in the mechanism of TCM intervention in anti-tumor effect of A549 cells in human lung adenocarcinoma / 国际中医中药杂志

Traditional Chinese Medicine (TCM) exerts anti-tumor effects by intervening in A549 cells of human lung adenocarcinoma, mainly including activating or inhibiting downstream target proteins of Bcl-2 and Bax, or forming RIP1/RIP3/MLKL complex bodies by affecting pathways such as PI3K/Akt, thereby inducing apoptosis in A549 cells of lung adenocarcinoma; blocks the cell growth phase, thereby inhibiting the proliferation of lung adenocarcinoma A549 cells; inhibits invasion and metastasis of A549 cells by affecting the MMPs pathway, STAT3 pathway, and regulating epithelial mesenchymal transition related factors; suppresses or activates the expression of related proteins or affect related signaling pathways, thereby reversing the resistance of lung cancer A549/DDP cell lines to cisplatin and paclitaxel.

Study on prediction of potential targets and mechanism of Zeqi Decoction in the treatment of lung adenocarcinoma / 国际中医中药杂志

Objective:To explore the potential molecular targets and mechanism of Zeqi Decoction in the treatment of lung adenocarcinoma (LUAD) through bioinformatics and cell experiment.Methods:The active components of Zeqi Decoction were collected based on TCMSP database and literature search. Then R software was used to screen differentially expressed genes in LUAD from TCGA and GEO databases. The co-expression module was obtained through weighted gene co-expression network analysis (WGCNA), and the potential targets were obtained after matching and mapping with targets of Zeqi Decoction. Enrichment analysis of GO function and KEGG pathway of targets was conducted. The results were experimentally verified. The lung adenocarcinoma cell lines A549 and H1299 were divided into blank control group and Zeqi Decoction group according to random number table. The inhibition rate of cell proliferation was detected by cell proliferation test (CCK-8); the expression of leukocyte differentiation antigen 36 (CD36) in A549 and H1299 cells was detected by Western blot; the levels of low density lipoprotein receptor (LDLR) and IL-6 were detected by ELISA.Results:Totally 157 anti-lung adenocarcinoma active components and 18 potential targets were obtained, mainly including CD36, IL6, LDLR, etc. The main target of Zeqi Decoction in the treatment of lung adenocarcinoma was lipid metabolism. The results showed that Zeqi Decoction could effectively inhibit the activity of A549 and H1299 cells and the levels of CD36, LDLR and IL-6.Conclusion:Zeqi Decoction can inhibit the inflammatory response by down-regulating the protein expressions of CD36 and LDLR, thereby slowing the proliferation of cells.

Características clínicas epidemiológicas de los pacientes con cáncer de pulmón en la provincia Camagüey 2017-2021

Introducción: El cáncer de pulmón es una de las enfermedades más graves y uno de los cánceres con mayor incidencia en las personas, responsable de los mayores índices de mortalidad oncológica a escala mundial. Objetivo: Analizar las características clínicas epidemiológicas de los pacientes con cáncer de pulmón. Métodos: Se realizó un estudio observacional descriptivo retrospectivo, con el objetivo de analizar las características clínicas epidemiológicas de los pacientes con el diagnóstico de cáncer de pulmón atendido en el Hospital Oncológico María Curie durante el quinquenio de enero de 2017 a diciembre de 2021. El universo de estudio incluyó a los 822 pacientes que fueron atendidos en el hospital durante el período antes señalado, con cáncer de pulmón. La muestra a discreción la conformaron 276 pacientes. Resultados: Predominio del cáncer de pulmón en los pacientes de 61 a 80 años de edad, sexo masculino, fumadores pasivos. La variedad cito-histológica con mayor incidencia fue el carcinoma de células pequeñas microcítico; debut de esta enfermedad en pacientes en estadio IV y con tratamiento recibido de radioterapia y quimioterapia en el 100 % de los pacientes. Conclusiones: Es un tumor predominante entre las neoplasias malignas, donde el diagnóstico oportuno permite tratar en estadios tempranos, lo cual favorece la sobrevida en pacientes.

Introduction: Lung cancer is one of the most serious diseases and one of the cancers with the highest incidence in people, responsible for the highest oncological mortality rates worldwide. Objective: To analyze the clinical-epidemiological characteristics of patients with lung cancer. Methods: A retrospective descriptive observational study was carried out, with the objective of analyzing the epidemiological clinical characteristics of patients diagnosed with lung cancer treated at the María Curie Oncological Hospital during the five-year period from January 2017 to December 2021. The universe of study included 822 patients who were treated in the hospital during the aforementioned period with lung cancer. The sample at discretion was made up of 276 patients. Results: Prevalence of lung cancer in patients between 61 and 80 years of age, male, passive smokers. The cyto-histological variety with the highest incidence was small cell microcytic carcinoma; debut of this disease in patients in stage IV and with treatment received with radiotherapy and chemotherapy in 100% of the patients. Conclusions: It is a predominant tumor among malignant neoplasms, where timely diagnosis allows treatment in early stages, which favors survival in patients.

Application value of self-pulling and latter transection technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy / 中华消化外科杂志

Objective:To investigate the application value of self-pulling and latter transection (SPLT) technique in double anti-reflux double-tract reconstruction of totally laparoscopic proximal gastrectomy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 103 patients with Siewert type Ⅱ adenocarcinoma of esophagogastric junction in clinical stage Ⅰ-Ⅱ who were admitted to Shanxi Cancer Hospital from January 2018 to January 2020 were collected. There were 65 males and 38 females, aged from 45 to 79 years, with a median age of 59 years. Of 103 patients, 49 cases undergoing totally laparoscopic proximal gastrectomy with double-tract reconstruction of SPLT were assigned into the SPLT group, 54 cases undergoing totally laparoscopic proximal gastrectomy with conventional double-tract reconstruction were assigned into the traditional group. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone inter-view to detect postoperative reflux esophagitis of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and the t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and the Wilcoxon test was used for comparison between groups. Count data were described as absolute numbers or percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Intraoperative situations: the operation time, digestive tract reconstruction time, volume of intraoperative blood loss, the number of inferior mediastinal lymph nodes dissected, cases with auxiliary incisions for the SPLT group were (261±48)minutes, (26±4)minutes, (114±42)mL, 8.0(6.5,9.5), 1, respectively. The above indicators were (244±42)minutes, (30±6)minutes, (118±46)mL, 5.5(4.0,8.0), 9 for the traditional group, respectively. There were significant differences in the digestive tract reconstruction time, the number of inferior mediastinal lymph nodes dissected and cases with auxiliary incisions between the two groups ( t=-3.34, Z=-4.05, χ2=4.72, P<0.05). There was no significant difference in the operation time or volume of intraoperative blood loss between the two groups ( t=1.87, -0.47, P>0.05). (2) Postoperative situations: duration of postopera-tive hospital stay and cases with postoperative complications were (11.5±2.7)days and 4 for the SPLT group, versus (12.5±4.3)days and 9 for the traditional group, showing no significant difference between the two groups ( t=-1.47, χ2=1.68, P>0.05). There were 13 of 103 patients with postopera-tive complications, including 5 cases of left pleural effusion, 4 cases of anastomotic leakage, 2 cases of mild pneumonia, 1 case of incision infection, 1 case of chylous leakage. Four patients had anasto-motic leakage at the esophagojejunostomy, the abdominal esophagus of whom was invaded by more than 1 cm. During the operation, mediastinal drainage tubes were placed through the abdominal wall. The 4 patients were cured after enteral and parenteral nutrition support and adequate drainage, and the remaining patients with complications were cured after symptomatic treatment. (3) Follow-up: of 49 patients in the SPLT group, 43 cases were followed up for (18±4)months. During the follow-up, 1 case showed reflux esophagitis by gastroscopy, with the incidence of 2.33%(1/43). Of 54 patients in the traditional group, 53 cases were followed up for (17±4)months. During the follow-up, 4 cases showed reflux esophagitis by gastroscopy, with the incidence of 7.55%(4/53). There was no significant difference in the incidence of reflux esophagitis between the two groups ( χ2=0.47, P>0.05). Conclusions:SPLT technology is feasible for double anti-reflux double-tract reconstruction of proximal gastrectomy. Compared with traditional double-tract reconstruction of totally laparos-copic proximal gastrectomy, SPLT technology can reduce the auxiliary incisions, increase the number of lower mediastinal lymph nodes dissected, and shorten the digestive tract reconstruction time.

Clinical efficacy of proximal gastrectomy and total gastrectomy in the treatment of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinical efficacy of proximal gastrectomy and total gastrectomy in the treatment of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 170 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Guangdong Provincial People′s Hospital from January 2010 to December 2018 were collected. There were 125 males and 45 females, aged from 30 to 85 years, with a median age of 64 years. Of the 170 patients, 82 cases undergoing proximal gastrectomy were allocated into the proximal gastrectomy group and 88 cases undergoing total gastrectomy were allocated into the total gastrectomy group. Observation indica-tors: (1) surgical and postoperative situations; (2) follow-up and survival; (3) analysis of prognostic factors. Follow-up was conducted using telephone interview and outpatient examination to detect survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. COX proportional hazard model was used for univariate and multivariate analyses. Variables with P<0.1 in univariate analysis were included for multivariate analysis. Results:(1) Surgical and postoperative situations. Cases with surgical approach as transthoracic or thoraco-abdominal approach, transabdominal approach, the operation time, cases with volume of intra-operative blood loss ≤100 mL or >100 mL, cases with length of proximal margin ≤1.5 cm or >1.5 cm, cases with radical surgery outcome as R 0, R 1, R 2, the number of lymph nodes harvest, cases with anastomotic leakage, cases with anastomotic stricture, cases with incision infection, cases with pleural infection or effusion, cases with abdominal infection or ascites were 61, 21, (211±18)minutes, 46, 36, 44, 38, 73, 6, 3, 15(9,22), 5, 2, 2, 4, 2 in the proximal gastrectomy group, respec-tively. The above indicators were 12, 76, (263±15)minutes, 27, 61, 45, 43, 82, 4, 2, 23(18,32), 4, 1, 3, 1, 4 in the total gastrectomy group, respectively. There were significant differences in the surgical approach, operation time, volume of intraoperative blood loss and the number of lymph nodes harvest between the two groups ( χ2=63.94, t=-25.50, χ2=11.19, Z=-5.62, P<0.05). There was no significant difference in the length of proximal margin or radical surgery outcome between the two groups ( χ2=0.11, Z=-0.95, P>0.05) and there was no significant difference in the anastomotic leakage, anastomotic stricture, incision infection, pleural infection or effusion, abdominal infection or ascites between the two groups ( P>0.05). (2) Follow-up and survival. All the 170 patients were followed up for 89(64,106)months. Of the 170 patients, the 5-year overall survival rates were 43.8% and 35.5% of the Siewert type Ⅱ and Ⅲ AEG patients, respectively, showing no significant difference between them ( χ2=0.87, P>0.05). Of the patients with Siewert type Ⅱ AEG, the 5-year overall survival rates were 41.7% and 54.3% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=1.05, P>0.05). Of the patients with Siewert type Ⅲ AEG, the 5-year overall survival rates were 31.3% and 37.5% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=0.33, P>0.05). The 5-year overall survival rates were 39.0% and 44.2% in the proximal gastrectomy group and the total gastrectomy group, respectively, showing no significant difference between the two groups ( χ2=0.63, P>0.05). Of the patients in TNM stage Ⅰ, stage Ⅱ, stage Ⅲ, the 5-year overall survival rates were 65.3%, 36.3%, 27.1% in the proximal gastrectomy group, versus 83.3%, 48.0%, 39.7% in the total gastrectomy group, showing no signifi-cant difference between the two groups ( χ2=0.02, 1.50, 1.21, P>0.05). (3) Analysis of prognostic factors. Results of univariate analysis showed that pathological N staging, degree of tumor differen-tiation and radical surgery outcome were related factors influencing prognosis of AEG patients ( hazard ratio=1.71, 1.70, 2.85, 95% confidence interval as 1.16-2.60, 1.15-2.50, 1.58-5.14, P<0.05). Results of multivariate analysis showed that pathological N staging and radical surgery outcome were independent factors influencing prognosis of AEG patients ( hazard ratio=1.55, 2.18, 95% confidence interval as 1.05-2.31, 1.18-4.02, P<0.05). Conclusions:There is no significant difference in the prognosis of Siewert type Ⅱ and Ⅲ AEG patients undergoing proximal gastrectomy or total gastrectomy. Proximal gastrectomy can be used for the treatment of advanced Siewert type Ⅱ and Ⅲ AEG.

Progress on surgical treatment in gastric cancer / 国际外科学杂志

There are high burden of disease including a high incidence, relatively high proportion of late stage when diagnosed and poor overall prognosis in China regarding to the diagnosis and treatment of gastric cancer. Surgery remains as the major treatment for gastric cancer. Based on the latest guidelines, endoscopic surgery or gastrectomy is performed for early gastric cancer, and the standard surgery for locally advanced gastric cancer is D2 lymphadenectomy. Besides, this article will discuss about other research hotspots, such as expansion of lymph node dissection in selected patients, construction methods of adenocarcinoma of esophagogastric junction, especially Siewert type Ⅱ, minimally invasive techniques (laparoscopic gastrectomy and robotic gastrectomy), the surgical treatment for elderly patients with gastric cancer will be discussed also.

Analysis of influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the influencing factors and regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 185 Siewert type Ⅱ and Ⅲ AEG patients in two medical centers (113 cases in Changzhi People's Hospital Affiliated to Changzhi Medical College and 72 cases in Heji Hospital Affiliated to Changzhi Medical College) from January 2017 to January 2022 were collected. There were 143 males and 42 females, aged (64±8)years. Patients underwent radical resection of AEG combined with inferior mediastinal lymph node dissection. Observation indicators: (1) clinicopathological charac-teristics of Siewert type Ⅱ and Ⅲ AEG patients; (2) analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG; (3) regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparsion between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Clinicopathological characteristics of Siewert type Ⅱ and Ⅲ AEG patients. Pathologic staging as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ, degree of tumor invasion as stage T1, T2, T3 and T4, length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were found in 30, 61, 75, 7, 3, 41, 79, 50, 101, 46, 18, 8 cases of the Siewert type Ⅱ and Ⅲ AEG patients without inferior mediastinal lymph node metastasis, respectively, versus 0, 2, 10, 0, 0, 0, 5, 7, 4, 3, 2, 3 cases of the Siewert type Ⅱ and Ⅲ AEG patients with inferior mediastinal lymph node metastasis, showing a significant differences between them ( Z=?2.21, ?2.49, ?2.22, P<0.05). (2) Analysis of influencing factors for inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. Results of univariate analysis showed that pathological staging, depth of tumor invasion and length of esophageal invasion were related factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=2.48, 3.26, 2.03, 95% confidence intervals as 1.02?6.01, 1.21?8.80, 1.18?3.51, P<0.05). Results of multivariate analysis showed that depth of tumor invasion and length of esophageal invasion were independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG ( odds ratio=4.01, 2.26, 95% confidence interval as 1.35?11.96, 1.26?4.06, P<0.05). The inferior mediastinal lymph node metastasis probability of AEG patients with the length of esophageal invasion >3 cm and ≤4 cm was 9.47 times that of AEG patients with the length of esophageal invasion ≤1 cm. (3) Regularity of inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The number of inferior mediastinal lymph nodes including No.110, No.111 and No.112 dissected in 185 patients of Siewert type Ⅱ and Ⅲ AEG were 127, 50 and 27. The number of lymph nodes dissected and the number of metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 69, 4, 42, 4, 4, 1, 12, 4 and 23, 0, 17, 0, 7, 2, 3, 0, respectively. There were significant differences in metastatic lymph nodes in No.110 and No.111 of patients with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm ( χ2=8.45, 7.30, P<0.05). Of the 185 patients of Siewert type Ⅱ and Ⅲ AEG, the ratio of cases with inferior mediastinal lymph nodes metastasis was 6.49%(12/185). The ratio of inferior mediastinal lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 3.81%(4/105), 6.12%(3/49), 10.00%(2/20), 27.27%(3/11), respectively. The ratio of No.110 lymph nodes metastasis in cases with length of esophageal invasion ≤1 cm, >1 cm and ≤2 cm, >2 cm and ≤3 cm, >3 cm and ≤4 cm were 2.86%(3/105), 6.12%(3/49), 5.00%(1/20), 27.27%(3/11), respectively, showing a significant difference among them ( χ2=8.26, P<0.05). Conclusions:Depth of tumor invasion and length of esophageal invasion are independent influening factors affecting inferior mediastinal lymph node metastasis in Siewert type Ⅱ and Ⅲ AEG. The rate of inferior mediastinal lymph node metastasis increases with the increase of the length of esophageal invasion.

Surgical strategies for adenocarcinoma of esophagogastric junction under the era of mini-invasive surgery / 中华消化外科杂志

With the continuous update and improvement of minimally invasive techni-ques, laparoscopic and robotic surgeries have increased significantly for the surgical treatment of adenocarcinoma of esophagogastric junction (AEG). Due to the anatomical particularity and biolo-gical characteristics of Siewert type Ⅱ AEG, surgical approach, the range of resection, lymph node dissection and digestive tract reconstruction cannot be unified at present, which is also the contro-versy between gastrointestinal surgery and thoracic surgery. Laparoscopic minimally invasive techni-que may be more conducive to lower mediastinal lymph node dissection. Laparoscopic surgery of AEG after neoadjuvant chemotherapy is safe and feasible. Robotic surgery may be the direction of minimally invasive surgery in the future. The authors mainly investigate strategies of minimally invasive surgery for the surgical treatment of AEG, and look forward to more clinical trials on Siewert type Ⅱ AEG surgery to guide surgical treatment.

SAMHD1 inhibits PD-L1 expression in lung adenocarcinoma cells / 国际肿瘤学杂志

Objective:To explore the correlation between SAM domain and HD domain-containing protein 1 (SAMHD1) and programmed death-ligand 1 (PD-L1) expression in lung adenocarcinoma.Methods:The expression of SAMHD1 in lung adenocarcinoma and its effect on prognosis were analyzed by online database GEPIA and Kaplan-Meier Plotter. The expression of SAMHD1 in lung adenocarcinoma cell lines was detected by quantitative real-time PCR (qPCR) and Western blotting. SAMHD1 gene was silenced in H1975, H1299 and LLC cells by small interfering RNA transfection and lentivirus infection, respectively. The mRNA and protein expression levels of PD-L1 in lung adenocarcinoma cells of control group, siSAMHD1-1 group and siSAMHD1-2 group were detected by qPCR and Western blotting. The membrane PD-L1 level was detected by flow cytometry. A mouse lung adenocarcinoma xenograft model was constructed. The PD-L1 levels in the tumor tissues of control group and shSAMHD1 group were detected by immunohistochemistry. Cell proliferation activities of the control, siSAMHD1-1 and siSAMHD1-2 groups were detected by CCK-8 assays.Results:The GEPIA database results showed that the mRNA expression of SAMHD1 in lung adenocarcinoma was lower than that in normal lung tissue (4.81±0.90 vs. 5.99±0.76, t=20.67, P<0.001) . The median overall survival time of patients with high SAMHD1 expression was significantly longer than that of patients with low SAMHD1 expression (109.0 months vs. 87.7 months, χ2=26.83, P=0.002) . The relative mRNA expression levels of SAMHD1 in A549, PC9, H1299 and H1975 cells were 1.00±0.02, 0.75±0.05, 3.49±0.19 and 7.25±0.38 ( F=589.00, P<0.001) , and the relative protein expression levels were 1.00±0.06, 0.34±0.07, 1.67±0.22 and 2.11±0.63 ( F=15.79, P=0.001) . In H1975 cells, the relative mRNA levels of PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 1.00±0.00, 1.54±0.26 and 2.89±0.13 ( F=102.30, P<0.001) , and the relative protein expression levels were 1.00±0.01, 1.50±0.10 and 1.52±0.33 ( F=6.65, P=0.030) . In H1299 cells, the relative mRNA levels of PD-L1 in the three groups were 1.00±0.08, 1.63±0.03 and 2.14±0.03 ( F=368.80, P<0.001) , and the relative protein levels of PD-L1 were 1.00±0.07, 1.88±0.35 and 2.05±0.38 ( F=10.66, P=0.011) . The expression level of PD-L1 in the siSAMHD1-1 and siSAMHD1-2 groups was higher than that in the control group (all P<0.05) . Flow cytometry results showed that in H1975 cells, the fluorescence intensity of membrane PD-L1 in the control, siSAMHD1-1 and siSAMHD1-2 groups were 246.83±27.59, 325.60±8.00 and 308.93±7.60 ( F=17.56, P=0.003) , and in H1299 cells, the fluorescence intensity of membrane PD-L1 in the three groups were 959.00±6.25, 1 084.33±7.64 and 1 085.33±21.22 ( F=86.74, P<0.001) . The fluorescence intensity of PD-L1 in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . In xenograft mouse model, the H-SCORE of PD-L1 in the shSAMHD1 group was higher than that in the control group (7.99±1.10 vs. 4.49±0.43, t=5.13, P=0.007) . The proliferative activities of H1975 cells in the control group, siSAMHD1-1 group and siSAMHD1-2 group at 72 h were 0.50±0.02, 0.75±0.05 and 0.73±0.06 ( F=25.01, P=0.001) . The proliferative activities of H1299 cells in the three groups at 72 h were 0.80±0.01, 1.00±0.04 and 0.93±0.07 ( F=13.90, P=0.006) . The cell proliferation activity in the siSAMHD1-1 group and siSAMHD1-2 group was higher than that in the control group (all P<0.05) . Conclusion:SAMHD1 silencing induces PD-L1 expression in lung adenocarcinoma.

Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy / 中华胃肠外科杂志

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

Experience and thoughts on digestive tract reconstruction after radical resection of adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

In the surgical treatment of adenocarcinoma of the esophagogastric junction (AEG), the scope of lymph node dissection, surgical approach selection, extent of tumor resection and digestive tract reconstruction have always been controversial, with the digestive tract reconstruction in AEG facing many challenges especially. The digestive tract reconstruction is related to the extent of resection. At present, the digestive tract reconstruction after total gastrectomy includes Roux-en-Y anastomosis, jejunum interposition and its derivatives. According to different reconstruction methods, they can be divided into tube anastomosis, linear anastomosis and manual anastomosis. Anti-reflux digestive tract reconstruction after proximal gastrectomy mainly includes esophagogastric anastomosis, interposition jejunum and double channel anastomosis. At present, double channel anastomosis is the most common reconstruction method in China. Based on the concept of interposition tubular stomach and reconstruction of gastric angle for anti-reflux, we propose "Giraffe" anastomosis, which moves artificial fundus and His angle downward to retain more residual stomach, showing good gastric emptying and anti-reflux effect. In this paper, combined with our clinical experience and understanding, we discuss the selection and technical key points of digestive tract reconstruction methods in AEG, and suggest that composite anti-reflux mechanism design may be the development trend of anti-reflux reconstruction in the future. The composite mechanism includes the retention of gastric electrical pacemaker in greater curvature of the middle part of gastric body to increase the emptying capacity of residual stomach, the reconstruction of gastric fundus and His angle anti-reflux barrier, and the establishment of an interposition tubular stomach acting as a buffer zone in Giraffe construction, and so on.

Safety and feasibility of intrathoracic modified overlap esophagojejunostomy in laparoscopic radical resection of Siewert type Ⅱ adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

Objective: The study aimed to investigate the safety and feasibility of intrathoracic modified overlap method in laparoscopic radical resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Methods: A descriptive case series study was conducted. The clinical data of 27 patients with Siewert type II AEG who underwent transthoracic single-port assisted laparoscopic total gastrectomy and intrathoracic modified overlap esophagojejunostomy in Guangdong Provincial Hospital of Chinese Medicine from May 2017 to December 2020 were retrospectively analyzed. The intrathoracic modified overlap esophagojejunostomy was performed as follows: (1) The Roux-en-Y loop was made; (2) The jejunum side was prepared extraperitoneal for overlap anastomosis; (3) The esophagus side was prepared intraperitoneal for overlap anastomosis; (4) The overlap esophagojejunostomy was performed; (5) The common outlet was closed after confirmation of anastomosis integrity without bleeding; (6) A thoracic drainage tube was inserted into the thoracic hole with the diaphragm incision closed. The intraoperative and postoperative results were reviewed. Results: All 27 patients were successfully operated, without mortality or conversion to laparotomy. The operative time, digestive tract reconstruction time and esophageal-jejunal anastomosis time were (327.5±102.0) minute, 50 (28-62) minute and (29.0±7.4) minute, respectively. The blood loss was 100 (20-150) ml. The postoperative time to flatus and postoperative hospital stay were (4.7±3.7) days and 9(6-73) days, respectively. Three patients (11.1%) developed postoperative grade III complications according to the Clavien-Dindo classification, including 1 case of anastomotic fistula with empyema, 1 case of pleural effusion and 1 case of pancreatic fistula, all of whom were cured by puncture drainage and anti-infective therapy. Conclusions: The intrathoracic modified overlap esophagojejunostomy is safe and feasible in laparoscopic radical resection of Siewert type II AEG.

Advantages and disadvantages of transthoracic approach for adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

Adenocarcinoma of the esophaogastric junction (AEG) has anatomical characteristics of spanning two organs and anatomical sites. Thoracic surgery and gastrointestinal surgery aim at the safe resection margin of esophagus, the scope of lower mediastinal lymph node dissection and whether transthoracic surgery will increase complications. However, there are great differences and controversies in the surgical approach, surgical method, lymph node dissection and extent of resection of AEG. For Siewert II AEG via abdominal mediastinal approach, due to the limitation of exposure and the difficulty of operation, it is difficult to acquire a satisfactory proximal resection margin, and very difficult to dissect the inferior mediastinal lymph nodes. The transthoracic approach can provide adequate exposure, reduce the difficulty of operation, obtain satisfactory resection margin of esophagus and allow lower mediastinal lymph node dissection, which may bring better prognosis. Although transthoracic approach may increase the incidence of pulmonary infection, the standard development of thoracoscopic technology will overcome the disadvantage of transthoracic approach for Siewert II AEG.

Current status and progression of minimally invasive surgery after neoadjuvant therapy for adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

The number of minimally invasive surgery (MIS) for adenocarcinoma of esophagogastric junction (AEG) has been increasing year by year. The key technical points such as surgical approach, lymph node dissection and GI tract reconstruction have gradually reached their maturity. With the emergence of proofs of evidence-based neoadjuvant therapy, neoadjuvant chemotherapy or neoadjuvant radiochemotherapy for advanced AEG is also gradually accepted by most surgeons and oncologists. European scholars have previously started researches on MIS after neoadjuvant therapy for esophageal cancer and AEG. Domestic scholars also raise practical suggestions on the application of neoadjuvant therapy for AEG via the cooperation between gastrointestinal and thoracic surgeons, demonstrating the trend in standardization and individualization. But there is still no consent to the indication of MIS after neoadjuvant therapy. Furthermore, there is also a lack of the standardization of technical points for MIS, GI tract reconstruction, short- and long-term outcomes. Such associated problems have been the hot controversy and exploration in recent years. This article describes current progress of neoadjuvant therapy for AEG, current status of MIS after the neoadjuvant therapy in Europe, America, East Asia, including China, and related researches plus future prospects, hoping for better clinical outcomes.

Management of anastomotic leakage after laparoscopic surgery for adenocarcinoma of esophagogastric junction / 中华胃肠外科杂志

The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing at home and abroad. Laparoscopic surgery has gradually become the main means of surgical treatment of this kind of tumor. However, due to the special anatomical position of the tumor, the high position away from the broken esophagus and the narrow space in the mediastinum, laparoscopic anastomosis has the characteristics of difficult anastomosis and high anastomosis position. There is a high risk of anastomotic leakage after operation, which may cause serious consequences. Early identification of anastomotic leakage and unobstructed drainage by various means are the key to treatment. With the development of endoscopic technology, endoscopic methods such as covered stent and vacuum-assisted closure further improve the treatment efficacy. As a salvage measure, surgical treatment can achieve good treatment outcome, while accompanied by risk of complications and mortality, so we must strictly grasp the indications.