Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy / 中华血液学杂志

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Prevalence of colorectal cancer in 2020: a comparative analysis between China and the world / 中华肿瘤杂志

Objective: To demonstrate the disease burden and epidemiological characteristics of colorectal cancer in different regions by analyzing the incidence and mortality data in China and worldwide in 2020. Methods: Estimation of the incidence and mortality data of colorectal cancer were obtained from the GLOBOCAN 2020 database. The incidence, death, age standardized incidence rate (ASIR) and age standardized mortality rate (ASMR) of colorectal cancer in China and 20 regions in the world were compared. The correlation between the Human Development Index (HDI) and ASIR/ASMR was analyzed. Results: In 2020, the number of new cases of colorectal cancer in the world reached 1 931 600, and the number of deaths reached 935 200. The incidence and mortality in all regions of the world continued to rise in the age group above 50 years old. The morbidity and mortality in male were higher than those in female. East Asia ranked the highest number of incidence cases and deaths in the world, which were 740 000 and 360 100 respectively. There were significant differences in incidence and mortality among regions in the world. The highest ASIR and ASMR were observed in Northern Europe (33.61/100 000) and Eastern Europe (14.53/100 000), whereas the lowest ASIR and ASMR were both observed in South-Central Asia (5.46/100 000 and 3.16/100 000). HDI had significant exponential relationship with ASIR (r(2)=0.59, P<0.001) and ASMR (r(2)=0.38, P<0.001). There were 555 500 new cases and 286 200 death cases of colorectal cancer in China, accounting for about 30% of the world and more than 75% of East Asia. The ASIR of China was 24.07/100 000, ranking at the medium level, while the ASMR was 12.07/100 000, ranking at the high level of world. Conclusion: The incidence and mortality of colorectal cancer are highly correlated with HDI. China is one of the countries with the heaviest disease burden of colorectal cancer in the world.

Building world leading surgical oncology for gastric cancer in China / 中华外科杂志

This century has seen significant advances in the treatment and research of gastric cancer in China. Chinese scholars have made a series of key technological breakthroughs in minimally invasive surgery, perioperative treatment and artificial intelligence diagnosis. These world-leading clinical researches have improved treatment outcomes and reduced surgical trauma. Global surveillance of trends in cancer survival 2000-14 reported that survival of gastric cancer in China has significantly improved during the last 20 years. This paper reviews the research history of surgical oncology for gastric cancer in China, summarises the experience and attempts to explore the future direction.

Establishment and data quality control of a multicenter prospective database for prevalence of abdominal complications after gastroenterological surgery / 中华胃肠外科杂志

As the main cause of secondary operation and postoperative death, the incidence of intraperitoneal infectious complications varies significantly in different medical centers in China. Due to the lack of national data, it is not possible to assess and develop appropriate diagnosis and treatment strategies properly. To provide a high-quality data platform for complication registration and clinical research, a multicenter prospective database for the Prevalence of Abdominal Complications After GastroEnterological surgery was established. Based on the Hospital Information System (HIS)of 20 medical centers in China, the electronic case reporting form (e-CRF) listed on the website was used to collect medical information of patients undergoing gastric or colorectal cancer surgery. The data were verified by on-site auditing, and data cleaning was performed by R software. After the data cleaning, the data in the database was checked and evaluated by the principle investigators and data administrators. When all data queries and questions were corrected and answered, the database was locked to establish a multicenter prospective database for postoperative abdominal infectious complications (the PACAGE database). The PACAGE database has rich information resources and high data quality and is a good data platform for complication registration and clinical research.

Comparison of safety of total laparoscopic versus laparoscopic-assisted radical gastrectomy for distal gastric cancer in older patients / 中华胃肠外科杂志

Objective: To compare the effectiveness of total laparoscopic versus laparoscopic-assisted distal gastrectomy and investigate the safety and replicability of total laparoscopic distal gastrectomy in older patients. Methods: This was a retrospective cohort study. The inclusion criteria were as follows: (1) age ≥65 years; (2) malignant gastric tumor diagnosed pathologically preoperatively; (3) Eastern Cooperative Oncology Group performance status score 0-1; (4) Grade I-III American Society of Anesthesiologists physical status; (5) preoperative clinical tumor stage I-III; (6) total laparoscopic or laparoscopic-assisted distal gastrectomy performed; and (7) gastrointestinal tract reconstruction using uncut Roux-en-Y or Billroth-II+Braun procedure. Patients who had received neoadjuvant therapy, undergone conversion to open surgery, or had serious comorbidities or incomplete data were excluded. The clinical data of 129 patients who met the above criteria and had undergone laparoscopic surgery for gastric cancer from January 2012 to December 2021 in the Gastrointestinal Cancer Center in the Beijing Cancer Hospital were analyzed. According to the operation method, the patients were divided into total laparoscopic group and laparoscopic-assisted group. Variables studied comprised: (1) surgical procedure and postoperative recovery; (2) postoperative pathological findings; and (3) postoperative complications. Measurement data with skewed distribution are represented as mean(quartile 1, quartile 3). Comparisons between groups were evaluated using the Mann-Whitney U test. Results: After propensity score matching in a 1:1 ratio, there were 40 patients in the total laparoscopic distal gastrectomy group and 40 in the laparoscopic-assisted distal gastrectomy group. Baseline characteristics did not differ significantly between the two groups (all P>0.05).Compared with the laparoscopic-assisted group, the total laparoscopic group had shorter main incisions (4.1±1.0 cm vs. 8.5±2.8 cm, t=9.375, P<0.001), time to fluid intake [4.0 (3.0, 4.8) days vs. 5.0 (4.0, 6.0) days, Z=2.167, P=0.030], and duration of indwelling abdominal drainage catheter [6.0 (6.0, 7.0) days vs. 7.0 (6.0, 8.0) days, Z=2.323, P=0.020]. Numerical Rating Scale scores on postoperative days 1 and 2 were higher in the total laparoscopic than the laparoscopic-assisted group [2.5 (1.0, 3.0) vs. 1.5 (1.0, 2.0), Z=1.980, P=0.048; 2.0 (1.0, 3.0) vs. 1.0 (1.0, 2.0), Z=2.334, P=0.020, respectively]. However, there were no significant differences between the groups in operation time, intraoperative blood loss, white blood cell count, hemoglobin concentration, or albumin concentration on postoperative day 1, time to ambulation, mean time to bowel movement, postoperative admission to the intensive care unit, length of postoperative hospital stay, or Numerical Rating Scale scores on postoperative day 3 (all P>0.05). There were also no significant differences between the two groups in maximum tumor diameter, pathological tumor type, total number of lymph nodes dissected, or total number of positive lymph nodes (all P>0.05). The incidence of postoperative complications was 15.0% (6/40) in the total laparoscopic group and the laparoscopic-assisted group; these differences are not significant (χ2<0.001, P>0.999). Conclusions: Compared with laparoscopic-assisted radical gastrectomy for distal gastric cancer, total laparoscopic surgery has the advantages of shorter incision, shorter time to fluid intake, and shorter duration of indwelling abdominal drainage catheter in older patients (age ≥65 years). Total laparoscopic radical gastrectomy for distal gastric cancer does not increase the risk of postoperative complications and could therefore be performed more frequently.

Dissection borders of laparoscopic lower mediastinal lymphadenectomy for adenocarcinoma of esophagogastric junction and the quality control / 中华胃肠外科杂志

The lower mediastinal lymphadenectomy is indicated for adenocarcinoma of esophagogastric junction (AEG), while the laparoscopic procedure shows some advantages. According to previous studies and results of IDEAL phase 2a study in our institute, the following structures are recommended as the dissection borders: the upper (cranial) is inferior wall of pericardium and pulmonary ligament; the lower (caudal) is diaphragm hiatus (esophagogastric junction); the front (ventral) is anterior inferior wall of pericardium and diaphragm; the back (dorsal) is anterior wall of aorta; the lateral is mediastinal pleura. The standard of quality control is still under investigation.

Implementation strategy of enhanced recovery after surgery in perioperative management of gastric cancer / 中华胃肠外科杂志

Enhanced recovery after surgery (ERAS) has deeply influenced the clinical practice of surgery, anesthesia and nursing since its inception in 1997. The successful implementation of perioperative ERAS in gastric cancer depends on continually boosting the awareness and acceptance of ERAS among medical staff, carrying out multidisciplinary collaboration, improving patients' compliance and combining key items to the clinical pathways. Future efforts should be made to explore the most appropriate implementation strategy of perioperative ERAS in gastric cancer.

Progress in gastric cancer with positive peritoneal cytology / 中华胃肠外科杂志

Gastric cancer with positive peritoneal cytology is a hotspot in the study of gastric cancer, and its prognosis is poor. Intraperitoneal free cancer cells may be associated with cancer cells migration, invasion and metastasis. Tumor T stage, peritoneal metastasis, lymph node metastasis, low histological differentiation, linitis plastica, adenocarcinoma of esophagogastric junction, and operation are the clinicopathological risk factors of gastric cancer with positive peritoneal cytology. Currently, the acquisition of free cancer cells is mainly through diagnostic laparoscopy combined with peritoneal lavage, and cytopathological examination is gold standard for diagnosis. Its treatment strategies are not in consensus, including preoperative chemotherapy combined with radical resection, postoperative chemotherapy and peritoneal local treatment, which can prolong the survival of patients. At present, postoperative chemotherapy is often used in China, and the best treatment strategies remain to be further studied.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms.@*METHODS@#Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance.@*RESULTS@#BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 μg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB).@*CONCLUSIONS@#BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

Computed Tomography Arteriography for Detecting the Origin of the Inferior Pyloric Artery in Patients with Gastric Cancer

OBJECTIVE: To analyze the detection rate of the inferior pyloric artery (IPA) in patients with gastric cancer by computed tomography arteriography (CTA). MATERIALS AND METHODS: Fifty-four patients (48 males and 6 females; mean age, 59.0 ± 1.5 years) who had undergone radical gastrectomy for gastric cancer from September 2016 to July 2017 at our institution were recruited prospectively. Patients underwent abdominal contrast-enhanced CT scans and CTA imaging reconstruction before the operation. The origin of the IPA in all cases was determined by a radiologist based on CTA images and verified by the surgeon. The accuracy of CTA in diagnosing the origin of the IPA was calculated. Dominant vessels of the origin were analyzed. RESULTS: IPAs were detected by CTA in 51 patients (94.4%). Among these, IPAs originated from the right gastroepiploic artery (RGEA) (24 cases), the gastroduodenal artery (GDA) (4 cases), and the anterior superior pancreaticoduodenal artery (ASPDA) (20 cases). In the remaining 3 cases, the IPAs contained two branches originating from the RGEA and ASPDA, respectively. During surgery, in 2 (3.7%) of the 54 cases of gastric cancer, IPAs could not be detected; the IPAs originated from the RGEA (22 cases), GDA (5 cases), and ASPDA (24 cases). One case had an IPA originating from both the RGEA and the GDA. Finally, the accuracy of CTA in diagnosing the origin artery of the IPA was 85.2% (46/54). CONCLUSION: CTA can detect the origin of the IPA accurately, which can aid surgeons while performing pylorus-preserving operations.

Current treatment status and trends of early gastric cancer in China: analyzed based on the data of China Gastrointestinal Cancer Surgery Union / 中国实用外科杂志

Gastric cancer is one of the most common cancersin China. The proportion of early gastric cancer(EGC) is stillrelatively low in China. The data of China Gastrointestinal Can-cer Surgery Union from 2014 to 2017 can reflect the currentstatus and trends of diagnose and treatment of EGC in China.The union collected data of 134,111 cases of gastric cancer in95 centers in China. The trend analysis was performed with da-ta from centers with at least 3 years data collected. Within allthe patients, the proportion of EGC was 19.7%. The propor-tions of EGC were higher in Zhejiang, Beijing, Jiangsu, Tian-jin, and Shanghai, and were lower in Qinghai, Hainan, InnerMongolia, Yunnan, and Guangxi. The proportion of EGC in-creased from 19.7% in 2014 to 20.9% in 2017. In terms oftreatment, the proportions of endoscopic treatment, laparoscop-ic surgery, and open surgery were 24.3%, 37.7%, and 38.0%.From 2014 to 2017, the proportions of endoscopic treatmentand laparoscopic surgery increased while the proportion ofopen surgery decreased. Among patients received surgery,5.9% of pT1 a patients and 19.6% of pT1 b patients were withlymph node metastasis. In conclusion, the proportion of EGCincreased slightly in China but was still lower than that of Ja-pan and South Korea. Minimally invasive treatment graduallybecome the main treatment method of EGC.

Endoscopic resection and salvage surgery for early gastric cancer / 中国实用外科杂志

Endoscopic resection(ER) is playing an increasingly important role in treatment of gastric cancer. However,many patients received endoscopic resection turned out to be non-curative. Thus, the following treatment after ER is worthy of discussion. Reviewing the recomandations of guidelines published by European Society for Medical Oncology(ESMO), National Comprehensive Cancer Network(NCCN) and Japanese Gastric Cancer Association(JGCA) and relevant articles, and also retrospectively analysis of cases in our center. In conclusion, for patients of eCura-C, surgery is recommended after considering relevant risks. Gastrectomy type and lymph node dissection range may refer to those for early gastric cancer.Further research is needed to predict lymph node metastasis more accurately. With the development of minimal invasive surgery, sentinel node navigation surgery and laparoscopic and endoscopic cooperative surgery will gain more and more attention.

Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation / 北京大学学报(医学版)

OBJECTIVE@#Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China.@*METHODS@#A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital.@*RESULTS@#In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis.@*CONCLUSION@#EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

Establishment of rat osteoarthritis model and the expression of MMP-13 and ADAMTS-5 in cartilage tissue / 局解手术学杂志

Objective To evaluate the feasibility of making the osteoarthritis (OA) model in the medial collateral ligament and the medial meniscus excision in rats,and to explore the mechanism of MMP-13 and ADAMTS-5 protein in the cartilage of rat osteoarthritis models.Methods Forty SD rats were randomly divided into model group(n =30) and sham operation group(n =10).The knee joint OA model was made from the medial collateral ligament of the knee and the medial meniscus,and the sham operation group was sutured after opening the capsule of the knee joint.Rats in the model group were killed at 4,6,and 8 weeks after the operation,and the sham operation group died of the rats at 8 weeks after the operation.The articular cartilage tissue of rats was taken.The expression level of MMP-13 and ADAMTS-5 protein in cartilage tissue was detected by Western blot and immunohistochemistry.Results Cartilage degeneration was observed in the model group 4 weeks after operation,and degeneration was further aggravated at 6 and 8 weeks.There was no significant degeneration in the sham operation group.There was a significant difference in the articular cartilage score between the two groups (P ＜ 0.05).The results of Western blot detection showed that the protein expression of MMP-13 and ADAMTS-5 was low in the sham operation group.The MMP-13 model began to rise for 4 weeks,and continued to rise in the 6th week,and the 8th week was lower than that of the previous one.The protein expression had significant difference in all groups at 4 weeks,6 weeks and 8 weeks (P ＜ 0.05).The ADAMTS-5 model began to rise for 6 weeks,and the expression level was maintained before the model was maintained for 8 weeks.The protein expression at 4 weeks compared to that at 6 weeks and 8 weeks had significant difference(P ＜0.05).The protein expression in rat articular cartilage tissue at 6 weeks and 8 weeks had no significant difference (P ＞ 0.05).The expression trend of immunohistochemical detection protein was consistent with that of Western blot.Conclusion The animal model of OA can be established by using the method of medial collateral ligament dissection and medial meniscectomy.The expression level of MMP-13 and ADAMTS-5 in different stages of OA has changed significantly.Further research is needed to explore its related signaling pathways.

Effect of MicroRNA-199 on Proliferation and Migration of Gastric Carcinoma Cells / 中国医学科学院学报

Objective To detect the expression of microRNA(miR)-199 in gastric carcinoma tissues and cell lines, and further explore the effect and molecular mechanism of miR-199 on the proliferation and migration of gastric carcinoma cell lines. Methods Reverse transcriptase-polymerse chain reaction was used to detect the expression of miR-199 in gastric carcinoma and adjacent normal tissue obtained from 51 patients and in gastric carcinoma cell lines and human gastric epithelial cell line GES-1. The gastric carcinoma cell lines over-expressing and low-expressing miR-199 were established to detect their proliferation and migration abilities. Dual-luciferase reporter assay was performed to detect the regulatory effect of miR-199 on the 3'untranslated region of TBL1XR1. Western blot was used to explore the miR-199-related mechanism. Results The relative expression of miR-199 in gastric carcinoma tissues was significantly lower than that in the adjacent normal tissue (0.2635±0.0303 vs. 1.6700±0.9613, t=13.95, P<0.001). The relative expressions of miR-199 in gastric carcinoma cell lines AGS (0.81, t=9.13, P<0.001), SGC-7901 (0.83, t=8.88, P<0.001), MKN28 (0.58, t=10.80, P<0.001), KATO-3 (0.60, t=10.31, P<0.001), MKN-45 (0.27, t=13.10, P<0.001) were significantly lower than that in the normal gastric cell line GES-1 (2.1). In miR-199 over-expressed cell lines, the cell proliferation and migration significantly decreased as compared with the control group of gastric carcinoma cells (731±13 vs. 345±18, t=24.90, P<0.001), and in miR-199 low-expressed group, the cell proliferation and migration increased compared with the control group of gastric carcinoma cells (257±16 vs. 657±8, t=32.59, P<0.001). Dual-luciferase reporter assay proved that miR-199 directly targeted on the 3' untranslated region of TBL1XR1. Western blot analysis showed that miR-199 inhibited the expression of TBL1XR1. Conclusion The over-expression of miR-199 in gastric carcinoma is associated with the decreased ability of proliferation and migration of gastric carcinoma cells by targeting TBL1XR1.

Clinical characteristics of lymph node metastasis in Siewert type II adenocarcinoma of the gastroesophageal junction / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the pattern of lymph node metastasis (LNM) in advanced Siewert type II adenocarcinoma of the gastroesophageal junction (AGEJ) in order to properly guide lymphadenectomy.</p><p><b>METHODS</b>From January 2009 to Jun 2011, a total of 86 patients with advanced Siewert type II AGEJ underwent radical esophagogastrectomy by thoracic-abdominal incision and two-field lymphadenectomy. The clinical characteristics, pathologic features, LNM, and influence factor of thoracic metastasis were retrospectively analyzed.</p><p><b>RESULTS</b>LNM was observed in 65 of the 86 cases (75.6%). Simple abdominal lymph node metastasis was observed in 49 of the 86 cases (57.0%), simple thoracic lymph node metastasis was 2.3%, and thoracic-abdominal metastasis was 16.3%, with a significant difference between the abdominal and thoracic metastatic patterns. LNM frequency was found in the lymph node groups No. 3, No. 1, No. 7, No. 110, No. 2 and No. 9 (from the highest to the lowest). The incidences of those lymph node metastases were 46.5%, 41.9%, 17.4%, 14.0%, 10.5%, and 5.8%, respectively. Vascular tumor embolus was the only independent factor for thoracic lymph node metastasis.</p><p><b>CONCLUSIONS</b>Abdominal lymph node metastases of advanced Siewert type II AGEJ mainly occur around the proximal stomach and the coeliac trunk. The metastatic rate of distal stomach and splenic perihilar lymph nodes is low, but metastatic rate of the group No.110 lymph nodes is high. The thoracic lymph node metastasis is only correlated with vascular tumor embolus.</p>

Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer.</p><p><b>METHODS</b>Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively.</p><p><b>RESULTS</b>Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05).</p><p><b>CONCLUSION</b>S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.</p>

Application of perioperative imatinib mesylate therapy in initial resectable primary local advanced gastrointestinal stromal tumor at intermediate or high risk / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of perioperative imatinib mesylate (IM) therapy for patients with initial resectable primary local advanced gastrointestinal stromal tumor (GIST) at intermediate or high risk on R0 resection rate and the prognosis.</p><p><b>METHODS</b>Forty-eight above GIST patients between December 2001 and February 2012 were divided into 2 groups: neoadjuvant group (15 cases, pre- and post-operation IM therapy) and adjuvant group (33 cases, post-operative IM therapy). R0 resection rate, complication rate, disease-free survival (DFS) and overall survival (OS) were analyzed and compared between the two groups.</p><p><b>RESULTS</b>The maximal tumor diameter and average tumor diameter were larger in neoadjuvant group as compared to adjuvant group (11.2 cm vs. 7.7 cm, P=0.005; 9.1 cm vs. 6.2 cm, P=0.014). The response rate of preoperative IM therapy was 93.3% (14/15). The R0 resection rate was 86.7% and 84.8% (P=1.000), and the complication rate was 13.3% and 9.1% (P=0.642) in neoadjuvant and adjuvant group respectively. The 3-year DFS was 55% and 41% (P=0.935), and 5-year OS was 83% and 75% (P=0.766) in neoadjuvant and adjuvant group respectively.</p><p><b>CONCLUSIONS</b>Resectable primary local advanced GIST at intermediate or high risk with larger tumor diameter receiving perioperative IM therapy can achieve the same R0 resection rate, complication rate, DFS and OS as the GIST with smaller diameter receiving operation first. Perioperative IM therapy has potential advantage.</p>