[Long-term outcomes of laparoscopic gastrectomy for locally advanced gastric cancer with serosa-invasion].

Objective: To evaluate the long-term outcomes and prognostic factors of locally advanced gastric cancer with serosa-invasion. Methods: This study is a retrospective cohort study. The clinical and pathological data of 495 patients with locally advanced gastric cancer with serosa-invasion who underwent laparoscopic radical gastrectomy in Department of General Surgery, the First Hospital Affiliated to Army Medical University from October 2012 to October 2018 was analyzed retrospectively. There were 356 males and 139 females with an age (M(IQR)) of 59 (16) years (range: 18 to 75 years). Observation indicators included postoperative results and long-term prognosis. The survival curve was drawn by the Kaplan-Meier method. Univariate and multivariate prognostic analysis was performed using the Cox proportional hazards model. Results: Among the 495 patients, a total of 57 patients (11.5%) were lost to follow-up, with a follow-up time of 89 (40) months (range: 23 to 134 months). The 5-year disease-free survival rate (DFS) and the 5-year overall survival rate (OS) were 56.0% and 58.2%, respectively. The 5-year DFS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 60.5%, 51.6%, 33.3%, respectively. The 5-year OS for patients with stage ⅡB, ⅢA, ⅢB, ⅢC were 71.2%, 62.2%, 54.1%, 39.3%, respectively. Multivariate analysis showed that age >65 years (DFS: HR=1.402, 95%CI: 1.022 to 1.922, P=0.036; OS: HR=1.461, 95%CI: 1.057 to 2.019, P=0.022), lymph node dissection number less than 25 (DFS: HR=1.348, 95%CI: 1.019 to 1.779, P=0.036; OS: HR=1.376, 95%CI: 1.035 to 1.825, P=0.028), pathological stage Ⅲ (DFS: HR=2.131, 95%CI: 1.444 to 3.144, P<0.01; OS: HR=2.079, 95%CI: 1.406 to 3.074, P<0.01), and no postoperative chemotherapy (DFS: HR=3.127, 95%CI: 2.377 to 4.113, P<0.01; OS: HR=3.768, 95%CI: 2.828 to 5.020, P<0.01) were independent prognostic factors for the decrease in DFS and OS rates. Conclusions: Laparoscopic radical gastrectomy for locally advanced gastric cancer with serosa-invasion could achieve satisfactory long-term oncological outcomes. More lymph node dissection and standardized postoperative adjuvant chemotherapy are expected to further improve the prognosis of patients with locally advanced gastric cancer with serous invasion after laparoscopic radical surgery.

[The present situation and future development for robotic gastrointestinal surgery in China].

After ten years of development in robotic gastrointestinal surgery in China, although the number of robot surgical systems is small, the growth rate of robotic gastrointestinal surgery has grown up. Robotic gastrointestinal surgeons used the advantage of robots to perform a variety of surgical procedures with high complexity and technical difficulty, and achieved satisfactory clinical results. The robotic gastrointestinal surgeons in China are also paying attention to clinical research while carrying out robotic surgery. The number of international publications on robotic gastrointestinal surgery is at the forefront. However, the development of a robotic surgical system with independent intellectual property rights, and the further standardization of robotic gastrointestinal surgery indications and operational procedures are issues that urgently need to be addressed.

[Application of da Vinci robotic surgical system in radical resection of gastric and colorectal cancer: a report of 647 cases].

OBJECTIVE: To investigate the feasibility and safety of robotic-assisted radical resection of gastric and colorectal cancer. METHODS: The clinical data of 305 patients who received radical resection of gastric cancer and 342 patients who received radical resection of colorectal cancer both accomplished by the da Vinci robotic surgical system at the Southwest Hospital, Third Military Medical University from March 2010 to December 2014 were retrospectively analyzed. In gastric cancer group, radical total gastrectomy were performed in 69 cases, proximal gastrectomy in 11 cases, distal gastrectomy in 213 cases and 12 cases of gastric stump cancer.In colorectal cancer group, radical resection of the right colon were performed in 6 cases, left colon in 4 cases, transverse colon in 1 case, sigmoid colon low anterior resection procedure in 24 cases, rectal low anterior resection procedure in 222 cases, abdominoperineal excision procedure in 79 cases and Hartmann procedure in 6 cases. RESULTS: All cases had robotic-assisted radical resection successfully. In gastric cancer group, the mean operation time was (226±62) minutes, the mean blood loss was (125±77) ml, the mean number of harvested lymph nodes was 34±10; the mean time for patients taking normal activity was (3.2±1.5) days, the mean time for gastrointestinal function recovery was (3.1±1.3) days, the mean time for taking liquid food was (3.5±1.9) days. The mean hospitalization was (7.9±3.7) days postoperatively. In colorectal group, the mean operation time was (181±61) minutes, the mean blood loss was (110±93) ml, the mean number of harvested lymph nodes was 19±6; the mean time for patients taking normal activity was (2.9±1.5) days, passage of first flatus was (2.7±1.7) days. The mean hospitalization was (7.1±1.6) days postoperatively. Surgical complications occurred in 28 patients (9.2%) of gastric cancer group and 30 patients (8.8%) of colorectal cancer group, all the cases were recovery before leaving hospital with non-operation therapy. The short-term efficiency was obvious. CONCLUSION: Robotic-assisted radical resection for gastric and colorectal cancer is a feasible and safe surgical procedure combined the minimal trauma and fast recovery.

[Robotics should be the mainstream surgical approach in gastrointestinal surgery].

The clinical application of robotic gastrointestinal surgery has made significant progress during the past 20 years. Increasing research have demonstrated that the robotic gastrointestinal surgery is safe and feasible, with the advantages in lymph node dissection, precise manipulation in narrow space, intraoperative suturing, and achieves satisfactory clinical outcomes. However, it also face challenges such as high costs, lack of high quality studies, and limited intelligent level. With the advancement of more high-quality evidence-based medical research and the development of new intelligent surgical robots, the robotic gastrointestinal surgery will be further standardized. We believe that the robotic surgery will become the mainstream of surgical treatment for gastrointestinal surgery.

Effects of CO(2) pneumoperitoneum on peritoneal macrophage function and peritoneal metastasis in mice with gastric cancer.

BACKGROUND: Whether laparoscopy with CO(2) pneumoperitoneum affects the peritoneal metastasis of gastric cancer is a pressing question. In light of the important impact change in peritoneal macrophage function has on the peritoneal metastasis of gastric cancer, this study investigated the change in peritoneal macrophage function in gastric cancer in the CO(2) pneumoperitoneum environment, as well as its effect on the peritoneal metastasis of gastric cancer. METHODS: An orthotopic transplantation model of murine forestomach carcinoma was established using the 615 mouse line. The mice bearing tumors were randomly divided into four groups (30 mice each group): anesthesia alone, laparotomy, mini-laparotomy, and CO(2) insufflation. After the operation, peritoneal macrophages were collected from 6 mice in each group and cultured. The phagocytosis of neutral red by macrophages and the levels of NO, TNF-α, IL-10, and VEGF produced by macrophages were measured after 12, 24, 48, and 72 h of culture. The remaining mice were observed after 2 weeks for the rate of peritoneal metastasis of forestomach carcinoma cells and the total weight of implanted nodules. RESULTS: In the laparotomy group, 4 mice died intraoperatively and 2 died in the CO(2) insufflation group. The uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the laparotomy group and mini-laparotomy group after 12 h of culture were all significantly higher than those in the anesthesia-alone group (p < 0.05). The corresponding levels in the CO(2) insufflation group after 12 h were all significantly lower than those in the anesthesia-alone group (p < 0.05). There were no significant differences among the four groups at 24, 48, and 72 h after culture. Comparing with those in the laparotomy group, the uptake of neutral red by peritoneal macrophages and the levels of NO, TNF-α, IL-10, and VEGF secreted by peritoneal macrophages in the CO(2) insufflation group were all significantly lower after 12 h of culture (p < 0.05), but did not differ significantly at 24, 48, and 72 h of culture (p > 0.05), and did not differ significantly in the mini-laparotomy group at all the time (p > 0.05). The rate of peritoneal metastasis of mouse forestomach carcinoma was 50% in the laparotomy group, 45.83% in the mini-laparotomy group, and 45.45% in the CO(2) insufflation group; this difference was not statistically significant (p > 0.05). The total weight of implanted nodules of mouse forestomach carcinoma was 1.02 ± 0.38 g in the laparotomy group, 0.97 ± 0.41 g in the mini-laparotomy group, and 0.93 ± 0.45 g in the CO(2) insufflation group, which was not a statistically significant difference (p > 0.05). CONCLUSION: CO(2) pneumoperitoneum neither significantly changes the phagocytosis and cytokine secretion functions of peritoneal macrophages in gastric cancer-bearing mice nor significantly promotes peritoneal metastasis of gastric cancer.

[Future prospect of robotic gastric cancer surgery].

Robotic gastric cancer surgery developed rapidly in recent years and its future prospect has received continuous attention. Compared with traditional laparoscopy, robotic surgery has obvious technical advantages and superior efficacy. Although some problems and deficiencies still exist, robotic gastric cancer surgery will be further popularized with more high-quality evidence-based medicine research and the development of new domestic surgical robots, and therefore bring greater benefits for more patients. We believe that robotic gastric cancer surgery will become the mainstream of minimally invasive surgery for gastric cancer.

[Comparison of clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer].

Objective: To compare the clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer patients. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) 18 to 75 years old; (2) gastric cancer proved by preoperative gastroscopy, CT and pathological results and tumor was suitable for D2 radical distal gastrectomy; (3) postoperative pathological diagnosis stage was T1-4aN0-3M0 (according to the AJCC-7th TNM tumor stage), and the margin was negative; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, and American Association of Anesthesiologists (ASA) grade 1 to 3; (5) no mental illness; (6) able to answer questionnaires independently; (7) patients agreed to undergo laparoscopic distal gastrectomy and signed an informed consent. Exclusion criteria: (1) patients with severe chronic diseases and American Association of Anesthesiologists (ASA) grade >3; (2) patients with other malignant tumors; (3) patients suffered from serious mental diseases; (4) patients received neoadjuvant chemotherapy or immunotherapy. According to the above criteria, clinical data of 200 patients who underwent laparoscopic distal gastrectomy at the Department of General Surgery of the First Affiliated Hospital of Army Medical University from January 2016 to December 2019 were collected. Of the 200 patients, 108 underwent uncut Roux-en-Y anastomosis and 92 underwent Billroth II with Braun anastomosis. The general data, intraoperative and postoperative conditions, complications, and endoscopic evaluation 1 year after the surgery were compared. Besides, the quality of life of two groups was also compared using the Chinese version of the European Organization For Research and Treatment of Cancer (EORTC) quality of life questionnaire-Core 30 (QLQ-C30) and quality of life questionnaire-stomach 22 (QLQ-STO22). Results: There were no significant differences in baseline data between the two groups (all P>0.05). All the 200 patients successfully underwent laparoscopic distal gastrectomy without intraoperative complications, conversion to open surgery or perioperative death. There were no significant differences between two groups in operative time, intraoperative blood loss, postoperative complications, time to flatus, time to removal of gastric tube, time to liquid diet, time to removal of drainage tube or length of postoperative hospital stay (all P>0.05). Endoscopic evaluation was conducted 1 year after surgery. Compared to Billroth II with Braun group, the uncut Roux-en-Y group had a significantly lower incidences of gastric stasis [19.8% (17/86) vs. 37.0% (27/73), χ(2)=11.199, P=0.024], gastritis [11.6% (10/86) vs. 34.2% (25/73), χ(2)=20.892, P<0.001] and bile reflux [1.2% (1/86) vs. 28.8% (21/73), χ(2)=25.237, P<0.001], and the differences were statistically significant. The EORTC questionnaire was performed 1 year after surgery, there were no significant differences in the scores of QLQ-C30 scale between the two groups (all P>0.05), while the scores of QLQ-STO22 showed that, compared to the Billroth II with Braun group, the uncut Roux-en-Y group had a lower pain score (median: 8.3 vs. 16.7, Z=-2.342, P=0.019) and reflux score (median: 0 vs 5.6, Z=-2.284, P=0.022), and the differences were statistically significant (all P<0.05), indicating milder symptoms. Conclusion: The uncut Roux-en-Y anastomosis is safe and reliable in laparoscopic distal gastrectomy, which can reduce the incidences of gastric stasis, gastritis and bile reflux, and improve the quality of life of patients after surgery.

[Effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection for rectal cancer].

Objective: To determine the effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection (LAR) for rectal cancer. Methods: Retrospective cohort study and propensity score matching were conducted. Case inclusion criteria: (1) pathologically confirmed rectal adenocarcinoma; (2) 18 to 80 years; (3) patients with middle to low rectal cancer undergoing laparoscopic LAR; (4) patients staging cT1-4aN0-2M0 or ycT1-4aN0-2M0 after neoadjuvant therapy; (5) the distance of 4-10 cm from tumor low margin to anal verge. Exclusion criteria: (1) abdominal surgery history (except appendicitis, cholecystitis, ectopic pregnancy); (2) anastomosis above the peritoneal reflection; (3) tumor distant metastasis or clinical staging of T4b during surgery; (4) conversion to open surgery; (5) severe incapacitating disease (American Society of Anesthesiologists classification IV or V, ASA). A total of 666 patients with middle to low rectal cancer undergoing laparoscopic LAR in The First Affiliated Hospital of Army Medical University from January 2017 to June 2020 were enrolled. There were 473 males and 193 females with the median age of 59 (18-80) years. Laparoscopic LAR with peritoneum reconstruction was performed in 188 cases (PR group), and laparoscopic LAR without peritoneum reconstruction was performed in 478 cases (NPR group). After 1:1 propensity score matching according to 1:1 based on age, gender, body mass index, TNM staging, ASA classification, intraoperative blood loss, distance from tumor low margin to anal edge, 153 cases were included in each group. Postoperative complications were classified according to Clavien-Dindo classification. Anastomotic leakage was defined and graded according to the International Study Group of Rectal Cancer (ISGRC) criteria. Results: After propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups (all P>0.05), indicating that these two groups were comparable. (1) Operative conditions: All the patients in both groups completed operation successfully. Compared with the NPR group, the PR group had longer operation time [(181.3±60.3) minutes vs. (168.9±51.5) minutes, t=2.185, P=0.029], shorter postoperative median hospital stay [8 (7, 10) days vs. 9 (7, 11) days, Z=-2.282, P=0.022], and the differences were statistically significant (P<0.05). (2) Postoperative complications: The overall morbidity of postoperative complication in PR group and NPR group was 20.3% (31/153) and 24.2% (37/153) respectively, and the incidence of anastomotic leakage was 9.8% (15/153) and 11.1%(17/153) respectively, whose differences were not statistically significant (both P>0.05). Compared with NPR group, PR group had lower morbidity of grade III to IV complications [3.9% (6/153) vs. 11.1% (17/153), χ(2)=5.688, P=0.017] and lower secondary operation rate [1.3% (2/153) vs. 5.9% (9/153), χ(2)=4.621, P=0.032], the differences were statistically significant (both P<0.05). Though PR group had lower incidence of grade C anastomoic leakage [1.3% (2/153) vs. 3.9% (6/153), χ(2)=2.054, P=0.152], but the differences were not statistically significant. (3) Postoperative inflammation: The difference of the procalcitonin level of both PR and NPR groups at postoperative 1-d, 3-d, and 5-d was statistically significant (F=5.222, P=0.010) in time-dependent manner, while the difference was not significant in the interaction effect (P>0.05). No statistically significant differences in the C-reactive protein level between two groups at postoperative 1-d, 3-d, and 5-d were found (all P>0.05). Conclusion: Peritoneum reconstruction in laparoscopic LAR can decrease the morbidity of postoperative complication of grade III to IV and the reoperation rate, and plays an important role in controlling the inflammatory reaction, which has great clinical value.

[Current situation and reflection on the robotic gastric cancer surgery in China].

Robotic gastric cancer surgery in China showed a broad application prospects with the development in the past ten years, but there are also prominent issues, such as low penetration, non-standard operation, and lack of high-quality research. This paper surmarizes the history and present situation, problems and consideration as well as future prospects of robotic gastric cancer surgery in China. The development of robotic gastric cancer surgery in China can be divided into three stages: initial exploratory stage (before 2013, the topics were mainly focused on surgical procedures, safety and feasibility of robotic gastrectomy), stable advancing stage (between 2014 and 2017, the number of centers, cases, types of gastrectomy, and clinical research were increased steadily), and rapid advancing stage (since 2018, the number of centers, cases, and clinical research were increased rapidly). The robotic gastric cancer surgery in China is still in the growth period. We should grasp the development direction of robotic gastrectomy and promote the rapid and favorable development of robotic gastric cancer surgery in China, which can bring benefits for patients.

Long non-coding RNA FTX promotes gastric cancer progression by targeting miR-215.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignant tumors in the world, which is seriously harmful to people's health. The increasing number of studies have shown that long non-coding RNA (lncRNA) is related to the occurrence of gastric cancer. In this study, we aimed at investigating the role of lnc FTX in the occurrence of gastric cancer. MATERIALS AND METHODS: The expression of FTX in gastric cancer patients and gastric cancer cell lines was detected by RT-qPCR. Univariate Kaplan-Meier method was used to analyze the relationship between FTX expression level, clinicopathological parameters and overall survival rate (OS). After transferring si-FTX and overexpression FTX plasmids into MGC-803 and SGC-7901, the expression of miR-215-3p was detected by RT-qPCR, and the changes of cell proliferation and cell cycle were detected by CCK-8 and flow cytometry. In addition, luciferase activity was used to detect whether miR-215-3p combined with FTX and SIVA1. Finally, Western blot (WB) was used to detect the change of SIVA1 protein expression by miR-215 mimic. RESULTS: We found that the expression of FTX in tumor tissues of 71 GC patients was higher than that in paracancerous tissues, and the prognosis of patients with high FTX was poor. The expression of FTX in gastric cancer cells was higher than that in normal human gastric epithelial cells (GES-1). Transferring overexpression plasmid of FTX into gastric cancer cells (MGC-803 and SGC-7901) promoted cell proliferation and the ratio of cells in G0-G1 phase was decreased. Transferring si-FTX to MGC-803 and SGC-7901 led to opposite results. There was a negative correlation between the expression of mi215-3p and FTX in MGC-803 and SGC-7901 gastric cancer cells, and luciferase results showed that mi215-3p could directly bind to FTX and regulate cell growth and cell cycle changes. In addition, luciferase results showed that mi215-3p could bind directly to SIVA1. What's more, RT-qPCR and WB results showed that mi215 mimic could promote the expression of MGC-803, SGC-7901 SIVA1mRNA and protein. CONCLUSIONS: According to these results, this study revealed that the previously neglected FTX-miR2153p-SIVA1 regulatory axis for the regulation of gastric cancer progression, which may be a potential target for the treatment of gastric cancer.

[Long-term efficacy of robotic radical total gastrectomy for gastric cancer and analysis of prognostic factors].

Objective: To analyze long-term outcomes and prognostic factors of gastric cancer patients after robotic radical total gastrectomy. Methods: A retrospective case-control study was conducted. Inclusion criteria: (1) receiving robotic radical total gastrectomy; (2) gastric adenocarcinoma was confirmed by postoperative pathology; (3) no previous history of other malignant tumors; (4) no preoperative chemotherapy or radiation therapy performed. Exclusion criteria: (1) age <18 years old or age >80 years old;(2)distant metastasis before surgery, or palliative surgery; (3) conversion to laparotomy;(4) R1 or R2 resection; (5)emergency surgery; (6) remnant gastric cancer or recurrence; (7)died of severe complications during hospitalization or within 1 month after surgery. Overall survival rates (OS) and disease-free survival rates (DFS) were evaluated using the Kaplan-Meier method. Cox regression analysis was used to identify prognosis factors for overall survival. Results: According to the above criteria, 166 gastric cancer patients who underwent robotic radical total gastrectomy between March 2010 and November 2018 were included in this study. Roux-en-Y reconstruction was performed in all patients. Reconstruction were achieved using extracorporeal method through a minilaparotomy in 149 case and intracorporeal anastomosis in 17 cases. The number of harvested lymph nodes was (34.8±17.5), and the number of harvested lymph nodes at group 2 was (10.1±6.7). The number of patients with lymph node metastasis of group 2 was 73 (44.0%). The median follow-up time was 25 months (range 2-109). There were 55 (33.1%) cases of recurrence during follow-up. The 3- and 5-year overall survival rates were 55.8% and 46.2% respectively. The 3- and 5-year disease-free survival rates were 53.4% and 45.4% respectively. The 5-year overall survival rates grouped based on TNM stage were 78.9% for stage I, 58.5% for stage II, and 37.1% for stage III. The 5-year disease-free survival rates grouped based on TNM stage were 78.9% for stage I, 59.2% for stage II, and 34.6% for stage III. Univariate analysis suggested that TNM stage, the number of harvested lymph nodes and number of harvested lymph nodes at group 2 were associated with overall survival rates (all P<0.05). Multivariate analyses revealed that TNM stage (P<0.001; stage IIIB: HR=5.357, 95%CI:1.182 to 24.275; stage IIIC: HR=11.937, 95%CI: 2.677 to 53.226) and number of harvested lymph nodes at group 2 (P=0.034; 6-10: HR=0.562,95%CI:0.326 to 0.969; >10: HR=0.388, 95%CI: 0.176 to 0.857) were independent prognostic factors for overall survival. Conclusion: The long-term outcomes of robotic radical total gastrectomy were satisfactory. TNM stage and number of harvested lymph nodes at group 2 were independent prognostic factors for overall survival.

[Comparison of clinical efficacy between proximal gastrectomy with double tract reconstruction and total gastrectomy with Roux-en-Y reconstruction for proximal gastric cancer].

Objective: To compare the clinical efficacy of proximal gastrectomy with double tract reconstruction (PG-DT) and total gastrectomy with Roux-en-Y reconstruction (TG-RY) for proximal gastric cancer. Methods: The retrospective study was conducted. Clinicopathological data of 132 patients with proximal gastric cancer confirmed by pathology who underwent PG-DT (n=51) or TG-RY (n=81) by the same surgeon team in Southwest Hospital of Army Military Medical University between January 2006 and December 2016 were collected. Patients with preoperative neoadjuvant therapy, non-R0 resection and non-adenocarcinoma confirmed by pathology were excluded. Observation indicators included intraoperative (operation time and blood loss); postoperative (time to flatus, hospital stay, total complications, metastasis of lymph nodes around distal side of stomach from cases undergoing TG-RY), follow-up (long-term hemoglobin level, incidence of anemia, and survival) parameters. Survival analysis was conducted using the Kaplan-Meier method, and Log-rank test was used to compare survival difference between two groups. Results: No statistically significant differences were found between two groups in the baseline data, including age, gender, BMI, hemoglobin level before operation, postoperative TNM stage, tumor size and histological differentiation between two groups (all P>0.05). There were no significant differences between PG-DT and TG-RY in intraoperative blood loss [200 (200) ml vs. 200 (195) ml, Z=-1.860, P=0.063], time to flatus [(2.7±1.0) days vs. (2.6±1.1) days, t=0.225, P=0.823], postoperative hospital stay [10(3) days vs. 10 (4) days, Z=-0.449, P=0.654] and morbidity of perioperative complications [5.9% (3/51) vs. 8.6% (7/81), χ(2)=0.081, P=0.775]. Compared with the TG-RY group, PG-DT group had longer total operative time [294 (97) minutes vs. 255 (71) minutes, Z=-3.148, P=0.002]. The hemoglobin data of 42 patients with PG-DT and 56 patients with TG-RY were collected 1 year after operation. The incidence of anemia in PG-DT group was lower than that of TG-RY group [64.2%(27/42) vs. 82.1% (46/56), χ(2)=4.072, P=0.045], and PG-DT group had higher level of hemoglobin than TG-RY group [(114.4±16.3) g/L vs. (106.6±15.0) g/L, t=2.435, P=0.017]. There were 4 cases (4/81, 4.9%) with metastasis of lymph nodes around distal side of stomach in TG-RY group. All of these 4 tumors were T4 in depth and were more than 5 cm in diameter. The median follow-up period was 26 (1 to 110) months. One-year, 3-year and 5-year survival rates were 93.2%, 65.3% and 55.0% in PG-DT group, and 85.8%, 63.8% and 47.2% in TG-RY group, respectively without significant difference (χ(2)=0.890, P=0.345). Conclusions: Compared with TG-RY, PG-DT has the same safety and feasibility for proximal gastric cancer. Although the operative time is a little longer than TG-RY, PG-DT has advantages in improving the postoperative hemoglobin level.

[Analysis on the technical characteristics and clinical efficacy of robotic-assisted intersphincteric resection for patients with low rectal cancer].

Objective: To explore the technical characteristics and short-term clinical efficacy of robotic-assisted intersphincteric resection (ISR) for patients with low rectal cancer. Methods: A retrospective cohort study was used. Inclusion criteria: (1) rigid colonoscopy showed lower margin of the tumor ≤5 cm from the anal verge; (2) preoperative rectal MRI or endorectal ultrasound revealed staging T1-2, or T3 patients receiving concurrent chemoradiotherapy; (3) patients less than 70 years old with good function of anal sphincter before surgery; (4) no synchronous multiple primary carcinoma, and no distant metastasis; (5) the method of operation was agreed by the patient. Exclusion criteria: (1) T4 stage tumors; (2) sphincter dysfunction before operation; (3) recurrent tumors; (4) lower edge of tumors beyond the dentate line; (5) death due to non-rectal cancer during follow-up and unsatisfactory follow-up data. The clinical data of 21 patients with low rectal cancer meeting inclusion criteria undergoing robotic-assisted ISR at our department from January 2015 to June 2018 were collected. Parameters during and after operation were observed. Anorectal manometry was performed at 3, 6, and 12 months after the operation, and anal function was evaluated at 3, 6, and 12 months after the closure of the stoma by Kirwan classification and Wexner fecal incontinence score. The key steps of the operation are as follows: according to the principle of total mesorectal excision, the robot continued to enter into the levator ani hiatusdistally, and dissectin the sphincter space; according to the scope of sphincter resection, ISRwas divided into partial ISR, subtotal ISR, and total ISR; subtotal and total ISR usually needed to be combined with transanal pathway. The reconstruction of digestive tract was performed by double stapler anastomosis under laparoscope orhand-sewnanastomosis under direct vision, and preventive ileostomy was completed in the right lower abdomen. Results: Of 21 patients, 13 were male and 8 were female with mean age of (57.5±16.3) years. All the patients successfully completed the operation without conversion to laparotomy. Fourteen cases (66.7%) adopted partial ISR through complete transabdominal approach, 6 cases (28.6%) adopted the subtotal ISR through combined transabdominal and transanal approachs, and 1 case (4.8%) adopted the total ISR through the combined transabdominal and transanal approachs. The total operation time was (213.1±56.3) minutes, including (27.3±5.4) minutes for mechanical arm installation and (175.7±51.6) minutes for robotic operation. The amount of intraoperative hemorrhage was (62.8±23.2) ml, and no blood transfusion was performed in any patient. All patients underwent prophylactic ileostomy, and the stoma was closed 3-6 months after the operation. Except one case of anastomotic leakage, all other stomas were closed successfully. The postoperative hospitalization time was (7.6±2.2) days, and time to fluid intake was (3.3±0.9) days. One case of anastomotic leakage, one case of anastomotic stenosis, one case of inflammatory external hemorrhoids and one case of urinary retention occurred after surgery,and all of them were cured by conservative treatment. The mean diameter of tumors was (2.9±1.2) cm, and the number of harvested lymph node was 12.8 ± 3.3. In the whole group, the circumcision margin was negative, the proximal margin was (12.2 ± 2.1) cm, the distal margin was (1.1 ± 0.4) with all negative, and the R0 resection rate was 100%. The results of anorectal manometry showed that the preoperative rest pressure, rectal maximum squeeze pressure, initial sensory volume and maximum tolerated volume were (45.19±8.46) mmHg, (128.18±18.80) mmHg, (44.33±10.11) ml and (119.00±19.28) ml, respectively;these parameters reduced significantly 3 months after operation and they were (23.44±5.54) mmHg, (93.72±12.15) mmHg, (17.72±5.32) ml and (70.44±10.9) ml, respectively. The differences were statistically significant (all P<0.001). The resting pressure and the rectal maximum squeeze pressure returned to preoperative levels 12 months after operation, which were (39.33±6.64) mmHg and (120.58±16.47) mmHg, respectively (both P>0.05), while the initial sensory volume and the maximum tolerated volume failed to reach the preoperative state, which were (30.67±7.45) ml and (92.25±10.32) ml, respectively (both P<0.05). The patients were followed up for (22.1±10.6) months without local recurrence and distant metastasis. Eighteen patients were evaluated for anal function: Kirwan classification was grade I for 6 cases, grade II for 7 cases, grade III for 4 cases, and grade IV for 1 case; Wexner incontinence score was 8.6±0.8; 14 cases had good defecation control. Conclusion: The clinical efficacy of ISR with Da Vinci robot in the treatment of low rectal cancer is satisfactory.

Identification of RIP3, a RIP-like kinase that activates apoptosis and NFkappaB.

The tumor necrosis factor receptor 1 (TNFR1) and the Fas receptor recruit complexes formed by the interactions between RIP kinase, TRADD, FADD and RAIDD - adaptor proteins that contain death domains - which in turn recruit other proteins to initiate signaling [1][2][3][4][5]. To identify proteins associated with the TNF signaling pathway, we performed a yeast two-hybrid interaction screen using RIP as bait. We isolated a kinase, RIP3, which shares homology with the kinase domain of RIP and RIP2 (also known as Rick or CARDIAK). RIP3 could be co-immunoprecipitated with RIP, TRAF2 and TNFR1 in mammalian cells. The carboxy-terminal domain of RIP3, like that of RIP, could activate the transcription factor NFkappaB and induce apoptosis when expressed in mammalian cells. Interestingly, this region shares no significant sequence homology to the death domain of RIP, the caspase-recruiting domain (CARD) of RIP2 [6][7][8] or any other apoptosis-inducing domain. As with RIP and RIP2, the kinase domain of RIP3 was not required for either NFkappaB activation or apoptosis induction. Overexpression of a dominant-negative mutant of RIP3 strongly inhibited the caspase activation but not the NFkappaB activation induced by TNFalpha. Therefore, RIP3 appears to function as an intermediary in TNFalpha-induced apoptosis.

Role of secreted protein acidic in hematogenous metastasis of gastric cancer.

OBJECTIVE: To investigate tumor microenvironment of metastasis (TMEM) and the expression of SPARC (secreted protein acidic and rich in cysteine) in gastric cancer, and their relationships with hematogenous metastasis. PATIENTS AND METHODS: Twenty-six pairs of cases with gastric cancer were enrolled, in which there were 26 cases with distant organ metastases and 26 cases of gastric cancer without organ metastases as controls. TMEM (by double-stained immunohistochemistry) and the expression of SPARC were determined in twenty-six pairs of cases. In addition, we selected 48 patients to detect the expression of SPARC, VEGF (vascular endothelial growth factor), and evaluated TAMs (tumor associated macrophages), MVD (the microvessel density), MPI (microvessel pericyte coverage index), and TMEM in gastric cancer tissues by immunohistochemistry. RESULTS: TMEM count was significantly higher in the metastatic gastric cancer tissues than that in non-metastatic cancer tissues in a case-control study (p<0.01). On the contrary, SPARC expression was lower in the metastatic gastric cancer tissues than that in non-metastatic cancer tissues. TMEM count, TAMs, and MVD were significantly correlated with invasion depth, histological type and TNM stage (p<0.05 or p<0.01). Expression of SPARC and VEGF were significantly correlated with tumor histological types, invasion depth, differentiation and lymph node metastasis of patients (p<0.05). SPARC and VEGF expression in stromal cells of gastric cancer tissues were significantly correlated with TAMs, MVD and MPI (p<0.05). In addition, SPARC expression was significantly inversely correlated with VEGF expression in gastric cancer tissues (p<0.05). CONCLUSIONS: TMEM was detected in initial gastric cancer resection and closely correlated with hematogenous metastasis. Furthermore, SPARC may be involved in gastric cancer metastasis by effecting on tumor microenvironment.

The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms.

Postoperative recurrence and metastasis have crucial roles in the poor prognosis of gastric cancer patients. Previous studies have indicated that gastric cancer originates from cancer stem cells (CSCs), and some investigators have found that a particular subset of CSCs possesses higher metastatic capacity. However, the specific mechanism remains uncertain. In the present study, we aimed to explore the biological functions of the inflammatory cytokine interleukin-17 (IL-17) in gastric cancer metastasis and the distinct IL-17-induced transformation of quiescent gastric CSCs. Our results showed that invasive gastric CSCs were CD26+ and CXCR4+ and were closely associated with increased metastatic ability. The quiescent gastric CSCs, which were CD26- and CXCR4-, were exposed to appropriate concentrations of IL-17; this resulted in the decreased expression of E-cadherin and the increased expression of vimentin and N-cadherin. In addition, the upregulation of IL-17 both in vitro and in vivo resulted in a significant induction of invasion, migration and tumor formation ability in gastric CSCs compared with the control group, which was not treated with IL-17. Further experiments indicated that the activation of the downstream phosphorylated signal transducer and activator of transcription 3 (STAT3) transcription factor pathway was facilitated by IL-17. On the contrary, the downregulation of STAT3 by the specific inhibitor Stattic significantly reversed the IL-17-induced epithelial-mesenchymal transition (EMT)-associated properties of quiescent gastric CSCs. Moreover, tumorigenesis and metastasis were suppressed. Taken together, we suggest that IL-17 is positively correlated with the transformation of quiescent gastric CSCs into invasive gastric CSCs and that targeting IL-17 may emerge as a possible novel therapeutic strategy for gastric cancer.

Effects of dexamethasone treatment on IL-1 receptor mRNA levels in vivo.

Using semiquantitative reverse transcriptasepolymerase chain reaction and Northern analysis, we observed in vivo up-regulation of interleukin-1 (IL-1) RI and IL-1RII mRNA levels in peripheral blood mononuclear cells (PBMCs) and neutrophils (PMNs) from Holstein cattle injected with dexamethasone (0.04 mg/kg). Baseline levels of IL-1RI mRNA were greater than IL-1RII mRNA levels in PBMCs and PMNs before dexamethasone treatment. This is in contrast with the previously reported predominance of IL-1RII in unstimulated human PMNs. IL-1RII mRNA was strongly induced in both bovine PBMCs and PMNs at 24 h and returned to baseline levels by 72 h, after dexamethasone injection. Conversely, the greatest increase in IL-1RI mRNA in PBMCs and PMNs was not detected until 72 h after dexamethasone injection. These data provide evidence for sequential in vivo up-regulation of first IL-1RII mRNA and later IL-1RI mRNA by dexamethasone that is consistent with the anti-inflammatory activity of glucocorticoids.

Regulation of luminol-dependent chemiluminescence and degranulation by bovine neutrophils stimulated with opsonized zymosan.

The purpose of this study was to elucidate likely signal transduction pathways in activated bovine neutrophils, by comparing the effects of various inhibitors on the bovine neutrophil respiratory burst and degranulation in vitro. The protein kinase C(PKC) inhibitors staurosporine, and chelerythine, and the beta-adrenergic receptor antagonist DL-propranolol, markedly inhibited opsonized zymosan (OZ) stimulated luminol-dependent chemiluminescence (LDCL). The G-protein inhibitor pertussis toxin (PT), the protein tyrosine inhibitor genistein, and the calcium channel blocker verapamil also reduced LDCL in a dose-dependent manner. In contrast, the lipoxygenase inhibitor zileuton had only a slight effect, and the cyclooxygenase inhibitor indomethacin had no effect on LDCL. The effects of these inhibitors on degranulation was also examined. Staurosporine, propranolol, and pertussis toxin significantly decreased primary granule (beta-glucosaminidase) release in response to OZ. These inhibitors also significantly reduced both phorbol myristate acetate (PMA)-induced primary and secondary granule (lactoferrin) release. Regulation of secondary granule (lactoferrin) release was complex, as it was significantly depressed by propranolol, enhanced by PT and unaffected by staurosporine. These findings suggest that PKC, beta-adrenergic receptors, G-proteins, protein tyrosine kinase(s) and Ca(2+) uptake, may all be involved in some part of the process of bovine neutrophil activation. Moreover, stimulation of LDCL and degranulation may be mediated through distinct signal transduction pathways.

Regulation of bovine interleukin-1 receptors.

Interleukin-1 is a key player in inflammation and the immune response. The interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL-1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies suggest a dynamic relationship among these receptors and ligands that regulates the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned and sequenced the bovine type I and II interleukin-1 receptors, and has begun to investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI and IL-1RII mRNA levels were upregulated in vitro by various mediators, including dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Conversely, IL-1RI mRNA levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated cattle. These findings suggest that early upregulation of IL-1RII, which is a decoy receptor, may be part of the anti-inflammatory action of glucocorticoids. Our investigations suggest that anti-inflammatory agents increase expression of the biologically inactive IL-1RII, as compared with the biologically active IL-1RI, in bovine leukocytes.

A comparison of the effects of signal transduction inhibitors on oxidative burst and degranulation in IL-I beta stimulated bovine neutrophils.

There is little information available on IL-1 mediated signal transduction in neutrophils from species other than humans. In this study, signal transduction pathway inhibitors were used to compare signaling pathways for the oxidative burst and degranulation in bovine neutrophils stimulated with rBoIL-1 beta. Protein kinase C inhibitors (staurosporine and chelerythine), DL-propranolol, pertussis toxin (PT), genistein and verapamil significantly inhibited rBoIL-1 beta (10 ng/ml) stimulated luminol-dependent chemiluminescence (LDCL) in a dose-dependent manner, while indomethacin and zileuton had no effect. Propranolol significantly decreased both primary and secondary granule release in response to rBoIL-1 beta. Staurosporine enhanced secondary but not primary granule release, and PT increased primary and secondary granule release. In addition, propranolol inhibited the shape change induced by rBoIL-1 beta and zymosan-activated serum, whereas PT markedly decreased the response induced by zymosan-activated serum, but not rBoIL-1 beta. These findings suggest that rBoIL-1 beta stimulation of the oxidative burst, degranulation, and shape change of bovine neutrophils are mediated through distinct signal transduction pathways.