BACKGROUND:Gastric cancer (GC) is one of the most common malignant tumor worldwide. Metastasis is leading cases of cancer-related death of GC. It has been found that N7-methylguanosine (m7G) modifications play an important role in cancer. However, the role of m7G modifications within mRNA and its "writer" METTL1 and WDR4 in tumors, particularly GC, has not been revealed. METHODS:RT-qPCR, WB and IHC were used to detect the expression of METTL1 and WDR4 in GC cells and tissues. Function-based experiments were performed using METTL1-WDR4 knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and nude mice models. Mechanistically, RNA-seq, MeRIP-seq, MeRIP-qPCR, western blot, dot blot, co-IP, ChIP and IHC stainings were performed. RESULTS:METTL1 and WDR4 were upregulated in GC patients. High expression of METTL1 and WDR4 were associated with poor prognosis. Silencing METTL1-WDR4 inhibited GC cell migration and proliferation in vitro and vivo. Mechanistically, METTL1-WDR4 can enhance the mRNA stability of PIK3C2B and AKT by promoting their m7G levels, which leading the overexpression of p-AKT. Interestingly, we also found that on the one hand, the transcription factor YY1 can promote the mRNA transcription expression of METTL1 and WDR4 at the same time, and on the other hand, METTL1-WDR4 can promote YY1 expression by increasing the level of m7G. This regulation presents positive feedback. Above all, METTL1 and WDR4 ultimately up-regulate the level of m7G and promote the malignant progression of GC. CONCLUSIONS:These findings suggest that METTL1-WDR4 might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for GC treatment by regulating m7G level.
Objective:To investigate the short-term outcomes of totally robotic surgical system and robotic surgical system assisted radical gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 290 patients who under-went robotic surgical system radical gastrectomy for gastric cancer in the First Affiliated Hospital of Army Medical University from January 2018 to November 2021 were collected. There were 208 males and 82 females, aged 58 (range, 24?84)years. Of the 290 patients, 125 patients undergoing totally robotic surgical system radical gastrectomy combined with reconstruction of digestive tract were divided into the totally robot group, and 165 patients undergoing robotic surgical system radical gastrectomy combined with a small midline incision-assisted reconstruction of digestive tract were divided into the robotic-assisted group. Observation indicators: (1) surgical and postoperative situations; (2) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the non-parameter rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical and postoperative situations. The operation time, volume of intraoperative blood loss, length of incision, duration of postoperative analgesic using, time to postoperative gastric tube removal, time to postoperative initial water intake, time to postoperative first anal flatus, duration of post-operative hospital stay were (246±43)minutes, (104±51)mL, 4(range, 3?6)cm, (2.2±0.5)days, 36(range, 10?112)hours, 62(range, 32?205)hours, 63(range, 18?138)hours, 8(range, 6?50)days in patients of the totally robot group, versus (296±59)minutes, (143±87)mL, 6(range, 3?13)cm, (3.6±0.7)days, 42(range, 12?262)hours, 90(range, 18?262)hours, 80(range, 16?295)hours, 9(range, 6?63)days in patients of the robotic-assisted group, showing significant differences in the above indicators between the two groups ( t=8.04, 4.42, Z=?13.98, t=18.46, Z=?5.47, ?5.87, ?6.14, ?4.04, P<0.05). (2) Post-operative complications. Cases with systemic related complications and cases with pulmonary infection were 7 and 4 in patients of the totally robot group, versus 31 and 16 in patients of the robotic-assisted group, showing significant differences in the above indicators between the two groups ( χ2=10.86, 4.68, P<0.05). Further analysis showed that there were significant differences in age ≥60 years, body mass index ≥25 kg/m 2, tumor diameter ≥3 cm, TNM staging as stage Ⅲ of cases with postoperative complications between the totally robot group and the robotic-assisted group ( odds ratio=0.44, 0.17, 0.40, 0.31, 95 confidence interval as 0.20?1.00, 0.03?0.88, 0.18?0.89, 0.11?0.84, P<0.05). Conclusion:Totally robotic surgical system radical gastrectomy for gastric cancer is safe and feasible with advantages of minimal trauma and quick recovery, especially for patients as age ≥60 years, body mass index ≥25 kg/cm 2, tumor diameter ≥3 cm and TNM stage Ⅲ in complication controlling.
外科住院医师规范化培训(简称住培)和课程思政的融合是毕业后医学教育的新课题,具有极为重要的意义.针对外科住培带教特点和融入课程思政的难点,结合外科住培融入课程思政的现状与存在的不足,剖析实现度不高的根源,思考解决核心问题的关键,提出外科住培融入课程思政的 3 种方式:利用教学活动融合课程思政,利用临床技能培训传递课程思政,利用临床带教示范课程思政.以探索外科住培融入课程思政教育的有效切入点、科学呈现方式和全新教学内容,探究外科住培融入课程思政直击人心的可行性.以期在向住院医师传授专业知识技能的同时,进行全方位人文素质培养,落实"立德树人"的教育方针,实现毕业后医学教育中课程知识传承与思政教育同向同行,为国家培养出德才兼备的高素质医学人才.
Objective: Robotic surgery has been increasingly used worldwide owing to its advanced features. However, the significant benefits of robotic total gastrectomy (RTG) over laparoscopic total gastrectomy (LTG) have yet to be demonstrated. We conducted a prospective cohort study to compare the safety and efficacy of robotic and laparoscopic total gastrectomy (LTG) with D2 lymphadenectomy for AGC. Methods: Between March 26, 2018 and July 30, 2021, 155 patients between 18 and 80 years of age with locally advanced gastric cancer (cT2-4a, N0/+, MO) were enrolled. The perioperative outcomes within 30 days after surgery were compared between the RTG (n = 69) and LTG (n = 73) groups on a per-protocol (PP) basis. Postoperative complications were evaluated according to the Clavien-Dindo classification. Results: The overall postoperative morbidity rate was 21.74% in the RTG group and 28.77% in the LTG group with no significant difference (P = 0.44), RTG was associated with a lower incidence of pneumonia (4.35% vs. 15.07%, P = 0.047). No mortality was observed in either group. There was no significant difference in the total operative time (284.48 vs. 271.73 min, P = 0.171), but RTG was associated with a lower estimated volume of blood loss (110 vs. 150 ml, P < 0.001) and more total retrieved lymph nodes (LNs) (41.36 vs 35.1, P = 0.019), more extraperigastric LNs (14.91 vs. 12.19, P = 0.024) and more LNs in the suprapancreatic areas (14.68 vs. 11.82, P = 0.017). The laboratory data (amylase, inflammatory, Albumin and T lymphocyte levels) of the RTG group were better than those of the LTG group. Conclusion: According to the results of this prospective cohort study, for patients with locally advanced gastric cancer, Robotic surgery has advantages over laparoscopic surgery for radical total gastrectomy with D2 lymphadenectomy performed by well-trained doctors.
Purpose: The objective of this study was to explore the risk factors for anorectal dysfunction after intersphincteric resection in patients with low rectal cancer.Methods: A total of 251 patients who underwent intersphincteric resection from July 2014 to June 2020 were included in this study, for which the Kirwan's grade, Wexner score, and anorectal manometric index were used to evaluate the anorectal function and other parameters including demographics, surgical features, and clinical and pathological characteristics. These parameters were analysed to explore the potential risk factors for anorectal function after intersphincteric resection.Results: In the 251 included patients, 98 patients underwent partial intersphincteric resection, 87 patients underwent subtotal intersphincteric resection, and 66 patients underwent total intersphincteric resection. There were 53 (21.1%) patients who had postoperative complications, while no significant difference was observed between the three groups. Furthermore, 30 patients (45.5%) in the total intersphincteric resection group were classified as having anorectal dysfunction (Kirwan's grade 3–5), which was significantly higher than that in the partial intersphincteric resection group (27.6%) and subtotal intersphincteric resection group (29.9%). The mean Wexner score of patients that underwent total intersphincteric resection was 7.9, which was higher than that of patients that had partial intersphincteric resection (5.9, p = 0.002) and subtotal intersphincteric resection (6.4, p = 0.027). The initial perceived volume was lower in the total intersphincteric resection group than in the partial and subtotal intersphincteric resection groups at 1, 3, and 6 months after intersphincteric resection. In addition, the resting pressure, maximum squeeze pressure, and maximum tolerated volume in the total intersphincteric resection group were worse than those in the partial and subtotal groups at 3 and 6 months after intersphincteric resection. Univariate and multivariate analyses suggested that an age ≥65, total intersphincteric resection, and preoperative chemoradiotherapy were independent risk factors for anorectal dysfunction (P = 0.023, P = 0.003, and P = 0.008, respectively). Among the 66 patients who underwent total intersphincteric resection, 17 patients received preoperative chemoradiotherapy, of which 12 patients (70.6%) were classified as having anorectal dysfunction.Conclusion: The current study concluded that age ≥65, total intersphincteric resection, and preoperative chemoradiotherapy were risk factors for anorectal dysfunction after intersphincteric resection. The morbidity of anorectal dysfunction after total intersphincteric resection for patients who received preoperative chemoradiotherapy was relatively high, and the indication should be carefully evaluated.
Background The robotic surgical system has several technical advantages over laparoscopic instruments. The technical feasibility and safety of robotic gastrectomy (RG) for gastric cancer have been reported by increasing number of studies. However, the long-term survival and recurrence outcomes after RG for locally advanced gastric cancer (AGC) have seldom been reported. This study aimed to compare long-term oncologic outcomes for patients with locally AGC after RG or laparoscopic gastrectomy (LG). Methods This study comprised 1170 patients underwent RG or LG, respectively, for locally AGC between March 2010 and February 2017. The primary outcome was the 3-year disease-free survival (DFS). The secondary endpoint included 3-year overall survival (OS) and recurrence patterns. One-to-one propensity score matching (PSM) was performed to reduce confounding bias. The outcomes were compared in PSM cohort. Results After PSM, a well-balanced cohort of 816 patients (408 in each group) were included in the analysis. The 3-year DFS rate was 76.2% in the robotic group and 70.1% in the laparoscopic group (P = 0.076). The 3-year OS rates was 76.7% in the robotic group and 73.3% in the laparoscopic group (P = 0.246). In the subgroup analyses for potential confounding variables, neither 3-year DFS nor 3-year OS survival were significantly different between the two groups (all P > 0.05). The two groups showed similar recurrence patterns within 3 years after surgery (P > 0.05). Conclusion For patients with locally AGC, RG can result in comparable long-term survival outcomes without an increase in recurrence rate.
Background Whether laparoscopic gastrectomy is suitable for patients with serosa-invasive gastric cancer remains controversial. We performed this study to evaluate the short- and long-term outcomes after laparoscopic gastrectomy compared with after open gastrectomy. Methods We retrospectively analyzed 906 consecutive patients with serosa-invasive gastric cancer from January 2004 to December 2014 in our center, who underwent laparoscopic gastrectomy or open gastrectomy with D2 lymphadenectomy. After propensity score matching, 334 patients were included in each group. Surgical conditions and short- and long-term results were compared. Results Laparoscopic gastrectomy was associated with less estimated blood loss and longer operation time, while the number of harvested lymph nodes was not significantly different between laparoscopic gastrectomy and open gastrectomy. Patients who underwent laparoscopic gastrectomy had an earlier time to first flatus, first diet, and first ambulation and were discharged earlier. Overall and pulmonary postoperative complication rates were lower in the laparoscopic gastrectomy group. With a minimum follow-up of 60 months, the 5-year overall survival was 39.3% in the laparoscopic gastrectomy group and 34.3% in the open gastrectomy group, and the 5-year disease-free survival was 36.4% in the laparoscopic gastrectomy group and 32.7% in the open gastrectomy group. Laparoscopic gastrectomy was associated with better 5-year overall survival in patients aged ≥60 years. The overall recurrence rates and patterns were not significantly different between the 2 groups. Conclusion Laparoscopic gastrectomy is an alternative surgical approach for patients with serosa-invasive gastric cancer in terms of short-term outcomes and long-term survival, and it might be more advantageous for certain populations.
In this study, we investigated the incidence and risk factors for postoperative complications after robotic gastrectomy (RG) in patients with gastric cancer. A total of 817 patients who underwent RG for gastric cancer between March 2010 and August 2019 were analyzed retrospectively. Postoperative complications were categorized according to the Clavien–Dindo classification, and possible risk factors were evaluated. Among 817 patients who underwent RG, overall, severe, local and systemic complication rates were 13.8, 4.2, 7.0 and 6.9%, respectively. Multivariable analysis revealed that an age of 70 years or older (P < 0.001) and multiorgan resection (P = 0.031) were independent risk factors for the occurrence of overall complications. Multivariable analysis showed that an age of 70 years or older (P = 0.005) and surgeons’ experience ≤ 25 cases (P = 0.004) were independent risk factors for severe complications. Regarding local complications, an age of 70 years or older (P < 0.001), multiorgan resection (P = 0.010) and surgeons’ experience ≤ 25 cases (P = 0.005) were identified as independent risk factors. An age of 70 years or older (P < 0.001), a BMI of 25 or higher (P = 0.045) and the presence of comorbidity (P = 0.029) were identified as independent risk factors for systemic complications. The present study demonstrated that RG is a safe and feasible procedure for the treatment of gastric cancer, and it has an acceptable postoperative morbidity. Elderly patients and insufficient surgeon experience were two major risk factors for the occurrence of complications following RG. We suggest that surgeons choose patients in good condition during their RG learning phase to reduce learning-associated morbidity.
Objective:To investigate the short-term outcomes of Da Vinci robotic versus laparoscopic and open surgery for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 404 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent radical gastrectomy in the First Hospital Affiliated to Army Medical University from January 2009 to April 2019 were collected. There were 331 males and 73 females, aged from 34 to 90 years, with a median age of 62 years. Of the 404 patients, 104 undergoing Da Vinci robotic radical gastrectomy were allocated into robotic group, 205 undergoing laparoscopic radical gastrectomy were allocated into laparoscopic group, and 95 undergoing open radical gastrectomy were allocated into open group. Observation indicators: (1) the propensity score matching conditions and comparison of general data among the three groups after propensity score matching; (2) surgical situations; (3) intraoperative lymph node dissection; (4) postoperative situations; (5) postoperative complications; (6) follow-up. Patients were followed up at postoperative 1 month by outpatient examination and telephone interview to detect survival and severe complications up to June 2019. The propensity score matching was used to perform 1∶2∶1 nearest neighbor matching by SPSS 23.0 and R software 3.6.1 Matchit among the robotic group, laparoscopic group and open group. Measurement data with normal distribution were represented as Mean± SD, and comparison among groups was done using one-way ANOVA analysis. Measurement data with skewed distribution were represented as M (range), and comparison was done using the Kruskal-Wallis H test. Comparison of ordinal data was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison among groups was done using the chi-square test. Results:(1) The propensity score matching conditions and comparison of general data among the three groups after propensity score matching: 312 of 404 patients had successful matching, including 78 in the robotic group, 156 in the laparoscopic group, and 78 in the open group. The age, cases in G1, G2, G3 (histopathological classification) and cases with proximal gastrectomy or total gastrectomy (surgical resection range) before matching were (62.2±1.0)years, 0, 37, 67, 13, 91 in the robotic group, (60.9±8.1)years, 0, 98, 107, 31, 174 in the laparoscopic group, and (58.5±9.8)years, 1, 32, 62, 27, 68 in the open group, showing significant differences among the three groups ( F=4.269, 6.356, χ2=10.416, P<0.05). The above indicators after matching were (61.2±10.8)years, 0, 28, 50, 12, 66 in the robotic group, (60.7±8.0)years, 0, 56, 100, 25, 131 in the laparoscopic group, and (60.7±8.4)years, 0, 25, 53, 18, 60 in the open group, showing no significant difference among the three groups ( F=0.074, 0.379, χ2=2.141, P>0.05). (2) Surgical situations: the surgical time, volume of intraoperative blood loss, length of surgical incision, length of proximal margin after matching were 300.0 minutes(range, 188.0-420.0 minutes), 137.5 mL(range, 50.0-400.0 mL), 6.0 cm(range, 3.0-12.0 cm), 2.5 cm(range, 1.5-5.5 cm) in the robotic group, 276.0 minutes(range, 180.0-400.0 minutes), 150.0 mL(range, 40.0-800.0 mL), 6.0 cm(range, 3.0-12.0 cm), 3.0 cm(range, 1.0-5.0 cm) in the laparoscopic group, and 244.5 minutes(range, 125.0-461.0 minutes), 200.0 mL(range, 55.0-800.0 mL), 20.0 cm(range, 18.0-25.0 cm), 2.0 cm(range, 1.0-5.5 cm) in the open group, showing significant differences among the three groups ( χ2=27.619, 30.069, 179.367, 11.560, P<0.05). (3) Intraoperative lymph node dissection: the number of lymph node dissected, the number of lymph node dissected in the first station, the number of diaphragmatic and periesophageal lymph node dissected were 30.5(range, 10.0-70.0), 18.0(range, 6.0-42.0), 4.0(range, 0-13.0) in the robotic group, 29.0(range, 12.0-79.0), 19.0(range, 6.0-47.0), 5.0(range, 0-15.0) in the laparoscopic group, and 29.0(range, 18.0-58.0), 18.0(range, 12.0-38.0), 5.0(range, 0-8.0) in the open group, showing no significant difference among the three groups ( χ2=3.676, 1.014, 0.827, P>0.05). The number of lymph node dissected in the second station, the number of lymph node dissected in the superior pancreatic region, the number of No.110 lymph node dissected, the number of No.111 lymph node dissected after matching were 9.0(range, 2.0-30.0), 9.0(range, 2.0-30.0), 1.0(range, 0-4.0), 0(range, 0-3.0) in the robotic group, 6.5(range, 0-25.0), 7.0(range, 0-25.0), 0(range, 0-3.0), 0(range, 0-4.0) in the laparoscopic group, and 6.5(range, 0-19.0), 6.5(range, 0-19.0), 0(range, 0-1.0), 0(range, 0-1.0) in the open group, showing significant differences among the three groups ( χ2=19.027, 24.368, 19.236, 11.147, P<0.05). (4) Postoperative situations: the time to first flatus, time to initial out-of-bed activities, duration of postoperative hospital stay, treatment expenses after matching were 3 days(range, 2-5 days), 2 days(range, 1-4 days), 9 days(range, 5-20 days), 10.6×10 4 yuan [range, (5.4-18.0)×10 4 yuan] in the robotic group, 3 days(range, 2-8 days), 2 days(range, 1-7 days), 9 days(range, 6-56 days), 8.6×10 4 yuan[range, (5.7-40.8)×10 4 yuan] in the laparoscopic group, and 4 days(range, 2-10 days), 4 days(range, 2-10 days), 11 days(range, 8-41 days), 8.4×10 4 yuan[range, (5.8-15.2)×10 4 yuan] in the open group, showing significant differences among the three groups ( χ2=28.487, 95.069, 39.443, 83.899, P<0.05). (5) Postoperative complications: the incidence of overall complications, incidence of severe complications (Clavien-Dindo classification ≥grade 3), incidence of gastrointestinal complications, incidence of incisional complications, incidence of respiratory complications, incidence of infection were 21.8%(17/78), 5.1%(4/78), 10.3%(8/78), 1.3%(1/78), 7.7%(6/78), 2.6%(2/78) in the robotic group, 21.8%(34/156), 7.1%(11/156), 5.1%(8/156), 1.3%(2/156), 11.5%(18/156), 3.8%(6/156) in the laparoscopic group, and 29.5%(23/78), 6.4%(5/78), 9.0%(7/78), 2.6%(2/78), 14.1%(11/78), 2.6%(2/78) in the open group, showing no significant difference among the three groups ( χ2=1.913, 0.321, 2.394, 0.866, 1.641, 0.335, P>0.05). (6) Follow-up: 312 patients after propensity score matching were follow up at postoperative 1 month. During the follow-up, 2 cases with severe complications died after discharge. No severe complication such as obstruction of input or output loop, dumping syndrome was found in the other 310 patients. Conclusions:The Da Vinci robotic radical gastrectomy is safe and feasible for locally advanced Siewert type Ⅱ and Ⅲ AEG. Compared with laparoscopic and open radical gastrectomy, Da Vinci robotic radical gastrectomy has more advantages in the number of lymph node dissected in the second station (especially in the superior pancreatic region).
Background: We aimed to evaluate the association between the vascular endothelial growth factor (VEGF) gene +936C>T polymorphism and digestive system tumors using a meta-analysis. Methods: Studies of the association between the VEGF+936C>T polymorphism and digestive system tumors published before December 2019 were searched in PubMed, EMBASE, Web of Sciences, the Chinese Biological and Medical Database (CBM), and the China National Knowledge Infrastructure (CNKI). The odds ratio and the corresponding 95% confidence interval were used as the effect indicators. A meta-analysis of original data was performed with different genetic models using the Stata 13.0 software. The reliability of the association was evaluated using the heterogeneity test, sensitivity analysis, false-positive report probability (FPRP), and bias test. Results: This meta-analysis included 37 publications with a total of 8568 digestive system tumor patients and 10,870 cases in the control populations. The overall combined analyses showed that the VEGF+936C>T gene polymorphism was significantly correlated with digestive system cancer susceptibility with the T allele increasing the risk of digestive system cancers. A stratified analysis based on ethnicity showed that the VEGF+936C>T gene polymorphism significantly increased the risk of digestive system tumors in both Asian and Caucasian populations. Additional stratified analyses based on tumor type showed that the VEGF +936C>T gene polymorphism was associated with colorectal cancer, oral cancer, and esophageal cancer. The sensitivity analysis (p < 0.2) and FPRP results also confirmed the reliability of these associations. Conclusions: This meta-analysis supported previous findings that the VEGF +936C>T gene polymorphism is significantly associated with an increased risk of the development of digestive system malignant tumors. This association still requires large-scale epidemiological studies for further validation.
Colorectal cancer (CRC) causes high morbidity and mortality worldwide, and noninvasive gut microbiome (GM) biomarkers are promising for early CRC diagnosis. However, the GM varies significantly based on ethnicity, diet and living environment, suggesting varied GM biomarker performance in different regions. We performed a metagenomic association analysis on stools from 52 patients and 55 corresponding healthy family members who lived together to identify GM biomarkers for CRC in Chongqing, China. The GM of patients differed significantly from that of healthy controls. A total of 22 microbial genes were included as screening biomarkers with high accuracy in additional 46 cases and 40 randomly selected healthy adults in Chongqing (area under the receive-operation curve (AUC) = 0.905, 95% CI 0.832-0.977). The classifier based on the identified 22 biomarkers also performed well in the cohort from Hong Kong (AUC = 0.811, 95% CI 0.715-0.907) and French (AUC = 0.859, 95% CI 0.773-0.944) populations. Quantitative PCR was applied for measuring three selected biomarkers in the classification of CRC patients in independent Chongqing population containing 30 cases and 30 controls and the best biomarker from Coprobacillus performed well with high AUC (0.930, 95% CI 0.904-0.955). This study revealed increased sensitivity and applicability of our GM biomarkers compared with previous biomarkers significantly promoting the early diagnosis of CRC.
Minimally invasive surgery experienced a rapid development in the past thirty years, of which the laparoscopy has been widely used in gastrointestinal surgery. Lymph node dissection is one of the difficulties of laparoscopic radical resection of gastric cancer. The lymph node dissection along the left gastroepiploic vessels is a difficult part, which usually causes bleeding and splenic injury. This article mainly introduce the indications, contraindications, surgical preparations, the difficulties and techniques during the lymph nodes dissection when the operator stood on the left side of the patients, and perioperative complications of lymph nodes dissection along the left gastroepiploic vessels.
Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. This prospective cohort study enrolled 46 patients with stage I–III gastric cancer that underwent resection with curative intent. Sixty resected tumor samples and 296 plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. ctDNA detection was correlated with clinicopathologic features and post-operative disease-free (DFS) and overall survival (OS). ctDNA was detected in 45% of treatment-naïve plasma samples. Primary tumor extent (T stage) was independently associated with pre-operative ctDNA positivity ( p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 95%CI, 7.991–61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916–21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.
e14571 Background: Identifying locoregional gastric cancer patients who are at high risk for relapse after resection could facilitate early intervention. By detecting molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict post-operative relapse in several cancers. Here, we aim to evaluate MRD detection by ctDNA and its association with clinical outcome in resected gastric cancer. Methods: This prospective cohort study enrolled 46 patients with stage I-III gastric cancer that underwent resection with curative intent. Resected tumor samples and plasma samples were obtained for targeted deep sequencing and longitudinal ctDNA profiling. Results: ctDNA was detected in 45% of treatment-naïve plasma samples. T stage was independently associated with pre-operative ctDNA positivity (p = 0.006). All patients with detectable ctDNA in the immediate post-operative period eventually experienced recurrence. ctDNA positivity at any time during longitudinal post-operative follow-up was associated with worse DFS and OS (HR = 14.78, 955 CI, 7.991-61.29, p < 0.0001 and HR = 7.664, 95% CI, 2.916-21.06, p = 0.002, respectively), and preceded radiographic recurrence by a median of 6 months. Conclusions: In locoregional gastric cancer patients treated with curative intent, these results indicate that ctDNA-detected MRD identifies patients at high risk for recurrence and can facilitate novel treatment intensification studies in the adjuvant setting to improve survival.
Backgrounds and purpose: Robotic surgery has been applied in gastric carcinoma over a decade. Although a series of studies were performed to investigate the short-term outcomes of robot-assisted gastrectomy, few papers were in view of long-term outcomes. The current study was aimed to explore the oncological outcomes of robotic gastrectomy for gastric cancer patients. Methods: A total of 606 gastric cancer patients who underwent robot assisted gastrectomy during March 2010 through March 2017, were enrolled in this research. The clinicopathologic characteristics, surgical procedures along with follow-up information and prognostic factors were recorded in detail. The disease-free survival and overall survival rates were tested by Kaplan-Meier analysis. Results: All the patients underwent the robotic surgery including 15 proximal gastrectomies, 403 distal gastrectomies, 169 total gastrectomies and 19 remnant gastrectomies. Fifiy-six (9.24%) patients were lost in the follow-up process (3-87 months, a media of 42 months). There were 119 recurrences observed, including 55 local recurrences, 51 peritoneal metastasis and 13 distant metastasis. The 3-year disease-free survival and overall survival were 73.60% and 74.24%, while the 5-year disease-free survivorship and overall survival rates were 68.73% and 69.33%. The 5-year overall survival rates grouped based on TNM stage were 96.58% for IA, 88.16% for IB, 87.03% for I IA, 80.62% foll6 58.50% for IIIA, 48.62% for IIIB, 45.32% for IIIC and 17.03% for IV. Conclusion: Robot-assisted gastrectomy is a valuable procedure for gastric cancer patients. Beside its feasibility and safety, it reveals an acceptable long-term clinical outcome.
Chronic inflammation is associated with all stages of cancer development. Moreover, a proinflammatory microenvironment resulted from chronic inflammation is considered to be an essential component of cancer. Interleukin-23 (IL-23) is a general proinflammatory factor; and is involved in tumor-associated inflammation in gastric cancer (GC). However, the direct effect of IL-23 on GC cells has been rarely reported. The aim of the study was to clarify the direct role of IL-23 in regulating GC progression, and to identify the underlying mechanism. In this study, Positive expression of IL-23R was observed in GC tissues and cell lines by using immunohistochemistry or immunofluorescence. In western blots, the expression of IL-23R was higher in GC tissues compared with adjacent normal tissues. Furthermore, IL-23R positive GC tissues were closely related with larger tumor size and worse T stage and clinical stage. By performing in vitro experiments, we found that IL-23 binding to its receptor promoted the migration and invasion of BGC-823 cells in vitro. Moreover, IL-23 induced the activation of STAT3 and epithelial-to-mesenchymal transition (EMT) in BGC-823 cells. Knocking down STAT3 in BGC-823 cells attenuated the effect of IL-23 on EMT and cell migration and invasion. Taken together, our study has firstly demonstrated the positive expression of IL-23R in human GC tissues and cell lines. IL-23 binding to its receptor promotes the migration and invasion of GC cells by inducing EMT through the STAT3 signaling pathway. This work provides a new mechanism for the oncogenic role of IL-23 on GC progression.
Objective: To explore the effect of different drugs on postoperative hyperalgesia in general anesthesia patients. Methods: A randomized controlled trial was conducted to detect the hyperalgesia of patients with general anesthesia from PubMed, Embase, Medline, CNKI and Wanfang databases. The visual analogue scale (VAS) assessment of hyperalgesia patients after anesthesia was extracted as well as the effects of various prophylactic agents on the incidence of side effects in postoperative patients. Multivariables meta-analysis was performed by Stata 14.0 software to explore the effectiveness of various drugs in preventing postoperative hyperalgesia and side effects. Results: A total of 12 articles included 983 patients were included in this study. The results showed that the selected drugs had a certain effect on the prevention of hyperalgesia after anesthesia, but the incidence of side effects caused by dexmedetomidine and diazepam was the lowest. Conclusion: From the prevention of hypersensitivity after anesthesia and reduce the incidence of postoperative side effects, it is recommended that the clinical preferred dextromethorphan, followed by the selective application of diazepam or flurbiprofen ester.
Substantial evidence suggests that the epithelial-mesenchymal transition (EMT) phenotype is associated with the invasive characteristics of cancer stem cells (CSCs),which possess an EMT phenotype that may predominate in tumor invasion and metastasis. However, the mechanisms for the generation and regulation of these CSCs have not been clearly defined. As hypoxia and EMT-related factors may have important functions in EMT-like CSCs, the aim of this study was to investigate the effects of hypoxia on these cells. CSCs were established from the gastric cancer cell lines MGC-803 and SGC7901, and the relationship between hypoxia and EMT-like CSCs was investigated in gastric cancer. After hypoxia treatment, some gastric CSCs exhibited a marked increase in hypoxia-inducible factor-1α (HIF-1α)expression and increased migration and invasion capabilities compared with the normoxic control. These CSCs were defined by activation of the mesenchymal cell marker Vimentin and by inhibition of the epithelial cell marker E-cadherin. Our analyses also show that HIF-1α was responsible for activating EMT via increased expression of the transcription factor Snail in gastric CSCs. Moreover, inhibition of Snail by shRNA reduced HIF-1α-induced EMT in gastric CSCs. The results demonstrated that hypoxia-induced EMT-like CSCs rely on HIF-1αto activate Snail, which may result in recurrence and metastasis of gastric cancer.
Objective To explore the clinical efficacy of single-port Da Vinci robotic surgical system in the radical resection of rectal cancer.Methods The retrospective descriptive study was conducted.The clinical data of one patient with rectal cancer who was admitted to the Southwest Hospital of the Third Military Medical University in June 2017 was collected.The patient underwent the first case of radical resection of rectal cancer with the single-port la Vinci robotic surgical system,and intraoperatively received laparoscopy-assisted digestive tract reconstruction.Observation indicators:(1) intra-and post-operative situations;(2) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to July 2017.Results (1) Intra-and post-operative situations:the patient underwent successful single-port Da Vinci robotic radical resection of rectal cancer.The operation time and volume of intraoperative blood loss were 145minutes and 20 mL,without blood transfusion.The using time of nonsteroidal analgesic drug,time for out-of-bed activity,time to anal exsufflation,time of fluid diet intake and time of pelvic drainage tube removal were 1 day,24hours,48 hours,72 hours and 4 days after operation,respectively.No postoperative complication was detected.Results of postoperative pathological examination:moderate-differentiated rectal adenocarcinoma invaded serosal layer,with negative circumferential margin,negative distal margin of rectum and mesenteric lymph node metastasis (1 of 16 harvested lymph nodes was positive).Pathologic staging was T4aN1M0 (stage Ⅲb).The patient was discharged from hospital at postoperative day 6.(2) Follow-up and survival:the patient was followed up for 1month,with a good survival.Conclusion Single-port Da Vinci robotic surgical system in the radical resection of rectal cancer is safe and feasible,with good short-term outcomes.
Background: Previous researchers have identified that the chemokine interleukin-17 (IL-17) was associated with survival time of patients with gastric cancer, but the roles of its receptors (IL-17R) in gastric cancer remain unknown. Our studies were designed to clarify the function of IL-17RA and to explore their potential role in gastric cancer. Materials and methods: The expression of IL-17RA was determined in primary gastric cancer tissues (n=101) using Real-time RT-PCR, immunohistochemistry, and western blotting. To investigate the functional significance of IL-17RA expression, IL-17RA expression and clinical parameters, multivariate survival was analyzed in patients with gastric cancer. Results: IL-17RA was overexpression in gastric cancer tissues compared with adjacent normal tissues (P<0.05). The elevated expression level of IL-17RA was observed correlated significantly with tumor progression (P=0.003), Lymphatic invasion (P=0.019), lymphoid nodal status (P=0.001), distant metastasis (P<0.001) of gastric cancer patients, TNM stage (P=0.0013) and was one of the independent prognostic factors for patient's overall survival. Conclusions: These results demonstrated that the expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis of gastric cancer. The IL-17-IL-17RA signaling mechanism may be a potential novel target.