| Section 1:Satety and feasibility of indocyanine green navigated regional lymphadenectomy in laparoscopic gastrectomy for gastric cancerObjective:Indocyanine green(ICG)has been used in laparoscopic and robotic sentinel node navigation surgery(SNNS).Nevertheless,its clinical safety and feasibility remain to be confirmed when ICG is used to map regional lymph nodes(LNs)for improving standardization.Therefore,we aimed at analyzing the clinical safety and feasibility of ICG for mapping regional LNs in laparoscopic gastrectomy for gastric cancer patients.Methods:From January,2019 to December,2019,gastric cancer patients who underwent laparoscopic radical gastrectomy in one group of Cancer Hospital,Chinese Academy of Medical Sciences,were retrospectively studied.Patients were divided into ICG group and conventional surgery group(control group)according to whether ICG was used as reported in medical records.(1)Clinicopathological characteristics were recorded,including gender,age,height and weight,ASA score,surgical procedures,maximum diameter of tumor,differentiation,lymphovascular invasion,perineural invasion,pTNM stage;(2)According to medical records,operation time,estimated blood loss,fever time,evacuation time and hospital stay were recorded.According to follow-up visits and medical records,30-day postoperative complications were recorded.(3)According to medical records and pathological reports,number of LNs dissected(overall,and in each LN station),as well as metastatic status(overall,and in each LN station)were recorded.Data of two groups was compared and non-compliance rate was calculated;(4)According to pathological reports,number of LNs dissected with and without fluorescence,as well as metastatic status,were recorded.Sensitivity,specificity,false negative and false positive rate were calculated when ICG was used to map metastatic LNs.Results:(1)128 patients were finally enrolled,with 52 patients in ICG group and 76 patients in conventional surgery group,respectively.There was no significant difference in clinicopathological characteristic baselines between two groups;(2)There was no significant difference in operation time(182.0±45.7min vs 179.5±48.6min,P=0.772),estimated blood loss(101.2± 176.2ml vs 88.6±93.8ml,P=0.600),fever time(2.3±1.3d vs 2.8±3.1d,P=0.139),evacuation time(3.5±0.9d vs 3.7±1.1d,P=0.139),hospital stay(7.3±2.3d vs 8.4±4.4d,P=0.127),and the incidence of 30-day postoperative complications(2/52 vs 8/76,P=0.167)between ICG and control group;(3)The median number of total LNs harvested in ICG group significantly increased than that in control group(46.5 versus 34,P=0.002),especially in LN stations from 7 to 12(15 vs 10,P<0.001).At LN station 4sb and 7,the median number of LNs retrieved in the ICG group was significantly larger than that in control group.For planned D2 lymphadenectomy cases,total number of LNs in station 11 and 12 was increased when ICG was used.Metastatic LNs harvested did not increase in ICG group.(5)Compared with conventional surgery group,non-compliance rate of LNs retrieval did not decrease in ICG group,while a significant decrease was found in subgroup BMI≥25kg/m2 when hierarchical analysis was done;(6)Fluorescence rate for all LNs was 88.3%.Sensitivity,specificity,false negative and false positive rate were 85.0%,15.0%,11.2%and 88.8%when ICG is used as metastatic LN tracer,respectively.ICG was not a metastasis-specific tracer.Conclusions:ICG navigated regional lymphadenectomy in laparoscopic gastrectomy was safe.Fluorescence rate of all LNs was satisfied.Compared with conventional surgery,ICG application increased total number of LNs retrieval.Non-compliance rate of LNs retrieval might decrease when ICG was used for overweight cases.For advanced stage cases,adequete lymphadenectomy should be done according to guidelines,for ICG was not a metastatic lymph node specific tracer.Relationship between preoperative body mass index and long-term prognosis of resectable gastric cancer patientsObjective:Obesity is associated with cancer mortality,and the malnutrition status of cancer patients may also be related to their long-term prognosis,according to previous studies.However,the relationships between specific BMI groupings and cancer survival are less clear.This retrospective study aimed to investigate the relationship between BMI and long-term survival of gastric cancer patients.Methods:This retrospective study included 2526 patients who underwent radical gastrectomy for resectable gastric cancer from Cancer hospital,Chinese Academy of Medical Sciences between September 2013 and June 2018.The patients were divided into four groups:group A(low BMI,<18.5 kg/m2),group B(normal BMI,18.5-24.9 kg/m2),group C(overweight,25-29.9 kg/m2),and group D(obese,≥ 30kg/m2).(1)Clinicopathological findings were recorded,including gender,age,preoperative weight loss,height and weight,preoperative diabetes,tumor location,maximum diameter of tumor,Borrmann classification,differentiation,lymphovascular invasion,perineural invasion,number of lymph nodes dissected and metastatic status,pTNM stage and 30-day postoperative complications.Survival outcomes were acquired by follow-up visits and medical records.(2)Kaplan-Meier life table method and the log-rank test,Cox proportional hazards models were used to assess the association between the predictor variables and outcomes,according to clinicopathological findings and survival outcomes.Results:(1)Preoperative>5%weight loss was more common in group A(31.1%).With the increase of BMI,the fewer cases of preoperative>5%weight loss there were in each group.Preoperative diabetes was more common in group D(19.6%).With the decline of BMI,the fewer cases of preoperative diabetes there were in each group.Upper-third gastric cancer was more common in group D(41.1%).With the decline of BMI,the fewer cases of upper-third gastric cancer there were in each group.(2)Incidence of 30-day postoperative complications was 9.2%,13.7%,14.0%and 25.0%from group A to group D,respectively.It significantly increased with increasing BMI(P=0.004).(3)The 5-year overall survival rates were 66.4%for group A,75.0%for group B,77.1%for group C,and 78.6%for group D.Significant difference was found among those groups(p=0.039).Strafied analysis suggested that the 5-year overall survival rate was significantly lower in group A than in group C(P=0.008)or group D(P=0.031).In multivariate analysis,relative to a normal BMI value,a BMI of<18.5 kg/m2 was associated with poor survival(hazard ratio:1.558,95%confidence interval:1.125-2.158,P=0.008),rather than higher BMI.Conclusions:Low BMI,but not high BMI,independently predicted poor survival in patients with resectable gastric cancer.High BMI might increase the incidence of 30-day postoperative complications.Section 3:Establishment of gastric signet ring cell carcinoma organoid model for therapeutic screeningObjective:Incidence of gastric signet ring carcinoma subtype is showing an increasing trend,while incidence of gastric cancer has the opposite pattern,globally.For advanced gastric cancer,signet ring cell carcinoma relates to adverse prognosis.There exists controversy in whether or not gastric signet ring cell carcinoma would benefit from neoadjuvant chemotherapy or adjuvant chemotherapy.Up to now,gastric cancer organoid has been established,being an important tool for studying pathogenesis,as well as therapeutic screening.Nevertheless,there is no gastric signet ring cell carcinoma specific organoid model.This study aimed at identifying methods for establishing gastric signet ring cell carcinoma organoid model and enabling individualized therapeutic screening.Methods:(1)Gastric cancer patients who underwent radical gastrectomy in Cancer Hospital,Chinese Academy of Medical Sciences from August,2020 to November,2020 were enrolled in this study.Gastric signet ring cell carcinoma(tumor composed more than 50%of signet ring cells)was defined as the treatment group,while poor differentiated adenocarcinoma(without any of signet ring cells)as the control group.Organoid models were established from tumor tissues,which were acquired from surgical dissected specimens;(2)To verify the morphological homogeneity,successfully established organoids were compared with matched tumor tissues by H&E,immunohistochemistry images;(3)To verify the genetic homogeneity,copy number variations and single nucleotide variants were analyzed from exome sequencing of organoid and matched tumor tissues;(4)IC50 values were calculated from data in experiment of treating organoids with different doses of antineoplastic agents.Results:(1)33 cases of gastric cancer patients were enrolled in this study,of which 12 patient-dervied organoid models were successfully eastablished.Seven gastric signet ring cell carcinoma organoid models were established from 11 signet ring cell carcinoma tissues in all;(2)Strong morphological homogeneity was verified by H&E and immunohistochemistry images of organoids and matched tumor tissues;(3)Gastric cancer organoids re-capitulated copy number variations and single nucleotide variants patterns in matched tumor tissues by exome sequencing;(4)Therapeutic screenng of gastric signet ring cell carcinoma and control group organoids were repeatable.Compared with organoids in the control group,IC50 value of fluorouracil and paclitaxel were higher in tested gastric signet ring cell carcinoma organoid samples,while IC50 value of docetaxel showed an opposite pattern.This organoid model enabled therapeutic screening.Conclusions:This study priliminarily established gastric signet ring cell carcinoma model,enabling therapeutic screening.This model offered an opportunity for potential therapeutic screening in clinical pratice,while its feasibility should be verified by larger sample trials. |
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