Objective:To investigate the application value of antegrade splenic superior region dissection first in laparoscopic total gastrectomy of obesity gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 obesity patients with gastric cancer who underwent laparoscopic total gastrectomy in Renji Hospital of Shanghai Jiaotong University School of Medicine from July 2018 to October 2023 were collected. There were 16 males and 5 females, aged (58±13)years. All 21 patients underwent laparoscopic total gastrec-tomy with antegrade splenic superior region dissection first. Observation indicators: operation time, volume of intraoperative blood loss, laparotomy conversion, intraoperative splenic hemorrhage or gastric hemorrhage, lymph node dissection, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay, postoperative complication. Measure-ment data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:All 21 patients underwent laparoscopic total gastrectomy success-fully, with the operation time of (283±47)minutes, time for splenogastric ligament and vascular manage-ment of (34±12)minutes, volume of intraoperative blood loss of (143±86)mL, and no laparotomy conversion. There was no intraoperative splenic hemorrhage or gastric haemorrhage. The total number of lymph node dissected in 21 patients was 375, with the number of lymph node dissected as (21±9)per case. Time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay in 21 patients were (3.1±0.7)days, (4.0±0.8)days and (10.1±3.0)days, respectively. There were 2 patients with postoperative complications, including 1 case of incision infection and 1 case of lung infection. The 2 patients with postoperative com-plications were recovered and discharged after conservative treatment. There was no death during the postoperative 30 days.Conclusion:The application of antegrade splenic superior region dissec-tion first in laparoscopic total gastrectomy is safe and feasible, which can reduce surgical difficulty.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Totally laparoscopic total gastrectomy is the most comlex procedure in gastric surgery, which involves the entire stomach removal, lymph node dissection and digestive tract recons-truction through minimally invasive techniques, among which laparoscopic esophagojejunostomy is a technological difficulty. Currently, three types of anastomoses are widely used, including stapled anastomosis with circular staplers or linear staplers, and hand suturing, but which is the best and safe anastomosis remains controversial. Based on team experience, the authors review the progress of esophagojejunostomy on stapled anastomosis or hand suturing, promote that how to select an appropriate esophagojejunostomy according to surgeon′s individual technical capabilities, operating habits and patient conditions, strive to achieve the precise and minimally invasive effect with the least trauma for patients.

Due to the particularity of tumor location, the surgery of esophagogastric junc-tion(EGJ) carcinoma needs to meet the safety of negative tumor margin, lymph node dissection and digestive tract reconstruction at the same time, which attracted more and more attention of esopha-gogastric surgeons. The current Siewert and Nishi classifications are based on the tumor epicenter, which is difficult to be accurately evaluated and measured before and during operation, and also lack of significance in determining the surgical methods and approach and lymph node dissection. The authors systematically analyze the limitations of Siewert and Nishi classification, discuss the relationship between esophageal invasion length and mediastinal lymph node metastasis and the role of esophageal invasion length on selection of surgical approach, and propose a modified classi-fication based on esophageal invasion length, including (1) malignant tumors with the upper or lower edge of tumor involving the zone of EGJ are defined as EGJ carcinoma; (2) EGJ carcinoma with the upper edge of tumor located 3.0 cm above the EGJ is classified as type Ⅰ; (3) EGJ carcinoma with the upper edge of tumor located 0?3.0 cm above the EGJ is classified as type Ⅱ; (4) EGJ carcinoma with the upper edge of tumor located 0?2.0 cm below the EGJ is classified as type Ⅲ.

Objective:To investigate the short-term efficacy of laparoscopic total gastrec-tomy with hand-sewn esophagojejunostomy versus Roux-en-Y anastomosis.Methods:The propen-sity score matching and retrospective cohort study was conducted. The clinicopathological data of 159 patients who underwent laparoscopic total gastrectomy in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to July 2021 were collected. There were 107 males and 52 females, aged 63(range, 28?79)years. Of 159 patients, 71 cases undergoing totally laparoscopic total gastrectomy with hand-sewn esophagojejunostomy were allocated into totally laparoscopic group and 88 cases undergoing laparoscopic-assisted total gastrectomy with Roux-en-Y anastomosis were allocated into laparoscopic-assisted group, respectively. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability method. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 159 patients, 112 cases were successfully matched, including 56 cases in the totally laparoscopic group and 56 cases in the laparoscopic-assisted group. Before propensity score matching, age, cases with tumor located in cardia or gastric body in the totally laparoscopic group were 61(range, 30?76)years, 26, 45, respectively. The above indicators in the laparoscopic-assisted group were 65(range, 28?79)years, 50, 38, respectively. There were significant differences in the above indicators between the two groups ( Z=?2.89, χ2=6.43, P<0.05). After propensity score matching, the males and females, age, body mass index, cases of American Society of Anesthesiologists classification Ⅰ, Ⅱ, Ⅲ and Ⅳ, tumor diameter, cases with tumor located in cardia or gastric body, cases in TNM stage Ⅰ, Ⅱ and Ⅲ of patients in the totally laparoscopic group were 40, 16, (62±9)years, (22.7±2.8)kg/m 2, 22, 26, 7, 1, 3.5(range, 0.6?17.0)cm, 24, 32, 22, 9, 25. The above indicators of patients in the laparoscopic-assisted group were 38, 18, (62±10)years, (22.7±3.2)kg/m 2, 19, 32, 5, 0, 4.0(range, 0.6?15.0)cm, 23, 33, 21, 7, 28, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.17, t=?0.09, ?0.04, Z=?0.12, ?0.82, χ2=0.04, Z=?0.42, P>0.05). The elimination of age and tumor location confounding bias ensured comparability between the two groups. (2) Intraoperative and postoperative conditions: after propensity score matching, the total operation time, time of esophagojejunostomy, postopera-tive 24-hour pain numerical score and time to first out-off bed activities were (310±49)minutes, (37±10)minutes, 2.3±0.8 and (2.4±0.7)days for patients in the totally laparoscopic group, versus (344±77)minutes, (44±12)minutes, 3.1±1.2 and (2.9±1.0)days in the laparoscopic-assisted group, showing significant differences between the two groups ( t=?2.85, ?3.05, ?4.20, ?3.10, P<0.05). (3) Perioperative complications: after propensity score matching, 6 cases of the patients in the totally laparoscopic group had Clavien-Dindo grade 2 or higher complications, including 2 cases of anas-tomotic leak, 1 case of anastomotic stenosis, 1 case of pleural effusion, 1 case of abdominal infection and 1 case of intestinal obstruction. The incidence of Clavien-Dindo grade 2 or higher complications was 10.7%(6/56). In the laparoscopic-assisted group, 5 patients had Clavien-Dindo grade 2 or higher complications, including 2 cases of anastomotic leak, 1 case of abdominal infection, 1 case of intestinal obstruction and 1 case of cholangitis. The incidence of Clavien-Dindo grade 2 or higher complications was 8.9%(5/56). There was no significant difference in the incidence of Clavien-Dindo grade 2 or higher complications between the two groups ( χ2=0.10, P>0.05). Patients with anas-tomotic leak were improved after puncture and drainage, secondary surgery and conservative treat-ment, and other complications were improved after symptomatic treatment. Conclusions:Com-pared with Roux-en-Y anastomosis in laparoscopic total gastrectomy, the time of hand-sewn esophagojejunostomy and esophago-jejunal anastomosis are shorter, patients have less postopera-tive pain and faster postoperative recovery. Both methods have good peri-operative safety.

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Objective:To investigate the application value of hand-sewn esophagojejunal anastomosis (EJA) in totally laparoscopic total gastrectomy (TLTG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 35 patients with early or advanced upper gastric cancer who were admitted to Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine between July 2018 and December 2019 were collected. There were 24 males and 11 females, aged (60±10)years, with a range of 35-75 years. All the 35 patients underwent TLTG combined with hand-sewn EJA. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) postoperative pathological examination; (4) follow-up and survival. Follow-up was conducted using telephone interview, outpatient examination, short message service and WeChat to detect tumor recurrence, metastasis and survival of patients up to January 2020.Measurement data with normal distribution were repressented as Mean± SD. Measurement data with skewed distribution were represented as M (range). Count data were expressed as absoulte numbers or persentages. Results:(1) Intraoperative situations: all the 35 patients underwent TLTG combined with hand-sewn EJA successfully. The operation time, volume of intraoperative blood loss, time of hand-sewn EJA, costs of consumables used in the intraoperative resection and reconstruction, and costs of consumables used in EJA of the 35 patients were 305 minutes(range, 232-406 minutes), 94 mL(range, 50-300 mL), 37 minutes(range, 20-65 minutes), 13 674 yuan(range, 11 929-15 255 yuan) and 491 yuan(range, 223-1 044 yuan), respectively. Of the 35 patients, 4 received intraoperative blood transfusion. (2) Postoperative situations: time to first out-of-bed activity, postoperative indwelling time of gastric tube, time to initial liquid diet intake, the time to abdominal drainage tube removal and duration of postoperative hospital stay of the 35 patients were 2 days(range, 1-3 days), 4 days(range, 2-11 days), 5 days(range, 4-12 days), 8 days(range, 5-15 days) and 9 days(range, 7-16 days), respectively. Of the 35 patients, 3 had perioperative complications. One patient had inflammation and infection in the pancreatic tail and was discharged at postoperative 16 days after conservative treatment of fasting, somatostatin to reduce the pancreatic secretion, adequate drainage, anti-infection and nutritional support. One had postoperative intestinal incomplete obstruction and was discharged at postoperative 12 days after treatment with gastrointestinal decompression and enema for relief of obstruction. One had pulmonary infection who was discharged at postoperative 9 days after symptomatic and supportive treatment. None of the 35 patients had perioperative anastomotic leakage or bleeding. Of the 35 patients, 1 was diagnosed with esophagojejunostomy stenosis at postoperative 2 months and was improved after endoscopic dilatation. The incidence of long-term anastomosis-related complications of the 35 patients was 2.9%(1/35). (3) Postoperative pathological examination: the pathological examination of the upper margin of intraoperative frozen section and postoperative paraffin section showed negative in the 35 patients. Of the 35 patients, 16 had tumor located at cardia including 4 cases with tumor involving in lower esophagus, 19 had tumor located at stomach; 21 had tumor pathological type as highly or moderately differentiated adenocarcinoma, 11 had poorly differentiated adenocarcinoma, 3 had signed-ring cell carcinoma; 14 had early gastric cancer, 21 had advanced gastric cancer; 7 had tumor invaded at mucosa lamina propria and muscularis, 7 had tumor invaded at submucosa, 1 had tumor invaded at muscularis, 1 had tumor invaded at subserosal, 17 had tumor invaded at serosal, 2 had tumor invaded at extra-serosal adipose tissue. The TNM staging of the 35 patients: 14 were in stage ⅠA , 2 in stage ⅠB, 4 in stage ⅡB, 3 in stage ⅢA, 4 in stage ⅢB and 8 in stage ⅢC. Of the 35 patients, 15 had vascular invasion and 16 had nerve invasion. The tumor diameter, the number of lymph nodes dissected and the number of positive lymph nodes of the 35 patients were 3.9 cm(range, 0.6-12.0 cm), 24(range, 10-40) and 2(range, 0-11). (4) Follow-up and survival: all the 35 patients were followed up for 1-18 months, with a median time of 5 months. Of the 35 patients, tumor recurrence or metastasis was not found in 34 patients, and the other 1 patient was diagnosed with liver metastases of tumor at postoperative 6 months and survived with tumor.Conclusion:Hand-sewn EJA in TLTG is safe and feasible.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

The world-wide incidence of adenocarcinoma of the esophagogastric junction has been on a rise in recent years.Surgical resection plays the most important role in the multimodal management for adenocarcinoma of esophagogastric junction.However,due to distinct anatomical position,biological features,epidemiology and surgical teams,many controversies and different cognitions exist among surgeons from the East and the West,including tumor staging and classification,regional lymphadenectomy,surgical approaches and extents of esophageal and gastric resection.A new TNM classification has renewed the staging system,while traditional Siewert classification still decides clinical surgical strategies.With the development of minimally invasive surgery and early detection for the lesion,it is possible to perform the operations combining laparoscopy and thoracoscopy in the future.A multidisciplinary team from digestive surgery,oncology,radiology and anesthesiology will be essential for optimal diagnosis and management.