Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

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.

Objective:To explore the clinical therapeutic effect and follow-up prognosis of preterm infants with neonatal respiratory distress syndrome (NRDS) managed by less invasive surfactant administration (LISA) and traditional intubation-surfactant-extubation (INSURE) of pulmonary surfactant (PS).Methods:Data during hospitalization and follow-up period of 187 NRDS preterm infants (gestational age 24 weeks to 31 + 6 weeks, and birth weight <1 500 g) admitted to the Department of Neonatology, the Women and Children′s Hospital of Chongqing Medical University from March 2019 to February 2021 were retrospectively analyzed.NRDS preterm infants who were injected with PS by LISA were included in the LISA group (144 cases), and those who were injected with PS by INSURE were included in the INSURE group (43 cases). The propensity score matching method was used to correct the confounding factors between groups, and the covariate equilibrium samples between groups were obtained (39 cases in each group). Clinical treatment effect and prognosis of physical development, hearing and vision development, nervous system development, respiratory system diseases and other conditions of the two groups of children were compared using the t test, Chi- square test and other statistical analysis methods as appropriate. Results:(1)Compared with that of the INSURE group, the incidence of BPD [12 cases (33.3%) vs.23 cases (63.9%), χ2=6.727, P=0.009] and ROP [13 cases (36.1%) vs.26 cases (72.2%), χ2=9.455, P=0.002] in the LISA group were significantly lower.The incidence of mild BPD [8 cases (22.2%) vs.16 cases (44.4%), χ2=4.000, P=0.046] and stage Ⅰ-Ⅱ ROP [11 cases (30.6%) vs.22 cases (61.1%), χ2=6.769, P=0.009] in the LISA group was significantly lower than that of the INSURE group.There was no significant difference in the incidence of moderate and severe BPD and stageⅢ ROP and above between groups (all P>0.05). (2)There were no statistical differences in the repeated use of PS, mechanical ventilation rate within 72 h, pneumothorax/pulmonary hemorrhage, grade Ⅲ-Ⅳ periventricula-rintraventricular hemorrhage, stage Ⅱ-Ⅲ neonatal necrotizing enterocolitis, sepsis, abnormal amplitude integrated electroencephalogram, mortality in 36 weeks of corrected gestational age, total oxygen inhalation duration and hospitalization duration between the two groups (all P>0.05). (3)Follow-up within 1 year of corrected age after discharge.There were no significant differences in extrauterine body mass, body length and head circumference development, visual development, hearing development, Neonatal Behavioral Neurological Assessment score at corrected gestational age of 40 weeks, Bayley Scales of Infants Development score at corrected gestational age of 6 months and age of 1 year, pneumonia and re-hospitalization due to respiratory diseases between groups (all P>0.05). Conclusions:PS administration with LISA technology can reduce the incidence of mild BPD and stage Ⅰ-Ⅱ ROP in premature infants with NRDS who had the gestational age of 24-31 + 6 weeks and birth weight<1 500 g, without increasing the risk of other complications.The long-term prognosis of them treated with PS administration with LISA and INSURE is similar.

Dermatomyositis (DM) with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (MDA5+DM) is a kind of occasional and rare autoimmune disease. Due to the fact that MDA5+DM patients are prone to suffer from the rapid progressive interstitial lung disease (RP-ILD), and the mortality rate is extremely high (all-cause mortality at 6 months is almost 50%). In addition to lung disease, patients with MDA5+DM also suffering from the skin and muscle symptoms. The biomarkers represented by the anti-MDA5 antibody titer, ferritin, KL-6 level and CD4 +/CXCR4 +T cell percentage are considered to relate with MDA5+DM-ILD′s severity, activity evaluation, therapeutic effect monitoring, and prognosis prediction. The current therapeutic strategies for the disease is mainly combined with immunosuppression. This work systemly summarizes the diagnosis and treatment progress of anti-mda5 antibody-related dermatomyositis, which not only contributes to the research work of related disciplines, but also provides reference for clinical diagnosis and treatment.

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.

Objective To investigate the efficacy and safety of the enhanced recovery after surgery (ERAS) protocol in patients with gastric gastrointestinal stromal tumors (GISTs) in favorable sites.Methods Between March 2015 and January 2017,86 gastric GISTs patients undergoing laparoscopic resection in favorable sites were retrospectively analyzed.The patients were divided into ERAS protocol group (n =44) and conventional protocol group (n =42).Perioperative data and postoperative recovery parameters were compared.Results Compared with conventional group,postoperative recovery parameters in ERAS group such as time to first flatus,the first defecation,return to normal diet,physical activity outof-bed,and the hospital stay were obviously shortened.The postoperative pain score [(3.1 ± 3.0) vs.(5.2±3.2),P ＜0.05] and insulin resistance [(4.0±7.5) vs.(9.5 ±2.2),P ＜0.05] were significantly reduced in the ERAS protocol group than in the conventional protocol group.However,no statistically significant differences were observed in terps of operation time and intraoperative blood loss (P ＞ 0.05).There were no martality in both groups.The postoperative complications were 4.5％ and 4.7％ respectively.Conclusion Laparoscopic technique in favorable sites combined with the ERAS protocol enhance postoperative recovery and shorten hospital stay in gastric GIST patients.