Comparison of short-and long-term outcomes of laparoscopic vs open resection for gastric gastrointestinal stromal tumors

AIM To compare the short-and long-term outcomes of laparoscopic(LR) vs open resection(OR) for gastric gastrointestinal stromal tumors(g GISTs).METHODS In total, 301 consecutive patients undergoing LR or OR for pathologically confirmed g GISTs from 2005 to 2014 were enrolled in this retrospective study. After exclusion of 77 patients, 224 eligible patients were enrolled(122 undergoing LR and 102 undergoing OR). The demographic, clinicopathologic, and survival data of all patients were collected. The intraoperative, postoperative, and long-term oncologic outcomes were compared between the LR and OR groups following the propensity score matching to balance the measured covariates between the two groups.RESULTS After 1:1 propensity score matching for the set of covariates including age, sex, body mass index, American Society of Anesthesiology score, tumor location, tumor size, surgical procedures, mitotic count, and risk stratification, 80 patients in each group were included in the final analysis. The baseline parameters of the two groups were comparable after matching. TheLR group was significantly superior to the OR group with respect to the operative time, intraoperative blood loss, postoperative first flatus, time to oral intake, and postoperative hospital stay(P < 0.05). No differences in perioperative blood transfusion or the incidence of postoperative complications were observed between the two groups(P > 0.05). No significant difference was found in postoperative adjuvant therapy(P = 0.587). The mean follow-up time was 35.30 ± 26.02(range, 4-102) mo in the LR group and 40.99 ± 25.07(range, 4-122) mo in the OR group with no significant difference(P = 0.161). Survival analysis showed no significant difference in the disease-free survival time or overall survival time between the two groups(P > 0.05).CONCLUSION Laparoscopic surgery for g GISTs is superior to open surgery with respect to intraoperative parameters and postoperative outcomes without compromising longterm oncological outcomes.

Ghrelin and gastrointestinal stromal tumors

Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors(GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and m RNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin(PI3K/AKT/m TOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/m TOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/m TOR pathway and the development of GISTs.

Dynamic observation of bone marrow suppression and chromosomal aberrations in patients with acute colchicine poisoning

Colchicine is a neutral lipophilic tricyclic alkaloid toxic to human cells containing tubulin,[1-2]and primarily stops the proliferation of active cells in the mitotic metaphase,such as intestinal mucosal cells and hematopoietic cells.It is widely used in treating gout and familial Mediterranean fever,while it is also used in establishing animal and plant experimental model.[3]In the recent study,treatment of patients affected by coronavirus disease 2019(COVID-19)with colchicine may prove a viable path.[4]The course of colchicine poisoning can be divided into three stages,[5]and most of the patients died in the second stage(2-7 d,the multiple organ injury stage).The cause of death was heart failure[6]and bone marrow hematopoietic failure in the terminal phase.[7]Hematopoiesis is a classic sign of colchicine poisoning.Many cases of colchicine poisoning have been comprehensively reported,and the target organs included heart,digestive tract,muscle,lung,kidney,hematopoietic system,etc.[8-11]This study aimed to investigate the injury of bone marrow hematopoietic system after colchicine poisoning and evaluate the therapeutic effect of bone marrow hematopoietic stimulation drugs.

Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability

Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.

Factors associated with early recurrence after curative surgery for gastric cancer

AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery.METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients' follow-up records and telephone followups.Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation.Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson's χ 2 test and Fisher's exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis.RESULTS: Of 417 gastric cancer patients, 80(19.2%)were diagnosed with early gastric cancer and the remaining 337(80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients(46.5%) experiencedrecurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo(range, 1-84 mo). Additionally, of these 194 patients,129(66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence(P < 0.05 each). For pT1 stage gastric cancer, tumor size(P = 0.011) and pN stage(P = 0.048) were associated with early recurrence of gastric tumors.Patient age, pT stage, pN stage, Lauren histotype,lymphovascular invasion, intraoperative chemotherapy,and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage gastric cancer(P < 0.05 each).CONCLUSION: Age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy are independent factors influencing early recurrence of pT2-4a stage gastric cancer.

Laparoscopic-endoscopic cooperative surgery for gastric submucosal tumors

AIM:To assess the feasibility,safety,and advantages of minimally invasive laparoscopic-endoscopic cooperative surgery(LECS)for gastric submucosal tumors(SMT).METHODS:We retrospectively analyzed 101 consecutive patients,who had undergone partial,proximal,or distal gastrectomy using LECS for gastric SMT at Peking Union Medical College Hospital from June 2006to April 2013.All patients were followed up by visit or telephone.Clinical data,surgical approach,pathological features such as the size,location,and pathological type of each tumor;and follow-up results were analyzed.The feasibility,safety and effectiveness of LECS for gastric SMT were evaluated,especially for patients with tumors located near the cardia or pylorus.RESULTS:The 101 patients included 43(42.6%)menand 58(57.4%)women,with mean age of 51.2±13.1 years(range,14-76 years).The most common symptom was belching.Almost all(n=97)patients underwent surgery with preservation of the cardia and pylorus,with the other four patients undergoing proximal or distal gastrectomy.The mean distance from the lesion to the cardia or pylorus was 3.4±1.3 cm,and the minimum distance from the tumor edge to the cardia was 1.5 cm.Tumor pathology included gastrointestinal stromal tumor in 78 patients,leiomyoma in 13,carcinoid tumors in three,ectopic pancreas in three,lipoma in two,glomus tumor in one,and inflammatory pseudotumor in one.Tumor size ranged from 1 to8.2 cm,with 65(64.4%)lesions<2 cm,32(31.7%)>2 cm,and four>5 cm.Sixty-six lesions(65.3%)were located in the fundus,21(20.8%)in the body,10(9.9%)in the antrum,three(3.0%)in the cardia,and one(1.0%)in the pylorus.During a median follow-up of 28 mo(range,1-69 mo),none of these patients experienced recurrence or metastasis.The three patients who underwent proximal gastrectomy experienced symptoms of regurgitation and belching.CONCLUSION:Laparoscopic-endoscopic cooperative surgery is feasible and safe for patients with gastric submucosal tumor.Endoscopic intraoperative localization and support can help preserve the cardia and pylorus during surgery.

Effect of Neoadjuvant Chemotherapy Treatment on Prognosis of Patients with Advanced Gastric Cancer:a Retrospective Study

Objective To evaluate the prognostic effects of neoadjuvant chemotherapy(NAC) in patients with local advanced gastric cancer. Methods We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. Results According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups(7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group(P=0.025). Conclusion In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.

MiR-30b suppresses tumor migration and invasion by targeting EIF5A2 in gastric cancer

AIM: To elucidate the potential biological role of mi R-30 b in gastric cancer and investigate the underlying molecular mechanisms of mi R-30 b to inhibit metastasis of gastric cancer cells.METHODS: The expression of mi R-30 b was detected in gastric cancer cell lines and samples by reverse transcription-polymerase chain reaction. CCK-8 assays were conducted to explore the impact of mi R-30 b overexpression on the proliferation of gastric cancer cells. Flow cytometry was used to examine the effect of mi R-30 b on the apoptosis. Transwell test was used for the migration and invasion assays. Luciferase reporter assays and Western blot were employed to validate regulation of putative target of mi R-30 b.RESULTS: The results showed that mi R-30 b was downregulated in gastric cancer tissues and cancer cell lines and functioned as a tumor suppressor. Overexpression of mi R-30 b promoted cell apoptosis,and suppressed proliferation,migration and invasion of the gastric cancer cell lines AGS and MGC803. Bioinformatic analysis identified the 3'-untranslated region of eukaryotic translation initiation factor 5A2(EIF5A2) as a putative binding site of mi R-30 b. Luciferase reporter assays and Western blot analysis confirmed the EIF5A2 gene as a target of mi R-30 b. Moreover,expression levels of theEIF5A2 targets E-cadherin and Vimentin were altered following transfection of mi R-30 b mimics.CONCLUSION: Our findings describe a link between mi R-30 b and EIF5A2,which plays an important role in mediating epithelial-mesenchymal transition.

Postoperative Early Standard and Sequential Nutritional Support in the Treatment of Gastroesophageal Anastomotic Fistula:a Case Report

GASTROESOPHAGEAL anastomotic fistula is aserious and potentially life-threatening complicationafter the resection of esophagus, gastricand cardia tumor.1 Before 1987, the incidenceof gastroesophageal anastomotic fistula is about 2%-4% inChina, and the mortality rate is as high as 50% or more.2 Inthe last 30 years, with the rapid development of clinicalnutrition support method, nutritional support.

Gastric cancer with severe immune thrombocytopenia: A case report

BACKGROUND Primary immune thrombocytopenia(ITP) is a rare autoimmune disease associated with a high bleeding risk. For those patients with gastric cancer, surgical treatment may be the only option for therapy. Here, we present the first case of gastric cancer with severe and medically refractory ITP treated by radical resection of the gastric cancer and splenectomy. CASE SUMMARY A 54-year-old female patient was admitted to our surgical department with a 2 mo history of decreased appetite, nausea, vomiting, and weight loss, which progressed to difficulty in feeding 3 d prior to her visit. According to her medical history, she was diagnosed with refractory ITP [platelets(PLT), 3000-8000/μL] 10 years ago. After admission, the patient underwent a splenectomy and a distal subtotal gastrectomy(D2 radical resection) with Roux-en-Y reconstruction simultaneously. She had an uneventful postoperative course with a slight increase in her PLT count. This case is unique in terms of the patient's complication of severe and medically refractory ITP.CONCLUSION Simultaneous splenectomy, preoperative PLT transfusion, and early enteral nutrition were important treatment methods for helping this patient recover.

Role of Cu element in biomedical metal alloy design

Biomedical metals are widely used as implant materials in the human or animal body to repair organs and restore function, such as heart valves, meninges, peritoneum and artificial organs.Alloying element affects the microstructure, mechanical property, corrosion resistance and wear resistance, but also influences the antibacterial and biological activity.Recently, antibacterial metal alloys have shown great potential as a new kind of biomedical materials, in which Cu has been widely used as antibacterial agent element.In addition, biodegradable metal alloys, including magnesium alloy and zinc alloy, also have attracted much attention worldwide.Cu was also used as alloying element to adjust the degradation rate.Thus, the role of Cu in the alloy design will be very important for the development of new alloy.In this paper, we summarized the recent research results on the Cu-containing metal alloy for biomedical application and hoped that this review would give more suggestions for the further development of biomedical metal alloy.