Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy:A case report

BACKGROUND Pulmonary lymphoepithelioma-like carcinoma(PLELC)is a rare type of nonsmall-cell lung cancer.Stomach lymphoepithelioma-like carcinoma(LELC)metastasis secondary to PLELC has not been reported recently.CASE SUMMARY A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC.Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region.Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus.Immunohistochemistry(IHC)of the biopsy suggested metastatic stomach LELC.Proximal gastrectomy showed that this 6.5 cm×5.0 cm mass was located in the stomach fundus near the cardia.Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration.IHC demonstrated that the tumor was positive for CK(AE1/AE3),p63,p40,p53,Ki-67(70%),and EGFR(3+)and negative for CK7,CK20,Her2,and CD10.In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA.Tumor programmed cell death ligand 1(PD-L1)expression score was 98%,and the combined positive score was 100,with no evidence of microsatellite instability.Thus,the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC.After discharge,this patient underwent PD-1 inhibitor treatment(toripalimab,240 mg)every 3 wk for ten cycles,and she has had no tumor recurrence.CONCLUSION For gastric LELC metastasis,PD-1 inhibitor therapy could become a new therapeutic approach,though there is still no evidence from large data sets to support this.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway

Background:Long non-coding RNAs(lncRNAs)plays an important role in the progression of gastric cancer(GC).Their involvement ranges from genetic regulation to cancer progression.However,the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods:We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction.A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells.In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line.RNA pull-down unveiled RP11-789C1.1 interacting proteins.Western blot analysis indicated the downstream pathway changes of RP11-789C1.1,and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin.Results:Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells.Mechanistically,RP11-789C1.1 inhibited checkpoint kinase 1(CHK1)phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related(ATR),a serine/threonine-specific protein kinase,promoted GC apoptosis,and mediated oxaliplatin sensitivity.Conclusion:In general,we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action,providing a theoretical basis for targeted GC therapy.

Advances in the study of gastric organoids as disease models

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques.These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research.This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids,and patient-derived organoids.The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed.The construction of gastric organoids involves several key steps,including cell extraction and culture,three-dimensional structure formation,and functional expression.Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori.In addition,in drug screening and development,gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials.They can also be used for precision medicine according to the specific conditions of patients with gastric cancer,to assess drug resistance,and to predict the possibility of adverse reactions.However,despite the impressive progress in the field of gastric organoids,there are still many unknowns that need to be addressed,especially in the field of regenerative medicine.Meanwhile,the reproducibility and consistency of organoid cultures are major challenges that must be overcome.These challenges have had a significant impact on the development of gastric organoids.Nonetheless,as technology continues to advance,we can foresee more comprehensive research in the construction of gastric organoids.Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

Construction and validation of a risk-prediction model for anastomotic leakage after radical gastrectomy: A cohort study in China

Objectives:Anastomotic leakage(AL)stands out as a prevalent and severe complication following gastric cancer surgery.It frequently precipitates additional serious complications,significantly influencing the overall survival time of patients.This study aims to enhance the risk-assessment strategy for AL following gastrectomy for gastric cancer.Methods:This study included a derivation cohort and validation cohort.The derivation cohort included patients who underwent radical gastrectomy at Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,from January 1,2015 to December 31,2020.An evidence-based predictor questionnaire was crafted through extensive literature review and panel discussions.Based on the questionnaire,inpatient data were collected to form a model-derivation cohort.This cohort underwent both univariate and multivariate analyses to identify factors associated with AL events,and a logistic regression model with stepwise regression was developed.A 5-fold cross-validation ensured model reliability.The validation cohort included patients from August 1,2021 to December 31,2021 at the same hospital.Using the same imputation method,we organized the validation-queue data.We then employed the risk-prediction model constructed in the earlier phase of the study to predict the risk of AL in the subjects included in the validation queue.We compared the predictions with the actual occurrence,and evaluated the external validation performance of the model using model-evaluation indicators such as the area under the receiver operating characteristic curve(AUROC),Brier score,and calibration curve.Results:The derivation cohort included 1377 patients,and the validation cohort included 131 patients.The independent predictors of AL after radical gastrectomy included age65 y,preoperative albumin<35 g/L,resection extent,operative time240 min,and intraoperative blood loss90 mL.The predictive model exhibited a solid AUROC of 0.750(95%CI:0.694e0.806;p<0.001)with a Brier score of 0.049.The 5-fold cross-validation confirmed these findings with a calibrated C-index of 0.749 and an average Brier score of 0.052.External validation showed an AUROC of 0.723(95%CI:0.564e0.882;p?0.006)and a Brier score of 0.055,confirming reliability in different clinical settings.Conclusions:We successfully developed a risk-prediction model for AL following radical gastrectomy.This tool will aid healthcare professionals in anticipating AL,potentially reducing unnecessary interventions.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Extremely well-differentiated adenocarcinoma of the stomach: Clinicopathological and immunohistochemical features

AIM： Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma （EWDA）, is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS： Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT： Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions （mean follow-up period, 56 too）. All 9 cases of EWDA could be classified into gastric phenotype （5 lesions） and intestinal phenotype （4 lesions）. The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION： Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.

Current gene therapy for stomach carcinoma

Gastric cancer is common in China [1-42],and its early diagnosis and treatment in advanced stage are difficult [31-50].In recent years ,gene study in cancer is a hotspot ,and great progress has been achieved [41-80] .Cancer gene therapy has shifted from the imagination into the laboratory and clinical trials.

Annual cost of illness of stomach and esophageal cancer patientsin urban and rural areas in China： A multi-center study

Objective： Stomach and esophageal cancer are imposing huge threats to the health of Chinese people whereasthere were few studies on the financial burden of the two cancers.Methods： Costs per hospitalization of all patients with stomach or esophageal cancer discharged betweenSeptember 2015 and August 2016 in seven cities/counties in China were collected, together with their demographicinformation and clinical details. Former patients in the same hospitals were sampled to collect information onannual direct non-medical cost, indirect costs and annual number of hospitalization. Annual direct medical cost wasobtained by multiplying cost per hospitalization by annual number of hospitalization. Annual cost of illness （ACI）was obtained by adding the average value of annual direct medical cost, direct non-medical cost and indirect cost,stratified by sex, age, clinical stage, therapy and pathologic type in urban and rural areas. Costs per hospitalizationwere itemized into eight parts to calculate the proportion of each part. All costs were converted to 2016 US dollars（1 USD：6.6423 RMB）.Results： Totally 19,986 cases were included, predominately male. Mean ages of stomach cancer and urbanpatients were lower than that of esophageal cancer and rural patients. ACI of stomach and esophageal cancerpatients were $10,449 and $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively. Greater ACIwas associated with male, non-elderly patients as well as those who were in stage I and underwent surgeries.Western medicine fee took the largest proportion of cost per hospitalization.Conclusions： The ACI of stomach and esophageal cancer was tremendous and varied substantially among thepopulation in China. Preferential policies of medical insurance should be designed to tackle with this burden andfurther reduce the health care inequalities.

Exophytic inflammatory myofibroblastic tumor of the stomach in an adult woman:A rare cause of hemoperitoneum

Inflammatory myofibroblastic tumor （INT） of the stomach in adults is extremely rare, with unpredictable prognosis. We present a 55-year-old woman with a gastric IMT. She experienced sudden abdominal pain 4 d previously. Physical examination showed mild abdominal tenderness in the hypogastrium, but no palpable abnormal abdominal mass. Abdominal CT showed a mass of approximately 8 cm in the gastrocolic ligament. On laparoscopic exploration, unexpected hemoperitoneum of approximately 1.5 L of blood was found, and an exophytic gastric mass of approximately 10 cm, appeared from the anterior wall of the gastric body along the greater curvature. Laparoscopy further showed that non- clotting blood in the abdominal cavity seemed to be from the gastric tumor. After conversion to open surgery for more precise evaluation of the cause of hemoperitoneum and the large friable tumor, gastric wedge resection, including the tumor, was conducted. The final diagnosis was consistent with IMT that originated from the gastric wall.

Detection of early gastric cancer using hydro-stomach CT:Blinded vs unblinded analysis

AIM:To evaluate the difference in diagnostic performance of hydro-stomach computed tomography(CT) to detect early gastric cancer(EGC) between blinded and unblinded analysis and to assess independent factors affecting visibility of cancer foci.METHODS:Two radiologists initially blinded and then unblinded to gastroscopic and surgical-histological findings independently reviewed hydro-stomach CT images of 110 patients with single EGC.They graded the visibility of cancer foci for each of three gastric segments(upper,middle and lower thirds) using a 4-point scale(1:definitely absent,2:probably absent,3:probably present,and 4:definitely present).The sensitivity and specificity for detecting an EGC were calculated.Intraobserver and interobserver agreements were analyzed.The visibility of an EGC was evaluated with regard to tumor size,invasion depth,gastric segments,histological type and gross morphology using univariate and multivariate analysis.RESULTS:The respective sensitivities and specificities [reviewer 1:blinded,20%(22/110) and 98%(215/220);unblinded,27%(30/110) and 100%(219/220)/reviewer 2:blinded,19%(21/110) and 98%(216/220);unblinded,25%(27/110) and 98%(215/220)] were not significantly different.Although intraobserver agreements were good(weighted κ = 0.677 and 0.666),interobserver agreements were fair(blinded,0.371) or moderate(unblinded,0.558).For both univariate and multivariate analyses,the tumor size and invasion depth were statistically significant factors affecting visibility.CONCLUSION:The diagnostic performance of hydrostomach CT to detect an EGC was not significantly different between blinded and unblinded analysis.The tumor size and invasion depth were independent factors for visibility.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

Effects of San Qi on Gastric Secretion and Protective Factors of Gastric Mucosa in the Rat with Precancerous Lesion of Stomach

In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste,effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.The results indicated that gastric secretion,gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly,and malondialdehyde (MDA) increased significantly (P<0.01) in the model group as compared with the normal group;after treatment with San Qi Powder for 12 weeks,both gastric secresion and GMBF increased,and MDA content decreased as compared with the negative control group (P<0.01),with no significant increase of aminohexose content.It is suggested that San Qi (三七 Radix Notoginseng) may improve gastric secretion,and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.

Incidence and survival of stomach cancer in a high-risk population of Chile

AIM:To study the incidence and survival rate of stomach cancer(SC)and its associated factors in a high risk population in Chile. METHODS:The population-based cancer registry of Valdivia,included in the International Agency for Research on Cancer system,covers 356 396 residents of Valdivia Province,Southern Chile.We studied all SC cases entered in this Registry during 1998-2002 (529 cases).Population data came from the Chilean census(2002).Standardized incidence rates per 100 000 inhabitants(SIR)using the world population, cumulative risk of developing cancer before age 75, and rate ratios by sex,age,ethnicity and social factors were estimated.Relative survival(EdererⅡmethod) and age-standardized estimates(Brenner method) were calculated.Specific survival rates(Kaplan-Meier) were measured at 3 and 5 years and survival curves were analyzed with the Logrank and Breslow tests. Survival was studied in relation to demographics, clinical presentation,laboratory results and medical management of the cases.Those variables significantly associated with survival were later included in a Cox multivariate model. RESULTS:Between 1998 and 2002,529 primary gastric cancers occurred in Valdivia(crude incidence rate 29.2 per 100000 inhabitants).Most cases were male(69.0%), residents of urban areas(57.5%)and Hispanic(83.2%), with a low education level(84.5%<8 school years). SC SIR was higher in men than women(40.8 and 14.8 respectively,P<0.001),risk factors were low education RR 4.4(95%CI:2.9-6.8)and 1.6,(95%CI:1.1-2.1) for women and men respectively and Mapuche ethnicity only significant for women(RR 2.2,95%CI:1.2-3.7).Of all cases,76.4%were histologically confirmed,11.5% had a death certificate only(DCO),56.1%were TNM stageⅣ;445 cases(84.1%)were eligible for survival analysis,all completed five years follow-up;42 remained alive,392 died of SC and 11 died from other causes. Specific 5-year survival,excluding cases with DCO,was 10.6%(95%CI:7.7-13.5);5-year relative survival rate was 12.3%(95%CI:9.1-16.1),men 10.9%(95%CI: 7.4-15.2)and women 16.1%(95%CI:9.5-24.5).Fiveyear specific survival was higher for patients aged<55 years(17.3%),with intestinal type of cancer(14.6%), without metastasis(22.2%),tumor size<4 cm(60.0%), without lymphatic invasion(77.1%),only involvement of the mucous membrane(100%).Statistically significant independent prognostic factors were:TNM staging, diffuse type,metastasis,supraclavicular adenopathy, palpable tumor,and hepatitis or ascites. CONCLUSION:Social determinants are the main risk factors for SC,but not for survival.An advanced clinical stage at consultation is the main cause of poor SC survival.

POTENTIATION OF DOCETAXEL ANTITUMOR ACTIVITY BY BATIMASTAT AGAINST MOUSE FORESTOMACH CARCINOMA

Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg) every 4 days for 3 injections (q4d×3), even that of BB 94 (30mg/kg i.p. qd×20) was observed. Tumor growth inhibition was greater for docetaxel batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB 94 (33.0%), and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Microsatellite instable double primary cancers of the colorectum and stomach exhibit less favorable outcome

AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a prognostic indicator by assessing MSI status of patients with double primary gastric and colorectal cancer (DPGCC).METHODS: Sixteen patients were studied, all of whom exhibited sporadic DPGCC, and had no family history of hereditary non-polyposis colorectal cancer, according to the Amsterdam criteria. A total of 32 cancers from 16DPGCC patients, and 216 single primary CRC, were assessed for MSI in 5 microsatellite loci, BAT25, BAT26,D2S123, D5S346, and D17S250.RESULTS: MSI was observed in 6 (37.5%) of 16 GC and 4 (25.0%) of 16 CRC. Thirty tumors (13.9%) out of 216single primary CRC and one tumor (16.7%) out of 6 double primary CRC were found to be microsatellite unstable. Of the 6 GC with MSI in DPGCC, 5 (31.3%) were MSI-high and one (6.3%) was MSI-low. In 5 of 16 DPGCC patients,the cancer recurred in or adjacent to the anastomosis or metastasized to the kidney or lung. The MSI-high DPGCC cases were associated with a younger age of onset (47.5 years vs 62.5 years), higher frequency of lymph node metastasis (100% vs 25%), and advanced Dukes stage (C, 100% vs 41.7%), as well as a higher frequency of recurrence or metastasis (100% vs 8.3%). Only recurrence or metastasis showed statistical significance by Fisher's exact test.CONCLUSION: Our data suggest that MSI may play an important role in the development of DPGCC, and that it may be used clinically as a molecular predictive marker for recurrence or late metastasis of DPGCC.

Angiopoietins/Tie-2 expression and angiogenesis in stomach carcinoma

Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.

CLINICAL STUDY ON ACUPUNCTURE TREATMENT OF STOMACH CARCINOMA PAIN

Clinical observation on 48 cases of stomach carcinoma pain indicated that acupuncture including filiform needle group and point-injection group had better therapeutic effects in treatment of stomach carcinoma pain when patient's mind was concentrated at the site of disease. After treatment for 2 months, the long-term effective rates of analgesia in both the filiform needle group and the point-injection group were similar to that in the western medicine group, all being about 81%. While the long-term markedly effective rates in the two groups were superior to that in the western medicine group. Life quality of the patients in all the groups were improved. The toxic action and side effects caused by chemotherapy were prevented, the high viscous state showed by indexes of blood rheology was improved, and the lowered Cu-Zu-SOD activity in erythrocytes in patients of stomach carcinoma was increased in the filiform needle group and the point-injection group. Based on the results of clinical study, we consider that acupuncture analgesic effect on stomach carcinoma is related to the increase of PLEK, improvement of cellular immune function and the elevation of life quality after acupuncture.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.