Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

Integrated approach to colorectal anastomotic leakage: Communication, infection and healing disturbances

Colorectal anastomotic leakage(CAL) remains a major complication after colorectal surgery. Despite all efforts during the last decades, the incidence of CAL has not decreased. In this review, we summarize the available strategies regarding prevention, prediction and intervention of CAL and categorize them into three categories: communication, infection and healing disturbances. These three major factors actively interact during the onset of CAL. We aim to provide an integrated approach to CAL based on its etiology. The intraoperative air leak test, intraoperative endoscopy, radiological examinations and stoma construction mainly aim to detect and to prevent communication between the intra- and extra-luminal content. Other strategies including postoperative drainage, antibiotics, and infectious-parameter evaluation are intended to detect and prevent anastomotic or peritoneal infection. Most currently available interventions for CAL focus on the control of communication and infection, while strategies targeting the healing disturbances such as lifestyle changes, oxygen therapy and evaluation of metabolic biomarkers still lack wide clinical application. This simplified categorization may contribute to an integrated understanding of CAL. We strongly believe that this integrated approach should be taken into consideration during clinical practice. An integrated approach to CAL could contribute to a better understanding of the etiology of CAL and eventually better patient outcome.

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.

Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1) Associates with Better Prognosis of Gastric Cancer Patients

Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling

AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a lowand a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.

Definition of colorectal anastomotic leakage: A consensus survey among Dutch and Chinese colorectal surgeons

AIM To determine the level of consensus on the definition of colorectal anastomotic leakage(CAL) among Dutch and Chinese colorectal surgeons.METHODS Dutch and Chinese colorectal surgeons were asked to partake in an online questionnaire. Consensus in the online questionnaire was defined as > 80% agreement between respondents on various statements regarding a general definition of CAL,and regarding clinical and radiological diagnosis of the complication.RESULTS Fifty-nine Dutch and 202 Chinese dedicated colorectal surgeons participated in the online survey. Consensus was found on only one of the proposed elements of a general definition of CAL in both countries: ‘extravasation of contrast medium after rectal enema on a CT scan'. Another two were found relevant according to Dutch surgeons: ‘necrosis of the anastomosis found during reoperation',and ‘a radiological collection treated with percutaneous drainage'. No consensus was found for all other proposed elements that may be included in a general definition.CONCLUSION There is no universally accepted definition of CAL in the Netherlands and China. Diagnosis of CAL based on clinical manifestations remains a point of discussion in both countries. Dutch surgeons are more likely to report ‘subclinical' leaks as CAL,which partly explains the higher reported Dutch CAL rates.

Prognosis of patients with gastric cancer and solitary lymph node metastasis

AIM:To investigate the relationship of solitary lymph node metastasis(SLNM)and age with patient survival in gastric cancer(GC).METHODS:The medical records databases of China’s Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People’s Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012.Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis.In total,936 patients with GC+SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up(range:13-2925 d)were collected.The Kaplan-Meier method was used to stratify patients by age(≤50 years-old,n=198;50-64 years-old,n=321;≥65 years-old,n=446)and by metastatic lymph node ratio[MLR<0.04(1/25),n=180;0.04-0.06(1/25-1/15),n=687;≥0.06(1/15),n=98]for 5-year survival analysis.The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS:The 5-year survival rate of the entire GC+SLNM patient population was 49.9%.Stratification analysis showed significant differences in survival time(post-operative days)according to age:≤50 yearsold:950.7±79.0 vs 50-64 years-old:1697.8±65.9 vs≥65 years-old:1996.2±57.6,all P<0.05.In addition,younger age(≤50 years-old)correlated significantly with mean survival time(r=0.367,P<0.001).Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time:<0.04:52.8%and 0.04-0.06:51.1%vs≥0.06:40.5%,P<0.05.The patients with the shortest survival times and rates were younger and had a high MLR(≥0.06):≤50 years-old:496.4±133.0 and 0.0%vs 50-65 years-old:1180.9±201.8 and 21.4%vs≥65 years-old:1538.4±72.4 and 37.3%,all P<0.05.The same significant trend in shorter survival times and rates for younger patients was seen with the mid-range MLR group(0.04-0.06),but the difference between the two older groups was not significant.No significant differences were found between the age groups of patients with MLR<0.04.Assessment of clinicopathological parameters identified age group,Borrmann type,histological type and tumor depth as the most important predictors of the survival rates and times observed for this study population.CONCLUSION:GC patients below 51 years of age with MLR of SLNM above 0.06 have shorter life expectancy than their older counterparts.

Imatinib mesylate in clinically suspected gastric stromal tumors

Gastrointestinal stromal tumors （GISTs） occur most frequently in the stomach.Diagnosis of gastric GIST is not always clear before surgery.Flexible endoscopy may suggest the nature of the lesion （a bulky tumor with preserved mucosa）; however,biopsy is rarely diagnostic.Therefore,diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained.Based on the excellent efficacy of imatinib mesylate （IM） in the treatment of GIST,we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors.In conclusion,the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

Evolution of viral RNA in a Chinese patient to interferon/ribavirin therapy for hepatitis C

Objective： The combination of interferon （IFN） and ribavirin （RBV） is the standard therapy for hepatitis C virus （HCV） infection. HCV genotype 2a has proved more amenable to the therapy, but its efficacy is yet fimited. This study aimed to investigate the mechanism of the poor response in a case ofHCV genotype 2a infection. Methods： We analyzed dynamic change of HCV RNA from a patient, infected with HCV genotype 2a, showing a poor virological response to 1FN/RBV as judged 12 weeks after initiation of the therapy by HCV clone sequencing. Then we constructed subgenomic Japanese fulminant hepatitis-1 （JFH1） replicon and different chimeric replicons with humanized Gaussia luciferase gene. The chimeric replicons were derived from subgenomic JFH1 replicon, in which the NS5A region was replaced by the patient＇s sequence from the pre/post- treatment, and the chimeric replicons＇ susceptibility to IFN were evaluated by relative Gausia Luciferase activity. Results： The pretreatment HCV sequences appeared almost uniform, and the quasispecies variation was further more simplified after 12 weeks of therapy. Besides, the quasispecies variation seemed to be more diversified in the NS5A, relatively, a region crucial for IFN response, and each of chimeric replicons exhibited distinct response to IFN. Conclusions： During the course of the chronic infection, HCV population seems to be adapted to the patient＇s immunological system, and further to be selected by combination of 1FN/RBV therapy, indicating quasispecies may completely eliminated by addition of other drugs with targets different from those of IFN. In addition, each different response of chimeric replicon to IFN is most likely related to amino acid changes in or near the IFN-sensitivity determining region （ISDR） of NSSA during chronic infection and IFN/RBV therapy.

Prognostic predictors in patients with sepsis after gastrointestinal tumor surgery:A retrospective study

BACKGROUND There have been different reports on mortality of sepsis;however,few focus on the prognosis of patients with sepsis after surgery.AIM To study the clinical features and prognostic predictors in patients with sepsis after gastrointestinal tumor surgery in intensive care unit(ICU).METHODS We retrospectively screened patients who underwent gastrointestinal tumor surgery at Peking University Cancer Hospital from January 2015 to December 2019.Among them,181 patients who were diagnosed with sepsis in ICU were included in our study.Survival was analysed by the Kaplan-Meier method.Univariate and multivariate adjusted analyses were performed to identify predictors of prognosis.RESULTS The 90-d all-cause mortality rate was 11.1%in our study.Univariate analysis showed that body mass index(BMI),shock within 48 h after ICU admission,leukocyte count,lymphocyte to neutrophil ratio,international normalized ratio,creatinine,procalcitonin,lactic acid,oxygenation index,and sequential organ failure assessment(SOFA)score within 24 h after ICU admission might be all significantly associated with the prognosis of sepsis after gastrointestinal tumor surgery.In multiple analysis,we found that BMI≤20 kg/m^(2),lactic acid after ICU admission,and SOFA score within 24 h after ICU admission might be independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery.Compared with SOFA score,SOFA score combined with BMI and lactic acid might have higher predictive ability(area under the receiver operating characteristic curve,0.859;95%confidence interval,0.789-0.929).CONCLUSION Lactic acid and SOFA score within 24 h after ICU admission are independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery.SOFA score combined with BMI and lactic acid might have good predictive value.

Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043]. CONCLUSION: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

Oncogenic potential of IDH1R132C mutant incholangiocarcinoma development in mice

AIM: To investigate whether IDH1R132 C mutant in combination with loss of p53 and activated Notch signaling promotes intrahepatic cholangiocarcinoma(ICC) development.METHODS: We applied hydrodynamic injection and sleeping beauty mediated somatic integration to induce loss of p53(via sh P53), activation of Notch [via intracellular domain of Notch1(NICD)] and/or overexpression of IDH1R132 C mutant together with the sleeping beauty transposase into the mouse liver. Specifically, we co-expressed sh P53 and NICD(sh P53/NICD, n = 4), sh P53 and IDH1R132C(sh P53/IDH1R132 C, n = 3), NICD and IDH1R132C(NICD/IDH1R132 C, n = 4), as well as NICD, sh P53 and IDH1R132C(NICD/sh P53/IDH1R132 C, n = 9) in mice. Mice were monitored for liver tumor development and euthanized at various time points. Liver histology was analyzed by hematoxylin and eosin staining. Molecular features of NICD/sh P53/IDH1R132 C ICC tumor cells were characterized by Myc tag, Flag tag, Ki-67, p-Erk and p-AKT immunohistochemical staining. Desmoplastic reaction in tumor tissues was studied by Picro-Sirius red staining.RESULTS: We found that co-expression of sh P53/NICD, sh P53/IDH1R132 C or NICD/IDH1R132 C did not lead to liver tumor formation. In striking contrast, coexpression of NICD/sh P53/IDH1R132 C resulted in ICC development in mice(P < 0.01). The tumors could be identified as early as 12 wk post hydrodynamic injection. Tumors rapidly progressed, and by 18 wk post hydrodynamic injection, multiple cystic lesions could be identified on the liver surface. NICD/sh P53/IDH1R132 C liver tumors shared multiple histological features of human ICCs, including hyperplasia of irregular glands. Importantly, all tumor cells were positive for the biliary epithelial cell marker cytokeratin 19. Extensive collagen fibers could be visualized in tumor tissues using Sirus red staining, duplicating the desmoplastic reaction observed in human ICC. Tumors were highly proliferative and expressed ectopically injected genes. Together these studies supported that NICD/sh P53/IDH1R132 C liver tumors were indeed ICCs. Finally, no p-AKT or p-ERK positive staining was observed, suggesting that NICD/sh P53/IDH1R132 C driven ICC development was independent of AKT/m TOR and Ras/MAPK signaling cascades. CONCLUSION: We have generated a simple, nongermline murine ICC model with activated Notch, loss of p53 and IDH1R132 C mutant. The study supported the oncogenic potential of IDH1R132 C.

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

BACKGROUND Current tumor regression grade(TRG)evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results.The recent six-tier system(JGCA2017-TRG)recommended by the Japanese Gastric Cancer Association(JGCA)is worth investigating,as four-tier TRG systems are favored in various parts of the world.AIM To compare the predictive accuracies of five published TRG systems.METHODS Data were retrospectively collected from patients with locally advanced gastric cancer(LAGC)who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution.Outcomes were overall survival(OS)and disease-free survival(DFS),which were evaluated separately using the following TRG systems:JGCA2017,JGCA,Becker,AJCC/CAP,and Mandard.RESULTS All five published TRG systems were independent predictors for OS and DFS.Concordance indices of the JGCA2017,JGCA,Becker,AJCC/CAP-TRG,and Mandard systems were 0.651/0.6480.652/0.649,0.693/0.695,0.688/0.685,and 0.674/0.675 for OS and DFS,respectively.The four-tier Becker system showed the highest c-index,which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems(P<0.05 in OS and DFS).When residual tumor percentages were reset as:“no residual tumor”,<10%,<100%,and“no response”,the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS,which was superior to the other five systems.CONCLUSION The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification.The four-tier Becker system is more suitable for LAGC patients.A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery

BACKGROUND There were few studies on the prognosis of tumor patients with sepsis after gastrointestinal surgery and there was no relevant nomogram for predicting the prognosis of these patients.AIM To establish a nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery in the intensive care unit(ICU).METHODS A total of 303 septic patients after gastrointestinal tumor surgery admitted to the ICU at Peking University Cancer Hospital from January 1, 2013 to December 31, 2020 were analysed retrospectively. The model for predicting the prognosis of septic patients was established by the R software package.RESULTS The most common infection site of sepsis after gastrointestinal surgery in the ICU was abdominal infection. The 90-d all-cause mortality rate was 10.2% in our study group. In multiple analyses, we found that there were statistically significant differences in tumor type, septic shock, the number of lymphocytes after ICU admission, serum creatinine and total operation times among tumor patients with sepsis after gastrointestinal surgery(P < 0.05). These five variables could be used to establish a nomogram for predicting the prognosis of these septic patients. The nomogram was verified, and the initial C-index was 0.861. After 1000 internal validations of the model, the C-index was 0.876, and the discrimination was good. The correction curve indicated that the actual value was in good agreement with the predicted value.CONCLUSION The nomogram based on these five factors(tumor type, septic shock, number of lymphocytes, serum creatinine, and total operation times) could accurately predict the prognosis of tumor patients with sepsis after gastrointestinal surgery.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

The 2023 update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric cancer.For advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

Current status of immunotherapy in gastric cancer

Gastric cancer is one of the most common cancer with high mortality and morbilidity in East Asia,especially in China.In recent year,new treatment strategies for gastric cancer have developed.Immune check point inhibitors(ICIs)have been detected as a new standard treatment in Gastric cancer,which helped to improve the prognosis of patients with gastric cancer.Attempts to combine immunotherapy have become one of the research focuses.In this article,application of immunotherapy in neoadjuvant therapy and translational treatment of gastric cnacer are reviewed.Which is expected to be a reference for comprehensive treatment plan of accurate treatment methods for gastric cancer patients.In order to provide experiences and reference to develop individualized treatment of gastric cancer in clinical practice.

The Chinese Society of Clinical Oncology(CSCO):Clinical guidelines for the diagnosis and treatment of gastric cancer,2021

There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.

The Chinese Society of Clinical Oncology(CSCO):clinical guidelines for the diagnosis and treatment of gastric cancer

China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.

Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes.However,the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer(GC)is unclear.In this study,we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis.Methods:We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction(PCR).Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown.RNA-sequencing was performed to identify differentially expressed genes,followed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA)to reveal key signaling pathways likely regulated by ISL1 in GC.Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)and by detecting glucose consumption and lactate production.The expression of glucose transporter 4(GLUT4)and ISL1 was assessed by Western blotting,immunohistochemistry,and immunofluorescent microscopy.The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4.Results:High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients.ISL1 knockdown inhibited cell proliferation both in vitro and in vivo.KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown,which was validated by reduced glucose uptake and lactate production,decreased ECAR,and increased OCR.Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter.Conclusion:ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.