Reconceptualization of immune checkpoint inhibitor-associated gastritis

In recent years,with the extensive application of immunotherapy in clinical practice,it has achieved encouraging therapeutic effects.While enhancing clinical efficacy,however,it can also cause autoimmune damage,triggering immunerelated adverse events(irAEs).Reports of immunotherapy-induced gastritis have been increasing annually,but due to its atypical clinical symptoms,early diagnosis poses a certain challenge.Furthermore,it can lead to severe complications such as gastric bleeding,elevating the risk of adverse outcomes for solid tumor patients if immunotherapy is interrupted.Therefore,gaining a thorough understanding of the pathogenesis,clinical manifestations,diagnostic criteria,and treatment of immune-related gastritis is of utmost importance for early identification,diagnosis,and treatment.Additionally,the treatment of immune-related gastritis should be personalized according to the specific condition of each patient.For patients with grade 2-3 irAEs,restarting immune checkpoint inhibitors(ICIs)therapy may be considered when symptoms subside to grade 0-1.When restarting ICIs therapy,it is often recommended to use different types of ICIs.For grade 4 irAEs,permanent discontinuation of the medication is necessary.

Research status and hotspots of tight junctions and colorectal cancer:A bibliometric and visualization analysis

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide and the second leading cause of cancer-related death.Over the past two decades,numerous researchers have provided important evidence regarding the role of tight junction(TJ)proteins in the occurrence and progression of CRC.The causal relationship between the presence of specific TJ proteins and the development of CRC has also been confirmed.Despite the large number of publications in this field,a bibliometric study to review the current state of research and highlight the research trends and hotspots in this field has not yet been performed.AIM To analyze research on TJs and CRC,summarize the field’s history and current status,and predict future research directions.METHODS We searched the Science Citation Index Expanded database for all literature on CRC and TJs from 2001-2023.We used bibliometrics to analyze the data of these papers,such as the authors,countries,institutions,and references.Co-authorship,co-citation,and co-occurrence analyses were the main methods of analysis.CiteSpace and VOSviewer were used to visualize the results.RESULTS A total of 205 studies were ultimately identified.The number of publications on this topic has steadily increased since 2007.China and the United States have made the largest contributions to this field.Anticancer Research was the most prolific journal,publishing 8 articles,while the journal Oncogene had the highest average citation rate(68.33).Professor Dhawan P was the most prolific and cited author in this field.Co-occurrence analysis of keywords revealed that“tight junction protein expression”,“colorectal cancer”,“intestinal microbiota”,and“inflammatory bowel disease”had the highest frequency of occurrence,revealing the research hotspots and trends in this field.CONCLUSION This bibliometric analysis evaluated the scope and trends of TJ proteins in CRC,providing valuable research perspectives and future directions for studying the connection between the two.It is recommended to focus on emerging research hotspots,such as the correlations among intestinal microbiota,inflammatory bowel disease,TJ protein expression,and CRC.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer

BACKGROUND Transanal endoscopic intersphincteric resection(ISR)surgery currently lacks sufficient clinical research and reporting.AIM To investigate the clinical effectiveness of transanal endoscopic ISR,in order to promote the clinical application and development of this technique.METHODS This study utilized a retrospective case series design.Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included.All patients underwent transanal endoscopic ISR as the surgical approach.We conducted this study to determine the perioperative recovery status,postoperative complications,and pathological specimen charac-teristics of this group of patients.RESULTS This study included 45 eligible patients,with no perioperative mortalities.The overall incidence of early complications was 22.22%,with a rate of 4.44%for Clavien-Dindo grade≥III events.Two patients(4.4%)developed anastomotic leakage after surgery,including one case of grade A and one case of grade B.Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients.The mean distance between the tumor lower margin and distal resection margin was found to be 2.30±0.62 cm.The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens.CONCLUSION Transanal endoscopic ISR is safe,feasible,and provides a clear anatomical view.It is associated with a low incidence of postoperative complications and favorable pathological outcomes,making it worth further research and application.

Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy

BACKGROUND At present,immune checkpoint inhibitors(ICIs)remain the 1st-line therapy me-thod for patients suffering from high microsatellite instability/deficient misma-tch repair metastatic colorectal cancer(mCRC).However,ICI treatments demon-strate minimal therapeutic efficacy against microsatellite stable(MSS)/proficient mismatch repair(pMMR)CRC.This is mainly because this type of tumor is a“cold tumor”with almost no lymphocyte infiltration.Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment,thereby exerting anti-tumor effects.AIM To investigate the effects of ICIs combined with bevacizumab monoclonal anti-body on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.METHODS A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a ran-domized controlled trial.In short,patients in the experimental group(n=60)were given sintilimab plus bevacizumab for 4 cycles,and those in the control group(n=50)patients were treated with FOLFIRI combined with bevacizumab for 4 cycles.The expression levels of cluster of differentiation(CD)8(+)T cells,tumor-associated macrophages(TAMs),and cancer-associated fibroblasts(CAFs)were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.RESULTS The positive expression rates of CD8(+)T lymphocytes(30%vs 50%),TAMs(23.30%vs 60%),and CAFs(23.30%vs 50%)before and after treatment in both groups exhibited statistical significance(P<0.05).Additionally,the therapeutic effects of both groups(partial remission:26.67%vs 10%;objective response rate:26.70%vs 10%)were significantly different(P<0.05).Although the experimental group showed a higher progression-free survival,median progression-free survival,and disease control rate than the control group,the difference was not statist-ically significant.Moreover,no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found(P>0.05).CONCLUSION ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer

BACKGROUND Laparoscopic radical gastrectomy is widely used,and perioperative complications have become a highly concerned issue.AIM To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery,guide perioperative treatment strategies for gastric cancer patients,and prevent serious complications.METHODS In total,998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model,and 398 patients were included in the validation group.The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected.Three machine learning methods,lasso regression,random forest,and artificial neural networks,were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy,and their prediction efficacy and accuracy were evaluated.RESULTS The constructed complication model,particularly the random forest model,could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy.It exhibited stable performance in external validation and is worthy of further promotion in more centers.CONCLUSION Using the risk factors identified in multicenter datasets,highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established.We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

From basic to clinical:Anatomy of Denonvilliers’fascia and its application in laparoscopic radical resection of rectal cancer

The total mesorectal excision(TME)approach has been established as the gold standard for the surgical treatment of middle and lower rectal cancer.This approach is widely accepted to minimize the risk of local recurrence and increase the long-term survival rate of patients undergoing surgery.However,standardized TME causes urogenital dysfunction in more than half of patients,thus lowering the quality of life of patients.Of note,pelvic autonomic nerve damage during TME is the most pivotal cause of postoperative urogenital dysfunction.The anatomy of the Denonvilliers’fascia(DVF)and its application in surgery have been investigated both nationally and internationally.Nevertheless,controversy exists regarding the basic to clinical anatomy of DVF and its application in surgery.Currently,it is a hotspot of concern and research to improve the postoperative quality of life of patients with rectal cancer through the protection of their urinary and reproductive functions after radical resection.Herein,this study systematically describes the anatomy of DVF and its appli-cation in surgery,thus providing a reference for the selection of surgical treatment modalities and the enhancement of postoperative quality of life in patients with middle and low rectal cancer.

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.

Change in expression of apoptosis genes after hyperthermia,chemotherapy and radiotherapy in human colon cancer transplanted into nude mice

AIM:To investigate the change in expression of p53 ,Bcl-2 ,and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy. METHODS:Human colon cancer cell line (HT29) was transplanted into the hind limbs of nude mice. Under laboratory simulated conditions of hyperthermia (43℃,60 min),the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches:hyperthermia,chemotherapy,radiotherapy,thermochemotherapy,thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane,cytoplasm and nuclei of tumor cells of p53,Bcl-2,and Bax after treatment,were observed by immunohistochemistry staining. RESULTS:All of the six treatment modalities down-regulated the expression of p53,Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia,with chemotherapy,and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ± 0.0013 vs 0.207 ± 0.027,P < 0.01) compared with any single therapy.CONCLUSION:Hyperthermia enhances the effect of radio-and chemotherapy on tumors by changing the expression of apoptosis genes,such as p53,Bcl-2 and Bax.

Influence of Perioperative Blood Transfusion on Prognosis in Patients with Colon Cancer

Objective： To explore the influence of perioperative blood transfusion on the postoperative survival of patients with colon cancer. Methods： Univariate and multivariate retrospective analyses were performed on the survival in a total of 723 colon cancer patients which were treated surgically during a period of 10 years. Results： Kaplan-Meier estimates showed that more than 800 mL perioperative blood transfusion was the survival predictor. Blood transfusion influenced significantly the prognosis of patients 40 years old and younger, those undergoing helicoloectomy left side, those with papillary adenocarcinoma, those with big tumors （diameter ≥ 8 cm）, those with stage Ⅰ tumors, those with lymphatic node metastases and those without liver metastases. In multivariate analysis only the tumor location, radicality of operation, lymphatic invasion, liver metastasis, depth of tumor invasion and TNM stage retained their significance. Conclusion： Perioperative blood transfusion is some extent. The indication of blood transfusion the prognostic factor for patients with colon cancer to must be restricted strictly, specially in patients younger than 40 years old, with right side lesion, papillary adenocarcinoma, big tumors （diameter ≥8 cm）, stage Ⅰ tumors and lymphatic node metastases or without liver metastases. But perioperative blood transfusion may not be deleterious for patients with staging Ⅳ disease and with distant metastases.

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.

Postoperative abdominal complications of gastric and colorectal cancer surgeries in China: a multicentered prospective registry-based cohort study

Surgical quality is critical in cancer treatment,as it not only determines the radical resection of the primary tumor but also allows expedited postoperative recovery and early continuation of adjuvant therapy.Postoperative complications are valuable met-rics for assessing surgical quality.In gastric and colorectal cancer surgeries,postoperative complications substantially postpone patients'recovery and,in extreme cases,pose life-threatening risks[1].