Annexin A1 induces oxaliplatin resistance of gastric cancer through autophagy by targeting PI3K/AKT/mTOR.

Resistance to oxaliplatin (OXA) is a major cause of recurrence in gastric cancer (GC) patients. Autophagy is an important factor ensuring the survival of cancer cells under chemotherapeutic stress. We aimed to investigate the role of OXA-related genes in autophagy and chemoresistance of gastric cancer cells. We established OXA-resistant gastric cancer cells and used RNA-seq to profile gene expression within OXA-resistant GC and corresponding parental cells. Immunohistochemistry and RT-qPCR was performed to detect gene expression in tissues of two cohorts of GC patients who received OXA-based chemotherapy. The chemoresistant effects of the gene were assessed by cell viability, apoptosis, and autophagy assays. The effects of the gene on autophagy were assessed with mRFP-GFP-LC3 and Western blotting (WB). Gene set enrichment analysis (GSEA) and WB were performed to detect the activity of PI3K/AKT/mTOR signaling under the regulation of the gene. The OXA-resistant property of GC cells is related to their enhanced autophagic activity. Based on RNA-seq profiling, ANXA1 was selected as a candidate, as it was upregulated significantly in OXA-resistant cells. Furthermore, we found that higher ANXA1 expression before chemotherapy was associated with subsequent development of resistance to oxaliplatin, and overexpression of ANXA1 promoted the resistance of gastric cancer cells to oxaliplatin. So, it may serve as a key regulator in GC chemo-resistance knockdown of ANXA1, via inhibiting autophagy, enhancing the sensitivity of OXA-resistant GC cells to OXA in vitro and in vivo. Mechanically, we identified that PI3K/AKT/mTOR signaling pathway was activated in the ANXA1 stable knockdown AGS/OXA cells, which leads to the suppression of autophagy. ANXA1 functions as a chemoresistant gene in GC cells by targeting the PI3K/AKT/mTOR signaling pathway and might be a prognostic predictor for GC patients who receive OXA-based chemotherapy.

Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application.

Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the "seed and soil" hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.

A nomogram of anastomotic stricture after rectal cancer: a retrospective cohort analysis.

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

BACKGROUND: The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS: This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS: Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS: LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

The value of intratumoral microbiota in the diagnosis and prognosis of tumors.

Intratumoral microbiota (ITM) are microorganisms present in tumor cells. ITM participate in tumor development by affecting tumor cells directly and the tumor microenvironment (TME), indirectly. Alterations in ITM instigate changes in tumor DNA, activate oncogenic pathways, induce tumor inflammatory responses, disrupt normal immune activity, and facilitate the secretion of effectors leading to tumor progression, metastasis, or diminished therapeutic effects. ITM varies significantly in different types of cancer cells and disease states. The presence of certain ITM serves as a predictor of various disease states. Thus, ITM predicts tumorigenesis, tumor grade, treatment efficacy, and prognosis, making it a potential tumor biomarker. The present study aimed to determine the mechanisms by which ITM affects tumor development, especially through the TME; highlight the significant potential of ITM in enhancing tumor diagnosis and prognosis; and outline future directions for ITM research, with a focus on the development of innovative tumor markers.

FANCA facilitates G1/S cell cycle advancement, proliferation, migration and invasion in gastric cancer.

The present study explores the function of FANCA gene, a pivotal member of the Fanconi anaemia (FA) pathway crucial for preserving genomic stability and preventing cancer, particularly in the context of gastric cancer (GC). Using immunohistochemistry, quantitative real-time PCR, and western blot analysis, we evaluate FANCA mRNA and protein expressions in GC cell lines. The relationship between FANCA expression and clinicopathological characteristics is also explored. Various assays, including CCK8, colony formation, wound healing, and Transwell assays, are used to assess functional changes in cells associated with FANCA. Flow cytometry is utilized to evaluate alterations in the cell cycle resulted from FANCA knockdown and overexpression. Our findings show elevated FANCA expression in GC cell lines, with levels correlated with pathologic stage and lymphatic metastasis. FANCA knockdown impedes cell proliferation, migration, and invasion and induces G1/S phase cell cycle arrest. Conversely, FANCA overexpression stimulates cell proliferation, migration, and invasion. In vivo xenograft experiments confirm the promotional role of FANCA in GC tumor progression. Moreover, FANCA overexpression is associated with the activation of cell cycle. Collectively, our results suggest that FANCA drives malignant cell behaviors in GC through the cell cycle pathway, highlighting its potential as a therapeutic target for the treatment of GC.

PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

Laparoscopic versus open distal gastrectomy for advanced gastric cancer in elderly patients: a propensity-score matched analysis.

BACKGROUND: Scarce research has reported the efficacy and safety of laparoscopic distal gastrectomy in elderly patients. This retrospective study aimed to compare the outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer in elderly patients. METHODS: A total of 303 elderly patients who underwent distal gastrectomy for advanced gastric cancer from June 2017 to June 2021 were enrolled. Variables used to calculate propensity score matching included sex, age, body mass index, American Society of Anesthesiologists, history of diabetes, and history of hypertension. The statistical significance of continuous variables was tested using an independent sample t test. chi-square or Fisher's exact tests were used for categorical variables. Kaplan-Meier curve and log-rank test were used for the evaluation of 3-year overall survival and recurrence-free survival. RESULTS: After performing 1:1 propensity score matching, 248 patients were included for analysis (laparoscopic = 124, open = 124). Compared with the open group, the laparoscopic group showed significant advantages in estimated blood loss (P < 0.001), pain scale on the first postoperative day (P = 0.002), time to first flatus (P = 0.004), time to first liquid diet (P = 0.005), hospital stays (P < 0.001), and total complications (P = 0.011), but devoted much more operation time (P < 0.001). No statistical difference was observed between the two groups in 3-year recurrence-free survival (P = 0.315) or overall survival (P = 0.159). CONCLUSIONS: Our analysis demonstrated that laparoscopic surgery had the advantages of less intraoperative blood loss, fewer postoperative complications, and faster postoperative recovery in distal gastrectomy for advanced gastric, indicating that laparoscopic distal gastrectomy is safe and effective for treating elderly patients with distal gastric cancer.

Modified Q-type purse-string suture duodenal stump embedding method for laparoscopic gastrectomy for gastric cancer.

OBJECTIVE: This study introduced the modified Q-type purse-string suture duodenal stump embedding method, a convenient way to strengthen the duodenum, and compared it to the conventional one to assess its efficacy and safety. METHODS: This retrospective analysis examined 612 patients who received laparoscopic gastrectomy for gastric Cancer at a single center. The patients were divided into Not Reinforced Group (n = 205) and Reinforced Group (n = 407) according to the surgical approach to the duodenal stump. The reinforced group was further divided into a modified Q-type purse-string suture embedding method group (QM, n = 232) and a conventional suture duodenal stump embedding method group (CM, n = 175) according to the methods of duodenal stump enhancement. Clinicopathological characteristics, operative variables, and short-term complications were documented and analyzed. RESULTS: The incidence of duodenal stump leakage(DSL) in the Not Reinforced Group was higher compared to the Reinforced Group, although the difference was not statistically significant [2.4% (5/205) vs 0.7% (3/407), p = 0.339]. Additionally, the Not Reinforced Group exhibited a higher rate of Reoperation due to DSL compared to the Reinforced Group [2 (1.0%) vs. 0, p = 0.046], with one patient in the Not Reinforced Group experiencing mortality due to DSL [1 (0.5%) vs 0, p = 0.158]. Subgroup analysis within the Reinforced Group revealed that the modified Q-type purse-string suture embedding group (QM) subgroup demonstrated statistically significant advantages over the conventional suture embedding group (CM) subgroup. QM exhibited shorter purse-string closure times (4.11 ± 1.840 vs. 6.05 ± 1.577, p = 0.001), higher purse-string closure success rates (93.1% vs. 77.7%, p = 0.001), and greater satisfaction with purse-string closure [224 (96.6%) vs 157 (89.7%), p = 0.005]. No occurrences of duodenal stump leakage were observed in the QM subgroup, while the CM subgroup experienced two cases [2 (1.1%)], though the difference was not statistically significant. Both groups did not exhibit statistically significant differences in secondary surgery or mortality related to duodenal stump leakage. CONCLUSION: Duodenal Stump Leakage (DSL) is a severe but low-incidence complication. There is no statistically significant relationship between the reinforcement of the duodenal stump and the incidence of DSL. However, laparoscopic reinforcement of the duodenal stump can reduce the severity of fistulas and the probability of Reoperation. The laparoscopic Q-type purse-string suture duodenal stump embedding method is a simple and effective technique that can, to some extent, shorten the operation time and enhance satisfaction with purse-string closure. There is a trend towards reducing the incidence of DSL, thereby improving patient prognosis to a certain extent.

Novel m7G-related lncRNA signature for predicting overall survival in patients with gastric cancer.

Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model's reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS' correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.

Global, Regional, and National Burden of Gastric Cancer in Adolescents and Young Adults, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

INTRODUCTION: Gastric cancer is a significant global health concern, ranking as the fifth most common cancer worldwide and the third leading cause of cancer-related mortality. While improvements in health awareness and medical technology have contributed to a decline in the incidence of gastric cancer in many countries, the rate of gastric cancer in adolescents and young adults (GCAYA) has shown an upward trend. Timely and effective strategies for screening, detection, and treatment are crucial for managing the burden of GCAYA and optimizing the allocation of medical resources. To this end, our study aimed to examine the distribution of the burden of GCAYA across different factors at the global, regional, and national levels between 1990 and 2019. By identifying and analyzing these factors, we can better inform efforts to combat this growing health challenge. METHODS: This study used data from the Global Burden of Disease database to analyze the global, regional, and national incidence, mortality, and disability-adjusted life years (DALY) GCAYA from 1990 to 2019. The age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALY rate (ASDR) of GCAYA were summarized and presented in a visually intuitive manner at the global, regional, and national levels. In addition, we calculated the estimated annual percentage change for each indicator of GCAYA globally, regionally, and nationally and visually displayed the results. Furthermore, we conducted an age-based analysis of adolescents and young adults with gastric cancer, comparing the age composition of deaths and the age burden of patients between 1990 and 2019. For the sake of brevity, we will use the abbreviation GCAYA to refer to gastric cancer among adolescents and young adults throughout the remainder of this article. RESULTS: From 1990 to 2019, the incidence of GCAYA has slightly increased globally. The number of newly diagnosed cases rose from 47,932 (95% uncertainty interval 44,592.9-51,005.7) in 1990 to 49,007 (45,007.7-53,078.1) in 2019, while the number of deaths decreased from 35,270 (32,579-37,678.5) to 27,895 (25,710.9-30,240.4). The global ASIR showed a declining trend, decreasing from 22.4 (95% uncertainty interval 21.2-23.6) per 100,000 in 1990 to 15.6 (14.1-17.2) per 100,000 in 2019. The age-standardized mortality rate also showed a declining trend, decreasing from 20.5 (19.2-21.6) per 100,000 in 1990 to 11.9 (10.8-12.8) per 100,000 in 2019. The ASDR also showed a declining trend, decreasing from 493.4 (463.7-523.7) per 100,000 in 1990 to 268.4 (245.5-290.6) per 100,000 in 2019. From 1990 to 2019, the incidence, mortality, and DALY of gastric cancer among male adolescents and young adults were higher than those of female adolescents and young adults. In 2019, the number of male adolescents and young adults with gastric cancer was 2.1 times higher than that of female individuals (368.9 [328.2-410.3] vs 178.2 [160.5-196.9]), the number of deaths was 1.1 times higher (14,971.6 [13,643.3-16,520.5] vs 12,923.6 [11,550.3-14,339]), and the DALY were 1.1 times higher (841,920.5 [766,655.5-927,598.8] vs 731,976.3 [653,421-814,242.8]). The incidence and DALY of GCAYA were higher in regions with high-middle and middle sociodemographic index countries. The age-standardized mortality rate of GCAYA in 198 countries and territories showed a decreasing trend, with the Republic of Korea showing the greatest decrease from 1,360.5 (1,300.3-51,416.5) per 100,000 in 1990 to 298.7 (270.1-328.4) per 100,000 in 2019, with an estimated annual percentage change of -5.14 (95% confidence interval -7.23 to -2.99). The incidence and DALY of GCAYA increased with age, with the highest proportion of patients being in the 35-39 years age group. In both 1990 and 2019, the age of death from GCAYA was mainly concentrated in the 35-39 years age group, accounting for approximately half of the total population. DISCUSSION: In the past 30 years, although the total number of new cases of GCAYA has increased with population growth, the ASIR and overall disease burden have shown a decreasing trend. This indicates progress in screening, diagnosis, treatment, education, and awareness efforts. However, the distribution of this disease remains uneven in terms of sex, age, development level, region, and country. To address these challenges, global health authorities should take appropriate measures such as optimizing screening programs, strengthening awareness and screening efforts for male individuals, enhancing prevention and control among the 35-39 years age group, improving infrastructure and health care resources in developing countries, promoting international cooperation, and implementing tailored measures.

Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation.

Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30-150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment. Video Abstract.

Intratumoural microbiota: from theory to clinical application.

Cancer is a major cause of high morbidity and mortality worldwide. Several environmental, genetic and lifestyle factors are associated with the development of cancer in humans and result in suboptimal treatment. The human microbiota has been implicated in the pathophysiological process of cancer and has been used as a diagnostic, prognostic and risk assessment tool in cancer management. Notably, both extratumoural and intratumoural microbiota are important components of the tumor microenvironment, subtly influencing tumorigenesis, progression, treatment and prognosis. The potential oncogenic mechanisms of action of the intratumoural microbiota include induction of DNA damage, influence on cell signaling pathways and impairment of immune responses. Some naturally occurring or genetically engineered microorganisms can specifically accumulate and replicate in tumors and then initiate various anti-tumor programs, ultimately promoting the therapeutic effect of tumor microbiota and reducing the toxic and side effects of conventional tumor treatments, which may be conducive to the pursuit of accurate cancer treatment. In this review, we summarise evidence revealing the impact of the intratumoural microbiota on cancer occurrence and progress and potential therapeutic and diagnostic applications, which may be a promising novel strategy to inhibit tumor development and enhance therapeutic efficacy. Video Abstract.

Prediction model of anastomotic leakage after anterior resection for rectal cancer-based on nomogram and multivariate analysis with 1995 patients.

BACKGROUND: Postoperative anastomotic leakage for rectal cancer shows higher morbidity with grievous concomitant symptoms. Accurate assessment of the incidence of anastomotic leakage, multivariate analysis, and establishment of a scientific prediction model can be useful to dispose of its possible severe clinical consequences. METHODS: This retrospective study collected 1995 consecutive patients who underwent anterior resection of rectal cancer with primary anastomosis at Northern Jiangsu People's Hospital between January 2016 and June 2022. Independent risk factors associated with anastomotic leakage were analyzed by univariate and multivariate logistic regression. The chosen independent risk factors were used to construct a nomogram risk prediction model whose availability was evaluated by using a bootstrapped-concordance index and calibration plots with R software. RESULTS: A total of 1995 patients who underwent anterior resection for rectal cancer were included while 120 patients were diagnosed with anastomotic leakage, an incidence of 6.0%. Univariate analysis and its concomitant multivariate cox regression analysis indicated that independent risk factors associated with anastomotic leakage included male gender (odds ratio (OR) = 2.873), diabetes (OR = 2.480), neoadjuvant therapy (OR = 5.283), tumor's distance from the anus verge < 5 cm (OR = 5.824), tumor size ≥ 5 cm (OR = 4.888), and the blood lose > 50 mL (OR = 9.606).We established a nomogram prediction model with proper applicability (concordance index, 0.83) and the calibration curve to justify its predictive ability that the predicted occurrence probability keeps a high degree of consistency with the actual occurrence probability. Meanwhile, the area under the receiver operating characteristic (ROC) curve was 0.83. CONCLUSIONS: The characteristics of patients and tumor surgery-related conditions can affect the incidence of anastomotic leakage. However, whether the surgical method will affect morbidity is still controversial. Our nomogram can be seen as an effective instrument to predict anastomotic leakage after anterior resection for rectal cancer precisely.

Evaluation of the safety and efficacy of perform enterectomy in colorectal cancer patients aged 80 or older. A meta-analysis and a systematic review.

BACKGROUND: Colorectal cancer (CRC) is one of the four most common cancers in the world. At present, human beings have stepped into an aging society, and the number of over eighties colorectal cancer patients has increased year by year. However, few high-quality studies focused on the post-operation complications and long-term outcomes of octogenarian patients with colorectal cancer. This meta-analysis, based on published studies, aims to assess the safety of treating octogenarian CRC patients with surgery. METHODS: Databases, including PubMed, Embase, and Cochrane Library were searched until July 2022. The incidence of preoperative comorbidities, postoperative complications, and mortality was assessed using odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Furthermore, the hazard ratios (HRs) with 95% CIs were applied for survival outcomes. RESULTS: A total of 13,790 patients with CRC in 21 studies were included. Our results demonstrated that octogenarian patients were associated with a higher burden of comorbidities (OR = 3.03; 95% CI: 2.03, 4.53; P = .000), high incidences of overall postoperative complications (OR = 1.63; 95% CI: 1.29, 2.06; P = .000), high internal medicine postoperative complications (OR = 2.38; 95% CI: 1.76, 3.21; P = .000), high in-hospital mortality (OR = 4.01; 95% CI: 3.06, 5.27; P = .000) and poor overall survival (OR = 2.13; 95% CI: 1.78, 2.55; P = .000). But there is no statistical difference in surgery-related postoperative complications(OR = 1.16; 95% CI: 0.94, 1.43; P = .16) and DFS (OR = 1.03; 95% CI: 0.83, 1.29; P = .775). CONCLUSIONS: Extremely elderly patients with colorectal cancer have the high burden of comorbidities, high postoperative complications and mortality. However, survival outcomes (DFS) in patients 80 years and older are similar to younger patients. Clinicians should administer individualized treatment for such patients. Physiologic age rather than chronological age should determine cancer management for each individual.

Predicting survival and prognosis in early-onset locally advanced colon cancer: a retrospective observational study.

OBJECTIVE: To predict cancer-specific survival, a refined nomogram model and brand-new risk-stratifying system were established to classify the risk levels of patients with early-onset locally advanced colon cancer (LACC). METHODS: The clinical factors and survival outcomes of LACC cases from the SEER database from 2010 to 2019 were retrieved retrospectively. Early-onset and late-onset colon cancer were grouped according to the age (50 years old) at diagnosis. Differences between groups were compared to identify mutual significant variables. A multivariate Cox regression analysis was further performed and then constructed a nomogram. We compared it with the AJCC-TNM system. The external validation was performed for evaluation. Finally, a risk-stratifying system of patients with early-onset LACC was established. RESULTS: A total of 32,855 LACC patients were enrolled in, 4548 (13.84%) patients were included in the early-onset LACC group, and 28,307 (86.16%) patients were included in the late-onset LACC group. The external validation set included 228 early-onset LACC patients. Early-onset colon cancers had poorer prognosis (T4, N2, TNM stage III, CEA, tumor deposit, and nerve invasion), and a higher proportion received radiotherapy and systemic therapy (P<0.001). In the survival analysis, cancer-specific survival (CSS) was better in patients with early-onset LACC than in those with late-onset LACC (P <0.001). This nomogram constructed based on the results of COX analysis showed better accuracy in CSS prediction of early-onset LACC patients than AJCC-TNM system in the training set and external validation set (0.783 vs 0.728; 0.852 vs 0.773). CONCLUSION: We developed a novel nomogram model to predict CSS in patients with early-onset LACC it provided a reference in prognosis prediction and selection of individualized treatment, helping clinicians in decision-making.

Evaluation of multiple biological indicators for the combined diagnosis of metastases from colorectal cancer-a retrospective study based on 1163 patients.

OBJECTIVE: This study aimed to investigate the efficacy of inflammatory markers (NLR, PLR) combined with tumor markers (CA50, CA199, CEA) in the diagnosis of colorectal cancer metastasis by a single-center retrospective study. METHODS: A total of 1163 CRC patients who received treatments in our hospital from January 2017 to December 2021 were enrolled retrospectively. Patients were grouped according to the absence of metastasis. The separate efficacy of tumor markers, NLR and PLR, was evaluated in the diagnosis of metastasis of colorectal cancer using ROC curve analysis, and their optimal cut-off values for distant metastases from colorectal cancer were determined. The area under the ROC curve (AUC) of the tumor markers combined with NLR and PLR was calculated by binary logistic regression analysis to evaluate the diagnostic efficacy of metastasis of colorectal cancer. In addition, patients were divided into two groups of high and low levels according to the optimal cut-off values, and the effects of NLR, PLR, and tumor markers on distant metastasis of colorectal cancer were evaluated using multiple logistic regression analysis. RESULT: The abnormal rate of CA50, CA199, CEA, NLR, and PLR in two subgroupsIt was statistically significant (P < 0.05). After AUC testifying, the diagnostic efficacy of NLR and PLR was equivalent to that of tumor marker (P > 0.05). In assessment of liver metastasis, peritoneal metastasis, and multiple metastasis, AUC of NLR and PLR with CRC-specific tumor markers showed higher predictive efficacy than AUC without combined NLR nor PLR. The CA50, CA199, CEA, PLR, and NLR were proved independently associated with metastasis using multiple logistic regression analysis (P < 0.05). CONCLUSION: NLR and PLR are noted tumor markers of colorectal cancer, which are characterized by noninvasive, high diagnostic efficacy, easy availability, and low cost. They can be combined with traditional tumor markers to evaluate and diagnose colorectal cancer metastasis by clinicians.

A nomogram for predicting the recurrence of small bowel obstruction after gastrectomy in patients with gastric cancer.

BACKGROUND: This study aimed to create a nomogram for predicting the recurrence of small bowel obstruction (SBO) after gastrectomy in patients with gastric cancer (GC) in order to provide better guidance for its diagnosis and treatment. METHODS: A total of 173 patients undergone gastrectomy and developed SBO from January 2015 to October 2022 were admitted into this case-control study. The risk factors of postoperative recurrent SBO were analyzed by univariate and multivariate regression, and a nomogram for predicting the recurrent SBO after gastrectomy was developed using R Studio. RESULTS: Thirty-nine cases of postoperative recurrent SBO occurred among the 173 GC patients who underwent radical gastrectomy, and the percentage of recurrent SBO was 22.54% (39/173). Age [odds ratio (OR) = 0.938, p = 0.026], WBC count (OR = 1.547, p < 0.001), tumor size (OR = 1.383, p = 0.024), postoperative metastasis (OR = 11.792, p = 0.030), and the interval from gastrectomy to first SBO (OR = 1.057, p < 0.001) were all identified as independent risk factors for postoperative recurrent SBO by logistic regression analysis. The receiver operating characteristic curve, the calibration curve, the model consistency index, and the decision curve analysis showed that the nomogram had good predictive performance. CONCLUSION: Based on these factors, we created a nomogram to predict the occurrence of postoperative recurrent SBO. This novel nomogram could serve as a crucial early warning indicator that would guide doctors to make informed decisions while managing patients with gastric cancer.

Heterogeneous cancer-associated fibroblasts: A new perspective for understanding immunosuppression in pancreatic cancer.

Immunotherapy has shown promising efficacy in the treatment of a wide range of cancers; however, it has had little effect on pancreatic cancer. Cancer-associated fibroblasts (CAFs), the predominant mesenchymal cells present in the pancreatic cancer microenvironment, are powerful supporters of the malignant progression of pancreatic cancer. CAFs can modify the microenvironment, establish a refuge to aid cancer cells in immune escape by secreting large amounts of extracellular matrix, and produce soluble cytokines and exosomal vesicles. Hence, CAFs are important contributors to the failure of immunotherapy. Current in-depth studies of CAFs have shown that CAFs are a heterogeneous population of mesenchymal cells; therefore, the functional complexity of their populations needs in-depth explorations in future studies. This review summarizes how heterogeneous CAFs help cancer cells achieve immune escape and suggests potential directions for using CAFs as targets to address immune escape.

Regulatory role of short-chain fatty acids in inflammatory bowel disease.

Inflammatory bowel disease (IBD) comprises a group of chronic inflammatory disorders of the gastrointestinal tract. Accumulating evidence shows that the development of IBD is always accompanied by the dysbiosis of the gut microbiota (GM), causing a decrease in prebiotic levels and an increase in harmful metabolite levels. This leads to persistent immune response and inflammation in the intestine, greatly impairing the physiological function of the gastrointestinal tract. Short-chain fatty acids (SCFAs) are produced by probiotic gut bacteria from a fiber-rich diet that cannot be digested directly. SCFAs with significant anti-inflammatory functions regulate immune function and prevent an excessive immune response, thereby delaying the clinical progression of IBD. In this review, we summarize the generation of SCFAs and their potential therapeutic effects on IBD. Furthermore, we suggest that SCFAs may modulate innate immune recognition and cytokine production to intervene in the progression of IBD. Additional randomized controlled trials and prospective cohort studies should also investigate the clinical impact of SCFA. Video Abstract.