Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1ß⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn's disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn's disease.

Long-term outcomes of 1-2 cm rectal neuroendocrine tumors after local excision or radical resection: A population-based multicenter study.

Objectives: Studies on rectal neuroendocrine tumors (R-NETs) that are 1-2 cm in size are limited, and the optimal treatment for these tumors is not well established. Methods: Data from patients with primary localized R-NETs 1-2 cm in size were retrospectively collected from 17 large-scale referral medical centers in China. Long-term prognosis, quality of life (QOL), and fecal incontinence were evaluated, and the effects of local excision (LE) or radical resection (RR) were elucidated using propensity score matching (PSM). Results: A total of 272 patients were included in this study; 233 underwent LE, and the remaining 39 underwent RR. Patients in the LE group showed lower tumor location, fewer postoperative Clavien-Dindo III-V complications, more G1 tumors, and lower tumor stage. There were no significant differences in the relapse-free survival or overall survival (OS) between the LE and RR groups after PSM. Patients in the LE group reported superior physical, role, emotional, social, and cognitive functions, global QOL, and Wexner fecal incontinence scores compared with those in the RR group (all P < 0.050). Eighteen (6.6%) patients had lymph node metastases. Multivariable analysis revealed that tumor location (odds ratio [OR] = 3.19, 95% confidence interval [CI] 1.04-10.07, P = 0.010), neutrophil-to-lymphocyte ratio (NLR) > 1.80 (OR = 4.50, 1.46-15.89, P = 0.012), and T3-T4 (OR = 36.31, 95% CI 7.85-208.62, P < 0.001) were independent risk factor for lymph node metastasis. Conclusions: R-NETs measuring 1-2 cm generally have a favorable prognosis, and there is no difference in postoperative survival between LE and RR. For patients without lymph node metastasis, LE should be the preferred choice; however, for patients with a higher tumor location, preoperative NLR >1.8 or T3/T4 tumors, RR should be considered.

Local Excision Versus Radical Resection for Grade 2 Rectal Neuroendocrine Tumors: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: Studies on the grade 2 rectal neuroendocrine tumors are limited and the optimal treatment for these tumors is not well established. OBJECTIVE: To compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors. DESIGN: Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the difference between surgery strategies. SETTINGS: Seventeen Chinese large-scale medical centers participated in this study. PATIENTS: A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed. MAIN OUTCOME MEASURES: Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies. RESULTS: A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes based on the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors ≤ 1.5 cm, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups (P >0.05). In patients with grade 2 rectal neuroendocrine tumors > 1.5 cm, relapse-free survival was significantly lower in the local excision group than in the radical resection group (P = 0.04). LIMITATIONS: The nature of retrospective review and relatively short follow-up period are limitations of this study. CONCLUSIONS: Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors ≤ 1.5 cm without metastasis, while radical resection is more beneficial in those > 1.5 cm. See Video Abstract.

Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.

BACKGROUND: In recent years, the significance of the nervous system in the tumor microenvironment has gained increasing attention. The bidirectional communication between nerves and cancer cells plays a critical role in tumor initiation and progression. Perineural invasion (PNI) occurs when tumor cells invade the nerve sheath and/or encircle more than 33% of the nerve circumference. PNI is a common feature in various malignancies and is associated with tumor invasion, metastasis, cancer-related pain, and unfavorable clinical outcomes. The colon and rectum are highly innervated organs, and accumulating studies support PNI as a histopathologic feature of colorectal cancer (CRC). Therefore, it is essential to investigate the role of nerves in CRC and comprehend the mechanisms of PNI to impede tumor progression and improve patient survival. CONCLUSION: This review elucidates the clinical significance of PNI, summarizes the underlying cellular and molecular mechanisms, introduces various experimental models suitable for studying PNI, and discusses the therapeutic potential of targeting this phenomenon. By delving into the intricate interactions between nerves and tumor cells, we hope this review can provide valuable insights for the future development of CRC treatments.

The impact of indirect notification of a cancer diagnosis and a risk model based on it to predict the prognosis of postoperative stage T3 esophageal cancer patients.

Chinese doctors are required to inform patients' direct relatives of a cancer diagnosis rather than the patients themselves. The disease may be hidden from patients by their family members, which could result in severe outcomes. We selected postoperative T3 esophageal cancer (EsC) patients hospitalized from June 2015 to December 2019 as research subjects. The patients were divided into a direct-notification group and an indirect-notification group. Several variables were used to evaluate both groups' 36-month progress-free survival (PFS). A risk prediction model of prognosis based on the risk score was established, which was assessed using the area under the curve (AUC) of the receiver operating characteristic curve. One hundred and thirteen patients were enrolled in the training group and forty-eight in the validation group. Cox multivariate regression analysis revealed that males, late stage, poor pathological differentiation, and indirect notification were independent worse risk factors for postoperative T3 stage EsC patients at 36-month PFS (hazard ratio (HR) = 0.454, 95% confidence interval (CI): 0.254-0.812, P = .008; HR = 1.560, 95% CI: 1.006-2.420, P = .047; HR = 0.595, 95% CI: 0.378-0.936, P = .025; HR = 2.686, 95% CI: 1.679-4.297, P < 0.001, respectively). The type of notification was the best correlation factor. The risk score was calculated as follows: risk score = 0.988 × cancer notification (indirect = 1, direct = 0)-0.790 × sex (female = 1, Male = 0) + 0.445 × stage (IIIB = 1, IIA + IIB = 0)-0.519 × pathological differentiation (moderately + well = 1, poorly = 0). The model had a sensitivity of 64.8% and specificity of 81.8%, with the AUC at 0.717 (95% CI: 0.614-0.810) in internal verification, and a sensitivity of 56.8% and specificity of 100%, with the AUC at 0.705 (95% CI: 0.651-0.849) in external validation. The model had good internal and external stability. The model showed a Brier score of 0.18. Indirect notification of a cancer diagnosis was an important negative predictor of postoperative EsC patients' PFS. The model displayed good accuracy and stability in the prediction of risk for cancer progression.

Lymph node ratio and hematological parameters predict relapse-free survival in patients with high grade rectal neuroendocrine neoplasms after radical resection: a multicenter prognostic study.

BACKGROUND: The prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection. METHODS: We reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010-April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging. RESULTS: A total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379-11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011-9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224-19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses. CONCLUSIONS: LNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging.

Fungal dysbiosis facilitates inflammatory bowel disease by enhancing CD4+ T cell glutaminolysis.

The fungal microbiota is an important component of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation. However, how fungi regulate inflammatory bowel disease (IBD) is poorly understood. This study found that intestinal fungi regulate immune responses in IBD. Antibiotic-mediated depletion of fungi facilitated the development of IBD. Fungi greatly enhanced oxidative phosphorylation (OXPHOS) by enhancing glutaminolysis. Mechanistically, we found that fungi could activate the dectin-1-Syk- NF-κB signaling pathway to promote the expression of key enzymes and transporters involved in glutaminolysis. In summary, our findings reveal that fungal interactions in the human gut could be a promising therapeutic target for IBD.

LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51.

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis. However, the effect of lncRNA on chemoresistance and RNA alternative splicing remains largely unknown. In this study, we identified a novel lncRNA, CACClnc, which was upregulated and associated with chemoresistance and poor prognosis in colorectal cancer (CRC). CACClnc promoted CRC resistance to chemotherapy via promoting DNA repair and enhancing homologous recombination in vitro and in vivo. Mechanistically, CACClnc specifically bound to Y-box binding protein 1 (YB1, a splicing factor) and U2AF65 (a subunit of U2AF splicing factor), promoting the interaction between YB1 and U2AF65, and then modulated alternative splicing (AS) of RAD51 mRNA, and consequently altered CRC cell biology. In addition, expression of exosomal CACClnc in peripheral plasma of CRC patients can effectively predict the chemotherapy effect of patients before treatment. Thus, measuring and targeting CACClnc and its associated pathway could yield valuable insight into clinical management and might ameliorate CRC patients' outcomes.

Mesenchymal Stem Cells Versus Placebo for Perianal Fistulizing Crohn's Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy for perianal fistulizing Crohn's disease (pfCD) has been extensively studies in the past decade. Its efficacy and safety had been preliminarily confirmed in some phase 2 or phase 3 clinical trials. This meta-analysis is performed to evaluate the efficacy and safety of MSCs-based therapy for pfCD. METHODS: Electronic databases (Pubmed, Cochrane Library, Embase) were searched for studies that reported the efficacy and safety of MSCs. And RevMan were used to assess the efficacy and safety. RESULTS: After screening, 5 randomized controlled trials (RCTs) were included in this meta-analysis. RevMan 5.4 for meta-analysis showed that: [Efficacy] Patients had definite remission after MSCs treatment, with an odds ratio (OR) of 2.06 (P < .0001, 95%CI 1.46, 2.89) vs controls. [Safety] The incidence of the most frequently reported TEAEs (treatment-emergent adverse events, TEAEs), perianal abscess and proctalgia, did not significantly increase due to the use of MSCs, with an OR of 1.07 in perianal abscess (P = .87, 95%CI 0.67, 1.72) vs controls, and an OR of 1.10 in proctalgia (P = .47, 95%CI 0.63, 1.92) vs controls. CONCLUSIONS: MSCs seem to be an effective and safe therapy for pfCD. MSCs based therapy has the potential to be used in combination with traditional therapies.

Intracorporeal reinforcement with barbed suture is associated with low anastomotic leakage rates after laparoscopic low anterior resection for rectal cancer: a retrospective study.

BACKGROUND: Anastomotic leakage (AL) is one of most severe postoperative complications following low anterior resection (LAR) for rectal cancer, and has an adverse impact on postoperative recovery. The occurence of AL is associated with several factors, while few studies explored the role of intracorporeal barbed suture reinforcement in it. METHODS: Consecutive cases underwent laparoscopic LAR for rectal cancer from Mar. 2018 to Feb. 2021 in our center were retrospectively collected. Cases were classified into the intracorporeal barbed suture reinforcement group and the control group according to whether performing intracorporeal reinforcement with barbed suture, and AL incidences were compared between two groups. Propensity score matching (PSM) was then performed based on identified risk factors to reduce biases from covariates between two groups. AL incidences in the matched cohort were compared. RESULTS: A total of 292 cases entered into the study, and AL incidences were significantly lower in the intracorporeal barbed suture reinforcement group compared with the control group (10.00% vs 2.82%, P = 0.024). Sex, BMI, preoperative adjuvant chemoradiotherapy and anastomotic level were chose for PSM analyses based on previous studies. In the matched cohort, the AL incidences were still significantly lower in the intracorporeal barbed suture reinforcement group (10.57% vs 2.44%, SD = 0.334). CONCLUSIONS: Intracorporeal barbed suture reinforcement is associated with low AL incidences after laparoscopic LAR for rectal cancer, which is a potential procedure for reducing AL and worthy of application clinically.

Evaluating treatment strategies for non-small cell lung cancer during COVID-19: A propensity score matching analysis.

We employed pandemic treatment strategies that we developed at the beginning of the coronavirus disease 2019 (COVID-19) pandemic, and it was not clear whether any adverse results were associated with our strategies. Therefore, we carried out a retrospective study to compare our pandemic treatment strategies with prepandemic protocols to determine whether the strategies used during the high-risk period of COVID-19 were appropriate. The observation period was September 2019 to February 2020. Patients hospitalized from December 2019 to February 2020 were included as an experimental group, and individuals hospitalized from September 2019 to November 2019 were included as a control group. All non-small cell lung cancer patients hospitalized during the observation period were included except for pediatric and obstetric patients, patients younger than 18 years old, and patients admitted only for routine follow-up examinations. Treatment strategies were evaluated based on the prognosis of the different treatment methods, including surgical and nonsurgical treatments and discontinuation of therapy. Survival curves were analyzed using the Kaplan-Meier method. Cox regression analysis was used for multivariate analysis of risk factors for progress-free survival. Propensity score matching was used for clinical characteristics to adjust for selection bias. Therapy discontinuation in the experimental group was significantly higher than in the control group (P < .001). The differences in cancer progression and the number of deaths between the 2 groups were not significant (P = .38 and .13, respectively). For late-stage patients, there were significant differences in nonsurgical treatment and discontinued therapy (P < .001 and < .001, respectively) between the 2 groups, while the cancer progression and death toll differences were not significant (P = .20 and .20, respectively). For early-stage patients, the differences in surgical treatment, discontinued therapy, cancer progression, and death toll were not significant (P = .24, 0.24, 0.61, and 0.49, respectively) between the 2 groups. Multivariate analysis revealed that temporary discontinuation of therapy did not predict poor progress-free survival independently (hazard ratio = 1.007, 95% confidence interval: 0.653-1.552, P = .98). For patients in geographical regions with a high risk for COVID-19 infections, temporarily suspending treatment for late-stage non-small cell lung cancer patients is not likely to significantly impact their prognosis if they can return to treatment within 3 months of discontinuation.

Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer.

Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC. Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein-protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apc min/+ and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes. Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK-STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC. Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC.

Targeting type Iγ phosphatidylinositol phosphate kinase overcomes oxaliplatin resistance in colorectal cancer.

Rationale: Oxaliplatin is a widely used chemotherapy drug for advanced colorectal cancer (CRC) and its resistance is a major challenge for disease treatment. However, the molecular mechanism underlying oxaliplatin resistance remains largely elusive. Methods: An integrative analysis was performed to determine differentially expressed genes involved in oxaliplatin resistance. Loss- and gain-of-function studies were employed to investigate the roles of type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) on oxaliplatin resistance in CRC cells. Exosomes derived from CRC cell lines were assessed for PD-L1 level and the ability to promote oxaliplatin resistance. Quantitative real-time PCR, immunofluorescence, luciferase reporter assay, Western blotting and other techniques were conducted to decipher the molecular mechanism. Results: PIPKIγ was identified as a critical gene related to oxaliplatin resistance in CRC. Genetic manipulation studies revealed that PIPKIγ profoundly facilitated oxaliplatin resistance and affected the expression of DNA damage repair proteins. Mechanistically, PIPKIγ promoted the expression of the immune checkpoint molecule PD-L1 via activation of NF-κB signaling pathway. Genetic silencing of PD-L1 did not affect CRC cell proliferation but significantly sensitized CRC cells to oxaliplatin. Notably, PD-L1 was revealed to be encapsulated in the exosomes, and the addition of exosomal PD-L1 to sh-PD-L1 CRC cells restored oxaliplatin resistance. Pharmacological hijacking PIPKIγ-exosomal PD-L1 axis largely reduced oxaliplatin resistance in CRC cells. In vivo experiments showed that PD-L1 loss significantly blocked oxaliplatin resistance and the addition of PD-L1-enriched exosomes promoted tumor growth and reduced mouse survival time. Conclusion: Our findings reveal a previous unprecedented role of PIPKIγ in oxaliplatin resistance and provide a key mechanism of exosomal PD-L1 in CRC with potential therapeutics.

D3 Versus D2 Lymphadenectomy in Right Hemicolectomy: A Systematic Review and Meta-analysis.

PURPOSE: D3 lymphadenectomy for right colon cancer improves oncological outcomes. This meta-analysis aimed to compare operation data, histopathological characteristics, perioperative conditions, and long-term survival after D3 and D2 lymphadenectomy in right hemicolectomy. METHODS: We searched PubMed, Embase, and the Cochrane Library for relevant articles (up to March 31, 2020). Random-effects and fixed-effects meta-analysis models were used. Review Manager (RevMan) version 5.3 and Stata version 15.1 were used for pooled estimates. RESULTS: After screening 714 articles, 7 articles with a total of 1368 patients were eligible for inclusion. Compared with D2, D3 lymphadenectomy improves results in terms of blood loss (weighted mean difference [WMD] = -20.63, 95% confidence interval [CI] -28.19 to -13.16, P < .01), harvested lymph nodes (WMD = 8.86, 95% CI 7.74 to 9.98, P < .01), 3-year overall survival (OS) (hazard ratio [HR] = 2.03, 95% CI 1.20 to 3.43, P < .01), 5-year OS (HR = 2.22, 95% CI 1.15 to 4.30, P = .02), and 5-year disease-free survival (DFS) (HR = 2.16, 95% CI 1.19 to 3.90, P = .01). There was no significant difference regarding operation time, anastomosis leakage, wound infection, overall morbidity, postoperative hospital stay, mortality, length of dissected colon, and 3-year DFS (P >= .05). CONCLUSIONS: It is suggested in this review that D3 lymphadenectomy is superior to D2 lymphadenectomy in terms of blood loss, harvested lymph nodes, 3-year OS, 5-year OS, and 5-year DFS. The conclusion must be drawn with caution due to the limited number of included studies. Further RCTs are needed for stronger evidence.

Nerve Dependence in Colorectal Cancer.

Cancerous invasion of nerves has been reported in a list of malignant tumors as a high-risk pathological feature and marker of poor disease outcome especially in neurotrophic cancers (such as in pancreas and prostate), indicating that although once neglected, nerves could have played a pivotal role in tumorigenesis and cancer progression. In colorectal cancer, perineural invasion, a specific form of tumor-nerve interaction referring to the identification of tumor cells in proximity to the nerve, has been recognized as a strong and independent prognosis predictor; denervation of autonomic nerves and enteric nerves have shown that the existence of these nerves in the gut are accompanied by promoted cancer proliferation, further supporting that nerve is a potential accomplice to shield and nurture tumor cells. However, the precise role of nerve in CRC and the pattern of interaction between CRC cells and nerve has not been unveiled yet. Here we aim to review some basic knowledge of the importance of nerves in CRC and attempt to depict a mechanistic view of tumor-nerve interaction during CRC development.

SIRT1 induces the accumulation of TAMs at colorectal cancer tumor sites via the CXCR4/CXCL12 axis.

Our previous work suggested that high SIRT1 expression by cancer cells predicted a poor colorectal cancer (CRC) prognosis, but its role in the tumor microenvironment was unclear. Here, we examined tumor-infiltrating lymphocytes (TILs) in CRC expressing different levels of SIRT1. We also established a co-culture system with monocytes, CD8+ T cells and patient-derived tumor organoids (PDOs) to study the relationships between immune cells and cancer cells. The percentage of CD8+ T cells was decreased and the percentage of macrophages was increased in SIRT1-high (SIRT1-hi) CRC. Co-culture results showed that tumor-associated macrophages (TAMs) from SIRT1-hi CRC inhibited the proliferation and anti-tumor activity of CD8+ T cells. Importantly, SIRT1-hi CRC were shown to modulate the migration and the activity of TAMs. RNA sequencing revealed that CD14+ monocytes in SIRT1-hi patients expressed higher levels of CXCR4. Mechanistically, SIRT1 expression was shown to promote CXCL12 expression by inhibiting the acetylation of p53. Our findings indicate that SIRT1 in CRC induces TAM migration through the CXCR4/CXCL12 pathway, and inhibits the proliferation and activity of CD8+ T cells, resulting in promotion of CRC progression.

Lymphadenectomy Around Inferior Mesenteric Artery in Low-Tie vs High-Tie Laparoscopic Anterior Resection: Short- and Long-Term Outcome of a Cohort of 614 Rectal Cancers.

BACKGROUND: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers. METHODS: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p<0.05 was considered significant. RESULTS: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT. CONCLUSION: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.

MIN score predicts primary response to infliximab/adalimumab and vedolizumab therapy in patients with inflammatory bowel diseases.

Infliximab/adalimumab (IFX/ADA) and vedolizumab (VDZ) are the most widely used biologics in inflammatory bowel diseases. Current models used to predict their efficacies are restricted to either Crohn's disease or ulcerative colitis or to only one type of biologic, which makes them limited in external validation. We therefore designed a comprehensive comparison among these models to identify the most meaningful predictors for patient responses. Several biomarkers and models were compared for their abilities to predict both IFX/ADA and VDZ responses by receiver operating characteristic curves. Least absolute shrinkage and selection operator regression was adopted to determine a simplified gene signature. Verification was performed in biopsy samples by immunohistochemical staining. The GIMATS module (based on counts of IgG plasma cells, inflammatory monocytes, activated T cells, and stromal cells) had the best overall performance for response prediction in both biologics (IFX/ADA, AUC = 0.720-0.853; VDZ, AUC = 0.661-0.728). Based on this module, patients were equally divided into 3 groups: M type (GIMATS-low, metabolism), with a preference for IFX/ADA; I type (GIMATS-high, immune), with a preference for VDZ; and N type (GIMATS-medium, normal), with no preference for either treatment. Furthermore, to improve clinical utility, a simplified 6-gene model, MIN score, was established to determine the baseline expression of G0S2, S100A9, SELE, CHI3L1, MMP1 and CXCL13 and function as a substitute for GIMATS module. Our study suggested that the classification of metabolic or immune type by MIN score was valuable for IBD diagnosis to assist with selection of IFX/ADA and VDZ.

Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.