Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

The Protective Role of TLR4 in Intestinal Epithelial Cells through the Regulation of the Gut Microbiota in DSS-Induced Colitis in Mice.

BACKGROUND: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. METHODS: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. RESULTS: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by ß-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. CONCLUSIONS: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.

Discovery of extracellular vesicle-delivered miR-185-5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer.

BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

Comparison of the short- and long-term prognosis of early-onset colorectal cancer compared with later-onset colorectal cancer: A systematic review and meta-analysis.

Background and Aims: The annual incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods: We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early- and later-onset patients and performed a prognostic analysis. Random-effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer-special survival (CSS), and disease-free survival (DFS). Network meta-analysis (NMA) was used to compare patients' long-term prognoses in different age subgroups. Results: After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta-analysis of the 5-year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74-0.99; relative risk [RR] 0.83, 95% CI, 0.78-0.89). No difference in prognosis was found between the two groups in terms of 5-year CSS (RR 0.99, 95% CI, 0.93-1.05), 5-year DFS (RR 0.90, 95% CI, 0.74-1.09), and short-term OS. In the NMA, patients aged <30 years had the worst outcome (surface under the cumulative ranking curve [SUCRA], 15.8%) in 5-year OS; consistent results were observed in the analysis of 5-year CSS (<30 years, SUCRA 4.5%), but the difference was not statistically significant. Conclusion: Although patients with early-onset CRC had better OS than those with later-onset CRC, there was no difference in the CSS. Meanwhile, the trend for survival was worse in younger patients, especially in those ages 18-29 years. Thus, more attention should be paid to early diagnosis and treatment of EOCRC. Systematic Review and Meta­Analysis Registration: The systematic review and Meta-analysis protocol was registered with PROSPERO (registration number CRD42022334697).

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

A retrospective case-series of influence of chronic hepatitis B on synchronous liver metastasis of colorectal cancer.

Main point: Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM. Objectives: This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC). Methods: Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM. Results: A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034). Conclusions: The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.

Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer.

Background: Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. The colonscopic score is a good tool for differentiating the severity of patients with DC. At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. Methods: Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. Results: In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. Conclusion: After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma.

Hydroxyphenylpyruvate Dioxygenase Is a Metabolic Immune Checkpoint for UTX-deficient Colorectal Cancer.

BACKGROUND & AIMS: Aberrant epigenetic events mediated by histone methyltransferases and demethylases contribute to malignant progression of colorectal cancer (CRC). However, the role of the histone demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in CRC remains poorly understood. METHODS: UTX conditional knockout mice and UTX-silenced MC38 cells were used to investigate UTX function in tumorigenesis and development of CRC. We performed time of flight mass cytometry to clarify the functional role of UTX in remodeling immune microenvironment of CRC. To investigate metabolic interaction between myeloid-derived suppressor cells (MDSCs) and CRC, we analyzed metabolomics data to identify metabolites secreted by UTX-deficient cancer cells and taken up by MDSCs. RESULTS: We unraveled a tyrosine-mediated metabolic symbiosis between MDSC and UTX-deficient CRC. Loss of UTX in CRC resulted in methylation of phenylalanine hydroxylase, preventing its degradation and subsequently increasing tyrosine synthesis and secretion. Tyrosine taken up by MDSCs was metabolized to homogentisic acid by hydroxyphenylpyruvate dioxygenase. Homogentisic acid modified protein inhibitor of activated STAT3 via carbonylation of Cys 176, and relieved the inhibitory effect of protein inhibitor of activated STAT3 on signal transducer and activator of transcription 5 transcriptional activity. This in turn, promoted MDSC survival and accumulation, enabling CRC cells to acquire invasive and metastatic traits. CONCLUSIONS: Collectively, these findings highlight hydroxyphenylpyruvate dioxygenase as a metabolic checkpoint to restrict immunosuppressive MDSCs and to counteract malignant progression of UTX-deficient CRC.

Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma.

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination. Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes. Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients. Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.

Construction of Nomogram-Based Prediction Model for Clinical Prognosis of Patients with Stage II and III Colon Cancer Who Underwent Xelox Chemotherapy after Laparoscopic Radical Resection.

Objective: To construct a nomogram-based prediction model for the clinical prognosis of patients with stage II and III colon cancer who underwent Xelox chemotherapy after laparoscopic radical resection based on large data sets. Methods: A total of 7,832 patients with colorectal cancer who received postoperative Xelox-based chemotherapy were screened from the Surveillance, Epidemiology, and End Results database (USA) as the training data set. In addition, 348 domestic patients were screened as the validation data set. Multivariate Cox regression analysis was performed to identify variables for inclusion in the nomogram-based prediction model. The predictive accuracy of the model was assessed using C-index and calibration curve. Results: Age, cell differentiation, nerve invasion, T and N stages of tumours, number of dissected lymph nodes, and carcinoembryonic antigen (CEA) level were found to influence the efficacy of postoperative chemotherapy. The nomogram-based prediction model was successfully constructed. The C-index of both the training set and validation set were higher than those of the 7th edition of TNM staging system published by the American Joint Commission on Cancer (C - index of training data set = 0.728, C - index of validation data set = 0.734). The prediction results of the model in the calibration curve showed a good fit with the actual situation. Conclusion: We successfully constructed a nomogram-based model to predict the clinical prognosis of patients with colorectal cancer receiving postoperative Xelox-based chemotherapy after laparoscopic radical resection, which showed good clinical application value for predicting the efficacy of postoperative Xelox-based chemotherapy in patients with colorectal cancer.

Short-Term Outcomes of Tri-Staple Versus Universal Staple in Laparoscopic Anterior Resection of Rectal and Distal Sigmoid Colonic Cancer: A Matched-Pair Analysis.

BACKGROUND: Anastomotic leakage is a serious complication in laparoscopic colorectal surgeries. To resolve this problem, a new stapling technology (Tri-staple) is developed. In this study, we aim to compare the short-term outcomes of Tri-staple versus Universal staple in laparoscopic anterior resection of rectal and distal sigmoid colonic cancer. METHODS: A total of 446 patients were admitted to our hospital and received laparoscopic anterior resection for rectal and distal sigmoid colonic cancer between January 2016 and December 2020. Among them, Tri-staples were used in 202 patients, and the Universal staples were used in 244 patients. Propensity score matching was performed, followed by a comparison between the two groups (Tri-staple vs. Universal staple) in the incidences of anastomotic leakage, bleeding, and reoperation. RESULTS: In total, 270 patients were included in this retrospective cohort study by the propensity score matching, with each group having 135 patients. Tri-staple group had a significant lower incidence of anastomotic leakage compared with the Universal staple group (4.44% vs. 11.11%, P < 0.05). The reoperation rate was also lower in Tri-staple group than the Universal staple group (3.70% vs. 8.15%, P < 0.05). The anastomotic bleeding rates, average postoperative hospital stay, average drain indwelling period, and average fasting period had no statistical differences between the two groups. CONCLUSION: The usage of Tri-staple in laparoscopic anterior resection of rectal and distal sigmoid colonic cancer is associated with lower postoperative complications compared with Universal staple. Future high-quality randomized controlled trials are needed to confirm our findings.

Constructing and Validating a Prognosis Predictive Nomogram for Cancer-Specific Survival in Rectal Cancer Patients Receiving Preoperative Radiotherapy.

Background A predictive tool is required to identify the cancer-specific survival in rectal cancer (RC) patients who have opted to receive preoperative radiotherapy.Methods A database containing the data on RC patients' records of Surveillance, Epidemiology, and End Results (SEER) receiving surgery during 2000-2014 was selected. All patients received neoadjuvant radiotherapy (NR). The correlation of clinicopathological parameters was analyzed using the Chi-square test and the survival risk factors were analyzed using the Cox proportional hazards analysis (univariate and multivariate). Finally, the nomogram was developed and validated to visually represent an accurate prediction of the probability of 3- and 5-year cancer-specific survival (CSS) based on the screened variables of the cohort.Results 11,499 rectal cancer patients were included in our cohort. Patients' records were randomly allocated to either the development or validation cohorts based on an equal ratio (1:1). Performing the multivariate Cox regression analysis incorporating these variables in the development cohort determined 11 independent prognostic factors. Statistically significant differences were recorded among subgroups using log-rank tests, which confirmed the appropriateness and acceptability of factor stratifications. Then, the nomogram was constructed and its concordance index (C-index) values in the development cohort (0.720) and validation cohort (0.717) were evaluated to be higher (P<0.05) than those of the AJCC stage (0.631 and 0.633 respectively). Also, the 3-year AUC values of this nomogram were higher than those of the AJCC stage in both the development cohort (0.746 vs. 0.631) and the validation cohort (0.745 vs. 0.640). Using DCA curves, the predictive potential of the currently developed nomogram outperformed the conventional AJCC staging system.Conclusion The nomogram model might be a more reliable tool to predict prognosis accurately in rectal cancer patients receiving preoperative radiotherapy.

Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas.

Human tumors harbor a plethora of microbiota. It has been shown that the composition and diversity of intratumor microbiome are significantly associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC). However, the association in Chinese patients as well as the effect of different microorganisms on inhibiting tumor growth are unclear. In this study, we collected tumor samples resected from long-term and short-term PDAC survivors and performed 16S rRNA amplicon sequencing. We found that the microbiome in samples with different survival time were significantly different, and the differential bacterial composition was associated with the metabolic pathways in the tumor microenvironment. Furthermore, administration of Megasphaera, one of the differential bacteria, induced a better tumor growth inhibition effect when combined with the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1) treatment in mice bearing 4T1 tumor. These results indicate that specific intratumor microbiome can enhance the anti-tumor effect in the host, laying a foundation for further clarifying the underlying detailed mechanism.

Hypoxic preconditioning promotes the immunosuppressive effects of mesenchymal stem cells in mice with colitis.

Mesenchymal stem cells are promising candidates for stem cell therapy in many diseases, especially in immune-associated diseases. Inflammatory bowel disease is a chronic autoimmune disease that can lead to colorectal cancer if it is not controlled. Mesenchymal stem cells are always under a hypoxic environment in vivo, whether in bone marrow or adipose tissue, whereas researchers always culture MSCs (mesenchymal stem cells) under normoxic conditions (21%). In this study, we aimed to investigate whether hypoxia (1%) affects the therapeutic effect of MSCs. We hypothesize that hypoxia may benefit the treatment efficacy of MSCs. We used DSS to induce IBD (inflammatory bowel disease) in mice and then injected MSCs that had been preconditioned under normoxic conditions (21%) and hypoxic conditions (1%). We found that compared with normoxic-preconditioned MSCs (n-MSCs), hypoxic-preconditioned MSCs (h-MSCs) could alleviate colon inflammation to a large extent, as determined by inflammatory cytokines and CD3+ T cell activation. Mechanistic studies showed that hypoxia could promote iNOS expression in MSCs. Therefore, our data suggest that hypoxia may be more appropriate than normoxia for facilitating MSCs exertion of therapeutic functions.

Body Composition and Response and Outcome of Neoadjuvant Treatment for Pancreatic Cancer.

To assess the correlation of body composition with the response and outcome of neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). One hundred and nineteen PDAC patients underwent curative resection after NAT. Computed tomography scans of the third lumbar vertebra were used to assess the body composition of these patients before and after NAT. Three distinct wasting phenotypes were identified during NAT, with 51 patients (42.9%) developing muscle and fat wasting (MFW), 17 patients (14.3%) developing fat-only wasting (FW), and 51 patients (42.9%) having no wasting (NW). The response rate was higher in the NW phenotype than in the MFW and FW phenotypes (P = 0.007). In univariate and multivariate analyses, histological grade, sarcopenia before NAT, and MFW during NAT were associated with decreased overall survival (OS). Sarcopenia before NAT and MFW during NAT were associated with decreased disease-free survival (DFS). Body composition was associated with the response and outcome of patients undergoing NAT for PDAC. The response rate was higher in patients having NW during NAT. Sarcopenia before NAT and MFW during NAT were associated with decreased OS and DFS.

Three-Port with Natural Orifice Specimen Extraction versus Conventional Laparoscopic Anterior Resection for Rectal-Sigmoid Cancer: A Matched Pair Analysis.

BACKGROUND: The conventional laparoscopic colorectal surgery requires four or more ports to accomplish the laparoscopic dissection, and a mini-laparotomy to remove the specimen, which is a main cause of postoperative pain and incision complications, and compromise the cosmetic results. Reduced port surgery and natural orifice specimen extraction (NOSE) surgery hold the promise to overcome these drawbacks. This study planned to compare peri-operative outcomes of patients with rectal-sigmoid cancer undergoing three-port laparoscopic anterior resection with NOSE (three-port NOSE LAR) to those of patients receiving conventional LAR. METHODS: Twenty-five patients with rectal-sigmoid cancer underwent three-port NOSE LAR between December 2018 and October 2020. For comparison, 50 patients with rectal-sigmoid cancer underwent conventional LAR in the same period were matched. The peri-operative outcomes were compared. RESULTS: Operating time of three-port NOSE group was slightly longer than that of conventional group (135 min vs. 121 min, p = .147). The incision length of three-port NOSE group was shorter than that of conventional group (2.9 cm vs. 7.4 cm, p = .000). Complication rates in three-port NOSE group and conventional group were similar (12.0% vs. 20.0%, p = .524). The tumor size was smaller in three-port NOSE group than the conventional group (2.1 cm vs. 3.5 cm, p = .000). Pain score was lower in three-port NOSE group than the conventional group at postoperative day 1 (1.6 vs. 3.0, p = 0.045) and day 2 (0.2 vs. 2.1, p = .003). The BIQ score was significantly higher in the three-port NOSE group compared to the conventional group (42.9 ± 3.5 vs. 38.2 ± 2.5, p = .002). CONCLUSIONS: Three-port NOSE LAR for rectal-sigmoid cancer is feasible and provides similar peri-operative outcomes compared to conventional LAR. It reduces postoperative pain and produces better cosmesis.

Metal-Organic Framework Hybrids Aid Metabolic Profiling for Colorectal Cancer.

Colorectal cancer (CRC) is the third most common fatal cancer worldwide, accounting for ≈10% of cancer-related mortality. Metabolic shift occurs from the very early stage during the development of CRC, which is of significant etiological and diagnostic importance toward precision medicine. Here, an advanced molecular tool to characterize the metabolic alterations in CRC, based on metal-organic framework (MOF) hybrids is reported. Consuming only 500 nL of plasma without any sample pretreatment, MOF hybrids yield direct metabolic fingerprints by laser desorption/ionization mass spectrometry in seconds. A diagnostic prediction model by a machine learning algorithm is constructed, to discriminate CRC patients from normal controls with an average area under the curve of 0.947 for the discovery cohort and 0.912 for the independent validation cohort. In addition, CRC-specific metabolic signature consisting of 34 potential biomarkers, based on the aforementioned diagnostic model is identified. The results advance the design of nanomaterial-based platforms for metabolic analysis and establish a new liquid biopsy tool for CRC screening compatible with the current clinical workflow in practice.