A nomogram to preoperatively predict the aggressiveness of non-functional pancreatic neuroendocrine tumors based on CT features.

OBJECTIVES: To develop a nomogram to predict the aggressiveness of non-functional pancreatic neuroendocrine tumors (NF-pNETs) based on preoperative computed tomography (CT) features. METHODS: This study included 176 patients undergoing radical resection for NF-pNETs. These patients were randomly divided into the training (n = 123) and validation sets (n = 53). A nomogram was developed based on preoperative predictors of aggressiveness of the NF-pNETs which were identified by univariable and multivariable logistic regression analysis. The aggressiveness of NF-pNETs was defined as a composite measure including G3 grading, N+, distant metastases, and/ or disease recurrence. RESULTS: Altogether, the number of patients with highly aggressive NF-pNETs was 37 (30.08 %) and 15 (28.30 %) in the training and validation sets, respectively. Multivariable logistic regression analysis identified that tumor size, biliopancreatic duct dilatation, lymphadenopathy, and enhancement pattern were preoperative predictors of aggressiveness. Those variables were used to develop a nomogram with good concordance statistics of 0.89 and 0.86 for predicting aggressiveness in the training and validation sets, respectively. With a nomogram score of 59, patients with NF-pNETs were divided into low-aggressive and high-aggressive groups. The high-aggressive group had decreased overall survival (OS) and disease-free survival (DFS). Moreover, the nomogram showed good performance in predicting OS and DFS at 3, 5, and 10 years. CONCLUSION: The nomogram integrating CT features helped preoperatively predict the aggressiveness of NF-pNETs and could potentially facilitate clinical decision-making.

The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.

OBJECTIVES: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. METHODS: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. RESULTS: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.

CT-determined low skeletal muscle mass predicts worse overall survival of gastric cancer in patients with cachexia.

BACKGROUND: There were controversies for the association between computed tomography (CT)-determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue. METHODS: We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut-offs for low SMM were defined as <52.4 (men) and < 38.5 cm2 /m2 (women), respectively. Overall survival (OS) was the primary endpoint. RESULTS: Of the 255 included GC patients, 117 (46%) were classified as having low SMM. Those with low SMM were associated with a higher level of circulating interleukin 6 and C reactive protein but a lower level of albumin than those of normal SMM. The univariate analysis showed that low SMM, tumor-node-metastasis (TNM) stage, body mass index (BMI), postoperative chemotherapy, and cachexia were significantly associated with OS, while in the multivariate analysis, only low SMM and TNM stage were significantly associated with OS. Kaplan-Meier survival curves with log-rank tests indicated that low SMM significantly predicted worse OS of GC. After grouping by cachexia, the low SMM significantly predicted worse OS in patients with cachexia instead of those without cachexia. CONCLUSIONS: CT-determined low SMM predicts worse OS of GC in patients with cachexia instead of those without cachexia, and greater attention should be paid to such patients with synchronous low SMM and cachexia.

Prognostic value of cachexia index in patients with colorectal cancer: A retrospective study.

Background: Current diagnostic criteria for cancer cachexia are inconsistent, and arguments still exist about the impact of cachexia on the survival of patients with colorectal cancer. In this study, we aim to investigate the prognostic value of a novel cachexia indicator, the cachexia index (CXI), in patients with colorectal cancer. Methods: The CXI was calculated as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio. The cut-off value of CXI was determined by the receiver operating characteristic (ROC) curves and Youden's index. The major outcomes were major complications, overall survival (OS), and recurrence-free survival (RFS). Results: A total of 379 patients (234 men and 145 women) were included. The ROC curves indicated that CXI had a significantly diagnostic capacity for the detection of major complications. Based on Youden's index, there were 231 and 148 patients in the low and high CXI groups, respectively. Patients in the low CXI group had significantly older age, lower BMI, and a higher percentage of cachexia and TNM stage II+III. Besides, Patients in low CXI group were associated with a significantly higher rate of major complications, blood transfusion, and longer length of stay. Logistic regression analysis indicated that low CXI, cachexia, and coronary heart disease were independent risk factors for the major complications. Kaplan Meier survival curves indicated that patients with high CXI had a significantly more favorable OS than those with low CXI, while no significant difference was found in RFS between the two groups. Besides, there were no significant differences in OS or RFS between patients with and without cachexia. The univariate and multivariate Cox regression analysis indicated that older age, low CXI, and coronary heart disease instead of cachexia were associated with a decreased OS. Conclusion: CXI was better than cachexia in predicting OS and could be a useful prognostic indicator in patients with colorectal cancer, and greater attention should be paid to patients with low CXI.

Development and external validation of a nomogram for individualized adjuvant imatinib duration for high-risk gastrointestinal stromal tumors: A multicenter retrospective cohort study.

INTRODUCTION: The main emphasis of the research about adjuvant imatinib for high-risk gastrointestinal stromal tumors (GISTs) is prolonging the treatment duration and ignores the heterogeneous that 10-year recurrence rates ranged from about 20%-100%. Thus, this study evaluated the effect of different durations of adjuvant imatinib on outcomes in high-risk GISTs to explore the feasibility of individual treatment. METHODS: We analyzed 855 high-risk GIST patients from three centers who underwent macroscopically complete resection between December 2007 and September 2020. The patients were divided into training (n =564) and two validation cohorts (n = 238 and53) based on their source. Recurrence-free survival (RFS) was the primary point. Cox multivariate analysis was used to develop the nomogram. C-index, time-dependent area under the curves, and calibration plots were used to assess the performance of the nomogram. RESULTS: Univariate analysis showed that longer adjuvant imatinib was significantly associated with better 5-year RFS (p < 0.0001). Further investigation identified that the same high-risk patients with lower tumor-associated recurrence risk benefitted little from prolonged treatment and that the recommended adjuvant imatinib duration was insufficient for those with higher recurrence risk. A nomogram for predicting 2-, 3-, and 5-year RFS based on different treatment durations and four major risk factors, namely, tumor site, size, mitotic count, and rupture status, was built and validated, with a C-index of 0.82, 0.74, and 0.70 in training and two external validation cohorts, respectively. An online dynamic nomogram was further developed for clinical applications (https://ruolinliu666.shinyapps.io/GIST/), offering predictive recurrence rates based on different treatment durations and tumor features. CONCLUSIONS: We developed a nomogram to predict the recurrence risk for high-risk patients according to tumor features and treatment durations of imatinib to help physicians on decision-making for individualized treatment duration.

Metabolic syndrome and the risk of colorectal cancer: a systematic review and meta-analysis.

PURPOSE: Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. METHODS: PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. RESULTS: MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26-1.47, P < 0.001), men (RR 1.33, 95% CI 1.21-1.47, P < 0.001), and women (RR 1.34, 95% CI 1.19-1.52, P < 0.001). The risk of colorectal cancer seemed to increase as the number of MetS components rose. Moreover, the high body mass index (BMI)/waist circumference (WC) and hyperglycemia were all significantly associated with a higher risk of colorectal cancer (RR 1.28 [1.20-1.37] and 1.31 [1.14-1.50] in both sexes, RR 1.31 [1.19-1.45] and 1.23 [1.03-1.46] in men, and RR 1.22 [1.02-1.46] and 1.63 [1.16-2.28] in women, respectively). CONCLUSIONS: MetS was significantly associated with a higher risk of colorectal cancer. The high BMI/WC or hyperglycemia might largely account for this association. Further analysis suggested that, as the number of MetS components increased, the risk of colorectal cancer rose.

Inflammatory bowel diseases and the risk of adverse health outcomes: Umbrella review of meta-analyses of observational studies.

BACKGROUND AND AIM: Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. METHODS: Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. RESULTS: This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as "high" quality, only 15% was classified as "moderate," and 65% of outcomes were rated as "very low." CONCLUSION: Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

Inflammatory bowel disease and risk of gastric, small bowel and colorectal cancer: a meta-analysis of 26 observational studies.

PURPOSE: The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. METHODS: We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. RESULTS: Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. CONCLUSIONS: IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

Sarcopenia and adverse health-related outcomes: An umbrella review of meta-analyses of observational studies.

OBJECTIVE: The purpose of this umbrella review was to assess the associations between sarcopenia and adverse health-related outcomes. DESIGN: An umbrella review of meta-analyses of observational studies. SETTING AND PARTICIPANTS: Patients with sarcopenia and controls without sarcopenia were included. MEASURES: The PubMed, Web of Science and Embase were searched for relevant systematic review and meta-analysis. AMSTAR and GRADE system were used for methodological quality and evidence quality assessments, respectively. RESULTS: Totally 54 outcomes extracted from 30 meta-analyses were analyzed. Twenty out of 21 prognostic outcomes indicated that sarcopenia was significantly associated with poorer prognosis of gastric cancer, hepatocellular cancer, urothelial cancer, head and neck cancer, hematological malignancy, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, esophageal cancer, and ovarian cancer. Besides, 10 out of 16 postoperative outcomes suggested that sarcopenia significantly increased the risk of multiple postoperative complications and prolonged the length of hospitalization of patients with digestive cancer. In age-related outcomes, sarcopenia significantly increased the risk of dysphagia, cognitive impairment, fractures, falls, hospitalization, and all-cause mortality of elderly populations. Moreover, sarcopenia was also associated with higher level of albuminuria, risk of depression, and several metabolic diseases. CONCLUSIONS AND IMPLICATIONS: Sarcopenia significantly affected a wide range of adverse health-related outcomes, particularly in patients of tumor and elderly populations. Because evidences of most outcomes were rated as "low" and "very low," more prospective cohort studies are required in the future.

M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer.

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163- macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163- macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163- macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.