Effects of Dietary Aflatoxin B1 on Hybrid Grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) Growth, Intestinal Health, and Muscle Quality.

This study investigated the effects of varying doses of dietary aflatoxin B1 (AFB1) on the growth, intestinal health, and muscle quality of hybrid grouper. Four diets with varying AFB1 concentrations (0, 30, 445, and 2,230 µg kg-1) were used. Elevating AFB1 concentrations led to a decline in growth indexes, specifically the weight gain rate and the specific growth rate, although the survival rate remained unchanged. Morphological indicators showed a dose-dependent decline with AFB1 exposure. Intestinal MDA content and hindgut reactive oxygen species (ROS) levels increased, while antioxidant indexes and digestive enzymes decreased with higher AFB1 levels. AFB1 negatively influenced hindgut tight junction protein and antioxidant-related gene expression while promoting inflammation-related gene expression. The presence of AFB1 in the experiment led to a decrease in beneficial intestinal bacteria, such as Prevotella, and an increase in harmful intestinal bacteria, such as Prevotellaceae_NK3B31_group. Muscle lipid and unsaturated fatty acid content significantly decreased, while muscle protein and liver AFB1 content increased dramatically with higher AFB1 concentrations. AFB1 caused myofibrillar cleavage and myofilament damage, leading to increased spaces between muscle fibers. In conclusion, diets with AFB1 levels exceeding 30 µg kg-1 inhibited hybrid grouper growth, while levels surpassing 445 µg kg-1 resulted in hindgut ROS accumulation, inflammation, elevated intestinal permeability, reduced digestive enzyme activity, and compromised muscle quality.

Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C).

INTRODUCTION: The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC. METHODS AND ANALYSIS: TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12). TRIAL REGISTRATION NUMBER: NCT05732493.

Effects of α-Lipoic Acid Supplementation on Growth Performance, Liver Histology, Antioxidant and Related Genes Expression of Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂).

This study aimed to assess the impact of α-lipoic acid on the growth performance, antioxidant capacity and immunity in hybrid groupers (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus) fed with a high-lipid diet. Groupers (8.97 ± 0.01 g) were fed six different diets, with α-lipoic acid content in diets being 0, 400, 800, 1200, 1600, and 2000 mg/kg, named S1, S2, S3, S4, S5, and S6, respectively. The results show that the addition of 2000 mg/kg α-lipoic acid in the diet inhibited the growth, weight gain rate (WGR), and specific growth rate (SGR), which were significantly lower than other groups. In serum, catalase (CAT) and superoxide dismutase (SOD) were significantly higher in the S5 group than in the S1 group. In the liver, CAT, SOD and total antioxidative capacity (T-AOC) levels were significantly increased in α-lipoic acid supplemented groups. α-lipoic acid significantly upregulated liver antioxidant genes sod and cat, anti-inflammatory factor interleukin 10 (il10) and transforming growth factor ß (tgfß) mRNA levels. Conclusion: the addition of 2000 mg/kg of α-lipoic acid inhibits the growth of hybrid groupers. In addition, 400-800 mg/kg α-lipoic acid contents improve the antioxidant capacity of groupers and have a protective effect against high-lipid-diet-induced liver oxidative damage.

Radiomics of skeletal muscle helps to predict gastrointestinal toxicity in locally advanced rectal cancer patients receiving neoadjuvant chemoradiotherapy.

Background: The skeletal muscle index (SMI) can serve as a surrogate for a patient's nutritional status, which is associated with treatment toxicity. This study aims to investigate the potential of baseline skeletal muscle radiomics features to predict gastrointestinal toxicity of neoadjuvant chemoradiotherapy for rectal cancer. Methods: A total of 214 rectal cancer patients (115, 49 and 50 in the training, internal and external validation set, respectively) who underwent neoadjuvant pelvic radiotherapy with capecitabine and irinotecan were retrospectively identified. The skeletal muscle at the level of the third lumber vertebra was contoured, and the radiomics features were extracted from computed tomography scans. In the training set, the least absolute shrinkage and selection operator (LASSO) regression algorithm was applied to select features that were most significantly associated with grade 3-4 gastrointestinal toxicity (diarrhea, nausea, vomiting and proctitis). The predictive performance and clinical utility were estimated using the area under the receiver operator characteristic curve (AUC), F1-score and decision curve analysis (DCA). Results: Nine features, including the SMI and eight radiomics features, were associated with grade 3-4 gastrointestinal toxicity and included in the logistic regression. This combined predictive model, which incorporated the SMI and radiomics features, showed better discrimination than the SMI alone, with an AUC of 0.856 (95 % CI: 0.782-0.929) in the training cohort, 0.812 (95 % CI: 0.667-0.956) in the internal validation cohort and 0.745 (95 % CI: 0.600-0.890) in the external validation cohort. DCA further verified the clinical utility of the combined predictive model. Conclusion: Radiomics features of skeletal muscle were significantly associated with gastrointestinal toxicity. The predictive model incorporating the SMI and radiomics features exhibits favorable discrimination and may be highly informative for clinical decision-makings.

Effects of High-Lipid Dietary Protein Ratio on Growth, Antioxidant Parameters, Histological Structure, and Expression of Antioxidant- and Immune-Related Genes of Hybrid Grouper.

The hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus) is a new species of grouper crossed from giant grouper (E. lanceolatus) as the male parent and brown-marbled grouper (E. fuscoguttatus) as the female parent. We hypothesized that optimal levels of dietary protein may benefit liver function. High-lipid diets are energetic feeds that conserve protein and reduce costs, and are a hot topic in aquaculture today. Therefore, the objective of the research is to investigated the effects of dietary protein level in high-lipid diets on serum and liver biochemistry, liver histology, and liver immune and antioxidant indexes and gene mRNA expression of the juvenile hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus). Six iso-lipidic (161 g/kg) diets were formulated containing graded levels of protein (510 as control, 480,450, 420, 390 and 360 g/kg). Each treatment consisted of three replicates and 30 fish (6.70 ± 0.02 g) in one replicate. After an 8-week feeding experiment, the results indicated the following: (1) With the decreasing of dietary protein level, the specific growth rate (SGR) of groupers increased gradually and then decreased; SGRs of the 390 and 360 g/kg groups were significantly lower than other groups (p < 0.05). (2) In terms of serum and liver, the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD), and the total antioxidant capacity (T-AOC) content, and the activity of immune enzymes such as lysozyme (LYS) and immunoglobulin (IgM) was significantly increased under the appropriate protein level. (3) Based on liver histology, we know that high or low dietary protein levels cause liver damage. (4) Dietary protein levels can significantly affect the mRNA expression levels of an anti-inflammatory factor gene (tgfß), pro-inflammatory factor genes (il6, il8), heat shock proteins, and antioxidant and immune genes (hsp70 and hsp90, gpx, nrf2, keap1). It is concluded that the appropriate protein level can promote the growth performance of groupers, improve antioxidant activity and immune enzyme activity in serum and liver, and enhance the expression of immune genes.

Lycopene Alleviates the Adverse Effects of Feeding High-Lipid Diets to Hybrid Grouper (♀Epinephelus fuscoguttatus ×♂E. lanceolatus).

It has been found that high-lipid diets (HLDs) disrupt lipid metabolism in fish, leading to an excessive accumulation of lipids in various tissues of the fish body. The objective of this study was to investigate if the inclusion of lycopene (LCP) in an HLD may mitigate the adverse consequences of excessive dietary lipid intake in hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus). The experimental design incorporated a control group (L0), which was administered a diet consisting of 42% protein and 16% lipid. The diets for groups L1, L2, and L3 were developed by augmenting the control diet with 100, 200, and 400 mg/kg LCP, respectively. The duration of the trial spanned a period of 42 days. The results of the study showed that the weight gain rate (WGR) and protein efficiency ratio (PER) of the three LCP treatment groups (L1, L2, and L3) tended to increase and then decrease, with a significant increase in WGR and PER in L2 (P < 0.05). Visceral somatic index and hepatic somatic index tended to decrease and then increase in all treatment groups, with a significant decrease in L2 (P < 0.05). In serum dietary LCP significantly reduced triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) content and significantly increased high-density lipoprotein (HDL) content (P < 0.05). In the liver, dietary LCP reduced TC, TG, and very LDL levels and improved lipoprotein lipase, hepatic lipase, fatty acid (FA) synthetase, and acetyl-CoA carboxylase activities. The number and area of hepatic lipid droplets decreased significantly with increasing LCP content. In the liver, the addition of appropriate levels of LCP significantly upregulated lipoprotein lipase (lpl) and peroxisome proliferator-activated receptor α (pparα). In summary, dietary LCP improves growth and reduces lipid deposition in the liver of hybrid grouper by increasing lipolytic metabolism and decreasing FA synthesis. Under the experimental conditions, the fitted curve analysis showed that the recommended LCP additions to the high lipid diet for juvenile hybrid grouper were 200-300 mg/kg.

Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E).

INTRODUCTION: Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a 'Watch & Wait' (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer. METHODS AND ANALYSIS: TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3-4 adverse effects rate and patients' quality of life. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05555888 (ClinicalTrials.gov).

RIFLE: a Phase II trial of stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer.

Background: Currently, the prognosis for metastatic colorectal cancer (mCRC) still remains poor. The management of mCRC has become manifold because of the varied advances in the systemic and topical treatment approaches. For patients with limited number of metastases, radical local therapy plus systemic therapy can be a good choice to achieve long-term tumor control. In this study, we aimed to explore the efficacy and safety of the combination of fruquintinib, tislelizumab, and stereotactic ablative radiotherapy (SABR) in mCRC (RIFLE study). Methods: RIFLE was designed as a single-center, single-arm, prospective Phase II clinical trial. A total of 68 mCRC patients who have failed the first-line standard treatment will be recruited in the safety run-in phase (n = 6) and the expansion phase (n = 62), respectively. Eligible patients will receive SABR followed by fruquintinib (5 mg, d1-14, once every day) and tislelizumab (200 mg, d1, once every 3 weeks) within 2 weeks from completion of radiation. The expansion phase starts when the safety of the treatment is determined (dose limiting toxicity occur in no more than one-sixth of patients in the run-in phase). The primary end point is the objective response rate. The secondary end points include the disease control rate, duration of response, 3-year progression-free survival rate, 3-year overall survival rate, and toxicity. Conclusions: The results of this trial will provide a novel insight into SABR in combination with PD-1 antibody and vascular endothelial growth factor receptor inhibitor in the systematic treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients. Trial registration: NCT04948034 (ClinicalTrials.gov).

Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report.

BACKGROUND: Currently, chemotherapy combined with immunotherapy is the established first-line standard treatment for advanced gastric cancer (GC). In addition, the combination of radiotherapy and immunotherapy is considered a promising treatment strategy. CASE SUMMARY: In this report, we present a case of achieving nearly complete remission of highly advanced GC with comprehensive therapies. A 67-year-old male patient was referred to the hospital because he presented with dyspepsia and melena for several days. Based on fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), endoscopic examination and abdominal CT, he was diagnosed with GC with a massive lesion and two distant metastatic lesions. The patient received mFOLFOX6 regimen chemotherapy, nivolumab and a short course of hypofractionated radiotherapy (4 Gy × 6 fractions) targeting the primary lesion. After the completion of these therapies, the tumor and the metastatic lesions showed a partial response. After having this case discussed by a multidisciplinary team, the patient underwent surgery, including total gastrectomy and D2 lymph node dissection. Postoperative pathology showed that major pathological regression of the primary lesion was achieved. Chemoimmunotherapy started four weeks after surgery, and examination was performed every three months. Since surgery, the patient has been stable and healthy with no evidence of recurrence. CONCLUSION: The combination of radiotherapy and immunotherapy for GC is worthy of further exploration.

Effects of choline supplementation on growth performance, liver histology, nonspecific immunity and related genes expression of hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatu) fed with high-lipid diets.

This study was conducted to evaluate the effect of dietary choline levels on growth performance, liver histology, nonspecific immunity and related gene expression of hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus) fed with high-lipid diets. The fish (initial body weight 6.86 ± 0.01 g) were fed diets containing different choline levels (0, 5, 10, 15, and 20 g/kg, named D1, D2, D3, D4, and D5, respectively) for 8 weeks. The results showed that:(1) dietary choline levels had no significant effect on final body weight (FBW), feed conversion rate (FCR), visceral somatic index(VSI) and condition factor (CF) compared with the control group (P > 0.05). However, the hepato somatic index (HSI) in the D2 group was significantly lower than that in the control group and the survival rate (SR) in the D5 group was significantly lower (P < 0.05). (2) with dietary choline level increasing, alkaline phosphatase (AKP) and superoxide dismutase (SOD) of serum showed a tendency to increase and then decrease, and the maximum values were obtained in the D3 group, but the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly (P < 0.05). (3) Immunoglobulin M (IgM), lysozyme (LYZ), catalase (CAT), total antioxidative capacity (T-AOC), and SOD in the liver all showed a trend of first increase and then decrease with the dietary choline level increased, and all of them achieved the maximum value at D4 group (P < 0.05), while reactive oxygen species (ROS) and malondialdehyde (MDA) in the liver decreased significantly (P < 0.05). (4) results from liver sections suggest that appropriate levels of choline can improve cell structure, compared with the control group, the damaged histological morphology of the liver was relieved and even returned to normal in D3 group. (5) in the D3 group, choline significantly upregulated the expression of hepatic sod and cat mRNA, whereas the expression of cat in the D5 group was significantly lower than that in the control group (P < 0.05); And the supply of choline stimulated a significant down-regulation of interleukin 6 (il6), myeloid differentiation factor 8 (myd88), toll-like receptor 22 (tlr22) mRNA expression levels in liver, while the expression of cellular tumor antigen p53 (p53) and interleukin 10 (il10) showed an upward and then downward trend (P < 0.05). In general, choline can improve the immunity of hybrid grouper by regulating non-specific immune-related enzyme activity and gene expression and reducing oxidative stress induced by high-lipid diet.

Transcriptomic Analysis of Liver in Silver sillago, Sillago sihama Fed with High-Level Low-Gossypol Cottonseed Meal in Replacement of Fishmeal Diet.

Understanding the molecular mechanisms involved in adaptation to alternate diets has become a significant concern, as increasing amounts of fishmeal (FM) protein in aquafeeds are being substituted with plant protein. Thus, the goal of this study was to assess growth performance, quality, and liver function of juvenile Sillago sihama (S. sihama) through growth indices, whole-body composition, histology of the liver, and RNA-sequencing (RNA-seq), after they were fed a formulated diet with 64% low-gossypol cottonseed meal (LCSM) for 56 days, compared to those fed a traditional FM-based diet. Indicators of growth, including final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio (PER), and condition factor (CF), were considerably lower in the 64% LCSM (R64) group than in the FM diet group. In the R64 diet, the whole crude lipid was significantly lower than in the FM diet. The hematoxylin-eosin section showed that dietary high levels of LCSM resulted in diffuse lipid vacuolation in the liver of S. sihama. According to a liver transcriptome analysis, high LCSM intake in the diet significantly impacted lipid synthesis and catabolism, elevated pathways for cholesterol synthesis, blocked several amino acid metabolic pathways, and adversely affected hepatic gluconeogenesis and glycolysis. The findings of this study indicate that feeding high levels of LCSM in S. sihama is harmful to the growth of the organism and can harm the liver's structural integrity, as well as obstruct the normal metabolism of amino acids, lipids, and carbohydrates. Therefore, it is not recommended to substitute LCSM for high levels of FM in the diet of S. sihama.

COVID-19 pandemic: impacts on air quality and economy before, during and after lockdown in China in 2020.

This paper comprehensively evaluates the dynamic effects on China's environment and economy during the COVID-19 pandemic. Results show that the COVID-19 lockdown resulted in a temporary improvement in air quality. Furthermore, nitrogen dioxide (NO2) levels in the atmosphere in China were 36% lower than in the week after last year's Lunar New Year holiday, but this also led to an economic downturn. Moreover, the aerosol optical depth (AOD) decreased significantly. During the back-to-work period, the economy recovered and there was an increase in energy consumption, and CO2, NO2 emissions sharply increased to pre-lockdown levels. In the post-lockdown period, the AOD was lower than that of the same period last year. This study can provide reference for environmental policy making, as it demonstrates to what extent the control of pollution sources can improve air quality. Precise emission reduction and regional joint prevention and control are important and effective means for the prevention and control of O3 pollution. The health and economic benefits of COVID-19 pandemic control measures are incalculable. And this can provide an effective scientific basis and theoretical support for the prevention and control of air pollution.

Prognostic significance of tumor deposits in radically resected gastric cancer: a retrospective study of a cohort of 1915 Chinese individuals.

BACKGROUND: Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients. METHODS: We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted. RESULTS: The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance. CONCLUSIONS: The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.

A study protocol of a randomized phase II trial of perioperative chemoimmunotherapy verses perioperative chemoimmunotherapy plus preoperative chemoradiation for locally advanced gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma: the NeoRacing study.

BACKGROUND: Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. METHODS: Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. DISCUSSION: The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

Protective ileostomy increased the incidence of rectal stenosis after anterior resection for rectal cancer.

BACKGROUND: In most of the views, rectal stenosis after anterior resection for rectal cancer results from pelvic radiotherapy. However, patients without receiving radiotherapy also suffer stenosis. In this study, we evaluated the factors associated with rectal stenosis after anterior rectal resection (ARR). METHODS: We conducted a retrospective study with ARR patients who underwent neoadjuvant chemoradiotherapy and the patients without radiotherapy. Patients who received watch and wait strategy with a clinical complete response after chemoradiotherapy were also included. Patients with colonoscopy follow-up were included for further analyses; 439 patients who underwent neoadjuvant chemoradiotherapy; 545 patients who received ARR without radiotherapy and 33 patients who received watch and wait strategy. Stenosis was diagnosed when a 12-mm diameter colonoscopy could not be passed through the rectum. Univariate and multivariate logistic regression analyses were performed to identify variables associated with rectal stenosis. RESULTS: According to the multivariate analysis in patients receiving ARR, both protective stoma and preoperative radiotherapy affected the occurrence of stenosis, with the odds ratios (ORs) of 3.375 and 2.251, respectively. According to the multivariate analysis, a preventive ileostomy was the only factor associated with stenosis both in patients receiving preoperative radiotherapy and without radiotherapy. Non-reversal ileostomy and long time between ileostomy and restoration increased the possibility of stenosis. In 33 patients who received watch and wait strategy, only one patient (3%) experienced stenosis. CONCLUSION: Both surgery and radiotherapy are risk factors for rectal stenosis in rectal cancer patients. Compared to preoperative radiotherapy, a protective ileostomy is a more critical factor associated with rectal stenosis.

Immune Score Predicts Outcomes of Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy.

BACKGROUND: Substantial evidence has demonstrated that tumor-infiltrating lymphocytes (TILs) are correlated with patient prognosis. The TIL-based immune score (IS) affects prognosis in various cancers, but its prognostic impact in gastric cancer (GC) patients treated with adjuvant chemoradiotherapy remains unclear. METHODS: A total of 101 GC patients who received chemoradiotherapy after gastrectomy were retrospectively analyzed in this study. Immunohistochemistry staining for CD3+ and CD8+ T-cell counts in both tumor center (CT) and invasive margin (IM) regions was built into the IS. Patients were then divided into three groups based on their differential IS levels. The correlation between IS and clinical parameters was analyzed. The prognostic impact of IS and clinical parameters was evaluated using Kaplan-Meier analysis and Cox proportional hazard regression analysis. Receiver operating characteristic (ROC) curves were plotted to compare the area under the curve (AUC) of IS with other clinical parameters. Nomograms for disease-free survival (DFS) and overall survival (OS) prediction were constructed based on the identified parameters. RESULTS: Finally, 20 (19.8%), 57 (56.4%), and 24 (23.8%) GC patients were identified with low, intermediate, and high IS levels, respectively. GC patients with higher IS levels exhibited better DFS (p < 0.001) and OS (p < 0.001). IS was an independent prognostic factor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. IS presented a better predictive ability than the traditional pathological tumor-node-metastasis (pTNM) staging system (AUC: 0.801 vs. 0.677 and 0.800 vs. 0.660, respectively) with respect to both DFS and OS. The C-index of the nomograms for DFS and OS prediction was 0.737 and 0.774, respectively. CONCLUSIONS: IS is a strong predictive factor for both DFS and OS in GC patients treated with adjuvant chemoradiotherapy, which may complement the traditional pTNM staging system.

Preoperative Chemoradiotherapy Versus Postoperative Chemoradiotherapy for Patients With Locally Advanced Gastric Cancer: A Retrospective Study Based on Propensity Score Analyses.

PURPOSE: Although adjuvant chemoradiotherapy (CRT) used to be recommended as a standard of care for locally advanced gastric cancer, this suggestion has been strongly challenged recently. However, clear evidence regarding the optimization of radiotherapy is lacking. The purpose of this study was to compare the effectiveness of preoperative CRT versus that of postoperative CRT for resectable or potentially resectable gastric cancer. METHODS: From January 2005 to December 2017, patients with clinical stage III/IVa (i.e., T3-4aN+M0 or T4bNxM0) locally advanced gastric cancer were retrospectively identified. Survival after preoperative CRT and postoperative CRT was assessed by unadjusted, propensity score matching (PSM) and inverse probability of treatment weight (IPTW) analyses. Moreover, exploratory subgroup analyses were performed, and toxicity and patterns of failure were also investigated. RESULTS: The median follow-up time was 32.5 months. A total of 82 and 463 patients were enrolled in the preoperative and postoperative CRT groups, respectively. After propensity score matching, preoperative CRT was associated with improved overall survival (OS) and disease-free survival (DFS) compared with postoperative CRT (3-year OS: 72.6 vs. 54.4%, log-rank p = 0.0021; 3-year DFS: 61.7 vs. 44.7%, log-rank p = 0.002). The unadjusted and IPTW analyses yielded consistent results. A complete pathologic response was achieved in 13.4% of the preoperative CRT group. Although the incidence of grade 3 or 4 adverse effects and surgical complications were similar between the two groups, significantly fewer patients experienced treatment interruptions or dose reductions due to toxic effects in the preoperative CRT setting than in the postoperative CRT setting (3.7 vs. 10.6%, p = 0.049). CONCLUSIONS: Compared with postoperative CRT, preoperative CRT was associated with improved OS and DFS, superior treatment compliance and comparable surgical complications for patients with locally advanced gastric cancer. Our findings provide important evidence for the optimal combination modalities of surgery and CRT in the absence of randomized clinical data.

Regulation of the regeneration of intestinal stem cells after irradiation.

BACKGROUND: Radiation enteritis is common in cancer patients with abdominal and pelvic malignant tumors that have received radiotherapy. Regeneration of intestinal stem cells is a critical process for intestine self-repairing post-irradiation. In this study, we attempted to find out the molecules that promote the regeneration of intestinal stem cells to repair the irradiation damage. METHODS: Male C57BL/6 mice were given a single dose of 12 Gy irradiation, and in vitro cultured organoids were given 6 Gy X-rays to construct the regeneration of intestinal stem cells. Hematoxylin and eosin (H&E) staining was performed for morphological observation. In situ hybridization was used to detect the expression of Lgr5, and immunofluorescence staining was adopted to detect the expression of CD44. FACS was used to sort CD44 positive cells of crypts. RNA was then extracted, and RNA-Seq was performed. The Wnt11 over-expression cell line was constructed to collect the Wnt11 conditioned medium (CM). RESULTS: The results showed both Lgr5 and CD44 located at the bottom of normal crypts. The expression of Lgr5 was lower at day 3.5, 5, but recovered at day 10 post-irradiation compared with the control. However, the expression of CD44 was higher at day 3.5, 5, but recovered at day 10 post-irradiation compared with the control group. The quantitative real-time polymerase chain reaction (qRT-PCR) assay showed consistent results. RNA-Seq results showed that Wnt11 was over-expressed in the irradiation group. After irradiation adding Wnt11 condition medium to culture, the intestinal organoids resulted in a bigger size and more buddings of the newborn organoids compared with the control group. CONCLUSIONS: The expression of CD44 increases during the radiation-induced regeneration of intestinal stem cells while Lgr5 decreases, adding Wnt11 CM can facilitate the proliferation of the newborn organoids after irradiation. Wnt11 is a potential target to promote the regeneration of intestinal stem cells to repair the radiation injury.

Quantifying skeletal muscle wasting during chemoradiotherapy with Jacobian calculations for the prediction of survival and toxicity in patients with gastric cancer.

BACKGROUND AND PURPOSE: This study aims to investigate changes in body composition during adjuvant chemoradiotherapy (CRT) quantitatively and visually in patients with gastric cancer and evaluate the correlation of the changes with survival and toxicity. MATERIALS AND METHODS: A total of 182 gastric cancer patients who underwent surgery and adjuvant CRT were included. CT images at the level of the third lumbar vertebra (L3) were analyzed to assess the areas of muscles. We further proposed a framework to quantify muscle changes using Jacobian calculations. Jacobian value (Jac) was calculated for each voxel of muscle by measuring the ratio of muscle changes, where Jac <1 indicated shrinkage and Jac >1 indicated expansion. Variances between the pre- and post-CRT body composition were quantitatively computed, and their impact on toxicity and long-term outcomes were studied. RESULTS: The skeletal muscle index decreased from 44.4 ± 7.4 cm2/m2 to 43.6 ± 7.0 cm2/m2 after CRT. Skeletal muscle wasting and Jac 0.35 ≥ 5% were negatively associated with overall survival (p = 0.036 and p = 0.008, respectively). A new prediction model combining clinical variables and Jacobian features was constructed, and yielded a c statistic of 0.78 (95% CI 0.68-0.87). Jac 0.75 to Jac 1.15 (-25%

Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers.

More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern of metastasis in 1889, now known as the "seed and soil" theory where distinct cancer types are found to metastasize to different tumor-specific sites. Our understanding of the biology of tumor metastasis and specifically the molecular mechanisms driving their formation are still limited, in particular, as it relates to the genesis of oligometastasis. In the following review, we discuss recent advances in general understanding of this metastatic behavior including the role of specific signaling pathways, various molecular features and biomarkers, as well as the interaction of carcinoma cells with their tissue microenvironments (both primary and metastatic niches). The unique features that underlie OMD provide potential targets for localized therapy. As it relates to clinical practice, OMD is emerging as treatable with surgical resection and/or other local therapy options. Strategies currently being applied in the clinical management of OMD will be discussed including surgical, radiation-based therapy, ablation procedures, and the results of emerging clinical trials involving immunotherapy.