Cross-sectional investigation of the distribution characteristics and prognostic significance of lateral lymph nodes in patients with rectal cancer.

BACKGROUND: Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking. METHODS: Between January 2013 and December 2016, patients with pathologically proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into seven categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLN characteristics and LLN risk scoring. RESULTS: A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs, and most patients developed measurable LLNs in the obturator cranial compartment. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with the largest LLN short-axis diameter >10 mm had a poor prognosis, which was similar to that in patients with simultaneous distant metastasis (SDM). Patients with LLN risk scoring ≥2 had a worse prognosis than those with LLN risk scoring <2, while better than those with SDM. CONCLUSION: This study suggests that LLR is the main locoregional recurrence pattern. Most rectal cancer patients have measurable LLNs on primary CT scan. However, patients with enlarged LLNs <10 mm or LLN risk scoring <2 still have a significantly better prognosis than patients with SDM, which indicated the potential value of locoregional treatment for these LLNs.

Head-to-head comparison of the diagnostic performance between 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer: a systematic review and meta-analysis.

This study aimed to compare the detection rates of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in colorectal cancer. A systematic search of major medical databases was conducted to identify studies up to September 2023. The primary outcome assessed was the detection rate of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in the primary tumor. Pooled risk ratios with a 95% CI were calculated using random-effect models to adjust for heterogeneity. Eight studies were included in the meta-analysis. 68Ga-FAPI-04 PET/CT has higher uptakes in lymph nodes, bone, and peritoneal metastasis compared with 18F-FDG PET/CT. The detection rate of 68Ga-FAPI-04 PET/CT based on lesion was better for lymph node metastasis (RR = 0.63, 95% CI 0.47-0.84, P = 0.002) and peritoneal metastasis (RR = 0.52, 95% CI 0.32-0.85, P = 0.009), both imaging modalities had essentially the same diagnostic efficacy in primary tumor (RR = 0.99, 95% CI 0.96-1.02, P = 0.49). 68Ga-FAPI-04 as a highly promising PET/CT tracer was superior to 18F-FDG PET/CT in colorectal cancer, especially in detecting lymph node metastases and peritoneal metastases.

Integrative analysis of senescence-related genes identifies robust prognostic clusters with distinct features in hepatocellular carcinoma.

INTRODUCTION: Senescence refers to a state of permanent cell growth arrest and is regarded as a tumor suppressive mechanism, whereas accumulative evidence demonstrate that senescent cells play an adverse role during cancer progression. The scarcity of specific and reliable markers reflecting senescence level in cancer impede our understanding of this biological basis. OBJECTIVES: Senescence-related genes (SRGs) were collected for integrative analysis to reveal the role of senescence in hepatocellular carcinoma (HCC). METHODS: Consensus clustering was used to subtype HCC based on SRGs. Several computational methods, including single sample gene set enrichment analysis (ssGSEA), fuzzy c-means algorithm, were performed. Data of drug sensitivities were utilized to screen potential therapeutic agents for different senescence patients. Additionally, we developed a method called signature-related gene analysis (SRGA) for identification of markers relevant to phenotype of interest. Experimental strategies consisting quantitative real-time PCR (qRT-PCR), ß-galactosidase assay, western blot, and tumor-T cell co-culture system were used to validate the findings in vitro. RESULTS: We identified three robust prognostic clusters of HCC patients with distinct survival outcome, mutational landscape, and immune features. We further extracted signature genes of senescence clusters to construct the senescence scoring system and profile senescence level in HCC at bulk and single-cell resolution. Senescence-induced stemness reprogramming was confirmed both in silico and in vitro. HCC patients with high senescence were immune suppressed and sensitive to Tozasertib and other drugs. We suggested that MAFG, PLIN3, and 4 other genes were pertinent to HCC senescence, and MAFG potentially mediated immune suppression, senescence, and stemness. CONCLUSION: Our findings provide insights into the role of SRGs in patients stratification and precision medicine.

T2WI-based texture analysis predicts preoperative lymph node metastasis of rectal cancer.

BACKGROUND: To prospectively develop and validate the T2WI texture analysis model based on a node-by-node comparison for improving the diagnostic accuracy of lymph node metastasis (LNM) in rectal cancer. METHODS: A total of 381 histopathologically confirmed lymph nodes (LNs) were collected. LNs texture features were extracted from MRI-T2WI. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator were used for feature selection to construct the LN rad-score. Then the clinical risk factors and LN texture features were combined to establish combined predictive model. Model performance was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Decision curve analysis (DCA) and nomogram were used to evaluate the clinical application of the model. RESULTS: A total of 107 texture features were extracted from LN-MRI images. After selection and dimensionality reduction, the radiomics prediction model consisting of 8 texture features showed well-predictive performance in the training and validation cohorts (AUC, 0.676; 95% CI 0.582-0.771) (AUC, 0.774; 95% CI 0.648-0.899). A clinical-radiomics prediction model with the best performance was created by combining clinical and radiomics features, 0.818 (95% CI 0.742-0.893) for the training and 0.922 (95% CI 0.863-0.980) for the validation cohort. The LN Rad-score in clinical-radiomics nomogram obtained the highest classification contribution and was well calibrated. DCA demonstrated the superiority of the clinical-radiomics model. CONCLUSION: The lymph node T2WI-based texture features can help to improve the preoperative prediction of LNM.

Reactive oxygen species in colorectal cancer adjuvant therapies.

Colorectal cancer (CRC), a prevalent global malignancy, often necessitates adjuvant therapies such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy to mitigate tumor burden in advanced stages. The efficacy of these therapies is significantly influenced by reactive oxygen species (ROS). Previous research underscores the pivotal role of ROS in gut pathology, targeted therapy, and drug resistance. ROS-mediated CRC adjuvant therapies encompass a myriad of mechanisms, including cell death and proliferation, survival and cell cycle, DNA damage, metabolic reprogramming, and angiogenesis. Preliminary clinical trials have begun to unveil the potential of ROS-manipulating therapy in enhancing CRC adjuvant therapies. This review aims to provide a comprehensive synthesis of studies exploring the role of ROS in CRC adjuvant therapies.

Comparison of laparoscopic lateral lymph node dissection for rectal cancer with and without routine resection of the visceral branches of internal iliac artery.

PURPOSE: This study aimed to explore the safety and feasibility of the modified lateral lymph node dissection (LLND) with routine resection of the visceral branches of internal iliac vessels (IIVs) for mid-low-lying rectal cancer. MATERIALS AND METHOD: Consecutive patients undergoing LLND for rectal cancer were divided into the routine visceral branches of the IIVs resection group (RVR group) and the NRVR group (without routine resection). The main outcomes were postoperative complications and the number of lateral lymph nodes harvested. RESULTS: From 2012 to 2021, a total of 75 and 57 patients were included in the RVR and NRVR group, respectively. The operative time was reduced in the RVR group (p = 0.020). No significant difference was observed between the two groups for the incidence of total, major, or minor postoperative complications. Pathologically confirmed LLNM were 24 (32%) patients in the RVR group and 12 (21.1%) in the NRVR group (p = 0.162). The number of lateral lymph nodes harvested had no significant difference between two groups (11 vs. 12, p = 0.329). CONCLUSION: LLND with routine resection of visceral branches of IIVs is safe and feasible, which brings no major complication or long-term urinary disorder.

Do treated rectal tumors appear differently on MRI after chemotherapy versus chemoradiotherapy?

PURPOSE: Increasing studies have focused on neoadjuvant chemotherapy (NCT) in rectal cancer. However, few studies explored the differences in radiographic variation between patients treated with NCT and neoadjuvant chemoradiotherapy (NCRT). METHODS: Stage II/III rectal cancer patients from March 2016 to December 2019 meeting the criteria treated with NCRT or NCT were included. MRI features, including tumor location, longitudinal length, DWI signal, MRI tumor regression grade (mrTRG), and radiomic texture features, before and after neoadjuvant treatments were reviewed. RESULTS: 116 patients with NCRT and 61 with NCT were analyzed. Among these patients, 46 patients in the NCRT group and 18 in the NCT group were responders with pathological TRG0-1. Within these responders, the mean tumor longitudinal length regression rate (TLRR) of the NCT group was 60.08 ± 11.17%, which was significantly higher than the 50.73 ± 15.28% of the NCRT group (p = 0.010). The proportion of high signal in the DWI image after NCT was higher than that of the NCRT group (88.89% vs 50.00%, p = 0.004). NCT responders had significantly higher median change rates than those of NCRT responders in 11 radiomic features, especially those shape features. CONCLUSION: MRI images change differently between responders treated with NCRT and those with NCT in rectal cancer. The tumor volumetry and some radiomic features change more obviously in NCT responders, and the tumor signal changes more obviously in NCRT responders. During the evaluation of the response of the tumor to the neoadjuvant treatments, images of patients should be treated differently.

Can Organoid Model Reveal a Key Role of Extracellular Vesicles in Tumors? A Comprehensive Review of the Literature.

Extracellular vesicles (EVs) are small membrane-bound vesicles that are released by cells into the extracellular environment. The role of EVs in tumors has been extensively studied, and they have been shown to play a crucial role in tumor growth, progression, and metastasis. Past research has mainly used 2D-cultured cell line models to investigate the role of EVs in tumors, which poorly simulate the tumor microenvironment. Organoid technology has gradually matured in recent years. Organoids are similar in composition and behavior to physiological cells and have the potential to recapitulate the architecture and function of the original tissue. It has been widely used in organogenesis, drug screening, gene editing, precision medicine and other fields. The integration of EVs and organoids has the potential to revolutionize the field of cancer research and represents a promising avenue for advancing our understanding of cancer biology and the development of novel therapeutic strategies. Here, we aimed to present a comprehensive overview of studies using organoids to study EVs in tumors.

Ferroptosis regulation by methylation in cancer.

Epigenetic regulation plays a critical role in cancer development and progression. Methylation is an important epigenetic modification that influences gene expression by adding a methyl group to nucleic acids and proteins. Ferroptosis is a new form of regulated cell death triggered by the accumulation of iron and lipid peroxidation. Emerging evidence have shown that methylation regulation plays a significant role in the regulation of ferroptosis in cancer. This review aims to explore the methylation regulation of ferroptosis in cancer, including reactive oxygen species and iron bio-logical activity, amino acid and lipid metabolism, and drugs interaction. The findings of this review may provide new insights and strategies for the prevention and treatment of cancer.

eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation.

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.

The same parastomal hernia repairs rate in the different approaches to colostomy.

PURPOSE: This study aimed to compare the parastomal hernia repairs rate in the different approaches to colostomy and investigate the risk factors for parastomal hernia formation in patients with permanent colostomies. METHODS: Consecutive rectal cancer patients who underwent abdominoperineal resection from June 2014 to July 2020 in West China Hospital were divided into two groups according to their surgical approach for permanent colostomies. The impact of different approaches to colostomy on parastomal hernia repairs was determined by comparing a group of patients receiving an extraperitoneal route to colostomy with a group receiving transperitoneal. Potential variables were evaluated first with univariate and then multivariate analyses to identify the risk factors for the formation of parastomal hernia. RESULTS: Two hundred two subjects in the transperitoneal group and 103 in the extraperitoneal group attended the follow-up visit with a median follow-up period of 33 (25th-75th percentiles, 17-46) months. Clinically and radiologically detectable parastomal hernias were present in 76 of 202 (37.6%) and 14 of 103 (13.6%) subjects in the transperitoneal and extraperitoneal groups during the follow-up period (p＜0.01). Besides, 10 of 76 (13.1%) subjects in the transperitoneal group and 2 of 14 (14.3%) subjects in the extraperitoneal group underwent a parastomal hernia operation during the follow-up (p = 0.82). In addition, the transperitoneal approach of colostomy (p = 0.002), older age (p＜0.001), and higher body mass index (p = 0.013) were identified as independent risk factors for the occurrence of parastomal hernia. CONCLUSIONS: Extraperitoneal colostomy decreased the detectable parastomal hernias but did not reduce the surgical repair rate of parastomal hernias.

Global Status of Research on Lateral Lymph Nodes in Rectal Cancer from 1994 to 2022: A Bibliometric Analysis.

Tremendous progress has been made in the field of lateral lymph nodes (LLNs) in rectal cancer, but no bibliometric analysis in this field has been carried out and published. To reveal the current status and trends in LLNs in rectal cancer, this bibliometric analysis was performed. Cooperation network, co-citation and keyword co-occurrence analyses were conducted. Annual publication, cooperation relationships among authors, institutions and countries, co-cited journal, co-cited author, co-cited reference and keywords were the main outcomes. A total of 345 studies were included in this bibliometric analysis. The number of articles published in this field has been increasing year by year. The authors, institutions and countries worked closely together in this field. Japan has the largest number of published articles, accounting for 51.59% of the total publications. International Journal of Colorectal Disease (30 papers, 8.70%) published the most papers in this field. The JCOG0212 trial was the most cited article. Preoperative chemoradiotherapy, multicenter, lateral lymph node dissection (LLND) and metastasis are recent hot keywords, and LLND had the highest burst strength. In conclusion, this bibliometric analysis found that Japanese institutions and authors dominated the field of LLNs in rectal cancer. The JCOG0212 trial was the most influential article, which had a significant impact on the development of guidelines. LLND is a hotspot in this field with the highest burst strength. Further prospective studies are needed in this field.

Methylene blue can increase the number of lymph nodes harvested in colorectal cancer: a meta-analysis.

AIM: The lymph node (LN) status plays an important role in colorectal cancer (CRC), which depends on adequate LN harvest. In some studies, methylene blue has been used to increase the number of LNs harvested in vitro. The purpose was to evaluate the effect of methylene blue staining on LN harvest during radical resection of CRC. METHODS: The Cochrane Library, MEDLINE, Embase, PubMed, and Web of Science were searched from the dates of inception until 15 October 2022. Studies were included if they were randomized controlled trials or nonrandomized controlled trials for radical resection of rectal cancer according to the principle of total mesorectal excision that compared the use of methylene blue with blank control in LN harvest. The primary outcomes were the number of LNs harvested and the incidence of fewer than 12 LNs harvested. RESULT: Of 328 articles found, a meta-analysis was conducted of 15 studies (2 randomized controlled trials and 13 non-randomized controlled trials) composed of 3104 patients. Meta-analysis showed that methylene blue could not only significantly increase the number of LNs harvested in CRC specimens (stained group 28.23 vs unstained group 16.15; weighted mean difference 12.08; 95% CI, 8.03-16.12; p < 0.001; I2 = 95%), but also reduce the incidence of fewer than 12 LNs harvested (methylene blue-stained group 7.91% vs unstained group 30.90%; OR 0.12; 95% CI, 0.05-0.26; p < 0.001; I2 = 78%). CONCLUSION: Methylene blue can increase the number of LNs harvested in CRC, reduce the incidence of fewer than 12 LNs harvested, and ensure the accuracy of LN staging.

The effect of BMI on long-term outcome in patients with rectal cancer and establishment of a nomogram prediction model.

BACKGROUND: The effects of body mass index (BMI) in patients with rectal cancer have been poorly studied and are still controversial. In this study, we aimed to assess the effect of BMI on the long-term outcome in patients with rectal cancer after radical surgery. MATERIALS AND METHODS: Between April 2012 and December 2020, patients who received total mesorectal excision (TME) surgery were enrolled in the study. Patients were divided into four groups according to BMI level. Kaplan-Meier survival curves with log-rank tests were used to analyze overall survival (OS), Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival. Univariate and multivariate analyses were performed to identify the risk factors associated with the long-term outcome. Nomograms were developed to predict the OS and DFS based on independent prognostic factors. RESULTS: A total of 688 patients were included in this study. The median follow-up time was 69 months. The 5-year OS rates of the control, underweight, overweight and obese groups were 79.2%, 62.2%, 88.7% and 86.3%, respectively. The 5-year DFS rates were 74.8%, 58.2%, 80.5% and 81.4%, respectively. Overweight (HR 0.534; 95% CI 0.332-0.860, p = 0.010) was an independent protective factor for OS and DFS (HR 0.675; 95% CI 0.461-0.989, p = 0.044). Underweight was an independent risk factor for DFS (HR = 1.623; 95% CI 1.034-2.548; p = 0.035), and had a trend to be an independent risk factor for OS (HR 1.594; 95% 0.954-2.663; p = 0.075). Nomograms were established to predict the 2-year OS, 5-year OS, 2-year DFS and 5-year DFS with an area under curve (AUC) of 0.767, 0.712, 0.746 and 0.734, respectively. CONCLUSIONS: For rectal cancer patients after radical surgery, overweight was an independent protective factor for OS and DFS. Underweight was an independent risk factor for DFS and had a trend to be an independent risk factor for OS. Nomograms incorporating BMI and other prognostic factors could be helpful to predict long-term outcome.

Technique to match mesorectal lymph nodes imaging findings to histopathology: node-by-node comparison.

BACKGROUND: Lymph node status is critical for staging rectal cancer and determining neoadjuvant therapy regimens. Establishing a matching between imaging and histopathological lymph nodes is fundamental for predicting lymph node status. This study reports a technique to achieve node-by-node pairing of mesorectal lymph nodes between imaging findings and histopathology. METHODS: Fifty-two patients with histopathologically verified rectal cancer underwent magnetic resonance imaging before surgery. The status of each lymph node in the surgical specimens was analyzed histopathologically and matched with preoperative imaging after the operation. RESULTS: A total of 346 mesorectal lymph nodes were located on imaging evaluation, of which 313 were confirmed histopathologically, and 33 were unmatched. The total success rate of the technique was 90.5%. Node-by-node analysis revealed 280 benign and 33 malignant nodal structures. CONCLUSION: The technique to match mesorectal lymph node imaging findings to histopathology was feasible and effective. It simplified the technical method and had a reasonable success matching rate, which could provide a standardized approach for obtaining a prospective correlation between imaging and histological findings, supporting all subsequent related studies at the level of mesorectal lymph nodes.

The diagnostic value of exosomal circular RNAs in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis. METHODS: A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance. RESULTS: Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively. CONCLUSION: Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Can patients with good tumor regression grading after neoadjuvant chemoradiotherapy be exempted from lateral lymph node dissection?

OBJECTIVE: To investigate whether lateral lymph node (LLN) dissection (LLND) can be exempted in patients with good tumor regression grading (TRG) after neoadjuvant chemoradiotherapy (nCRT)? METHODS: A retrospective study was conducted on consecutive patients with advanced rectal cancer who underwent nCRT and total mesorectal resection plus selective LLND at our institution. The primary outcomes are the relationship between LLN metastasis (LLNM) and magnetic resonance imaging TRG (mrTRG) and the relationship between LLNM and pathological TRG (pTRG). RESULTS: A total of 91 patients were included, of which 24 patients (26.4%) had LLNM, 67 patients (73.6%) had no LLNM. There were significant differences of the maximum short-axis of LLN before and after nCRT, short-axis reduction rate of the LLN with maximum short-axis, length diameter reduction rate of primary tumor, mrTRG, and pTRG between the two groups. Multivariate logistic regression showed that mrTRG (P = 0.026) and pTRG (P = 0.013) were independent predictors for LLNM. The combination used by mrTRG and the maximum short-axis of LLNs ≥ 8 mm before nCRT and the maximum short-axis of LLN ≥ 5 mm after nCRT achieved specificity of 0.970, positive predictive value (PPV) of 0.867, and negative predictive value (NPV) of 0.855. The same combination used by pTRG achieved the specificity of 0.970, PPV of 0.857 and NPV of 0.844. CONCLUSION: The suspected positive LLNs tend to be sterilized by nCRT in patients who have a very good response to nCRT. It is rational to avoid LLND in patients whose primary tumor and LLNs both show good response to nCRT.