Management of internal iliac and obturator lymph nodes in mid-low rectal cancer.

In rectal cancer treatment, the diagnosis and management of lateral pelvic lymph nodes (LLN) are critical for preventing local recurrence. Over time, scholars have reached a consensus: when imaging suggests LLN metastasis, combining neoadjuvant chemoradiotherapy (nCRT) with selective LLN dissection (LLND) can mitigate the risk of recurrence. Selective LLND typically encompasses lymph nodes in the internal iliac and obturator regions. Recent studies emphasize distinctions between internal iliac and obturator lymph nodes regarding prognosis and treatment outcomes, prompting the need for differentiated diagnostic and treatment approaches.

MRI-based Radiomics Model for Preoperative Prediction of Lateral Pelvic Lymph Node Metastasis in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: To develop a magnetic resonance imaging (MRI)-based radiomics model for preoperative prediction of lateral pelvic lymph node (LPLN) metastasis (LPLNM) in patients with locally advanced rectal cancer MATERIALS AND METHODS: We retrospectively enrolled 263 patients with rectal cancer who underwent total mesorectal excision and LPLN dissection. Radiomics features from the primary lesion and LPLNs on baseline MRI images were utilized to construct a radiomics model, and their radiomics scores were combined to develop a radiomics scoring system. A clinical prediction model was developed using logistic regression. A hybrid predicting model was created through multivariable logistic regression analysis, integrating the radiomics score with significant clinical risk factors (baseline Carcinoembryonic Antigen (CEA), clinical circumferential resection margin status, and the short axis diameter of LPLN). This hybrid model was presented with a hybrid clinical-radiomics nomogram, and its calibration, discrimination, and clinical usefulness were assessed. RESULTS: A total of 148 patients were included in the analysis and randomly divided into a training cohort (n = 104) and an independent internal testing cohort (n = 44). The hybrid clinical-radiomics model exhibited the highest discrimination, with an area under the receiver operating characteristic (AUC) of 0.843 [95% confidence interval (CI), 0.706-0.968] in the testing cohort compared to the clinical model [AUC (95% CI) = 0.772 (0.589-0.856)] and radiomics model [AUC (95% CI) = 0.731 (0.613-0.849)]. The hybrid prediction model also demonstrated good calibration, and decision curve analysis confirmed its clinical usefulness. CONCLUSION: This study developed a hybrid MRI-based radiomics model that incorporates a combination of radiomics score and significant clinical risk factors. The proposed model holds promise for individualized preoperative prediction of LPLNM in patients with locally advanced rectal cancer. DATA AVAILABILITY STATEMENT: The data presented in this study are available on request from the corresponding author.

Fascia- vs vessel-oriented lateral lymph node dissection for rectal cancer: Short-term outcomes and prognosis in a single-center experience.

BACKGROUND: For the management of lateral lymph node (LLN) metastasis in patients with rectal cancer, selective LLN dissection (LLND) is gradually being accepted by Chinese scholars. Theoretically, fascia-oriented LLND allows radical tumor resection and protects of organ function. However, there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND. Through a preliminary study with a small sample size, we found that fascia-oriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs. In this study, we increased the sample size and refined the postoperative functional outcomes. AIM: To compare the effects of fascia- and vessel-oriented LLND regarding short-term outcomes and prognosis. METHODS: We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021. The short-term outcomes included perioperative outcomes and postoperative functional outcomes. The prognosis was measured based on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 105 patients were included in the final analysis and were divided into fascia- and vessel-oriented groups that included 41 and 64 patients, respectively. Regarding the short-term outcomes, the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group. There were no significant differences in the other short-term outcomes. The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group. In addition, there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups. In terms of prognosis, there was no significant difference in PFS or OS between the two groups. CONCLUSION: It is safe and feasible to perform fascia-oriented LLND. Compared with vessel-oriented LLND, fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.

UTP18-mediated p21 mRNA instability drives adenoma-carcinoma progression in colorectal cancer.

Colorectal cancer (CRC) often develops slowly from adenoma, but the underlying mechanism remains unclear, hampering the prevention or treatment of colorectal adenoma-carcinoma progression. In this study, we use in-depth quantitative proteomics combined with survival analysis, revealing that the ribosome protein U3 small nucleolar RNA-associated protein 18 homolog (UTP18) is consistently upregulated in the progression of colorectal adenoma to carcinoma and is associated with adenoma recurrence, effective serodiagnosis, and poor prognosis of CRC. Furthermore, deSUMOylation induces the nucleocytoplasmic transport of UTP18, driving cell-cycle progression and tumorigenesis via mediation of the instability of p21 mRNA. In addition, the growth and ribosome biogenesis of adenoma organoids is found to be promoted by overexpression of UTP18. Thus, UTP18 contributes to multiple roles in adenogenesis and malignancy of CRC, suggesting that it could be a potential biomarker and drug target for colorectal adenoma and cancer.

Evaluating short-term and survival outcomes of natural orifice specimen extraction surgery for colorectal cancer: A single-centre retrospective study.

Background: Natural orifice specimen extraction surgery (NOSES) has been confirmed as an alternative approach without auxiliary incisions. The purpose of this study was to investigate the short-term and survival outcomes of NOSES versus conventional laparoscopic surgery (LAP) in treatment of sigmoid and high rectal cancer. Method: The retrospective study was conducted at single centers between January 2017 to December 2021. Relevant data included clinical demographics, pathological features, operative parameters, postoperative complications and survival outcomes were collected and analyzed. All procedures were performed using either a NOSES or a conventional LAP approach. Propensity score matching (PSM) was conducted to balance clinical and pathological features between the two groups. Results: After PSM, a total of 288 patients were eventually included in this study, 144 in each group. Patients in the NOSES group experienced faster recovery of gastrointestinal function (2.6 ± 0.8 vs. 3.6 ± 0.9 day, P = 0.037), less pain and less analgesia required (12.5% vs. 33.3%, P < 0.001). In addition, the incidence of surgical site infection in the LAP group was significantly higher than that in the NOSES group (12.5% vs. 4.2%, P = 0.011), especially incision-related complications (8.3% vs. 2.1%, P = 0.017). After a median follow-up of 32 (range, 3-75) months, the two groups had similar 3-year overall survival rates (88.4% vs. 88.6%; P = 0.850) and disease-free survival rates (82.9% vs. 77.2%; P = 0.494). Conclusion: The transrectal NOSES procedure is a well-established strategy with advantages in reducing postoperative pain, faster recovery of gastrointestinal function, and less incision-related complications. In addition, the long-term survival is similar between NOSES and conventional laparoscopic surgery.

Epidemiological trends and novel prognostic evaluation approaches of patients with stage II-IV colorectal neuroendocrine neoplasms: A population-based study with external validation.

Objective: This study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification. Methods: Among all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital's independent cohort of 62 patients with CRNENs was used as the external validation cohort. Results: In the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90-5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient. Conclusion: Over the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.

HAMP as a Prognostic Biomarker for Colorectal Cancer Based on Tumor Microenvironment Analysis.

Colorectal cancer (CRC) is the most common digestive tumor in the world and has a high mortality rate. The development and treatment of CRC are related to the immune microenvironment, but immune response-related prognostic biomarkers are lacking. In this study, we used The Cancer Genome Atlas (TCGA) to explore the tumor microenvironment (TME) and weighted gene coexpression network analysis (WGCNA) to identify significant prognostic genes. We also identified differentially expressed genes in the TCGA data and explored immune-related genes and transcription factors (TFs). Then, we built a TF regulatory network and performed a comprehensive prognostic analysis of an lncRNA-associated competitive endogenous RNA network (ceRNA network) to build a prognostic model. CCR8 and HAMP were identified both in the WGCNA key module and as immune-related genes. HAMP had good prognostic value for CRC and was highly expressed in CRC tissues and had a negative correlation with CD4+ T cells and M0 macrophages based on immunohistochemistry and immunofluorescence staining of clinical specimens.We found that HAMP had high prognostic and therapeutic target value for CRC and was associated with liver metastasis. These analysis results revealed that HAMP may be a candidate immune-related prognostic biomarker for CRC.

Development and Validation of a Nomogram and a Comprehensive Prognostic Analysis of an LncRNA-Associated Competitive Endogenous RNA Network Based on Immune-Related Genes for Locally Advanced Rectal Cancer With Neoadjuvant Therapy.

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. In recent years, neoadjuvant chemoradiotherapy (CRT) has been the most comprehensive treatment for locally advanced rectal cancer (LARC). In this study, we explored immune infiltration in rectal cancer (RC) and identified immune-related differentially expressed genes (IRDEGs). Then, we identified response markers in datasets in GEO databases by principal component analysis (PCA). We also utilized three GEO datasets to identify the up- and downregulated response-related genes simultaneously and then identified genes shared between the PCA markers and three GEO datasets. Based on the hub IRDEGs, we identified target mRNAs and constructed a ceRNA network. Based on the ceRNA network, we explored prognostic biomarkers to develop a prognostic model for RC through Cox regression. We utilized the specimen to validate the expression of the two biomarkers. We also utilized LASSO regression to screen hub IRDEGs and built a nomogram to predict the response of LARC patients to CRT. All of the results show that the nomogram and prognostic model offer good prognostic value and that the ceRNA network can effectively highlight the regulatory relationship. hsa-mir-107 and WDFY3-AS2 may be prognostic biomarkers for RC.

Evaluation of radical surgical treatment in the management of 58 locally advanced rectal neuroendocrine neoplasms, one multicenter retrospective study.

BACKGROUND: Locally advanced rectal neuroendocrine neoplasms (NENs) are rare, and the therapeutic effects of surgery in improving the prognosis have been questioned in previous reports. MATERIALS AND METHODS: The research included 58 consecutive patients with locally advanced rectal NENs from three Chinese medical centers between 2000 and 2020. All have received radical surgical treatment. The clinicopathological and survival data were collected. Kaplan-Meier methods and a Cox proportional hazards regression model were used to evaluate the prognosis and identify independent prognostic factors. RESULTS: All patients were followed up for a median period of 36 (2-125) months. Of the 58 patients, 13 (22.4%) had G1 neuroendocrine tumors (NETs), 15 (25.9%) had G2 NETs, 6 (10.3%) had G3 NETs, and the remaining 24 (41.4%) patients had G3 neuroendocrine carcinomas (NECs). The 1-year and 3-year disease-free survival (DFS) rates were 64.5% and 48.8%, respectively. The 1-year and 3-year overall survival (OS) rates were 90.5% and 75.4%, respectively. Univariate analysis demonstrated that tumor differentiation (p = 0.002), gross morphology (p = 0.009), T stage (p = 0.024), and extramural vascular invasion (p = 0.009) were associated with the OS. The subsequent multivariate analysis confirmed that tumor differentiation [hazard ratio (HR) = 6.002, 95% confidence interval (CI): 1.210-29.767, p = 0.028] and gross morphology (HR = 3.438, 95% CI: 1.038-11.382, p = 0.043) were independent prognostic factors affecting the clinical outcomes. CONCLUSIONS: Rectal NENs are a heterogeneous group of diseases. The survival benefits obtained from surgery vary widely based on the tumor clinicopathological features. Patients with G3 NECs and ulcerative mass are at high risks of poor prognosis.

Functional magnetic resonance imaging reveals differences in brain activation in response to thermal stimuli in diabetic patients with and without diabetic peripheral neuropathy.

INTRODUCTION: Diabetes affects both the peripheral and central nervous systems. The aim of this study was to explore the changes in brain activity in response to thermal stimuli in diabetic patients with and without diabetic peripheral neuropathy (DPN) using functional magnetic resonance imaging (fMRI). METHODS: A total of 36 right-handed volunteers were enrolled: eight patients with Type-2 diabetes mellitus and DPN, 13 patients with Type-2 diabetes mellitus lacking DPN (NDPN patients), and 15 healthy volunteers (HV). Blood oxygenation level-dependent baseline scans were performed, first without any stimuli, and then with four sessions of thermal stimuli (0, 10, 34, and 44°C, in a random order) applied to the lateral side of the right lower extremity. There was a 240-s rest interval between each thermal stimulation. Each stimulation session consisted of three cycles of 30 s of stimulation followed by 30 s of rest. After each stimuli session, the participant rated pain and itch perception on a visual analog scale. The fMRI data series were analyzed by using Statistical Parametric Mapping 8 and Data Processing Assistant for Resting-State fMRI. RESULTS: In response to temperature stimuli, DPN patients showed stronger activation than HV and NDPN patients, not only in brain areas that participate in somatosensory pathways (right insula, left caudate nucleus, frontal gyrus, and cingulate cortex), but also in the cognition-related cerebral areas (right temporal lobe, left hippocampus, and left fusiform gyrus). Activation of vermis 1-3 was greater in NDPN patients than in HV in response to 0°C stimulation. CONCLUSIONS: fMRI may be useful for the early detection of central nervous system impairment caused by DPN. Our results indicate that central nervous system impairment related to diabetic neuropathy may not be limited to motion- and sensation-related cortical regions. Cognition-associated cerebral regions such as the hippocampus and fusiform gyrus are also affected by functional changes caused by DPN. This suggests that fMRI can detect the early stages of cognitive impairment in DPN patients before the symptoms become clinically significant.