Early Contrast-Enhanced MR for Diagnosing Complete Tumor Response of Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy: A Retrospective Comparative Study.

BACKGROUND: This study assessed the performance of early contrast-enhanced magnetic resonance (ECE-MR) in the detecting of complete tumor response (ypT0) in patients with esophageal squamous cell carcinoma following neoadjuvant therapy. PATIENTS AND METHODS: Preoperative MR images of consecutive patients who underwent neoadjuvant therapy and surgical resection were reviewed retrospectively. The accuracy of ECE-MR and T2WI+DWI was evaluated by comparing the findings with pathological results. Receiver operating characteristic curve analysis was used to assess the diagnostic performance, and DeLong method was applied to compare the areas under the curves (AUC). Chi-squared analysis was conducted to explore the difference in pathological changes. RESULTS: A total of 198 patients (mean age 62.6 ± 7.8 years, 166 men) with 201 lesions were included. The AUC of ECE-MR was 0.85 (95% CI 0.79-0.90) for diagnosing ypT1-4, which was significantly higher than that of T2WI+DWI (AUC 0.69, 95% CI 0.63-0.76, p < 0.001). The diagnostic performance of both T2WI+DWI and ECE-MR improved with increasing tumor stage. The AUCs of ECE-MRI were higher in ypT1 and ypT2 tumors than T2WI+DWI. Degree 2-3 tumor-infiltrating lymphocytes and neutrophils were commonly seen in ypT0 tumors misdiagnosed by ECE-MR. CONCLUSIONS: Visual evaluation of ECE-MR is a promising diagnostic protocol for the detection of complete tumor response, especially for differentiation with early stage tumors. The accurate diagnosis of complete tumor response after neoadjuvant therapy using imaging modalities is of important significance for clinical decision-making for patients with esophageal squamous cell carcinoma. It is hoped that early contrast-enhanced MR will provide supportive advice for the development of individualized treatment options for patients.

Fully semantic segmentation for rectal cancer based on post-nCRT MRl modality and deep learning framework.

PURPOSE: Rectal tumor segmentation on post neoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) has great significance for tumor measurement, radiomics analysis, treatment planning, and operative strategy. In this study, we developed and evaluated segmentation potential exclusively on post-chemoradiation T2-weighted MRI using convolutional neural networks, with the aim of reducing the detection workload for radiologists and clinicians. METHODS: A total of 372 consecutive patients with LARC were retrospectively enrolled from October 2015 to December 2017. The standard-of-care neoadjuvant process included 22-fraction intensity-modulated radiation therapy and oral capecitabine. Further, 243 patients (3061 slices) were grouped into training and validation datasets with a random 80:20 split, and 41 patients (408 slices) were used as the test dataset. A symmetric eight-layer deep network was developed using the nnU-Net Framework, which outputs the segmentation result with the same size. The trained deep learning (DL) network was examined using fivefold cross-validation and tumor lesions with different TRGs. RESULTS: At the stage of testing, the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were applied to quantitatively evaluate the performance of generalization. Considering the test dataset (41 patients, 408 slices), the average DSC, HD95, and MSD were 0.700 (95% CI: 0.680-0.720), 17.73 mm (95% CI: 16.08-19.39), and 3.11 mm (95% CI: 2.67-3.56), respectively. Eighty-two percent of the MSD values were less than 5 mm, and fifty-five percent were less than 2 mm (median 1.62 mm, minimum 0.07 mm). CONCLUSIONS: The experimental results indicated that the constructed pipeline could achieve relatively high accuracy. Future work will focus on assessing the performances with multicentre external validation.

Extranodal Extension at Pretreatment MRI and the Prognostic Value for Patients with Rectal Cancer.

Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Inpp5e Regulated the Cilium-Related Genes Contributing to the Neural Tube Defects Under 5-Fluorouracil Exposure.

Primary cilia are crucial for neurogenesis, and cilium-related genes are involved in the closure of neural tubes. Inositol polyphosphate-5-phosphatase (Inpp5e) was enriched in primary cilia and closely related to the occurrence of neural tube defects (NTDs). However, the role of Inpp5e in the development of NTDs is not well-known. To investigate whether Inpp5e gene is associated with the neural tube closure, we established a mouse model of NTDs by 5-fluorouracil (5-FU) exposure at gestational day 7.5 (GD7.5). The Inpp5e knockdown (Inpp5e-/-) mouse embryonic stem cells (mESCs) were produced by CRISPR/Cas9 system. The expressions of Inpp5e and other cilium-related genes including intraflagellar transport 80 (Ift80), McKusick-Kaufman syndrome (Mkks), and Kirsten rat sarcoma viral oncogene homolog (Kras) were determined, utilizing quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot, PCR array, and immunofluorescence staining. The result showed that the incidence of NTDs was 37.10% (23 NTDs/62 total embryos) and significantly higher than that in the control group (P < 0.001). The neuroepithelial cells of neural tubes were obviously disarranged in NTD embryos. The mRNA and protein levels of Inpp5e, Ift80, Mkks, and Kras were significantly decreased in NTD embryonic brain tissues, compared to the control (P < 0.05). Knockdown of the Inpp5e (Inpp5e-/-) reduced the expressions of Ift80, Mkks, and Kras in mESCs. Furthermore, the levels of α-tubulin were significantly reduced in NTD embryonic neural tissue and Inpp5e-/- mESCs. These results suggested that maternal 5-FU exposure inhibited the expression of Inpp5e, which resulted in the downregulation of cilium-related genes (Ift80, Mkks, and Kras), leading to the impairment of primary cilium development, and ultimately disrupted the neural tube closure.

Small arteriole sign: an imaging feature for staging T4a colon cancer.

OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

TFEB: a double-edged sword for tumor metastasis.

Transcription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspects, including tumor-associated macrophages (TAMs) and EMT. In this review, we described the detailed mechanism of TFEB-mediated regulation of metastasis. In addition, we also described the activation and inactivation of TFEB in several aspects, including the mTORC1 and Rag GTPase systems, ERK2, and AKT. However, the exact process by which TFEB regulates tumor metastasis remains unclear in some pathways, which requires further studies.

Cytosine arabinoside exposure induced cytotoxic effects and neural tube defects in mice and embryo stem cells.

Cytosine arabinoside (Ara-C) is one of the most widely used chemotherapeutic agents for hematological malignancies. The residues of Ara-C have been detected in wastewater and river water with increased usage and discharge. As the ability to cross the placenta and the teratogenicity at low ng/L levels, the toxic effects on pregnant women and infants have been concerned. The toxicity of Ara-C exposure on early embryonic neurodevelopment has not been fully elucidated. In this study, pregnant C57BL/6 mice were injected with different doses of Ara-C on Gestation day (GD) 7.5 and assessed on GD11.5 and GD13.5 to explore the neural developmental effects of Ara-C. HE staining, immunofluorescence, western blot, EdU assay, and flow cytometry were utilized to determine the toxic effects of Ara-C in vivo and in vitro. Our results showed that Ara-C (15-22.5 mg/kg body weight) induced the occurrence of neural tube defects (NTDs). The expression of PH3 was markedly reduced in embryos with Ara-C-induced NTDs, compared to the control group (P < 0.05). In contrast, cell apoptosis was markedly increased. Increased expression levels of GFAP and decreased Nestin were observed in the embryonic brain tissues in Ara-C induced NTDs. The level of ß-catenin was also decreased on both GD11.5 and GD13.5. These results were confirmed in vitro using mouse Sv129 embryonic stem cells (mESC). Ara-C at a dose comparable to the environment level (0.05 nM) had cytotoxicity. Impaired Wnt/ß-catenin signaling pathway is involved in Ara-C exposure induced imbalance between cell proliferation, apoptosis, and differentiation, which might contribute to Ara-C-induced occurrence of NTDs. Our data indicated the environmental concentration of Ara-C had cytotoxicity and that maternal exposure to Ara-C induced NTDs. These results might provide more information to understand the environmental toxic impact of Ara-C on neurodevelopment.

Genetic Effects of ITPK1 Polymorphisms on the Risk of Neural Tube Defects: a Population-Based Study.

Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case-control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17-6.05], P = 0.017; OR = 2.22, 95% CI [1.02-4.80], P = 0.041; and OR = 2.33, 95% CI [1.00-5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

BMP/Smad Pathway Is Involved in Lithium Carbonate-Induced Neural-Tube Defects in Mice and Neural Stem Cells.

Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3 treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3 at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels of Bmp2, Bmp4, Smad1, Smad5, Smad8 and Runx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3 or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3 exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3 exposure via inositol deficiency.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Objective: The accurate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) remains challenging. Few studies have investigated pathologic complete response (ypCR) prediction in patients with residual flat mucosal lesions after treatment. This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer (LARC). Methods: Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital. Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed, and a nomogram was constructed by incorporating the significant predictors. Results: Of the 246 patients with residual flat mucosal lesions included in the final analysis, 56 (22.8%) had ypCR. Univariate and multivariate analyses showed that pretreatment cT stage (pre-cT) ≤T2 (P=0.016), magnetic resonance tumor regression grade (MR-TRG) 1-3 (P=0.001) and residual mucosal lesion depth =0 mm (P<0.001) were associated with a higher rate of ypCR. A nomogram was developed with a concordance index (C-index) of 0.759 and the calibration curve showed that the nomogram model had good predictive consistency. The follow-up time ranged from 3.0 to 113.3 months, with a median follow-up time of 63.77 months. The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival (DFS) or overall survival (OS). Conclusions: Completely flat mucosa, early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT. Endoscopic mucosal re-evaluation before surgery is important, as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Unraveling the Mechanisms of Clinical Drugs-Induced Neural Tube Defects Based on Network Pharmacology and Molecular Docking Analysis.

Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein-protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant.

Microglia coordinate cellular interactions during spinal cord repair in mice.

Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.

Contrast-enhanced MRI for T Restaging of Locally Advanced Rectal Cancer Following Neoadjuvant Chemotherapy and Radiation Therapy.

Background Accurate restaging of rectal cancer is crucial in the selection of candidates for local excision after neoadjuvant chemotherapy and radiation therapy (NCRT). The conventional approach of combined T2-weighted imaging and diffusion-weighted imaging (DWI) at MRI has been found to have limitations in restaging. Purpose To determine the diagnostic performance of contrast-enhanced MRI in distinguishing between pathologic stage ypT0-1 and ypT2-4 rectal cancer after NCRT compared with T2-weighted imaging and DWI by using surgical pathologic specimens as the reference standard. Materials and Methods This retrospective study evaluated MRI scans in all consecutive patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT in Peking University Cancer Hospital (Beijing, China) from January 2014 to October 2018. All MRI features obtained before and after NCRT were evaluated by two experienced radiologists, independently and blinded to personal, clinical, and histopathologic information. The post-NCRT yT stage was assigned based on high b value (b = 1000 sec/mm2) DWI with T2-weighted imaging (protocol 1) in the first round and on contrast-enhanced MRI scans (protocol 2) in a second round. The diagnostic accuracies for the differentiation of pathologic stage ypT0-1 from ypT2-4 tumors with the two protocols were compared. Multivariable regression analysis was used to explore the independent predictors of pathologic stage ypT0-1 tumors. Results A total of 328 patients (mean age, 57 years ± 10 [SD]; 227 men; 69%) were enrolled. The area under the receiver operating characteristic curve of the contrast-enhanced MRI protocol in predicting pathologic stage ypT0-1 tumors was 0.81 (95% CI: 0.77, 0.85), which was better than that of the T2-weighted DWI protocol (0.66; 95% CI: 0.60, 0.71; P < .001). Multivariable logistic regression analysis showed that yT stage after NCRT on contrast-enhanced MRI scans was the only independent predictor of pathologic stage ypT0-1 tumors (P < .001). Conclusion Contrast-enhanced MRI provides accurate differentiation of ypT0-1 from ypT2-4 tumors after neoadjuvant chemotherapy and radiation therapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Zins and Santiago in this issue.

Spinal Cord Injury Impairs Lung Immunity in Mice.

Pulmonary infection is a leading cause of morbidity and mortality after spinal cord injury (SCI). Although SCI causes atrophy and dysfunction in primary and secondary lymphoid tissues with a corresponding decrease in the number and function of circulating leukocytes, it is unknown whether this SCI-dependent systemic immune suppression also affects the unique tissue-specific antimicrobial defense mechanisms that protect the lung. In this study, we tested the hypothesis that SCI directly impairs pulmonary immunity and subsequently increases the risk for developing pneumonia. Using mouse models of severe high-level SCI, we find that recruitment of circulating leukocytes and transcriptional control of immune signaling in the lung is impaired after SCI, creating an environment that is permissive for infection. Specifically, we saw a sustained loss of pulmonary leukocytes, a loss of alveolar macrophages at chronic time points postinjury, and a decrease in immune modulatory genes, especially cytokines, needed to eliminate pulmonary infections. Importantly, this injury-dependent impairment of pulmonary antimicrobial defense is only partially overcome by boosting the recruitment of immune cells to the lung with the drug AMD3100, a Food and Drug Administration-approved drug that mobilizes leukocytes and hematopoietic stem cells from bone marrow. Collectively, these data indicate that the immune-suppressive effects of SCI extend to the lung, a unique site of mucosal immunity. Furthermore, preventing lung infection after SCI will likely require novel strategies, beyond the use of orthodox antibiotics, to reverse or block tissue-specific cellular and molecular determinants of pulmonary immune surveillance.

Real-world colorectal cancer diagnostic pathways in Ontario, Canada: A population-based study.

OBJECTIVE: This study aimed to identify colorectal cancer (CRC) diagnostic pathways and describe patients in those pathway groups. METHODS: This was a cross-sectional study of CRC patients in Ontario, Canada, diagnosed 2009-2012 that used linked administrative data at ICES. We used cluster analysis on 11 pathway variables characterising patient presentation, symptoms, procedures and referrals. We assessed associations between patient- and disease-related characteristics and diagnostic pathway group. We further characterised the pathways by diagnostic interval and number of related physician visits. RESULTS: Six diagnostic pathways were identified, with three adhering to provincial diagnostic guidelines: screening (N = 4494), colonoscopy (N = 10,066) and imaging plus colonoscopy (N = 3427). Non-adherent pathways were imaging alone (N = 2238), imaging and emergency presentation (N = 2849) and no pre-diagnostic workup (N = 887). Patients in adherent pathways were younger, had fewer comorbidities, lived in less deprived areas and had earlier stage disease. The median diagnostic interval length varied across pathways from 12 to 126 days, correlating with the number of CRC-related visits. CONCLUSIONS: This study demonstrated substantial variations in real-world CRC diagnostic pathways and 25% were diagnosed through non-adherent pathways. Those patients were older, had more comorbid disease and had higher stage cancer. Further research needs to identify and describe the reasons for divergent diagnostic processes.

MRI measurements predict major low anterior resection syndrome in rectal cancer patients.

PURPOSE: Current low anterior resection syndrome (LARS) score is lagging behind and only based on clinical symptoms patient described. Preoperative imaging indicators which can be used to predict LARS is unknown. We proposed preoperative MRI parameters for identifying major LARS. METHODS: Patients receiving curative restorative anterior resection from Sept. 2007 to Sept. 2015 were collected to complete LARS score (median 75.7 months since surgery). MRI measurements associated with LARS were tested, and a multivariate logistic model was conducted for predicting LARS. Receiver operating characteristic curve was used to evaluate the model. RESULTS: Two hundred fifty-five patients undergoing neoadjuvant chemoradiotherapy and 72 patients undergoing direct surgery were enrolled. The incidence of major LARS in NCRT group was significantly higher (53.3% vs.34.7%, P = 0.005). In patients with neoadjuvant chemoradiotherapy, the thickness of ARJ (TARJ), the distance between the tumor's lower edge and anal rectal joint (DTA), and sex were independent factors for predicting major LARS; ORs were 0.382 (95% CI, 0.198-0.740), 0.653 (95% CI, 0.565-0.756), and 0.935 (95% CI, 0.915-0.955). The AUC of the multivariable model was 0.842 (95% CI, 0.794-0.890). In patients with direct surgery, only DTA was the independent factor for predicting major LARS; OR was 0.958 (95% CI, 0.930-0.988). The AUC was 0.777 (95% CI: 0.630-0.925). CONCLUSIONS: Baseline MRI measurements have the potential to predict major LARS in rectal cancer, which will benefit the decision-making and improve patients' life quality.

Correlation and prognostic value of CT-detected extramural venous invasion and pathological lymph-vascular invasion in colon cancer.

PURPOSE: To explore the association between CT-detected extramural vascular invasion (ctEMVI) and lymph-vascular invasion (LVI) in colon cancer, and analyze the prognostic value of ctEMVI in different conditions of LVI. METHODS: This single-center, retrospective study included 448 colon cancer patients from January 2015 to December 2017. Preoperative CT features and clinical and pathological data were collected. Associations between ctEMVI and LVI were tested. Univariate and multivariate logistic regression was performed. Multivariate Cox regression was performed adjusted with propensity score(PS). Kaplan-Meier method was used to compare survival differences between the ctEMVI and LVI groups. A 1:1 patient pairing was conducted using PS matching to assess the prognostic effect of ctEMVI in LVI subgroups. RESULTS: Among the 448 patients, there were 261 men and 187 women, with an average age of 63 ± 12 years. The coincidence rate of ctEMVI and LVI was 73.9%. The k coefficient for identifying ctEMVI was 0.84. ctEMVI and LVI were both independent risk factors for overall survival (ctEMVI: HR 2.8, 95% CI 1.5-5.5; LVI: HR 2.2, 95% CI 1.2-4.1) and metastasis-free survival (ctEMVI: HR 3.3, 95% CI 1.7-6.4; LVI: HR 2.4, 95% CI 1.3-4.5) adjusted with PS. In the LVI(+) subgroup, the prognosis of ctEMVI(+) was significantly worse than that of ctEMVI(-); in the LVI(-) subgroup, the prognosis of different ctEMVI states was similar. CONCLUSION: ctEMVI is an independent prognostic risk factor and has different prognostic value in different LVI states. It is recommended to perform the evaluation in routine work, especially for patients with positive LVI.

Corresponding Changes of Autophagy-Related Genes and Proteins in Different Stages of Knee Osteoarthritis: An Animal Model Study.

OBJECTIVE: To investigate the effect of autophagy expression levels of different weight-bearing states and different stages of osteoarthritis in animal models, as well as the corresponding mechanisms. METHODS: We used the male Sprague-Dawley (SD) rats (12-week-old, SPF) to establish the OA animal models by modified Hulth method, and grouped animal models according to the length of time after surgery and different weight-bearing areas. RT-qPCR was carried out for detection of autophagy-related genes such as Atg7, Atg12, P62, etc. Western blot analysis was used to detect the expression levels of corresponding autophagy-related proteins such as LC3B, P62, etc. T test was performed for statistical analysis to compare different groups, while the differences were deemed statistically significant with P < 0.05. Transmission electron microscopy was used to observe the autophagosome to demonstrate the level of autophagy expression and the status of the chondrocytes. RESULTS: The results of the RT-qPCR testing showed that when the weight-bearing cartilage of the 4-week group (relatively mild) was compared with that of the 10-week group (relatively severe), there were statistically significant differences in all the genes tested, in detail: Atg3 (P < 0.01), Atg7 (P < 0.01), Atg12 (P < 0.01), P62 (P < 0.0001). The expression of autophagy-related mRNA in the 4-week group is increased compared with that of the 10-week group. As for the expression of proteins, Western blotting showed that in the comparison between the 4- and the 10-week groups, statistically significant results include Atg12 (P < 0.01) in the non-weight-bearing area, with decreased autophagy in the 10-week group compared with that of the 4-week group, while expression of LC3B (P < 0.05) protein was significantly higher in the 4-week group than in the control in the non-weight-bearing area. The expression of LC3B (P < 0.0001) and P62 (P < 0.05) in the 10-week group were higher than that of the control. Transmission electron microscope showed that autophagy in the weight-bearing area is stronger than that in the non-weight-bearing area, and autophagy in the 4-week group is stronger than in the 10-week group for the weight-bearing area. CONCLUSIONS: The expression of autophagy varies during different stages of osteoarthritis, in which the autophagy is stronger in the early stage of osteoarthritis, and gradually decreases with the progression of the disease. Autophagy in different weight-bearing areas may also be different.

Correlation Between the Distance to Mesorectal Fascia and Prognosis of cT3 Rectal Cancer: Results of a Multicenter Study From China.

BACKGROUND: The cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer have several limitations. OBJECTIVE: This study proposed that the distance between the deepest tumor invasion and mesorectal fascia on pretherapy MRI can distinguish the prognosis of patients with cT3 rectal cancer. DESIGN: This is a cohort study. SETTING: This study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort. PATIENT: Patients who had cT3 rectal cancer with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in 4 centers in China from January 2013 to September 2014. INTERVENTION: Baseline MRI with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion, and mesorectum thickness were measured. MAIN OUTCOME MEASURES: The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operating characteristic curves, supported by a 5-year progression rate from the prospective cohort, and was then validated in a retrospective cohort. RESULTS: There were 124 and 274 patients included in the prospective and independent validation cohorts. The distance between the deepest tumor invasion and mesorectal fascia was the only predictor for cancer-specific death (HR, 0.1; 95% CI, 0.0-0.7) and was also a significant predictor for distant recurrence (HR, 0.4; 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patients classified as T3a/b and T3c/d. LIMITATIONS: The sample size is relatively small, and the study focused on cT3 rectal cancers with a negative mesorectal fascia. CONCLUSIONS: A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI can distinguish cT3 rectal cancer from a different prognosis. We recommend using the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI for local and systemic risk assessment and providing a tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682.CORRELACIÓN ENTRE LA DISTANCIA DE LA FASCIA MESORRECTAL Y EL PRONÓSTICO DEL CÁNCER DE RECTO cT3: RESULTADOS DE UN ESTUDIO MULTICÉNTRICO DE CHINAANTECEDENTES:Los criterios de subestadificación cT3 basados en la profundidad extramural de invasión tumoral en el cáncer de recto tienen varias limitaciones.OBJETIVO:Este estudio propuso que la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética preterapia puede distinguir el pronóstico de los pacientes con cT3.DISEÑO:Estudio de cohorte.ENTORNO CLINICO:El estudio incluyó una cohorte observacional, prospectiva, unicéntrica, y una cohorte de validación retrospectiva, multicéntrica e independiente.PACIENTE:Se incluyeron pacientes con cáncer de recto cT3 con fascia mesorrectal negativa sometidos a quimio-radioterapia neoadyuvante seguida de cirugía radical en cuatro centros de China desde enero de 2013 hasta septiembre de 2014.INTERVENCIÓN:Imágenes de resonancia magnética de referencia fueron medidas con la distancia entre la invasión tumoral más profunda y la fascia mesorrectal; la profundidad extramural de la invasión tumoral y el grosor del mesorrecto.PRINCIPALES MEDIDAS DE VALORACION:El límite de la distancia entre la invasión tumoral más profunda y la fascia mesorrectal se determinó mediante curvas características operativas del receptor dependientes del tiempo y se apoyó en la tasa de progresión a 5 años de la cohorte prospectiva, y luego se validó en una cohorte retrospectiva.RESULTADOS:Se incluyeron 124 y 274 pacientes en la cohorte de validación prospectiva e independiente, respectivamente. La distancia entre la invasión tumoral más profunda de la fascia mesorrectal fue el único predictor de muerte específica por cáncer (Hazard ratio: 0.1, 95% CI, 0,0-0,7); y también fue un predictor significativo de recurrencia distante Hazard ratio: 0,4, 95% CI, 0,2-0,9). No se observaron diferencias estadísticamente significativas en el pronóstico entre los pacientes clasificados como T3a/b y T3c/d.LIMITACIONES:El tamaño de la muestra es relativamente pequeño y el estudio se centró en los cánceres de recto cT3 con fascia mesorrectal negativa.CONCLUSIONES:Un límite de 7 mm de distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia puede distinguir el cáncer de recto cT3 de diferentes pronósticos. Recomendamos la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia para la evaluación del riesgo local y sistémico, proporcionando un programa personalizado de tratamiento neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B682. (Traducción- Dr. Francisco M. Abarca-Rendon).