Development and Validation of a Nomogram Based on DCE-MRI Radiomics for Predicting Hypoxia-Inducible Factor 1α Expression in Locally Advanced Rectal Cancer.

RATIONALE AND OBJECTIVES: The expression levels of hypoxia-inducible factor 1 alpha (HIF-1α) have been identified as a pivotal marker, correlating with treatment response in patients with locally advanced rectal cancer (LARC). This study aimed to develop and validate a nomogram based on dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinical features for predicting the expression of HIF-1α in patients with LARC. MATERIALS AND METHODS: A total of 102 patients diagnosed with locally advanced rectal cancer were divided into training (n = 71) and validation (n = 31) cohorts. The expression statuses of HIF-1α were histopathologically classified, categorizing patients into high and low expression groups. The intraclass correlation coefficient (ICC), minimum redundancy maximum relevance (mRMR), and the least absolute shrinkage and selection operator (LASSO) were employed for feature selection to construct a radiomics signature and calculate the radiomics score (Rad-score). Univariate and multivariate analyses of clinical features and Rad-score were applied, and the clinical model and the nomogram were constructed. The predictive performance of the nomogram incorporating clinical features and Rad-score was assessed using Receiver Operating Characteristics (ROC) curves, decision curve analysis (DCA), and calibration curves. RESULTS: Seven radiomics features from DCE-MRI were used to build the radiomics signature. The nomogram incorporating CEA, Ki-67 and Rad-score had the highest AUC values in the training cohort and in the validation cohort (AUC: 0.918 and 0.920). Decision curve analysis showed that the nomogram outperformed the clinical model and radiomics signature in terms of clinical utility. In addition, the calibration curve for the nomogram demonstrated good agreement between prediction and actual observation. CONCLUSION: The nomogram based on DCE-MRI radiomics and clinical features showed favorable predictive efficacy and might be useful for preoperatively discriminating the expression of HIF-1α.

Machine learning models based on quantitative dynamic contrast-enhanced MRI parameters assess the expression levels of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes in advanced gastric carcinoma.

Objective: To explore the effectiveness of machine learning classifiers based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the expression levels of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes (TILs) in patients with advanced gastric cancer (AGC). Methods: This study investigated 103 patients with confirmed AGC through DCE-MRI and immunohistochemical staining. Immunohistochemical staining was used to evaluate CD3+, CD4+, and CD8+ T-cell expression. Utilizing Omni Kinetics software, radiomics features (Ktrans, Kep, and Ve) were extracted and underwent selection via variance threshold, SelectKBest, and LASSO methods. Logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost) are the four classifiers used to build four machine learning (ML) models, and their performance was evaluated using 10-fold cross-validation. The model's performance was evaluated and compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: In terms of CD3+, CD4+, and CD8+ T lymphocyte prediction models, the random forest model outperformed the other classifier models in terms of CD4+ and CD8+ T cell prediction, with AUCs of 0.913 and 0.970 on the training set and 0.904 and 0.908 on the validation set, respectively. In terms of CD3+ T cell prediction, the logistic regression model fared the best, with AUCs on the training and validation sets of 0.872 and 0.817, respectively. Conclusion: Machine learning classifiers based on DCE-MRI have the potential to accurately predict CD3+, CD4+, and CD8+ tumor-infiltrating lymphocyte expression levels in patients with AGC.

Preliminary MRS study of critical values of relevant brain metabolites in elderly Chinese patients with post-stroke cognitive impairment.

Objective: Proton magnetic resonance spectroscopy (1H-MRS) was applied in this study to detect metabolite changes in the brain of post-stroke cognitive impairment (PSCI) and normal volunteers. The levels of N-acetylaspartate (NAA) and creatinine (Cr) and in the frontal lobe, hippocampus and cingulate gyrus were measured to distinguish patients with post-stroke cognitive impairment (PSCI) and normal control group (NC). The relationship between them and cognitive function was explored and a critical value of the metabolite ratio was predicted. This study may serve as a reference for the diagnosis of cognitive dysfunction after stroke. Methods: A total of 46 patients with PSCI (PSCI group, all patients are unilateral cerebral infarction or intracerebral haemorrhage) were screened by the Mini-Mental Status Examination (MMSE), and 35 healthy volunteers were selected as normal control group (NC group). The general information of gender, age, and education level was matched between the two groups. Two groups of subjects were examined using MRS and evaluated for cognitive function using the MMSE test and the Montreal Cognitive Assessment Scale (MoCA). The correlation between MRS and neurobehavioral scale (MMSE test and MoCA scale) was analysed, and the possible demarcation points of the brain metabolism of PSCI were evaluated. Result: The MMSE and MoCA scores of patients with PSCI were lower significantly when compared with those of the NC group (P < 0.05). The NAA/Cr values of the bilateral hippocampus, bilateral frontal lobe and bilateral anterior and posterior cingulate gyrus in the PSCI group were lower than those in the NC group (P < 0.05). The NAA/Cr cut-off value for the right frontal lobe was 1.533, and the NAA/Cr sensitivity, specificity and Youden index for the right frontal lobe were 0.943, 0.935, and 0.878. Conclusion: NAA/Cr values in the MRS bilateral frontal, bilateral hippocampus and bilateral anterior and posterior cingulate gyrus were reduced in the cognitively impaired post-stroke patients compared to the normal control group. MRS was also found to be correlated with the score of neurobehavioral scale (MMSE test and MoCA scale) and the combination of the two could evaluate cognitive dysfunction more comprehensively and objectively. NAA/Cr value of the right frontal lobe < 1.533 indicated that PSCI may occur. In accordance with this cut-off point, PSCI could be detected as early as possible and timely intervention could be carried out.

Association between radiomics features of DCE-MRI and CD8+ and CD4+ TILs in advanced gastric cancer.

Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer. Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density. Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630-0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = -0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = -0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856). Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.

TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer.

PURPOSE: This study aims to evaluate the value of tissue inhibitors of MMPs-2 (TIMP-2) to indicate 5-Fluorouracil (5-Fu) resistance status in colorectal cancer. METHODS: The 5-Fu resistance of colorectal cancer cell lines was detected using Cell-Counting Kit-8 (CCK-8) and calculated using IC50. Enzyme-linked immunosorbent assay (ELISA) and real time-quantitative polymerase chain reaction (RT-qPCR) were used to detect TIMP-2 expression level in the culture supernatant and serum. Twenty-two colorectal cancer patients' TIMP-2 levels and clinical characteristics were analyzed before and after chemotherapy. Additionally, the patient-derived xenograft (PDX) model of 5-Fu resistance was used to evaluate the feasibility of TIMP-2 as a predictive biomarker of 5-Fu resistance. RESULTS: Our experimental results display that TIMP-2 expression is elevated in colorectal cancer drug-resistant cell lines, and its expression level is closely related to 5-Fu resistance. Moreover, TIMP-2 in colorectal cancer patient serum undergoing 5-Fu-based chemotherapy could indicate their drug resistance status, and its efficacy is higher than CEA and CA19-9. Finally, PDX model animal experiments reveal that TIMP-2 can detect 5-Fu resistance in colorectal cancer earlier than tumor volume. CONCLUSION: TIMP-2 is a good indicator of 5-Fu resistance in colorectal cancer. Monitoring the serum TIMP-2 level can help the clinician identify 5-Fu resistance in colorectal cancer patients earlier during chemotherapy.

Arteriocolonic fistula of inferior mesenteric artery aneurysm: A case with lower gastrointestinal and intra-abdominal hemorrhage.

Introduction: Arteriocolonic fistula of Inferior Mesenteric Artery Aneurysm (IMAA) refers to a spontaneous formation of pathological communication between the artery and the adjacent gastrointestinal tract. It is a rare, life-threatening condition primarily manifesting as abdominal pain, gastrointestinal bleeding, abdominal pulsating masses. However, its clinical manifestations are usually atypical with a difficult diagnosis and treatment. Case presentation: We report a rare case of a 50-year-old male with a hemorrhagic shock due to primary arteriocolonic fistula of IMAA. Instead of sigmoidectomy, super selective transcatheter arterial embolization (TAE) was performed after diagnostic angiography. Postoperatively, dynamic contrast-enhanced abdominal computed tomography (CT) demonstrated no recanalization of the aneurysm, absence of abnormal collateral vessels, no active hemorrhage. The patient was discharged uneventfully after 2 weeks without abdominal pain or tension. Discussion: Colorectal tumor rupture is a major cause of lower gastrointestinal bleeding (LGIB), with IMAA being an uncommon etiology. Because of the high mortality of explorative laparotomy with an unclear bleeding site, diagnostic angiography and therapeutic TAE are viable options for diagnosing hemodynamic instability. Conclusion: Arteriocolonic fistulas commonly occur secondary to a pseudoaneurysm formed at the anastomosis of the transplanted blood vessel after an artery surgery, which ruptures and penetrates into the intestine. We reported a unique case of primary arteriocolonic fistula of IMAA: aneurysm rupture and bleeding from the abdomen into the hematochezia. After multidisciplinary consultations, our patient obtained the best outcome using the most minimally invasive surgical methods. With an abdominal artery aneurysm presenting with colorectal hemorrhage, arteriocolonic fistula of IMAA should be suspected.

DCE-MRI radiomics models predicting the expression of radioresistant-related factors of LRP-1 and survivin in locally advanced rectal cancer.

Objective: Low-density lipoprotein receptor-related protein-1 (LRP-1) and survivin are associated with radiotherapy resistance in patients with locally advanced rectal cancer (LARC). This study aimed to evaluate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the preoperative assessment of LRP-1 and survivin expressions in these patients. Methods: One hundred patients with pathologically confirmed LARC who underwent DCE-MRI before surgery between February 2017 and September 2021 were included in this retrospective study. DCE-MRI perfusion histogram parameters were calculated for the entire lesion using post-processing software (Omni Kinetics, G.E. Healthcare, China), with three quantitative parameter maps. LRP-1 and survivin expressions were assessed by immunohistochemical methods and patients were classified into low- and high-expression groups. Results: Four radiomics features were selected to construct the LRP-1 discrimination model. The LRP-1 predictive model achieved excellent diagnostic performance, with areas under the receiver operating curve (AUCs) of 0.853 and 0.747 in the training and validation cohorts, respectively. The other four radiomics characteristics were screened to construct the survivin predictive model, with AUCs of 0.780 and 0.800 in the training and validation cohorts, respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics models. Conclusion: DCE-MRI radiomics models are particularly useful for evaluating LRP-1 and survivin expressions in patients with LARC. Our model has significant potential for the preoperative identification of patients with radiotherapy resistance and can serve as an essential reference for treatment planning.

Imaging Manifestations of Intrahepatic Reactive Lymphoid Hyperplasia: A Case Report and Literature Review.

Reactive lymphoid hyperplasia (RLH) of the liver is a rare benign disease. This article describes a 77-year-old female patient with RLH of the liver. The patient was admitted to the hospital due to atrial fibrillation. A liver tumor was incidentally found during abdominal enhanced CT. Further magnetic resonance imaging (MRI) and PET/CT showed four lesions in the liver. The imaging findings suggested hepatocellular carcinoma (HCC), but it was not consistent that the patient had no history of liver cirrhosis and hepatitis, and a variety of tumor markers were within the normal range. The largest lesion was surgically removed and microscopically diagnosed as RLH of the liver. The pathology included a large number of reactive hyperplastic lymphoid follicles. Immunohistochemical examination showed that the infiltrating lymphocytes were polyclonal. The authors believe that the perinodular enhancement on MRI, the obvious limitation of diffusion on DWI, the insignificant increase of SUVmax on PET-CT delayed phase, and the support of clinical data can help distinguish liver RLH from lymphoma and HCC.

Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer.

Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC). Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score. Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p < 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively). Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.

Individualized treatment for gastric cancer with rib metastasis: A case report.

BACKGROUND: Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even less common. The clinical prognosis of GC with bone metastasis is poor given the lack of an effective treatment. CASE SUMMARY: A 70 year old man was referred to Shaoxing People's Hospital with left chest pain and slight dyspnea. Chest computed tomography (CT) revealed a metastatic lesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers in the angle and antrum of the stomach, and tumor biomarkers including CEA and CA-199 were clearly increased. In addition, lymph node metastasis in the lesser curvature of the stomach was identified by positron emission tomography/CT scanning. Further pathological examination confirmed metastatic adenocarcinoma in the rib and medium-low differentiated adenocarcinoma in the gastric space. The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB). Based on multidisciplinary team opinions, the patient received five courses of chemotherapy (CAPOX plus aptinib), and then underwent rib resection and laparoscopic radical distal gastrectomy. The patient started four courses of chemotherapy after surgery, and then capecitabine and aptinib were administered orally for 3 mo. Follow-up was performed on an outpatient basis using abdominal/chest CT and tumor biomarkers. The patient exhibited an overall survival greater than 2 years, and the disease-free survival was approximately 18 mo. His adverse events were tolerable. CONCLUSION: The incidence of GC with rib metastases is extremely low, and patients can obtain more benefits from individualized treatment formulated by multidisciplinary team. Chemotherapy plus surgery might represent an alternative option for GC with rib metastasis.

Dual-targeting strategy using trastuzumab and lapatinib in a patient with HER2 gene amplification in recurrent metachronous metastatic gallbladder carcinoma.

Gallbladder carcinoma (GBC) is a rare and highly aggressive tumor. Early diagnosis is challenging, which results in a poor prognosis using systemic therapy. Recent studies have identified a subset of GBC patients with HER2 gene (ERBB2) amplification that could benefit from HER2-targeted therapy. Here, we report one patient with recurrent metachronous GBC with metastasis, who received the combination of trastuzumab and lapatinib. This approach achieved a partial response for both the brain and the lung metastases. This study demonstrated that HER2 inhibition is a promising therapeutic strategy for GBC with HER2 amplification and, combined with lapatinib, it can effectively target brain metastasis.

A Comparison between Prethoracoscopy Localization of Small Pulmonary Nodules by Means of Medical Adhesive versus Hookwire.

PURPOSE: To compare prethoracoscopy localization of small pulmonary nodules (SPNs) by means of medical adhesive versus hookwire. MATERIALS AND METHODS: One hundred seven patients who underwent video-assisted thoracoscopic surgery resection for SPNs were consecutively recruited in this retrospective cohort study. Patients were divided into 2 groups according to the material used for localization of the SPNs: the medical adhesive group (n = 88) and the hookwire group (n = 19). The baseline data were collected, and operation waiting time (OWT; the time gap between localization and surgery), wedge resection performing time (WRPT), pathologic result, and complications of the 2 groups were assessed. RESULTS: All SPNs were successfully marked. No differences in pathologic result (P = .676), wedge resection, or segmentectomy rate (P = .679) were observed. OWT was markedly longer in the medical adhesive group than in the hookwire group (P < .001), whereas WRPT was similar in the 2 groups (P = .926). There were significantly (P = .004) fewer complications in the medical adhesive group (37.42%) than in the hookwire group (15.79%). Regarding individual complications, hemorrhage occurred significantly less in the medical adhesive group than in the hookwire group (9% vs 68%; P < .001), and no differences of cough, pneumothorax, or chest pain were found between the 2 groups (all P > .05). Multivariate logistic regression analysis further validated that hookwire was independently correlated with a higher risk of complication occurrence (P = .008) and hemorrhage occurrence (P < .001) compared with medical adhesive. CONCLUSIONS: Compared with hookwire, localization via medical adhesive can achieve a flexible time gap between localization and surgery. It also decreases the complication rate and increases convenience owing to no need for an anchor hook.

Protein phosphatase 1 inhibits p53 signaling by dephosphorylating and stabilizing Mdmx.

The activation and stabilization of the p53 protein play a major role in the DNA damage response. Protein levels of p53 are tightly controlled by transcriptional regulation and a number of positive and negative posttranslational modifiers, including kinases, phosphatases, E3 ubiquitin ligases, deubiquitinases, acetylases and deacetylases. One of the primary p53 regulators is Mdmx. Despite its RING domain and structural similarity with Mdm2, Mdmx does not have an intrinsic ligase activity, but inhibits the transcriptional activity of p53. Previous studies reported that Mdmx is phosphorylated and destabilized in response to DNA damage stress. Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity. Our results suggest that PP1 is a crucial component in the ATM-Chk2-p53 signaling pathway.