Whole-tumor amide proton transfer-weighted imaging histogram analysis to predict pathological extramural venous invasion in rectal adenocarcinoma: a preliminary study.

OBJECTIVES: To evaluate amide proton transfer-weighted (APTw)-derived whole-tumor histogram analysis parameters in predicting pathological extramural venous invasion (pEMVI) positive status of rectal adenocarcinoma (RA). METHODS: Preoperative MR including APTw imaging of 125 patients with RA (mean 61.4 ± 11.6 years) were retrospectively analyzed. Two radiologists reviewed each case's EMVI status based on the MR-based modified 5-point scale system with conventional MR images. The APTw histogram parameters of primary tumors were obtained automatically using whole-tumor volume histogram analysis. The independent risk factors markedly correlated with pEMVI-positive status were assessed using univariate and multivariate logistic regression analyses. Diagnosis performance was assessed by receiver operating characteristic curve (ROC) analysis. The AUCs were compared using the Delong method. RESULTS: Univariate analysis demonstrated that MR-tumor (T) stage, MR-lymph node (N) stage, APTw-10%, APTw-90%, interquartile range, APTw-minimum, APTw-maximum, APTw-mean, APTw-median, entropy, kurtosis, mean absolute deviation (MAD), and robust MAD were significantly related to pEMVI-positive status (all p < 0.05). Multivariate analysis demonstrated that MR-T stage (OR = 4.864, p = 0.018), MR-N stage (OR = 4.967, p = 0.029), interquartile range (OR = 0.892, p = 0.037), APT-minimum (OR = 1.046, p = 0.031), entropy (OR = 11.604, p = 0.006), and kurtosis (OR = 1.505, p = 0.007) were the independent risk factors enabling prediction of pEMVI-positive status. The AUCs for diagnostic ability of conventional MRI assessment, the APTw histogram model, and the combined model (including APTw histogram and clinical variables) were 0.785, 0.853, and 0.918, respectively. The combined model outperformed the APTw histogram model (p = 0.013) and the conventional MRI assessment (p = 0.006). CONCLUSIONS: Whole-tumor histogram analysis of APTw images combined with clinical factors showed better diagnosis efficiency in predicting EMVI involvement in RA. KEY POINTS: • Rectal adenocarcinomas with pEMVI-positive status are typically associated with higher APTw-SI values. • APTw-minimum, interquartile range, entropy, kurtosis, MR-T stage, and MR-N stage are the independent risk factors for EMVI involvement. • The best prediction for EMVI involvement was obtained with a combined model of APTw histogram and clinical variables (area under the curve, 0.918).

Evaluation of the Modulation Effects Evoked by Different Transcutaneous Auricular Vagus Nerve Stimulation Frequencies Along the Central Vagus Nerve Pathway in Migraine: A Functional Magnetic Resonance Imaging Study.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising treatment option for migraines. This study aims to investigate the modulation effects of different taVNS frequencies along the central vagus nerve pathway in migraineurs. MATERIALS AND METHODS: Twenty-four migraineurs were recruited for a single-blind, crossover magnetic resonance imaging (MRI) study. The study consisted of two taVNS MRI scan sessions, in which either 1-Hz or 20-Hz taVNS was applied in a random order. Seed-based static and dynamic functional connectivity (FC) analyses were performed using two key nodes of the vagus nerve pathway, the nucleus tractus solitarius (NTS) and the locus coeruleus (LC). RESULTS: Static FC (sFC) analysis showed that 1) continuous 1-Hz taVNS resulted in an increase of NTS/LC-occipital cortex sFC and a decrease of NTS-thalamus sFC compared with the pre-1-Hz taVNS resting state, 2) continuous 20-Hz taVNS resulted in an increase of the LC-anterior cingulate cortex (ACC) sFC compared with the pre-20-Hz taVNS resting state, 3) 1-Hz taVNS produced a greater LC-precuneus and LC-inferior parietal cortex sFC than 20 Hz, and 4) 20-Hz taVNS increased LC-ACC and LC-super temporal gyrus/insula sFC in comparison with 1 Hz. Dynamic FC (dFC) analysis showed that compared with the pre-taVNS resting state, 1-Hz taVNS decreased NTS-postcentral gyrus dFC (less variability), 20-Hz taVNS decreased dFC of the LC-superior temporal gyrus and the LC-occipital cortex. Finally, a positive correlation was found between the subjects' number of migraine attacks in the past four weeks and the NTS-thalamus sFC during pre-taVNS resting state. CONCLUSIONS: 1-Hz and 20-Hz taVNS may modulate the sFC and dFC of key nodes in the central vagus nerve pathway differently. Our findings highlight the importance of stimulation parameters (frequencies) in taVNS treatment.

Development of MR-based preoperative nomograms predicting DNA copy number subtype in lower grade gliomas with prognostic implication.

OBJECTIVES: We aimed to determine the value of MR-based preoperative nomograms in predicting DNA copy number (CN) subtype in lower grade glioma (LGG) patients. METHODS: The overall survival (OS) data were analyzed. MRI data of 170 subjects were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analysis. RESULTS: CN2 subtype was associated with shortest median OS (CN2 subtype vs. others: 46.8 vs. 221.7 months, p < 0.05). The time-dependent receiver operating characteristic for the CN2 subtype was 0.80 (95% CI: 0.74-0.85) for survival at 1 year, 0.80 (95% CI: 0.75-0.85) for survival at 2 years, and 0.77 (95% CI: 0.73-0.83) for survival at 3 years. On multivariate analysis, hemorrhage (OR: 0.118; p < 0.001; 95% CI: 0.037-0.376), poorly defined margin (OR: 4.592; p < 0.001; 95% CI: 1.965-10.730), extranodular growth (OR: 0.247; p = 0.006; 95% CI: 0.091-0.671), and volume ≥ 60 cm3 (OR: 4.734.256; p < 0.001; 95% CI: 2.051-10.924) were associated with CN1 subtype (AUC: 0.781). Proportion CE tumor (OR: 5.905; p = 0.007; 95% CI: 1.622-21.493), extranodular growth (OR: 9.047; p = 0.001; 95% CI: 2.349-34.846), width ≥ median (OR: 0.231; p = 0.049; 95% CI: 0.054-0.998), and depth ≥ median (OR: 0.192; p = 0.023; 95% CI: 0.046-0.799) were associated with CN2 subtype (AUC: 0.854). Necrosis/cystic (OR: 6.128; p = 0.007; 95% CI: 1.635-22.968), hemorrhage (OR: 5.752; p = 0.002; 95% CI: 1.953-16.942), poorly defined margin (OR: 0.164; p < 0.001; 95% CI: 0.063-0.427), and volume ≥ median (OR: 4.422; p < 0.001; 95% CI: 1.925-10.160) were associated with CN3 subtype (AUC: 0.808). All three nomograms showed good discrimination and calibration. Decision curve analysis supported that all nomograms were clinically useful. The average accuracy of the tenfold cross-validation was 0.680 (CN1), 0.794 (CN2), and 0.894 (CN3), respectively. CONCLUSIONS: The shortest OS was observed in patients with CN2 subtype. This preliminary radiogenomics analysis revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. KEY POINTS: • This preliminary radiogenomics analysis of LGG revealed that the MR-based preoperative nomograms provide individualized prediction of DNA copy number subtype in LGG patients. • The AUC for the ROC curve was 0.781 for CN1 subtype, 0.854 for CN2 subtype, and 0.808 for CN3 subtype. Decision curve analysis supported that all nomograms were clinically useful. • The sensitivity was 0.779 (CN1), 0.731 (CN2), and 0.851 (CN3), respectively. The specificity was 0.664 (CN1), 0.872 (CN2), and 0.625 (CN3), respectively. And the accuracy was 0.717 (CN1), 0.849 (CN2), and 0.692 (CN3), respectively.

A Rare EGFR-SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Growing evidence supports gene fusions as good candidates for molecularly targeted therapy in CRC. Here we describe a case of a 63-year-old man who had a radical right hemicolectomy procedure 24 months ago. Pathological diagnosis indicated colorectal adenocarcinoma with stage pT4N2bMx. During re-examination in December 2016, positron emission tomography/computed tomography scans indicated relapse with multiple lymph nodes metastasis. Then the patient received a nine-cycle combination treatment of XELOX and bevacizumab and showed progressive disease (PD). Subsequently, the patient was treated with bevacizumab plus FOLFIRI for 2 months before discontinuation because of adverse events. Paraffin sections of postoperative colorectal tissue were subjected to next-generation sequencing, and epidermal growth factor receptor (EGFR) amplification and rare EGFR-SEPT14 fusion were identified. The patient then received erlotinib, an EGFR tyrosine kinase inhibitor (TKI), and achieved a partial response. However, the patient subsequently showed PD, and a new variant, EGFRvIII, appeared in metastasis, which may be involved in erlotinib resistance. We suggest that there is value in treating patients harboring EGFR fusions with EGFR TKI therapy, and EGFR-SEPT14 fusion may be used as a therapeutic target for CRC. KEY POINTS: To the authors' knowledge, this is the first report of EGFR-SEPT14 fusion in colorectal cancer. The patient achieved a partial response after treatment with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. This report expands the list of gene fusions in colorectal cancer and highlights new targets for the therapeutic intervention. EGFRvIII may be involved in erlotinib resistance, which is rare in colorectal cancer.

The Instant Effects of Continuous Transcutaneous Auricular Vagus Nerve Stimulation at Acupoints on the Functional Connectivity of Amygdala in Migraine without Aura: A Preliminary Study.

Background: A growing body of evidence suggests that both auricular acupuncture and transcutaneous auricular vagus nerve stimulation (taVNS) can induce antinociception and relieve symptoms of migraine. However, their instant effects and central treatment mechanism remain unclear. Many studies proved that the amygdalae play a vital role not only in emotion modulation but also in pain processing. In this study, we investigated the modulation effects of continuous taVNS at acupoints on the FC of the bilateral amygdalae in MwoA. Methods: Thirty episodic migraineurs were recruited for the single-blind, crossover functional magnetic resonance imaging (fMRI) study. Each participant attended two kinds of eight-minute stimulations, taVNS and sham-taVNS (staVNS), separated by seven days in random order. Finally, 27 of them were included in the analysis of seed-to-voxel FC with the left/right amygdala as seeds. Results: Compared with staVNS, the FC decreased during taVNS between the left amygdala and left middle frontal gyrus (MFG), left dorsolateral superior frontal gyrus, right supplementary motor area (SMA), bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus, so did the FC of the right amygdala and left MFG. A significant positive correlation was observed between the FC of the left amygdala and right SMA and the frequency/total time of migraine attacks during the preceding four weeks. Conclusion: Continuous taVNS at acupoints can modulate the FC between the bilateral amygdalae and pain-related brain regions in MwoA, involving the limbic system, default mode network, and pain matrix, with obvious differences between the left amygdala and the right amygdala. The taVNS may produce treatment effects by modulating the abnormal FC of the amygdala and pain networks, possibly having the same central mechanism as auricular acupuncture.

Case report: Metastatic refractory undifferentiated small round-cell sarcoma successfully treated with surufatinib and camrelizumab.

Background: Undifferentiated small round-cell sarcomas (uSRCSs) are a subgroup of sarcomas that are difficult to diagnose. Some uSRCSs have specific gene re-arrangements, but others do not. Currently, there is no specific treatments for advanced uSRCSs, and its treatment is largely based on general experience with sarcomas, which includes chemotherapy, targeted therapy, and immunotherapy. In this article, we report a patient with uSRCS who responded to treatment with anti-VEGF inhibitor surufatinib and anti-PD-1 inhibitor camrelizumab after progression on first-line chemotherapy, second-line anlotinib combined with immunotherapy, and third-line chemotherapy. Case description: In July 2020, a 37-year-old female patient was diagnosed with advanced uSRCS. Results for the Ewing sarcoma RNA binding protein 1 and Wilms tumor suppressor (EWSR1/WT1) fusion gene were negative. The patient was also negative with BCOR (BCL6 co-repressor) and CIC (capicua transcriptional repressor) fusion gene. The next-generation sequencing results revealed point mutations on Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB), Transcription Factor Binding To IGHM Enhancer 3 (TFE3), Mucin 16 (MUC16), and AXL (Axl, also called UFO, ARK, and Tyro7, is part of a family of receptor tyrosine kinases). The patient received 4 cycles of the Ifosfamide and epirubicin hydrochloride regimen, and her best objective response was stable disease. On November 3, 2020, a computed tomography (CT) scan revealed progressive disease (PD). Two cycles of camrelizumab (a programmed death-1 inhibitor) plus anlotinib (an anti- vascular endothelial growth factor drug) were administered, but PD was again observed. Thus, a regimen of gemcitabine plus docetaxel was adopted. Unfortunately, the disease progressed once again after two cycles of the treatment. On February 4, 2021, the patient began to receive targeted therapy with surufatinib combined with camrelizumab. A CT scan showed that the tumor achieved a partial response. As of April 2023, the patient had a progression-free survival time of 26 months. Conclusions: Surufatinib in combination with camrelizumab could be effective in the treatment of advanced uSRCSs.

Cystic renal mass screening: machine-learning-based radiomics on unenhanced computed tomography

PURPOSE: The present study compares the diagnostic performance of unenhanced computed tomography (CT) radiomics-based machine learning (ML) classifiers and a radiologist in cystic renal masses (CRMs). METHODS: Patients with pathologically diagnosed CRMs from two hospitals were enrolled in the study. Unenhanced CT radiomic features were extracted for ML modeling in the training set (Guangzhou; 162 CRMs, 85 malignant). Total tumor segmentation was performed by two radiologists. Features with intraclass correlation coefficients of >0.75 were screened using univariate analysis, least absolute shrinkage and selection operator, and bidirectional elimination to construct random forest (RF), decision tree (DT), and k-nearest neighbor (KNN) models. External validation was performed in the Zhuhai set (45 CRMs, 30 malignant). All images were assessed by a radiologist. The ML models were evaluated using calibration curves, decision curves, and receiver operating characteristic (ROC) curves. RESULTS: Of the 207 patients (102 women; 59.1 ± 11.5 years), 92 (41 women; 58.0 ± 13.7 years) had benign CRMs, and 115 (61 women; 59.8 ± 11.4 years) had malignant CRMs. The accuracy, sensitivity, and specificity of the radiologist's diagnoses were 85.5%, 84.2%, and 91.1%, respectively [area under the (ROC) curve (AUC), 0.87]. The ML classifiers showed similar sensitivity (94.2%-100%), specificity (94.7%-100%), and accuracy (94.3%-100%) in the training set. In the validation set, KNN showed better sensitivity, accuracy, and AUC than DT and RF but weaker specificity. Calibration and decision curves showed excellent and good results in the training and validation set, respectively. CONCLUSION: Unenhanced CT radiomics-based ML classifiers, especially KNN, may aid in screening CRMs.

Quantitative parameters in novel spectral computed tomography: Assessment of Ki-67 expression in patients with gastric adenocarcinoma.

BACKGROUND: The level of Ki-67 expression has served as a prognostic factor in gastric cancer. The quantitative parameters based on the novel dual-layer spectral detector computed tomography (DLSDCT) in discriminating the Ki-67 expression status are unclear. AIM: To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma (GC). METHODS: Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma. Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt (kev), the slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (nIC), effective atomic number (Zeff) and normalized Zeff (nZeff) in the arterial phase (AP) and venous phase (VP) were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma. Spearman's correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups. RESULTS: Thirty-seven and 71 patients were classified as having low and high Ki-67 expression, respectively. CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, and Zeff-related parameters were significantly higher, but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status, and other analyzed parameters showed no statistical difference between the two groups. Spearman's correlation analysis showed that CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, Zeff, and nZeff exhibited a negative correlation with Ki-67 status, whereas IC and nIC had positive correlation with Ki-67 status. The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status [area under the curve (AUC) = 0.967; sensitivity 95.77%; specificity 91.89%)]. Nevertheless, the differentiating capabilities of single-variable model were moderate (AUC value 0.630 - 0.835). In addition, the nZeff VP and nICVP (AUC 0.835 and 0.805) showed better performance than CT40 kev-VP, CT70 kev-VP and CT100 kev-VP (AUC 0.630, 0.631 and 0.662) in discriminating the Ki-67 status. CONCLUSION: Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma. Zeff and IC may be useful parameters for evaluating the Ki-67 expression.

Enhanced and unenhanced: Radiomics models for discriminating between benign and malignant cystic renal masses on CT images: A multi-center study.

BACKGROUND: Machine learning algorithms used to classify cystic renal masses (CRMs) nave not been applied to unenhanced CT images, and their diagnostic accuracy had not been compared against radiologists. METHOD: This retrospective study aimed to develop radiomics models that discriminate between benign and malignant CRMs in a triple phase computed tomography (CT) protocol and compare the diagnostic accuracy of the radiomics approach with experienced radiologists. Predictive models were established using a training set and validation set of unenhanced and enhanced (arterial phase [AP] and venous phase [VP]) CT images of benign and malignant CRMs. The diagnostic capabilities of the models and experienced radiologists were compared using Receiver Operating Characteristic (ROC) curves. RESULTS: On unenhanced, AP and VP CT images in the validation set, the AUC, specificity, sensitivity and accuracy for discriminating between benign and malignant CRMs were 90.0 (95%CI: 81-98%), 90.0%, 90.5% and 90.2%; 93.0% (95%CI: 86-99%), 86.7%, 95.2% and 88.3%; and 95.0% (95%CI: 90%-100%), 93.3%, 90.5% and 92.1%, respectively, for the radiomics models. Diagnostic accuracy of the radiomics models differed significantly on unenhanced images in the training set vs. each radiologist (p = 0.001 and 0.003) but not in the validation set (p = 0.230 and 0.590); differed significantly on AP images in the validation set vs. each radiologist (p = 0.007 and 0.007) but not in the training set (p = 0.663 and 0.663); and there were no differences on VP images in the training or validation sets vs. each radiologist (training set: p = 0.453 and 0.051, validation set: p = 0.236 and 0.786). CONCLUSIONS: Radiomics models may have clinical utility for discriminating between benign and malignant CRMs on unenhanced and enhanced CT images. The performance of the radiomics model on unenhanced CT images was similar to experienced radiologists, implying it has potential as a screening and diagnostic tool for CRMs.

Early Fractional Amplitude of Low Frequency Fluctuation Can Predict the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation Treatment for Migraine Without Aura.

Migraine is a common primary headache disorder. Transcutaneous auricular vagus nerve stimulation (taVNS) has been verified to be effective in patients with migraine without aura (MWoA). However, there are large interindividual differences in patients' responses to taVNS. This study aimed to explore whether pretreatment fractional amplitude of low frequency fluctuation (fALFF) features could predict clinical outcomes in MWoA patients after 4-week taVNS. Sixty MWoA patients and sixty well-matched healthy controls (HCs) were recruited, and migraineurs received 4-week taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the significant differences of fALFF were detected between MWoA patients and HCs using two-sample t-test. A mask of these significant regions was generated and used for subsequent analysis. The abnormal fALFF in the mask was used to predict taVNS efficacy for MWoA using a support vector regression (SVR) model combining with feature select of weight based on the LIBSVM toolbox. We found that (1) compared with HCs, MWoA patients exhibited increased fALFF in the left thalamus, left inferior parietal gyrus (IPG), bilateral precentral gyrus (PreCG), right postcentral gyrus (PoCG), and bilateral supplementary motor areas (SMAs), but decreased in the bilateral precuneus and left superior frontal gyrus (SFG)/medial prefrontal cortex (mPFC); (2) after 4-week taVNS treatment, the fALFF values significantly decreased in these brain regions based on the pretreatment comparison. Importantly, the decreased fALFF in the bilateral precuneus was positively associated with the reduction in the attack times (r = 0.357, p = 0.005, Bonferroni correction, 0.05/5), whereas the reduced fALFF in the right PoCG was negatively associated with reduced visual analog scale (VAS) scores (r = -0.267, p = 0.039, uncorrected); (3) the SVR model exhibited a good performance for prediction (r = 0.411, p < 0.001),which suggests that these extracted fALFF features could be used as reliable biomarkers to predict the treatment response of taVNS for MWoA patients. This study demonstrated that the baseline fALFF features have good potential for predicting individualized treatment response of taVNS in MWoA patients, and those weight brain areas are mainly involved in the thalamocortical (TC) circuits, default mode network (DMN), and descending pain modulation system (DPMS). This will contribute to well understanding the mechanism of taVNS in treating MWoA patients and may help to screen ideal patients who respond well to taVNS treatment.

Utility of dual-layer spectral-detector CT imaging for predicting pathological tumor stages and histologic grades of colorectal adenocarcinoma.

Objectives: To assess the utility of Dual-layer spectral-detector CT (DLCT) in predicting the pT stage and histologic grade for colorectal adenocarcinoma (CRAC). Methods: A total of 131 patients (mean 62.7 ± 12.9 years; 72 female, 59 male) with pathologically confirmed CRAC (35 pT1-2, 61 pT3, and 35 pT4; 32 high grade and 99 low grade), who received dual-phase DLCT were enrolled in this retrospective study. Normalized iodine concentration (NIC), slope of the spectral HU curve (λHU), and effective atomic number (Eff-Z) were measured for each lesion by two radiologists independently. Intraobserver reliability and interobserver agreement were assessed. The above values were compared between three pT-stage and two histologic-grade groups. The correlation between the pT stages and above values were assessed. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic efficacy. Results: Intra-class correlation coefficients were ranged from 0.856 to 0.983 for all measurements. Eff-Z [7.21(0.09) vs 7.31 (0.10) vs 7.35 (0.19)], NICAP [0.11 (0.05) vs 0.15 (0.08) vs 0.15 (0.08)], NICVP [0.27 (0.06) vs 0.34 (0.11) vs 0.35 (0.12)], λHUAP [1.20 (0.45) vs 1.93 (1.18) vs 2.37 (0.91)], and λHUVP [2.07 (0.68) vs 2.35 (0.62) vs 3.09 (1.07)] were significantly different among pT stage groups (all P<0.001) and exhibited a positive correlation with pT stages (r= 0.503, 0.455, 0.394, 0.512, 0.376, respectively, all P<0.001). Eff-Z [7.37 (0.10) vs 7.28 (0.08)], NICAP[0.20 (0.10) vs 0.13 (0.08)], NICVP[0.35 (0.07) vs 0.31 (0.11)], and λHUAP [2.59 (1.11) vs 1.63 (0.75)] in the high-grade group were markedly higher than those in the low-grade group (all P<0.05). For discriminating the advanced- from early-stage CARC, the AUCs of Eff-Z, NICAP, NICVP, λHUAP, and λHUVP were 0.83, 0.80, 0.79, 0.86, and 0.68, respectively (all P<0.001). For discriminating the high- from low-grade CARC, the AUCs of Eff-Z, NICAP, NICVP, and λHUAP were 0.81, 0.81, 0.64, and 0.81, respectively (all P<0.05). Conclusions: The quantitative parameters derived from DLCT may provide new markers for assessing pT stages and histologic differentiation in patients with CRAC.

Case Report: Two Cases of Soft-Tissue Sarcomas: High TMB as a Potential Predictive Biomarker for Anlotinib Combined With Toripalimab Therapy.

Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study.

Predicting response to tVNS in patients with migraine using functional MRI: A voxels-based machine learning analysis.

Background: Migraine is a common disorder, affecting many patients. However, for one thing, lacking objective biomarkers, misdiagnosis, and missed diagnosis happen occasionally. For another, though transcutaneous vagus nerve stimulation (tVNS) could alleviate migraine symptoms, the individual difference of tVNS efficacy in migraineurs hamper the clinical application of tVNS. Therefore, it is necessary to identify biomarkers to discriminate migraineurs as well as select patients suitable for tVNS treatment. Methods: A total of 70 patients diagnosed with migraine without aura (MWoA) and 70 matched healthy controls were recruited to complete fMRI scanning. In study 1, the fractional amplitude of low-frequency fluctuation (fALFF) of each voxel was calculated, and the differences between healthy controls and MWoA were compared. Meaningful voxels were extracted as features for discriminating model construction by a support vector machine. The performance of the discriminating model was assessed by accuracy, sensitivity, and specificity. In addition, a mask of these significant brain regions was generated for further analysis. Then, in study 2, 33 of the 70 patients with MWoA in study 1 receiving real tVNS were included to construct the predicting model in the generated mask. Discriminative features of the discriminating model in study 1 were used to predict the reduction of attack frequency after a 4-week tVNS treatment by support vector regression. A correlation coefficient between predicted value and actual value of the reduction of migraine attack frequency was conducted in 33 patients to assess the performance of predicting model after tVNS treatment. We vislized the distribution of the predictive voxels as well as investigated the association between fALFF change (post-per treatment) of predict weight brain regions and clinical outcomes (frequency of migraine attack) in the real group. Results: A biomarker containing 3,650 features was identified with an accuracy of 79.3%, sensitivity of 78.6%, and specificity of 80.0% (p < 0.002). The discriminative features were found in the trigeminal cervical complex/rostral ventromedial medulla (TCC/RVM), thalamus, medial prefrontal cortex (mPFC), and temporal gyrus. Then, 70 of 3,650 discriminative features were identified to predict the reduction of attack frequency after tVNS treatment with a correlation coefficient of 0.36 (p = 0.03). The 70 predictive features were involved in TCC/RVM, mPFC, temporal gyrus, middle cingulate cortex (MCC), and insula. The reduction of migraine attack frequency had a positive correlation with right TCC/RVM (r = 0.433, p = 0.021), left MCC (r = 0.451, p = 0.016), and bilateral mPFC (r = 0.416, p = 0.028), and negative with left insula (r = -0.473, p = 0.011) and right superior temporal gyrus/middle temporal gyrus (r = -0.684, p < 0.001), respectively. Conclusions: By machine learning, the study proposed two potential biomarkers that could discriminate patients with MWoA and predict the efficacy of tVNS in reducing migraine attack frequency. The pivotal features were mainly located in the TCC/RVM, thalamus, mPFC, and temporal gyrus.

Case report: A case of duodenal adenocarcinoma achieving significantly long survival treating with immune checkpoint inhibitors and chemotherapy without positive biomarkers.

Small bowel adenocarcinoma (SBA), particularly duodenal adenocarcinoma (DA), is a rare gastrointestinal cancer with a dismal prognosis. Data on SBA treatments are limited, and the therapeutic strategy remains uncertain. Currently, chemotherapy is the most used treatment; however, it has a poor median progression-free survival (mPFS) of no more than five months in the second-line setting. We report a case with DA that responded well to the immune checkpoint inhibitor (ICI) tislelizumab plus irinotecan in the second-line treatment. To our knowledge, this is the first report of administering ICIs plus chemotherapy to SBA. Despite the absence of microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB), the patient with TP53/KRAS mutation achieved a significantly long PFS of 17 months, and the benefit is still ongoing. The mechanism of this remarkable efficacy might be associated with an increase in tumor immunogenicity after chemotherapy. The current study presents a promising effect of ICIs plus chemotherapy on SBA, affirming the need to investigate the clinical value of this combination in SBA and the underlying mechanism behind it.

Combination of Anti-EGFR and Anti-VEGF Drugs for the Treatment of Previously Treated Metastatic Colorectal Cancer: A Case Report and Literature Review.

The standard third-line treatment of metastatic colorectal cancer (mCRC) includes the small-molecule anti-vascular drugs (Regofenib and Fruquintinib) and the chemotherapy drug trifluridine and tipiracil hydrochloride (TAS-102). There is no standard treatment for mCRC if the third-line treatment failed. Therefore, it is a pressing need to develop new therapeutic approaches to improve the survival of patients who developed drug resistance to the third-line treatment. In this study, we report a case of mCRC with RAS/BRAF wild-type, who was successfully treated using cetuximab in combination with fruquintinib after resistance to chemotherapy, bevacizumab, cetuximab and regorafenib. This patient responded to this combination regimen. Then, we discuss the mechanisms of action of this combination. Furthermore, we introduce the clinical trials on the combination regimens of anti-EGFR with anti-vascular monoclonal antibodies. Finally, we discuss the clinical explorations of using combination of anti-EGFR with small-molecule anti-VEGF drugs and their potential benefits. The clinical effects of small-molecule anti-vascular drugs in combination with anti-EGFR in the treatment of CRC warrant further explored.

Predicting Treatment Response of Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using Amide Proton Transfer MRI Combined With Diffusion-Weighted Imaging.

OBJECTIVE: To evaluate amide proton weighted (APTw) MRI combined with diffusion-weighted imaging (DWI) in predicting neoadjuvant chemoradiotherapy (NCRT) response in patients with locally advanced rectal cancer (LARC). METHODS: 53 patients with LARC were enrolled in this retrospective study. MR examination including APTw MRI and DWI was performed before and after NCRT. APTw SI, ADC value, tumor size, CEA level before and after NCRT were assessed. The difference of the above parameters between before and after NCRT was calculated. The tumor regression grading (TRG) was assessed by American Joint Committee on Cancer's Cancer Staging Manual AJCC 8th score. The Shapiro-Wilk test, paired t-test and Wilcoxon Signed Ranks test, two-sample t-test, Mann-Whitney U test and multivariate analysis were used for statistical analysis. RESULTS: Of the 53 patients, 19 had good responses (TRG 0-1), 34 had poor responses (TRG 2-3). After NCRT, all the rectal tumors demonstrated decreased APT values, increased ADC values, reduced tumor volumes and CEA levels (all p < 0.001). Good responders demonstrated higher pre-APT values, higher Δ APT values, lower pre- ADC values and higher Δ tumor volumes than poor responders. Pre-APT combined with pre-ADC achieved the best diagnostic performance, with AUC of 0.895 (sensitivity of 85.29%, specificity of 89.47%, p < 0.001) in predicting good response to NCRT. CONCLUSION: The combination of APTw and DWI may serve as a noninvasive biomarker for evaluating and identifying response to NCRT in LARC patients.

Gastric Cancer Harboring an ERBB3 Mutation Treated with a Pyrotinib-Irinotecan Combo: A Case Study.

Gastric cancer is common, especially in East Asian countries, and is associated with high recurrence and mortality rates. Currently, there is no standard third-line treatment for metastatic gastric cancer. In this report, we present the case of a 69-year-old man with advanced gastric cancer, whose tumor was negative for human epidermal growth factor receptor 2 (HER2) according to immunohistochemical analysis. Next-generation sequencing performed on paraffin sections of the postoperative tumor samples indicated the presence of the ERBB3 V104L mutation. The patient received irinotecan plus pyrotinib as a third-line therapy and achieved a progression-free survival of 7.6 months with a high quality of life. Therefore, the combined administration of irinotecan and pyrotinib may improve the clinical condition of patients with gastric cancer harboring an ERBB3 mutation. Moreover, ERBB3 could be a potential therapeutic target for gastric cancer.

Clinicopathological characteristics and prognosis of gastrointestinal stromal tumors containing air-fluid levels.

An air-fluid level within a gastrointestinal stromal tumor (GIST) is unusual and indicates the presence of a fistula within the lumen of the GI tract. Until recently, the optimal management of such patients was not clear-cut. This retrospective study investigated the clinicopathological characteristics, surgical procedures, pre-and post-operative management, and prognosis of patients with GIST containing an air-fluid level. Data of GIST patients, spanning 5 years, including 17 GIST patients with air-fluid levels in the experimental group and 34 GIST patients without air-fluid levels in the control group, were retrieved from two hospitals in China. The clinicopathological characteristics, types of surgery, management, and clinical outcomes of GIST patients were compared between the two groups. GISTs containing air-fluid levels were significantly different from GISTs without air-fluid levels regarding tumor morphology, NIH risk category, invasion of adjacent organs, and necrosis or ulceration. Most GIST patients with air-fluid levels (14/17, 82.4%) received open surgery, significantly higher than the 20.6% in the control group. Targeted therapy with Imatinib mesylate (IM) was implemented in all GIST patients in the experimental group (17/17, 100%); markedly higher than those (3/34, 8.8%) in the control group. During follow-up, recurrence and death rates (5.9% and 5.9%) in the experimental group were higher than those (2.9% and 0%) in the control group. Open surgery is commonly performed in GIST patients with air-fluid levels who also require targeted therapy with IM. The Torricelli-Bernoulli sign could be a risk factor, adversely affecting the patient's prognosis.

Zinner syndrome: an updated pooled analysis based on 214 cases from 1999 to 2020: systematic review.

Zinner syndrome (ZS) is a rare anomaly of the Wolffian duct. We searched for case reports and case series to identify the most effective methods for examination and treatment. The PubMed/Medline, Embase, and Scopus databases were searched. Our searches yielded 160 case reports/case series and included 214 patients. The mean age at diagnosis was 29.35 years. The R:L distribution was 1:1. The most common symptoms were: frequency (24.3%), dysuria (23.1%) and perineal pain (20.2%) in ZS patients with clinical symptoms. The diagnostic investigations used most frequently were magnetic resonance imaging (MRI) (67.8%) and ultrasonography (65.0%). Maximum flow rate on uroflowmetry, semen ejaculate volume, sperm count, and sperm motility were significantly lower in patients with ZS. Among 193 patients with treatment details, 65.8% underwent surgery; 9.8% underwent aspiration; 24.3% were followed with observation. Two patients died after surgery; all other patients remained asymptomatic after surgery. Fifty-two patients had complications and comorbidities. In patients with ZS, the most common symptoms are seminal vesicle cyst enlargement and compression of the bladder, ureter, and reproductive system. The diagnosis mostly depends on radiological examination. Surgery may be effective, but complications may occur.

Analgesic effects of balanced acupuncture versus body acupuncture in low-back and leg pain patients with lumbar disc herniation, as assessed by resting-state functional magnetic resonance imaging.

Balanced acupuncture, a single-acupoint balance therapy, regulates the balance of the cerebral center, and is characterized by exerting quick effects and a short treatment course. A total of 20 low-back and leg pain patients with lumbar disc herniation were treated with balanced acupuncture or body acupuncture. Central mechanisms of varied acupunctures were compared using resting-state functional MRI. Patients from both groups received functional MRI before and after acupuncture. Functional connectivity in brain regions that were strongly associated with the bilateral amygdala was analyzed utilizing AFNI software. Visual analogue scale scores were greater in the balanced acupuncture group compared with the body acupuncture group. Function of the endogenous pain regulation network was enhanced in patients in the balanced acupuncture group, but was not changed in the body acupuncture group. This result indicates that the analgesic effects of body acupuncture do not work through the central nervous system. These data suggest that balanced acupuncture exerts analgesic effects on low-back and leg pain patients with lumbar disc herniation by regulating the function of the endogenous pain regulation network.