A prospective study on using shear wave elastography to predict the ypT0 stage of rectal cancer after neoadjuvant therapy: a new support for the watch-and-wait approach?

Introduction: The diagnostic accuracy of traditional imaging examination in predicting ypT stage of rectal cancer after neoadjuvant therapy is significantly reduced, which would affect patients' subsequent treatment choices. This study aimed to investigate the use of endorectal shear wave elastography (SWE) for diagnosing ypT0 stage of rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: Sixty patients with rectal cancer were prospectively recruited in this study. Data on endorectal ultrasound (ERUS) and SWE parameters were collected before nCRT and 6-8 weeks after nCRT. Postoperative pathological results were the gold standard for evaluating the diagnostic accuracy of SWE and ERUS in predicting the ypT0 stage of rectal cancer after nCRT. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of the SWE parameters that best corresponded to the ypT0 stage and analyze the sensitivity, specificity, and accuracy. Results: The diagnostic accuracies of using ERUS to predict the ypT and ypT0 stages of rectal cancer after nCRT were 58.1% (18/31) and 64.3% (9/14), respectively. The ROC curve was constructed with the lesion's Emean, Emean corrected (EC), Emean difference (ED), Emean corrected differencede (ECD), Emean descendding rate (EDR) and Emean corrected descendding rate (ECDR) values after nCRT, the cut-off values of diagnosing the ypT0 stage were 64.40 kPa, 55.45 kPa, 72.55 kPa, 73.75 kPa, 50.15%, and 55.93%, respectively; the area under the curve (AUC) for diagnosing the ypT0 stage was 0.924, 0.933, 0.748, 0.729, 0.857 and 0.861, respectively. The EC value showed the best diagnostic performance. Conclusion: SWE could improve the accuracy of conventional ERUS in diagnosing the ypT0 stage of rectal cancer after nCRT. It is expected to become a new method to help predict pathological complete responses in clinical practice and provide new evidence for the watch-and-wait approach.

Corrigendum: brain microvascular endothelial cell-derived HMGB1 facilitates monocyte adhesion and transmigration to promote JEV neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Corrigendum: Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion.

Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.

Contrast-enhanced ultrasound imaging for intestinal lymphoma.

BACKGROUND: Intestinal lymphoma is a rare tumor. Contrast-enhanced ultrasound (CEUS) findings of intestinal lymphoma have not been reported previously, and the relationship between CEUS and clinicopathological features and prognostic factors is still unknown. AIM: To describe the B-mode US and CEUS features of intestinal lymphoma and investigate the correlation of CEUS and histopathological features. METHODS: This was a single-center retrospective study. Eighteen patients with histologically confirmed intestinal lymphoma underwent B-mode US and CEUS examinations between October 2016 and November 2019. We summarized the features of B-mode US and CUES imaging of intestinal lymphoma and compared the frequency of tumor necrosis in intestinal lymphomas with reference to different pathological subtypes (aggressive or indolent) and clinical stage (early or advanced). The time-intensity curve parameters of CEUS were also compared between patients with normal and elevated serum lactate dehydrogenase. RESULTS: In B-mode imaging, four patterns were observed in intestinal lymphoma: Mass type (12/18, 66.7%), infiltration type (1/18, 5.6%), mesentery type (4/18, 22.2%) and mixed type (1/18, 5.6%). All cases were hypoechoic and no cystic areas were detected. On CEUS, most cases (17/18, 94.4%) showed arterial hyperechoic enhancement. All cases showed arterial enhancement followed by venous wash out. A relatively high rate of tumor necrosis (11/18, 61.1%) was observed in this study. Tumor necrosis on CEUS was more frequent in aggressive subtypes (10/13, 76.9%) than in indolent subtypes (1/5, 20.0%) (P = 0.047). There were no correlations between tumor necrosis and lesion size and Ann Arbor stage. There was no significant difference in time-intensity curve parameters between normal and elevated lactate dehydrogenase groups. CONCLUSION: B-mode US and CEUS findings of intestinal lymphoma are characteristic. We observed a high rate of tumor necrosis, which appeared more frequently in aggressive pathological subtypes of intestinal lymphoma.

Comparison of sonographic characteristics of primary thyroid lymphoma and anaplastic thyroid carcinoma.

BACKGROUND: Although primary thyroid lymphoma (PTL) and anaplastic thyroid carcinoma (ATC) both account for a rare portion of the morbidity of all thyroid malignancies, the therapeutic methods and prognosis for these two diseases are different. The purpose of this study was to investigate the sonographic characteristics of PTL and ATC and to compare the sonographic findings of PTL and ATC. METHODS: The study included 42 patients with histopathologically proven PTL (n=27) and ATC (n=15). The Clinical characteristics and sonographic findings were retrospectively reviewed and compared between the two groups. RESULTS: The mean age of patients with ATC was not significantly different from that in patients with PTL (P=0.601). The female-to-male ratio of patients with ATC was significantly lower than that of patients with PTL (P=0.029). Both PTL and ATC commonly present as a relatively large, solid mass on sonography with compressive symptoms, in which hoarseness was seen more frequently in ATC group (66.7%) than in PTL group (14.8%) (P=0.001). There is no significant difference in thyroid size, nodular size, margin, shape, echo texture, echogenicity, cystic change, vascularity and local invasion on sonography between ATC and PTL groups. Echogenic strands, markedly hypoechoic and enhanced posterior echo were seen more frequently in PTL group (92.6%, 92.6%, and 85.2%, respectively) than those in ATC group (6.7%, 60.0%, and 33.3%, respectively) (P<0.05), and calcification was seen more frequently in ATC group (80.0%) than in PTL group (0%) (P<0.001). Three ultrasound patterns were observed for PTL including diffuse type (25.9%), nodular type (48.2%) and mixed type (25.9%), while all ATC cases presented with nodular type (100.0%). Associated Hashimoto's thyroiditis occurred more frequently in PTL group (59.3%) than in ATC group (20.0%) (P=0.023). CONCLUSIONS: Certain sonographic features as a markedly hypoechogenicity, the presence of an enhanced posterior echo and linear echogenic strands, lack of calcification and associated Hashimoto's thyroiditis were valuable for distinguishing PTL from ATC. In contrast, heterogeneous echogenicity, uncircumscribed margin, irregular shape, and vascular pattern were not specific features for differential diagnosis.

Time-intensity curve parameters in rectal cancer measured using endorectal ultrasonography with sterile coupling gels filling the rectum: correlations with tumor angiogenesis and clinicopathological features.

The primary aim of this study was to investigate the relationship between contrast-enhanced ultrasonography (CEUS) imaging parameters and clinicopathological features of rectal carcinoma and assess their potential as new radiological prognostic predictors. A total of 66 rectal carcinoma patients were analyzed with the time-intensity curve of CEUS. The parameter arrival time (AT), time to peak enhancement (TTP), wash-in time (WIT), enhanced intensity (EI), and ascending slope (AS) were measured. Microvessel density (MVD) was evaluated by immunohistochemical staining of surgical specimens. All findings were analysed prospectively and correlated with tumor staging, histological grading, and MVD. The mean values of AT, TTP, WIT, EI, and AS value of the rectal carcinoma were 10.84 ± 3.28 s, 20.61 ± 5.52 s, 9.78 ± 2.83 s, 28.68 ± 4.67 dB, and 3.20 ± 1.10, respectively. A positive linear correlation was found between the EI and MVD in rectal carcinoma (r = 0.295, P = 0.016), and there was a significant difference for EI among histological grading (r = -0.264, P = 0.007). EI decreased as T stage increased with a trend of association noted (P = 0.096). EI of contrast enhanced endorectal ultrasonography provides noninvasive biomarker of tumor angiogenesis in rectal cancer. CEUS data have the potential to predict patient prognosis.

Novel mutations of CYP27B1 gene lead to reduced activity of 1α-hydroxylase in Chinese patients.

Pseudovitamin D-deficiency rickets (PDDR) is an autosomal recessive disorder resulting from a defect in renal 25-hydroxyvitamin D 1α-hydroxylase, the key enzyme in the pathway of vitamin D metabolism. We identified ten different mutations in the 1α-hydroxylase gene (CYP27B1) in eight Chinese families with PDDR by DNA-sequence analysis. Six of them are novel missense mutations: G57V, G73W, L333F, R432C, R459C, and R492W; three are novel deletion mutations: c48-60del, c1310delG, and c1446delA; and an insertion mutation c1325-1332insCCCACCC reported previously. Functional assay revealed that the missense mutants identified in this study retain 5.5-12.1% 1α-hydroxylase activity of the wild type. The study describes nine novel mutations in addition to 37 known mutations of CYP27B1 gene and shows the correlation between these mutations and the clinical findings of 1α-hydroxylase deficiency.