A narrative review of deep learning in thyroid imaging: current progress and future prospects.

Background and Objective: Deep learning (DL) has contributed substantially to the evolution of image analysis by unlocking increased data and computational power. These DL algorithms have further facilitated the growing trend of implementing precision medicine, particularly in areas of diagnosis and therapy. Thyroid imaging, as a routine means to screening for thyroid diseases on large-scale populations, is a massive data source for the development of DL models. Thyroid disease is a global health problem and involves structural and functional changes. The objective of this study was to evaluate the general rules and future directions of DL networks in thyroid medical image analysis through a review of original articles published between 2018 and 2023. Methods: We searched for English-language articles published between April 2018 and September 2023 in the databases of PubMed, Web of Science, and Google Scholar. The keywords used in the search included artificial intelligence or DL, thyroid diseases, and thyroid nodule or thyroid carcinoma. Key Content and Findings: The computer vision tasks of DL in thyroid imaging included classification, segmentation, and detection. The current applications of DL in clinical workflow were found to mainly include management of thyroid nodules/carcinoma, risk evaluation of thyroid cancer metastasis, and discrimination of functional thyroid diseases. Conclusions: DL is expected to enhance the quality of thyroid images and provide greater precision in the assessment of thyroid images. Specifically, DL can increase the diagnostic accuracy of thyroid diseases and better inform clinical decision-making.

Deep learning-assisted ultrasonic diagnosis of cervical lymph node metastasis of thyroid cancer: a retrospective study of 3059 patients.

Objective: This study aimed to develop a deep learning system to identify and differentiate the metastatic cervical lymph nodes (CLNs) of thyroid cancer. Methods: From January 2014 to December 2020, 3059 consecutive patients with suspected with metastatic CLNs of thyroid cancer were retrospectively enrolled in this study. All CLNs were confirmed by fine needle aspiration. The patients were randomly divided into the training (1228 benign and 1284 metastatic CLNs) and test (307 benign and 240 metastatic CLNs) groups. Grayscale ultrasonic images were used to develop and test the performance of the Y-Net deep learning model. We used the Y-Net network model to segment and differentiate the lymph nodes. The Dice coefficient was used to evaluate the segmentation efficiency. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the classification efficiency. Results: In the test set, the median Dice coefficient was 0.832. The sensitivity, specificity, accuracy, PPV, and NPV were 57.25%, 87.08%, 72.03%, 81.87%, and 66.67%, respectively. We also used the Y-Net classified branch to evaluate the classification efficiency of the LNs ultrasonic images. The classification branch model had sensitivity, specificity, accuracy, PPV, and NPV of 84.78%, 80.23%, 82.45%, 79.35%, and 85.61%, respectively. For the original ultrasonic reports, the sensitivity, specificity, accuracy, PPV, and NPV were 95.14%, 34.3%, 64.66%, 59.02%, 87.71%, respectively. The Y-Net model yielded better accuracy than the original ultrasonic reports. Conclusion: The Y-Net model can be useful in assisting sonographers to improve the accuracy of the classification of ultrasound images of metastatic CLNs.

A Local and Global Feature Disentangled Network: Toward Classification of Benign-Malignant Thyroid Nodules From Ultrasound Image.

Thyroid nodules are one of the most common nodular lesions. The incidence of thyroid cancer has increased rapidly in the past three decades and is one of the cancers with the highest incidence. As a non-invasive imaging modality, ultrasonography can identify benign and malignant thyroid nodules, and it can be used for large-scale screening. In this study, inspired by the domain knowledge of sonographers when diagnosing ultrasound images, a local and global feature disentangled network (LoGo-Net) is proposed to classify benign and malignant thyroid nodules. This model imitates the dual-pathway structure of human vision and establishes a new feature extraction method to improve the recognition performance of nodules. We use the tissue-anatomy disentangled (TAD) block to connect the dual pathways, which decouples the cues of local and global features based on the self-attention mechanism. To verify the effectiveness of the model, we constructed a large-scale dataset and conducted extensive experiments. The results show that our method achieves an accuracy of 89.33%, which has the potential to be used in the clinical practice of doctors, including early cancer screening procedures in remote or resource-poor areas.

Multimodal ultrasound imaging of primary thyroid schwannoma: A case report.

RATIONALE: Primary schwannoma of the thyroid gland is very rare, and its preoperative diagnosis is difficult. PATIENT CONCERNS: We report the case of a thyroid nodule in an 18-year-old woman, who presented with a mass in her left neck with stiffness and normal thyroid function. However, the patient complained of numbness in her left upper extremity, and ultrasound (US) features were suspicious of malignancy. DIAGNOSES: Multimodal US imaging was performed using B-mode, color doppler, ultrasonic elastography (UE), and contrast-enhanced ultrasound (CEUS). CEUS revealed heterogeneous enhancement and "target sign" within the tumor. The nodule was suspicious for malignancy and classified as TI-RADS 4b, while the elasticity values measured by UE indicated a benign lesion. Fine needle aspiration (FNA) was subsequently performed in the markedly contrast-enhanced area for biopsy. Cytological results revealed a benign schwannoma. INTERVENTION: The patient underwent left lobe resection. Postoperative pathology confirmed it to be a primary benign schwannoma of the thyroid. OUTCOMES: After thyroidectomy, the patient was followed-up with US. At present, all laboratory tests and thyroid imaging are normal, and the numbness of the left upper limb has disappeared. LESSONS: The combination of different US modalities is useful for the diagnosis of thyroid lesions. FNA performed under CEUS guidance improves the accuracy of biopsy sampling.

Partially cystic thyroid cancer on conventional and elastographic ultrasound: a retrospective study and a machine learning-assisted system.

BACKGROUND: Thyroid carcinoma constitutes the vast majority of all thyroid cancer, most of which is the solid nodule type. No previous studies have examined combining both conventional and elastic sonography to evaluate the diagnostic performance of partially cystic thyroid cancer (PCTC). This retrospective study was designed to evaluate differentiation of PCTC from benign partially cystic nodules with a machine learning-assisted system based on ultrasound (US) and elastography. METHODS: Patients with suspicious partially cystic nodules and finally confirmed were included in the study. We performed conventional US and real-time elastography (RTE). The US features of nodules were recorded. The data set was entered into 6 machine-learning algorithms. Sensitivity, specificity, accuracy, and area under the curve (AUC) were calculated. RESULTS: A total of 177 nodules were included in this study. Among these nodules, 81 were malignant and 96 were benign. Wreath-shaped feature, micro-calcification, and strain ratio (SR) value were the most important imaging features in differential diagnosis. The random forest classifier was the best diagnostic model. CONCLUSIONS: US features of PCTC exhibited unique characteristics. Wreath-shaped partially cystic nodules, especially with the appearance of micro-calcifications and larger SR value, are more likely to be malignant. The random forest classifier might be useful to diagnose PCTC.

Ultrasound Diagnosis of Breast Lymphoma and the Identification of Breast Infiltrating Ductal Carcinoma.

OBJECTIVES: By analyzing the B-mode ultrasound and color Doppler flow imaging characteristics of breast lymphoma (BL) and breast infiltrating ductal carcinoma (BIDC), we expected to discriminate these diseases. METHODS: Thirty-two patients with BL and 30 with BIDC confirmed pathologically were selected. The BL group was divided into nodular and diffuse groups. We analyzed and compared the general and imaging characteristics of the BL subgroups and the BIDC group. RESULTS: The mean maximum diameter of BL was 54.93 ± 43.74 cm, and that of BIDC was 23.90 ± 6.79 cm (P < .05). The differences between the nodular BL and BIDC groups in a circumscribed margin (60.00% versus 20.00%), calcification (20.00% versus 53.33%), aggregation characteristics (0.00% versus 53.33%), and density (73.33% versus 10.00%) were statistically significant (P < .05). The differences between the diffuse BL and BIDC groups in calcification (6.67% versus 53.33%), aggregation characteristics (6.67% versus 53.33%) and density (40.00% versus 10.00%) were statistically significant (P < .05). The difference in a circumscribed margin (60% versus 13.33%) between the BL subgroups was statistically significant (P < .05). The blood flow signal in BL lesions was richer than that in BIDC lesions (P < .05). CONCLUSIONS: Extrasuperior-quadrant single lesions in the BL group were larger than those in the BIDC group. The edges of the lesions in the nodular BL group were circumscribed and dense. Lesions in the diffuse BL group did not have a circumscribed margin, calcification, aggregation characteristics, or density. The blood flow signal in BL lesions was richer than that in BIDC lesions.

Effectiveness evaluation of computer-aided diagnosis system for the diagnosis of thyroid nodules on ultrasound: A systematic review and meta-analysis.

BACKGROUND: More and more automated efficient ultrasound image analysis techniques, such as ultrasound-based computer-aided diagnosis system (CAD), were developed to obtain accurate, reproducible, and more objective diagnosis results for thyroid nodules. So far, whether the diagnostic performance of existing CAD systems can reach the diagnostic level of experienced radiologists is still controversial. The aim of the meta-analysis was to evaluate the accuracy of CAD for thyroid nodules' diagnosis by reviewing current literatures and summarizing the research status. METHODS: A detailed literature search on PubMed, Embase, and Cochrane Libraries for articles published until December 2018 was carried out. The diagnostic performances of CAD systems vs radiologist were evaluated by meta-analysis. We determined the sensitivity and the specificity across studies, calculated positive and negative likelihood ratios and constructed summary receiver-operating characteristic (SROC) curves. Meta-analysis of studies was performed using a mixed-effect, hierarchical logistic regression model. RESULTS: Five studies with 536 patients and 723 thyroid nodules were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) for CAD system were 0.87 (95% confidence interval [CI], 0.73-0.94), 0.79 (95% CI 0.63-0.89), 4.1 (95% CI 2.5-6.9), 0.17 (95% CI 0.09-0.32), and 25 (95% CI 15-42), respectively. The SROC curve indicated that the area under the curve was 0.90 (95% CI 0.87-0.92). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and DOR for experienced radiologists were 0.82 (95% CI 0.69-0.91), 0.83 (95% CI 0.76-0.89), 4.9 (95% CI 3.4-7.0), 0.22 (95% CI 0.12-0.38), and 23 (95% CI 11-46), respectively. The SROC curve indicated that the area under the curve was 0.96 (95% CI 0.94-0.97). CONCLUSION: The sensitivity of the CAD system in the diagnosis of thyroid nodules was similar to that of experienced radiologists. However, the CAD system had lower specificity and DOR than experienced radiologists. The CAD system may play the potential role as a decision-making assistant alongside radiologists in the thyroid nodules' diagnosis. Future technical improvements would be helpful to increase the accuracy as well as diagnostic efficiency.

Toxicity Evaluation and Anti-Tumor Study of Docetaxel Loaded mPEG-Polyester Micelles for Breast Cancer Therapy.

In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.

Contrast-enhanced ultrasound diagnosis of hepatic metastasis of concurrent medullary-papillary thyroid carcinoma: A case report.

RATIONALE: Co-occurrence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) in the same thyroid gland with liver metastasis is a rare condition. To our knowledge, the utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. PATIENT CONCERNS: A 33-year-old female was referred to our hospital due to the increase in plasma calcitonin concentration and carcino-embryonic antigen 12 months after her total thyroidectomy. To find metastasis, she received laboratory tests, gray-scale US, and CEUS. In our paper, ethical approval was not necessary, as this article is a case report, which is based on the clinical information of the patient. Because our case does not refer to the patient's privacy, informed consent is not necessary. DIAGNOSES: Gray-scale abdominal ultrasound image demonstrated a mildly hyperechoic nodule in the liver. In CEUS, the nodules were hyperenhanced in the arterial phase. In the late arterial phase, the enhancement was washed out quickly. The nodules presented hypoenhancement in the portal and parenchymal phase, which conformed to the hepatic metastasis. INTERVENTIONS: The patient received thyroid and liver surgery. OUTCOMES: She was free of disease for 10 months at the time of this report. LESSONS: In this case, liver metastases from MTC can be detected and characterized reliably as hypoenhancing lesions during the portal venous and late phases of CEUS, washing out starts early, and is marked. We suspect MTC is a kind of tumor that tends to have rich blood supply and consider contrast-enhanced ultrasound as a suitable method for the follow-up of patients with MTC.

Primary follicular thyroid carcinoma metastasis to the kidney and widespread dissemination: A case report.

Distant metastases are more common in follicular thyroid carcinoma (FC) than in papillary thyroid carcinoma. However, FC metastasis to the kidney with eggshell calcification, as observed in the present case, is rare. The current report presents a case of a 67-year-old woman exhibiting a solitary tumor in the mid pole of the left kidney. Radical nephrectomy was performed, as the tumor was diagnosed as a primary renal carcinoma using contrast-enhanced computed tomography. Once the tumor was confirmed to be FC, total thyroidectomy was performed. Following administration of an oral therapeutic dose of 100 mCi 131I, functional imaging demonstrated the presence of multifocal metastases in the chest and abdomen. Euthyrox® was prescribed orally to aid normal thyroid function. Follow-up 6 months later using radionuclide imaging demonstrated the disappearance of the multifocal metastases in the chest and abdomen. The distant metastasis of FC may represent the initial symptom of the primary lesion, which was neglected. Ultrasound is an effective method to examine nodules located on the thyroid.

Targeting adeno-associated virus and adenoviral gene therapy for hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) heavily endangers human heath worldwide. HCC is one of most frequent cancers in China because patients with liver disease, such as chronic hepatitis, have the highest cancer susceptibility. Traditional therapeutic approaches have limited efficacy in advanced liver cancer, and novel strategies are urgently needed to improve the limited treatment options for HCC. This review summarizes the basic knowledge, current advances, and future challenges and prospects of adeno-associated virus (AAV) and adenoviruses as vectors for gene therapy of HCC. This paper also reviews the clinical trials of gene therapy using adenovirus vectors, immunotherapy, toxicity and immunological barriers for AAV and adenoviruses, and proposes several alternative strategies to overcome the therapeutic barriers to using AAV and adenoviruses as vectors.

Application of shear wave elastography in fine needle aspiration biopsy for thyroid nodule.

Ultrasound guided fine needle aspiration biopsy (FNAB) is the first-line procedure in diagnosing thyroid nodules. However, emerging studies have reported its unsatisfactory cell sample for cytology evaluation. In this case report, shear wave elastography (SWE) guided FNAB on a thyroid nodule is presented. Biopsies were performed on both hard and soft areas of the same nodule on the SWE image. Cytological results demonstrated the sufficient diagnostic components and typical nuclear features of papillary carcinoma found on the specimen from the hard area. This case study indicates SWE is a useful complementary tool to conventional B-mode ultrasound in guiding thyroid nodule FNAB.

[Contrast-enhanced ultrasonography findings for papillary thyroid carcinoma and its pathological bases ].

OBJECTIVE: To investigate the findings of contrast enhanced ultrasound for papillary thyroid carcinoma and its pathological bases. METHODS: Seventy two (72) patients with thyroid nodules underwent routine conventional ultrasound and color Doppler examination, and 86 nodules with TI RADS 3 were examined by contrast-enhanced ultrasound (CEUS . Histopathological examination was kept as standard reference and the findings of CEUS were analyzed. Pathological studies of all nodules were made after post-operative CD34 immunohistochemistry staining examination. RESULTS: Of the total 86 nodules, Adler CDFl classification grades were: grade 0-26. grade I-34. grade II-23 and grade III-3 nodules respectively. Enhancement pattern on CEUS showed that there was low enhancement on 71 nodules, iso enhancement on 12 and high enhancement on 3 nodules. The differences of echo mean intensity. the peak intensity, area under the curve for enhancement intensity and CD34 count between the nodules and surrounding tissue were statistical significant (P < 0. 001). CONCLUSION: Low enhancement pattern on CEUS is the most common finding for papillary thyroid carcinoma, which is related to the difference of microvessel density between the nodules and surrounding tissues in papillary thyroid carcinoma.

[The perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonograph. under different reference conditions ].

OBJECTIVE: To determine the perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonography (CEUS) under different reference conditions. METHODS: The CEUS perfusion patterns of 78 superficial lymph node lesions were compared with their pathology results. Time-intensity curves were used for comparison between benign and malignant lymph nodes. RESULTS: Inhomogeneous hyperenhancement was the main perfusion pattern (7/17, 41. 2%) in metastatic lymph nodes; compared with homogeneous hyperenhancement (2/4, 50. 0%) in lymphoma, homogeneous hyperenhancement and isoenhancement (6/52, 11. 5%) in reactive lymph nodes, and circle enhancement (2/4,50. 0%) in tuberculosis. Benign lymph nodes showed different mean value, peak intensity and area under the curve compared with their surrounding arteries (P<0. 05). But the differences in mean value, rise time, time to peak, peak intensity and the area under the curve between benign lymphadenopathy and their surrounding tissues were not statistically significant (P>0. 05). Malignant lymph nodes showed different mean value and peak intensity compared with their surrounding arteries and tissues (P<0. 05). The differences in time to peak between malignant lymph nodes and their surrounding tissues were also statistically significant (P< 0. 05). CONCLUSION: Different CEUS perfusion patterns are associated with different types of lymph node lesions. Time intensity curves with surrounding tissues as reference condition offer great values for the differential diagnosis of superficial lymphadenopathy.

Tumor suppressor in lung cancer-1 (TSLC1) mediated by dual-regulated oncolytic adenovirus exerts specific antitumor actions in a mouse model.

AIM: The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. METHODS: The recombinant virus Ad·sp-E1A(Δ24)-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad·sp-E1A(Δ24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad·sp-E1A(Δ24)-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. RESULTS: Infection of A549 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad·sp-E1A(Δ24)-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad·sp-E1A(Δ24)-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad·sp-E1A(Δ24)-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. CONCLUSION: The oncolytic adenovirus Ad·sp-E1A(Δ24)-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.

[Lateral neck lymph node metastasis in cN0 papillary thyroid carcinoma].

OBJECTIVE: To study the pattern of lymph node spread in papillary thyroid carcinoma (PTC) with clinically negative node (cN0). METHODS: A total of 106 patients with cN0 PTC who underwent total or subtotal thyroidectomy plus unilateral or bilateral lateral neck dissection (LND, level II-V or level I-V) at West China Hospital of Sichuan University between April 2004 and August 2010 were analyzed retrospectively. RESULTS: The lateral neck lymph node metastasis in cN0 PTC was significantly associated with sex (male, P = 0.007), tumor stage (T3/T4, P = 0.006), tumor size (> 1 cm, P = 0.014) and the number of positive central lymph nodes (≥ 2, P < 0.001), but not with age and multifocal tumor. Level III (47/116, 40.5%) was the most prevalent metastatic site, followed by level IV (41/116, 35.3%), level II (18/116, 15.5%) and level V (2/29, 6.9%). Of the cases with lymph node metastases in level III and IV, 89.8% (79/88) of primary thyroid tumors existed in the lower and middle sites of the thyroid lobes, while in the cases with lymph node metastases in level II, 77.8% (14/18) of primary thyroid tumors in the upper sites of the thyroid lobes, and 83.3% of cases with level II metastases were accompanied with level III metastases. Two cases with level V metastases were accompanied with metastases in levels II, III and IV. CONCLUSIONS: LND should be considered for cN0 PTC in male, with T3/T4 lesions and positive central lymph nodes ≥ 2, and the range of dissection should include level III and IV. Dissection of level II should be considered in cN0 PTC with primary tumor localized in the upper site of the thyroid lobe or with level III metastasis. Dissection of level V should be considered at present of metastases in level II, III, and IV. For cN0 PTC with tumor size < 1 cm, confined to the thyroid and without lymph node metastasis in the central compartment, LND is not recommended.

[Related factors of central lymph node metastasis in papillary thyroid carcinoma].

OBJECTIVE: To study the related factors of central lymph node (CLN) metastasis in papillary thyroid carcinoma (PTC),the indications and the extent of central neck dissection (CND). METHODS: A total of 153 cases treated between Jan. 2009 and Dec. 2010 was analysed retrospectively. Of the cases 28 males and 125 cases females, with a mean age of (44 ± 14) years. T1, T2, and T3 diseases accounted for 51, 10 and 81 cases, respectively; I, II, III and IV diseases for 88, 3, 26 and 36 cases, respectively. Multifocal tumors were found in 63 cases. The related clinicopathologic factors were analyzed, including sex, age, tumor size, extrathyroidal extension, and multifocal tumor. RESULTS: All the cases had total/near total thyroidectomy and CND, of them 64 cases had unilateral neck dissection and 18 cases had bilateral neck dissection. CLN metastases existed in 68.6% (105/153) cases, 37.2% (57/153) for unilateral and 31.4% (48/153) for bilateral respectively. The rates of CLN metastasis were 86.6% (71/82) in cN1 cases and 47.9% (34/71) cN0 cases, respectively,and the rates of bilateral CLN metastases were 45.1% (37/82) in cN1 cases and 15.5% (11/71) in cN0 cases. Multivariate analysis showed that extrathyroidal extension (P = 0.002, OR = 3.502) was an independent risk factor for CLN metastasis and that lateral neck lymph node metastasis (P = 0.028, OR = 3.080), surrounding tissue invasion (P = 0.014, OR = 3.113), and maximum tumor diameter greater than 1 cm (P = 0.012, OR = 3.732) were independent risk factors for bilateral CLN metastases. CONCLUSIONS: It is indicated that ipsilateral CND should be obligatory for PTC. Intraoperative frozen section examination should be routine. Bilateral CND should be conducted when ipsilateral CLN metastases accompanied by one of following issues such as more invasive tumor (surrounding tissue invasion, T3 or T4 disease), maximum tumor diameter greater than 1 cm, and lateral neck lymph node metastasis.

Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice.

BACKGROUND: To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo. METHODS: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis. RESULTS: The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors. CONCLUSION: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.

Role of contrast-enhanced ultrasound in decision support for diagnosis and treatment of hepatic artery thrombosis after liver transplantation.

OBJECTIVE: To assess role of contrast-enhanced ultrasound (CEUS) in decision support for diagnosis and treatment of hepatic artery thrombosis (HAT) after liver transplantation. MATERIALS AND METHODS: Between January 2005 and January 2011, 605 patients underwent liver transplantation in our medical center. All the liver transplant recipients received Doppler ultrasound scanning and CEUS examination was performed in 45 patients with suspected HAT on Doppler ultrasound. Sensitivity, specificity, accuracy, positive predict value and negative predictive value of CEUS in diagnosing HAT were determined based on the results from angiography, surgery and clinical follow-up. RESULTS: Fourteen HATs, including one late HAT, were diagnosed by CEUS. Twelve HAT cases were confirmed by angiographic and/or surgical findings, while the late HAT and other 31 patients with negative CEUS finding were confirmed by the clinical follow-up. There was a false positive HAT diagnosed by CEUS in which angiography revealed a patent hepatic artery. The sensitivity, specificity, accuracy, positive predict value and negative predictive value of CEUS in diagnosing HAT were 100%, 96.9%, 97.8%, 92.9% and 100%, respectively. In our series of 605 liver transplants, the incidence and mortality of HAT was 2.2% (13/605) and 53.8% (7/13), respectively. CONCLUSIONS: Our study demonstrates the important role of CEUS in decision support for diagnosis and treatment of HAT after liver transplantation. When HAT is suspected by Doppler ultrasound, CEUS shall immediately be performed to elucidate its nature. A negative CEUS finding shall avoid invasive angiography. Such as, CEUS may alter the clinical workflow on HAT detection after liver transplantation.