[A survey on the practice of bronchoscopy in county-level hospitals of China].

Objective: To investigate the bronchoscopy resource allocation and technology application in county-level hospitals in China. Methods: A cross-sectional survey was conducted. In 2021, 12 provinces were sampled from all provinces in China according to the regional Gross Domestic Product (GDP) and the number of counties, in which a total of 291 county-level hospitals were randomly enrolled. Two county-level hospitals which carried out bronchoscopy technology in each province were randomly sampled to investigate the status of bronchoscopy resources, technical application, decontamination and anesthesia by using questionnaires. Independent sample t test or two related sample nonparametric test were used for comparison between groups. Spearman correlation analysis was used to explore the correlation. Bilateral P<0.05 was considered statistically significant. Results: According to the sampling results, it was estimated that in the county-level hospitals, the proportion of those performing bronchoscopy was 11.4% (9.9%, 13.8%), which was significantly correlated with the population in the province (r=0.64, P=0.025) and the regional GDP (r=0.65, P=0.025).The 24 county-level hospitals interviewed were equipped with (1.6±1.0) bronchoscopes on average, and the number of hospitals with electronic bronchoscopes and fiberoptic bronchoscopes was 22 (91.7%) and 6 (25.0%), respectively. Six (25.0%) hospitals performed bronchoscopy every working day. Twelve (50.0%) hospitals had relatively permanent physicians and nurses. All operating doctors had received special training. There was a significant increase in the number of bronchoscopy cases per hospital in 2020 compared to 2019 [140(70, 335) vs. 100(29, 254), P=0.001]. All hospitals used standard cleaning and sterilization workbenches, cleaning agents and disinfectants. Surface anesthesia was available in 24 hospitals, and bronchoscopy techniques under sedation and analgesia were performed in 10 (41.7%) hospitals. Atropine was still used to prevent airway secretions in 2 (8.3%) hospitals,although not recommended by guidelines. Conclusions: There was a large gap between the current status of bronchoscopy technology in county-level hospitals and the standards of the National Health Commission, together with regional disparities. Bronchoscopist training in the standardization and the decontamination work met the requirements. In some hospitals, the use of complementary medicines was not standardized or the sedatives were not given routinely according to the guidelines. We should promote the popularization and standardization of bronchoscopy technology, and strengthen the allocation of related resources in China's county hospitals.

The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Circulating cytokines and monocyte subpopulations as biomarkers of outcome and biological activity in sunitinib-treated patients with advanced neuroendocrine tumours.

BACKGROUND: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. METHODS: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. RESULTS: Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. CONCLUSIONS: Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.

Prediction of microvascular invasion of hepatocellular carcinoma by pre-operative CT imaging.

OBJECTIVE: The aim of this study was to diagnose microvascular invasion in patients with solitary hepatocellular carcinoma (HCC) from pre-operative CT imaging. METHODS: 102 patients with solitary HCC who underwent curative hepatectomy were retrospectively included in our study. The pre-operative 3-phase CT imaging and laboratory data for the 102 patients were reviewed. Tumour size, tumour margin, peritumoral enhancement and α-fetoprotein level were assessed. Surgical pathology was reviewed; tumour differentiation, liver fibrosis score and microvascular invasion were recorded. RESULTS: The histopathological results revealed that 50 HCCs were positive and the other 52 were negative for microvascular invasion. Univariate analysis revealed that tumour size (p = 0.036), higher Edmondson-Steiner grade (p = 0.047) and non-smooth tumour margin (p < 0.001) showed statistically significant associations with microvascular invasion. Multivariate logistic regression analysis showed that non-smooth tumour margin had a statistically significant association with microvascular invasion only (p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the non-smooth tumour margin in the prediction of microvascular invasion were 66%, 86.5%, 82.5% and 72.6%, respectively. CONCLUSION: Non-smooth tumour margin in pre-operative CT had a statistically significant association with microvascular invasion. More aggressive treatment should be considered in HCC patients with suspected positive microvascular invasion.

Increased mobilisation of circulating endothelial progenitors in von Hippel-Lindau disease and renal cell carcinoma.

BACKGROUND: Circulating endothelial cells (CECs) are a candidate biomarker for monitoring angiogenesis in cancer. Circulating endothelial cell subsets are mobilised by angiogenic mediators. Because of the highly angiogenic phenotype of renal cell carcinoma (RCC), we sought to assess the potential of CECs as a marker of RCC in patients with von Hippel-Lindau (VHL) disease and those with sporadic RCC. METHODS: We performed multicolour flow cytometry to enumerate CECs in patients with RCC, patients with VHL disease with and without RCC, and normal subjects. Two subsets of CECs were evaluated: mature CECs (mCECs) and circulating endothelial progenitors (CEPs). RESULTS: In patients with VHL disease and RCC and those with sporadic RCC (N=10), CEPs and the CEP:mCEC ratio were higher than in normal subjects (N=17) (median CEPs: 0.97 vs 0.19 cells µl(-1), respectively, P<0.01; median CEP:mCEC: 0.92 vs 0.58, respectively, P=0.04). However, in patients with VHL without RCC, CECs were not increased. In paired pre- and post-nephrectomy RCC patient samples (N=20), CEPs decreased after surgery (median difference 0.02 cells µl(-1), -0.06 to 1.2; P=0.05). CONCLUSION: Circulating endothelial progenitors were elevated in RCC, but not in patients with VHL without RCC. Circulating endothelial progenitor enumeration merits further investigation as a monitoring strategy for patients with VHL.

Multiple receptor tyrosine kinases regulate HIF-1alpha and HIF-2alpha in normoxia and hypoxia in neuroblastoma: implications for antiangiogenic mechanisms of multikinase inhibitors.

Novel treatment approaches are needed for children with advanced neuroblastoma. Studies with neuroblastoma cells have indicated the presence of a hypoxia-driven vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-1 autocrine loop modulating hypoxia-inducible factor-1alpha (HIF-1alpha). Whether other receptor tyrosine kinases (RTKs) are capable of modulating HIF-1alpha levels and whether RTKs can regulate HIF-2alpha as well is largely unknown. We evaluated neuroblastoma cell lines for expression of various RTKs. Although cell lines were heterogeneous in the expression of VEGFR-1, -3, c-Kit and RET, most cells expressed PDGFR-alpha and -beta. Ligand-induced activation of multiple RTKs upregulated HIF-1alpha levels, whereas activation of VEGFR-1 alone upregulated HIF-2alpha. Multitargeted tyrosine kinase inhibitor sunitinib reduced hypoxia-induced rises in HIF-1alpha and HIF-2alpha through mechanisms involving effects on both mRNA levels and protein stability. In addition, sunitinib and sorafenib had direct effects on tumor cell viability in vitro. In a neuroblastoma xenograft model, tumor growth inhibition by sunitinib was associated with inhibition of angiogenesis and reduced HIF-1alpha levels. These findings show that multiple RTKs may regulate the HIF axis in normoxia and hypoxia and suggest that multikinase inhibitors may exert antiangiogenic effects not only by direct effects on endothelial cells, but also by blocking compensatory hypoxia- and ligand-induced changes in HIF-1alpha and HIF-2alpha.

The management of papillary lesion of the breast by core needle biopsy.

BACKGROUND: The purpose of this study was to determine the accuracy of core needle biopsy (CNB) diagnoses of papillary breast lesions, and to identify the risk factors and histologic features, compared with excisional biopsy (EB). METHOD: We retrospectively reviewed 1,682 sonographically guided core needle biopsies performed at one single medical center from January 2001 through December 2005, and identified 41 papillary lesions. Surgical correlation was available for 35 cases, 2 cases were loss follow-up and 4 cases diagnosed as papilloma by core needle biopsy were followed up with imaging for at least 24 months. RESULTS: The pathologic diagnoses for the 35 papillary lesions obtained at core biopsy were benign in 24 cases, atypical in 7, and malignant in 4. Of those diagnosed as benign lesions at CNB, 7/24 turned out to be malignant. In the hyperplasia group, 5/7 were malignant. The total upgrade rate was 39%. The positive predict value was 100% and negative predict value was 61%. CONCLUSION: All papillary lesions of the breast diagnosed by CNB should be excised because a substantial number of lesions were upgraded of diagnoses at excision.

Computer-aided diagnosis using morphological features for classifying breast lesions on ultrasound.

OBJECTIVES: To develop and evaluate a computer-aided diagnosis (CAD) system with automatic contouring and morphological analysis to aid in the classification of breast tumors using ultrasound. METHODS: We evaluated 118 breast lesions (34 malignant and 84 benign tumors). Each tumor contour was automatically extracted from the digitized ultrasound image. Nineteen practical morphological features from the extracted contour were calculated and principal component analysis (PCA) was applied to find independent features. A support vector machine (SVM) classifier utilized the selected principal vectors to identify the breast tumor as benign or malignant. In this study, all the cases were sampled with k-fold cross-validation (k = 10) to evaluate the performance by receiver-operating characteristics (ROC) curve analysis. RESULTS: The areas under the ROC curves for the proposed CAD systems using all morphological features and the lower-dimensional principal vector were 0.91 and 0.90, respectively. The classification ability for breast tumors using morphological information was good. CONCLUSIONS: This system differentiates benign from malignant breast tumors well and therefore provides a clinically useful second opinion. Moreover, the morphological features are nearly setting-independent and thus available to various ultrasound machines.

Shaping ability of progressive versus constant taper instruments in curved root canals of extracted teeth.

AIM: To compare the shaping ability of progressive versus constant taper shaft instruments in curved root canals of extracted human teeth. METHODOLOGY: A total of 40 root canals of mandibular molars with curvatures ranging between 20 degrees and 40 degrees were divided into two groups of 20 canals each and embedded in a muffle system. The root canals sectioned horizontally at three levels before preparation and then remounted into the mould. All root canals were prepared with ProTaper (progressive taper) or Hero Shaper (constant taper) instruments. Pre- and post-instrumentation radiographs and cross-sectional images were obtained. The parameters evaluated were: working safety (instrument failure, apical blockage and loss of working length) and shaping ability (straightening, cross-sectional area, transportation and centring ability). The data were analysed statistically using Student's t-test. RESULTS: No instrument fractured during preparation. One Hero Shaper instrument permanently deformed. Both instrument systems maintained working length well. The canals prepared with Hero Shaper instruments were straightened to a lesser degree (P < 0.05). ProTaper instruments removed more dentine in the coronal and the middle sections of the canals. Canals prepared with Hero Shaper instruments had less transportation (P < 0.01) and better centring ability (P < 0.05) in the apical section. CONCLUSIONS: Both instrument systems were safe to use and maintained working length well. The canals prepared with Hero Shaper had less transportation and were better centred in the apical region, possibly because their smaller taper reduced instrument stiffness.

Shaping ability of progressive versus constant taper instruments in simulated root canals.

AIM: To compare the shaping ability of progressive versus constant taper shaft designed instruments in simulated root canals. METHODOLOGY: Simulated L- and S-shaped resin canals were prepared by ProTaper (progressive taper) and high elasticity in rotation 642 (Hero 642) (constant taper) instruments (n = 10 canals in each case). The pre- and post-instrumentation images were recorded and assessment of the canal shape was completed with image pro plus 5.0. The width of resin removed was measured at 9 measuring points. Incidence of canal aberrations, instrument fracture, preparation time and change of working length were recorded. In addition, the change of curvature and centring ability were also assessed. The data were analysed statistically using Student's t-test or Fisher's exact-test. RESULTS: In both canal types, Hero 642 instruments prepared canals more rapidly (P < 0.01) and maintained working length significantly more accurately than ProTaper instruments (P < 0.05). In canals prepared with Hero 642 instruments, there was less change in curvature. Instrumentation with ProTaper results in transportation towards the outer aspect of the L-shaped curved canals in the apical part and the inner aspect of the S-shaped canals at the curve. Hero 642 instruments had a better centring ability in the apical part of the canal, but resulted in shapes with a poor taper. CONCLUSIONS: ProTaper and Hero 642 instruments prepared curved canals rapidly, maintained working length well and were relatively safe without creating perforations and danger zones. In both canal types, Hero 642 instruments maintained the original canal curvature better, and had a better centring ability in curved canals because of its constant taper design. The taper prepared by Hero 642 instruments in the coronal part of the canal was generally poor.

Voxel-based detection of white matter abnormalities in mild Alzheimer disease.

OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer disease (AD) by diffusion tensor imaging and to determine their topographic relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD and 16 normal age-matched volunteers underwent diffusion tensor imaging and three-dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry was conducted to detect regions of gray matter atrophy in the AD group relative to the control group. Fractional anisotropy (FA) maps were processed using SPM2 to make voxel-wise comparison of anisotropy in whole brain between the two groups. The relationship between locations of abnormalities in the white and gray matter was examined. RESULTS: Significant reductions in anisotropy were found in the white matter of both medial temporal lobes, bilateral temporal stems, bilateral superior longitudinal fasciculi, bilateral internal capsules, and cerebral peduncles, as well as the white matter of left middle temporal gyrus and right superior parietal lobule, the body and genu of the corpus callosum, and the right lateral capsule in patients with AD. Although the decrease in FA was consistent with cortical volumetric reduction in both temporal lobes, the widespread involvement of bilateral superior longitudinal fasciculi was dominant in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.

Bilateral retrocaval ureters with IVC duplication.

We report a rare case of bilateral retrocaval ureters associated with duplicated inferior renal cava. A 69-year-old woman was sent to our emergency room for abdominal pain. Multidetector computed tomogram with multiplanar reconstruction revealed duplicated inferior renal cavae and the bilateral ureters were positioned behind the duplicated inferior vena cava. To our knowledge, coexistence of bilateral retrocaval ureters and duplicated inferior renal cavae has not been reported in the literature.

Image segmentation feature selection and pattern classification for mammographic microcalcifications.

Since microcalcifications in X-ray mammograms are the primary indicator of breast cancer, detection of microcalcifications is central to the development of an effective diagnostic system. This paper proposes a two-stage detection procedure. In the first stage, a data driven, closed form mathematical model is used to calculate the location and shape of suspected microcalcifications. When tested on the Nijmegen University Hospital (Netherlands) database, data analysis shows that the proposed model can effectively detect the occurrence of microcalcifications. The proposed mathematical model not only eliminates the need for system training, but also provides information on the borders of suspected microcalcifications for further feature extraction. In the second stage, 61 features are extracted for each suspected microcalcification, representing texture, the spatial domain and the spectral domain. From these features, a sequential forward search (SFS) algorithm selects the classification input vector, which consists of features sensitive only to microcalcifications. Two types of classifiers-a general regression neural network (GRNN) and a support vector machine (SVM)--are applied, and their classification performance is compared using the Az value of the Receiver Operating Characteristic curve. For all 61 features used as input vectors, the test data set yielded Az values of 97.01% for the SVM and 96.00% for the GRNN. With input features selected by SFS, the corresponding Az values were 98.00% for the SVM and 97.80% for the GRNN. The SVM outperformed the GRNN, whether or not the input vectors first underwent SFS feature selection. In both cases, feature selection dramatically reduced the dimension of the input vectors (82% for the SVM and 59% for the GRNN). Moreover, SFS feature selection improved the classification performance, increasing the Az value from 97.01 to 98.00% for the SVM and from 96.00 to 97.80% for the GRNN.

Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification.

OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced-stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.

Identification of genes expressed in the epithelium of porcine oviduct containing early embryos at various stages of development.

As a first step toward elucidation of the action of factors secreted by the epithelium of oviduct, differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used in this study to identify transcripts of such oviductal factors in gilts carrying various stages of early embryo development post hormone-induced ovulation. A total of 13 differentially expressed transcripts were identified between 50 and 120 hr post-hCG injection (between 1- and 8-cell embryonic stages). Twelve of these transcripts were found to be initially expressed at 96 hr post-hCG injection (at 4-cell embryonic stage) and beyond. Three of such genes were shown by sequence analysis to be the porcine transforming growth factor-alpha, the porcine transforming growth factor-beta-binding protein II and a porcine astral natriuretic factor receptor-like transcript. Only one differentially expressed gene was detected between 50-60 and 85 hr post-hCG injection, and this gene turned out to be the porcine follicle-stimulating hormone receptor. The remaining eight transcripts detected by DDRT-PCR were novel. Moreover, most of these newly expressed genes were found to be turned on at a time coincidental with that of the 4-cell block of porcine embryos cultured in vitro. Our results demonstrate that DDRT-PCR is a feasible approach for rapid identification of genes that are differentially expressed in oviductal epithelium. Some of the genes thus identified may be important for unhindered development of embryos in the oviduct.

Effects of radiotherapy for nasopharyngeal carcinoma on the paranasal sinuses: study based on computed tomography scanning.

OBJECTIVE: The purpose of this study was to determine if radiotherapy for nasopharyngeal carcinoma causes mucosal disease of the paranasal sinuses. DESIGN: This study was a retrospective study. SETTING: This study was conducted at a tertiary care centre. METHOD: A series of 69 newly diagnosed patients, without pre-existing sinus disease, who were treated with high-dose radiotherapy participated. MAIN OUTCOME MEASURES: The prevalence, severity, and time course of mucosal abnormalities were analyzed, as judged by consecutive computed tomographies (CTs). RESULTS: The CT study revealed that 58.8% of the postirradiation scans had mucosal disease of the sinuses. The maxillary sinus had the highest prevalence (42.3%) without statistical significance (p = .10). The difference by McNemar test for two follow-up scans was not significant (p = .48) and by Kappa test was significant (p = .04). The relationship between the prevalence and the time course post radiotherapy revealed that it remained a high prevalence until after the 4-year follow-up scans. CONCLUSIONS: The results of this study confirm that chronic sinus disease is a common late complication of radiotherapy and it persists for years. Thus, aggressive treatment is indicated.

A case of extra-hepatic portal vein aneurysm: evaluation by 3-dimensional computerized tomography angiogram.

Portal vein aneurysms (PVAs) are rare lesions associated with congenital vascular anomalies or chronic portal hypertension. Although usually benign, they occasionally lead to complications such as aneurysmal rupture, porto-systemic shunts, mural thrombosis in the portal vein, and compression of the biliary tract. So far, the diagnosis of these lesions has been dependent on 2-dimensional imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI), or invasive procedures such as percutaneous transhepatic portography. Here we present the first documented case of an extra-hepatic portal vein aneurysm evaluated by 3-dimensional CT angiography. This easily performed and accurate imaging technique may obviate the need for invasive angiographic procedures in the future for the 3-dimensional characterization of deep vascular malformations in the portal circulation.