[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.

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.

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.

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.

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.

Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1.

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.

Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31.

A basic helix-loop-helix phosphoprotein gene, G0S8, was recently isolated by differential screening of cDNA from human blood mononuclear cells stimulated with a T cell mitogen and cycloheximide. In this study, G0S8 expression was examined in normal and malignant hematopoietic cells by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). G0S8 expression was observed in most fresh samples of acute myelogenous leukemia (AML) (28/30) and most cases of adult acute lymphoblastic leukemia (ALL) (9/11) regardless of clinical classification. G0S8 mRNA was also detected in all cases tested of chronic myelogenous leukemia (CML) in blast crisis. However, G0S8 expression was not detected in CML patients in chronic phase, nor in normal bone marrow or other hematopoietic cells. G0S8 has been mapped using fluorescence in situ hybridization (FISH) to human chromosome 1q31, the same site reported for the B cell homolog BL34/1R20 and within a region implicated in the development of hematological malignancies. The consistent observation of G0S8 mRNA in patient samples of acute leukemia suggests that G0S8 expression may either play a role in leukemogenesis or represent a common consequence of dysregulated growth.

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.

A structurally abnormal breakpoint cluster region gene in a transcription factor, hLH-2-negative human leukemia cell line.

hLH-2, a transcription factor that contains double cysteine rich regions (LIM motifs) and a homeobox (Hox) DNA-binding domain shows aberrant high expression in all cases of chronic myelogenous leukemia (CML). This gene has been mapped to the chromosome 9q33-34.1, the same region as the reciprocal translocation that creates the breakpoint cluster region (BCR)-ABL chimera of the Philadelphia chromosome (Ph'). To investigate the possible involvement between the BCR-ABL fusion gene and hLH-2 in the pathogenesis of CML, an hLH-2-negative CML cell line, JK-1 that carries double Ph' chromosomes, was examined. Like other CML cells, high BCR-ABL fusion mRNA levels are expressed, but no transcript of hLH-2 was detected in JK-1 cells as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the CML cell line, K-562, an additional rearrangement of the BCR gene was observed in JK-1 as determined by Southern blot hybridization; however, the hLH-2 gene was normal. These findings raise interesting questions about the possible roles of either the abnormal BCR gene or other genetic events such as the complex chromosomal abnormalities that result in hLH-2 being turned off in JK-1 cells.

Capillary electrophoretic determination of the constituents of paeoniae radix.

A method combining the techniques of capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) has been developed to separate a total of eight peony constituents. The CZE method was used to determine the content of paeonol, oxypaeoniflorin, benzoic acid, pentagalloylglucose and gallic acid, and MEKC technique based on sodium cholate was applied to analyze albiflorin, paeoniflorin, benzoyla biflorin, paeonol and oxypaeoniflorin. Linearity around two orders of magnitude of concentration was generally obtained and limits of detection for these compounds were in the range of 2.6-23.7 micrograms/ml. The relative standard deviations of migration times were less than 1.43% (n = 6). Contents of peony constituents in an ethanol-water extract of Paeonia lactiflora Pall. sample could easily be determined by this method.

Glaucoma with inflammatory precipitates on the trabecular meshwork: a report of Grant's syndrome with ultrasound biomicroscopy of precipitates.

BACKGROUND: The syndrome of inflammatory precipitates on the trabecular meshwork is a rare form of inflammatory glaucoma that was described by Chandler and Grant in 1968 and subsequently given the eponym Grant's syndrome. METHODS: We present two cases of elevated intraocular pressure associated with inflammatory precipitates on the trabecular meshwork in otherwise relatively quiet eyes, consistent with Grant's syndrome. We review the epidemiology, clinical features, and mechanism of this syndrome. In addition, we demonstrate the use of ultrasound biomicroscopy for imaging angle inflammatory precipitates. RESULTS: Our patients demonstrate the cardinal features of Grant's syndrome, including acute onset, significant elevation of tension, trabecular meshwork precipitates in an otherwise quiet eye, limited response to typical pressure lowering agents, excellent response to topical steroids, evidence of recurrence with bilaterality, and systemic association with sarcoidosis. Ultrasound biomicroscopy proves to be a useful adjunct for pathologic imaging. CONCLUSIONS: The syndrome of glaucoma with inflammatory precipitates on the trabecular meshwork is a rare entity that should be considered as a possible diagnosis of elevated intraocular pressures in otherwise apparently quiet eyes.

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.

Cytogenetic analysis of bone marrow from patients with primary myelodysplastic syndrome.

Of 34 patients with primary myelodysplastic syndrome (MDS), 26 (76.5%) were found to have chromosome defects using an improved bone marrow culture method and high-resolution G-banding technique induced by actinomycin D. The frequency of abnormalities varied among the subtypes: 1/2 in refractory anaemia with ringed sideroblasts; 18/24 in refractory anaemia; 5/6 in refractory anaemia with excess of blasts (RAEB); and 2/2 in refractory anaemia with excess of blasts in transformation. The most frequent abnormalities, either single, double or complex defects, were -5/5q-, -7, +8 and +21; 16q-/16p-, +19 and -X were also common. The percentage of aneuploid cells, in particular hypodiploid cells, was increased. The abnormalities were detected more frequently in complex aberrations associated with RAEB and RAEB in transformation. The presence of -5/5q- as a sole aberration was associated with longer mean survival time (greater than 18 months) but multiple (more than two) chromosomal abnormalities were associated with a poorer prognosis and a mean survival time of only 7.5 months. Chromosome follow-up studies indicated that patients with -7, +8, +21, -X and complex defects, increased hypodiploid cells and karyotpic evolution were likely to have a high risk of transformation to leukaemia or to a more severe subtype of MDS with a short overall mean survival time. These defects, mostly of the deleted type, are assumed to play a specific role in the pathogenesis of myelodysplasia. Repeated chromosomal analyses during the clinical course convey more accurate prognostic criteria for patients.

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.

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.