[Pleurodesis with an Autologous Blood Patch in the Treatment of Persistent Air Leak after Lung Resection].

Objective To evaluate the efficacy and risks of autologous blood patch pleurodesis in patients with persistent air leak(PAL)after lung resection. Methods A total of 97 patients with PAL after lung resection in Beijing Shijitan Hospital from October 2014 to October 2019 were retrospectively reviewed,including 53 treated by autologous blood patch pleurodesis and 44 by the conventional way.The therapeutic effect,adverse reactions and complications were analyzed. Results All the patients with PAL were cured with autologous blood patch pleurodesis.Most air leaks(81.1%)ceased within 48 hours after treatment,and the left 18.9% patients got cured after a repeat.The mean tube retention time and the mean in-hospital stay were 8.4 days and 10.0 days in the autologous blood patch pleurodesis group and 13.5 days and 15.3 days in the conventional treatment group.A prolonged drainage time(P=0.00)and in-hospital stay(P=0.00)were observed in the conventional treatment group.No severe complications were observed except two patients developed slight fever and cutaneous emphysema. Conclusion In our experience,the autologous blood patch pleurodesis is an effective way with low risk of adverse reactions in the treatment of PAL.

[Time-Determination and Contribution Analysis of Transport, Retention, and Offshore Backflow to Long-Term Sand-Dust Coupling].

Continuous on-line observation of particulate matter and PM2.5 chemical composition was conducted from October 15th to November 7th 2019 in East China. During the observation period, a wide range of dust-related processes took place. According to supplementary urban air quality assessment affected by dust (hereafter referred to as supplementary provisions), the observations were divided into four stages including pre-dust event, dust Ⅰ, dust Ⅱ, and post-dust event. The dust Ⅰ stage represented the processes of transportation and retention, while the dust Ⅱ stage represented processes of backflow from the sea and scavenging. The start time of the studied dust event was October 29th 08:00-09:00 based on the supplementary provisions, dust tracers, and air quality models; however, disagreements existed between these data sources with respect to the finishing time. The supplementary provisions could not effectively distinguish backflow dust from sea, and results from different dust tracers were variable. The WRF-CMAQ model simulated dust variation trends well but overestimated short-term suspended dust and backflow dust. PM10, PM2.5, and trace element concentrations were much higher during dust events than during non-dust periods, with highest daily concentrations of (234.8±125.5), (76.8±22.5), and (17.54±10.5) µg·m-3, respectively, which occurred on October 29th. During the dust event, concentration of crustal elements were remarkably high in PM2.5. At the same time, secondary ions (SO42-, NO3-, and NH4+) contributed less to PM2.5 mass concentrations. Four major crustal elements (Al, Si, Ca, and Fe) accounted for 23.5% and 13.7% of the mass concentration of PM2.5 and secondary ions accounted for 24.3% and 41.9% during dust Ⅰ and dust Ⅱ stages, respectively. Based on PMF source apportionment, Ca abundance, PM2.5/PM10 in dust sources, and the reconstruction of crustal material, dust particulates accounted for 43.4%-50.0% of PM2.5 and backflow dust accounted for 19.2%-24.7% of PM2.5.

[Audit Indicators and Suggested Ranges for Data Validation of Chemical Components in Ambient PM2.5: A Case Study of the Yangtze River Delta].

Diagnostic indicators for the validation of PM2.5 compositional data were calculated, based on the monitoring results of approximately 2100 ambient samples collected in the Yangzi River Delta from 2014 to 2017. According to the results of a correlation analysis, we propose that the audit indexes of the monitoring data of PM2.5 components in ambient air should include:equivalent ratios of anion-cation charge balance(A/C), the consistency between sum of all measured components(∑species) and weighed PM2.5, the consistency between mass reconstructed PM2.5(PM2.5, reconstructed) and weighed PM2.5, the chemical consistency between elemental S and water-soluble SO42-, elemental K and water-soluble K+, and the chemical consistency of theoretical and tested NH4+. The double-sided 95% reference ranges of anion-cation equivalent balance (A/C), ∑species/PM2.5, PM2.5, reconstructed/PM2.5, S/SO42-, and K/K+ ratios were determined in terms of P2.5 and P97.5 as follows:(0.82, 1.35), (0.63, 0.94), (0.62, 1.00), (0.28, 0.50), and (0.66, 2.31). These diagnostic indicators were helpful for judging the errors of chemical component analysis and retain seasonal variation stability. In most cases, NH4+ existed in the form of NH4NO3 and (NH4)2SO4 in spring and summer. With the approach of autumn and winter, it transformed to NH4NO3, (NH4)2SO4, and NH4Cl. The results of literature verification showed the pass rate of A/C was 87.1% and the rate of other indexes was 100%, indicating that the above audit indexes we propose could be applied to not only the Yangzi River Delta but the entire country. Furthermore, there were certain conditions in applying the diagnostic indicators. The S/SO42- ratio worked well with PM2.5 ≥ 40 µg·m-3 in summer and with 60 µg·m-3 ≤ PM2.5 ≤ 140 µg·m-3 in spring, autumn, and winter. Other audit indexes were available universally in all weathers under the condition of PM2.5 ≥ 60 µg·m-3.

Targeting the ubiquitin-proteasome pathway to overcome anti-cancer drug resistance.

Drug resistance is a major obstacle in the field of pre-clinical and clinical therapeutics. The development of novel technologies and targeted therapies have yielded new modalities to overcome drug resistance, but multidrug resistance (MDR) remains one of the major challenges in the treatment of cancer. The ubiquitin-proteasome system (UPS) has a central role in regulating the levels and activities of a multitude of proteins as well as regulation of cell cycle, gene expression, response to oxidative stress, cell survival, cell proliferation and apoptosis. Therefore, inhibition of the UPS could represent a novel strategy for the treatment and overcoming of drug resistance in chemoresistant malignancies. In 2003, bortezomib was approved by the FDA for the treatment of multiple myeloma (MM). However, due to its limitations, second generation proteasome inhibitors (PIs) like carfilzomib, ixazomib, oprozomib, delanzomib and marizomib were introduced which displayed clinical activity in bortezomib-resistant tumors. Past studies have demonstrated that proteasome inhibition potentiates the anti-cancer efficacy of other chemotherapeutic drugs by: i) decreasing the expression of anti-apoptotic proteins such as TNF-α and NF-kB, ii) increasing the levels of Noxa, a pro-apoptotic protein, iii) activating caspases and inducing apoptosis, iv) degrading the pro-survival protein, induced myeloid leukemia cell differentiation protein (MCL1), and v) inhibiting drug efflux transporters. In addition, the mechanism of action of the immunoproteasome inhibitors, ONX-0914 and LU-102, suggested their therapeutic role in the combination treatment with PIs. In the current review, we discuss various PIs and their underlying mechanisms in surmounting anti-tumor drug resistance when used in combination with conventional chemotherapeutic agents.

Application of Ventana immunocytochemical analysis on ThinPrep cytology slides for detection of ALK rearrangement in patients with advanced non-small-cell lung cancer.

BACKGROUND: Ventana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non-small-cell lung carcinoma (NSCLC). However, tumor tissues are often not readily obtainable, and cytology specimens and may be the only tumor material available for diagnosis and molecular marker analysis. In this study, we evaluated the feasibility of ALK immunocytochemistry (ICC) on ThinPrep slides and determined a suitable scoring system for interpretation of the results. METHODS: One hundred twenty-one fine-needle aspirate (FNA) specimens from metastatic lesions of NSCLC were analyzed. ALK rearrangement was detected on ThinPrep cytology slides using the Ventana immunocytochemistry ALK-D5F3 system, which adopts two scoring systems for interpretation of the ICC results. The results were subsequently confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis and fluorescence in situ hybridization (FISH). RESULTS: Among the 121 ICC specimens, 16 that were considered ALK-positive by either scoring system were referred for PCR analysis. Among the ALK ICC-negative cases, 33 had correlated FISH ALK results. A total of 49 specimens that exhibited either a positive or negative ICC result with a correlated ALK status were analyzed statistically. ICC results showed a high concordance rate with the results of PCR/FISH analysis. The sensitivity and specificity of ALK ICC by the binary scoring algorithm were 68.75 and 96.97%, respectively. These values increased to 93.75 and 96.97%, respectively, when interpreted by the semiquantified interpretation system. CONCLUSIONS: ALK ICC analysis on ThinPrep slides is a reliable ALK testing method, and the semiquantified interpretation system on cytology specimens is recommended rather than the binary scoring algorithm on tissue specimens.

A cocktail of p16INK4a and Ki-67, p16INK4a and minichromosome maintenance protein 2 as triage tests for human papillomavirus primary cervical cancer screening.

Most human papillomavirus (HPV) infections are transient and additional triage approaches should be built after HPV-based primary cervical cancer screening. We evaluated the accuracy of p16/Ki-67 and p16/mcm2 dual staining as biomarkers for triaging HPV positive women in China. 4070 participants aged 35 to 64 years attending ongoing cervical cancer screening were enrolled in 2015-2016. Cervical exfoliated cells were collected for HPV DNA analysis and the residual positive specimens were tested for liquid-based cytology and biomarkers. Women infected with HPV 16/18 type or other 12 high-risk HPV types with abnormal cytology results received colposcopy. We found the positive rates of both biomarkers increased significantly with histology severity. p16/Ki-67 positivity in HPV16/18 group, other 12 high-risk HPV group and HPV negative group was 50.0%, 33.7% and 8.9%, respectively. The corresponding p16/mcm2 positivity was 70.0%, 56.3% and 6.7%, respectively. The sensitivity and specificity of p16/Ki-67 for CIN2+ in all HPV-positive women were 91.7% and 63.5%, with a referral rate of 36.2%, while p16/mcm2 were 87.5% and 42.1%, with a referral rate of 58.4%, respectively. The sensitivity of p16/Ki-67 increased to 95.8% for CIN2+ and 100% for CIN3+ when combined with high-grade cytology, without decrease in specificity. Our studies suggest that p16/Ki-67 is an efficient triaging biomarker for HPV-positive women and could reduce colposcopy workload. p16/mcm2 is more sensitive compared with cytology for identifying cervical lesions.

Influence of presence/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma.

BACKGROUND: Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice. METHODS: Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection. RESULTS: One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids. CONCLUSIONS: The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids.

2-Trifluoromethyl-2-Hydroxypropionamide Derivatives as Novel Reversal Agents of ABCG2 (BCRP)-Mediated Multidrug Resistance: Synthesis and Biological Evaluations.

It has been postulated that one of the biggest impediments to a successful chemotherapy is the phenomena of multidrug resistance (MDR) in cancer cells. One of the main mechanisms of MDR is overexpression of the ATP-binding cassette (ABC) transporters in cancer cells which alters absorption, distribution, metabolism, and excretion of various chemotherapeutic drugs. Efforts have been made to find effective inhibitors of ABC transporters. However, none has been approved clinically. This study shows that a novel compound 3-chloro-N-(2-hydroxyphenyl)-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido) benzamide (compound 7d), one of the 2-trifluoromethyl-2-hydroxypropionamide derivatives could reverse ABCG2 (BCRP)-mediated MDR. Cytotoxicity studies show that compound 7d sensitizes the ABCG2-overexpressing cells to chemotherapeutic drugs mitoxantrone and SN-38, which are well-established substrates of the ABCG2 transporter. Western blotting results indicate that compound 7d does not significantly alter the protein level of the ABCG2 transporter. Accumulation and efflux studies demonstrate that compound 7d increases intracellular accumulation of mitoxantrone by inhibiting the function of ABCG2. Overall, these findings indicate a potential use for compound 7d as an adjuvant agent for chemotherapy to inhibit the function of the clinically relevant ABC transporter and sensitize tumor cells to chemotherapeutic drugs. J. Cell. Biochem. 118: 2420-2429, 2017. © 2017 Wiley Periodicals, Inc.

p16/Ki-67 co-expression associates high risk human papillomavirus persistence and cervical histopathology: a 3-year cohort study in China.

PURPOSE: To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. METHODS: We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. RESULTS: Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). CONCLUSIONS: p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China.

PURPOSE: To analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women. METHODS: 1079 women attending ongoing cervical cancer screening and 211 "enriched" women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result. RESULTS: p16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%. CONCLUSIONS: p16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China.

Improvement in the Detection of Cystic Metastatic Papillary Thyroid Carcinoma by Measurement of Thyroglobulin in Aspirated Fluid.

Cystic change in metastatic lymph nodes of papillary thyroid carcinoma (PTC) is a diagnostic challenge for fine needle aspiration (FNA) because of the scant cellularity. The aim of this study was to evaluate the measurement of thyroglobulin in fine needle aspirate (Tg-FNA) for detecting metastatic PTC in patients with cystic neck lesions and to validate the optimal cutoff value of Tg-FNA. A total of 75 FNA specimens of cystic lesions were identified, including 40 of metastatic PTC. Predetermined threshold levels of 0.04 (minimum detection level), 0.9, 10.0, and 77.0 ng/mL (maximum normal serum-Tg level) were used to evaluate the diagnostic accuracy of Tg-FNA for metastatic PTC detection. The areas under the receiver operating characteristic curve for diagnosing metastatic PTC of Tg-FNA values of 0.04, 0.9, 10.0, and 77.0 ng/mL were 0.5 (95% confidence interval [CI], 0.382-0.618), 0.645 (95% CI, 0.526-0.752), 0.945 (95% CI, 0.866-0.984), and 0.973 (95% CI, 0.907-0.996), respectively. With a cutoff value of 77.0 ng/mL, the combination of Tg-FNA and FNA cytology showed superior diagnostic power (97.5% sensitivity and 100% specificity) compared to FNA cytology alone (80% sensitivity and 100% specificity). We recommend a Tg-FNA cutoff of 77.0 ng/mL, the maximum normal serum-Tg level, for cystic neck lesions.

Detection of BRAF c.1799T > A (p.V600E) mutation using residual routine fine-needle aspiration specimens of papillary thyroid carcinoma.

BACKGROUND: BRAF p.V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC) and has been used as a diagnostic and prognostic marker in PTC. The aim of this study was to investigate the utility of preoperative BRAF p.V600E mutation analysis as an adjunctive diagnostic and prognostic tool to routine fine-needle aspiration (FNA). METHODS: Specimens were collected from thyroid nodules by FNA. Cytology diagnosis and BRAF p.V600E testing were performed on these specimens. Molecular and cytological results were correlated with histology outcomes. RESULTS: A total of 195 patients with thyroid nodules were enrolled, including 25 benign lesions and 170 PTCs. BRAF p.V600E testing was successfully performed in all specimens. The combination of BRAF p.V600E testing and cytology improved the sensitivity of cytology from 70% to 85.3% (P = 0.001). This significant increase in sensitivity was due to the detection of PTC by BRAF p.V600E testing in the nodules with atypical or suspicious PTC cytology results. Patients with BRAF p.V600E-positive tumors were significantly older than those who did not harbor mutations (45.6 years vs. 39.8 years, P = 0.002). No correlations between BRAF p.V600E mutation and other clinical-pathology parameters were observed. CONCLUSIONS: Detection of BRAF p.V600E mutation can be successfully carried out using residual liquid-based materials. It can be performed as a diagnostic tool to supplement traditional thyroid FNA, especially in cases with atypical or suspicious PTC. However, the role of BRAF p.V600E in guidance of the extent of thyroidectomy and nodal clearance requires further study.

Factors Influencing the Reliability of Thyroid Fine-Needle Aspiration: Analysis of Thyroid Nodule Size, Guidance Mode for Aspiration and Preparation Method.

OBJECTIVE: We aimed to clarify the influence of ThinPrep preparation, nodule size and guidance mode on the accuracy of thyroid fine-needle aspiration (FNA). METHODS: A total of 1,240 thyroid FNAs were reviewed and 489 cases with histological correlations were enrolled in this study. RESULTS: Of the 489 total cases examined, 101 were processed with both ThinPrep and conventional preparation and 388 entirely with ThinPrep. The overall nondiagnostic rate, sensitivity and accuracy of FNA were 2.0, 91.0 and 89.4%, respectively. The cases with a preoperative ultrasound (n = 469) were grouped according to nodule size. The nondiagnostic rate, sensitivity and accuracy of FNA did not differ significantly with nodule size (p1 = 0.339, p2 = 0.179, p3 = 0.119). A total of 101 resections were performed with palpation-guided FNA and 388 were performed with ultrasound-guided FNA. The nondiagnostic rates, sensitivity and accuracy of FNA were similar in these two groups. CONCLUSIONS: The ThinPrep technique is a valid method for thyroid FNA and is effective for thyroid nodules ≥ 0.5 cm. The reliability of FNA results is not reduced with larger nodules. The use of palpation-guided FNA for palpable solid nodules is also effective.

Association between tobacco use and the upper gastrointestinal microbiome among Chinese men.

PURPOSE: Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. METHODS: We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. RESULTS: Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. CONCLUSIONS: Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.

Risks of proteinuria associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a systematic review and meta-analysis.

BACKGROUND: Vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) have emerged as an effective targeted therapy in the treatment of cancer patients, the overall incidence and risk of proteinuria associated these drugs is unclear. We performed a systematic review and meta-analysis of published clinical trials to quantify the incidence and risk of proteinuria associated with VEGFR-TKIs. METHODOLOGY: Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to May 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating VEGFR-TKIs in cancer patients with adequate data on proteinuria. Statistical analyses were conducted to calculate the summary incidence, Odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. PRINCIPAL FINDINGS: A total of 6,882 patients with a variety of solid tumors from 33 clinical trials were included in our analysis. The incidence of all-grade and high-grade (grade 3 or higher) proteinuria was 18.7% (95% CI, 13.3%-25.6%) and 2.4% (95% CI, 1.6%-3.7%), respectively. Patients treated with VEGFR-TKIs had a significantly increased risk of all-grade (OR 2.92, 95%CI: 1.09-7.82, p = 0.033) and high-grade proteinuria (OR 1.97, 95%CI: 1.01-3.84, p = 0.046) when compared to patients treated with control medication. No evidence of publication bias was observed. CONCLUSIONS: The use of VEGFR-TKIs is associated with a significant increased risk of developing proteinuria. Physicians should be aware of this adverse effect and should monitor cancer patients receiving VEGFR-TKIs.

Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China.

OBJECTIVE: The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. METHODS: A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n=25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone. RESULTS: LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests. CONCLUSIONS: The results of the current study support the use of the cervical cancer screening guidelines in China.

Impact of molecular testing in the diagnosis of thyroid fine needle aspiration cytology: data from mainland China.

BACKGROUND: The molecular work-up of thyroid nodules from fine needle aspiration samples has given clinicians a new level of diagnostic information. The aim of the present study was to evaluate the utility of molecular analysis in thyroid fine needle aspiration samples from a Chinese population. METHODS: Specimens were collected from thyroid nodules by fine needle aspiration. Cytology diagnosis and genes analysis were performed and correlated with histology outcome. RESULTS: A total of 83 patients with thyroid nodules were enrolled, including 20 benign lesions and 63 papillary carcinomas. BRAF and RAS mutations and RET/PTC gene rearrangements were found in 65.1%, 0%, and 1.6% of papillary carcinomas, respectively. No gene alterations were found in benign lesions. The combination of BRAF testing and cytology improved the accuracy of cytology from 69.9% to 89.2% (P < 0.05). Moreover, BRAF testing confirmed 82.4% of papillary carcinomas with suspicious cytology and identified 33.3% of papillary carcinomas with atypia cytology. CONCLUSIONS: Of the three candidate markers, BRAF testing showed diagnostic utility in fine needle aspiration. Combining BRAF testing with cytology improves the accuracy of fine needle biopsy. Those who have positive BRAF and malignant or suspicious malignant cytology can undergo thyroidectomy without a frozen section.

ß-Elemene, a compound derived from Rhizoma zedoariae, reverses multidrug resistance mediated by the ABCB1 transporter.

In the present in vitro study, we examined the effect of the compound ß-elemene on the response of KB-C2 cells overexpressing the ABCB1 transporter to specific antineoplastic compounds. The MTT assay was used to determine the effects of ß-elemene in combination with other anticancer drugs on ABCB1-overexpressing cancer cell lines. Furthermore, we used [3H]-paclitaxel accumulation, efflux assay, immunofluorescence experiments, western blot assays and docking analysis to ascertain the mechanism of action of ß-elemene. The incubation of KB-C2 cells overexpressing ABCB1 transporter with ß-elemene (100 µM) significantly augmented the antineoplastic efficacy of colchicine, vinblastine and paclitaxel when compared to KB-C2 cells incubated with these drugs alone. In HEK293 cells overexpressing the ABCB1 transporter, ß-elemene significantly increased the cytotoxicity of paclitaxel. In addition, 100 µM of ß-elemene significantly increased the accumulation of [3H]-paclitaxel and this was due to a decrease in [3H]-paclitaxel efflux when compared to controls. The incubation of KB-C2 cells with ß-elemene (100 µM) for 72 h did not significantly alter the expression of ABCB1 protein levels. Immunofluorescence experiments indicated that ß-elemene did not significantly alter the subcellular localization of the ABCB1 transporter. Docking analysis indicated that ß-elemene binds to the drug-binding site of ABCB1 transporter. Finally, ß-elemene at 100 µM partially (~50%) increased the sensitivity of the BCRP-overexpressing cell line, NCI-H460/MX20, to mitoxantrone, but ß-elemene did not significantly alter the resistance of MRP1-transfected HEK293/MRP1 cells to vincristine. Overall, our in vitro findings indicated that ß-elemene potentiates the cytotoxic effects of various antineoplastic drugs in cell lines overexpressing the ABCB1 transporter and that this is due to the inhibition of the efflux component of the ABCB1 transporter.

[Detection of EGFR and K-ras mutations in non-small cell lung cancer using cytological specimens].

OBJECTIVE: To validate the feasibility for detecting EGFR and k-ras mutations using cytological specimens. METHODS: Cytological specimens including fine-needle aspiration (FNA), pleural effusion (PLE) and fiberoptic bronchoscopic (FOB) brushing were collected from patients with non-small cell lung cancer (NSCLC ) from January 2011 to July 2011 at the Department of Cytology, Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS). Polymerase chain reaction (PCR) was carried out to amplify EGFR exons 18-21 and k-ras codons 12-13, and then the PCR products sequencing and analysis were performed. RESULTS: Fifty cytological specimens were collected including 19 cases of FOB, 9 cases of FNA, 22 cases of PLE. Of them DNA was successfully extracted in 43 cases, and specific PCR amplification products sequencing were performed in 42 cases. EGFR mutations were detected in 14 of 42 specimens (33.3%), the frequencies of EGFR mutations in exons 19, 20 and 21 were 16.7% (7/42), 4.8% (2/42) and 11.9% (5/42), respectively, and no mutation was found in exon 18. Higher frequencies of EGFR mutations were detected in exons 19 and 21 (85.7%). Mutations were identified in 38.7% (12/31) cases of adenocarcinoma. K-ras mutations were found in 2 of 42 specimens (4.8%). EGFR and K-ras mutations were not found in the same case. CONCLUSIONS: Cytological specimens are feasible for detecting EGFR and K-ras mutation. This is especially beneficial in patients in whom histological materials can not be obtained.