Assessment of BRCA1 and BRCA2 Germline Variant Data From Patients With Breast Cancer in a Real-World Data Registry.

PURPOSE: The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power. METHODS: Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines. RESULTS: In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality. CONCLUSION: We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.

Sinonasal squamous cell carcinoma in the United States: Temporal and geographic patterns associated with HPV testing and positivity.

OBJECTIVES: Human papillomavirus (HPV) has emerged as a potential etiological factor in sinonasal squamous cell carcinoma (SNSCC), but a clear understanding of HPV prevalence and its temporal patterns in SNSCC remains elusive. This study aimed to investigate temporal trends in HPV testing and positivity rates, and explore demographic and geographic factors associated with these trends. METHODS: A retrospective cohort study included patients diagnosed with invasive SNSCC between 2011 and 2017 from the US National Cancer Database (NCDB). Prevalence ratios (PR) of HPV positivity and testing rates were estimated with the corresponding 95% confidence interval (95% CI). RESULTS: The overall HPV testing rate was 45.4 % (N = 1762/3880), and the prevalence of HPV testing significantly decreased during the study period (adjusted PR: 0.97, 95 % CI: 0.95 - 0.99, p < 0.001). Overall HPV positivity frequency was 37.3 % (N = 650/1741), and the overall prevalence of HPV positive tumors significantly increased during the study period (adjusted PR: 1.04, 95 % CI: 1.02 - 1.05, p < 0.001). The increase in HPV positivity rate was observed solely in the white population (unadjusted PR: 1.10, 95 % CI: 1.06 - 1.14; p < 0.001). A significant geographical variation was observed for both HPV testing (range: 28.6 % - 61.7 %) and positivity (range: 28.3 % - 44.7 %). CONCLUSIONS: This study provides novel insights into the temporal trends and demographic factors associated with HPV testing and positivity in SNSCC. Despite increasing HPV positivity rates, disparities in testing rates persist, highlighting the need for standardized testing protocols and targeted interventions.

Effect of Dexmedetomidine on Apoptosis and Early Cognitive Dysfunction in Rats Following Propofol Anesthesia.

Background: To address the intricate interplay between surgical anesthesia, hippocampal apoptosis, and early cognitive dysfunction in rats, this study delves into the impact of dexmedetomidine (DEX). With a focus on understanding the alterations in the PI3K/Akt pathway, our investigation aims to shed light on the comprehensive dynamics of these processes. Methods: Sixty healthy Sprague-Dawley rats were randomly divided into three groups: controls (intraperitoneal saline injection), group A (intraperitoneal propofol injection), and group A + DEX (intraperitoneal propofol and DEX injection), with 20 rats in each group. Cognitive function in the three groups was evaluated using [specify the cognitive function tests, e.g., Morris Water Maze]. The assessment was conducted at various postoperative time points. We employed Hematoxylin-eosin (HE) staining, flow cytometry (FC), Western blot (WB), and real-time fluorescence quantitation polymerase chain reaction (RT-qPCR) to examine hippocampal apoptosis and gene expression. Results: Rats in groups A and A + DEX exhibited higher cognitive scores (NSS) and escape latencies at each postoperative time point, along with a lower proportion of swimming distance (SD) in the target quadrant (TQ) compared to controls. Group A + DEX demonstrated lower NSS and escape latency than controls, accompanied by a higher proportion of SD in TQ. Apoptosis rates of hippocampal cells were higher in groups A and A + DEX than in controls, although they were relatively lower in group A + DEX (P < .05). Regarding gene expression, the relative expression (RE) of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and Bax and caspase3 were altered. Group A + DEX showed higher RE of Bcl-2, PI3K, pAkt, mRNA expression of Bcl-2 and PI3K, and lower Bax and caspase3 than group A (P < .05). For a detailed understanding of the magnitude of these changes, specific values or ranges are provided in the subsequent results section. Conclusion: In conclusion, the combined use of surgical anesthesia with DEX demonstrates a modulatory effect on the PI3K/Akt signaling pathway. This intervention proves effective in reducing hippocampal cell apoptosis post-surgery, thereby alleviating neurological impairments and ameliorating early cognitive dysfunction in rats. Our findings underscore the potential therapeutic impact of DEX in enhancing cognitive outcomes following surgical procedures. The observed reduction in hippocampal cell apoptosis and improvement in cognitive function suggest that DEX may hold promise as a neuroprotective agent in the perioperative setting. These outcomes highlight the clinical relevance of considering DEX as an adjunctive therapy to mitigate cognitive dysfunction associated with surgery. Further investigations and clinical trials are warranted to validate and extend these findings, potentially offering a novel avenue for improving patient outcomes and advancing perioperative care strategies.

Association between adjuvant radiation treatment and breast cancer-specific mortality among older women with comorbidity burden: A comparative effectiveness analysis of SEER-MHOS.

BACKGROUND: The National Comprehensive Cancer Network suggested that older women with low-risk breast cancer (LRBC; i.e., early-stage, node-negative, and estrogen receptor-positive) could omit adjuvant radiation treatment (RT) after breast-conserving surgery (BCS) if they were treated with hormone therapy. However, the association between RT omission and breast cancer-specific mortality among older women with comorbidity is not fully known. METHODS: 1105 older women (≥65 years) with LRBC in 1998-2012 were queried from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey data resource and were followed up through July 2018. Latent class analysis was performed to identify comorbidity burden classes. A propensity score-based inverse probability of treatment weighting (IPTW) was applied to Cox regression models to obtain subdistribution hazard ratios (HRs) and 95% CI for cancer-specific mortality considering other causes of death as competing risks, overall and separately by comorbidity burden class. RESULTS: Three comorbidity burden (low, moderate, and high) groups were identified. A total of 318 deaths (47 cancer-related) occurred. The IPTW-adjusted Cox regression analysis showed that RT omission was not associated with short-term, 5- and 10-year cancer-specific death (p = 0.202 and p = 0.536, respectively), regardless of comorbidity burden. However, RT omission could increase the risk of long-term cancer-specific death in women with low comorbidity burden (HR = 1.98, 95% CI = 1.17, 3.33), which warrants further study. CONCLUSIONS: Omission of RT after BCS is not associated with an increased risk of cancer-specific death and is deemed a reasonable treatment option for older women with moderate to high comorbidity burden.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Racial and Ethnic Variations in Pre-Diagnosis Comorbidity Burden and Health-Related Quality of Life Among Older Women with Breast Cancer.

BACKGROUND: This study examined racial/ethnic differences in comorbidity burden and health-related quality of life (HRQOL) among older women before breast cancer diagnosis. METHODS: From Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked data resource, 2513 women diagnosed with breast cancer at ≥ 65 years between 1998 and 2012 were identified and grouped based on comorbidity burden using latent class analysis. Pre-diagnosis HRQOL was measured using SF-36/VR-12 and summarized to physical (PCS) and mental component summary (MCS) scores. The adjusted least-square means and 95% confidence intervals were obtained according to comorbidity burden and race/ethnicity. The interactions were examined with 2-way ANOVA. RESULTS: The latent class analysis revealed four comorbid burden classes, with Class 1 being the most healthy and Class 4 being the least healthy. African American (AA) and Hispanic women were more likely to be in Class 4 than non-Hispanic white (NHW) women (18.6%, 14.8%, and 8.3%, respectively). The mean PCS was 39.3 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There were no racial/ethnic differences in Classes 1 and 2, while NHW women reported significantly lower PCS scores than AA women in Classes 3 and 4. The mean MCS was 51.4 and differed by comorbidity burden and race/ethnicity (Pinteraction < 0.001). There was no racial/ethnic difference in Class 3; however, AA women reported lower MCS scores than Asian/Pacific Islander women in Class 1, and AA and Hispanic women reported lower MCS scores than NHW women in Classes 2 and 4. CONCLUSION: Comorbidity burden negatively affected HRQOL but differentially for racial/ethnic groups. As the comorbidity burden increases, NHW women are more concerned with physical HRQOL, while AA and Hispanic women are more concerned with mental HRQOL.

Long non-coding RNA TLR8-AS1 induces preeclampsia through increasing TLR8/STAT1 axis.

OBJECTIVE: Our current study tried to assay the role of long noncoding RNAs (lncRNAs) TLR8-AS1 in regulating preeclampsia. METHODS: TLR8-AS1 expression was examined in the clinical placental tissues of preeclampsia patients and the trophoblast cells induced by lipopolysaccharide (LPS). Then, different lentivirus was infected into trophoblast cells to study the role of TLR8-AS1 in cell functions. Furthermore, interactions among TLR8-AS1, signal transducer and activator of transcription 1 (STAT1) and toll-like receptor 8 (TLR8) were determined. A rat model of preeclampsia induced by N(omega)-nitro-L-arginine methyl ester was developed to validate the in-vitro findings. RESULTS: High expression of TLR8-AS1 was detected in placental tissues of preeclampsia patients and LPS-induced trophoblast cells. In addition, overexpression of TLR8-AS1 arrested the proliferation, migration and invasion of trophoblast cells, which was related to the upregulation of TLR8 expression. Mechanistically, TLR8-AS1 recruited STAT1 to bind to the TLR8 promoter region, and thus promoted the transcription of TLR8. Meanwhile, overexpression of TLR8-AS1 was shown to aggravate preeclampsia by elevating TLR8 in vivo . CONCLUSION: Our study confirmed that TLR8-AS1 aggravated the progression of preeclampsia through increasing the expression of STAT1 and TLR8.

MR Finding of Extraventricular Neurocytoma.

OBJECTIVE: To determine the MR (magnetic resonance), pathologic, and clinical findings of extraventricular neurocytoma (EVN). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Radiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China, from January 2020 to March 2022. METHODOLOGY: The MR radiological and pathological data of 11 patients with EVNs proved by histopathology after surgery were analysed retrospectively. Above-mentioned features were studied. RESULTS: There were 5 men and 6 women, ages ranging from 16 to 56 years. Seven cases (63.6%) were located in the cerebral hemisphere, three cases (27.3%) in the cerebellar hemisphere, and one case in cervical cord. Ten cases (91.0%) were cystic-solid, and one case was predominantly solid with small cystic components. Six cases (54.5%) had mild peritumoural ooedema. The signal was isointense (8/11, 72.7%) or hypointense (3/11, 27.3%) on T1WI, and isointense (1/11, 9.1%) or hyperintense (10/11, 90.9%) on T2WI; all cases showed hyperintense on FLAIR and restricted diffusion on DWI. Haemorrhage was found in two cases (18.2%) and flow-void was found in one case (9.1%). All the tumours demonstrated contrast enhancement. CONCLUSION: An accurate diagnosis of EVN is difficult to be made preoperatively. It should be considered when a solid-cystic tumour with the solid part showing isointense on T1WI, hyperintense on FLAIR with mild to moderate enhancement especially restricted diffusion on DWI sequence in patients aged 20-30. When the radiologic manifestations are atypical, more aggressive treatment should be chosen. KEY WORDS: Neurocytoma, Extraventricular, Clinical, Imaging characteristics, MRI.

Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

Imaging features of sentinel lymph node mapped by multidetector-row computed tomography lymphography in predicting axillary lymph node metastasis.

INTRODUCTION: Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. METHODS: 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. RESULTS: Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58-91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773-0.939, P < 0.001), respectively. CONCLUSION: ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.

CT-guided core needle biopsy of the lung in patients with primary malignancy suspected of lung metastasis: 5-year experience from a single institution.

PURPOSE: We aimed to evaluate the diagnostic accuracy and safety profile of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) in patients with primary malignancy suspected of lung metastasis and assess possible factors associated with nondiagnostic results. METHODS: All PTNBs with core needle performed in our hospital from January 2014 to January 2019 were retrospectively reviewed. Overall, 108 cases were found to have a history of primary malignancy with suspected lung metastasis. Patient demographics, lesion characteristics, procedure techniques and complications were evaluated as predictors of overall diagnosis, final diagnosis of lung metastasis, and nondiagnostic results. Statistical analysis was performed using univariate analysis. RESULTS: The overall diagnostic accuracy of PTNB was 83.3%. Lung metastasis was found in 52.8% of PTNBs (57 of 108) and nondiagnostic results were present in 27.6% (18 of 108). Of the 18 cases with nondiagnostic results, 11 cases had a final diagnosis of lung metastasis (61.1%), yielding PTNB a sensitivity of 83.8% and specificity of 100% for the detection of lung metastasis. Smaller lesion size (p = 0.014), pneumothorax (p = 0.026), and hemoptysis (p = 0.014) were significantly associated with overall nondiagnostic results. Similarly, smaller lesion size (p = 0.047), pneumothorax (p = 0.019), high-grade pulmonary hemorrhage (p = 0.019), and hemoptysis (p = 0.012) were significantly correlated with unsuccessful biopsies in the diagnosis of lung metastasis. CONCLUSION: CT-guided core needle biopsy of the lung in patients with primary malignancy suspected of lung metastasis has a high diagnostic accuracy with acceptable complication rates. Small lesion size, pneumothorax, high-grade pulmonary hemorrhage, and hemoptysis are significantly associated with nondiagnostic results in the final diagnosis of lung metastasis. Repeat biopsy and clinical/radiological follow-up should be considered in cancer patients with nondiagnostic results due to the high probability of lung metastasis.

The Effect of SLC2A3 Expression on Cisplatin Resistance of Colorectal Cancer Cells.

Background: To study the molecular mechanism of cisplatin chemotherapy resistance in colorectal cancer cells and to explore the effect of miRNA in regulating the expression of glucose transporter 3 (SLC2A3) and the proliferation and migration of colon cancer cells. Methods: All samples were obtained from the People's Hospital of Wuhai, Wuhai, China between June 2019 and June 2020. Real-time quantitative PCR (qRT-PCR) was carried out to check the expression of miR-103a in these cell lines. Western blotting and Luciferase reporter gene detection confirmed the regulation of the miR-103a/SLC2A3 axis. Western blotting detected the activation of SLC2A3, caspased-9 and -3. Results: The expression of SLC2A3 protein in colon cancer cell lines was significantly higher than that of normal colon cancer cells, while the expression of SLC2A3 miRNA showed no significant difference (P<0.05). Then, through clone formation analysis, SLC2A3 was closely related to the proliferation of human colon cancer cells. Functional recovery experiments showed that increasing the expression of miR-103a could reverse the abnormal proliferation caused by overexpression of SLC2A3. Conclusion: Overall, miR-103a can inhibit the proliferation of human colon cancer cells by targeting SLC2A3, and this result will provide a potential target for the treatment of colon cancer.

Evaluation of Diet Quality Among American Adult Cancer Survivors: Results From 2005-2016 National Health and Nutrition Examination Survey.

BACKGROUND: Diet quality among adult cancer survivors is low, and there is minimal information on the Healthy Eating Index (HEI)-2015 score, a measure of diet quality and adherence to the 2015-2020 Dietary Guidelines for Americans, in this population. OBJECTIVE: This study aimed to examine HEI-2015 total and component scores and associated factors among adult cancer survivors. Also, this study examined which dietary components needed the most change to improve diet quality in this population. DESIGN: The National Health and Nutrition Examination Survey (NHANES) is an ongoing nationally representative population-based cross-sectional study that is conducted annually. PARTICIPANTS/SETTING: In all, 1971 adults with a self-reported cancer diagnosis in their lifetime (both individuals with cancer currently and those that are cancer-free) from NHANES 2005-2016 were included in this study. MAIN OUTCOME MEASURES: HEI-2015 total and 13 component scores were calculated using the simple scoring algorithm method from the average of 2 24-hour recalls. STATISTICAL ANALYSES: The associations of the HEI-2015 total score with sociodemographic, lifestyle, and health-related factors were analyzed using the least square means comparisons. A multivariable survey regression model was used to identify associations with the HEI-2015 total score after adjustment for potential confounders. The 13 component scores were also compared by participant characteristics to identify target food groups for subgroup-specific nutrition intervention. RESULTS: The average HEI-2015 total score was 55.6 (95% confidence interval = 54.8-56.4). Factors associated with the HEI-2015 total score included age, race/ethnicity, education, smoking status, body mass index, and oral health status. Overall, poor adherence to the 2015-2020 Dietary Guidelines for Americans was found for most HEI-2015 components, with Whole Grains, Greens and Beans, Sodium, and Fatty Acids components having less than 50% of the maximum possible scores. CONCLUSIONS: Results indicate poor diet quality among American adult cancer survivors, with significant disparities observed across sociodemographic and lifestyle factors, particularly education levels, body mass index, and smoking status. Nutrition interventions for cancer survivors should consider focusing on improving diet quality by increasing intakes of whole grains and greens and beans, lowering sodium consumption, and achieving a healthy balance of fatty acids (ie, a favorable ratio of unsaturated fats to saturated fats).

Halofuginone inhibits tumorigenic progression of 5-FU-resistant human colorectal cancer HCT-15/FU cells by targeting miR-132-3p in vitro.

5-Fluorouracil (5-FU)-based chemotherapy is the first-line option for patients with advanced colorectal cancer (CRC). However, the development of chemoresistance is the primary cause of treatment failure. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been demonstrated to exert strong anti-proliferative effects. However, to the best of our knowledge, whether HF inhibits the progression of 5-FU-resistant human CRC HCT-15/FU cells, and the underlying mechanisms, remain unknown. In the present study, the effects of HF on HCT-15/FU cells were assessed in vitro. The results revealed that HF inhibited HCT-15/FU cell viability as demonstrated by the MTT and colony formation assays. Following treatment of HCT-15/FU cells with HF, the migratory and invasive capacities of the cells were significantly decreased. MicroRNA (miRNA/miR)-sequencing data, subsequent miRNA trend analysis and reverse transcription-quantitative PCR all demonstrated that miR-132-3p expression was increased following treatment with HF in a dose-dependent manner. Western blot analysis indicated that following treatment with HF, the expression levels of proteins associated with proliferation, invasion and metastasis in cells were markedly downregulated. These results suggested that HF inhibited the proliferation, invasion and migration of HCT-15/FU cells by upregulating the expression levels of miR-132-3p. Therefore, miR-132-3p may serve as a molecular marker, which may be used to predict CRC resistance to 5-FU, and HF may serve as a novel clinical treatment for 5-FU-resistant CRC.

Risk factors associated with pulmonary hemorrhage and hemoptysis following percutaneous CT-guided transthoracic lung core needle biopsy: a retrospective study of 1,090 cases.

BACKGROUND: Pulmonary hemorrhage and hemoptysis are the second-most common and potentially life-threatening complications after pneumothorax following percutaneous computed tomography-guided transthoracic lung biopsy (PCTLB). Preventing hemorrhagic complications after PCTLB requires an accurate estimation of risk factors. This study investigated the risk factors associated with pulmonary hemorrhage and hemoptysis following PCTLB, and whether the ratio of main pulmonary artery diameter (mPAD) to ascending aorta diameter (mPAD/AAD ratio) is a risk factor. METHODS: We retrospectively analyzed 1,090 cases of PCTLB obtained from 1,050 patients using a core needle. The risk factors for overall pulmonary hemorrhage, higher-grade pulmonary hemorrhage, and hemoptysis were evaluated by multivariate analysis of patient characteristics, computed tomography (CT) imaging data including pulmonary artery diameter (mPAD) to ascending aorta diameter (mPAD/AAD) ratio, technical variables related to the biopsy, and pathologic findings. RESULTS: Pulmonary hemorrhage occurred in 31.38% (342/1,090) of PCTLB cases, including lower-grade (24.4%, 266/1,090) and higher-grade hemorrhage (6.97%, 76/1,090). The incidence of hemoptysis was 3.03% (33/1,090). Multivariate analysis revealed significant associations between overall pulmonary hemorrhage and lesion location in the lower lobe, subsolid and smaller lesions, greater lesion depth, and lung metastases. For higher-grade pulmonary hemorrhage, an mPAD/AAD ratio >1, smaller lesions, greater lesion depth, emphysema, and lung metastases were risk factors. Risk factors for hemoptysis were history of hypertension and lower- and higher-grade pulmonary hemorrhage. CONCLUSIONS: Pulmonary artery enlargement detected by CT (mPAD/AAD ratio >1) is independently associated with higher-grade pulmonary hemorrhage following PCTLB.

Comparison of the therapeutic effects of adipose­derived and bone marrow mesenchymal stem cells on erectile dysfunction in diabetic rats.

The aim of the present study was to compare the effects of adipose­derived mesenchymal stem cell (ADSC) and bone marrow mesenchymal stem cell (BMSC) transplantation into the corpora cavernosa of diabetic rats with erectile function. ADSCs and BMSCs were isolated and identified by flow cytometry. Rats with streptozocin­induced diabetes were screened using apomorphine to obtain a rat model of diabetic erectile dysfunction, followed by transplantation of ADSCs and BMSCs into the corpora cavernosa. Two weeks later, the rats were again injected with apomorphine, the intracavernous pressure (ICP) and mean arterial pressure (MAP) of the penile tissue were measured, and the corpus cavernosum tissues were harvested. Angiogenic endothelial nitric oxide synthase (eNOS) expression was detected by western blotting and immunofluorescence analysis. The blood vessels in the corpus cavernosum were observed following hematoxylin and eosin (H&E) staining, and the expression of collagen was detected by Sirius Red staining. The cellular ultrastructure was examined by transmission electron microscopy. Intracavernous injection of ADSCs significantly increased ICP and ICP/MAP. Western blotting and immunofluorescence results revealed that ADSC treatment improved the expression of eNOS in the penile tissue of diabetic rats. The H&E staining results demonstrated that ADSC treatment promoted revascularization of the corpus cavernosum, and the results of Sirius Red staining revealed that ADSC treatment reduced penile collagen in diabetic rats. Transmission electron microscopy examination revealed that the ultrastructure of the tissues in the ADSC­treated group was more complete compared with that in the untreated diabetic model group. In conclusion, ADSCs were found to be more effective compared with BMSCs in treating diabetes­related erectile dysfunction.

Endoscopic ultrasonography-guided poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) thermogel tunnel creation for natural orifice transluminal endoscopic surgery in porcine model.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is a minimal invasive treatment. However, tissue dissection under endoscopy is still challenging due to the flexibility of endoscopy body and there is still no effective method for establishing a tunnel towards the targeted area. We previously showed that a new kind of thermogel could be submucosallly injected and served as a cushion for endoscopic dissection. Thus, in this study we investigated the feasibility and safety of tunnel creation using poly (lactic acid-co-glycolic acid)-poly (ethylene glycol)-poly (lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel for NOTES in a porcine model. METHODS: We prepared an injectable thermogel composed of PLGA-PEG-PLGA triblock copolymers which exhibited a low-viscous sol at room temperature and spontaneously transformed into a no-flowing gel at body temperature. This thermogel was used in NOTES in pigs. The success rate and adverse events were observed. RESULTS: The PLGA-PEG-PLGA thermogels were successfully injected to the targeted areas under the guide of endoscopic ultrasonography and the tunnels were created by sucking the gel during NOTES as the endoscopy went forwards in all the three animals. The necropsy of the pigs showed no evidence of iatrogenic injury. No serious bleeding and perforation was observed. The results demonstrated that thermogel injection and tunnel creation by suction during NOTES were feasible, which simplified the procedure of tissue dissection and developed a new method of identifying the targeted area for surgical interventions without causing severe tissue damage. CONCLUSION: The application of thermogel for tunnel creation in NOTES could optimize current procedures and may have a promising prospect in clinical application.

In Vitro Expression of Cytokeratin 19 in Adipose-Derived Stem Cells Is Induced by Epidermal Growth Factor.

BACKGROUND Cytokeratin 19 (CK19) is a typical epithelial marker. In this study, we determined whether epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) could enhance CK19 expression in adipose-derived stem cells (ADSCs), thereby inducing the differentiation of ADSCs into epithelial-like cells. MATERIAL AND METHODS ADSCs were isolated from perinephric fat, and the expression of CD29, CD90, and CD105 was confirmed. Following isolation, ADSCs were cultured in static medium or medium containing EGF or bFGF. RESULTS Flow cytometry revealed that EGF and bFGF could alter mesenchymal stem cell markers as well as the cell cycle of ADSCs. Western blotting and immunofluorescence revealed that after 14 days, EGF treatment enhanced the expression of CK19 in ADSCs. CONCLUSIONS Our findings offer important insight for the clinical use of ADSCs in the generation of epithelial-like cells in the future.