Salpingectomy for ectopic pregnancy reduces ovarian cancer risk-a nationwide study.

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy.

Possible overdiagnosis of early-stage lung adenocarcinoma among never-smokers in Taiwan.

10-year survival for never-smokers with >1 cm but ≤3 cm AIS/BAC/MIA was not inferior to that of the matched referents, pointing to possible overdiagnosis. Clinicians might consider adhering to Lung-RADS and watchful waiting for these non-solid nodules. https://bit.ly/41U6kxs.

Losses of lifetime employment duration and productivity for patients with different subtypes and stages of lung cancer.

BACKGROUND: How different subtypes and stages of lung cancer affect morbidity- and mortality-associated productivity have not been investigated. This study quantified the losses of lifetime employment duration and productivity among patients with various subtypes and stages of lung cancer. METHODS: We identified nationwide lung cancer patients diagnosed at the ages of 50-64 between 2011 and 2019. Monthly survival probabilities were weighted by monthly employed-to-population ratios and working salaries to estimate lifetime employment duration and productivity. We compared lifetime employment duration and productivity of patients with those of the age-, sex-, calendar year-matched general population for losses of lifetime employment duration and productivity, which were multiplied by pathology and stage shifts based on the first-round screening of Taiwan Lung Cancer Screening in Never Smoker Trial (TALENT) to calculate the savings of lifetime employment duration and productivity. RESULTS: Lung cancer patients had shorter survival and employment duration than the referents. Patients with lung cancers other than adenocarcinoma experienced greater losses of lifetime employment duration and productivity as compared to adenocarcinoma patients. Applying the estimations of never-smoking patients to 100 lung cancer patients with pathology and stage shifts based on the TALENT, the savings of lifetime employment duration and productivity were 132.2 (95% prediction interval: 116.2-147.4) years and 3353 (95% prediction interval: 2914-3802) thousand US dollars, respectively. CONCLUSIONS: Early diagnosis of lung cancer would save the losses of employment duration and lifetime productivity. Future evaluation of the cost-effectiveness of lung cancer screening could consider incorporating these societal impacts.

Estimation of disability free life expectancy in non small cell lung cancer based on real world data.

To quantify the societal impact of disability in patients with non-small cell lung cancer (NSCLC), this study estimated the disability-free life expectancy (DFLE), loss-of-DFLE and explored their associations with quality-adjusted life expectancy (QALE) and loss-of-QALE. We interlinked national databases and applied a rolling-over algorithm to estimate the lifetime survival function for patients with NSCLC. Using the EuroQOL-5 Dimension (EQ-5D) and Barthel index (BI), we repeatedly measured the quality-of-life and disability functions of NSCLC patients who visited our hospital from 2011 to 2020. Age-, sex-matched referents were simulated from lifetables of the same calendar year of diagnosis. We categorized BI scores ≤ 70 as in need of long-term care and constructed linear mixed models to estimate the utility values and disability scores. We collected 960 cases and 3088 measurements. The proportions of measurements without disability at age 50-64 and in stage I-IIIa, 50-64 and stage IIIb-IV, 65-89 and stage I-IIIa and 65-89 and stage IIIb-IV were 97.3%, 89.3%, 94.8%,78.3%, corresponding to DFLEs of 15.3, 2.4, 6.8, 1.2 years and losses-of-DFLE of 8.1, 20.7, 4.0, 8.6 years, respectively, indicating that advanced stage had a stronger effect than old age. Survivors in advanced stages showed increased demands for assistance in almost all subitems. The DFLEs seemed to be approximate to the QALEs and the latter were shorter than the former due to discomfort and depression. From a societal perspective, future health technology assessment should consider the impact of lifetime duration of functional disability. Early diagnosis of NSCLC may decrease the burden of long-term care.

Endometrial Cancer Detection Using a Cervical DNA Methylation Assay (MPap) in Women with Abnormal Uterine Bleeding: A Multicenter Hospital-Based Validation Study.

BACKGROUND: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. METHODS: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. RESULTS: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. CONCLUSIONS: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

PM2.5 exposure and risk of lung adenocarcinoma in women of Taiwan: A case-control study with density sampling.

BACKGROUND AND OBJECTIVE: The prevalence of smoking among women in Taiwan is <5%, but the incidence of lung cancer remains high. This study determined the association between PM2.5 (fine particulate matter with an aerodynamic diameter of ≤2.5 µm) exposure and lung cancer among women in Taiwan. METHODS: In total, 21,301 female lung cancer cases nationwide were newly diagnosed between 2012 and 2017. Each case was age-, sex- and calendar year-matched with four controls randomly selected from the general population. Allowing a latent period of 5 years, we estimated the PM2.5 and nitrogen dioxide (NO2 ) exposures for each individual according to the residential changes from 2000. We adopted self-reported smoking statuses for the cases, while those of controls were estimated using annual surveys in each residential county. We performed multiple logistic regression analyses to examine the associations between PM2.5 and NO2 exposures and incident lung cancer cases. RESULTS: The ORs of lung adenocarcinoma for the third (30.5-35.1 µg/m3 ), fourth (35.1-39.3 µg/m3 ) and fifth PM2.5 exposure quintiles (39.3-48.1 µg/m3 ) relative to the first quintile were 1.10 (95% CI: 1.04-1.16), 1.12 (95% CI: 1.06-1.19) and 1.10 (95% CI: 1.04-1.16), respectively, after adjusting for smoking, residence and comorbidities. A dose-response relationship (p = 0.004) was found. The associations persisted with a 10-year latency and were not detected for small-cell and squamous cell carcinoma after control for smoking. We did not observe a similar effect for NO2 exposure. CONCLUSION: Residential PM2.5 exposure higher than 30 µg/m3 was associated with an increased risk of lung adenocarcinoma in women of Taiwan.

Acute Mesenteric Vein Thrombosis in a Pregnant Patient at 10 Weeks Gestation: A Case Report.

Acute abdominal pain during pregnancy is challenging, both from a diagnostic and management perspective. A non-localized, persistent pain out of proportion to physical examination is a sign that advanced imaging may be necessary. Mesenteric venous thrombosis in a pregnant patient is extremely rare, but if diagnosis is delayed, can be potentially fatal to both the mother and the fetus. We present here a pregnant patient in the tenth week of gestation with classic clinical manifestations of mesenteric vein thrombosis and the corresponding findings on magnetic resonance imaging (MRI) and computed tomography (CT).

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Ovarian cancer detection by DNA methylation in cervical scrapings.

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological cancer, worldwide, largely due to its vague and nonspecific early stage symptoms, resulting in most tumors being found at advanced stages. Moreover, due to its relative rarity, there are currently no satisfactory methods for OC screening, which remains a controversial and cost-prohibitive issue. Here, we demonstrate that Papanicolaou test (Pap test) cervical scrapings, instead of blood, can reveal genetic/epigenetic information for OC detection, using specific and sensitive DNA methylation biomarkers. RESULTS: We analyzed the methylomes of tissues (50 OC tissues versus 6 normal ovarian epithelia) and cervical scrapings (5 OC patients versus 10 normal controls), and integrated public methylomic datasets, including 79 OC tissues and 6 normal tubal epithelia. Differentially methylated genes were further classified by unsupervised hierarchical clustering, and each candidate biomarker gene was verified in both OC tissues and cervical scrapings by either quantitative methylation-specific polymerase chain reaction (qMSP) or bisulfite pyrosequencing. A risk-score by logistic regression was generated for clinical application. One hundred fifty-one genes were classified into four clusters, and nine candidate hypermethylated genes from these four clusters were selected. Among these, four genes fulfilled our selection criteria and were validated in training and testing set, respectively. The OC detection accuracy was demonstrated by area under the receiver operating characteristic curves (AUCs) in 0.80-0.83 of AMPD3, 0.79-0.85 of AOX1, 0.78-0.88 of NRN1, and 0.82-0.85 of TBX15. From this, we found OC-risk score, equation generated by logistic regression in training set and validated an OC-associated panel comprising AMPD3, NRN1, and TBX15, reaching a sensitivity of 81%, specificity of 84%, and OC detection accuracy of 0.91 (95% CI, 0.82-1) in testing set. CONCLUSIONS: Ovarian cancer detection from cervical scrapings is feasible, using particularly promising epigenetic biomarkers such as AMPD3/NRN1/TBX15. Further validation is warranted.

Combined genetic mutations and DNA-methylated genes as biomarkers for endometrial cancer detection from cervical scrapings.

BACKGROUND: Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promising biomarker. We assessed the usefulness of combining genetic and epigenetic biomarkers from cervical scrapings to detect endometrial carcinomas. METHODS: We performed a retrospective case-control study of 96 consecutive cervical scrapings from patients with abnormal uterine bleeding who underwent surgery for diagnostic evaluation. Thirty and 16 cases were diagnosed with type I and type II endometrial cancers, respectively. The remaining non-cancer cases included normal endometrium (n = 12), benign uterine lesions (n = 20), and endometrial hyperplasia (n = 18). Quantitative methylation-specific PCR and mass spectrometry were used for DNA methylation and genetic mutation analysis. Logistic regression was used to evaluate the clinical performance of these candidate biomarkers. RESULTS: We tested the effectiveness of the methylation status of four genes (BHLHE22, CDO1, TBX5, and HAND2) in endometrial cancer detection. The area under the receiver operating characteristic curves ranged from 0.703 to 0.878, and panels of hypermethylated BHLHE22/CDO1/HAND2 (87.0% sensitivity and 86.0% specificity) and BHLHE22/CDO1/TBX5 (89.1% sensitivity and 80.0% specificity) showed significant differences and could distinguish benign from malignant endometrial lesions. The sensitivity and specificity in endometrial cancer detection for BHLHE22/CDO1 were 84.8% and 88.0%, respectively. Both type I and II endometrial carcinomas could be detected using a BHLHE22/CDO1-based methylation profile, suggesting that they may have common epigenomes. Moreover, PTEN and TP53 mutations were found in 63.3% of type I and 93.6% of type II endometrial cancers. Unexpectedly, PTEN and TP53 mutations were commonly found in cervical scrapings of the normal endometrium (25% and 33.3%, respectively) and in cases with benign uterine lesions (10% and 50%, respectively). Finally, combinations of any one mutation of PTEN and TP53 mutations had a sensitivity of 91.3%, but a specificity of only 42.0%. CONCLUSIONS: Adding PTEN/TP53 mutation testing to BHLHE22/CDO1-based methylation testing did not improve the detection of endometrial cancer.

Paired Box-1 (PAX1) Activates Multiple Phosphatases and Inhibits Kinase Cascades in Cervical Cancer.

DNA methylation alteration, such as global hypomethylation and localized hypermethylation, within the promoters of tumor suppressor genes, is an important risk factor in cervical cancer. The potential use of DNA methylation detection, in cervical cancer screening or triage of mildly abnormal cytology, has recently been demonstrated. In particular, PAX1 DNA methylation testing was approved as an adjunct to cytology, in Taiwan, and is now undergoing registration trials in China. However, the function of PAX1 in cancer biology remains largely unknown. Here, we show that PAX1 inhibits malignant phenotypes upon oncogenic stress. Specifically, PAX1 expression inhibited the phosphorylation of multiple kinases, after challenges with oncogenic growth factors such as EGF and IL-6. Analogously, PAX1 activated a panel of phosphatases, including DUSP1, 5, and 6, and inhibited EGF/MAPK signaling. PAX1 also interacted with SET1B, increasing histone H3K4 methylation and DNA demethylation of numerous phosphatase-encoding genes. Furthermore, hypermethylated PAX1 associated with poor prognosis in cervical cancer. Taken together, this study reveals, for the first time, the functional relevance of PAX1 in cancer biology, and further supports the prospect of targeting multifold oncogenic kinase cascades, which jointly contribute to multiresistance, via epigenetic reactivation of PAX1.

TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions.

DNA hypermethylation is a driving force in carcinogenesis. However, the role of active DNA hypomethylation in cancer remains largely unknown. This process, facilitated by ten-eleven translocation methylcytosine dioxygenase 1 (TET1), which oxidizes 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5hmC), has never been studied in cervical cancer. Here, we found that TET1 and 5hmC correlative increases from normal cervix to Low-grade squamous intraepithelial lesion (LSIL), maximizing in High-grade squamous intraepithelial lesion (HSIL), and decreasing in invasive cancer. Full-length HPV-immortalized HSIL cells demonstrated higher TET1/5hmC levels, and stemness properties, compared to invasive cancer cells. TET1 silencing promoted the epithelial-mesenchymal transition (EMT), to transform precancerous cells in vivo. TET1 increased 5hmC in the ZEB1 and VIM promoters, surprisingly, silencing both genes. TET1 interaction with the histone modifiers, LSD1 and EZH2, on the ZEB1 promoter, resulted in gene silencing, via loss of histone H3K4 trimethylation, and gain of histone H3K27 trimethylation. Taken together, TET1 promotes stemness properties, and inhibits EMT, in HSIL cells, through 5hmC-dependent and -independent mechanisms.

Presurgical Identification of Uterine Smooth Muscle Malignancies through the Characteristic FDG Uptake Pattern on PET Scans.

The unidentified presence of uterine smooth muscle malignancies poses a tremendous risk in women planning surgery for presumed benign leiomyomas. We sought to investigate whether preoperative FDG PET may be useful to identify leiomyosarcomas (LMS) and smooth muscle tumors of uncertain malignant potential (STUMP). Methods. We investigated patients with rapidly growing uterine masses which were suspected of being malignant on ultrasound or MRI. Among the 21 patients who underwent FDG PET, we identified 7 LMS, 1 STUMP, and 13 leiomyomas. PET-derived parameters and FDG uptake patterns were analyzed retrospectively. Results. The SUVmax values of LMS/STUMP (range: 3.7-11.8) were significantly higher than those observed in leiomyomas (range: 2.0-9.4; P=0.003) despite a significant overlap. The metabolic tumor/necrosis ratio was significantly higher in LMS/STUMP than in leiomyomas (P < 0.001), with no significant intergroup overlaps. All LMS/STUMP revealed a characteristic pattern of FDG uptake, identifying a specific "hollow ball" sign (corresponding to areas of coagulative tumor necrosis). In contrast, this sign was invariably absent in patients with leiomyomas. Conclusion. The characteristic FDG uptake pattern instead of SUV on PET images allows identifying LMS/STUMP in patients with rapidly growing uterine masses, avoiding the deleterious consequences of regular surgery for presumed benign leiomyomas.

Predictors of hospital mortality in adult trauma patients receiving extracorporeal membrane oxygenation for advanced life support: a retrospective cohort study.

BACKGROUND: Using extracorporeal membrane oxygenation (ECMO) to provide advanced life support in adult trauma patients remains a controversial issue now. The study was aimed at identifying the independent predictors of hospital mortality in adult trauma patients receiving ECMO for advanced cardiopulmonary dysfunctions. METHODS: This retrospective study enrolled 36 adult trauma patients receiving ECMO due to advanced shock or respiratory failure in a level I trauma center between August 2006 and October 2014. Variables collected for analysis were demographics, serum biomarkers, characteristics of trauma, injury severity score (ISS), damage-control interventions, indications of ECMO, and associated complications. The outcomes were hospital mortality and hemorrhage on ECMO. The multivariate logistic regression method was used to identify the independent prognostic predictors for the outcomes. RESULTS: The medians of age and ISS were 36 (27-49) years and 29 (19-45). Twenty-three patients received damage-control interventions before ECMO. Among the 36 trauma patients, 14 received ECMO due to shock and 22 for respiratory failure. The complications of ECMO are major hemorrhages (n = 12), acute renal failure requiring hemodialysis (n = 10), and major brain events (n = 7). There were 15 patients died in hospital, and 9 of them were in the shock group. CONCLUSIONS: The severity of trauma and the type of cardiopulmonary dysfunction significantly affected the outcomes of ECMO used for sustaining patients with post-traumatic cardiopulmonary dysfunction. Hemorrhage on ECMO remained a concern while the device was required soon after trauma, although a heparin-minimized protocol was adopted. TRIAL REGISTRATION: This study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601610B0) on December 12, 2016. All of the data were extracted from December 14, 2016, to March 31, 2017.

The impacts of baseline ventilator parameters on hospital mortality in acute respiratory distress syndrome treated with venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS. METHODS: This retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality. RESULTS: The causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079-1.565, p < 0.001) was found to be the only baseline ventilator parameter that independently affected the hospital mortality in these ECMO-treated patients. CONCLUSION: Since the duration of MV before ECMO institution was strongly correlated to the outcome of adult respiratory ECMO, medical centers are suggested to find a suitable prognosticating tool to determine the starting point of respiratory ECMO among their candidates with different duration of MV. TRIAL REGISTRATION: This study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601483B0 ) on November 23, 2016. All of the data were extracted from December 1, 2016, to January 31, 2017.

Is There a Preinterventional Mechanical Ventilation Time Limit for Candidates of Adult Respiratory Extracorporeal Membrane Oxygenation.

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a useful life support in severe acute respiratory distress syndrome (ARDS). Although prolonged mechanical ventilation (MV) before institution of ECMO is known to be a poor prognostic factor for outcomes of VV-ECMO, a reasonable deadline for this period has not been defined yet. To discover the answer, we reviewed a 9 year institutional experience of adult respiratory ECMO in VV configuration and investigate the relationship between the MV time before ECMO and in-hospital mortality. This retrospective study included 129 adult patients receiving VV-ECMO for ARDS in a single institution from 2007 to 2016. Important demographic and clinical data before ECMO intervention were collected for analyses of in-hospital mortality. The MV time before ECMO independently predicted hospital death in adult respiratory ECMO here. While compared to the patients receiving MV for 7 days or less, the patients receiving MV for more than 7 days before ECMO showed a higher in-hospital mortality rate (77% vs. 38%, p < 0.001). They also experienced a more significant deterioration in respiratory function during MV before the institution of ECMO. Therefore, from the clinical observation, we thought that a 7 day period might be an acceptable limit on MV time before institution of VV-ECMO. Integrating other respiratory parameters into the current PaO2/FiO2 (PF) ratio-based inclusion criteria of adult respiratory ECMO might be helpful to reduce the risk of prolonged MV in selected patients.

Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings.

PURPOSE: Endometrial cancer is a common gynecologic cancer whose incidence is increasing annually worldwide. Current methods to detect endometrial cancer are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, but limited use for detecting endometrial cancer. EXPERIMENTAL DESIGN: We analyzed two methylomics databases of endometrioid-type endometrial cancer. Using nonnegative matrix factorization algorithm clustered the methylation pattern and reduced the candidate genes. We verified in pools DNA from endometrial cancer tissues and cervical scrapings, and validated in 146 cervical scrapings from patients with endometrioid-type endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n = 56) using quantitative methylation-specific PCR (QMSP). The logistic regression was used to evaluate the performance of methylation signal and gene combination. RESULTS: We filtered out 180 methylated genes, which constituted four consensus clusters. Serial testing of tissues and cervical scrapings detected 14 genes that are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4, had the best performance. Individual genes were sensitivity of 83.7%-96.0% and specificity of 78.7%-96.0%. A panel comprising any two of the three hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were also applied to cervical scrapings of type II endometrial cancer patients, and detected in 13 of 14 patients. CONCLUSIONS: This study demonstrates the potential use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of cervical scrapings. Clin Cancer Res; 23(1); 263-72. ©2016 AACR.

Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in Adults: Prognostic Factors for Outcomes.

Despite a therapeutic option for severe acute respiratory distress syndrome (ARDS), the survival benefit of venovenous extracorporeal membrane oxygenation (VV-ECMO) is still controversial in adults. This study was aimed at investigating the prognostic factors for ECMO-treated ARDS in adult patients.From 2012 to 2015, 49 patients (median age: 57 years) received VV-ECMO in our institution and were included in this retrospective study. The indication of VV-ECMO was a severe hypoxemia (PaO2/FiO2 ratio <70 mmHg) under mechanical ventilation (MV) with a peak inspiratory pressure (PIP) >35 cmH2O and a FiO2 >0.8. To decrease the impact of pulmonary injuries associated with the high-pressure ventilation, the settings of MV on VV-ECMO were downgraded according to our protocol. Outcomes of this study were death on VV-ECMO and death in hospital. Important demographic and clinical data during the treatment were collected for outcome analyses.All patients experienced significant improvements in arterial oxygenation on VV-ECMO. Twenty-four hours after initiation of VV-ECMO, the median PaO2/FiO2 ratio increased from 58 to 172 mmHg (P < 0.001) and the median SaO2 increased from 86% to 97% (P < 0.001). In the meantime, the MV settings were also effectively downgraded. The median PIP decreased from 35 to 29 cmH2O (P < 0.001) and the median tidal volume decreased from 7 to 5 ml/kg/min (P < 0.001). Twelve patients died during the treatment of VV-ECMO and 21 patients died before hospital discharge. Among all of the pre-ECMO variables, the pre-ECMO pulmonary dynamic compliance (PCdyn) <20 mL/cmH2O was identified to be the prognostic factor of death on VV-ECMO (odds ratio [OR]: 6, 95% confidence interval [CI]: 1-35, P = 0.03), and the pre-ECMO duration of MV >90 hours was the prognostic factor of death before hospital discharge (OR: 7, 95% CI: 1-29, P = 0.01).VV-ECMO was a useful salvage therapy for severe ARDS in adults. However, the value of PCdyn and the duration of MV before intervention with VV-ECMO may significantly affect the patients' outcomes.