Evaluating major anthropogenic VOC emission sources in densely populated Vietnamese cities.

Volatile organic compounds (VOCs) play an important role in urban air pollution, both as primary pollutants and through their contribution to the formation of secondary pollutants, such as tropospheric ozone and secondary organic aerosols. In this study, more than 30 VOC species were continuously monitored in the two most populous cities in Vietnam, namely Ho Chi Minh City (HCMC, September-October 2018 and March 2019) and Hanoi (March 2019). In parallel with ambient VOC sampling, grab sampling was used to target the most prevalent regional-specific emission sources and estimate their emission factors (EFs). Emission ratios (ERs) obtained from ambient sampling were compared between Vietnamese cities and other cities across the globe. No significant differences were observed between HCMC and Hanoi, suggesting the presence of similar sources. Moreover, a good global agreement was obtained in the spatial comparison within a factor of 2, with greater ER for aromatics and pentanes obtained in the Vietnamese cities. The detailed analysis of sources included the evaluation of EF from passenger cars, buses, trucks, motorcycles, 3-wheeled motorcycles, waste burning, and coal-burning emissions. Our comparisons between ambient and near-source concentration profiles show that road transport sources are the main contributors to VOC concentrations in Vietnamese cities. VOC emissions were calculated from measured EF and consumption data available in Hanoi and compared with those estimated by a global emission inventory (EDGAR v4.3.2). The total VOC emissions from the road transport sector estimated by the inventory do not agree with those calculated from our observations which showed higher total emissions by a factor of 3. Furthermore, the inventory misrepresented the VOCs speciation, mainly for isoprene, monoterpenes, aromatics, and oxygenated compounds. Accounting for these differences in regional air quality models would lead to improved predictions of their impacts and help to prioritise pollution reduction strategies in the region.

Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer.

BACKGROUND: This is an update of the Cochrane Review published in Issue 4, 2015. Cervical cancer is one of the most frequent cause of death from gynaecological cancers worldwide. Many new cervical cancer cases in low-income countries present at an advanced stage. Standard care in Europe and the US for locally advanced cervical cancer (LACC) is chemoradiotherapy. In low-income countries, with limited access to radiotherapy, LACC may be treated with chemotherapy and hysterectomy. It is not certain if this improves survival. It is important to assess the value of hysterectomy with radiotherapy or chemotherapy, or both, as an alternative. OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment with radiotherapy or chemotherapy, or both, in women with LACC (Stage IB2 to III) is safe and effective compared with standard treatment alone. SEARCH METHODS: We searched CENTRAL, MEDLINE via Ovid, Embase via Ovid, LILACS, trial registries and the grey literature up to 3 February 2022. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared treatments involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with LACC International Federation of Gynecology and Obstetrics (FIGO) Stages IB2 to III. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We independently assessed study eligibility, extracted data and assessed the risk of bias. Where possible, we synthesised overall (OS) and progression-free (PFS) or disease-free (DFS) survival in a meta-analysis using a random-effects model. Adverse events (AEs) were incompletely reported and we described the results of single trials in narrative form. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: From the searches we identified 968 studies. After deduplication, title and abstract screening, and full-text assessment, we included 11 RCTs (2683 women) of varying methodological quality. This update identified four new RCTs and three ongoing RCTs. The included studies compared: hysterectomy (simple or radical) with radiotherapy or chemoradiotherapy or neoadjuvant chemotherapy (NACT) versus radiotherapy alone or chemoradiotherapy (CCRT) alone or CCRT and brachytherapy. There is also one ongoing study comparing three groups: hysterectomy with CCRT versus hysterectomy with NACT versus CCRT. There were two comparison groups for which we were able to do a meta-analysis. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone Two RCTs with similar design characteristics (620 and 633 participants) found no difference in five-year OS between NACT with hysterectomy versus CCRT. Meta-analysis assessing 1253 participants found no evidence of a difference in risk of death (OS) between women who received NACT plus hysterectomy and those who received CCRT alone (HR 0.94, 95% CI 0.76 to 1.16; moderate-certainty evidence). In both studies, the five-year DFS in the NACT plus surgery group was worse (57%) compared with the CCRT group (65.6%), mostly for Stage IIB. Results of single trials reported no apparent difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between groups (very low-quality evidence). Hysterectomy (simple or radical) with neoadjuvant chemotherapy versus radiotherapy alone Meta-analysis of three trials of NACT with hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received NACT plus hysterectomy had less risk of death (OS) than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93; I2 = 0%; moderate-quality evidence). However, a significant number of participants who received NACT plus hysterectomy also had radiotherapy. There was no difference in the proportion of women with disease progression or recurrence (DFS and PFS) between NACT plus hysterectomy and radiotherapy groups (RR 0.75, 95% CI 0.53 to 1.05; I2 = 20%; moderate-quality evidence). The certainty of the evidence was low or very-low for all other comparisons for all outcomes. None of the trials reported quality of life outcomes. AUTHORS' CONCLUSIONS: From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with LACC who are treated with radiotherapy or CCRT alone. The overall certainty of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The certainty of the evidence for NACT and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate. The same occurred for the comparison involving NACT and hysterectomy compared with CCRT alone. Evidence from other comparisons was generally sparse and of low or very low-certainty. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials assessing medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.

δ13C methane source signatures from tropical wetland and rice field emissions.

The atmospheric methane (CH4) burden is rising sharply, but the causes are still not well understood. One factor of uncertainty is the importance of tropical CH4 emissions into the global mix. Isotopic signatures of major sources remain poorly constrained, despite their usefulness in constraining the global methane budget. Here, a collection of new δ13CCH4 signatures is presented for a range of tropical wetlands and rice fields determined from air samples collected during campaigns from 2016 to 2020. Long-term monitoring of δ13CCH4 in ambient air has been conducted at the Chacaltaya observatory, Bolivia and Southern Botswana. Both long-term records are dominated by biogenic CH4 sources, with isotopic signatures expected from wetland sources. From the longer-term Bolivian record, a seasonal isotopic shift is observed corresponding to wetland extent suggesting that there is input of relatively isotopically light CH4 to the atmosphere during periods of reduced wetland extent. This new data expands the geographical extent and range of measurements of tropical wetland and rice δ13CCH4 sources and hints at significant seasonal variation in tropical wetland δ13CCH4 signatures which may be important to capture in future global and regional models. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.

Investigation of East Asian Emissions of CFC-11 Using Atmospheric Observations in Taiwan.

Recent findings of an unexpected slowdown in the decline of CFC-11 mixing ratios in the atmosphere have led to the conclusion that global CFC-11 emissions have increased over the past decade and have been attributed in part to eastern China. This study independently assesses these findings by evaluating enhancements of CFC-11 mixing ratios in air samples collected in Taiwan between 2014 and 2018. Using the NAME (Numerical Atmospheric Modeling Environment) particle dispersion model, we find the likely source of the enhanced CFC-11 observed in Taiwan to be East China. Other halogenated trace gases were also measured, and there were positive interspecies correlations between CFC-11 and CHCl3, CCl4, HCFC-141b, HCFC-142b, CH2Cl2, and HCFC-22, indicating co-location of the emissions of these compounds. These correlations in combination with published emission estimates of CH2Cl2 and HCFC-22 from China, and of CHCl3 and CCl4 from eastern China, are used to estimate CFC-11 emissions. Within the uncertainties, these estimates do not differ for eastern China and the whole of China, so we combine them to derive a mean estimate that we term as being from "(eastern) China". For 2014-2018, we estimate an emission of 19 ± 5 Gg year-1 (gigagrams per year) of CFC-11 from (eastern) China, approximately one-quarter of global emissions. Comparing this to previously reported CFC-11 emissions estimated for earlier years, we estimate CFC-11 emissions from (eastern) China to have increased by 7 ± 5 Gg year-1 from the 2008-2011 average to the 2014-2018 average, which is 50 ± 40% of the estimated increase in global CFC-11 emissions and is consistent with the emission increases attributed to this region in an earlier study.

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: To assess the within-trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. METHODS: Within-trial economic evaluation of no screening (C) vs either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second-line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. RESULTS: Using a CA125-ROCA cost of £20, the within-trial results show USS to be strictly dominated by MMS, with the MMS vs C comparison returning an incremental cost-effectiveness ratio (ICER) of £91 452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15, the ICER becomes £77 818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30 033 per LYG, while Markov modelling produces an ICER of £46 922 per QALY. CONCLUSION: Analysis suggests that, after accounting for the lead time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared with the within-trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort.

Persistence of fimbrial tissue on the ovarian surface after salpingectomy.

BACKGROUND: Salpingectomy is recommended as a risk-reducing strategy for epithelial tubo-ovarian cancer. The gold standard procedure is complete tubal excision. OBJECTIVE: The purpose of this study was to assess the presence of residual fimbrial/tubal tissue on ovarian surfaces after salpingectomy. STUDY DESIGN: Prospective analysis of patients who underwent salpingo-oophorectomy with or without hysterectomy for benign indications, early cervical cancer, or low-risk endometrial cancer at a UK National Health Service Trust. Salpingectomy with or without hysterectomy was performed initially, followed by oophorectomy within the same operation. Separately retrieved tubes and ovaries were sectioned serially and examined completely histologically. The main outcome measure was histologically identified fimbrial/ tubal tissue on ovarian surface. Chi-square/Fisher's exact tests were used to evaluate categoric variables. RESULTS: Twenty-five consecutive cases (mean age, 54.8 ± 5.0 years) that comprised 41 adnexae (unilateral, 9; bilateral, 16) were analyzed. Seventeen (68.0%), 5 (20.0%), and 3 (12.0%) procedures were performed by consultant gynecologists, subspecialty/specialist trainees, and consultant gynecologic oncologists, respectively. Twelve of 25 procedures (48.0%) were laparoscopic, and 13 of 25 procedures (52.0%) involved laparotomy. Four of 25 patients (16.0%; 95% confidence interval, 4.5-36.1%) or 4 of 41 adnexae (9.8%; 95% confidence interval, 2.7-23.1%) showed residual microscopic fimbrial tissue on the ovarian surface. Tubes/ovaries were free of adhesions in 23 cases. Two cases had dense adnexal adhesions, but neither had residual fimbrial tissue on the ovary. Residual fimbrial tissue was not associated significantly with surgical route or experience (consultant, 3/20 [15%]; trainee, 1/5 [20%]; P=1.0). CONCLUSION: Residual fimbrial tissue remains on the ovary after salpingectomy in a significant proportion of cases and could impact the level of risk-reduction that is obtained.

Evidence for strong, widespread chlorine radical chemistry associated with pollution outflow from continental Asia.

The chlorine radical is a potent atmospheric oxidant, capable of perturbing tropospheric oxidative cycles normally controlled by the hydroxyl radical. Significantly faster reaction rates allow chlorine radicals to expedite oxidation of hydrocarbons, including methane, and in polluted environments, to enhance ozone production. Here we present evidence, from the CARIBIC airborne dataset, for extensive chlorine radical chemistry associated with Asian pollution outflow, from airborne observations made over the Malaysian Peninsula in winter. This region is known for persistent convection that regularly delivers surface air to higher altitudes and serves as a major transport pathway into the stratosphere. Oxidant ratios inferred from hydrocarbon relationships show that chlorine radicals were regionally more important than hydroxyl radicals for alkane oxidation and were also important for methane and alkene oxidation (>10%). Our observations reveal pollution-related chlorine chemistry that is both widespread and recurrent, and has implications for tropospheric oxidizing capacity, stratospheric composition and ozone chemistry.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening.

PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.

Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer.

BACKGROUND: Cervical cancer is the second commonest cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. Sources suggest that a very high proportion of new cervical cancer cases in developing countries are at an advanced stage (IB2 or more) and more than a half of these may be stage III or IV. Cervical cancer staging is based on findings from clinical examination (FIGO) staging). Standard care in Europe and US for stage IB2 to III is non-surgical treatment (chemoradiation). However in developing countries, where there is limited access to radiotherapy, locally advanced cervical cancer may be treated with a combination of chemotherapy and hysterectomy (surgery to remove the womb and the neck of the womb, with or without the surrounding tissues). It is not certain if this improves survival. Therefore, it is important to systematically assess the value of hysterectomy in addition to radiotherapy or chemotherapy, or both, as an alternative intervention in the treatment of locally advanced cervical cancer (stage IB2 to III). OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment with radiation or chemotherapy, or both, in women with locally advanced cervical cancer (stage IB2 to III) is safe and effective compared with standard treatment alone. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, MEDLINE, EMBASE and LILACS up to February 2014. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared treatment protocols involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with advanced stage (IB2 to III) cervical cancer presenting for the first time. DATA COLLECTION AND ANALYSIS: We assessed study eligibility independently, extracted data and assessed risk of bias. Where possible, overall and progression or disease-free survival outcomes were synthesised in a meta-analysis using the random-effects model. Adverse events were incompletely reported so results of single trials were described in narrative form. MAIN RESULTS: We included seven RCTs (1217 women) of varying methodological quality in the review; most trials were at moderate or high risk of bias.Three were multi-centre trials, two were single-centre trials, and in two trials it was unclear if they were single or multi-centre. These trials compared the following interventions for women with locally advanced cervical cancer (stages IB2 to III):hysterectomy (simple or radical) with radiotherapy (N = 194) versus radiotherapy alone (N = 180); hysterectomy (simple or radical) with chemoradiotherapy (N = 31) versus chemoradiotherapy alone (N = 30); hysterectomy (radical) with chemoradiotherapy (N = 111) versus internal radiotherapy with chemoradiotherapy (N = 100); hysterectomy (simple or radical) with upfront (neoadjuvant) chemotherapy (N = 298) versus radiotherapy alone (N = 273).One trial (N = 256) found no difference in the risk of death or disease progression between women who received attenuated radiotherapy followed by hysterectomy and those who received radiotherapy (external and internal) alone (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.61 to 1.29). This trial also reported no difference between the two groups in terms of adverse effects (18/129 grade 3 or 4 adverse effects in the hysterectomy and radiation group and 19 cases in 18/121 women in the radiotherapy alone group). There was no difference in 5-year tumour-free actuarial survival (representation of the probable years of survivorship of a defined population of participants) or severe complications (grade 3) in another trial (N = 118) which reported the same comparison (6/62 versus 6/56 in the radiation with surgery group versus the radiotherapy alone group, respectively). The quality of the evidence was low for all these outcomes.One trial (N = 61) reported no difference (P value > 0.10) in overall and recurrence-free survival at 3 years between chemoradiotherapy and hysterectomy versus chemoradiotherapy alone (low quality evidence). Adverse events and morbidity data were not reported.Similarly, another trial (N = 211) found no difference in the risk of death (HR 0.65, 95% CI 0.35 to 1.21, P value = 0.19, low quality evidence), disease progression (HR 0.70, 95% CI 0.31 to 1.34, P value = 0.24, low quality evidence) or severe late complications (P value = 0.53, low quality evidence) between women who received internal radiotherapy versus hysterectomy after both groups had received external-beam chemoradiotherapy.Meta analysis of three trials of neoadjuvant chemotherapy and hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received neoadjuvant chemotherapy plus hysterectomy had less risk of death than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93, I(2) = 0%, moderate quality evidence). However, a significant number of the participants that received neoadjuvant chemotherapy plus hysterectomy had radiotherapy as well. There was no difference in the proportion of women with disease progression or recurrence between the two groups (RR 0.75, 95% CI 0.53 to 1.05, I(2) = 20%, moderate quality evidence).Results of single trials reported no apparent (P value > 0.05) difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between the two groups (low quality evidence).Quality of life outcomes were not reported in any of the trials. AUTHORS' CONCLUSIONS: From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with locally advanced cervical cancer who are treated with radiotherapy or chemoradiotherapy alone. The overall quality of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The quality of the evidence for neoadjuvant chemotherapy and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate, with evidence from other comparisons of low quality. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials that assess medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.

Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening.

OBJECTIVE: To assess the performance of ultrasonography in a multimodal ovarian cancer screening strategy. DESIGN: Prospective ovarian cancer screening trial between December 1986 and June 1993. SETTING: General practice, occupational health departments and an ovarian cancer screening clinic at a London teaching hospital. POPULATION: Postmenopausal women, ≥ 45 years with a raised CA125. METHODS: Volunteers with a CA125 ≥ 30 U/mL underwent a pelvic ultrasound. Scans were classified as normal, abnormal (ovarian volume ≥ 8.8 mL) or equivocal (normal volume with abnormal morphology). Abnormal ovarian morphology was subclassified as simple cyst (single, thin walled cyst with no septa or papillary projections) or complex (all other abnormalities). Volunteers with abnormal scans were referred for a gynaecological opinion. Follow up was via the cancer registry and postal questionnaires. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive predictive value of different ultrasound criteria for detection of index cancer (e.g. primary invasive epithelial carcinoma of the ovary and fallopian tube). RESULTS: Seven hundred and forty-one women underwent 1219 scans and 20 index cancers occurred during a median follow up of 6.8 years. The sensitivity for detection of ovarian cancer of different ultrasound criteria was 100% for abnormal morphology, 89.5% for abnormal volume and 84% for complex morphology. The highest specificity (97%) and positive predictive value (37.2%) was achieved using complex morphology. CONCLUSION: A variety of ultrasound criteria can achieve high sensitivity, specificity and positive predictive value for index cancers in postmenopausal women with an elevated CA125. Use of ovarian morphology to interpret ultrasound may increase sensitivity and use of complex ovarian morphology may increase the positive predictive value.

Using skype as an alternative for residency selection interviews.

BACKGROUND: Residency interviews can place significant time and financial burdens on applicants. OBJECTIVE: To determine whether the use of Skype as a screening tool during interview season in a family medicine residency is cost-effective and time-efficient for the applicant and the residency program. METHODS: We surveyed 2 groups of medical students during interviews for our family medicine program. Thirty-two students were interviewed via our face-to-face, traditional interview (TI) process, and 10 students, the second group, who did not meet the program's standard interview selection criteria for TI, underwent our Skype interview (SI) process. RESULTS: Using an unpaired t test, we found that the applicants' costs of an SI were significantly less than a TI, $566 (95% confidence interval [CI] $784-$349, P < .001). Direct cash savings plus indirect salary savings to the program were $5,864, with a time savings of 7 interview days. Three of the applicants who were participants in the SI limb of the study were in our final rank order list. CONCLUSIONS: For interviewing in family medicine residencies, use of Skype may be a cost-effective and time-efficient screening tool for both the applicant and the program. Alternate uses of SI may include the time-sensitive, postmatch Supplemental Offer and Acceptance Program.

Primary chemotherapy for inoperable ovarian, fallopian tube, or primary peritoneal cancer with or without delayed debulking surgery.

OBJECTIVE: To describe the outcome of primary chemotherapy for women with advanced-stage epithelial ovarian or primary peritoneal cancer and delayed surgery when optimal debulking surgery cannot be achieved at diagnosis. METHODS: Between 1998 and 2006, we retrospectively reviewed the overall survival and examined prognostic markers in consecutive patients who were not suitable for initial radical surgery because of the extent of disease and/or poor performance status. They were treated with a policy of primary platinum-based chemotherapy, followed whenever possible in responding patients by debulking surgery. RESULTS: A total of 171 patients received least one cycle of chemotherapy. Eighty-six patients proceeded to surgery and 53 (31% of 171 and 62% of 86) had optimal (<1 cm) residual disease. Eighty-five patients did not undergo surgery because they remained unfit or had not responded sufficiently to chemotherapy. The median overall survival was 18.7 months (95% confidence interval [CI], 16.5-24.2). The median OS in the surgical group for optimal and suboptimal surgery was 40.8 (95% CI, 32.5-50.0) and 22.5 (95% CI, 17.7-37.1) months (P = 0.005). On multivariate analysis, interval surgery and optimal surgery were the only independent prognostic factors (hazard ratios, 0.45 and 0.43, respectively; P = 0.009). In the nonsurgical group, CA125 response was an independent prognostic factor (hazard ratio, 0.34; P = 0.001) with an OS of 21.7 months (95% CI, 14.0-35.4) in women with a normal CA125 after treatment compared with 6.7 (95% CI, 4.5-7.8) months. CONCLUSIONS: In one third of the women, the tumor was optimally debulked after primary chemotherapy and their median survival was 40.8 months. Suboptimal debulking surgery after primary chemotherapy did not result in a better survival than that achieved after a chemotherapy response alone, suggesting that surgery may be avoided when imaging after chemotherapy demonstrates residual disease that cannot be optimally debulked.

Impact on mortality and cancer incidence rates of using random invitation from population registers for recruitment to trials.

BACKGROUND: Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status. METHODS: Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs) were calculated based on national mortality (2005) and cancer incidence (2006) statistics. The Index of Multiple Deprivation (IMD 2007) was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations. RESULTS: The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived) than the national average, those who joined the trial were less deprived. CONCLUSIONS: Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent to use the various mortality and incidence rates presented as guides for calculating event rates and power in RCTs involving women.

Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort.

BACKGROUND: The increase in the worldwide incidence of endometrial cancer relates to rising obesity, falling fertility, and the ageing of the population. Transvaginal ultrasound (TVS) is a possible screening test, but there have been no large-scale studies. We report the performance of TVS screening in a large cohort. METHODS: We did a nested case-control study of postmenopausal women who underwent TVS in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) following recruitment between April 17, 2001, and Sept 29, 2005. Endometrial thickness and endometrial abnormalities were recorded, and follow-up, through national registries and a postal questionnaire, documented the diagnosis of endometrial cancer. Our primary outcome measure was endometrial cancer and atypical endometrial hyperplasia (AEH). Performance characteristics of endometrial thickness and abnormalities for detection of endometrial cancer within 1 year of TVS were calculated. Epidemiological variables were used to develop a logistic regression model and assess a screening strategy for women at higher risk. Our study is registered with ClinicalTrials.gov, number NCT00058032, and with the International Standard Randomised Controlled Trial register, number ISRCTN22488978. FINDINGS: 48,230 women underwent TVS in the UKCTOCS prevalence screen. 9078 women were ineligible because they had undergone a hysterectomy and 2271 because their endometrial thickness had not been recorded; however, 157 of these women had an endometrial abnormality on TVS and were included in the analysis. Median follow-up was 5·11 years (IQR 4·05-5·95). 136 women with endometrial cancer or AEH within 1 year of TVS were included in our primary analysis. The optimum endometrial thickness cutoff for endometrial cancer or AEH was 5·15 mm, with sensitivity of 80·5% (95% CI 72·7-86·8) and specificity of 86·2% (85·8-86·6). Sensitivity and specificity at a 5 mm or greater cutoff were 80·5% (72·7-86·8) and 85·7% (85·4-86·2); for women with a 5 mm or greater cutoff plus endometrial abnormalities, the sensitivity and specificity were 85·3% (78·2-90·8) and 80·4% (80·0-80·8), respectively. For a cutoff of 10 mm or greater, sensitivity and specificity were 54·1% (45·3-62·8) and 97·2% (97·0-97·4). When our analysis was restricted to the 96 women with endometrial cancer or AEH who reported no symptoms of postmenopausal bleeding at the UKCTOCS scan before diagnosis and had an endometrial thickness measurement available, a cutoff of 5 mm achieved a sensitivity of 77·1% (67·8-84·3) and specificity of 85·8% (85·7-85·9). The logistic regression model identified 25% of the population as at high risk and 39·5% of endometrial cancer or AEH cases were identified within this high risk group. In this high-risk population, a cutoff at 6·75 mm achieved sensitivity of 84·3% (71·4-93·0) and specificity of 89·9% (89·3-90·5). INTERPRETATION: Our findings show that TVS screening for endometrial cancer has good sensitivity in postmenopausal women. The burden of diagnostic procedures and false-positive results can be reduced by limiting screening to a higher-risk group. The role of population screening for endometrial cancer remains uncertain, but our findings are of immediate value in the management of increased endometrial thickness in postmenopausal women undergoing pelvic scans for reasons other than vaginal bleeding.

Hormonal therapy in advanced or recurrent endometrial cancer.

BACKGROUND: Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. OBJECTIVES: To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. MAIN RESULTS: We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). AUTHORS' CONCLUSIONS: We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or recurrent endometrial cancer. However, a large number of patients would be needed to demonstrate an effect on survival and none of the included RCTs had a sufficient number of patients to demonstrate a significant difference. In the absence of a proven survival advantage and the heterogeneity of patient populations, the decision to use any type of hormonal therapy should be individualised and with the intent to palliate the disease. It is debatable whether outcomes such as quality of life, treatment response or palliative measures such as relieving symptoms should take preference over overall and PFS as the major objectives of future trials.

Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: Ovarian cancer has a high case-fatality ratio, with most women not diagnosed until the disease is in its advanced stages. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomised controlled trial designed to assess the effect of screening on mortality. This report summarises the outcome of the prevalence (initial) screen in UKCTOCS. METHODS: Between 2001 and 2005, a total of 202 638 post-menopausal women aged 50-74 years were randomly assigned to no treatment (control; n=101 359); annual CA125 screening (interpreted using a risk of ovarian cancer algorithm) with transvaginal ultrasound scan as a second-line test (multimodal screening [MMS]; n=50 640); or annual screening with transvaginal ultrasound (USS; n=50 639) alone in a 2:1:1 ratio using a computer-generated random number algorithm. All women provided a blood sample at recruitment. Women randomised to the MMS group had their blood tested for CA125 and those randomised to the USS group were sent an appointment to attend for a transvaginal scan. Women with abnormal screens had repeat tests. Women with persistent abnormality on repeat screens underwent clinical evaluation and, where appropriate, surgery. This trial is registered as ISRCTN22488978 and with ClinicalTrials.gov, number NCT00058032. FINDINGS: In the prevalence screen, 50 078 (98.9%) women underwent MMS, and 48 230 (95.2%) underwent USS. The main reasons for withdrawal were death (two MMS, 28 USS), non-ovarian cancer or other disease (none MMS, 66 USS), removal of ovaries (five MMS, 29 USS), relocation (none MMS, 39 USS), failure to attend three appointments for the screen (72 MMS, 757 USS), and participant changing their mind (483 MMS, 1490 USS). Overall, 4355 of 50 078 (8.7%) women in the MMS group and 5779 of 48 230 (12.0%) women in the USS group required a repeat test, and 167 (0.3%) women in the MMS group and 1894 (3.9%) women in the USS group required clinical evaluation. 97 of 50 078 (0.2%) women from the MMS group and 845 of 48 230 (1.8%) from the USS group underwent surgery. 42 (MMS) and 45 (USS) primary ovarian and tubal cancers were detected, including 28 borderline tumours (eight MMS, 20 USS). 28 (16 MMS, 12 USS) of 58 (48.3%; 95% CI 35.0-61.8) of the invasive cancers were stage I/II, with no difference (p=0.396) in stage distribution between the groups. A further 13 (five MMS, eight USS) women developed primary ovarian cancer during the year after the screen. The sensitivity, specificity, and positive-predictive values for all primary ovarian and tubal cancers were 89.4%, 99.8%, and 43.3% for MMS, and 84.9%, 98.2%, and 5.3% for USS, respectively. For primary invasive epithelial ovarian and tubal cancers, the sensitivity, specificity, and positive-predictive values were 89.5%, 99.8%, and 35.1% for MMS, and 75.0%, 98.2%, and 2.8% for USS, respectively. There was a significant difference in specificity (p<0.0001) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers. INTERPRETATION: The sensitivity of the MMS and USS screening strategies is encouraging. Specificity was higher in the MMS than in the USS group, resulting in lower rates of repeat testing and surgery. This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group. The prevalence screen has established that the screening strategies are feasible. The results of ongoing screening are awaited so that the effect of screening on mortality can be determined.

Recruitment to multicentre trials--lessons from UKCTOCS: descriptive study.

OBJECTIVE: To describe the factors that contributed to successful recruitment of more than 200,000 women to the UK Collaborative Trial of Ovarian Cancer Screening, one of the largest ever randomised controlled trials. DESIGN: Descriptive study. SETTING: 13 NHS trusts in England, Wales, and Northern Ireland. PARTICIPANTS: Postmenopausal women aged 50-74; exclusion criteria included ovarian malignancy, bilateral oophorectomy, increased risk of familial ovarian cancer, active non-ovarian malignancy, and participation in other ovarian cancer screening trials. MAIN OUTCOME MEASURES: Achievement of target recruitment, acceptance rates of invitation, and recruitment rates. RESULTS: The trial was set up in 13 centres with 27 adjoining local health authorities. The coordinating centre team was led by one of the senior investigators, who was closely involved in planning and day to day trial management. Of 1 243,282 women invited, 23.2% (288 955) replied that they were eligible and would like to participate. Of those sent appointments, 73.6% (205 090) attended for recruitment. The acceptance rate varied from 19% to 33% between trial centres. Measures to ensure target recruitment included named coordinating centre staff supporting and monitoring each centre, prompt identification and resolution of logistic problems, varying the volume of invitations by centre, using local non-attendance rates to determine the size of recruitment clinics, and organising large ad hoc clinics supported by coordinating centre staff. The trial randomised 202,638 women in 4.3 years. CONCLUSIONS: Planning and trial management are as important as trial design and require equal attention from senior investigators. Successful recruitment needs constant monitoring by a committed proactive management team that is willing to explore individual solutions for different centres and use central resources to improve local recruitment. Automation of trial processes with web based trial management systems is crucial in large multicentre randomised controlled trials. Recruitment can be further enhanced by using information videos and group discussions. Trial registration Current Controlled Trials ISRCTN22488978.

Gas chromatography negative ion chemical ionization mass spectrometry: application to the detection of alkyl nitrates and halocarbons in the atmosphere.

Alkyl nitrates and very short-lived halocarbon species are important atmospheric trace gas species that are present in the low to sub parts per trillion concentration range. This presents an analytical challenge for their detection and quantification that requires instrumentation with high sensitivity and selectivity. In this paper, we present a new in situ gas chromatograph negative ion chemical ionization mass spectrometer (GC/NICI-MS) coupled to a non-cryogen sample pre-concentration system. This instrument, with detection limits of <0.01 ppt, is capable of detecting and quantifying a large suite of alkyl nitrate and halocarbon species with high sensitivity and precision. The effects of ion source temperature and reagent gas pressure on the ionization efficiency of the NICI mode are investigated and the results are used to optimize the sensitivity. The NICI mode is compared to the more frequently used electron impact (EI) ionization and the enhancements in sensitivity are presented for all the calibrated compounds.