Aims
Treatment with anti‐HER2 therapy could be beneficial for patients with HER2‐positive endometrial and ovarian clear cell carcinoma (CCC). We studied HER2 overexpression by immunohistochemistry ...(IHC) using three different antibodies, including concordance with amplification by in‐situ hybridisation (ISH).
Methods and results
IHC and ISH were performed on tissue microarrays of 101 tumours: 58 endometrial pure CCC, 19 endometrial mixed carcinomas with a CCC component and 24 ovarian pure CCC. IHC was performed using SP3, 4B5 and HercepTest antibodies, and was scored by two independent observers. ISH was performed using dual‐colour silver ISH. Using IHC, agreement was poor between SP3/4B5 (61.4%), poor between SP3/HercepTest (68.3%) and reasonable between 4B5/HercepTest (75.2%). Interobserver agreement was substantial to almost perfect for all antibodies (SP3: linear weighted κ = 0.89, 4B5: κ = 0.90, HercepTest: κ = 0.76). HER2‐positivity by ISH was 17.8% (endometrial pure CCC: 24.1%, endometrial mixed: 0%, ovarian pure CCC: 16.7%). IHC/ISH concordance was poor, with a high false‐negative rate of all three IHC antibodies: sensitivity (38.9–50.0%) and positive predictive value (PPV) (37.5–58.3%) were poor; specificity (81.9–94.0%) and negative predictive value (NPV) (87.1–88.3%) were reasonable. When excluding 2+ cases, sensitivity declined (26.7–43.8%) but PPV (80.0–87.5%) and specificity (98.6–98.7%) improved.
Conclusions
In ovarian and endometrial CCC, there is considerable difference in HER2 overexpression by different IHC antibodies and marked discordance with ISH. As such, no single antibody can be considered conclusive for determining HER2 status in CCC. Based on these results, the lack of predictive value of different HER2 testing methods, as used in other studies, could be explained.
Objective
To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals.
Methods
...Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50–500 mm
3
), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference.
Results
Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days.
Conclusion
All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals.
Key Points
•
Lung nodules are common in CT lung cancer screening, most being benign
•
Short-term follow-up CT can identify fast-growing intermediate-size lung nodules
•
Most fast-growing nodules on short-term follow-up CT still prove to be benign
•
A new volume-doubling time (VDT) cut-off is proposed for lung screening
•
The optimised VDT cutoff may decrease false-positive case referrals for lung cancer
To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic
-pathogenic variant (PV) ...carriers.
We included
-PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO. We then compared clinical characteristics, including parity and oral contraceptive pill (OCP) use, for women with and without HGSC at RRSO.
Of the 2,557 included women, 1,624 had
, 930 had
, and three had both
-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for
-PV and 46.8 years (27.6-77.9) for
-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%)
-PV and 6 (0.6%)
-PV carriers had HGSC at RRSO, with the fallopian tube identified as the primary site in 73%. The prevalence of HGSC in women who underwent RRSO at the recommended age was 0.4%. Among
PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective.
We detected HGSC in 1.5% (
-PV) and 0.6% (
-PV) of RRSO specimens from asymptomatic
-PV carriers. Consistent with the fallopian tube hypothesis, we found most lesions in the fallopian tube. Our results highlight the importance of timely RRSO with total removal and assessment of the fallopian tubes and show the protective effects of long-term OCP.
Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic ...procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15–20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40–50%.
Re-wilding North America Donlan, Josh
Nature,
08/2005, Letnik:
436, Številka:
7053
Journal Article
Recenzirano
Donlan et al offers a plan for restoring animals that disappeared 13,000 years ago from Pleistocence North America. They suggest Pleistocene re-wilding, a series of carefully managed ecosystem ...manipulations using closely related species as proxies for extinct large vertebrates, as the solution to the declining population of wild animals.
•LDCT screening detects early-stage lung cancer in both high- and low-risk populations.•Nearly 70% of participants with detected lung cancer in low-risk population are women.•Early detection by LDCT ...screening is 4–5 times of that in clinical diagnosis setting.•LDCT screening detected more adenocarcinoma compared to not screening.
To evaluate the efficiency of low-dose computed tomography (LDCT) screening for lung cancer in China by analyzing the baseline results of a community-based screening study accompanied with a meta-analysis.
A first round of community-based lung cancer screening with LDCT was conducted in Tianjin, China, and a systematic literature search was performed to identify LDCT screening and registry-based clinical studies for lung cancer in China. Baseline results in the community-based screening study were described by participant risk level and the lung cancer detection rate was compared with the pooled rate among the screening studies. The percentage of patients per stage was compared between the community-based study and screening and clinical studies.
In the community-based study, 5523 participants (43.6% men) underwent LDCT. The lung cancer detection rate was 0.5% (high-risk, 1.2%; low-risk, 0.4%), with stage I disease present in 70.0% (high-risk, 50.0%; low-risk, 83.3%), and the adenocarcinoma present in 84.4% (high-risk, 61.5%; low-risk, 100%). Among all screen-detected lung cancer, women accounted for 8.3% and 66.7% in the high- and low-risk group, respectively. In the screening studies from mainland China, the lung cancer detection rate 0.6% (95 %CI: 0.3%–0.9%) for high-risk populations. The proportions with carcinoma in situ and stage I disease in the screening and clinical studies were 76.4% (95 %CI: 66.3%–85.3%) and 15.2% (95 %CI: 11.8%–18.9%), respectively.
The stage shift of lung cancer due to screening suggests a potential effectiveness of LDCT screening in China. Nearly 70% of screen-detected lung cancers in low-risk populations are identified in women.
BACKGROUND AND OBJECTIVES
The diagnosis of pulmonary nodules of unknown origin is challenging, and such nodules are not always suitable for transthoracic needle biopsy. With the advent of video ...assisted thoracic surgery (VATS) and CT‐guided percutaneous hookwire localization (CT‐PHL) we hypothesized that the combination of these two procedures will improve early diagnosis.
METHODS
Selection criteria were a nodule not well approachable with fine needle biopsy and the therapeutic consequences of a diagnosis as assessed by the multidisciplinary oncology board. Efficacy and safety of the combination of CT‐PHL prior to VATS was studied in terms of, histological diagnosis, complete resection rate, complications, conversion rate to thoracotomy, and duration of procedures.
RESULTS
A total of 150 pulmonary nodules were located and resected in 150 patients. The median nodule diameter was 9 mm (range 4‐24) and located within 30 mm of the pleural surface (median 7, range 0‐29). The resection was complete in 96%, and in 100% a definitive histological diagnosis was obtained. Complications requiring intervention during the CT‐procedure occurred in 11 patients (7.3%). Complications of VATS consisted of major complications (2.0%) and minor complications (4.0%). The 30 Day mortality was 1.4% and in hospital mortality 0.7%. Conversion to thoracotomy occurred in 4.7% patients. Median CT‐localization time was 25 min (range 5‐72), median VATS time was 49 min (range 14‐169).
CONCLUSIONS
CT‐PHL is a very efficient and safe procedure prior to VATS for pulmonary nodules and allows in 96% radical resection with a diagnostic accuracy of 100%.
•Lowering screening start age by 5 years led to 4.6 more detected LCs in 1000 women.•Lowering screening start age by 5 years induced 1.2 more LCs per 1000 women.•Further reduction of radiation dose ...of CT scans is effective in reducing radiation risk.
The US has recently lowered the entry age for lung cancer screening with low-dose computed tomography (LDCT) from 55 to 50 years. The effect of the younger age for starting screening on the rates of screen-detected and radiation-induced lung cancers in women remains unclear.
A modeling study was conducted. A static cohort of 100,000 heavy female smokers was simulated to undergo annual lung cancer screening with LDCT. The number of screen-detected lung cancers (benefit) and radiation-induced lung cancers (harm) per 1000 screenees were calculated for scenarios with two starting ages (55–50 years) and fixed stopping age (75 years). The benefit-harm ratio and incremental benefit-harm ratio (IBHR) were calculated for each scenario.
For annual screening from 55 to 75 years, the number of screen-detected and radiation-induced lung cancers was 112.4 and 2.2, respectively. For annual screening from 50 to 75 years, those numbers were 117.0 and 3.4, respectively. The benefit-harm ratio decreased from 51 to 35 and the IBHR decreased from 6.3 to 4.0 when lowering the screening starting age from 55 to 50 years.
The risk of radiation induced lung cancers increased by 50% when lowering the screening starting age by 5 years in women. However, the benefits of LDCT lung cancer screening still outweigh the assumed radiation harm.
In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be ...helpful to select high risk patients and/or to develop strategies to prevent local recurrences.
This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables.
Relevant studies were identified by an extensive online electronic search in July 2017.
Studies reporting prognostic factors specific for local recurrences of vulvar carcinoma were included.
Two review authors independently performed data selection, extraction and assessment of study quality. The risk difference was calculated for each prognostic factor when described in two or more studies.
Twenty-two studies were included; most of all were retrospective and mainly reported pathologic prognostic factors. Our review indicates an estimated annual local recurrence rate of 4% without plateauing. The prognostic relevance for local recurrence of vulvar carcinoma of all analyzed variables remains equivocal, including pathologic tumor free margin distance <8mm, presence of lichen sclerosus, groin lymph node metastases and a variety of primary tumor characteristics (grade of differentiation, tumor size, tumor focality, depth of invasion, lymphovascular space invasion, tumor localization and presence of human papillomavirus).
Current quality of data on prognostic factors for local recurrences in vulvar carcinoma patients does not allow evidence-based clinical decision making. Further research on prognostic factors, applying state of the art methodology is needed to identify high-risk patients and to develop alternative primary and secondary prevention strategies.
•We estimated a local recurrence rate of 4% per year without plateauing.•Prognostic relevance of a pathological free margin of <8mm remains questionable.•For all other variables analyzed, prognostic relevance remains equivocal.
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