Previous studies have reported that anal cancer incidence has increased in individual countries; however, age-specific trends were not examined in detail. This study describes pooled and ...country-specific anal cancer incidence trends by sex, age (all ages, <60 and 60+ years) and histological subtype (all subtypes, squamous cell carcinoma SCC and adenocarcinoma ADC).
Five-year incidence and population-at-risk data were obtained from IARC's Cancer Incidence in Five Continents for the years 1988-1992 to 2008-2012. The standardised rate ratios (SRRs) for 2008-2012 vs 1988-1992 and the 5-year average percent change (AvPC) during the period were used to assess changes in the age-standardised incidence rates.
During the study period, there were significant increases in the incidence of SCC in both men and women of all age groups with significant increasing trend, and these increases were highest in those aged <60 years (SRR = 2.34 95% CI:2.11-2.58 in men and SRR = 2.76 95% CI:2.54-3.00 in women). By contrast, there were significant decreases in the incidence of ADC in men and women of all ages (SRR = 0.60 95% CI:0.54-0.67) and (SRR = 0.63 95% CI:0.56-0.71, respectively), with similar decreases in those aged <60 years and 60+ years. These competing trends still resulted in significant increases in the overall incidence of anal cancer in men and women of all ages groups with significant increasing trend. The SRRs in men of all ages, <60 years and 60+ years were 1.35 (95% CI:1.28-1.42), 1.77 (95% CI:1.62-1.92) and 1.08 (95% CI:1.00-1.15), respectively. The corresponding SRRs in women were 1.75 (95% CI:1.67-1.83), 2.31 (95% CI:2.14-2.48) and 1.38 (95% CI 1.31-1.46), respectively.
Increases in the incidence of anal SCC has driven an overall increase in anal cancer incidence; this may be associated with changing sexual behaviours and increasing levels of HPV exposure in younger cohorts. The findings further reinforce the importance of HPV vaccination.
The aim of this study was to assess trends in the age‐specific incidence of vulvar cancer in 13 high‐income countries satisfying a priori conditions regarding the availability of cancer registry data ...over a 20‐year period; these were Canada, the United States, nine European countries, Australia and Japan. Five‐yearly incidence and population at risk were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents for the years 1988–1992 (Volume 7) to 2003–2007 (Volume 10). The 5‐yearly average percent change (AvPC) over the period and standardised rate ratios (SRRs) for 2003–2007 versus 1988–1992 were used to assess changes in the age‐standardised incidence rates of vulvar cancer for all ages, and for <60 years and 60+ years. During the study period, the 5‐yearly AvPC across the 13 countries increased by 4.6% (p = 0.005) in women of all ages, and 11.6% (p = 0.02) in those <60 years. No change was observed in women aged 60+ years (5‐yearly AvPC = 0.1%, p = 0.94). The SRR for 2003–2007 versus 1988–1992 was significantly elevated in women <60 years of age (SRR = 1.38, 95% CI: 1.30–1.46), but not in women of 60+ years (SRR = 1.01, 95% CI: 0.97–1.05). The increase in incidence in women <60 years of age drove a significant increase in the overall SRR in women of all ages (SRR = 1.14, 95% CI: 1.11–1.18). Some differences in the specific findings at the individual country level were observed. The findings are consistent with changing sexual behaviours and increasing levels of exposure to human papillomavirus (HPV) in cohorts born around/after about 1950, but younger cohorts offered HPV vaccination are likely to receive some protection against developing vulvar cancer in the future.
What's new?
While the incidence of vulvar cancer appears to be stable or rising in some developed countries, age‐specific trends remain unclear. Nonetheless, previous work suggests that vulvar cancer incidence has risen particularly in women under age 60, possibly owing to increased human papillomavirus (HPV) infection. Here, age‐specific trends in vulvar cancer incidence were explored across multiple countries. Age‐standardised incidence rate of vulvar cancer in women under 60 was found to have increased significantly in the last 20 years in high‐income countries. Changing sexual behaviors and increasing HPV exposure in women born about 1950 or later likely factor into this trend.
Background
Although discordance in HER2 positivity between primary and metastatic lesions is well established, changes in HER2 positivity after anti-HER2 therapy have not been well evaluated in ...gastric cancer. We aimed to evaluate whether HER2 expression in gastric cancer is affected by trastuzumab therapy.
Methods
We enrolled 48 HER2-positive advanced gastric cancer patients treated with trastuzumab-containing first-line chemotherapy and had paired biopsies at baseline and after progression.
Results
At baseline, HER2 was positive, with immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)+ in five patients, and with IHC 3+ in 43 patients. Fourteen patients (29.1%) exhibited loss of HER2 positivity on post-progression biopsy: 10 with IHC 0 or 1+, and four with IHC 2+/ISH−. HER2 remained positive on second biopsy in 34 patients: four with IHC 2+/ISH+, and 30 with IHC 3+. Median
H
-scores decreased from 225 to 175 (
p
= 0.047).
HER2
genetic heterogeneity was defined in one of 34 ISH-assessable patients (2.9%) at baseline and seven of 32 (21.9%) at second biopsy. Among 13 patients who received second-line trastuzumab emtansine, three showed HER2-negative conversion; they had no objective response and short progression-free survival (1.2, 1.3, and 3.4 months). Patients with stable HER2 status had a 44% response rate and median progression-free survival of 2.7 (0.4–36.8) months.
Conclusion
A substantial portion of HER2-positive patients showed HER2-negative conversion with increased
HER2
genetic heterogeneity after failure of trastuzumab-containing chemotherapy. Loss of HER2 positivity could be predictive of second-line anti-HER2 treatment, suggesting a need to reexamine HER2 status before initiating second-line anti-HER2 therapy.
Post-transcatheter aortic valve implantation (TAVI) computed tomography (CT) findings have not been fully elucidated, except hypoattenuating leaflet thickening (HALT). The objective of this study was ...to describe cardiac CT findings after TAVI, and investigate factors associated with HALT. This retrospective study included patients who underwent TAVI and post-TAVI cardiac CT scans. On CT, abnormal findings such as hypoattenuating subvalvular thickening (HAST), thrombus within the sinus of Valsalva, HALT, and leaflet motion limitation were thoroughly reviewed. Clinical and CT findings were compared between patients with HALT and those without HALT. Logistic regression analysis was performed to determine factors associated with HALT. A total of 138 patients (64 male, mean 78.5 ± 5.2 years of age) with post-TAVI CT scans were included. The median duration from TAVI to CT was 17.5 days (interquartile range, 3 to 390.8 days). HAST and thrombus within the sinus of Valsalva were detected in 32 (23%) and 5 (4%) patients, respectively. HALT and leaflet motion limitations were found in 25 (18%) and 20 (14%) of patients, respectively. Pannus was diagnosed in 2 patients. TAVI device implant duration (odds ratio OR, 1.5; p = 0.01), hypertension (OR, 0.2; p = 0.03), and HAST (OR, 4.9; p = 0.003) were associated with HALT. Implant durations were longer in patients with HAST, HALT, or leaflet motion limitation (p < 0.05, for all). In conclusion, HAST, HALT, thrombus within the sinus of Valsalva, and leaflet motion limitation are not uncommon after TAVI. Implant duration, hypertension, and HAST are associated with HALT.
Objective
Universal tumour testing for Lynch syndrome (LS) in all incident colorectal cancers (CRCs) and sequential diagnostic genetic testing is cost‐effective in Australia. Because of this, our ...study aimed to understand factors underlying possible decisions faced by tumour test‐positive CRC patients and their at‐risk relatives throughout the LS diagnosis pathway.
Methods
Semi‐structured telephone interviews were conducted with 23 participants, using four hypothetical scenarios. Vignette‐guided closed‐ and open‐ended questions asked about LS genetic testing uptake, discussing diagnosis with at‐risk relatives, and risk‐reducing interventions. Personal perspectives on genetic testing were collected pre‐post vignette discussion. Inductive thematic analysis was performed on open‐ended questions. Decisional pathway diagrams were developed to convey factors influencing complex decision‐making processes.
Results
Participant responses incorporated unfolding scenario information, resulting in three decision themes: (1) wanting to know one's LS status; (2) informing family about LS; (3) navigating risk‐reducing interventions. Across all themes, ‘knowledge’ emerged as a facilitator, and ‘negative emotional experience’ as a barrier. Personal supportive views toward genetic testing increased post‐interview.
Conclusions
When communicating with tumour test‐positive CRC patients or their relatives about LS genetic testing, providing guidance/resources to inform decisions around risk‐reducing interventions and informing family members is critical. Scenario‐driven interviews provide insight into what individuals might do when facing complex healthcare decisions and could aid informed decision‐making. This approach may be applicable in other conditions, particularly with mainstreaming being increasingly introduced into the genetic context.
X-ray coronary angiography is a primary imaging technique for diagnosing coronary diseases. Although quantitative coronary angiography (QCA) provides morphological information of coronary arteries ...with objective quantitative measures, considerable training is required to identify the target vessels and understand the tree structure of coronary arteries. Despite the use of computer-aided tools, such as the edge-detection method, manual correction is necessary for accurate segmentation of coronary vessels. In the present study, we proposed a robust method for major vessel segmentation using deep learning models with fully convolutional networks. When angiographic images of 3302 diseased major vessels from 2042 patients were tested, deep learning networks accurately identified and segmented the major vessels in X-ray coronary angiography. The average F1 score reached 0.917, and 93.7% of the images exhibited a high F1 score > 0.8. The most narrowed region at the stenosis was distinctly captured with high connectivity. Robust predictability was validated for the external dataset with different image characteristics. For major vessel segmentation, our approach demonstrated that prediction could be completed in real time with minimal image preprocessing. By applying deep learning segmentation, QCA analysis could be further automated, thereby facilitating the use of QCA-based diagnostic methods.
There is limited data regarding the association between sarcopenia and clinical outcomes in patients who underwent transcatheter aortic valve implantation (TAVI). From the prospective ASAN-TAVI ...registry, we evaluated a total of 522 patients with severe aortic stenosis who underwent TAVI between March 2010 and November 2018. Routine pre-TAVI computed tomography scan was used to calculate the skeletal muscle index (SMI), which was defined as skeletal muscle area at the L3 level divided by height squared; subject patients were classified into the gender-specific tertile groups of SMI. The patients’ mean age was 79 years and 49% were men. Mean SMI values were 41.3 ± 6.7 cm2/m2 in men and 34.1 ± 6.5 cm2/m2 in women. The Kaplan–Meier estimates of all-cause mortality at 12 months were higher in the low-tertile group than in the mid- and high-tertile groups (15.5%, 7.1%, and 6.2%, respectively; p = 0.036). In multivariate analysis, low-tertile of SMI was an independent predictor of mortality (vs high-tertile of SMI, hazard ratio 2.69; 95% confidence interval, 1.18 to 6.12; p = 0.019). The all-cause mortality was substantially higher in the groups with high-surgical risk plus low SMI tertile. The risk assessment with addition of SMI on conventional STS-PROM score was significantly improved by statistical measures of model reclassification and discrimination. In patients who underwent TAVI, sarcopenia measured by SMI was significantly associated with an increased risk of 1-year mortality. The prognostic impact of SMI-measured sarcopenia was more prominent in patients with high surgical risks.
Invasive fractional flow reserve (FFR) is a standard tool for identifying ischemia-producing coronary stenosis. However, in clinical practice, over 70% of treatment decisions still rely on visual ...estimation of angiographic stenosis, which has limited accuracy (about 60%-65%) for the prediction of FFR < 0.80. One of the reasons for the visual-functional mismatch is that myocardial ischemia can be affected by the supplied myocardial size, which is not always evident by coronary angiography. The aims of this study were to develop an angiography-based machine learning (ML) algorithm for predicting the supplied myocardial volume for a stenosis, as measured using coronary computed tomography angiography (CCTA), and then to build an angiography-based classifier for the lesions with an FFR < 0.80 versus ≥ 0.80.
A retrospective study was conducted using data from 1,132 stable and unstable angina patients with 1,132 intermediate lesions who underwent invasive coronary angiography, FFR, and CCTA at the Asan Medical Center, Seoul, Korea, between 1 May 2012 and 30 November 2015. The mean age was 63 ± 10 years, 76% were men, and 72% of the patients presented with stable angina. Of these, 932 patients (assessed before 31 January 2015) constituted the training set for the algorithm, and 200 patients (assessed after 1 February 2015) served as a test cohort to validate its diagnostic performance. Additionally, external validation with 79 patients from two centers (CHA University, Seongnam, Korea, and Ajou University, Suwon, Korea) was conducted. After automatic contour calibration using the caliber of guiding catheter, quantitative coronary angiography was performed using the edge-detection algorithms (CAAS-5, Pie-Medical). Clinical information was provided by the Asan BiomedicaL Research Environment (ABLE) system. The CCTA-based myocardial segmentation (CAMS)-derived myocardial volume supplied by each vessel (right coronary artery RCA, left anterior descending LAD, left circumflex LCX) and the myocardial volume subtended to a stenotic segment (CAMS-%Vsub) were measured for labeling. The ML for (1) predicting vessel territories (CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA) and CAMS-%Vsub and (2) identifying the lesions with an FFR < 0.80 was constructed. Angiography-based ML, employing a light gradient boosting machine (GBM), showed mean absolute errors (MAEs) of 5.42%, 8.57%, and 4.54% for predicting CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA, respectively. The percent myocardial volumes predicted by ML were used to predict the CAMS-%Vsub. With 5-fold cross validation, the MAEs between ML-predicted percent myocardial volume subtended to a stenotic segment (ML-%Vsub) and CAMS-%Vsub were minimized by the elastic net (6.26% ± 0.55% for LAD, 5.79% ± 0.68% for LCX, and 2.95% ± 0.14% for RCA lesions). Using all attributes (age, sex, involved vessel segment, and angiographic features affecting the myocardial territory and stenosis degree), the ML classifiers (L2 penalized logistic regression, support vector machine, and random forest) predicted an FFR < 0.80 with an accuracy of approximately 80% (area under the curve AUC = 0.84-0.87, 95% confidence intervals 0.71-0.94) in the test set, which was greater than that of diameter stenosis (DS) > 53% (66%, AUC = 0.71, 95% confidence intervals 0.65-0.78). The external validation showed 84% accuracy (AUC = 0.89, 95% confidence intervals 0.83-0.95). The retrospective design, single ethnicity, and the lack of clinical outcomes may limit this prediction model's generalized application.
We found that angiography-based ML is useful to predict subtended myocardial territories and ischemia-producing lesions by mitigating the visual-functional mismatch between angiographic and FFR. Assessment of clinical utility requires further validation in a large, prospective cohort study.
Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD ...progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD.
In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture.
Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD.
cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.
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