ImportanceAlthough atherosclerosis represents the primary driver of coronary artery disease, evaluation and treatment approaches have historically relied upon indirect markers of atherosclerosis th... Show moreImportanceAlthough atherosclerosis represents the primary driver of coronary artery disease, evaluation and treatment approaches have historically relied upon indirect markers of atherosclerosis that include surrogates (cholesterol), signs (angina), and sequelae (ischemia) of atherosclerosis. Direct quantification and characterization of atherosclerosis may encourage a precision heart care paradigm that improves diagnosis, risk stratification, therapeutic decision-making, and longitudinal disease tracking in a personalized fashion.ObservationsThe American College of Cardiology Innovations in Prevention Working Group introduce the Atherosclerosis Treatment Algorithms that personalize medical interventions based upon atherosclerosis findings from coronary computed tomography angiography (CTA) and cardiovascular risk factors. Through integration of coronary CTA-based atherosclerosis evaluation, clinical practice guidelines, and contemporary randomized controlled trial evidence, the Atherosclerosis Treatment Algorithms leverage patient-specific atherosclerosis burden and progression as primary targets for therapeutic intervention. After defining stages of atherosclerosis severity by coronary CTA, Atherosclerosis Treatment Algorithms are described for worsening stages of atherosclerosis for patients with lipid disorders, diabetes, hypertension, obesity, and tobacco use. The authors anticipate a rapid pace of research in the field, and conclude by providing perspectives on future needs that may improve efforts to optimize precision prevention of coronary artery disease. Importantly, the Atherosclerosis Treatment Algorithms are not endorsed by the American College of Cardiology, and should not be interpreted as a statement of American College of Cardiology policy.Conclusions and RelevanceWe describe a precision heart care approach that emphasizes atherosclerosis as the primary disease target for evaluation and treatment. To our knowledge, this is the first proposal to use coronary atherosclerosis burden and progression to personalize therapy selection and therapy changes, respectively. Show less
A cogent and comprehensive pathologic report is essential for optimal patient management, cancer staging, and prognostication. This article details the International Collaboration on Cancer... Show moreA cogent and comprehensive pathologic report is essential for optimal patient management, cancer staging, and prognostication. This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the vulval carcinoma reporting data set. It describes the "core" and "noncore" elements to be included in pathology reports for vulval carcinoma, inclusive of clinical, macroscopic, microscopic, and ancillary testing considerations. It provides definitions and commentary for the evidence and/or consensus-based deliberations for each element included in the data set. The commentary also discusses controversial issues, such as p16/human papillomavirus testing, tumor grading and measurements, as well as elements that show promise and warrant further evidence-based study. A summary and discussion of the updated vulval cancer staging system by the International Federation of Obstetricians and Gynaecologists (FIGO) in 2021 is also provided. We hope the widespread implementation of this data set will facilitate consistent and accurate reporting, data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and serve as a platform to improve patient outcomes. Show less
Primary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International... Show morePrimary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International Collaboration on Cancer Reporting (ICCR) is developing standardized, evidence-based reporting data sets for multiple cancer sites. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary vaginal carcinomas and present the core and noncore data elements with explanatory commentaries. This data set has incorporated the updates in the 2020 World Health Organization Classification of Female Genital Tumours, 5th edition. The data set addresses controversial issues such as tumor grading, margin assessment, and the role of ancillary studies. The adoption of this data set into clinical practice will help ensure standardized data collection across different countries, facilitate future research on vaginal carcinomas, and ultimately lead to improvements in patient care. Show less
Background: Extended pelvic nodal dissection (ePLND) represents the gold standard for nodal staging in prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) radioguided surgery (RGS)... Show moreBackground: Extended pelvic nodal dissection (ePLND) represents the gold standard for nodal staging in prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) radioguided surgery (RGS) could identify lymph node invasion (LNI) during robotassisted radical prostatectomy (RARP).Objective: To report the planned interim analyses of a phase 2 prospective study (NCT04832958) aimed at describing PSMA-RGS during RARP.Design, setting, and participants: A phase 2 trial aimed at enrolling 100 patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging with a risk of LNI of >5% was conducted. Overall, 18 patients were enrolled between June 2021 and March 2022. Among them, 12 patients underwent PSMA-RGS and represented the study cohort.Surgical procedure: All patients received Ga-68-PSMA positron emission tomography (PET)/magnetic resonance imaging; Tc-99m-PSMA-I&S was synthesised and administered intravenously the day before surgery, followed by single-photon emission computed tomography/computed tomography. A Drop-In gamma probe was used for in vivo measurements. All positive lesions (count rate >= 2 compared with background) were excised and ePLND was performed.Measurements: Side effects, perioperative outcomes, and performance characteristics of robot-assisted PSMA-RGS for LNI were measured.Results and limitations: Overall, four (33%), six (50%), and two (17%) patients had intermediate-risk, high-risk, and locally advanced PCa. Overall, two (17%) patients had pathologic nodal uptake at PSMA PET. The median operative time, blood loss, and length of stay were 230 min, 100 ml, and 5 d, respectively. No adverse events and intraoperative complications were recorded. One patient experienced a 30-d complication (ClavienDindo 2; 8.3%). Overall, three (25%) patients had LNI at ePLND. At per-region analyses on 96 nodal areas, sensitivity, specificity, positive predictive value, and negative predictive value of PSMA-RGS were 63%, 99%, 83%, and 96%, respectively. On a per-patient level, sensitivity, specificity, positive predictive value, and negative predictive values of PSMA-RGS were 67%, 100%, 100%, and 90%, respectively.Conclusions: Robot-assisted PSMA-RGS in primary staging is a safe and feasible procedure characterised by acceptable specificity but suboptimal sensitivity, missing micrometastatic nodal disease.Patient summary: Prostate-specific membrane antigen radioguided robot-assisted surgery is a safe and feasible procedure for the intraoperative identification of nodal metastases in cN0cM0 prostate cancer patients undergoing robot-assisted radical prostatectomy with extended pelvic lymph node dissection. However, this approach might still miss micrometastatic nodal dissemination. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. Show less
We developed the bitterling as a unique, well-studied model organism in the area of the evolutionary ecology of brood parasitism. The bitterling-mussel relationship, interspecific mussel host... Show moreWe developed the bitterling as a unique, well-studied model organism in the area of the evolutionary ecology of brood parasitism. The bitterling-mussel relationship, interspecific mussel host preference, and mussel gill structure are studied in detail, to help understand the developmental adaptation of bitterling embryos in response to their mussel hosts. Our complete stage series of the bitterling species R. ocellatus in Chapter 2 is a new, character-based systems that are compatible with the widely-used zebrafish staging system. With time-lapse video, we demonstrated the dynamic processes of hatching moment of the rosy bitterling in real time, which indicates the hatching process is mechanical rather than enzymatic. In Chapter 3, we described the neuroanatomy of bitterling for the first time, filling the gaps in the previous embryonic research in various bitterling taxa. Combined with the molecular analysis of brain early development in Chapter 4, brain development in the rosy bitterling is compared with that in the zebrafish. In Chapter 5, we studied the morphogenetic process of blastokinesis in the bitterling embryo, and its possible relation to brood parasitism. Show less
Laven, P.; Beltman, J.J.; Bense, J.E.; Aa, M.A. van der; Gorp, T. van; Vos, M.C.; ... ; Kruitwagen, R.F.P.M. 2021
Background: Incomplete surgical staging of patients with early-stage epithelial ovarian cancer (EOC) has been reported in up to 98% of cases, when based on the International Federation of... Show moreBackground: Incomplete surgical staging of patients with early-stage epithelial ovarian cancer (EOC) has been reported in up to 98% of cases, when based on the International Federation of Obstetrics and Gynecology (FIGO) staging procedure. The aim of the present retrospective study was to clarify the reasons for incomplete staging.Methods: The PRISMA (Prevention Recovery Information System for Monitoring and Analysis) technique was used to evaluate cases with FIGO I-IIa EOC based on incomplete staging from five gynecologic oncologic center hospitals in the Netherlands in the period 2010-2014.Results: Fifty cases with an incomplete surgical staging of EOC according to national guidelines were included. The most common reasons for incomplete staging were insufficient random biopsies of the peritoneum (n = 34, 68%), and less than ten lymph nodes being resected and/or found at pathology (n = 16, 32%). The most mentioned reason for not performing biopsies was, besides forgetting to do so, believing that after careful inspection and palpation, taking biopsies is irrelevant and/or already are being taken while performing a hysterectomy (peritoneum of cul-de-sac, bladder). The value of contralateral pelvic lymph node dissection in case of a unilateral ovarian malignancy was also doubted, influencing the number of lymph nodes resected.Conclusions: The most important reasons for incomplete staging in EOC are, besides omitting elements by accident, questioning the importance of obligatory elements of the staging procedure. A structured list of staging steps during surgery and more evidence-based consensus concerning these obligatory elements might increase the number of complete staging procedures in EOC. (C) 2021 Published by Elsevier Inc. Show less
Smolle, M.A.; Sande, M. van de; Hayes, A.; Bergovec, M.; Smith, H.G.; Liegl-Atzwanger, B.; ... ; Leithner, A. 2021
Background: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not... Show moreBackground: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not improving prognostic accuracy in comparison to the 7th version. This study aimed at investigating the prognostic accuracy of both AJCC-versions in STS-patients treated at European tertiary sarcoma centres.Methods: 1032 patients (mean age: 60.7 +/- 16.3 years; 46.0% [n = 475] females; median follow-up: 38.6 months), treated at five tertiary sarcoma centres for localised, intermediate or high-grade STS of extremities and trunk were retrospectively included. Uni- and multivariate Cox-regression models and Harrell's C-indices were calculated to analyse prognostic factors for overall survival (OS) and assess prognostic accuracy.Results: In univariate analysis, prognostic accuracy for OS was comparable for both AJCC-versions (C-index: 0.620 [8th] vs. 0.614 [7th]). By adding margins, age, gender, and histology to the multivariate models, prognostic accuracy of both versions could be likewise improved (C-index: 0.714 [8th] vs. 0.705 [7th]). Moreover, tumour depth did not significantly contribute to prognostic accuracy of the 8th version's multivariate model (C-index for both models: 0.714). Stratification into four main T-stages based on tumour size only, as implemented in the 8th version, significantly improved prognostic accuracy between each category. However, T-stages as defined in the 7th version had poorer discriminatory power (C-index: 0.625 [8th] vs. 0.582 [7th]).Conclusion: Both AJCC-versions perform equally well regarding prognostic accuracy. Yet, simplification of the 8th version by omitting tumour depth as T-stage-defining parameter, whilst emphasizing the importance of tumour size, should be considered advantageous. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Introduction: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we... Show moreIntroduction: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process.Methods: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting.Results: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits.Conclusion: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. Show less
The research is dedicated to Gilbert Blin’s work in staging operas of the seventeenth and eighteenth centuries. Nourished by a decade of productions for the Boston Early Music Festival, the first... Show moreThe research is dedicated to Gilbert Blin’s work in staging operas of the seventeenth and eighteenth centuries. Nourished by a decade of productions for the Boston Early Music Festival, the first objective of his dissertation is to enable a better understanding of both his creative and interpretive processes in the operatic field. The main research question he attempts to answer in his dissertation can be phrased as follows: how can a post-modern stage director use historical research for creative purposes? The title of this dissertation, The Reflections of Memory, is the appellation Gilbert Blin has been giving to his current approach as an artist and constitutes a conceptual answer to this question Show less
Our current mycosis fungoides (MF) and Sezary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sezary counts but results... Show moreOur current mycosis fungoides (MF) and Sezary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sezary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry.No large study comparing blood-class as defined by Sezary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p < 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis.For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4thornCD7-or CD4+CD26- where B0<250/mu L, B1 = 250/mu l -<1000/mu L and B2 >= 1000/mu L plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known. (C) 2018 The Authors. Published by Elsevier Ltd. Show less
To outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT)... Show moreTo outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT) and treatment response assessment.PubMed, Embase and the Cochrane library were searched identifying all articles related to the use of MRI in oesophageal cancer. Data regarding the value of MRI in the areas of interest were extracted in order to calculate sensitivity, specificity, predictive values and accuracy for group-related outcome measures.Although historically poor, recent improvements in MRI protocols and techniques have resulted in better imaging quality and the valuable addition of functional information. In recent studies, similar or even better results have been achieved using optimised MRI compared with other imaging strategies for T- and N-staging. No studies clearly report on the role of MRI in oesophageal tumour delineation and real-time guidance for RT so far. Recent pilot studies showed that functional MRI might be capable of predicting pathological response to treatment and patient prognosis.In the near future MRI has the potential to bring improvement in staging, tumour delineation and real-time guidance for RT and assessment of treatment response, thereby complementing the limitations of currently used imaging strategies.aEuro cent MRI's role in oesophageal cancer has been somewhat limited to date.aEuro cent However MRI's ability to depict oesophageal cancer is continuously improving.aEuro cent Optimising TN-staging, radiotherapy planning and response assessment ultimately improves individualised cancer care.aEuro cent MRI potentially complements the limitations of other imaging strategies regarding these points. Show less
The term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of... Show moreThe term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of diagnosis. In recent years, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas and different classification schemes were used. In the new WHO-EORTC consensus classification for cutaneous lymphomas published in 2005, three major groups of primary cutaneous B-cell lymphoma are distinguished: primary cutaneous marginal zone B-cell lymphoma and primary cutaneous follicle center lymphoma with a good prognosis, and primary cutaneous diffuse large B-cell lymphoma, leg type with an intermediate prognosis. Studies presented in this thesis focus on three aspects of these primary cutaneous B-cell lymphomas: (1) the clinical usefulness of the WHO-EORTC classification in daily practice, (2) the validity of prognostic parameters reported in previous studies and identified in patient groups classified according to previously used classification schemes and (3) optimal management for the different types of primary cutaneous B-cell lymphomas as defined in the WHO-EORTC classification. Show less
