This thesis aims to assess the differences and similarities between autoantibody-positive and autoantibody-negative RA from the start of complaints to the end of the disease. The described research... Show moreThis thesis aims to assess the differences and similarities between autoantibody-positive and autoantibody-negative RA from the start of complaints to the end of the disease. The described research was performed with the ultimate goal to clarify whether autoantibody-negative and autoantibody-positive RA are distinct diseases that require different diagnoses and treatment. Show less
Objective We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term... Show moreObjective We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term following ischemic stroke. Methods Data were used from the PROSpective Cohort with Incident Stroke-Berlin. NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within 7 days after the first-ever stroke. Seropositivity was defined as titers >= 1:10, low titers as <= 1:100 and high titers as > 1:100. We assessed CF at 1, 2 and 3 years after stroke with the Telephone Interview for Cognitive Status-modified (TICS-m) and used crude and propensity score adjusted inverse probability weighted generalized linear models to estimate the impact of NMDAR1-abs serostatus on TICS-m. Results Data on NMDAR1-abs (median day of sampling = 4[IQR = 2-5]) were available in 583/621 PROSCIS-B patients (39% female; median NIHSS = 2[IQR = 1-4]; median MMSE = 28[IQR:26-30]), of whom 76(13%) were seropositive (IgM: n = 48/IgA: n = 43/IgG: n = 2). Any NMDAR1-abs seropositivity had no impact on TICS-m compared to seronegative patients (beta crude = 0.69[95%CI = - 0.84 to 2.23]; beta adjusted = 0.65[95%CI = - 1.00 to 2.30]). Patients with low titers scored better on TICS-m compared to seronegative patients (beta crude = 2.33[95%CI = 0.76 to 3.91]; beta adjusted = 2.47[95%CI = 0.75 to 4.19]); in contrast, patients with high titers scored lower on TICS-m (beta crude = -2.82[95%CI = - 4.90 to - 0.74], beta adjusted = - 2.96[95%CI = - 5.13 to - 0.80]), compared to seronegative patients. Conclusion In our study, NMDAR1-abs seropositivity did not affect CF over 3 years after a first mild to moderate ischemic stroke. CF differed according to NMDAR1-abs serum titer, with patients with high NMDAR1-abs titers having a less favorable cognitive outcome compared to seronegative patients. Show less
Lauper, K.; Ludici, M.; Mongin, D.; Bergstra, S.A.; Choquette, D.; Codreanu, C.; ... ; Finckh, A. 2022
Background: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line... Show moreBackground: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i. Show less
Aims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with... Show moreAims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. Methods: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. Results: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolicload factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. Conclusion: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased leftventricular diastolic function, more apparent in females than in males. Show less
Over the last decades, increasingly so in the last years, epidemiological methods have been refined, making it challenging to keep abreast of all methodological developments. The choice of the data... Show moreOver the last decades, increasingly so in the last years, epidemiological methods have been refined, making it challenging to keep abreast of all methodological developments. The choice of the data analytical method directly influences the interpretation and clinical meaning of results of an analysis, yet it is undesirable that technical considerations define the subject of the investigation. Having a deeper understanding of the impact that data analytical decisions can have on the interpretation of numerical results of a study would help to apply analytical tools that are both suitable and appropriate to answer clinical questions. The aim of this thesis was to investigate the impact of choices regarding the design and statistical analysis of a study on the meaning of its numerical results in two sets of case studies in research into causal effects (Part I) and prediction research (Part II). The thesis concludes with a discussion on the role and importance of clinical research questions and estimands. Clearly defining a clinically relevant estimand ensures that data analytical decisions yield meaningful results. Making targeted research questions central to quantitative clinical research can reduce fallacious confidence in (complex) methods and can add to intelligibility of findings. Show less
Heus, E. de; Duijts, S.F.A.; Zwan, J.M. van der; Kapiteijn, E.; Dijkum, E.J.M.N. van; Herpen, C.M.L. van; Merkx, M.A.W. 2022
Introduction: Epidemiological discrepancies exist between rare and common can-cers. The aim of this population-based study was to compare rare versus common adult solid cancers in the Netherlands,... Show moreIntroduction: Epidemiological discrepancies exist between rare and common can-cers. The aim of this population-based study was to compare rare versus common adult solid cancers in the Netherlands, by providing incidence, prevalence and survival rates, evaluating trends in survival and comparing individual entities within domains and families.Methods: All adult patients with malignant solid cancers in the Netherlands between 1995 and 2019 were identified from the Netherlands Cancer Registry. Data on patient, tumour and treatment characteristics were collected, and relative survival and survival trends were ana-lysed.Results: A total of 170,628 patients with rare adult solid cancers and 806,023 patients with common adult solid cancers were included. Rare cancers accounted for 18% of all cancer di-agnoses (mean incidence), and 15% of the total ten-year cancer prevalence during 2010-2019. Overall 5-year survival was worse for rare cancers than for common cancers (52.0% versus 68.7%). Between 1995-1999 and 2015-2019, 5-year survival rates for rare cancers increased to a lesser extent (from 46.2% to 52.6%, i.e. 6.4%) than for common cancers (56.9% Show less
Schuttevaer, R.; Boogers, W.; Brink, A.; Dijk, W. van; Steenwinkel, J. de; Schuit, S.; ... ; Alsma, J. 2022
Objectives To investigate whether the Charlson Comorbidity Index (CCI) predicted short-term and long-term mortality in patients with a bloodstream infection visiting the emergency department (ED)... Show moreObjectives To investigate whether the Charlson Comorbidity Index (CCI) predicted short-term and long-term mortality in patients with a bloodstream infection visiting the emergency department (ED) and compare it to the often-validated National Early Warning Score (NEWS). Design A retrospective cohort study. Setting A tertiary hospital in the Netherlands. Participants Adult patients attending the ED with a blood culture-proven infection between 2012 and 2017 were included. We collected the comorbidities from the CCI and the vital signs from the NEWS. Main outcomes Short-term mortality (30-day) and long-term mortality (1 year). We assessed the predictive performance by discrimination, expressed as the area under the curve (AUC). Results We included 1039 patients with a blood culture-proven infection. Mortality was 10.4% within 30 days and 27.8% within 1 year. On average patients had two comorbidities (ranging from 0 to 6). Highly prevalent comorbidities were malignancy (30.2%) and diabetes mellitus (20.5%). The predictive performance of the CCI was highest for 1-year mortality (AUC 0.696 (95%CI) (0.660 to 0.732)) and better compared with the NEWS (AUC (95% CI) 0.594 (0.555 to 0.632)). For prediction of 30-day mortality, the NEWS was superior (AUC (95% CI) 0.706 (0.656 to 0.756)) to the comorbidities of the CCI (AUC (95% CI) 0.568 (0.507 to 0.628)). Conclusions We found that presenting comorbidity (ie, the CCI) is most useful to prognosticate long-term outcome in patients with bloodstream infection in the ED. Short-term mortality is more accurately predicted by deviating vital signs (ie, the NEWS). Show less
A direct comparison of two methods for estimating the treated incidence of schizophrenia: the first-contact design (current standard) vs. an electronic psychiatric case-register (new method). The... Show moreA direct comparison of two methods for estimating the treated incidence of schizophrenia: the first-contact design (current standard) vs. an electronic psychiatric case-register (new method). The assumptions underlying the first-contact design are tested. The causes of 2 to 4-fold difference in estimates are conceptualized in a 3-dimensional model. The model is tested on the Norther European incidence literature. Show less
Kok, A.A.L.; Pan, K.Y.; Rius-Ottenheim, N.; Jorg, F.; Eikelenboom, M.; Horsfall, M.; ... ; Penninx, B.W.J.H. 2022
Background: Little is known about the longer-term impact of the Covid-19 pandemic beyond the first months of 2020, particularly for people with pre-existing mental health disorders. Studies... Show moreBackground: Little is known about the longer-term impact of the Covid-19 pandemic beyond the first months of 2020, particularly for people with pre-existing mental health disorders. Studies including pre-pandemic data from large psychiatric cohorts are scarce. Methods: Between April 2020 and February 2021, twelve successive online questionnaires were distributed among participants of the Netherlands Study of Depression and Anxiety, Netherlands Study of Depression in Older Persons, and Netherlands Obsessive Compulsive Disorder Association Study (N = 1714, response rate 62%). Outcomes were depressive symptoms, anxiety, worry, loneliness, perceived mental health impact of the pandemic, fear of Covid-19, positive coping, and happiness. Using linear mixed models we compared trajectories between subgroups with different pre-pandemic chronicity of disorders and healthy controls. Results: Depressive, anxiety and worry symptoms were stable since April-May 2020 whereas happiness slightly decreased. Furthermore, positive coping steadily decreased and loneliness increased - exceeding pre-Covid and April-May 2020 levels. Perceived mental health impact and fear of Covid-19 fluctuated in accordance with national Covid-19 mortality rate changes. Absolute levels of all outcomes were poorer with higher chronicity of disorders, yet trajectories did not differ among subgroups. Limitations: The most vulnerable psychiatric groups may have been underrepresented and results may not be generalizable to lower income countries. Conclusions: After a year, levels of depressive and worry symptoms remained higher than before the pandemic in healthy control groups, yet not in psychiatric groups. Nevertheless, persistent high symptoms in psychiatric groups and increasing loneliness in all groups are specific points of concern for mental health care professionals. Show less
Hitzl, W.; Stamm, T.; Kloppenburg, M.; Ritter, M.; Gaisberger, M.; Zee-neuen, A. van der 2022
Background The present study aimed to predict the expected number of patients with osteoarthritis (OA) in Austria up to the year 2080. Methods Demographic data and population projections between... Show moreBackground The present study aimed to predict the expected number of patients with osteoarthritis (OA) in Austria up to the year 2080. Methods Demographic data and population projections between 2019 and 2080 were obtained from European authorities. Information about recent age- and sex-stratified prevalence of patients with self-reported physician-diagnosed OA was obtained from the Austrian Health Interview Survey (n = 15,771). Projections were stratified by age and sex; sensitivity analyses were performed based on aging, main (most likely), and growth scenarios of the population. Results Based on the projection, the overall increase in the total number of patients with OA from 2019 to 2080 will be 38% for men and women. In 2019, the highest number of OA-patients nested in the groups of persons aged 70-79 (n = 238,749) and 60-69 (n = 237,729) years. In 2080, the 80+ age group is predicted to have the highest number of OA with 421,548 individuals (i.e. factor 3.45 and factor 2.48 increase in the male and female group, respectively, compared to 2019), followed by the group aged 70-79 with 314,617 individuals (factor 1.45 and factor 1.28 increase in the male and female group, respectively, compared to 2019). Similar trends were found in the ageing and growing scenarios. Conclusions The projected increase in the occurrence of OA will likely lead to a substantial socioeconomic burden for the Austrian healthcare system in the near and far future. The current findings plead for the development of sustainable concepts for the treatment and prevention of OA by European authorities. Show less
This thesis describes studies on methods for answering questions about causality, specifically so-called what-if questions, in the presence of methodological obstacles such as confounding, missing... Show moreThis thesis describes studies on methods for answering questions about causality, specifically so-called what-if questions, in the presence of methodological obstacles such as confounding, missing data, and measurement error. Show less
Coeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It... Show moreCoeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It occurs frequently in both children and adults, affecting 1-4% of the population. The disease is associated with both gastrointestinal and extra-intestinal symptoms related to malabsorption and/or immune activation, and autoantibodies to tissue transglutaminase. Removal of gluten from the diet results in resolution of symptoms and enteropathy in the majority of patients. A good diagnostic work-up is important to avoid unnecessary restrictive diets in children. In this review on pediatric coeliac disease, we address epidemiology including predisposing environmental factors and possible preventive strategies, as well as the clinical presentation, diagnosis and follow-up. Show less
In the last decade, through Clinical Outcome Assessment, and especially measurement of patient-reported outcome measures (PROM)s, we, among others, have initiated a shift in focus from meningioma... Show moreIn the last decade, through Clinical Outcome Assessment, and especially measurement of patient-reported outcome measures (PROM)s, we, among others, have initiated a shift in focus from meningioma tumors to meningioma patients. In various studies we describe an improvement in surgical approaches for skull base meningioma. Nevertheless, patient functioning remains impaired in the long-term. We describe that on average nine years after treatment or diagnosis patients still suffer from participation restrictions in social situations with their friends, family, and at work. Often, at the outpatient clinic, we do not pay enough attention to these problems, especially as patient visits become less frequent in the long-term. Importantly, functioning of patients and their informal caregivers (i.e., close relatives/friends) is strongly interdependent. Moreover, patients and healthcare providers find different outcomes and care processes relevant. This underlines the importance of implementation of PROMs in clinical practice. The studies in this thesis suggest that meningioma care trajectories could benefit from the use of 1) case managers guiding patients and their informal caregivers, 2) implementation of PROMs, and 3) prediction models assisting in the identification of individual patients at high risk of long-term lowered functioning. Ideally, these trajectories should follow the value-based healthcare (VBHC) principles. Show less
Bizzarri, D.; Reinders, M.J.T.; Beekman, M.; Slagboom, P.E.; BBMRI-NL; Akker, E.B. van den 2022
Background Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples,... Show moreBackground Missing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. `metabolomics', is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage metabolomics to impute missing data in clinical variables routinely assessed in large epidemiological and clinical studies.Methods To this end, we have employed similar to 26,000 H-1-NMR metabolomics samples from 28 Dutch cohorts collected within the BBMRI-NL consortium, to create 19 metabolomics-based predictors for clinical variables, including diabetes status (AUC(5-Fold CV) = 0.94) and lipid medication usage (AUC(5-Fold CV) = 0.90).Findings Subsequent application in independent cohorts confirmed that our metabolomics-based predictors can indeed be used to impute a wide array of missing clinical variables from a single metabolomics data resource. In addition, application highlighted the potential use of our predictors to explore the effects of totally unobserved confounders in omics association studies. Finally, we show that our predictors can be used to explore risk factor profiles contributing to mortality in older participants.Interpretation To conclude, we provide H-1-NMR metabolomics-based models to impute clinical variables routinely assessed in epidemiological studies and illustrate their merit in scenarios when phenotypic variables are partially incomplete or totally unobserved. Copyright (C) 2021 The Author(s). Published by Elsevier B.V. Show less
Background: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Epidemiological data on SVT-related mortality rate is not available to date.& nbsp;Methods:... Show moreBackground: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Epidemiological data on SVT-related mortality rate is not available to date.& nbsp;Methods: We investigated time trends in SVT-related mortality rate, 2008-2019, in Veneto, an Italian high income region of approximatively 5,000,000 inhabitants. SVT-related deaths were identified by the following ICD-10 codes: I81 (portal vein thrombosis), K75.1 (phlebitis of portal vein), K76.3 (liver infarction), K76.5 (hepatic veno-occlusive disease) or I82.0 (Budd-Chiari syndrome).& nbsp;Results: During the study period, a total of 557,932 deaths were recorded. SVT was reported in 823 cases; 776 (94%) consisted of portal vein thrombosis. The age-standardized SVT-related mortality rate varied from 1.47 (year 2008) to 1.52 (year 2019) per 100,000 person-years. An increase in the cause-specific annual mortality rate was observed in women (0.56 in 2008 to 1.04 per 100,000 person-years in 2019; average annual percent change +5.7%, 95%CI +3.1; +8.3%). In men, the cause-specific mortality rate moved from 2.53 in 2008 to 2.03 per 100,000 person-years in 2019 (average annual percent change-1.2%, 95%CI-4.0; +1.6%). After conditioning for age and sex, the odds of having a concomitant liver disease were higher for SVT-related deaths (OR 31.6; 95% CI 17.1-37.0) compared with non-SVT-related deaths. This also applies to gastrointestinal cancers (OR 1.28; 95% CI 1.07-1.55), although to a lesser extent.& nbsp;Conclusions: We report first epidemiological estimates of SVT-related mortality in a Western country. These values will serve as a reference to weight novel potential factors associated with SVT-related death and interpret them from an epidemiological perspective. Show less
The increasing amount and complexity of data over the past decades have given rise to new sorts of questions, also in the field of infectious disease epidemiology. This thesis proposes methods to... Show moreThe increasing amount and complexity of data over the past decades have given rise to new sorts of questions, also in the field of infectious disease epidemiology. This thesis proposes methods to analyze data available at multiple resolution levels and to combine different data types in infectious disease surveillance. Hereby using techniques central to data science. Show less
Due to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors... Show moreDue to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors associated with CBC. We observed significant associations for a polygenic risk score of common germline variants (PRS313) and for different adjuvant systemic therapy regimens with (subtype-specific) CBC risk. These factors may be incorporated in CBC risk prediction models together with other known and available risk factors. For support of clinical decision making more biological information is needed to understand CBC development in women with invasive breast cancer and DCIS. As a first step towards implementation of a risk prediction model, we performed an exploratory interview study, which showed that patients had varying preferences for graphical presentation of probabilities in a CBC prediction model. In future studies, the prediction model should be incorporated in a decision support tool and implemented in clinical practice. This tool can then help to better identify women at high risk of CBC who may benefit from prophylactic surgery, while the estimates can also be used to reassure patients who are at low risk of developing CBC. Show less
A cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but... Show moreA cross-sectional relationship between low-grade inflammation -characterized by increased blood levels of Creactive protein (CRP) and pro-inflammatory cytokines- and anxiety has been reported, but the potential longitudinal relationship has been less well studied. We aimed to examine whether basal and lipopolysaccharide (LPS-)induced levels of inflammatory markers are associated with anxiety symptom severity over the course of nine years. We tested the association between basal and LPS-induced inflammatory markers with anxiety symptoms (measured with the Beck's Anxiety Inventory; BAI, Fear Questionnaire; FQ and Penn's State Worry Questionnaire; PSWQ) at 5 assessment waves over a period up nine years. We used multivariate-adjusted mixed models in up to 2867 participants of the Netherlands Study of Depression and Anxiety (NESDA). At baseline, 43.6% of the participants had a current anxiety disorder, of which social phobia (18.5%) was most prevalent. Our results demonstrated that baseline inflammatory markers were significantly associated with several outcomes of anxiety at baseline over nine subsequent years. BAI subscale of somatic (arousal) symptoms of anxiety, and FQ subscale of agoraphobia demonstrated the strongest effects with standardized betacoefficients of up to 0.14. The associations were attenuated by 25%-30% after adjusting for the presence of (comorbid) major depressive disorder (MDD), but remained statistically significant. In conclusion, we found that participants with high levels of inflammatory markers have on average high levels of anxiety consisting of physical arousal and agoraphobia, which tended to persist over a period of nine years, albeit with small effect sizes. These associations were partly driven by co-morbid depression. Show less
Jain, P.; Finger, P.T.; Fili, M.; Damato, B.; Coupland, S.E.; Heimann, H.; ... ; Amer Joint Comm Canc Ophthal 2021
Background To relate conjunctival melanoma characteristics to local control. Methods Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9... Show moreBackground To relate conjunctival melanoma characteristics to local control. Methods Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. Results 288 patients had a mean initial age of 59.7 +/- 16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. Conclusion This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management. Show less
Introduction: Whereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important... Show moreIntroduction: Whereas neoadjuvant chemo(radio)therapy is increasingly used in pancreatic cancer, it is currently not recommended for other periampullary (non-pancreatic) cancers. This has important implications for the relevance of the preoperative diagnosis for pancreatoduodenectomy. This retrospective multicentre cohort study aimed to determine the frequency of clinically relevant misdiagnoses in patients undergoing pancreatoduodenectomy for pancreatic or other periampullary cancer. Methods: Data from all consecutive patients who underwent a pancreatoduodenectomy between 2014 and 2018 were obtained from the prospective Dutch Pancreatic Cancer Audit. The preoperative diagnosis as concluded by the multidisciplinary team (MDT) meeting was compared with the final postoperative diagnosis at pathology to determine the rate of clinically relevant misdiagnosis (defined as missed pancreatic cancer or incorrect diagnosis of pancreatic cancer). Results: In total, 1244 patients underwent pancreatoduodenectomy of whom 203 (16%) had a clinically relevant misdiagnosis preoperatively. Of all patients with a final diagnosis of pancreatic cancer, 13% (87/ 679) were preoperatively misdiagnosed as distal cholangiocarcinoma (n = 41, 6.0%), ampullary cancer (n = 27, 4.0%) duodenal cancer (n = 16, 2.4%), or other (n = 3, 0.4%). Of all patients with a final diagnosis of periampullary (non-pancreatic) cancer, 21% (116/565) were preoperatively incorrectly diagnosed as pancreatic cancer. Accuracy of preoperative diagnosis was 84% for pancreatic cancer, 71% for distal cholangiocarcinoma, 73% for ampullary cancer and 73% for duodenal cancer. A prediction model for the preoperative likelihood of pancreatic cancer (versus other periampullary cancer) prior to pancreatoduodenectomy demonstrated an AUC of 0.88. Discussion: This retrospective multicentre cohort study showed that 16% of patients have a clinically relevant misdiagnosis that could result in either missing the opportunity of neoadjuvant chemotherapy in patients with pancreatic cancer or inappropriate administration of neoadjuvant chemotherapy in patients with non-pancreatic periampullary cancer. A preoperative prediction model is available on www.pancreascalculator.com. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
