Measuring and correcting staff variability in large-scale OSCEs.

CONTEXT: Objective Structured Clinical Examinations (OSCEs) are an increasingly popular evaluation modality for medical students. While the face-to-face interaction allows for more in-depth assessment, it may cause standardization problems. Methods to quantify, limit or adjust for examiner effects are needed. METHODS: Data originated from 3 OSCEs undergone by 900-student classes of 5th- and 6th-year medical students at Université Paris Cité in the 2022-2023 academic year. Sessions had five stations each, and one of the three sessions was scored by consensus by two raters (rather than one). We report OSCEs' longitudinal consistency for one of the classes and staff-related and student variability by session. We also propose a statistical method to adjust for inter-rater variability by deriving a statistical random student effect that accounts for staff-related and station random effects. RESULTS: From the four sessions, a total of 16,910 station scores were collected from 2615 student sessions, with two of the sessions undergone by the same students, and 36, 36, 35 and 20 distinct staff teams in each station for each session. Scores had staff-related heterogeneity (p<10-15), with staff-level standard errors approximately doubled compared to chance. With mixed models, staff-related heterogeneity explained respectively 11.4%, 11.6%, and 4.7% of station score variance (95% confidence intervals, 9.5-13.8, 9.7-14.1, and 3.9-5.8, respectively) with 1, 1 and 2 raters, suggesting a moderating effect of consensus grading. Student random effects explained a small proportion of variance, respectively 8.8%, 11.3%, and 9.6% (8.0-9.7, 10.3-12.4, and 8.7-10.5), and this low amount of signal resulted in student rankings being no more consistent over time with this metric, rather than with average scores (p=0.45). CONCLUSION: Staff variability impacts OSCE scores as much as student variability, and the former can be reduced with dual assessment or adjusted for with mixed models. Both are small compared to unmeasured sources of variability, making them difficult to capture consistently.

Outcome and survival were similar with laparoscopic and open pancreatectomy in 102 solid pseudopapillary neoplasms.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors predominantly in young women. We report the largest single-center cohort study comparing resection of SPNP by laparoscopic approach (LA) and the open approach (OA). METHOD: Between 2001 and 2021, 102 patients (84% women, median age: 30) underwent pancreatectomy for SPNP and were retrospectively studied. Demographic, perioperative, pathological, early and the long-term results were evaluated between patients operated by LA and those by OA. RESULTS: Population included 40 LA and 62 OA. There were no significant differences in demographics data between the groups. A preoperative biopsy by endoscopic ultrasound was performed in 45 patients (44%) with no difference between the groups. Pancreatoduodenectomy (PD) was less frequently performed by LA (25 vs 53%, p = 0.004) and distal pancreatectomy (DP) was more frequently performed by LA (40 vs 16%, p = 0.003). In the subgroup analysis by surgical procedure, LA-PD was associated with one mortality, less median blood loss (180 vs 200 ml, p = 0.034) and fewer harvested lymph nodes (11 vs 15, p = 0.02). LA-DP was associated with smaller median tumor size on imaging (40 vs 80mm, p = 0.048), shorter surgery (135 vs 190 min, p = 0.028), and fewer complications according to the median comprehensive complication index score (0 vs 8.7, p = 0.048). LA-Central pancreatectomy was associated with shorter surgery (160 vs 240, p = 0.037), less median blood loss (60 vs 200, p = 0.043), and less harvested lymph nodes (5 vs 2, p = 0.025). After a median follow-up of 60 months, two recurrences (2%) were observed and were unrelated to the approach. CONCLUSIONS: The LA for SPNP appears to be safe, should be applied cautiously in case of PD for large lesion, and was not associated with recurrence.

CARECOS study: Medical students' empathy as assessed with the CARE measure by examiners versus standardized patients during a formative Objective and Structured Clinical Examination (OSCE) station.

PURPOSE: To assess the Consultation And Relational Empathy (CARE) measure as a tool for examiners to assess medical students' empathy during Objective and Structured Clinical Examinations (OSCEs), as the best tool for assessing empathy during OSCEs remains unknown. METHODS: We first assessed the psychometric properties of the CARE measure, completed simultaneously by examiners and standardized patients (SP, either teachers - SPteacher - or civil society members - SPcivil society), for each student, at the end of an OSCE station. We then assessed the qualitative/quantitative agreement between examiners and SP. RESULTS: We included 129 students, distributed in eight groups, four groups for each SP type. The CARE measure showed satisfactory psychometric properties in the context of the study but moderate, and even poor inter-rater reliability for some items. Considering paired observations, examiners scored lower than SPs (p < 0.001) regardless of the SP type. However, the difference in score was greater when the SP was a SPteacher rather than a SPcivil society (p < 0.01). CONCLUSION: Despite acceptable psychometric properties, inter-rater reliability of the CARE measure between examiners and SP was unsatisfactory. The choice of examiner as well as the type of SP seems critical to ensure a fair measure of empathy during OSCEs.

Appropriate use of morphological imaging for assessing treatment response and disease progression of neuroendocrine tumors.

Neuroendocrine tumors (NETs) are relatively rare neoplasms displaying heterogeneous clinical behavior, ranging from indolent to aggressive forms. Patients diagnosed with NETs usually receive a varied array of treatments, including somatostatin analogs, locoregional treatments (ablation, intra-arterial therapy), cytotoxic chemotherapy, peptide receptor radionuclide therapy (PRRT), and targeted therapies. To maximize therapeutic efficacy while limiting toxicity (both physical and economic), there is a need for accurate and reliable tools to monitor disease evolution and progression and to assess the effectiveness of these treatments. Imaging morphological methods, primarily relying on computed tomography (CT) and magnetic resonance imaging (MRI), are indispensable modalities for the initial evaluation and continuous monitoring of patients with NETs, therefore playing a pivotal role in gauging the response to treatment. The primary goal of assessing tumor response is to anticipate and weigh the benefits of treatments, especially in terms of survival gain. The World Health Organization took the pioneering step of introducing assessment criteria based on cross-sectional imaging. This initial proposal standardized the measurement of lesion sizes, laying the groundwork for subsequent criteria. The Response Evaluation Criteria in Solid Tumors (RECIST) subsequently refined and enhanced these standards, swiftly gaining acceptance within the oncology community. New treatments were progressively introduced, targeting specific features of NETs (such as tumor vascularization or expression of specific receptors), and achieving significant qualitative changes within tumors, although associated with minimal or paradoxical effects on tumor size. Several alternative criteria, adapted from those used in other cancer types and focusing on tumor viability, the slow growth of NETs, or refining the existing size-based RECIST criteria, have been proposed in NETs. This review article aims to describe and discuss the optimal utilization of CT and MRI for assessing the response of NETs to treatment; it provides a comprehensive overview of established and emerging criteria for evaluating tumor response, along with comparative analyses. Molecular imaging will not be addressed here and is covered in a dedicated article within this special issue.

European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes.

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow-up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET-associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work-up as well as therapeutic management of the individual hormonal syndromes in well-differentiated, grade 1-3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.

High Tumor Uptake on 18F-FDOPA PET/CT Indicates Poor Prognosis in Patients with Metastatic Midgut Neuroendocrine Tumors: A Study from the Groupe d'étude des Tumeurs Endocrines and ENDOCAN-RENATEN Network.

PET/CT with 6-18F-fluoro-l-dopa (18F-FDOPA) has high diagnostic performance for midgut neuroendocrine tumors (NETs). We explored the prognostic role of 18F-FDOPA PET/CT uptake in metastatic midgut NETs. Methods: We included, in a test cohort (n = 166) and a full external validation cohort (n = 86), all consecutive patients with metastatic midgut NETs who underwent 18F-FDOPA PET/CT in 5 expert centers from 2010 to 2021. We measured the maximal uptake (SUVmax and SUVpeak) of the tumor and nontumor liver on each 18F-FDOPA PET/CT scan. We measured overall survival (OS) from the time of PET/CT and assessed prognostic factors using Kaplan-Meier and multivariable Cox proportional-hazards analyses in the test cohort, with replication in the validation cohort. Results: Patients had similar characteristics in both cohorts. In the test cohort, median follow-up was 60.3 mo. Patients with an SUVpeak tumor-to-liver (T/L) ratio of more than 4.2 had significantly shorter survival than those with a ratio of 4.2 or less (P = 0.01), with a 5-y OS rate of 74.1% ± 4.5% versus 95% ± 3.4%, respectively. On multivariable analysis, an SUVpeak T/L ratio of more than 4.2 remained associated with shorter OS (hazard ratio, 2.30; 95% CI, 1.02-5.22; P = 0.046) after adjustment for age, grade, number of previous lines, number of metastatic sites, and presence of carcinoid syndrome. In the validation cohort, the 5-y OS rate was 100% versus 57.8% ± 12.5% in patients with an SUVpeak T/L ratio ≤ 4.2 or > 4.2, respectively (P = 0.075). An increasing SUVpeak T/L ratio over time tended to have a pejorative prognostic impact. Conclusion: Tumor uptake on 18F-FDOPA PET/CT is an independent prognostic factor in patients with metastatic midgut NETs.

Management and outcomes of carcinoid heart disease with liver metastases of midgut neuroendocrine tumours.

OBJECTIVE: Despite recent advances in surgical and interventional techniques, knowledge on the management of carcinoid heart disease (CHD) remains limited. In a cohort of patients with liver metastases of midgut neuroendocrine tumours (NETs), we aimed to describe the perioperative management and short-term outcomes of CHD. METHODS: From January 2003 to June 2022, consecutive patients with liver metastases of midgut NETs and severe CHD (severe valve disease with symptoms and/or right ventricular enlargement) were included at Beaujon and Bichat hospitals. All patients underwent clinical evaluation and echocardiography. RESULTS: Out of 43 (16%) consecutive patients with severe CHD and liver metastases of midgut NETs, 79% presented with right-sided heart failure. Tricuspid valve replacement was performed in 26 (53%) patients including 19 (73%) cases of combined pulmonary valve replacement. The 30-day postoperative mortality rate was high (19%), and preoperative heart failure was associated with worse survival (p=0.02). Epicardial pacemakers were systematically implanted in operated patients and 25% were permanently paced. A postoperative positive right ventricular remodelling was observed (p<0.001). A greater myofibroblastic infiltration was observed in pulmonary versus tricuspid valves (p<0.001), suggesting that they may have been explanted at an earlier stage of the disease than the tricuspid valve, with therefore potential for evolution. CONCLUSIONS: We observed a high postoperative mortality rate and baseline right-sided heart failure was associated with worse outcome. In surviving patients, a positive right ventricular remodelling was observed. Prospective, multicentre studies are warranted to better define the management strategy and to identify biomarkers associated with outcome in CHD.

Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors: Alternatives to RECIST.

RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06-3.40; p = .03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p = .91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. CLINICAL TRIAL REGISTRATION: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as "E-NETNET-L-E-CT" July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.

Spatial and temporal heterogeneity of digestive neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are initially monoclonal neoplasms that progressively become polyclonal, with very different genotypic and phenotypic characteristics leading to biological differences, including the Ki-67 proliferation index, morphology, or sensitivity to treatments. Whereas inter-patient heterogeneity has been well described, intra-tumor heterogeneity has been little studied. However, NENs present a high degree of heterogeneity, both spatially within the same location or between different lesions, and through time. This can be explained by the emergence of tumor subclones with different behaviors. These subpopulations can be distinguished by the Ki-67 index, but also by the expression of hormonal markers or by differences in the intensity of uptake on metabolic imaging, such as 68Ga-somatostatin receptor and Fluorine-18 fluorodeoxyglucose positron emission tomography. As these features are directly related to prognosis, it seems mandatory to move toward a standardized, improved selection of the tumor areas to be studied to be as predictive as possible. The temporal evolution of NENs frequently leads to changes in tumor grade over time, with impact on prognosis and therapeutic decision-making. However, there is no recommendation regarding systematic biopsy of NEN recurrence or progression, and which lesion to sample. This review aims to summarize the current state of knowledge, the main hypotheses, and the main implications regarding intra-tumor spatial and temporal heterogeneity in digestive NENs.

Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours.

PURPOSE: There is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET. METHODS: We performed a pooled univariate analysis of reported toxicity in patients treated in five phase 2 and phase 3 clinical trials with MKI in the GEP NET setting: sunitinib (SU11248, SUN1111), Pazopanib (PAZONET), sorafenib-bevacizumab (GETNE0801) and Lenvatinib (TALENT). Differential toxicities between male and female patients were evaluated considering relationship with study drug and different weights of each trial by random effect adjustment. RESULTS: We found nine toxicities which were more frequent in female patients (leukopenia, alopecia, vomiting, headache, bleeding, nausea, dysgeusia, neutrophil count decreased and dry mouth) and two toxicities being more frequent in male patients (Anal Symptoms and Insomnia). Asthenia and diarrhoea were the only severe (Grade 3-4) toxicities more frequent in female patients. CONCLUSIONS: Sex-related differences in toxicity with the MKI treatment require targeted information and individualised management of patients with NET. Differential reporting of toxicity should be promoted when clinical trials are published.

Carcinoid heart disease in patients with midgut neuroendocrine tumours.

Carcinoid heart disease (CHD) is the main complication of carcinoid syndrome (CS) associated with metastatic small intestine neuroendocrine tumours (NETs). The pathophysiology of CHD is partly understood but vasoactive hormones secreted by NETs, especially serotonin, play a major role, leading to the formation of fibrous plaques. These plaque-like deposits involve the right side of the heart in >90% of cases, particularly the tricuspid and pulmonary valves, which become thickened, retracted and immobile, resulting in regurgitation or stenosis. CHD represents a major diagnostic and therapeutic challenge for patients with NET and CS and is associated with increased risk of morbidity and mortality. CHD often occurs 2-5 years after the diagnosis of metastatic NET, but diagnosis of CHD can be delayed as patients are often asymptomatic for a long time despite severe heart valve involvement. Circulating biomarkers (5HIAA, NT-proBNP) are relevant tools but transthoracic echocardiography is the key examination for diagnosis and follow-up of CHD. However, there is no consensus on the optimal indications and frequency of TTE and biomarker dosing regarding screening and diagnosis. Treatment of CHD is complex and requires a multidisciplinary approach. It relies on antitumour treatment, control of CS and surgical valve replacement in cases of severe CHD. However, cardiac surgery is associated with a high risk of mortality, notably due to perioperative carcinoid crisis and right ventricular dysfunction. Timing of surgery is the most crucial point of CHD management and relies on the case-by-case determination of the optimal compromise between tumour progression, cardiac symptoms and CS control.

Putting undergraduate medical students in AI-CDSS designers' shoes: An innovative teaching method to develop digital health critical thinking.

INTRODUCTION: Digital health programs are urgently needed to accelerate the adoption of Artificial Intelligence and Clinical Decision Support Systems (AI-CDSS) in clinical settings. However, such programs are still lacking for undergraduate medical students, and new approaches are required to prepare them for the arrival of new and unknown technologies. At University Paris Cité medical school, we designed an innovative program to develop the digital health critical thinking of undergraduate medical students that consisted of putting medical students in AI-CDSS designers' shoes. METHODS: We followed the six steps of Kern's approach for curriculum development: identification of needs, definition of objectives, design of an educational strategy, implementation, development of an assessment and design of program evaluation. RESULTS: A stand-alone and elective AI-CDSS program was implemented for fourth-year medical students. Each session was designed from an AI-CDSS designer viewpoint, with theoretical and practical teaching and brainstorming time on a project that consisted of designing an AI-CDSS in small groups. From 2021 to 2022, 15 students were enrolled: they rated the program 4.4/5, and 80% recommended it. Seventy-four percent considered that they had acquired new skills useful for clinical practice, and 66% felt more confident with technologies. The AI-CDSS program aroused great enthusiasm and strong engagement of students: 8 designed an AI-CDSS and wrote two scientific 5-page articles presented at the Medical Informatics Europe conference; 4 students were involved in a CDSS research project; 2 students asked for a hospital internship in digital health; and 1 decided to pursue PhD training. DISCUSSION: Putting students in AI-CDSS designers' shoes seemed to be a fruitful and innovative strategy to develop digital health skills and critical thinking toward AI technologies. We expect that such programs could help future doctors work in rapidly evolving digitalized environments and position themselves as key leaders in digital health.

Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET.

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.

FOLFOX-bevacizumab chemotherapy in patients with metastatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are highly vascularized neoplasms. While FOLFOX chemotherapy has shown efficacy in patients with advanced NETs, its combination with antiangiogenics has been scarcely described. Here, we report the efficacy and tolerance of FOLFOX-bevacizumab in this setting. We retrospectively studied all consecutive patients with metastatic NET treated by FOLFOX-bevacizumab in two expert centers from 2013 to 2020. We assessed time to treatment failure (TTF), objective response rate (ORR) and toxicity. We explored factors associated with TTF and ORR using multivariate analyses. We included 57 patients (35.1% female, median age 61.7 years), with pancreatic (66.7%), small-intestine (14%) or lung (7%) NETs. Most patients (57.9%) had extra-hepatic metastases and G3 NETs accounted for 40.3% of cases. Patients received a median of 17 cycles of treatment, including a median of seven cycles of bevacizumab and/or 5-fluorouracile maintenance. Median TTF was 15.5 months (95% CI: 9.8-21.2) and was shorter in patients age > 60 years (HR 2.56, 95% CI: 1.16-5.64), p = .020) and >1 previous systemic treatment line (HR 4.15, 95% CI: 1.96-8.78), p < .001). The ORR was 42.9% and was higher in cases of performance status at 0 (OR 5.25, 95% CI: 1.13-24.35), p = .034) and G3 NET (OR 5.39, 95% CI: 1.23-23.52), p = .025). The FOLFOX-bevacizumab combination has promising efficacy in patients with progressive metastatic NETs and notably for G3 NETs, for which optimal treatment as yet remains ill-defined. Hence, it could be a relevant alternative to alkylating-based chemotherapy in this setting and should be further explored prospectively.

Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment.

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was measured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test. Results The study included 119 patients (mean age, 60 years ± 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in responders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treatments, with better discrimination than RECIST and mRECIST. Keywords: CT, Chemoembolization, Embolization, Abdomen/GI, Liver Supplemental material is available for this article. © RSNA, 2023.

eOSCE stations live versus remote evaluation and scores variability.

BACKGROUND: Objective structured clinical examinations (OSCEs) are known to be a fair evaluation method. These recent years, the use of online OSCEs (eOSCEs) has spread. This study aimed to compare remote versus live evaluation and assess the factors associated with score variability during eOSCEs. METHODS: We conducted large-scale eOSCEs at the medical school of the Université de Paris Cité in June 2021 and recorded all the students' performances, allowing a second evaluation. To assess the agreement in our context of multiple raters and students, we fitted a linear mixed model with student and rater as random effects and the score as an explained variable. RESULTS: One hundred seventy observations were analyzed for the first station after quality control. We retained 192 and 110 observations for the statistical analysis of the two other stations. The median score and interquartile range were 60 out of 100 (IQR 50-70), 60 out of 100 (IQR 54-70), and 53 out of 100 (IQR 45-62) for the three stations. The score variance proportions explained by the rater (ICC rater) were 23.0, 16.8, and 32.8%, respectively. Of the 31 raters, 18 (58%) were male. Scores did not differ significantly according to the gender of the rater (p = 0.96, 0.10, and 0.26, respectively). The two evaluations showed no systematic difference in scores (p = 0.92, 0.053, and 0.38, respectively). CONCLUSION: Our study suggests that remote evaluation is as reliable as live evaluation for eOSCEs.

Life expectancy and likelihood of surgery in multiple endocrine neoplasia type 1: AFCE and GTE cohort study.

BACKGROUND: The overall natural history, risk of death and surgical burden of patients with multiple endocrine neoplasia type 1 (MEN1) is not well known. METHODS: Patients with MEN1 from a nationwide cohort were included. The survival of patients with MEN1 was compared with that of the general population using simulated controls. The cumulative probabilities of MEN1-specific operations and postoperative mortality were assessed, and surgical sequences were analysed using sunburst charts and Venn diagrams. RESULTS: A total of 1386 patients with MEN1 were included. Life expectancy was significantly reduced in patients with MEN1 compared with simulated controls from the general population, with a lifetime difference of 15 years. Mutations affecting the JunD interaction domain had a significant negative impact on survival. Survival for patients with MEN1 compared with the general population improved over time. The probability of experiencing at least one specific MEN1 operation was above 95 per cent after 75 years, and most patients had surgery at least twice during their lifetime. Time to a 50 per cent risk of MEN1 surgery was 30.5 years for patients born after 1960, compared with 47.9 years for those born before 1960. Sex and mutations affecting the JunD interacting domain had no impact on time to first surgery. There was considerable heterogeneity in surgical sequences, with no specific clinical pathway. CONCLUSION: Life expectancy was significantly lower among patients with MEN1 compared with the general population, and further decreased in patients with mutations affecting the JunD interacting domain. Almost all patients underwent at least one MEN1-specific operation during their lifetime, but there was no standardized sequence of surgery.

Immunophenotypic and molecular characterization of pancreatic neuroendocrine tumors producing serotonin.

Serotonin producing pancreatic neuroendocrine tumors (SP-PanNET) account for 0.58-1.4% of all pancreatic neuroendocrine tumors (PanNET). They may present with atypical symptoms, such as acute pancreatitis and are often radiologically characterized by main pancreatic duct dilatation. SP-PanNET are well differentiated neuroendocrine tumors (NET) distinct from classical PanNET by atypical serotonin secretion and abundant dense stroma deposition, like serotonin producing ileal NET leading in some cases to difficulties to reliably distinguish SP-PanNET from ileal NET metastases. The biology and molecular profile of SP-PanNET remain poorly characterized and the cell of origin within the pancreas is unclear. To address these questions, we analyzed a large cohort of SP-PanNET by immunohistochemistry (n = 29; ATRX, DAXX, MENIN, Islet1, PAX6, PDX1, ARX, CDX2), whole genome copy number array (Oncoscan™) and a large NGS panel (NovoPM™) (n = 10), FISH (n = 13) and RNA sequencing (n = 24) together with 21 ileal NET and 29 nonfunctioning PanNET (NF-PanNET). These analyses revealed a unique genomic profile with frequent isolated loss of chromosome 1 (14 cases-61%) and few pathogenic mutations (KMT2C in 2 cases, ARID1A in 1 case). Unsupervised RNAseq-based clustering showed that SP-PanNET were closer to NF-PanNET than ileal NET with an exclusive beta cell-like signature. SP-PanNET showed TGF-ß pathway activation signatures associated with extracellular matrix remodeling and similar signature were reproduced in vitro when pancreatic stellate cells were exposed to serotonin. SP-PanNET immunohistochemical profile resemble that of ileal NET except for PDX1 and PAX6 expression to a lesser extend suggesting that these two markers may be useful to diagnose SP-PanNET. Taken together, this suggests that SP-PanNET are a very specific PanNET entity with a peculiar biology leading to the characteristic fibrotic aspect.

Laparoscopic-assisted liver transplantation: A realistic perspective.

Laparoscopic approach was rarely described in recipients for liver transplantation (LT). We report the feasibility and safety of laparoscopic-assisted LT (LA-LT) in patients with unresectable liver metastases of neuroendocrine tumors. Total hepatectomy was performed laparoscopically with graft implantation through an upper midline incision. Liver grafts were retrieved from deceased donors. From July 2019 to July 2021, six patients (4 women, 2 men) underwent LA-LT. Median age and BMI were 46 (29-54) and 24 (19-35) kg/m2 , respectively. Implanted grafts were reduced (n = 3), full (n = 2), and a right split liver (n = 1). Median surgical time was 405 min (390-450) and median blood loss was 425 ml (250-600). Median cold and warm ischemia times were 438 min (360-575) and 35 min (30-40), respectively. Median anhepatic phase was 51 min (40-67) and midline incision was 14 cm (13-20) long. On postoperative day 5, median prothrombin index and serum bilirubin levels were 95% (70-117) and 11 (10-37) µmol/L, respectively. No Clavien-Dindo > III complications were encountered. Median hospital stay was 12 days (10-14). After a median follow-up of 8 (8-32) months, all patients were alive without tumor recurrence or adverse event. This preliminary series suggests that in selected patients, LA-LT is a safe and effective option.