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This is a protocol for a Cochrane Review (prototype). The objectives are as follows: This systematic review aims to summarize the available scientific literature on the effect of mindfulness-based approaches in children and adults with Chronic Tic Disorder (CTD) or Tourette Disorder (TD). More specifically, the research question is: What is the effectiveness of mindfulness-based interventions in reducing tic severity and improving overall functioning, quality of life, and co-occurring symptoms in children and adults with CTD or TD?

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(1) Background: Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Attention deficit and hyperactivity disorder (ADHD) is a common comorbidity of TS that adds further impairment. Cognitive-behavioural therapy (CBT) has shown efficacy in treating tics, yet its effectiveness in individuals with TS and comorbid ADHD remains unclear. Also, it is suggested that ADHD characteristics like executive dysfunction and inattention could hinder the response to CBT. This study aims to compare the response to CBT for tics and its maintenance six months post-therapy among TS individuals with and without ADHD symptoms. (2) Methods: In this study, 55 TS participants who completed 14-week CBT for tics were split into high (TS+) or low (TS-) ADHD symptomatology groups. Outcomes were evaluated using the Yale Global Tic Severity Scale (YGTSS) regarding global tic severity and motor and vocal tic frequency post-CBT and at a 6-month follow-up. (3) Results: No significant group difference was found regarding improvements post-CBT (n = 55), nor the maintenance six months later (n = 45). (4) Conclusions: ADHD symptoms may not hinder the response to CBT or its maintenance, suggesting that TS individuals with ADHD symptoms may not require specialized CBT interventions.

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Background: Tourette syndrome (TS) and Chronic Tic Disorder (CT) are neurodevelopmental conditions involving motor and/or phonic tics. Youth with tics may encounter feelings of isolation, diminished self-esteem and quality of life, and academic difficulties. A growing body of scientific literature suggests sex differences in youth with tics, but findings have been mixed so far. Because symptom severity peaks around puberty, understanding sex differences in tic manifestations and associated symptoms during this critical period is essential. Therefore, we aimed to assess sex differences related to tic symptoms, action planning styles, quality of life, and externalizing/internalizing symptoms in youth with tics. Methods: Our sample consisted of 66 youths with tics (19 girls) aged 7-14 (mean = 10 years). Youths were assessed with clinical interviews, as well as self- and parent-reported inventories evaluating tic symptoms, psychological profiles, and quality of life. Results: While no differences in tic symptoms were found, girls exhibited lower functional inflexibility, reduced overall functional planning effectiveness, and higher impairment in the psychological well-being subscale than boys. Additionally, girls had reduced general life satisfaction and social self-esteem. Boys reported more explosive outbursts, higher levels of hyperactivity, and more difficulties with self-concept. Conclusions: Our analyses suggested differences in several manifestations associated with tics. This introduces new perspectives that refine our understanding of sex differences. A better understanding of sex differences in tic disorders may eventually improve outcomes for all individuals living with these conditions.

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Background/Objectives: Tourette Syndrome (TS), Obsessive Compulsive Disorder (OCD), and Body-Focused Repetitive Behaviors (BFRB) are three disorders that share many similarities in terms of phenomenology, neuroanatomy, and functionality. However, despite the literature pointing toward a plausible spectrum of these disorders, only a few studies have compared them. Studying the neurocognitive processes using Event-Related Potentials (ERPs) offers the advantage of assessing brain activity with excellent temporal resolution. The ERP components can then reflect specific processes known to be potentially affected by these disorders. Our first goal is to characterize 'when' in the processing stream group differences are the most prominent. The second goal is to identify 'where' in the brain the group discrepancies could be. Methods: Participants with TS (n = 24), OCD (n = 18), and BFRB (n = 16) were matched to a control group (n = 59) and were recorded with 58 EEG electrodes during a visual counting oddball task. Three ERP components were extracted (i.e., P200, N200, and P300), and generating sources were modelized with Standardized Low-Resolution Electromagnetic Tomography. Results: We showed no group differences for the P200 and N200 when controlling for anxiety and depressive symptoms, suggesting that the early cognitive processes reflected by these components are relatively intact in these populations. Our results also showed a decrease in the later anterior P300 oddball effect for the TS and OCD groups, whereas an intact oddball effect was observed for the BFRB group. Source localization analyses with sLORETA revealed activations in the lingual and middle occipital gyrus for the OCD group, distinguishing it from the other two clinical groups and the controls. Conclusions: It seems that both TS and OCD groups share deficits in anterior P300 activation but reflect distinct brain-generating source activations.

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BACKGROUND: During the last century, life expectancy has doubled. As a result, senior patients with cancer are more frequently referred for possible surgery. Pancreatic surgery is a complex surgery associated with significant postoperative morbidity. Surgical decision-making in the elderly population can be difficult because outcomes in the elderly are poorly defined. Our objective is to characterize differences in mortality and morbidity for pancreatic surgery in the elderly population. METHODS: A retrospective review of all patients undergoing pancreatic head surgery in our tertiary referral center from 2015 to 2021 was conducted. Analysis was performed for the entire cohort, classifying patients into three age groups: <70 years, 70-79 years, and ≥80 years. Data from these three groups were compared, including comorbidity, oncologic outcomes and postoperative complications. RESULTS: A total of 326 patients underwent pancreatic head resection. The 90-day mortality increased from 2.9% to 5.3% to 15.4% with increasing age (p = 0,015). There were no differences among the three groups in terms of postoperative morbidity. There was no difference in disease-free survival (DFS), but overall survival was better in patients under 70 years (p = 0,046). CONCLUSION: Compared to younger patients, patients over 80 years old have a higher risk of mortality despite similar postoperative morbidity.

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Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss-of-function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103-28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3-binding and DIX domains, but preserving the ß-catenin-binding domain. Ninety-one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.

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OBJECTIVES: Emergency department (ED) visits for high blood pressure are increasing in frequency. We aimed to map those patients' trajectory, from referral sources to the type of care received at the ED to anticipated actions for future high blood pressure concerns, and to better understand their reasons for consulting the ED for high blood pressure values. METHODS: Between 2018 and 2020, patients who presented to the Montreal Heart Institute's ED for elevated blood pressure were recruited in a prospective observational study including a post hoc structured telephone interview and medical chart review. Five possible referral sources were predetermined. We provided proportions and 95% confidence intervals. RESULTS: A total of 100 patients were recruited (female: 59%, mean age: 69 ± 12). A majority (93%, 95% CI 88-98%) possessed a home blood pressure device, among which 46% (95% CI 36-56%) remembered receiving advice for its use. The main referral sources for high blood pressure to the ED were self-reference (53%, 95% CI 43-63%), advice of a lay person (19%, 95% CI 11-27%) or a nurse (13%, 95% CI 6-20%). Mainly, patients reported being concerned by concomitant symptoms or experiencing acute medical consequences (44%, 95% CI 34-54%), having followed the recommendation of a third party (33%, 95% CI 24-42%), or having concerns about their medication (6%, 95% CI 1-11%). Two weeks following their ED visits, consulting ED remained the main choice for future concerns about high blood pressure for 27% of participants. When specifically asked if they would return to the ED for elevated blood pressure, 73% (95% CI 64-83%) said yes. CONCLUSIONS: Most patients who consulted the ED for elevated blood pressure values were self-referred. More can be done to promote blood pressure education, effective use of personal blood pressure devices, and recommendations for patients and health professionals when confronted with high blood pressure results.

RéSUMé: OBJECTIFS: Les visites aux services d'urgence pour hypertension artérielle (TA) sont de plus en plus fréquentes. Nous avons cherché à cartographier le parcours de ces patients, depuis les sources d'orientation jusqu'au type de soins reçus aux urgences, en passant par les mesures prévues en cas de problèmes futurs de tension artérielle élevée, et à mieux comprendre les raisons pour lesquelles ils consultent les urgences pour des valeurs de tension artérielle élevées. MéTHODES: Entre 2018 et 2020, les patients qui se sont présentés aux urgences de l'Institut de cardiologie de Montréal pour une TA élevée ont été recrutés dans le cadre d'une étude observationnelle prospective comprenant une entrevue téléphonique structurée post-hoc et un examen des dossiers médicaux. Cinq sources de référence possibles ont été prédéterminées. Nous avons fourni des proportions et des intervalles de confiance à 95 %. RéSULTATS: Au total, 100 patients ont été recrutés (femmes : 59 %, âge moyen : 69 ± 12). Une majorité (93%, IC à 95% 88-98%) possédait un tensiomètre à domicile, parmi lesquels 46% (IC à 95% 36-56%) se souvenaient avoir reçu des conseils pour son utilisation. Les principales sources d'orientation vers les urgences en cas de tension artérielle élevée étaient l'auto-référence (53 %, IC 95 % 43-63 %), le conseil d'un tiers non-professionnel de la santé (19 %, IC à 95 % 11-27 %) ou d'une infirmière (13 %, IC à 95 % 6-20 %). Principalement, les patients ont déclaré être préoccupés par des symptômes concomitants ou des conséquences médicales aiguës (44 %, IC à 95 %, 34-54 %), avoir suivi la recommandation d'un tiers (33 %, IC à 95 %, 24-42 %) ou avoir des préoccupations au sujet de leurs médicaments (6 %, IC à 95 %, 1-11 %). Deux semaines après leur visite au service d'urgence, la consultation du service d'urgence est restée le principal choix en cas de préoccupations futures concernant l'hypertension artérielle pour 27 % des participants. À la question spécifique de savoir s'ils retourneraient aux urgences pour une TA élevée, 73% (IC à 95% 64-83%) ont répondu oui. CONCLUSIONS: La plupart des patients qui ont consulté les urgences pour des valeurs élevées de la tension artérielle se sont adressés d'eux-mêmes. Il y a place à l'amélioration pour promouvoir l'éducation sur la TA, l'utilisation efficace des appareils de pression artérielle personnels et les recommandations aux patients et aux professionnels de la santé lorsqu'ils sont confrontés à des résultats élevés en matière de TA.

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BACKGROUND: Tourette syndrome (TS) can be accompanied by neurocognitive impairment. Only a few studies have focused on executive function assessment in TS using design fluency, providing preliminary results. This study aimed to characterize the detailed design fluency profile of children with TS compared with neurotypical children, while addressing the central concern of frequent comorbidities in studies on TS by considering tic severity and attention-deficit/hyperactivity disorder (ADHD) symptoms and diagnosis. METHODS: Sixty-one children aged between 6 and 15 years participated and were divided into a TS group (n = 28 (with ADHD n = 15)) and a control group (n = 33). Our objective was addressed by examining a wide range of measures of the Five-Point-Test, presumably sensitive to frontostriatal dysfunction. The total number of designs, repetitions, repetition ratio, unique designs, and numerical, spatial, and total strategies were examined for the total duration of the test (global measures) and at five equal time intervals (process measures). RESULTS: The TS group produced significantly fewer numerical strategies. Groups did not differ in other global or process measures. ADHD did not affect performance. CONCLUSIONS: Children with TS do not inherently show general executive dysfunction but may present with subtle neurocognitive characteristics here revealed by comprehensive design fluency profiles.

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BACKGROUND: The aim of this study was to present an overview of variations of the hepatic artery from the origin to the segmental branching. METHODS: Abdominal Computed Tomography performed on consecutive patients in our tertiary center between 2019 and 2020 were analyzed. Hepatic arterial branching and its relationship to the portal veins were reported. RESULTS: Out of 500 imaging, 16 anatomic patterns were found for the origin of hepatic artery, with 65.6% conventional origin at celiac axis (n = 328); 10 patterns for the left hepatic artery, 23 for segment IV artery, and more than 21 for the right hepatic artery (RHA), with conventional branching in respectively 66.8%, 39.6% and in 46.4% of patients. Conventional anatomy from celiac axis to segmental branching was found in 10.4% of patients. CONCLUSION: Dedicated thin-section imaging appears to be essential for preoperative planning in liver surgery, given the high variability of arterial distribution and their surgical implications.

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Background: Although the COVID-19 pandemic has increased the incidence of distress in youth, some children show increased resilience, emphasizing the need to better understand the predictors of distress in youth. Objective: This longitudinal study aimed to assess the combined impact of known socio-emotional predictors of stress-related psychopathology, namely anxiety sensitivity, anxiety trait, intolerance to uncertainty, and rumination, on COVID-related distress in healthy youth. Method: A total of 92 parent-child dyads that previously participated in a laboratory-based experiment assessing observational fear learning in families between 2017 and 2019 (T0) were recontacted. Of them, 84 children aged between 9 and 14 agreed to participate. They completed online questionnaires in June 2020 (T1), September 2020 (T2), December 2020 (T3), and March 2021 (T4). Participants were free of mental illness at T0 and T1. To create a socio-emotional composite score (SECS), we measured anxiety sensitivity (Childhood Anxiety Sensitivity Index) at T0, trait anxiety (Trait subscale of the State-Trait Anxiety Inventory for Children (STAI-C)), intolerance to uncertainty (Intolerance of Uncertainty Scale for Children), and trait rumination (Children's Response Style Scale) at T1 and created a weighted z-score. To assess symptoms of anxiety, post-traumatic stress (PTS), and depression in reaction to COVID-19, participants completed the State subscale of the STAI-C, the Children's Revised Impact of Event Scale, and the Children's Depression Inventory at T1-T4. Three general linear models were run with sex, age group (9-11 and 12+ years old), and SECS as predictors. Results: Analyses revealed a SECS*Time interaction, with higher SECS predicting elevated anxiety symptoms at T1 and T4, and elevated PTS symptoms at T1 and T2. Conclusion: These results suggest that healthy youth endorsing high levels of socio-emotional vulnerability to psychopathology have a higher risk of suffering from anxiety and PTS, but not depressive symptoms, in the year following a major stressor.

Antecedentes: Aunque la pandemia de COVID-19 ha aumentado la incidencia de angustia en jóvenes, algunos niños muestran una mayor resiliencia, relevando la necesidad de comprender mejor los predictores de la angustia en los jóvenes.Objetivo: Este estudio longitudinal tuvo como objetivo evaluar el impacto combinado de los predictores socioemocionales conocidos de la psicopatología relacionada con el estrés, como son la sensibilidad a la ansiedad, rasgos ansiosos, intolerancia a la incertidumbre y rumiación, en la angustia relacionada con COVID en jóvenes sanos.Método: 92 díadas de padres e hijos que participaron previamente en un experimento de laboratorio que evaluó el aprendizaje del miedo observacional en familias entre 2017 y 2019 (T0) fueron contactados nuevamente. Participaron 84 niños de entre 9 y 14 años. Completaron cuestionarios en línea en junio de 2020 (T1), septiembre de 2020 (T2), diciembre de 2020 (T3) y marzo de 2021 (T4). Los participantes estaban libres de enfermedad mental en T0 y T1. Para crear una puntuación socioemocional compuesta (SECS), medimos la sensibilidad a la ansiedad (Índice de sensibilidad a la ansiedad infantil) en T0, rasgo de ansiedad (subescala de rasgo del Inventario de ansiedad estado-rasgo para niños (STAI-C)), intolerancia a la incertidumbre (escala de intolerancia a la incertidumbre para niños) y rasgo de rumiación (Escala de estilo de respuesta en niños) en T1 y se creó una puntuación z ponderada. Para evaluar los síntomas de ansiedad, estrés postraumático (PTS) y depresión en reacción al COVID-19, los participantes completaron la subescala de estado de STAI-C, la escala de impacto de eventos para niños revisada, y el inventario de depresión infantil en T1­T4. Se ejecutaron tres modelos lineales generales con sexo, grupo de edad (9­11 y 12+ años) y SECS como predictores.Resultados: Los análisis revelaron una interacción entre el tiempo y la puntuación socioemocional compuesta (SECS), donde un SECS más alto predice síntomas de ansiedad elevados en T1 y T4, y síntomas elevados de PTS (Estrés post traumático) en T1 y T2.Conclusión: Estos resultados sugieren que la juventud sana que presenten altos niveles de vulnerabilidad socioemocional a la psicopatología, tiene un mayor riesgo desufrir de ansiedad y síndrome de estrés postraumático, pero no síntomas depresivos, en el año siguiente a un evento estresante mayor.

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Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific to it, as approximately 80% of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Methods leading to the diagnosis of LS have considerably evolved in recent years and so have tumoral tests for LS screening and for the discrimination of LS-related to MSI-sporadic tumors. In this review, we address the hallmarks of LS, including the clinical, histopathological, and molecular features. We present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with the current strategies, which should be taken into account to improve the diagnosis of LS and avoid inappropriate clinical management.

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BACKGROUND: We aimed to compare the predictive performance of three distinct clinical models purported to predict the resolution of aldosteronoma-associated hypertension after adrenalectomy. METHODS: A tri-institutional database of aldosteronoma patients who underwent adrenalectomy between 2004 and 2019 was retrospectively reviewed. The three models of interest incorporate various preoperative clinical factors, such as age and sex. The predictive accuracy, as measured by area under the curve of receiver operator characteristic, was estimated. Receiver operator characteristic was evaluated across the whole cohort, then stratified by treatment location. RESULTS: A total of 200 patients were included (91 American, 109 French). The clinicodemographic variables between groups were similar; the French cohort had a lower mean body mass index (P = .02). The overall complete clinical resolution of hypertension after adrenalectomy for the entire data set was 45.5% (n = 91). The regression coefficients in the Utsumi et al (2014) Japanese model produced a superior overall area under the curve (0.78, 95% confidence interval [CI] [0.71-0.84]). This model also performed best when the cohort was stratified by treatment location (French area under the curve = 0.74, 95% CI [0.64-0.83], US area under the curve = 0.82, 95% CI [0.72-0.91]). CONCLUSION: When comparing three predictive models of aldosteronoma-associated hypertension resolution after adrenalectomy, the Utsumi et al model demonstrated the highest predictive validity across all cohorts. Counseling based on this model regarding probability of cure is recommended.

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Importance: Adrenal venous sampling is recommended prior to adrenalectomy for all patients with hyperaldosteronism; however, cross-sectional imaging resolution continues to improve, while the procedure remains invasive and technically difficult. Therefore, certain patients may benefit from advancing straight to surgery. Objective: To determine whether clinical and biochemical resolution varied for patients with primary aldosteronism with unilateral adenomas who underwent adrenal venous sampling vs those who proceeded to surgery based on imaging alone. Design, Setting, and Participants: Retrospective, international cohort study of patients treated at 3 tertiary medical centers from 2004 to 2019, with a median follow-up of approximately 6 months. A total of 217 patients were consecutively enrolled. Exclusion criteria consisted of unknown postoperative serum aldosterone level and imaging inconsistent with unilateral adenoma with a normal contralateral gland. A total of 125 patients were included in the analysis. Data were analyzed between October 2019 and July 2020. Exposures: Adrenal venous sampling performed preoperatively. Main Outcomes and Measures: The primary outcome measurements were the clinical and biochemical success rates of surgery for the cure of hyperaldosteronism secondary to aldosterone-producing adenoma. Results: A total of 125 patients were included (45 cross-sectional imaging with adrenal venous sampling and 80 imaging only). The mean (SD) age of the study participants was 50.2 (10.6) years and the cohort was 42.4% female (n = 53). Of those patients for whom race or ethnicity were reported (n = 80), most were White (72.5%). Adrenal venous sampling failure rate was 16.7%, and the imaging concordance rate was 100%. Relevant preoperative variables were similar between groups, except ambulatory systolic blood pressure, which was higher in the imaging-only group (150 mm Hg; interquartile range [IQR], 140-172 mm Hg vs 143 mm Hg, IQR, 130-158 mm Hg; P = .03). Resolution of autonomous aldosterone secretion was attained in 98.8% of imaging-only patients and 95.6% of adrenal venous sampling patients (P = .26). There was no difference in complete clinical success (43.6% [n = 34] vs 42.2% [n = 19]) or partial clinical success (47.4% [n = 37] vs 51.1% [n = 23]; P = .87) between groups. Complete biochemical resolution was similar as well (75.9% [n = 41] vs 84.4% [n = 27]; P = .35). There was no difference in clinical or biochemical cure rates when stratified by age, although complete clinical success rates downtrended in the older cohorts, and sample sizes were small. Conclusions and Relevance: Given the improved sensitivity of cross-sectional imaging in detection of adrenal tumors, adrenal venous sampling may be selectively performed in appropriate patients with clearly visualized unilateral adenomas without affecting outcomes. This may facilitate increased access to surgical cure for aldosterone-producing adenomas and will decrease the incidence of morbidities associated with the procedure.

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OBJECTIVE: We previously described a family in which predisposition to pheochromocytoma (PCC) segregates with a germline heterozygous KIF1B nucleotide variant (c.4442G>A, p.Ser1481Asn) in three generations. During the clinical follow-up, one proband's brother, negative for the KIF1B nucleotide variant, developed a bilateral PCC at 31 years. This prompted us to reconsider the genetic analysis. DESIGN AND METHODS: Germline DNA was analyzed by next-generation sequencing (NGS) using a multi-gene panel plus MLPA or by whole exome sequencing (WES). Tumor-derived DNA was analyzed by SnapShot, Sanger sequencing or NGS to identify loss-of-heterozygosity (LOH) or additional somatic mutations. RESULTS: A germline heterozygous variant of unknown significance in MAX (c.145T>C, p.Ser49Pro) was identified in the proband's brother. Loss of the wild-type MAX allele occurred in his PCCs thus demonstrating that this variant was responsible for the bilateral PCC in this patient. The proband and her affected grandfather also carried the MAX variant but no second hit could be found at the somatic level. No other pathogenic mutations were detected in 36 genes predisposing to familial PCC/PGL or familial cancers by WES of the proband germline. Germline variants detected in other genes, TFAP2E and TMEM214, may contribute to the multiple tumors of the proband. CONCLUSION: In this family, the heritability of PCC is linked to the MAX germline variant and not to the KIF1B germline variant which, however, may have contributed to the occurrence of neuroblastoma (NB) in the proband.

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BACKGROUND: Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas. METHODS: We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort. RESULTS: We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04). CONCLUSION: F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.

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Beta-catenin, encoded by the CTNNB1 gene, plays an important role in cell proliferation. Mutations of CTNNB1 are oncogenic in several tumor types and are often associated with a nuclear abnormal expression. However, such mutations have only rarely been reported in non-small cell lung carcinomas and their clinical signification is not well described. Our study was conducted on 26 CTNNB1-mutated non-small cell lung carcinomas. Tumors were routinely tested by next generation sequencing for mutations in exon 3 of CTNNB1 gene. Twenty three cases were from a series of 925 tumors (2.48%). The hospital files and pathological data, from surgical samples (n = 16), small biopsies (n = 5) and trans-bronchial fine needle aspirations (n = 5), were reviewed. Immunohistochemistry was performed with an anti-beta-catenin antibody. There were 10 female and 16 male patients aged 52 to 83. Eleven of 25 patients were no-smoking or light smokers. Three cases were diagnosed while under treatment with EGFR tyrosine kinase inhibitor. There were 25 adenocarcinomas and 1 squamous cell carcinoma. Most adenocarcinomas had a papillary component and were TTF1-positive. One case was a well-differentiated fetal adenocarcinoma. Eleven cases (42%) with CTNNB1 mutations showed associated EGFR mutations. The frequency of CTNNB1 mutations was higher among EGFR mutated carcinomas. Immunohistochemistry showed heterogeneous nuclear or cytoplasmic abnormal expression. Our study shows that CTNNB1 mutations mostly occur in TTF1-positive adenocarcinomas with a papillary pattern. These mutations are often associated with EGFR mutations and possibly interfer in the mechanism of resistance to tyrosine kinase inhibitors. Our experience suggests that immuno-histochemistry cannot be used for screening.

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