Lifelong Surveillance Research Articles

Abstract 10580: Machine Learning-Assisted Echocardiographic Identification of Children at High Risk for Treatment-Related Cardiomyopathy: A Proof-of-Concept Study

Introduction: Childhood cancer survivors require life-long surveillance for treatment-related cardiomyopathy/heart failure (CHF). Ultimately, we aim to use machine learning to aid in echocardiographic discrimination of survivors more likely to develop future CHF. For this feasibility pilot, we built two proof-of-concept deep convolutional neural networks (DCNNs) tasked with binary classification of present/future CHF versus no CHF with the aim of assessing optimal data input format and model architecture. Methods: From a robust multi-institutional surveillance echo dataset, we selected pilot data comprising 171 parasternal short axis echo clips, 52 from 5 CHF+ (present and future CHF) and 119 from 21 CHF- patients. We built two DCNN models differing in frame selection for input data (Fig. 1), both tasked with binary classification of CHF+ vs. CHF-. We used holdout subsets in a 10-fold cross-validation framework to test model performance and Student’s t test (paired) to compare model performance. Results: Classification performance was similar, with mean AUROC values of 0.59 ± 0.09 and 0.53 ± 0.11 (p=0.14) for the models trained on Type I and Type II montages, respectively (Fig. 2). Conclusions: The DCNN framework is feasible for a model tasked with classifying CHF status, and we are optimistic that a similar model can be trained with pre-CHF diagnosis (case) vs control patient images to facilitate machine learning-assisted identification of childhood cancer survivors more likely to develop CHF in the future.

PSUN375 What Blindness and Paraganglioma Have in Common? A Rare Case of Paraganglioma Syndrome

Abstract Background Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with an annual incidence in the U.S. of 500-1600 cases per year. Approximately 30-35% of PPGLs harbor germline mutations, while 35-40% are due to somatic mutations. Recent studies have identified the association between somatic mutations of the hypoxia-inducible factor 2 alpha (HIF2A) gene and a new syndrome of PPGLs associated with congenital polycythemia. Patients present with recurrent PPGLs, congenital malformation of intracranial veins, malformation of macula and retina, and type I Chiari malformations. Case A 44-year-old man with history of in-utero stroke, congenital blindness, polycythemia and spinal stenosis had an incidental para-aortic lesion found during workup of back pain. He experienced episodic palpitations associated with diaphoresis, headache and uncontrolled hypertension for the past eight year. There was no family history of neuroendocrine tumors. Dedicated abdominal computer tomography with contrast showed a right adrenal enhancing lesion measuring 1.4×1.2 cm and a conglomerate of heterogenous enhancing periaortic lesions measuring up to 5 cm in the mid-abdomen. Biochemical work up revealed plasma free normetanephrine of 27.5 nmol/L (0.00-0.89) and plasma free metanephrines of 0.49 nmol/L (0.00-0.49). Gallium 68 DOTATATE scan showed multiple avid retroperitoneal lesions measuring up to 4.4 cm and an avid right adrenal nodule. He underwent right adrenalectomy and para-aortic lesion resection with perio-operative alpha blockade. Pathology confirmed synchronous pheochromocytoma (1.5 cm, Ki-67< 1%, with capsular and periadrenal fat invasion) and paraganglioma (9.3 cm, Ki-67 < 1%, with lymphovascular invasion and one out of nine lymph nodes positive for metastatic disease). Post-operatively, his metanephrines normalized and a six-months positron emission tomography scan showed no evidence of disease. Genetic testing has been delayed. Discussion This case illustrates a rare syndrome of PPGLs, congenital blindness, and polycythemia, likely due to somatic mutations of HIF2a. HIF is an alpha/beta heterodimer. HIF2a becomes a transcription factor after dimerization with HIF2b. Any mutations that stabilize HIF protein leads to transcription of hypoxia inducible genes resulting in angiogenesis, polycythemia, and tumorigenesis. In our patient, we suspect the stroke in-utero may have been related to abnormal intracranial angiogenesis and/or polycythemia. Recognition of this syndrome and lifelong surveillance is imperative due to risk of recurrence of PPGL. Targeted therapies such as a HIF2a inhibitor have been proposed and trials are ongoing. Our patient remains disease free on radiographic and biochemical surveillance. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Reintervention does not affect long-term survival after fenestrated endovascular aneurysm repair.

Fenestrated endovascular aneurysm repair (FEVAR) is increasingly used in the treatment of juxtarenal aortic aneurysms and short-neck infrarenal aneurysms. Reinterventions (REIs) occur frequently, contributing to patient morbidity and resource utilization. We sought to determine whether REI affects long-term survival after FEVAR. A single-institution retrospective review of all Cook Zenith fenestrated (ZFEN; Cook Medical, Inc, Bloomington, IN) repairs was performed. Patients with ≥6months of follow-up and without adjunctive branch modifications were included. REI was defined as any aneurysm, device, target branch, or access-related intervention after the index procedure. REIs were categorized as early (<30days) or late (≥30days), by indication (ie, branch, endoleak, limb related, access related, other), and by target branch or device components. Patients were stratified into REI vs no REI groups and branch REI vs non-branch REI groups. Of 219 consecutive ZFEN repairs from 2012 to 2021, 158 patients met the inclusion criteria. Of these 158 patients, 41 (26%) required a total of 51 REIs (10 early and 41 late) during a mean follow-up of 33.9months. The most common indication for REI was branch-related (31 of 51; 61%), with the renal arteries the most frequently affected (26 of 51; 51%). The only differences found in baseline, aneurysm, and device characteristics were a higher mean Society for Vascular Surgery comorbidity score (9.6 vs 7.9; P= .04) and larger suprarenal neck angle (23.3° vs 17.1°; P= .04) in the no REI group. In contrast, the REI group had a larger mean proximal seal zone diameter (26.3mm vs 25.1mm; P= .03) and device diameter (31.9mm vs 30.0mm; P= .002) compared with the no REI group. Technical success and operative characteristics were similar between the groups, except for a longer mean fluoroscopy time (74.9minutes vs 60.8minutes; P= .01) and longer median length of stay (2 vs 2days; P= .006) for the REI group. Although the rate of early (<30days) major adverse events was greater for the REI group (24.4% vs 6.0%; P= .001), the difference in 30-day mortality was not statistically significant (4.9% vs 0.9%; P= .10). On Kaplan-Meier analysis, freedom from REI at 1 and 5years was 85.7% and 62.6%, respectively, for the overall cohort. No difference was found in the estimated 5-year survival between the REI and no REI groups (62.8% vs 63.5%; log-rank, P= .87) and branch REI and non-branch REI groups (71.8% vs 49.9%; log-rank, P= .16). On multivariate analysis, REI was not an independent predictor for mortality. However, age, Society for Vascular Surgery comorbidity score, and preoperative maximum aneurysm diameter each increased the hazard of death (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12 [P= .007]; HR, 1.10; 95% CI, 1.01-1.18 [P= .02]; HR, 1.05; 95% CI, 1.02-1.08 [P= .003], respectively). After ZFEN, 41 patients (26%) had required a total of 51 REIs, with most occurring ≥30days after the index procedure, and 61% were branch related, with no influence on 5-year survival. Age, comorbidity, and baseline aneurysm diameter independently predicted mortality. The use of FEVAR mandates lifelong surveillance and protocols to maintain branch patency. Despite their relative frequency, REIs did not influence 5-year postprocedural survival.

Epigenetic regulation of MIR145 core promoter controls miR-143/145 cluster in bladder cancer progression and treatment outcome

Owing to its highly heterogeneous molecular landscape, bladder cancer (BlCa) is still characterized by non-personalized treatment and lifelong surveillance. Motivated by our previous findings on miR-143/145 value in disease prognosis, we have studied the underlying epigenetic regulation of the miR-143/145 cluster in BlCa. Expression and DNA methylation of miR-143/145 cluster were analyzed in our screening (n= 162) and The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA; n= 412) cohorts. Survival analysis was performed using tumor relapse and progression as clinical endpoints for non-muscle-invasive bladder cancer (NMIBC; TaT1), while disease progression and patients' death were used for muscle-invasive bladder cancer (MIBC; T2-T4). TCGA-BLCA served as validation cohort. Bootstrap analysis was carried out for internal validation, while decision curve analysis was used to evaluate clinical benefit. TCGA-BLCA and screening cohorts highlighted MIR145 core promoter as the pivotal, epigenetic regulatory region on cluster's expression. Lower methylation of MIR145 core promoter was associated with aggressive disease phenotype, higher risk for NMIBC short-term progression, and poor MIBC survival. MIR145 methylation-fitted multivariate models with established disease markers clearly enhanced patients' risk stratification and prediction of treatment outcome. MIR145 core promoter methylation was identified as a potent epigenetic regulator of miR-143/145 cluster, supporting modern personalized risk stratification and management in BlCa.

Chronic Thoracic Aortic Dissection: How to Treat, When to Intervene.

Thoracic aortic dissection (AD) is associated with increased morbidity and mortality. Acute aortic syndrome is the first presentation of the disease in most cases. While acute AD management follows concrete guidelines because of its urgent and life-threatening nature, chronic AD is usually overlooked, although it concerns a wide spectrum of patients surviving an acute event. Acute AD survivors ultimately enter a chronic aortic disease course. Patients with chronic thoracic AD (CTAD) require lifelong surveillance and a proportion of them may present with symptoms and late complications demanding further surgical or endovascular treatment. However, the available data concerning the management of CTAD is sparse in the literature. The management of patients with CTAD is challenging as far as determining the best medical therapy and deciding on intervention are concerned. Until recently, there were no guidelines or recommendations for imaging surveillance in patients with chronic AD. The diagnostic methods for imaging aortic diseases have been improved, while the data on new endovascular and surgical approaches has increased significantly. In this review, we summarize the current evidence in the diagnosis and management of CTAD and the latest recommendations for the surgical/endovascular aortic repair of CTAD.

Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance.

Bladder cancer is one of the top ten most common cancers and top ten causes of cancer death globally. 5-year survival rates have decreased in Australia from 66% to 55% in the past three decades. The current gold standard for diagnosis is cystoscopy. However, cystoscopies are an invasive and health-resource intensive procedure which has sub-optimal sensitivity for flat lesions such as CIS (carcinoma in situ) and low specificity for differentiating inflammation from cancer - hence requiring biopsies under anesthesia. Frequent and life-long surveillance cystoscopy is required for most patients since there are high rates of progression and local recurrence in high-risk non-muscle invasive cancer (NMIBC) as well as poor outcomes associated with delayed detection of muscle-invasive bladder cancer (MIBC). There is an unmet need for a non-invasive test to provide better discrimination and risk-stratification of bladder cancer which could aid clinicians by improving patient selection for cystoscopy; enhanced risk stratification methods may guide the frequency of surveillance cystoscopies and inform treatment choices. Exosomes, which are nano-sized extracellular vesicles containing genetic material and proteins, have been shown to have functional roles in the development and progression of bladder cancer. Exosomes have also been demonstrated to be a robust source of potential biomarkers for bladder cancer diagnosis and prognosis and may also have roles as therapeutic agents. In this review, we summarize the latest evidence of biological roles of exosomes in bladder cancer and highlight their clinical significance in bladder cancer diagnosis, surveillance and treatment.

Thoracic endovascular repair for blunt traumatic thoracic aortic injury: Long-term results.

This study aims to evaluate the endoprosthesis complications in patients undergoing TEVAR for blunt traumatic thoracic aortic injury, through long-term clinical and diagnostic follow-up. During the study interval (November 2000-October 2020), a total of 38 patients (63% male; average age 37.5years) with thoracic aortic injury underwent thoracic endovascular aortic repair. Patients underwent routine follow-up with clinical examination and radiological evaluation (CT-angiography or MRI-angiography plus chest radiograph), scheduled at 1month, at 6months (only in the cases of thoracic aortic dissection), at 1year after the procedure and every 1year thereafter. Technical success was achieved in 38 procedures (100%). The TEVAR-related mortality rate was 0%. No immediate major complications related to the endovascular procedure were observed. The median duration of diagnostic follow-up was 80months. A total of four procedure-related complications (10.5%) were identified at the follow-up. Three (7.9%) distal infoldings and collapses of the thoracic endoprosthesis and one (2.6%) type Ia endoleak were observed. No thrombosis of the prosthesis, nor signs of aortic pseudocoarctation were identified. No further complications related to endograft (endoleaks, infections, rupture, partial or complete thrombosis) occurred. No changes in the native aorta, stenosis, or increases in the endograft's diameters were observed. A total of 20 patients (52.6%) underwent MRI-angiography examinations, while a total of 34 patients (89.5%) underwent chest radiographs at the follow-up. In all cases, CT-angiography examinations were performed at the follow-up. Procedure-related complications were observed within one year of TEVAR, limiting concerns related to the durability of the prosthesis. No morphological changes in the aorta were observed despite long-term follow-up. The consequences of lifelong surveillance in terms of radiation exposure deserve special consideration, especially in younger patients treated for TAI.

SLOfit Lifelong: A model for leveraging citizen science to promote and maintain physical fitness and physical literacy across the lifespan.

SLOfit Lifelong is a public health initiative which was created to upgrade a well-established, national physical fitness surveillance system for Slovenian schoolchildren that has been collecting annual fitness and health data for over three decades. The ultimate objective of creating SLOfit Lifelong was to build a modern societal infrastructure with the capacity and ability to detect future causal associations between childhood physical fitness trends and future health outcomes based on the lifelong surveillance of one's own fitness status. By instilling citizens with an ambition to test, understand, and follow-up their own physical fitness and health status (including related health risk factors), this initiative provides the technical support and expert feedback needed to engender greater individual control over understanding (and thus modulating), one's own physical fitness status as they progress into older adulthood. This perspective paper details the extensive approach taken to devise appropriate fitness test batteries for adults and older adults which can also relate to the student version of the original SLOfit test database, including establishing criterion health risk zones and a public approach to establish this national, citizen-driven health feedback framework. Through its sophisticated online web applications, social media, print media, and outreach workshops, SLOfit Lifelong provides the expert support for public health engagement by fostering positive lifelong physical literacy experiences an individual can enjoy across their aging journey.

708TiP BD4QoL: A multicenter randomized trial for monitoring quality of life (QoL) by intelligent tools in head and neck cancer (HNC) survivors after curative treatment

HNC survivors suffer from high physical, psychological and socioeconomic burdens. Achieving cancer-free survival with an optimal QoL is the primary goal for HNC patients (pts) management. Therefore, maintaining lifelong surveillance is critical. This can be carried out by advanced analysis of environmental, emotional and behavioral data unobtrusively collected from mobile devices. The aim of this clinical trial is to reduce, with specific non-invasive tools (i.e., their mobile devices), the proportion of HNC survivors experiencing a clinically meaningful reduction in QoL during post-treatment follow-up.

Institutional transition from invasive to non-invasive imaging in children with univentricular heart defects: safety and cost savings.

Patients with univentricular heart defects require lifelong imaging surveillance. Recent advances in non-invasive imaging have enabled replacing these patients' routine catheterisation. Our objective was to describe the safety and cost savings of transition of a tertiary care children's hospital from routine invasive to routine non-invasive imaging of low-risk patients with univentricular heart defects. This single-centre cohort study consists of 1) a retrospective analysis of the transition from cardiac catheterisation (n = 21) to CT angiography (n = 20) before bidirectional Glenn operation and 2) a prospective study (n = 89) describing cardiac magnetic resonance before and after the total cavopulmonary connection in low-risk patients with univentricular heart defects. Pre-Glenn: The total length of CT angiography was markedly shorter compared to the catheterisation: 30 min (range: 20-60) and 125 min (range: 70-220), respectively (p < 0.001). Catheterisation used more iodine contrast agents than CT angiography, 19 ± 3.9 ml, and 10 ± 2.4 ml, respectively (p < 0.001). Controlled ventilation was used for all catheterised and 3 (15%) CT angiography patients (p < 0.001). No complications occurred during CT angiography, while they emerged in 19% (4/21) catheterisation cases (p < 0.001). CT angiography and catheterisation showed no significant difference in the radiation exposure. Pre-/post-total cavopulmonary connection: All cardiac magnetic resonance studies were successful, and no complications occurred. In 60% of the cardiac magnetic resonance (53/89), no sedation was performed, and peripheral venous pressure was measured in all cases. Cost analysis suggests that moving to non-invasive imaging yielded cost savings of at least €2500-4000 per patient. Transition from routine invasive to routine non-invasive pre-and post-operative imaging is safely achievable with cost savings.

Effect of a Decision Aid on Agreement Between Patient Preferences and Repair Type for Abdominal Aortic Aneurysm

Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair. To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive. In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021. Presurgical consultation using a decision aid vs usual care. The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios. Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70). Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures. ClinicalTrials.gov Identifier: NCT03115346.

Endoscopic surveillance alone is feasible and safe in type I gastric neuroendocrine neoplasms less than 10 mm in diameter

PurposeType I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10 mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs.MethodsRetrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003–2019.ResultsFollowing initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10 mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11 mm g-NENs.ConclusionsPatients with ≤10 mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2–3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma.

Clinical and molecular features of patients with COL1-related disorders: Implications for the wider spectrum and the risk of vascular complications.

Abnormalities in type I procollagen genes (COL1A1 and COL1A2) are responsible for hereditary connective tissue disorders including osteogenesis imperfecta (OI), specific types of Ehlers‐Danlos syndrome (EDS), and COL1‐related overlapping disorder (C1ROD). C1ROD is a recently proposed disorder characterized by predominant EDS symptoms of joint and skin laxity and mild OI symptoms of bone fragility and blue sclera. Patients with C1ROD do not carry specific variants for COL1‐related EDS, including classical, vascular, cardiac‐valvular, and arthrochalasia types. We describe clinical and molecular findings of 23 Japanese patients with pathogenic or likely pathogenic variants of COL1A1 or COL1A2, who had either OI‐like or EDS‐like phenotypes. The final diagnoses were OI in 17 patients, classical EDS in one, and C1ROD in five. The OI group predominantly experienced recurrent bone fractures, and the EDS group primarily showed joint hypermobility and skin hyperextensibility, though various clinical and molecular overlaps between OI, COL1‐related EDS, and C1ROD as well as intrafamilial phenotypic variabilities were present. Notably, life‐threatening vascular complications (vascular dissections, arterial aneurysms, subarachnoidal hemorrhages) occurred in seven patients (41% of those aged >20 years) with OI or C1ROD. Careful lifelong surveillance and intervention regarding bone and vascular fragility could be required.

Evaluation of the Effectiveness of Endovascular Treatment of Type 2 Endoleaks

Endovascular abdominal aortic aneurysm repair (EVAR) is a safe and minimally invasive alternative to open surgical repair for infra renal aortic aneuvrysm. EVAR requires lifelong post-procedural surveillance. Endoleaks represent the main complication. Type II endoleaks (EL2) are the most frequent and tend to be indolent. Most practitioners do not treat in EL2 as long as they are associated with stable aneurysm diameter. European guidelines recommend treatment in case of aneurysm growth. Several techniques can be offered, such as transarterial embolization and translumbar embolization. This study reports the experience and results of a single center for EL2 endovascular treatment. The aim of this study was to determine more precisely the efficacity of embolization for type 2 endoleaks treatment. A single center cohort of patients treated for EL2 with endovascular technique between 1998 and 2018 was formed to perform a descriptive analysis. Preoperative sizing, risk factors of endoleaks and intraoperative data were collected. Computed topography (CT) scans were regularly performed after EVAR to detect endoleak recurrence. Clinical recurrence was defined as the persistence of aneurysm sac growth and radiological recurrence was defined as the occurrence of EL2 on a post-embolization CT scan. Data related to reintervention, overall mortality and aneurysm related mortality were also collected. Kaplan-Meier survival analyses were used to determine the rates of reoperation-free survival and recurrence-free survival. Six hundred seven patients underwent an endovascular treatment for abdominal aorta aneurysm between 1998 and 2018. One hundred forty-five type 2 endoleaks occurred during this period. Nineteen patients (median age 76years), underwent endovascular treatment for EL2, with immediate success on 15 patients (8 transarterial embolization, 8 direct sac puncture and 3 combined procedures). During follow-up, 5 patients required a new translumbar embolization and 6 required an open surgery for recurrence of the EL2. Six patients died, 2 of them of causes related to the aneurysm. At 59,6months median follow-up, 53% of the patients presented a radiologic recurrence, with a sac growth of more than 5mm since last procedure in 4 patients (24%). Long term clinical recurrence of type 2 endoleaks treated by endovascular procedures appear to be frequent in our experience, leading to several deaths and requiring open surgical treatment.

Endocrine manifestations of paediatric intracranial germ cell tumours: from diagnosis to long-term follow-up.

We examined endocrine manifestations in a cohort of paediatric patients with IC-GCTs at diagnosis and during follow-up, integrating clinical, radiological, histopathological and laboratory data. Diabetes insipidus (DI), growth hormone deficiency (GHD), hypothyroidism, adrenal insufficiency, precocious puberty (PP)/hypogonadism were diagnosed clinically and biochemically. The prevalence of endocrine manifestations was compared to survival rates. Our population included 55 children (37 males, 18 females) diagnosed with IC-GCT with a median follow-up of 78.9 months from diagnosis (range 0.5-249.9). At tumour diagnosis, 50.9% patients displayed endocrinopathies: among them, 85.7% were affected by DI, 57.1% central adrenal insufficiency, 50% central hypothyroidism, 28.5% GHD, 10.7% hypogonadotrophic hypogonadism, 10.7% PP. These patients presented predominantly with suprasellar germinoma. If not diagnosed previously, endocrine disorders arose 15.15 months (1.3-404.2) after end of treatment (EOT) in 16.4% patients. At least one endocrinopathy was identified in 67.3% of subjects at last follow-up visit, especially GHD and adrenal insufficiency. DI, hypothyroidism, and adrenal insufficiency occurred earlier than other abnormalities and frequently preceded tumour diagnosis. Subjects with and without endocrine manifestations who survived beyond 12 months after EOT did not show significant difference in overall survival and progression-free survival (p = 0.28 and p = 0.88, respectively). Endocrinopathies were common presenting symptoms in our population. If present at diagnosis, they often persisted hence after. The spectrum of endocrinopathies expanded during follow-up up to 33.7 years after EOT. Although they did not seem to affect survival rate in our cohort, close lifelong surveillance is mandatory to provide the best care for these patients.

Endovascular Juxtarenal Aortic Aneurysm Repair Using the ALTO Abdominal Stent Graft System: The First Case Series

The ALTO abdominal stent graft system (Endologix Inc., Irvine, CA, USA) is a latest-generation polymer-based device used to treat patients with abdominal aortic aneurysms. The present study describes the first case series of patients with abdominal aortic aneurysms, including two patients with juxtarenal aneurysms, treated using the ALTO stent graft system. Six males were treated using the ALTO device at a single public center. All procedures were uneventful, and the dosimetric results recorded in terms of kerma-area product and fluoroscopy time were similar to those reported in previous studies. At the 1-month follow-up, computed tomography angiography showed no evidence of endoleak, device migration, thrombosis, or structural graft failure. This clinical series demonstrates that the use of the ALTO stent graft system is associated with promising patient outcomes. Lifelong postoperative imaging surveillance may highlight possible late failures and suggest potential graft improvements.

Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance.

Simple SummaryAt least 10% of pheochromocytomas (PHEOs) and paragangliomas (PPGLs) may recur after the initial surgery. The optimal follow-up time for these tumors remains unknown. We present a cohort of recurrent PPGLs in a clinical care setting of a quaternary center. In this paper, we describe recurrence patterns based on tumor location (head and neck paragangliomas, thoracoabdominal paragangliomas, and pheochromocytomas). We report that the overall mean delay of recurrence was 9.7 years and that one-third of the cohort had a recurrence more than 10 years after the initial surgery. Additionally, 17.6% of recurrent PHEOs were smaller than the predicted cutoff for recurrence (5 cm). Finally, more than 50% of recurrent PPGLs harbored a germline mutation in a susceptibility gene. In sum, this paper supports that overall, the safest option remains a lifelong follow-up.At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) may recur after the initial surgery. Guidelines recommend annual screening for recurrence in non-metastatic tumors for at least 10 years after the initial surgical resection and lifelong screening in high-risk patients. However, recent data suggest that a shorter follow-up might be appropriate. We performed a retrospective analysis on patients with PPGLs who had local and/or metastatic recurrences between 1995 and 2020 in our center. Data were available for 39 cases of recurrence (69.2% female) including 20 PHEOs (51.3%) and 19 PGLs (48.7%) (13 head and neck (HNPGL) and 6 thoracoabdominal (TAPGL)). The overall average delay of recurrence was 116.6 months (14–584 months) or 9.7 years and the median was 71 months or 5.9 years. One-third of the cohort had a recurrence more than 10 years after the initial surgery (10–48.7 years). The average tumor size at initial diagnosis was 8.2 cm for PHEOs, 2.7 cm for HNPGLs, and 9.6 cm for TAPGLs. Interestingly, 17.6% of PHEOs were under 5 cm at the initial diagnosis. Metastatic recurrence was identified in 75% of PHEOs, 15.4% of HNPGLs, and 66.7% of TAPGLs. Finally, 12/23 (52.2%) patients with recurrence who underwent genetic testing carried a germline mutation. Overall, the safest option remains a lifelong follow-up.

Existing Ethical Tensions in Xenotransplantation.

The genetic modification of pigs as a source of transplantable organs is one of several possible solutions to the chronic organ shortage. This paper describes existing ethical tensions in xenotransplantation (XTx) that argue against pursuing it. Recommendations for lifelong infectious disease surveillance and notification of close contacts of recipients are in tension with the rights of human research subjects. Parental/guardian consent for pediatric xenograft recipients is in tension with a child's right to an open future. Individual consent to transplant is in tension with public health threats that include zoonotic diseases. XTx amplifies concerns about justice in organ transplantation and could exacerbate existing inequities. The prevention of infectious disease in source animals is in tension with the best practices of animal care and animal welfare, requiring isolation, ethologically inappropriate housing, and invasive reproductive procedures that would severely impact the well-being of intelligent social creatures like pigs.

Problematic rise of vitamin B6 supplementation overuse and potential risk to bariatric surgery patients

ObjectivesDue to the increased prevalence of obesity in the world, bariatric surgeries are on the rise and necessitate life-long surveillance for deficiencies; hence the recommended vitamin supplementation in these patients. However, inadequate multivitamin supplementation may induce vitamin B6 overload. MethodsWe reviewed all vitamin B6 dosages at the university hospitals of Poitiers, Tours, Bordeaux, and Limoges for the past 5 to 8 years. Analyses were performed by high-performance liquid chromatography, coupled with a fluorescence detector on whole blood samples. ResultsDuring the study period, there was an increase in the number of vitamin B6 dosages. Deficiencies were detected early in Poitiers and Limoges, but were negligible by 2020. However, during the same time period, the number of overdoses increased, reaching close to 40% of dosages at all centers. ConclusionsPyridoxin overload is not possible through food-derived pyridoxin; hence, combined with the fact that most vitamin supplements contain vitamin B6, inadequate vitamin supplementation is likely the cause of the observed increase in overdoses. High doses of vitamin B6 can induce polyneuropathy, particularly targeting motor neurons; thus, the increase of overdoses is worrying. In light of the possible risks and the ease with which these could be averted (better formulation of supplements), the precaution principle requires a definition of clear guidelines for vitamin supplementation, especially in patients undergoing bariatric surgery.

Complex and Successful Management of a Symptomatic Isolated Abdominal Aortic Aneurysm in a Pregnant Woman with Marfan Syndrome.

Aortopathies associated to Marfan syndrome (MFS) are important causes of maternal death during pregnancy. We present a 27-year-old and 24-week pregnant MFS woman who arrived to the emergency department with increasing abdominal pain; an obstetric ultrasound showed an Abdominal Aortic Aneurysm (AAA), a multislice computed tomography angiography (CTA) confirmed and demonstrated a 7.3centimeter (cm) infrarenal AAA without evidence of dissection. A multidisciplinary committee determined that an open repair would lead to a significantly high maternal-fetal morbidity and mortality. Although endovascular repair (EVAR) in MFS patients remains controversial, an urgent bridge therapy was considered to be the best option. She was transferred to the angiography suite for EVAR to prevent AAA rupture and ensure a satisfactory pregnancy. The patient and fetus presented no complications during the procedure and were discharged 3days later. She continued her pregnancy without eventualities and an elective C-section was performed on week 36. A CTA imaging at 12months revealed type 1A and 3 endoleaks, we decided to perform endograft explant and a definitive open repair, there were no complications during the procedure, the patient is currently asymptomatic. Our case illustrates a complex decision and management that successfully avoid morbidity and mortality of a MFS mother and her product; additionally, this experience reinforces the need for lifelong and close surveillance in these patients.