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Paraganglioma is a tumor developed from paraganglia, which are groups of neuroendocrine cells located along the vascular and nerve axes of the head and neck and along the spine. These tumors are benign and still localized in more than 80% of cases. Middle mediastinal paragangliomas represent less than 1% of mediastinal tumors and grow from the superior or middle mediastinal autonomic ganglion; they mostly are non-functional and are found in older patients. The often large volume and complex location of these tumors make their surgical resection challenging forcing the surgical team to resort to cardiopulmonary bypass and practice transfection of the aortic artery. We successfully operated an 80-year-old patient by clamshell incision without bypass or arterial procedure.

Upregulated p38 signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38 signaling and accelerates PA-SMC proliferation. The activity of p38 signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1). Activated p38 induces DUSP1 expression, forming a negative feedback loop. Prostacyclin IP receptor agonists (prostacyclin and selexipag) are used to treat PAH. In this study, we aimed to verify whether IP receptor agonists affect DUSP1 expression and accelerate the proliferation of PA-SMCs. PA-SMCs were treated with BMP2, ET-1, prostacyclin, and MRE-269, an active metabolite of selexipag, either alone or in combination. We quantified mRNA expressions using real-time quantitative polymerase chain reaction. Pulmonary artery specimens and PA-SMCs were obtained during lung transplantation in patients with PAH. Both prostacyclin and MRE-269 increased DUSP1 expression. Combined treatment with BMP2 and ET-1 induced cyclin D1 and DUSP1 expression and increased PA-SMC proliferation. MRE-269 attenuated BMP2/ET-1-induced cell proliferation. ET-1 increased DUSP1 expression in PA-SMCs from control patients but not in PA-SMCs from patients with PAH. This study showed that the p38/DUSP1 negative feedback loop is impaired in PAH, contributing to unregulated p38 activation and PA-SMC hyperplasia. IP receptor agonist MRE-269 increases DUSP1 expression and inhibit p38-mediated PA-SMC proliferation. Future elucidation of the detailed mechanism underlying reduced DUSP1 expression would be informative for PAH treatment.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Adrenocortical carcinoma is a rare and aggressive tumour. The only curative treatment is surgery with negative margins. In most series, the average lesion size ranges from 5.5 to 15 cm. We report the case of a 27-year-old female with hyperandrogenism and Cushing syndrome due to a right adrenocortical carcinoma of 19.7 cm. The tumour abutting on liver and vena cava and the presence two nodules in liver required extensive surgery including a right posterior sectionectomy and an en bloc resection of the adrenal mass together with the right kidney and the gallbladder. The vena cava was also resected with a reconstruction using a pericardial patch since it was invaded on its border. Pathological examination confirmed an adrenocortical carcinoma, with tumour invasion of vessels, tumour capsule, vena cava and two metastases in the liver (pT4N0M1). All margins were negative. Three months after surgery, two lung nodules, cardio-phrenic and internal mammary adenomegalies were noticed on a PET/CT scan, justifying the initiation of chemotherapy, alongside with mitotane. After a 10-month follow-up, CT scan was stable excepted for a lung nodule growing from 4 to 7 mm. Targeted stereotaxic radiotherapy was then administered. Twenty-two months after surgery, the patient has improved considerably and all signs of hyperandrogenism and Cushing syndrome have resolved. This case of adrenocortical carcinoma illustrates one of the largest tumours among those reported. It demonstrates the feasibility and effectiveness of a multimodal approach in its treatment even if it is giant and at high risk.

Therapeutic angiogenesis aims at promoting the growth of blood vessels to restore perfusion in ischemic tissues or aid tissue regeneration. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis in development, repair, and disease. However, exploiting VEGF for therapeutic purposes has been challenging and needs to take into account some key aspects of VEGF biology. In particular, the spatial localization of angiogenic signals within the extracellular matrix is crucial for physiological assembly and function of new blood vessels. Fibrin is the provisional matrix that is universally deposited immediately after injury and supports the initial steps of tissue regeneration. It provides therefore several ideal features as a substrate to promote therapeutic vascularization, especially through its ability to present growth factors in their physiological matrix-bound state and to modulate their availability for signaling. Here, we provide an overview of fibrin uses as a tissue-engineering scaffold material and as a tunable platform to finely control dose and duration of delivery of recombinant factors in therapeutic angiogenesis. However, in some cases, fibrin has also been associated with undesirable outcomes, namely the promotion of fibrosis and scar formation that actually prevent physiological tissue regeneration. Understanding the mechanisms that tip the balance between the pro- and anti-regenerative functions of fibrin will be the key to fully exploit its therapeutic potential.

[This corrects the article DOI: 10.3389/fcvm.2021.827515.].

La COVID-19 est une maladie infectieuse émergente virale causée par la souche de coronavirus SARSCoV-2. Après presque deux années de pandémie, les cliniciens ont beaucoup progressé dans les connaissances des manifestations cliniques de la maladie, notamment en mettant en avant la place du glycocalyx endothélial. Ce dernier est une structure complexe micro-fibrillaire située au pôle apical de la cellule endothéliale, constituant la barrière histologique entre la cellule et la lumière vasculaire et se comportant comme un organe à part entière. L’étude physiopathologique de ce dernier a permis de mettre en évidence l’intérêt de celui-ci dans la compréhension de la COVID-19 et de ses complications. Cette revue a donc pour but d’appréhender cette maladie sous un angle différent et se propose de résumer les données pertinentes pour le clinicien que nous avons apprises depuis deux ans.

The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Not applicable. DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Lipomatous tumors are the most common soft tissue tumors, including a large variety of benign and malignant lesions. Hiber noma is a benign lipomatous tumor originating from the brown adipose tissue inherited from the fetus. The diagnosis is often incidental, since the large majority are asymptomatic or very slow growing. Differential diagnosis with other lipomatous tumors is often challenging. Hence the diagnostic work-up is large and must be multidisciplinary. Biopsy and large resection with safe margins are the standard of care. We describe a 48-year-old male patient with a history of a painless, mobile, slow growing right sub-clavicular mass apparently evolving for eleven years. This patient underwent ultrasound, mammography, MRI, CT Scan and ultrasound guided large core biopsy at different points in time. We describe this case of a well-documented hibernoma of the sub-clavicular region in line with the current literature.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.

Bariatric surgery diminishes the incidence of many kinds of neoplasms, but gastro-esophageal cancers may occur after bariatric procedures. Most esophageal neoplasms arise on Barrett's esophagus, which may be worsened by bariatric surgery, especially restrictive procedures. Endoscopic resections may cure cancer in its early stages, but surgery may be required in more advanced cases. A 62-year-old patient with history of adjustable gastric banding, sleeve gastrectomy then Roux-en-Y gastric bypass presented with an early Barrett's adenocarcinoma. Endoscopic treatment was first applied but the patient required surgery due to positive margins on the resected specimen. As the early tumor was located in the esophagus' lower third, a limited resection with eso-jejunal anastomosis was planned. However, as the previous bariatric did not allow a proper reconstruction, a total esophagectomy with colonic interposition had to be performed. Eso-gastric malignancies remain rare after weight loss procedures, but more cases will arise due to the increasing incidence of bariatric surgery. Esophageal resection and reconstruction becomes increasingly challenging along with the number of bariatric procedures performed on the same patient. Endoscopic screening is of paramount importance before any obesity surgery or to assess any new onset of symptoms after a bariatric procedure, as endoscopic resections may cure cancer in its early stages. Endoscopic screening and treatment remains of paramount importance, especially after multiple bariatric procedures as surgery and reconstruction gets increasingly challenging. Whenever surgery is required, a proper planning and individual approach is compulsory, as well as a back-up plan.

Background: Cardiac surgery is associated with a high rate of intraoperative transfusion, requiring pre- ordering or ordering of packed red blood cell (PRBC) before surgery. Our institutional strategy is based on a systematic type and screen (T/S) ordering of 3 PRBCs at the blood bank then stored in a dedicated refrigerator in the operating room for each patient scheduled for cardiac surgery. However, these PRBC units are not always transfused and are therefore at risk of destruction if temperature fluctuations are detected during transport and storage processes. In addition, these orders represent a burden for the blood bank. Therefore, it is relevant to move towards a more tailored PRBC order before cardiac surgery and challenge the systematic ordering protocol. Methods: The Transfusion Understanding Scoring Tool (TRUST) and the Transfusion Risk and Clinical Knowledge (TRACK) Score are designed to stratify blood transfusion needs in cardiac surgery. We retrospectively performed both scores for each patient scheduled for cardiac surgery. Then, we compared their performance to predict PRBC transfusion and determined the optimal threshold to optimize the preoperative PRBC order reflecting the needs of our population managed with our local standards. Results: Receiver operating characteristic (ROC) curves for prediction of PRBC transfusion using the two scores were computed for the whole cohort (n=1249). Both scores performed well (areas under ROC curves: 0.81 and 0.82 (95% CI) using the TRACK Score and the TRUST, respectively). A TRUST < 3 identified a subgroup of patients (53.6%) at low risk of transfusion. The availability of 1 T/S PRBC in the OR would cover the needs of the majority (92.5%) of this group. Conclusions: In our institution, the use of the TRUST preoperatively could offer a more tailored T/S PRBC order for the intraoperative period, especially in the low-risk transfusion group.

Hepatic abscess is a rare condition but comes with heavy consequences if not diagnosed and managed properly. Early detection of this pathology is challenging because of the variety and lack of specificity of symptoms but is necessary for accurate management. We report a case of pyogenic liver abscess secondary to the migration of an ingested fish bone in a 74-year-old female. We used laparoscopic surgery to drain the abscess, remove the foreign body responsible and look for the perforation site. Parenteral antibiotherapy was added to the surgical treatment. Early diagnosis of hepatic abscess caused by the migration of a foreign body remains a challenge. In our opinion, laparoscopic surgery associated with antibiotics is the safest and most effective therapeutic option.

Un traumatisme de l'artère subclavière proximale droite est peu fréquent et tend à être associé à la formation d'un pseudoanévrysme. Actuellement, le traitement de choix consiste en une exclusion du pseudo-anévrysme par un stent placé par voie endovasculaire. La chirurgie ouverte est un défi chirurgical en raison de la position anatomique de l’artère subclavière et est associée à un taux élevé de morbidité et de mortalité. Nous présentons le cas d'un patient de 71 ans ayant un pseudoanévrysme de l'artère subclavière proximale droite 11 ans après un accident de voiture. L’objectif est de démontrer que la pathologie a été traitée avec succès par chirurgie vasculaire après échecs de plusieurs procédures endovasculaires. Un pontage aorto-carotido-subclavier droit a été réalisé par abord combiné associant une sternotomie complète à une cervicotomie droite. Le suivi à 6 semaines confirme l’exclusion du pseudo-anévrysme et la perméabilité des troncs revascularisés.

European surgeons were the first worldwide to use robotic techniques in cardiac surgery and major steps in procedure development were taken in Europe. After a hype in the early 2000s case numbers decreased but due to technological improvements renewed interest can be noted. We assessed the current activities and outcomes in robotically assisted cardiac surgery on the European continent. Data were collected in an international anonymized registry of 26 European centers with a robotic cardiac surgery program. During a 4-year period (2016-2019), 2,563 procedures were carried out [30.0% female, 58.5 (15.4) years old, EuroSCORE II 1.56 (1.74)], including robotically assisted coronary bypass grafting ( = 1266, 49.4%), robotic mitral or tricuspid valve surgery ( = 945, 36.9%), isolated atrial septal defect closure ( = 225, 8.8%), left atrial myxoma resection ( = 54, 2.1%), and other procedures ( = 73, 2.8%). The number of procedures doubled during the study period (from = 435 in 2016 to = 923 in 2019). The mean cardiopulmonary bypass time in pump assisted cases was 148.6 (63.5) min and the myocardial ischemic time was 88.7 (46.1) min. Conversion to larger thoracic incisions was required in 56 cases (2.2%). Perioperative rates of revision for bleeding, stroke, and mortality were 56 (2.2%), 6 (0.2 %), and 27 (1.1%), respectively. Median postoperative hospital length of stay was 6.6 (6.6) days. Robotic cardiac surgery case numbers in Europe are growing fast, including a large spectrum of procedures. Conversion rates are low and clinical outcomes are favorable, indicating safe conduct of these high-tech minimally invasive procedures.

Myelolipoma is a rare mesenchymal tumor consisting of adipose tissue and hematopoietic cells. Found usually in the adrenal region, however, few cases have been reported in extra-adrenal regions, most frequently in the presacral region. It is important to recognize such tumor, as it can attain massive size and causes pressure symptoms, and needs to be differentiated from malignant tumors, including liposarcomas. Although CT and MRI can suggest a diagnosis of myelolipoma, these are not conclusive. The hematopoietic cells are enhanced by a Tc-albumin nanocolloid scintigraphy and help to distinguish myolipoma from other entities.

80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70-8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39-8·80) and upper-middle-income countries (2·06, 1·11-3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26-11·59) and upper-middle-income countries (3·89, 2·08-7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consist

Airway stenting offers good palliation and improves the quality of life in patients with inoperable bronchotracheal stenosis. However, in some cases, the management of stenting can be life-threatening. Hence, a strategy for maintaining oxygenation and hemodynamic stability should be anticipated to avoid critical situations. Herein, we report the use of extracorporeal membrane oxygenation (ECMO) in bronchotracheal stenting management to secure oxygenation and facilitate interventions. We retrospectively reviewed all patients who underwent rigid bronchoscopy under ECMO support for the management of bronchotracheal stenting at CHU UCL Namur hospital (Belgium), between January 2009 and December 2019. We included 14 bronchoscopy cases performed on 11 patients (3 patients underwent 2 bronchoscopies) in this study; 12 were performed on males and 2 on females. The median age was 54 years. There were 11 benign and 3 malignant etiologies for the central airway obstruction/stenosis. Eight cases were supported by venovenous ECMO and six by venoarterial ECMO. The median ECMO time was 267 minutes. The weaning of ECMO support was successful in all cases. In most cases, the procedures were performed effectively and safely. Only two local complications caused by the cannulation of ECMO were reported, and anticoagulation was adapted to avoid bleeding at the operating site and clot formation in the system. Elective ECMO support was helpful and safe for the high-risk management of bronchotracheal stenting with rigid bronchoscopy and was not associated with any additional significant complications.

During the deconfinement period after the coronavirus disease-2019 (COVID-19) pandemic, the number and characteristics of psychiatric visits changed in our emergency department (ED). We aimed to assess changes in the number of visits and characterize the profiles of these patients. In this retrospective observational study, we examined the number of psychiatric ED visits and their proportion among the total number of ED visits. We also evaluated psychiatric visits characteristics during a one-month period after the declaration of deconfinement, and we compared those characteristics to characteristics observed during the same month over the previous 4 years. The number of psychiatric visits to our emergency department during deconfinement was similar to the number observed in the same month of previous years. However, the proportion of psychiatric visits to our emergency department among all visits to the ED rose during deconfinement to a level never before observed. The mean proportion of psychiatric admissions to all ED admissions rose from 3.5% in past years to 5.3% during deconfinement (p = 0.013). Moreover, during deconfinement, more visits (80%) were without an acute intoxication compared to past years (58.5%; p = 0.031). Also, in the deconfinement period, more visits lacked a follow-up consultation organized at discharge (40%) compared to the historical period (25%, p = 0.036). The deconfinement period after the first wave COVID-19 changed the number and type of psychiatric emergency medicine consultations at our hospital, suggesting a psychiatric impact of confinement during this pandemic. These findings will be of interest to practitioners and politicians in the coming months.

Graves' disease may be associated with thyroid cancer, particularly differentiated thyroid cancer. Medullary thyroid cancer (MTC) is less common. The occurrence of sporadic MTC in Graves' disease in the presence of a RET proto-oncogene has never been reported.: A 63-year-old woman was referred for Graves' disease. A thyroid ultrasound disclosed five nodules, one of which was classified as Eu-Tirads 5 with a size of 6.7 × 6.5× 11 mm. Fine needle aspiration was reported as Bethesda class IV follicular neoplasm of a Hürthle cell subtype. Calcitonin level was found to be elevated. A total thyroidectomy confirmed the diagnosis of MTC and a bilateral cervical lymphadenectomy was performed, with four lymph nodes being infiltrated by MTC. Genetic testing revealed a M918T mutation in the RET proto-oncogene.: MTC may occur in Graves' disease, especially if a nodule is present. In this case, genetic testing should always be performed even if MTC is sporadic. Increased incidence of thyroid cancer in autoimmune thyroid diseases, as well as the link existing between autoimmunity, inflammation and carcinogenesis, leads us to hypothesize that the association here reported is not coincidental.

The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.

Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to "small for size syndrome" (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the "small for size syndrome" after extended hepatectomy or small liver transplantation.

Rare cases of carcinoid syndromes can develop from either gastrointestinal neuroendocrine tumors (NETs) without liver metastasis or large retroperitoneal involvement. We report a case of a patient with isolated flushing highly suggestive of carcinoid syndrome caused by an ileal NET with adjacent lymph node metastases but with no liver metastases. The final diagnose was delayed for this patient due to a combination of misleading clinical presentation and negative usual screening tests (urinary 5-HIAA and serum chromogranine A). Given its high sensitivity and specificity, Ga-DOTATATE PET/CT confirmed the diagnosis of neuroendocrine tumor. Therefore, this case reminds clinicians that carcinoid syndrome may manifest as flushing only and highlights that imaging is a major aspect of the evaluation and diagnosis of patients with suspected gastrointestinal NETs.

Lack of standardization in the Roux-en-Y gastric bypass (RY-GBP) is quite well established. We all learned the basics of the technique, but a lot of differences do exist in performing each step of the procedure. Based on scientific evidences, coming from an extensive and meticulous review of the literature of the last 20 years, we thus address the different technical steps of the procedure and their importance to try and propose a standardization of RYGBP. A lot of possibilities exist at each and every step of a RYGBP. They influence the postoperative complications, the end weight loss (EWL), weight regain, and resolution of obesity bounded comorbidities. Furthermore, lack of standardization leads to problems regarding comparison of scientific data in the related literature.

This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels. Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020. A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso. The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.

BACKGROUND : In a previous quality control assessment of the management of STEMI in our centre–a tertiary centre in a rural area–we observed a decrease in intrahospital delays over time (2004→2013) from 98→39 minutes (median) but unchanged extrahospital delays (203–220 minutes). AIM :To elucidate the determinants of these long extrahospital delays, 181 patients, undergoing PCI for STEMI (2013–2017) in our centre, were carefully interviewed. The first medical contact (FMC) allowed to assess 2 periods: onset of symptoms–FMC (period 1) and FMC–diagnosis (period 2). Results are given as mean values (median). RESULTS :In 36%, the FMC took place via the general practitioner (GP). Period 1 was associated with the type of FMC (GP: 210 ± 294, median = 79 min/EM call: 78 ± 114, median = 43 min/direct hospital admission: 222 ± 44, median = 115 min), the moment of symptoms onset (0–4 am: 198 ± 192, median 142 min/8–12 am: 96 ± 126, median 60 min), age (70–80 y: 262 ± 324, median 120 min/50–60 y: 198 ± 438, median 63 min) and the distance to our PCI centre expressed in minutes by car (< 30′: 108 ± 156, median = 60 min/ > 60′: 216 ± 288, median = 116 min). Period 2 was depending on the type of FMC (GP: 234 ± 600, median 56 min/EM call: 31 ± 29, median 22 min/direct hospital admission: 25 ± 55, median 10 min). CONCLUSION :In our local experience, FMC via the GP in case of STEMI is a major determinant for a longer extrahospital delay and should therefore be discouraged.

To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cut-off values for annual volume of pancreatoduodenectomies (<60 vs. ≥60). Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared < 60 (4% vs. 10%, p = 0.046). In multivariable analysis, annual volume < 60 pancreatoduodenectomies (OR 3.78, 95%CI 1.18-12.16, p = 0.026), age (OR 1.07, 95%CI 1.01-1.14, p = 0.046), and estimated blood loss ≥2L (OR 11.89, 95%CI 2.64-53.61, p = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95%CI 1.56-5.26, p = 0.001) and estimated blood loss ≥2L (OR 3.52, 95%CI 1.25-9.90, p = 0.017) were associated with major complications. This pan-European prospective snapshot study found a 5% in-hospital after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Paragangliomas are rare tumors representing a therapeutic challenge. We present a case report of surgical resection of carotid body tumor without preoperative embolization. Our therapeutic attitude is based on controversial benefits of the embolization for those tumors. The major indication for the preoperative embolization is to reduce intraoperative blood loss, but this benefit is not demonstrated. Also, because the relative rarity of this tumor, the confounding factors relative to the surgeon and radiologist experience, no randomized trial can be performed. So, our case report can be useful to participate to increase the number of reported cases, and define the therapeutic approach for this rare tumor.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows extended hepatectomy in patientswith an extremely small future liver remnant (FLR). Current rodent models of ALPPS do not include resection resulting ininsufficient-for-survival FLR, or they do incorporate liver mass reduction prior to ALPPS. Differences in FLR volume andsurgical procedures could bias our understanding of physiological and hemodynamic mechanisms. We aimed to establish arat ALPPS model with minimal FLR without prior parenchymal resection. In rodents, the left median lobe (LML) represents10% of total liver. Partial hepatectomy (PHx) sparing LML and pericaval parenchyma represents our reference 87%resection. Thefirst step in the procedure is either portal vein ligation (PVL) corresponding to ligation of all but the LMLportal branches, or PVL with transection between the left and right median lobe segments (PVLT), and is defined as ALPPSstage-1. Second, ligated lobes were removed: PVL-PHx represents a conventional 2-stage hepatectomy, while PVLTfollowed by PHx is a strict reproduction of human ALPPS. In Group A, liver hypertrophy was analyzed after PVL (n=38),PVLT (n=47), T (n=10), and sham (n=10); In group B, mortality and FLR hypertrophy was assessed after PHx (n=42),Sham-PHx (n=6), PVL-PHx (n=37), and PVLT-PHx (n=45). In group A, PVLT induced rapid FLR hypertrophycompared to PVL (p< 0,05). Hepatocyte proliferation was higher in PVLT remnants (p< 0,05). In group B, PHx had a 5-daymortality rate of 84%. Sham operation prior to PHx did not improve survival (p=0.23). In both groups, major fatalitiesoccurred within 48 h after resection. PVL or PVLT prior to PHx reduced mortality to 33.3% (p=0,007) or 25% (p=0.0002) respectively, with no difference between the 2 two-stage procedures (p=0.6). 7-day FLR hypertrophy was higherafter the PVLT-PHx compared to PVL-PHx and PHx (p=0.024). Our model reproduces human ALPPS with FLR that isinsufficient for survival without liver

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

BACKGROUND: CD8+ CD30+ primary cutaneous T-cell lymphomas (PCTCL) are rare entities with overlapping pathological features and variable outcome. OBJECTIVES: We sought to highlight the importance of correlation between pathological findings and clinical presentation for correct classification of the disease. MATERIALS & METHODS: Two cases of CD8+ CD30+ PCTCL were investigated. The first patient presented with a multiple necro-erythematous lesion of the limb and the second with a papulo-necrotic lesion of the eyelid. RESULTS: Despite a different clinical presentation, pathological findings were similar in both cases. Clinico-pathological correlation led to a diagnosis of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma in the first case and primary cutaneous anaplastic large-cell lymphoma in the second. The first patient died shortly after diagnosis and the second is alive without recurrence. CONCLUSIONS: Clinico-pathological correlation is essential for the correct identification of these rare diseases.

Excessive portal hypertension with compensatory arterial constriction of the future liver remnant (FLR) is considered the main cause of SFSS after major hepatectomy. ALPPS combines portal vein ligation and parenchymal transection to obtain rapid hypertrophy of FLR for patients needing marginal hepatectomy, with high risk of postoperative SFSS. This procedure sets the FLR in the same hemodynamic portal conditions as in SFSS, and yet, patients survive, and obtain boosted FLR hypertrophy. [...]

OBJECTIVES: Postoperative complications after Laparoscopic sleeve gastrectomy (LSG) can dramatically compromise patient's outcome. The aim of this study is to analyze the per- and postoperative short-term outcomes after LSG and to assess predictive risk factors of complications. METHODS: The study group consisted of 790 patients (610 women and 180 men) who underwent LSG In 2014. All interventions were performed by 18 experienced surgeons members of the Club Coelio. Data about preoperative work-up, surgical techniques, 30-days postoperative morbidity and mortality were collected. Endpoints were perioperative morbidity and mortality and assessment of potential risk factors for complications. RESULTS: Mean age and body mass index were respectively 39 years and 41.5kg/m2. Ninety-one patients (11.5%) had previous bariatric surgery. Morbidity rate was 4.7% (37/790) including 16 leaks (2.0%) and 9 bleedings (1.1%) and no deaths. Risk factors for leak were: previous adjustable banding (p = .0051), with no difference between removal of the banding and LSG in 1 or 2 steps, and type of endostapler (p = .0129). CONCLUSIONS: Leakage after Sleeve was rare but still observed even in experienced hands. The leak rate is particularly high when LSG is performed after adjustable gastric banding removal.

The incidence of thyroid cancer has increased markedly in recent decades, but has been stable in terms of mortality rates. For the most part, these cancers are treated with surgery, which may or may not be followed by radioactive iodine depending on the tumor subtype. Still, many of these cancers will recur and may be treated with radioactive iodine or another surgery. It is unclear what treatment is best for cases of locally advanced or metastatic thyroid cancer that are refractory to radioactive iodine. Chemotherapy has a very low response rate. However, in the past few years, several systemic therapies, primarily targeted, have emerged to improve the overall survival of these patients. Alternative treatments are also of interest, namely peptide receptor radionuclide therapy or immunotherapy.

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)-based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell-based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF-expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS-purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

Coronary artery bypass grafting (CABG) remains the most common cardiac surgery performed today worldwide. The history of this procedure can be traced back for more than 100 years, and its development has been touched by several pioneers in the field of cardiac surgery, who have contributed with both their successes and failures. With ever increasing follow up and number of patients treated, thinking regarding optimal CABG technique evolves continually. This article reviews the history of CABG from its early experimental work to recent technological advances.

This study measured the prevalence of chronic venous disease (CVD, C1-C6), chronic venous insufficiency (C3-C6) in 23 countries. The possible influence of risk factors was assessed. Patient recruitment was carried out by general practitioners. Patient characteristics, prevalence of risk factors, and C-classification were recorded. We assessed differences in prevalence and risk factors between Asia (A), Eastern Europe (EE), Latin America (LA), and Western Europe (WE). A total of 99 359 patients were included. The prevalence of CVD (51.9% A, 70.18% EE, 68.11% LA, and 61.65% WE) was significantly ( P < .001) lower in A. Risk factors such as age, obesity, smoking, having regular exercise, use of birth control pills, prolonged standing and sitting, and having a positive family history differ significantly between regions. After model-based probabilities corrected for risk factors, significant differences in the probability of having CVD were only found in the older age-group (>65 years). The lowest prevalence was noted in A. Chronic venous disease is very common and the prevalence varies between different geographical areas. After correcting for risk factors, these differences diminished.

Clinical vignette : Since the mid-nineties, minimally invasive direct coronary artery bypass grafting (MIDCAB) has evolved thanks to technological development of robotically assisted coronary surgery known as totally endoscopic coronary artery bypass (TECAB). Here, we report the case of a 51-year old lady with typical angina pectoris without any other relevant comorbidity. The angiogram showed a single and severe lesion at the ostium of the left anterior descending (LAD) coronary artery. Following an interdisciplinary heart team approach, a TECAB was proposed and accepted by the patient. This tutorial demonstrates the technical aspects of a single beating-heart TECAB. [...]

While acromio-clavicular dislocations are common lesions, the association with sterno-clavicular joint dislocation proves to be very rare, with less than fifty cases reported worldwide. We have herein presented the case of a 56-year-old man with a traumatic postero-superior acromio-clavicular and anterior sternoclavicular dislocation following a car accident. Due to late presentation, he received a conservative treatment with excellent results regarding pain, mobility, and strength, yet with poor cosmetic outcome. In spite of the current trend towards surgical reduction and lesion stabilization, conservative treatment of bipolar clavicle dislocation proves to be a safe and easy means to obtain functional recovery. Of note is that this measure does not correct esthetic deformity, with uncertain long-term consequences.

PURPOSE: To compare different types of knee arthroplasty, in selected patients with a knee score above 80 points, for their post-operative changes in anteroposterior (AP) laxity and proprioception. METHODS: Four groups of each ten patients were tested for AP translation after different types of arthroplasty with a KT-1000 device at 30°, 60° and 90° of flexion. Proprioception of the joint was evaluated by joint position sense with three different tests. Clinical outcome of stability and proprioceptive testing was analysed by comparing the results of three (KSS, KOOS and FJS-12) patient-reported outcome measurement scores (PROMS) for each of the different implant types. RESULTS: Anteroposterior laxity was observed at 30° and 90° of flexion for the two PS TKA designs included in this study, but not for the UKA or the medial pivot design. All knee designs, except UKA, had an increased laxity at 60° of flexion. Proprioceptive testing was inconclusive. PROMS were not able to identify differences in clinical outcome among different knee designs in these selected patients, despite observed differences in AP laxity. CONCLUSION: Increased AP laxity is a result of the surgical procedure in knee arthroplasty. UKA is the only design mimicking native laxity of the knee. A medial pivot design can obtain the same result as UKA at 30° and 90° of flexion, but not at the importantly cited 60° of flexion as tested under non-load-bearing conditions. The clinical relevance of this study is that despite of an important range of AP translations among the different knee designs, good-to-excellent patient-reported outcome was observed within the findings of this study.

BACKGROUND: Laparoscopic liver surgery (LLS) gained popularity bringing several advantages including decreased morbidity and reduction of length of hospital stay compared to open. METHODS: To understand practice and evolution of LLS in Belgium, a 20-questions survey was sent to all members of the Royal Belgian Society for Surgery, the Belgian Section of Hepato-Pancreatic and Biliary Surgery and the Belgian Group for Endoscopic Surgery. RESULTS: Thirty-seven surgical units representing 61 surgeons performing LLS in Belgium responded: 50% from regional hospitals, 28% from university and 22% from peripheral hospitals. Replies from high volume centers (>50 liver-surgery/year) were 19%. More than 25% of liver procedures were performed laparoscopically in 35% of centers. LLS is adopted since more than 15-years in 14.5% of centers with an increasing rate reported in 59%. Low relevance of LLS in the hospital organization (26.5%) and lack of time in surgical schedules (12%) or of specific training (9%) are the main barriers for further diffusion. More than 80% of the responders agreed to participate to a national prospective registry. CONCLUSION: LLS is mainly performed in experienced HPB units with an increasing interest in peripheral centers. A prospective national registry will be useful by providing real data in terms of indications, morbidity and overall evolution.