Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Résection à visée curatrice de métastase hépatiques de cancers colorectaux initialement non résécables,après chimiothérapie par FOLFIRINOX

Objectifs de l'étude: Déterminer le taux de résection chirurgicale complète des métastases hépatiques non résécables d'emblée après chimiothérapie selon le protocole FOLFIRlNOX ou ERBIRlNOX et réaliser une analyse descriptive et de survie de la population prise en charge chirurgicalement au CRLC Val d'Aurelle. Matériels et méthodes: Il s'agit d'une étude rétrospective d'une série de 36 patients recensés entre octobre 2000 et décembre 2009. Le suivi a été mené jusqu'en décembre 2010. Les caractéristiques de la tumeur primitive, des métastases hépatiques après relecture scanographique, les paramètres chirurgicaux et les données postopératoires ont été analysées. Une comparaison entre les sous-groupes de patients opérés d'une chirurgie hépatique en un temps et d'une chirurgie séquentielle a été effectuée. Résultats: Sur les 100 patients ayant reçu la chimiothérapie, 36 ont été jugés résécabies en préopératoire et 28 ontété réséqués complètement. Le nombre moyen de métastases hépatiques était de 7,6 par patient, leur taille maximale de 50 mm (21-132) et leur répartition bilobaire dans 76% des cas. 21 patients ont été opérés en un temps et 12 planifiés pour une chirurgie séquentielle. 58% des patients opérés en deux temps ont été au terme de la procédure. Aucun patient n'est décédé en postopératoire et la morbidité était faible (34% dont 89% de grade 1 et II de la classification de Dindo). Après un suivi médian de 39 mois, les survies globale et sans récidive à 5 ans des patients en résection complète étaient respectivement de 38% et 12%. Conclusion: Cette étude confirme les bons résultats oncologiques des patients en résection complète. Ceci peut êtrt expliqué par l'efficacité de la chimiothérapie par Fo!frrinox, par le choix de la stratégie chirurgicale qui est adaptée à chaque situation clinique et par le faible taux de morbimortalité.MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery

International audiencePURPOSE:Fluorescence-guided surgery (FGS) provides surgeons with new opportunities to improve real-time cancer nodule detection and tumor margin visualization. Currently, the most important challenge in this field is the development of fluorescent dyes that specifically target tumors. We developed, characterized and evaluated SGM-101, an innovative antibody-dye conjugate in which the fluorochrome BM104, which has an absorbance band centered at 700 nm, is coupled to a chimeric monoclonal antibody (mAb) against carcinoembryonic antigen (CEA).METHODS:The dye to mAb ratio, binding to CEA and photobleaching of SGM-101 were determined. FGS was performed and results analyzed using different mouse models of human digestive tumors.RESULTS:SGM-101 allowed the detection of tumor nodules in three different colon cancer models: LS174T human colorectal adenocarcinoma cell-induced peritoneal carcinomatosis (PC) and liver metastases, and orthotopic grafts of HT29 human colorectal adenocarcinoma cells. In the PC model, submillimeter-sized nodules were detected during SGM-101-based FGS and SGM-101 predictive positive values ranged from 99.04% to 90.24% for tumor nodules >10 mg and nodules <1 mg, respectively. Similarly, in the orthotopic model of pancreatic cancer using BxPC3 (pancreas adenocarcinoma) cells, SGM-101 could clearly delineate tumors in vivo with a tumor-to-background ratio of 3.5, and penetrated in tumor nodules, as demonstrated by histological analysis. Free BM105 dye (BM104 with an activated ester for conjugation to the antibody) and an irrelevant conjugate did not induce any NIR fluorescence.CONCLUSION:These preclinical data indicate that SGM-101 is an attractive candidate for FGS of CEA-expressing tumors and is currently assessed in clinical trials

Associer les démarches de chemin clinique et d’éducation thérapeutique

International audienceThe integration of the therapeutic education of the patient into a clinical pathway approach helps to optimise nursing practice. Despite some limits, this method allows the position of the caregiver to evolve, going beyond the required methodological framework. It results in the emergence of several new educational facets which are essential for the patient and enable them to become a player in their own care.L’intégration de l’éducation thérapeutique du patient à une démarche d’élaboration de chemin clinique permet d’optimiser la pratique soignante. Malgré quelques limites, cette méthode conduit à l’évolution de la posture du soignant dépassant le cadre méthodologique requis. Elle fait émerger plusieurs facettes éducatives nouvelles et essentielles pour le patient, replacé comme acteur

Oncological Outcomes after Liver Venous Deprivation for Colorectal Liver Metastases: A Single Center Experience

International audienceColorectal liver metastases (CRLM) are the major cause of death in patients with colorectal cancer (CRC). The cornerstone treatment of CRLM is surgical resection. Post-operative morbidity and mortality are mainly linked to an inadequate future liver remnant (FLR). Nowadays preoperative portal vein embolization (PVE) is the most widely performed technique to increase the size of the future liver remnant (FLR) before major hepatectomies. One method recently proposed to increase the FLR is liver venous deprivation (LVD), but its oncological impact is still unknown. The aim of this study is to report first short- and long-term oncological outcomes after LVD in patients undergoing right (or extended right) hepatectomy for CRLM. Seventeen consecutive patients undergoing LVD between July 2015 and May 2020 before an (extended) right hepatectomy were retrospectively analyzed from an institutional database. Post-operative and follow-up data were analyzed and reported. Primary outcomes were 1-year and 3-year overall survival (OS) and hepatic recurrence (HR). Postoperative complications occurred in 8 patients (47%). No deaths occurred after surgery. HR occurred in 9 patients (52.9%). 1-year and 3-year OS were 87% (95% confidence interval [CI]: ±16%) and 60.3%, respectively (95% CI: ±23%). Median Disease-Free Survival (DFS) was 6 months (CI 95%: 4.7–7.2). With all the limitations of a retrospective study with a small sample size, LVD showed similar oncological outcomes compared to literature reports for Portal Vein Embolization (PVE)

Distal Pancreatectomy with Celiac Axis Resection (Modified Appleby Procedure) and Arterial Reconstruction for Locally Advanced Pancreatic Adenocarcinoma After FOLFIRINOX Chemotherapy and Chemoradiation Therapy

International audienceBackground: Resectability of pancreatic carcinoma (PC) is directly linked to vascular extension (Tempero MA et al. in J Natl Compr Canc Netw 15(8):1028–1061, 2017. https://doi.org/10.6004/jnccn.2017.0131; Isaji S et al. in Pancreatology 18(1):2–11, 2018. https://doi.org/10.1016/j.pan.2017.11.011). Involvement of the celiac axis (CA) is typically a contraindication to surgery. High postoperative morbidity and subsequent poor prognosis have been observed in this case, especially for contact > 180° requiring arterial resection (Tempero MA et al. 2017). Recent medical advances in PC treatment, such as FOLFIRINOX-based chemotherapy eventually followed by chemoradiation therapy, offer the potential to select tumour for surgery and to obtain a negative-margin resection even in case of unresectable PC at diagnosis (Suker M et al. in Lancet Oncol 17(6):801–10, 2016. https://doi.org/10.1016/s1470-2045(16)00172-8; Pietrasz D et al. in Ann Surg Oncol 26(1):109–117, 2019. https://doi.org/10.1245/s10434-018-6931-6). A major pathologic response has been observed in more than 20% of patients after this treatment and is associated with an improved survival (Suker M et al. 2016; Pietrasz D et al. 2019). This evolution allows aggressive surgical strategies with the possibility of long-term disease control for patients showing a good response to induction treatment.Patient: This video presents the case of a 66-year-old man diagnosed with a locally advanced ductal adenocarcinoma of the pancreatic body with a 360° involvement of the CA and the hepatic artery. After eight courses of FOLFIRINOX chemotherapy and a capecitabin-based chemoradiation, a surgical exploration was planned for potential resection.Technique: The key steps of the procedure are presented, i.e. surgical exposition, assessment of resectability with frozen sections of peri-arterial tissues, en bloc resection (Strasberg SM et al. in Surgery 133(5):521–527, 2003. https://doi.org/10.1067/msy.2003.146), and primary end-to-end arterial reconstruction.Conclusion: A modified Appleby operation for locally advanced PC is a technically challenging but feasible procedure in experienced teams. It offers the possibility of en bloc R0 resection of a locally advanced PC with the potential of long-term disease local control. This video may help surgeons to perform this complex intervention

Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy

International audiencePressurized intraperitoneal aerosol chemotherapy (PIPAC) is a technique to directly deliver chemotherapeutic drugs in the abdomen for the treatment of peritoneal metastases. Pressurization improves the treatment efficacy but increases the risk of exposure for the medical/non-medical staff who can be exposed by dermal or ocular contact, or inhalation of aerosols containing the cytotoxic drugs. The aim of this study was to evaluate the risk of exposure for the medical/non-medical staff (nurses, surgeons, anaesthesiologists and cleaning personnel; n = 13) during PIPAC with oxaliplatin performed according to the protocol recommended in France. Blood samples were collected 1 h before and immediately after PIPAC, and urine samples 1 h before, and then 3 h and the morning after PIPAC. In the control, non-exposed group (n = 7), only one urine and blood sample were collected. Surface contamination in the operating room was assessed in water- and Surfanios-impregnated wipe samples. The total elemental platinum in each sample was quantified by inductively coupled plasma mass spectrometry, using a method adapted to quantify trace amounts (ng.L−1) in very low volumes (100 μl). No surface contamination was detected. Although 25% of urine samples in the exposed group contained platinum, no statistical difference was observed in urine and plasma samples collected before and after PIPAC and with the control group samples. These findings suggest that the French PIPAC protocol does not increase the risk of exposure to platinum in all staff categories involved. This protocol could be considered in future occupational policies and consensus statement

Perioperative impact of liver venous deprivation compared with portal venous embolization in patients undergoing right hepatectomy: preliminary results from the pioneer center

International audienceBACKGROUND:Preoperative portal vein embolization (PVE) is currently the standard technique used routinely to increase the size of the future remnant liver (FRL) before major hepatectomies. The degree of hypertrophy (DH) is approximatively 10% and requires on average six weeks. ALPPS is faster and achieves a good DH but with a higher morbidity and mortality. One method recently proposed to increase the FRL is liver venous deprivation (LVD), but its clinical and operative impact is still unknown. The aim of this study is to compare intra- and postoperative morbidity/mortality and the histological evaluation of the liver parenchyma between PVE and LVD in patients undergoing anatomic right hepatectomy.METHODS:Fifty-three consecutive patients undergoing PVE and LVD before a major hepatectomy were retrospectively analysed between 2015 and 2017. In order to reduce the bias, only potential standard right hepatectomies were selected. Surgical resections and the radiologic procedures were performed by the same Institution. Intra-operative parameters (transfusions, perfusions, bleeding, operative time), postoperative complications (Clavien-Dindo and ISGLS criteria), and histological findings were compared.RESULTS:To induce FRL growth 16 patients underwent PVE and 13 LVD. One patient of the PVE group was not resected due to peritoneal metastases. Surgery was performed for hepatocellular carcinoma (PVE =9, LVD =3), metastases (PVE =5, LVD =10), or others diseases (PVE =2, LVD =0). Per- and post-operative morbidity/mortality rates after PVE and LVD procedures were null. No differences between the two groups were found in terms of intraoperative bleeding (median: 550 vs. 1,200 mL; P=0.36), hepatic pedicle clamping (5 vs. 3 patients; P=0.69), intraoperative red blood cells transfusions (median: 622 vs. 594; P=0.42) and operative time (median: 270 vs. 330 min; P=0.34). Post-operative course was similar when comparing both medical and surgical complications in the two arms (PVE n=7, LVD n=10, P=0.1). Major complications (Clavien-Dindo ≥ IIIa) occurred in 3 patients undergoing PVE and in 1 patient of the LVD group (P=0.6). No difference in biliary leak (P=0.1), haemorrhage (P=0.2) and liver failure (P=0.64) was found. One cirrhotic patient in the group of PVE died of post-operative liver failure due to left portal vein thrombosis. Although we experienced a more marked liver damage when assessing on neoplastic liver parenchyma, no statistical difference was observed in terms of atrophy (P=0.19), necrosis (P=0.5), hemorrhage (P=0.42) and sinusoidal dilatation (P=0.69).CONCLUSIONS:Despite the limitations of our study, to our knowledge this is the first report to compare the two techniques LVD is a promising and safe procedure to induce a fast FRL hypertrophy, showing similar mortality/morbidity rates during and after surgery compared to PVE

Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results

International audienceBACKGROUND:Motion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment.MATERIALS AND METHODS:Between May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients.RESULTS:With a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an intrahepatic progression "out of field". Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm).CONCLUSION:The clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating