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Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.
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BACKGROUND: Hepatocellular carcinoma (HCC) have a dismal prognosis and any effective neoadjuvant treatment has been validated to date. We aimed to investigate the role of neoadjuvant transarterial chemoembolization (TACE) in upfront resectable HCC larger than 5 cm. METHODS: This is a multicentric retrospective study comparing outcomes of large HCC undergoing TACE followed by surgery or liver resection alone before and after propensity-score matching (PSM). RESULTS: A total of 384 patients were included of whom 60 (15.6%) received TACE. This group did not differ from upfront resected cases neither in terms of disease-free survival (p = 0.246) nor in overall survival (p = 0.276). After PSM, TACE still did not influence long-term outcomes (p = 0.935 and p = 0.172, for DFS and OS respectively). In subgroup analysis, TACE improved OS only in HCC ≥10 cm (p = 0.045), with a borderline significance after portal vein embolization/ligation (p = 0.087) and in single HCC (p = 0.052). CONCLUSIONS: TACE should not be systematically performed in all resectable large HCC. Selected cases could however potentially benefit from this procedure, as patients with huge and single tumors or those necessitating of a PVE.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Terapia Neoadjuvante , Pontuação de Propensão , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Europa (Continente) , Hospitais com Alto Volume de Atendimentos , Resultado do Tratamento , Prognóstico , Intervalo Livre de Doença , Fatores de TempoRESUMO
INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.
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BACKGROUND: A preoperative surgical strategy before hepatectomy for hepatocellular carcinoma is fundamental to minimize postoperative morbidity and mortality and to reach the best oncologic outcomes. Preoperative 3D reconstruction models may help to better choose the type of procedure to perform and possibly change the initially established plan based on conventional 2D imaging. METHODS: A non-randomized multicenter prospective trial with 136 patients presenting with a resectable hepatocellular carcinoma who underwent open or minimally invasive liver resection. Measurement was based on the modification rate analysis between conventional 2D imaging (named "Plan A") and 3D model analysis ("Plan B"), and from Plan B to the final procedure performed (named "Plan C"). RESULTS: The modification rate from Plan B to Plan C (18%) was less frequent than the modification from Plan A to Plan B (35%) (OR = 0.32 [0.15; 0.64]). Concerning secondary objectives, resection margins were underestimated in Plan B as compared to Plan C (-3.10 mm [-5.04; -1.15]). CONCLUSION: Preoperative 3D imaging is associated with a better prediction of the performed surgical procedure for liver resections in HCC, as compared to classical 2D imaging.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Imageamento Tridimensional , Hepatectomia/métodos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.
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COVID-19 , Neoplasias do Colo , Neoplasias Colorretais , COVID-19/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Hospitais Universitários , Humanos , Pandemias , RNA Viral , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND & AIMS: Patients with hepatocellular carcinoma (HCC) displaying overexpression of immune gene signatures are likely to be more sensitive to immunotherapy, however, the use of such signatures in clinical settings remains challenging. We thus aimed, using artificial intelligence (AI) on whole-slide digital histological images, to develop models able to predict the activation of 6 immune gene signatures. METHODS: AI models were trained and validated in 2 different series of patients with HCC treated by surgical resection. Gene expression was investigated using RNA sequencing or NanoString technology. Three deep learning approaches were investigated: patch-based, classic MIL and CLAM. Pathological reviewing of the most predictive tissue areas was performed for all gene signatures. RESULTS: The CLAM model showed the best overall performance in the discovery series. Its best-fold areas under the receiver operating characteristic curves (AUCs) for the prediction of tumors with upregulation of the immune gene signatures ranged from 0.78 to 0.91. The different models generalized well in the validation dataset with AUCs ranging from 0.81 to 0.92. Pathological analysis of highly predictive tissue areas showed enrichment in lymphocytes, plasma cells, and neutrophils. CONCLUSION: We have developed and validated AI-based pathology models able to predict the activation of several immune and inflammatory gene signatures. Our approach also provides insights into the morphological features that impact the model predictions. This proof-of-concept study shows that AI-based pathology could represent a novel type of biomarker that will ease the translation of our biological knowledge of HCC into clinical practice. LAY SUMMARY: Immune and inflammatory gene signatures may be associated with increased sensitivity to immunotherapy in patients with advanced hepatocellular carcinoma. In the present study, the use of artificial intelligence-based pathology enabled us to predict the activation of these signatures directly from histology.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Inteligência Artificial , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Curva ROCRESUMO
BACKGROUND: Posthepatectomy liver failure (PHLF) is a rare but dreaded complication. The aim was to test whether a combination of non-invasive biomarkers (NIBs) and CT data could predict the risk of PHLF in patients who underwent resection of hepatocellular carcinoma (HCC). METHODS: Patients with HCC who had liver resection between 2012 and 2020 were included. A relevant combination of NIBs (NIB model) to model PHLF risk was identified using a doubly robust estimator (inverse probability weighting combined with logistic regression). The adjustment variables were body surface area, ASA fitness grade, male sex, future liver remnant (FLR) ratio, difficulty of liver resection, and blood loss. The reference invasive biomarker (IB) model comprised a combination of pathological analysis of the underlying liver and hepatic venous pressure gradient (HVPG) measurement. Various NIB and IB models for prediction of PHLF were fitted and compared. NIB model performances were validated externally. Areas under the curve (AUCs) were corrected using bootstrapping. RESULTS: Overall 323 patients were included. The doubly robust estimator showed that hepatitis C infection (odds ratio (OR) 4.33, 95 per cent c.i. 1.29 to 9.20; P = 0.001), MELD score (OR 1.26, 1.04 to 1.66; P = 0.001), fibrosis-4 score (OR 1.36, 1.06 to 1.85; P = 0.001), liver surface nodularity score (OR 1.55, 1.28 to 4.29; P = 0.031), and FLR volume ratio (OR 0.99, 0.97 to 1.00; P = 0.014) were associated with PHLF. Their combination (NIB model) was fitted externally (2-centre cohort, 165 patients) to model PHLF risk (AUC 0.867). Among 129 of 323 patients who underwent preoperative HVPG measurement, NIB and IB models had similar performances (AUC 0.753 versus 0.732; P = 0.940). A well calibrated nomogram was drawn based on the NIB model (AUC 0.740). The risk of grade B/C PHLF could be ruled out in patients with a cumulative score of less than 160 points. CONCLUSION: The NIB model provides reliable preoperative evaluation with performance at least similar to that of invasive methods for PHLF risk prediction.
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Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Biomarcadores , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Falência Hepática/diagnóstico , Falência Hepática/etiologia , Neoplasias Hepáticas/patologia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos RetrospectivosRESUMO
INTRODUCTION AND OBJECTIVES: Liver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. RESULTS: A total of 84% of the patients were male, and the median age was 66 years old (IQR 58-74). Thirty-nine (33%) had Child-Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6-6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55-110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p<0.001), portal veinous invasion (p=0.003) and cirrhosis (p=0.020). Using these factors, we created a simple recurrence-risk scoring system that classified three groups with distinct disease-free survival medians (p<0.001): no risk factors (65 months), 1 risk factor (36 months), and ≥2 risk factors (8.9 months). CONCLUSION: Liver resection is the only curative option for large HCC, and we confirmed that survival could be acceptable in experienced centres. Recurrence is the primary issue of surgery, and we proposed a simple preoperative score to help identify patients with the most worrisome prognosis and possible candidates for combined therapy.
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Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Humanos , Masculino , Idoso , Feminino , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Doença Hepática Terminal/cirurgia , Recidiva Local de Neoplasia , Índice de Gravidade de Doença , Cirrose Hepática/complicaçõesRESUMO
BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic required a rapid surge of healthcare capacity to face a growing number of critically ill patients. For this reason, a support reserve of physicians, including surgeons, were required to be reassigned to offer support. OBJECTIVE: To realize a survey on the educational programs deployed (face-to-face or e-learning focusing on infective area, basic gestures, COVID clinical management and intensive care medicine), and their impact on behavior change (Kirkpatrick 3) of the target population of surgeons, measured on a five modalities Likert scale. DESIGN: Cross-sectional online e-survey (NCT04732858) within surgeons from the Assistance Publique - Hôpitaux de Paris network, metropolitan area of Paris, France. RESULTS: Cross-sectional e-Survey: among 382 surgeons invited, 37 (9.7%) participated. The effectiveness of the educational interventions on behavior changes was rated within the highest region of the Likert scale by 15% (n = 3) and 22% (n = 6) for 'e-learning' and 'face-to-face' delivery modes, respectively. CONCLUSIONS: Despite the low response rate, this survey suggests an overall low impact on behaviour change among responders affiliated to a surgical discipline.
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OBJECTIVE: To compare 2 techniques of remnant liver hypertrophy in candidates for extended hepatectomy: radiological simultaneous portal vein embolization and hepatic vein embolization (HVE); namely LVD, and ALPPS. BACKGROUND: Recent advances in chemotherapy and surgical techniques have widened indications for extended hepatectomy, before which remnant liver augmentation is mandatory. ALPPS and LVD typically show higher hypertrophy rates than portal vein embolization, but their respective places in patient management remain unclear. METHODS: All consecutive ALPPS and LVD procedures performed in 8 French centers between 2011 and 2020 were included. The main endpoint was the successful resection rate (resection rate without 90-day mortality) analyzed according to an intention-to-treat principle. Secondary endpoints were hypertrophy rates, intra and postoperative outcomes. RESULTS: Among 209 patients, 124 had LVD 37 [13,1015] days before surgery, whereas 85 underwent ALPPS with an inter-stages period of 10 [6, 69] days. ALPPS was mostly-performed for colorectal liver metastases (CRLM), LVD for CRLM and perihilar cholangiocarcinoma. Hypertrophy was faster for ALPPS. Successful resection rates were 72.6% for LVD ± rescue ALPPS (n = 6) versus 90.6% for ALPPS (P < 0.001). Operative duration, blood losses and length-of-stay were lower for LVD, whereas 90-day major complications and mortality were comparable. Results were globally unchanged for CRLM patients, or after excluding the early 2âyears of experience (learning-curve effect). CONCLUSIONS: This study is the first 1 comparing LVD versus ALPPS in the largest cohort so far. Despite its retrospective design, it yields original results that may serve as the basis for a prospective study.
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Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Hepatectomia/métodos , Veias Hepáticas/cirurgia , Análise de Intenção de Tratamento/métodos , Neoplasias Hepáticas/terapia , Veia Porta/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: Standardized and robust risk-stratification systems for patients with hepatocellular carcinoma (HCC) are required to improve therapeutic strategies and investigate the benefits of adjuvant systemic therapies after curative resection/ablation. APPROACH AND RESULTS: In this study, we used two deep-learning algorithms based on whole-slide digitized histological slides (whole-slide imaging; WSI) to build models for predicting survival of patients with HCC treated by surgical resection. Two independent series were investigated: a discovery set (Henri Mondor Hospital, n = 194) used to develop our algorithms and an independent validation set (The Cancer Genome Atlas [TCGA], n = 328). WSIs were first divided into small squares ("tiles"), and features were extracted with a pretrained convolutional neural network (preprocessing step). The first deep-learning-based algorithm ("SCHMOWDER") uses an attention mechanism on tumoral areas annotated by a pathologist whereas the second ("CHOWDER") does not require human expertise. In the discovery set, c-indices for survival prediction of SCHMOWDER and CHOWDER reached 0.78 and 0.75, respectively. Both models outperformed a composite score incorporating all baseline variables associated with survival. Prognostic value of the models was further validated in the TCGA data set, and, as observed in the discovery series, both models had a higher discriminatory power than a score combining all baseline variables associated with survival. Pathological review showed that the tumoral areas most predictive of poor survival were characterized by vascular spaces, the macrotrabecular architectural pattern, and a lack of immune infiltration. CONCLUSIONS: This study shows that artificial intelligence can help refine the prediction of HCC prognosis. It highlights the importance of pathologist/machine interactions for the construction of deep-learning algorithms that benefit from expert knowledge and allow a biological understanding of their output.
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Carcinoma Hepatocelular/mortalidade , Aprendizado Profundo , Hepatectomia/métodos , Neoplasias Hepáticas/mortalidade , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to analyze risk factors of local recurrence (LR) after exclusive laparoscopic thermo-ablation (TA) with or without associated liver resection. METHODS: Between 2012 and 2017, among 385 patients who underwent 820 TA in our department, 65 (17%) patients (HCC = 11, LM = 54) had exclusive laparoscopic TA representing 112 lesions (HCC = 17, LM = 95). TA was associated with other procedures in 57% of cases (liver resection 81%). All TA were done without liver clamping. Median tumor size was 1.8 cm [ranges from 0.3 to 4.5], 18% of the lesions were larger than 3 cm in size and 11% close to major liver vessels. Tumors locations were 77.5% in right liver, 36% in S7&S8, and 46% in S7&S8&S4a. RESULTS: Mortality was nil and morbidity rate 15.4% including Dindo-Clavien > II grade 3%. The median follow-up was 24 months [0.77-75]. Per lesion LR rate after TA was 18% (n = 19 patients) with a mean time of 7.6 months. Among patients with LR, 18 (95%) could have been re-treated successfully (new resection = 11, re-TA = 7). Multivariate analyses revealed that tumor location in S7 alone, S7&S8 and/or S7, S8, or S4a were independent risk factors of LR after TA. CONCLUSIONS: Exclusive laparoscopic TA is a safe and an effective tool to treat liver malignancies with or without liver resection. Other than classical risk factors, tumor location in upper segments of the liver, are independent risk factors for LR.
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Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Typically, the axillary arch is defined as a fleshy slip running from latissimus dorsi to the anterior aspect of the humerus. Phylogeny seems to give the most relevant and plausible explanation of this anatomical variant as a remnant of the panniculus carnosus. However, authors are not unanimous about its origin. We report herein the incidence of axillary arch in a series of 40 human female dissections and present an embryologic and a comparative study in three domestic mammals. MATERIALS AND METHODS: Forty formalin-preserved Caucasian human female cadavers, one rat (Rattus norvegicus), one rabbit (Oryctolagus cuniculus) and one pig (Sus scrofa domesticus) cadavers were dissected bilaterally. A comparative, analytical and a descriptive studies of serial human embryological sections were carried out. RESULTS: We found an incidence of axillary arch of 2.5% (n = 1 subject of 40) in Humans. We found a panniculus carnosus inserted on the anterior aspect of the humerus only in the rat and the rabbit but not in the pig. The development of the latissimus dorsi takes place between Carnegie stage 16-23, but the embryological study failed to explain the genesis of the axillary arch variation. However, comparative anatomy argues in favour of a panniculus carnosus origin of the axillary arch. CONCLUSIONS: With an incidence of 2.5% of cases, the axillary arch is a relatively frequent variant that should be known by clinician and especially surgeons. Moreover, while embryology seems to fail to explain the genesis of this variation, comparative study gives additional arguments which suggest a possible origin from the panniculus carnosus.
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Variação Anatômica , Úmero/anormalidades , Músculos Superficiais do Dorso/anormalidades , Idoso , Idoso de 80 Anos ou mais , Animais , Cadáver , Dissecação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Coelhos , Ratos , Estudos Retrospectivos , Sus scrofaRESUMO
BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is an important risk factor for hepatocellular carcinoma (HCC). Despite effective antiviral therapies, the risk for HCC is decreased but not eliminated after a sustained virologic response (SVR) to direct-acting antiviral (DAA) agents, and the risk is higher in patients with advanced fibrosis. We investigated HCV-induced epigenetic alterations that might affect risk for HCC after DAA treatment in patients and mice with humanized livers. METHODS: We performed genome-wide ChIPmentation-based ChIP-Seq and RNA-seq analyses of liver tissues from 6 patients without HCV infection (controls), 18 patients with chronic HCV infection, 8 patients with chronic HCV infection cured by DAA treatment, 13 patients with chronic HCV infection cured by interferon therapy, 4 patients with chronic hepatitis B virus infection, and 7 patients with nonalcoholic steatohepatitis in Europe and Japan. HCV-induced epigenetic modifications were mapped by comparative analyses with modifications associated with other liver disease etiologies. uPA/SCID mice were engrafted with human hepatocytes to create mice with humanized livers and given injections of HCV-infected serum samples from patients; mice were given DAAs to eradicate the virus. Pathways associated with HCC risk were identified by integrative pathway analyses and validated in analyses of paired HCC tissues from 8 patients with an SVR to DAA treatment of HCV infection. RESULTS: We found chronic HCV infection to induce specific genome-wide changes in H3K27ac, which correlated with changes in expression of mRNAs and proteins. These changes persisted after an SVR to DAAs or interferon-based therapies. Integrative pathway analyses of liver tissues from patients and mice with humanized livers demonstrated that HCV-induced epigenetic alterations were associated with liver cancer risk. Computational analyses associated increased expression of SPHK1 with HCC risk. We validated these findings in an independent cohort of patients with HCV-related cirrhosis (n = 216), a subset of which (n = 21) achieved viral clearance. CONCLUSIONS: In an analysis of liver tissues from patients with and without an SVR to DAA therapy, we identified epigenetic and gene expression alterations associated with risk for HCC. These alterations might be targeted to prevent liver cancer in patients treated for HCV infection.
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Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Adulto , Animais , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Epigênese Genética , Europa (Continente) , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Japão , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos SCID , Distribuição Aleatória , Resposta Viral SustentadaRESUMO
Background The recently described "macrotrabecular-massive" (MTM) histologic subtype of hepatocellular carcinoma (HCC) (MTM-HCC) represents an aggressive form of HCC and is associated with poor survival. Purpose To investigate whether preoperative MRI can help identify MTM-HCCs in patients with HCC. Materials and Methods This retrospective study included patients with HCC treated with surgical resection between January 2008 and February 2018 and who underwent preoperative multiphase contrast material-enhanced MRI. Least absolute shrinkage and selection operator (LASSO)-penalized and multivariable logistic regression analyses were performed to identify clinical, biologic, and imaging features associated with the MTM-HCC subtype. Early recurrence (within 2 years) and overall recurrence were evaluated by using Kaplan-Meier analysis. Multivariable Cox regression analysis was performed to determine predictors of early and overall recurrence. Results One hundred fifty-two patients (median age, 64 years; interquartile range, 56-72 years; 126 men) with 152 HCCs were evaluated. Twenty-six of the 152 HCCs (17%) were MTM-HCCs. LASSO-penalized logistic regression analysis identified substantial necrosis, high serum α-fetoprotein (AFP) level (>100 ng/mL), and Barcelona Clinic Liver Cancer (BCLC) stage B or C as independent features associated with MTM-HCCs. At multivariable analysis, substantial necrosis (odds ratio = 32; 95% confidence interval [CI] = 8.9, 114; P < .001), high serum AFP level (odds ratio = 4.4; 95% CI = 1.3, 16; P = .02), and BCLC stage B or C (odds ratio = 4.2; 95% CI = 1.2, 15; P = .03) were independent predictors of MTM-HCC subtype. Substantial necrosis helped identify 65% (17 of 26; 95% CI: 44%, 83%) of MTM-HCCs (sensitivity) with a specificity of 93% (117 of 126; 95% CI: 87%, 97%). In adjusted models, only the presence of satellite nodules was independently associated with both early (hazard ratio = 3.7; 95% CI: 1.5, 9.4; P = .006) and overall (hazard ratio = 3.0; 95% CI: 1.3, 7.2; P = .01) tumor recurrence. Conclusion At multiphase contrast-enhanced MRI, substantial necrosis helped identify macrotrabecular-massive hepatocellular carcinoma subtype with high specificity. © RSNA, 2020.
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Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Idoso , Carcinoma Hepatocelular/classificação , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/classificação , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The role of robotic surgery for partial mesorectal excision (PME) in patients with high rectal cancer (RC) remains unexplored. This study aimed to compare the operative and postoperative outcomes of robotic (R-PME) versus laparoscopic (L-PME) PME for high RC. METHODS: This was a single-center propensity score cohort study of consecutive patients diagnosed with RC in the high rectum (>10 to 15 cm from the anal verge) who underwent surgery between September 2012 and May 2019. RESULTS: Of 131 selected patients (50 R-PME and 81 L-PME), 88 were matched using propensity score (44 per group). Operative and postoperative variables were similar between R-PME and L-PME patients, except for operative time (220 min and 190 min, respectively; p < 0.0001). No conversion was needed. Overall morbidity was 15.9%; 4 patients (4.5%) developed anastomotic leakage. The mean hospital stay was 7.25 days for R-PME vs. 7.64 days for L-PME (p = 0.597). R0 resection was achieved in 100% of R-PME and 90.9% of L-PME (p = 0.116). Only 3 patients (1 R-PME, 2 L-PME) received a permanent stoma (p = 1). No group differences were observed for overall or disease-free survival rates at 5 years. The costs of R-PME were significantly higher than those of L-PME. CONCLUSION: Minimally invasive surgery can be performed safely for PME in high RC. No difference can be detected between R-PME and L-PME for both short- and long-term outcomes, leaving the choice of the surgical approach to the surgeon's experience. Specific health economic studies are needed to evaluate the cost-effectiveness of robotic surgery for RC.
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Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Estudos de Coortes , Humanos , Pontuação de Propensão , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether image texture parameters analysed on pre-operative contrast-enhanced computed tomography (CT) can predict overall survival and recurrence-free survival in patients with hepatocellular carcinoma (HCC) treated by surgical resection. METHODS: We retrospectively included all patients operated for HCC who had liver contrast-enhanced CT within 3 months prior to treatment in our centre between 2010 and 2015. The following texture parameters were evaluated on late-arterial and portal-venous phases: mean grey-level, standard deviation, kurtosis, skewness and entropy. Measurements were made before and after spatial filtration at different anatomical scales (SSF) ranging from 2 (fine texture) to 6 (coarse texture). Lasso penalised Cox regression analyses were performed to identify independent predictors of overall survival and recurrence-free survival. RESULTS: Forty-seven patients were included. Median follow-up time was 345 days (interquartile range [IQR], 176-569). Nineteen patients had a recurrence at a median time of 190 days (IQR, 141-274) and 13 died at a median time of 274 days (IQR, 96-411). At arterial CT phase, kurtosis at SSF = 4 (hazard ratio [95% confidence interval] = 3.23 [1.35-7.71] p = 0.0084) was independent predictor of overall survival. At portal-venous phase, skewness without filtration (HR [CI 95%] = 353.44 [1.31-95102.23], p = 0.039), at SSF2 scale (HR [CI 95%] = 438.73 [2.44-78968.25], p = 0.022) and SSF3 (HR [CI 95%] = 14.43 [1.38-150.51], p = 0.026) were independently associated with overall survival. No textural feature was identified as predictor of recurrence-free survival. CONCLUSIONS: In patients with resectable HCC, portal venous phase-derived CT skewness is significantly associated with overall survival and may potentially become a useful tool to select the best candidates for resection. KEY POINTS: ⢠HCC heterogeneity as evaluated by texture analysis of contrast-enhanced CT images may predict overall survival in patients treated by surgical resection. ⢠Among texture parameters, skewness assessed at different anatomical scales at portal-venous phase CT is an independent predictor of overall survival after resection. ⢠In patients with HCC, CT texture analysis may have the potential to become a useful tool to select the best candidates for resection.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Hepatectomia , Neoplasias Hepáticas/diagnóstico , Tomografia Computadorizada Multidetectores/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , França/epidemiologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVES: The aim of this study was to compare the results between laparoscopic hepatectomy and open hepatectomy in two French university hospitals, for the management of hepatocellular carcinoma (HCC) using a propensity score matching. MATERIALS AND METHODS: A patient in the laparoscopic surgery group (LA) was randomly matched with another patient in the open approach group (OA) using a 1:1 allocated ratio with the nearest estimated propensity score. Matching criteria included age, presence of comorbidities, American Society of Anesthesiologists score, and resection type (major or minor). Patients of the LA group without matches were excluded. Intraoperative and postoperative data were compared in both groups. Survival was compared in both groups using the following matching criteria: number and size of lesions, alpha-fetoprotein rate, and cell differentiation. RESULTS: From January 2012 to January 2017, a total of 447 hepatectomies were consecutively performed, 99 hepatectomies of which were performed for the management of hepatocellular carcinomas. Forty-nine resections were performed among the open approach (OA) group (49%), and 50 resections were performed among the laparoscopic surgery (LA) group (51%). Mortality rate was 2% in the LA group and 4.1% in the OA group. After propensity score matching, there was a statistical difference favorable to the LA group regarding medical complications (54.55% versus 27.27%, p = 0.04), and operating times were shorter (p = 0.03). Resection rate R0 was similar between both groups: 90.91% (n = 30) in the LA group and 84.85% (n =) in the OA group. There was no difference regarding overall survival (p = 0.98) and recurrence-free survival (p = 0.42). CONCLUSIONS: Laparoscopic liver resection for the management of HCC seems to provide the same short-term and long-term results as compared to the open approach. Laparoscopic liver resections could be considered as an alternative and become the gold standard in well-selected patients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The national ranking examination (NRE) marks the end of the second cycle (6th university year) of French medical studies and ranks students allowing them to choose their specialty and city of residency. We studied the potential predictive factors of success at the 2015 NRE by students attending a French School of Medicine. METHODS: From March 2016 to March 2017, a retrospective study of factors associated with the 2015 NRE success was conducted and enrolled 242 students who attended their sixth year at the school of medicine of Reims. Demographic and academic data collected by a home-made survey was studied using univariate and then multivariate analysis by generalized linear regression with a threshold of p < 0.05 deemed significant. RESULTS: The factors independently associated with a better ranking at the NRE were the motivation for the preparation of the NRE (gain of 3327 ± 527 places, p < 0.0001); to have participated in the NRE white test organized by la Revue du Praticien in November 2014 (gain of 869 ± 426 places, p < 0.04), to have participated in the NRE white test organized by la conférence Hippocrate in March 2015 (+ 613 places ±297, p < 0.04). The factors independently associated with poor NRE ranking were repeating the first year (loss of 1410 places ±286, p < 0.0001), repeating a year during university course (loss of 1092 places ±385, p < 0.005), attendance of hospital internships in 6th year (loss of 706 places ±298, p < 0.02). CONCLUSIONS: The student motivation and their white tests completion were significantly associated with success at the NRE. Conversely, repeating a university year during their course and attendance of 6th year hospital internships were associated with a lower ranking.
Assuntos
Avaliação Educacional , Escolaridade , Faculdades de Medicina , Adulto , Feminino , Previsões , França , Humanos , Masculino , Estudos Retrospectivos , Estudantes de Medicina , Adulto JovemRESUMO
PURPOSE: While anatomical variations of the subscapular vessels are frequently encountered during axillary dissection, little is found in the literature. The aim of this cadaveric study was to define arterial and venous anatomical variations and frequencies of the subscapular vascular pedicle and its terminal/afferent vessels in women. METHODS: We performed 80 dissections of the axillary region on forty female formalin-embalmed cadavers. Each anatomical arrangement was photographed and recorded on a scheme before analysis. RESULTS: We propose a new classification of the subscapular pedicle variations. We observed three types of subscapular arterial variation. The type Ia was the most frequent arrangement (71% of our dissections), the type Ib was observed in 11% and the type II in 18% of cases. We observed four types of subscapular venous variation. The type Ia was observed in 63% of cases, the type Ib in 14%, the type II in 14% and the type III in 10% of cases. CONCLUSIONS: This knowledge of the anatomical variation arrangement and frequencies of the subscapular vascular pedicle will assist the surgeon when dissecting the axillary region for malignant or reconstructive procedures.