Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

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.

IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation.

IL-17A is considered to guide liver inflammation and fibrosis. From twenty-two human liver samples of different fibrosis stages (F0 to F4), IL-17A, IL-22, and TGFß1 protein expression in liver tissue lysates were analyzed. Ten paired samples of liver tissue (F0-F1 stage) and blood from the same patient were used to analyze intrahepatic and blood T-lymphoid IL-17A+ cells by flow cytometry. The analyses have been performed regardless of pathology, considering the stage of fibrosis. Human liver tissue was used for the primary human liver slice cultures, followed by subsequent cytokine stimulation and fibrotic markers' analysis by ELISA. IL-17A production in human liver tissue was significantly higher in the early fibrotic stage compared with the advanced stage. Th17 T cells and, to a lesser extent, MAIT cells were the main sources of IL-17A in both compartments, the liver and the blood. Moreover, the presence of liver Th17IL-17A+INFγ+ cells was detected in the liver. IL-17A stimulation of human liver slice culture increased the expression of profibrotic and pro-inflammatory markers. IL-17A, secreted by Th17 and MAIT cells in the liver, triggered fibrosis by inducing the expression of IL-6 and profibrotic markers and could be a target for antifibrotic treatment. Further amplitude studies are needed to confirm the current results.

Adult human liver slice cultures: Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs.

BACKGROUND: Liver fibrosis can result in end-stage liver failure and death. AIM: To examine human liver fibrogenesis and anti-fibrotic therapies, we evaluated the three dimensional ex vivo liver slice (LS) model. METHODS: Fibrotic liver samples (F0 to F4 fibrosis stage according to the METAVIR score) were collected from patients after liver resection. Human liver slices (HLS) were cultivated for up to 21 days. Hepatitis C virus (HCV) infection, alcohol (ethanol stimulation) and steatosis (palmitate stimulation) were examined in fibrotic (F2 to F4) liver slices infected (or not) with HCV. F0-F1 HLS were used as controls. At day 0, either ursodeoxycholic acid (choleretic and hepatoprotective properties) and/or α-tocopherol (antioxidant properties) were added to standard of care on HLS and fibrotic liver slices, infected (or not) with HCV. Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay. RESULTS: The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs. Expression of the biomarkers of fibrosis and the progression to steatosis (estimated by triglycerides production) was increased with the addition of HCV and /or ethanol or palmitate. From day 15 of the follow-up studies, a significant decrease of both transforming growth factor ß-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures. CONCLUSION: These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver (viral, alcoholic, nonalcoholic steatohepatitis liver diseases) and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.

Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model.

AIM: To evaluate the antiviral potency of a new anti-hepatitis C virus (HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 µm-thick slices (2.7 × 10(6) cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant (multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription - polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dose-dependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect (compared to hydroxychloroquine EC50 = 1.17 µmol/L). CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dose-dependent manner without cytotoxic effect.

Two-stage liver transplantation using auxiliary laparoscopically harvested grafts in adults: Emphasizing the concept of "hypersmall graft nursing".

BACKGROUND: Living donor liver transplantation is limited by the donor's risk in case of right liver donation and by the risk of small-for-size syndrome on the recipient in case of left lobe transplantation. This study aimed at evaluating the feasibility and results of two-stage liver transplantation using auxiliary hyper small grafts harvested laparoscopically and discussing relevant technical insights and issues that still need to be overcome. METHODS: Retrospective analysis involving two patients operated at a tertiary referral center. The recipients underwent left lateral sectionectomy and then auxillary liver transplantation using laparoscopically harvested left lateral section. The native right liver was transiently left in place to sustain the initially small functional graft functional during its hypertrophy. RESULTS: No donor experienced postoperative complication. After 7days, the hypertrophy rate was 112% (105-120). Doppler assessments during the first two postoperative weeks showed progressive portal vein inflow decrease in the right native livers and portal vein inflow increase in the grafts. Liver biopsies on postoperative day 7 showed no lesion of overperfusion. No recipient experienced liver failure or small-for-size syndrome. Second stage hepatectomy of the native liver was undertaken in one patient. In the other patient, biliary stenosis on postoperative day 30 precluded second stage hepatectomy. This patient required retransplantation after one year. CONCLUSIONS AND RELEVANCE: The current strategy increases donor safety and may allow increasing the pool of available grafts. Refinements in the management of the native right liver are however required to improve the feasibility rate of this strategy.

Best practices to optimize intraoperative photography.

BACKGROUND: Intraoperative photography is used extensively for communication, research, or teaching. The objective of the present work was to define, using a standardized methodology and literature review, the best technical conditions for intraoperative photography. MATERIALS AND METHODS: Using either a smartphone camera, a bridge camera, or a single-lens reflex (SLR) camera, photographs were taken under various standard conditions by a professional photographer. All images were independently assessed blinded to technical conditions to define the best shooting conditions and methods. RESULTS: For better photographs, an SLR camera with manual settings should be used. Photographs should be centered and taken vertically and orthogonal to the surgical field with a linear scale to avoid error in perspective. The shooting distance should be about 75 cm using an 80-100-mm focal lens. Flash should be avoided and scialytic low-powered light should be used without focus. The operative field should be clean, wet surfaces should be avoided, and metal instruments should be hidden to avoid reflections. For SLR camera, International Organization for Standardization speed should be as low as possible, autofocus area selection mode should be on single point AF, shutter speed should be above 1/100 second, and aperture should be as narrow as possible, above f/8. For smartphone, use high dynamic range setting if available, use of flash, digital filter, effect apps, and digital zoom is not recommended. CONCLUSIONS: If a few basic technical rules are known and applied, high-quality photographs can be taken by amateur photographers and fit the standards accepted in clinical practice, academic communication, and publications.

Long-term outcomes following aggressive management of recurrent hepatocellular carcinoma after upfront liver resection.

BACKGROUND: Long-term outcomes of patients who experience recurrence after liver resection (LR) of hepatocellular carcinoma (HCC) are uncertain. METHODS: The characteristics of 58 patients were obtained from a retrospective database at two time points: primary resection and recurrence. Patterns of recurrence, treatment strategies, and long-term survival rates were analyzed. RESULTS: The recurrence was inside the Milan criteria (Milan+) in 19 patients (32.7 %), 11 of whom were already eligible for a liver transplant (LT) at the time of primary liver resection (LR). Treatment of the recurrence included the following procedures: salvage LT (n = 6; 10.3 %), repeat LR (n = 7; 12.1 %), percutaneous radiofrequency ablation (RFA) and/or transarterial chemoembolization (TACE) (n = 24; 41.3 %), systemic chemotherapy (n = 15; 25.8 %), and best supportive care (n = 12; 20.7 %). With a mean follow-up of 26.9 ± 27.9 months, the overall 1-, 3-, and 5-year survival rates of the 58 patients with HCC recurrence after primary LR were 57.3, 42.5, and 35.3 %, respectively. In the multivariate analysis the presence of esophageal varices (p = 0.001), an AFP level >200 µg/L (p = 0.03) and a Milan- recurrence pattern (p = 0.05) were independent predictors of decreased survival. The overall 5-year survival of patients who experienced Milan+ recurrence was comparable to that of Milan+ patients who underwent primary LR (62.5 % vs. 66.3 %, p = 0.48). CONCLUSIONS: Aggressive management of recurrent HCC after upfront LR improves patient survival. The pattern of recurrence is an independent predictor of survival which can be used as a selection criterion for salvage LT.

Lessons learned from the first 100 laparoscopic liver resections: not delaying conversion may allow reduced blood loss and operative time.

BACKGROUND: The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN: The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS: Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 ± 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 ± 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS: Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic(®) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate.

Efficient replication of primary or culture hepatitis C virus isolates in human liver slices: a relevant ex vivo model of liver infection.

UNLABELLED: The development of human cultured hepatitis C virus (HCV) replication-permissive hepatocarcinoma cell lines has provided important new virological tools to study the mechanisms of HCV infection; however, this experimental model remains distantly related to physiological and pathological conditions. Here, we report the development of a new ex vivo model using human adult liver slices culture, demonstrating, for the first time, the ability of primary isolates to undergo de novo viral replication with the production of high-titer infectious virus as well as Japanese fulminant hepatitis type 1, H77/C3, and Con1/C3. This experimental model was employed to demonstrate HCV neutralization or HCV inhibition, in a dose-dependent manner, either by cluster of differentiation 81 or envelope protein 2-specific antibodies or convalescent serum from a recovered HCV patient or by antiviral drugs. CONCLUSION: This new ex vivo model represents a powerful tool for studying the viral life cycle and dynamics of virus spread in native tissue and also allows one to evaluate the efficacy of new antiviral drugs.

Pneumatosis intestinalis associated with treatment of cancer patients with the vascular growth factor receptor tyrosine kinase inhibitors sorafenib and sunitinib.

Recently, pneumatosis intestinalis has been described in patients receiving bevacizumab, a monoclonal antibody to VEGF-A. Pneumatosis intestinalis is a condition characterized by subserosal and submucosal gas-filled cysts in the gastrointestinal tract. We report on pneumatosis intestinalis in patients receiving oral anti-VEGF agents. Patients shared the following characteristics: long-term (> 4 months) exposure to anti-VEGF agents, lack of other factors predisposing to pneumatosis intestinalis, and lack of recent surgical intervention. Taken together, these observations suggest that pneumatosis intestinalis is a probable class-effect of anti-VEGF agents.

Temporary placement of partially covered self-expandable metal stents for anastomotic biliary strictures after liver transplantation: a prospective, multicenter study.

BACKGROUND: Management of anastomotic biliary strictures after liver transplantation deserves optimization. OBJECTIVE: To evaluate placement and removal of partially covered self-expandable metal stents (PCSEMSs) in this setting. DESIGN: Prospective, multicenter, uncontrolled study. SETTING: Three French academic hospitals with liver transplantation units and tertiary referral endoscopy centers. PATIENTS: Twenty-two patients (18 men, 4 women, aged 49.7 ± 12 years) with anastomotic biliary stricture. Seventeen (77.3%) presented stricture recurrence after plastic stenting. INTERVENTIONS: PCSEMSs were placed across the stricture for 2 months and then removed. Patients were followed by clinical examination and liver function tests 1, 3, 6, 9, and 12 months after PCSEMS removal. MAIN OUTCOME MEASUREMENT: The ability to remove PCSEMS. RESULTS: PCSEMS placement was successful in all patients, after sphincterotomy in 21 patients. Stent-related complications included minor pancreatitis (3 patients), transient pain (1 patient), and cholangitis (1 patient). Stent removal was achieved in all patients but 2 whose stents had migrated distally. Partial stent dislocation was noted in 5 patients (upward in 4, downward in 1). Complications associated with stent removal were minor, including self-contained hemorrhage (1 patient) and fever (1 patient). The stricture persisted at the end of treatment in 3 patients (13.6%), all of whom had stent migration or dislocation. Recurrence of anastomotic stricture after initial success occurred in 9 of 19 patients (47.4%) within 3.5 ± 2.1 months. Sustained stricture resolution was observed in 10 of 19 patients (52.6%), 45.6% from an intent-to-treat perspective. LIMITATIONS: Uncontrolled study with limited follow-up. CONCLUSIONS: Temporary placement and removal of PCSEMSs in anastomotic biliary strictures after liver transplantation is feasible, although sometimes demanding. Stent migration may impair final outcome.

Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of choice.

BACKGROUND: A pancreatic fistula (PF) is the most common complication after pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%. The aim of the present study was to analyse the treatment of a complicated PF comparing the surgical approach with conservative techniques. METHODS: From January 2000 through to August 2006, 121 patients were submitted for PD. The study consisted of 70 men and 47 women, with a median age of 60 years (SD +/- 12). The main indications for PD were pancreatic duct carcinoma in 52 patients (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11 (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS: Thirty-five patients (30%) developed a PF. Amongst these, 20 were managed conservatively and 14 were reoperated. These two groups of patients were compared with patients without a PF for analysis. There was no significant difference in the mean age, the gender ratio, American Society of Anesthesiologists (ASA) classification, surgical time and blood replacement, number of associated procedures, vascular resection and type of reconstruction between the three groups. There were five post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of hospital stay (P < 0.001) were greater in the surgical group. The medium delay between the pancreatic resection and reoperation was 10 days (range, 3-32 days). Completion splenopancreatectomy was required in five patients whereas conservative treatment including debridement and drainage was applied in nine patients. CONCLUSION: The surgical approach for a PF is associated with a higher mortality and morbidity. There is no advantage in performing completion pancreatectomy (CP) instead of extensive drainage as a result of the same mortality and morbidity rates and the risk of endocrine insufficiency. In cases of complicated PF, radiological or surgical conservative treatment is recommended.

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway.

Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle alpha-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (P<0.05) and elevated collagen levels in supernatants (P=0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

Treatment of stage IVA hepatocellular carcinoma: should we reappraise the role of surgery?

HYPOTHESIS: A subset of patients with stage IVA hepatocellular carcinoma (HCC) and preserved liver function may benefit from hepatic resection. DESIGN: Retrospective review of a prospectively collected database. SETTING: An academic tertiary care hepatobiliary unit. PATIENTS: Twenty patients who underwent surgical treatment for stage IVA HCC between July 1998 and October 2004 were identified from the database. INTERVENTION: Intraoperative ablation of HCC nodules was combined with resection in 6 patients (30%) to increase resectability. Three patients also underwent resection of extrahepatic tumors. Five patients (25%) had macroscopic invasion of the portal vein and 2 patients (10%) underwent thrombectomy of the vena cava. MAIN OUTCOME MEASURES: Intraoperative data, recurrence, and long-term survival rates were analyzed. RESULTS: Postoperative mortality and morbidity were 5% and 30%, respectively. The median number of resected tumors per patient was 3, and the median diameter of the largest tumor was 60 mm. With a median follow-up of 23 months, 14 patients (70%) developed recurrence. Treatment of recurrence was possible in 10 patients and included transarterial chemoembolization in 7 patients (35%), of whom 2 (10%) had radiofrequency ablation first, and systemic chemotherapy in 3 patients (15%). Median survival time was 32 months, and the actuarial 1-, 3-, and 5-year survival rates were 73%, 56%, and 45%, respectively. CONCLUSIONS: Long-term survival can be achieved using an aggressive surgical approach in select patients with advanced HCC. Patients with stage IVA HCC should be followed up by a multidisciplinary team because recurrence is common and sequential treatments may prolong survival.

Hepatocellular carcinoma developed on compensated cirrhosis: resection as a selection tool for liver transplantation.

The objective of this study was to evaluate the histological profile obtained from primary resection of hepatocellular carcinoma (HCC) as a selection tool for liver transplantation (LT). The natural history of HCC depends on its histological features. The clinical effectiveness of resection as a selection tool for salvage or de principe LT has been previously advocated. Between 1987 and 2006, 20 patients underwent a resection prior to LT. Long-term survival of these 20 patients was compared to that of 73 patients who underwent primary LT. Histological features of the resected specimen were compared to those of the recurrences. Feasibility, morbidity, and mortality of LT following primary resection were also analyzed. Mean follow-up was 3.8 +/- 4.4 and 2.7 +/- 4.5 years from resection and LT, respectively; 6 patients died. The mean 1-, 3-, 5-, and 10-year overall survival rates were 71%, 61%, 55%, and 45% and 74%, 66%, 66%, and 40% after primary transplantation and primary resection, respectively (not significant). At LT, 14 patients had a recurrence, but histological study of the recurrence was not possible in 2 (complete necrosis). For 9 patients (75%), histological features of both primary and recurrent tumors were exactly the same. Four patients had recurrence following LT; in each case, primary and recurrent nodules shared the same histological markers of poor prognosis. De principe transplantation was proposed to 6 patients because of poor prognosis histological features on the resected specimen. All these patients are alive without recurrence with a mean follow-up of 55 months. In conclusion, the natural history of HCC can be predicted on the basis of the histological profile of the resected specimen, which may be used as a selection tool for LT. De principe LT in patients within Milan criteria with poor prognosis histological features may be an optimal strategy.

Primitive neuroectodermal tumor of the myometrium with cardio-vascular symptoms.

BACKGROUND: Non-bacterial thrombotic endocarditis is a severe complication of cancer, rarely reported in gynecologic tumors. However, it can be inaugural and lead to complex diagnostic pathways. CASE: A 40-year-old woman presented with a stroke, related to an endocarditis. The valvular vegetation was surgically removed, and a malignant node was resected. A PET-scan led to the diagnosis of a myometrial tumor, which was found to be a primitive neuroectodermal tumor (PNET). The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and systemic chemotherapy which allowed a complete remission of tumoral and cardio-vascular symptoms. CONCLUSION: To our knowledge, this is the first case report of a PNET of the myometrium revealed by cardio-vascular symptoms.