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Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008-2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter-relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0months (95% CI, 5.1-7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4months in those with PS>1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1months in patients with PS 0-1, no ascites and Vp1-Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

INTRODUCTION: Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but the selection criteria and priority are still debated. AIMS: To ascertain the number and features of patients with HCC who undergo transplantation in a Western country, the number of patients eligible for LT according to the American Association for the Study of Liver Diseases (AASLD) guidelines, the number of patients who actually undergo transplantation and whether adherence affects survival. METHODS: This is a retrospective analysis from a multicentre Italian database of 2042 cases of HCC, recruited prospectively and consecutively. Kaplan-Meier (log rank) and Cox multivariate analysis estimated survival. RESULTS: Patients who had undergone transplantation (50, 2.5%, with no change over time) had a median survival of 133 months, significantly influenced by the number of lesions and alpha-fetoprotein levels, which were found to be independent predictors of survival on multivariate analysis. Milan criteria were fulfilled in 68%, impacting on survival, whereas 48% fulfilled AASLD guidelines, without such an impact. Two hundred and twenty-eight (11%) patients were eligible for LT according to AASLD; in this group, alpha-fetoprotein levels and Child-Pugh class were independent predictors of survival. CONCLUSION: Among patients with HCC, those undergoing LT represent a small minority; even fewer (1%) are those who undergo transplantation according to AASLD guidelines, adherence to which only marginally affects survival. Overall, LT impact on HCC patients' treatment is very limited

BACKGROUND & AIMS: Patients with cryptogenic cirrhosis (CC) can develop hepatocellular carcinoma (HCC), although the clinical characteristics of HCC in these patients have not been completely defined. We aimed to characterize the clinical features of patients diagnosed with HCC after CC during a 15-year period (1992-2006). METHODS: The clinical characteristics of 45 consecutive CC patients with HCC were analyzed, along with modality of diagnosis, tumor stage, treatment, survival, and causes of death. Data were compared with those of 426 consecutive patients with HCC and only hepatitis C virus (HCV) infection, diagnosed during the same period at the Italian Liver Cancer group centers. RESULTS: HCC patients with CC had similar impairments in liver function as patients with HCV infection (Child-Pugh class A: 53% vs 65%; P = .141). However, the HCC patients with CC had lower aminotransferase levels (P < .001) and higher platelet counts (P < .001). HCC was significantly less likely to be diagnosed during surveillance in CC patients (29% vs 64%; P < .0001). Patients with CC had a significantly greater prevalence of advanced HCC stage, according to Milano criteria (69% vs 41%; P < .0005), larger HCC size (4.9 vs 3.0 cm; P = .0001), lower amenability to any treatment (27% vs 42%; P = .036), and shorter survival times (P = .009, log-rank test) compared with HCV patients. Causes of death were similar in the 2 groups. CONCLUSIONS: Compared with HCV patients, HCC in CC patients often is diagnosed at an advanced stage, probably owing to lack of surveillance; this leads to limited treatment options and shorter survival times.

Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (29%) patients were qualified for atezolizumab-bevacizumab therapy. The main exclusion causes were Child-Pugh class and Performance Status. Adopting the more permissive inclusion criteria of SHARP trial, 535 patients became eligible. The median overall survival of tyrosine-kinase inhibitors patients was 14.9 months, longer in eligible patients than in their counterpart due to better baseline liver function and oncological features.Conclusion: Real-world data indicate that less than one-third of hepatocellular carcinoma patients treated with tyrosine-kinase inhibitors are potentially eligible to atezolizumab-bevacizumab according to the reg-istration trial criteria. These patients have a longer survival than the non-eligible ones. If the selection criteria of atezolizumab-bevacizumab trial are maintained in clinical practice, tyrosine-kinase inhibitors will remain the most used systemic therapy for hepatocellular carcinoma patients.(c) 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Introduction Meloidae are distributed in temperate and arid regions but are also common in subtropical and tropical savannahs. These insects contain cantharidin, a vesicant substance that can cause poisoning by ingestion and dermatitis by direct contact. Material and Methods We describe recurrent Meloidae-related dermatitis outbreaks and their health impact by analyzing medical consultation records and meteorological data. Results Between 2015 and 2019, dermatitis outbreaks took place at a French military base at the end of the rainy season, from July to August, with 100 cases reported in 2015, 74 in 2017, 100 in 2018, and 36 in 2019. In 2017, the incidence rate was 4.4% for the base’s population. Initial medical consultations represented 31.5% of total medical care activity. Meloidae were identified as Cyaneolytta fryi. Conclusions These outbreaks of burn-like lesions, although clinically benign, can place a considerable burden on the medical activity of health care facilities. The diagnosis of Meloidae dermatitis is exclusively anamnestic and clinical and requires reported contact with the insect. The treatment protocol is that of standard burn care, and the best preventive measure is to avoid bright white lights. Military personnel, foreign workers, and travelers venturing into the Sahel should be warned of the risks associated with these beetles.

Dr. Di Micoli, Dr. Buccione, Prof. Trevisani: TakoTsubo cardiomyopathy (TTC), also known as transient left ventricular apical ballooning syndrome, is a clinical entity characterized by (1) reversible left ventricular apical wall motion abnormalities, (2) typical electrocardiographic changes and (3) relatively minor elevation of troponine, creatinine-kinase (CK) and CK-MB that mimics an acute myocardial infarction (AMI) without any acute obstructive coronary disease [1]. Typically, the left ventricular imbalance almost always recovers in a period of days to weeks, so that the management and prognosis of this condition are clearly different from those of AMI [2]. TTC is generally observed in post-menopausal women without prior history of heart disease or clear risk factors for coronary artery disease, who have often experienced recent emotional or physical stress, non-cardiac surgery or extracardiac diseases [1]. Recently, TTC has also been described in critically ill patients without prior heart disease admitted to a medical intensive care unit for severe non-cardiac diseases, such as sepsis, acute respiratory failure, systemic inflammatory response syndrome, anaphylaxis and trauma injuries [3, 4]. Herein, we report a case of TTC occurring in a cirrhotic man, waiting for liver transplantation (LT), probably favored by the intravenous infusion of terlipressin, a synthetic analog of vasopressin (AVP), for the treatment of hepato-renal syndrome (HRS). A 67-year-old Caucasian man with hepatitis B virusrelated cirrhosis and ascites, waiting for LT, was admitted to our unit because of the onset of hepatic encephalopathy, and the worsening of renal sodium retention. As a candidate for LT, he had undergone clinical, laboratory and instrumental tests aimed at excluding extrahepatic diseases precluding surgery. Myocardial single photon emission computed tomography had excluded ischemic damage, and trans-thoracic echocardiography had ruled out dyskinesia of ventricular segments and documented a normal (65%) left ventricular ejection fraction (LVEF). On admission, the patient presented with peripheral edema, ascites and grade III hepatic encephalopathy. Daily diuresis was around 200 mL. The ongoing therapy included oral diuretics (furosemide 25 mg b.i.d. and spironolactone 100 mg b.i.d.), lamivudine and tenofovir for HBV infection control, norfloxacine (400 mg/day) for secondary prophylaxis of the spontaneous peritoneal peritonitis, lactulose, and periodic albumin infusion. The serum creatinine was 2.2 mg/dL and blood urea nitrogen 0.9 g/dL, while serum electrolyte concentrations were normal (sodium 138 mEq/L, potassium 3.5 mEq/L, calcium 8.9 mg/dL and magnesium 2.6 mEq/L). The hemoglobin level was 10.4 g/dL, platelet count 134.000/lL, leukocytes 8.0 9 10/mmc, serum bilirubin 18.8 mg/dL, albumin 3.4 g/dL, INR 2.11. A. Di Micoli D. Buccione V. Santi L. Bastagli M. Bernardi F. Trevisani Dipartimento di Medicina Clinica, Alma Mater Studiorum-Universita degli Studi di Bologna, Bologna, Italy

Although not frequently, hepatocellular carcinoma (HCC) can ensue in a non-cirrhotic liver. As compared to cirrhotic HCC, this kind of tumour has some peculiarities, such as: (a) a lower male preponderance and a bimodal age distribution; (b) a lower prevalence of the three main risk factors (hepatitis B and C virus infections and alcohol abuse), with an increased prevalence of other etiologic factors, such as exposure to genotoxic substances and sex hormones, inherited diseases, genetic mutations; (c) a more advanced tumour stage at the time of diagnosis, as it is usually detected due to the occurrence of cancer-related symptoms, outside any scheduled surveillance program; (d) a much higher amenability to hepatic resection, due to the low risk of liver failure even after extended parenchymal mutilation; (e) overall and disease-free survivals after resection of non-advanced tumours (meeting the Milano criteria) comparable to that obtained with liver transplantation in cirrhotic patients carrying an early tumour; (f) overall survival strictly dependent on tumour burden (and its recurrence) and barely influenced by liver function.

Acquired nevoid telangiectasia (ANT) is observed in several conditions including primary cutaneous disorders, systemic autoimmune disease and hyperestrogenism occurring in puberty, pregnancy and chronic liver disease. We describe a patient in whom ANT was a presenting sign of autoimmune hyperthyroidism, which improved after thyroidectomy. A 43-year-old Caucasian woman experienced an asymptomatic development of multiple widespread red skin lesions, diagnosed to be ANT. Blood tests revealed increased serum levels of free tri-iodothyronine and thyroxine and suppressed thyroid-stimulating hormone. Other causes of ANT were excluded. ANT improved but did not disappear after thyroidectomy. The possible pathogenetic factors linking ANT and Graves’ disease, such as an immune-mediated process, altered estrogen metabolism or vasodilatation associated with hyperdynamic circulation, are discussed.