Using a weaning immunosuppression protocol in liver transplantation recipients with hepatocellular carcinoma: A compromise between the risk of recurrence and the risk of rejection?

Hepatocellular carcinoma (HCC) recurrence rate after liver transplantation (LT) is still up to 1520%, despite a careful selection of candidates and optimization of the management within the waiting list. To reduce tumour recurrence, the currently adopted post-transplant strategies are based on the administration of a tailored immunosuppression (IS) regimen. Drug-induced depression of the immune system is essential in preventing graft rejection, however has a well-established association with oncogenesis. The immune system has a key role as a defending mechanism against cancer development, preventing vascular invasion and metastasis. Thus, IS drugs represent one of few modifiable non-oncological risk factors for tumour recurrence. In HCC recipients, a tailored IS therapy, with the aim to minimize drugs' doses, is essential to gain the optimal balance between the risk of rejection and the risk of tumour recurrence. So far, a complete withdrawal of IS drugs after LT is reported to be safely achievable in 25% of patients (defined as "operational tolerant"), without the risk of patient and graft loss. The recent identification of non-invasive "bio-markers of tolerance", which permit to identify patients who could successfully withdraw IS therapies, opens new perspectives in the management of HCC after LT. IS withdrawal could potentially reduce the risk of tumour recurrence, which represents the major drawback in HCC recipients. Herein, we review the current literature on IS weaning in patients who underwent LT for HCC as primary indication and we report the largest experiences on IS withdrawal in HCC recipients

Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p &lt; 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p &lt; 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

Hepatocellular carcinoma in children: Hepatic resection and liver transplantation

Hepatocellular carcinoma (HCC) is a rare malignancy in children and at the time of diagnosis up to 80% of pediatric HCC are unresectable due to large and multiple lesions. The majority of pediatric HCC occurs on a background of normal liver, and consequently the absence of concomitant chronic liver disease generally allows tolerating pre-and post-operative chemotherapy. Based on the large experiences of adult HCC and pediatric hepatoblastoma, in the last years a multidisciplinary aggressive treatment composed of surgical resection and chemotherapy (based on cisplatin and doxorubicin) has been proposed, improving patient outcomes and recurrence rate in children with HCC. However, the overall survival rate in children with HCC is not satisfactory yet; while the 5-year survival rate may achieve up to 70-80% in non-metastatic resectable HCC, it remains &lt;20% in children with unresectable HCC. The mainstay of the pediatric HCC therapeutic strategy is the radical tumor resection, weather by hepatic resection or liver transplantation, nevertheless the best surgical approaches as well as the optimal neoadjuvant and adjuvant treatment are still under debate. Different strategies have been explored to convert unresectable HCC into resectable tumors by extending criteria for surgical treatment and/or associating multi-modal treatments, such as systemic and local-regional therapy, but universal recommendation needs to be defined yet. The purpose of this review is to outline the role of different surgical approaches, including hepatic resection and liver transplantation, in pediatric HCC with or without underlying chronic liver disease

“Salus Populi Suprema Lex”: Considerations on the Initial Response of the United Kingdom to the SARS-CoV-2 Pandemic

In several countries worldwide, the initial response to coronavirus disease 2019 (COVID-19) has been heavily criticized by general public, media, and healthcare professionals, as well as being an acrimonious topic in the political debate. The present article elaborates on some aspects of the United Kingdom (UK) primary reaction to SARS-CoV-2 pandemic; specifically, from February to July 2020. The fact that the UK showed the highest mortality rate in Western Europe following the first wave of COVID-19 certainly has many contributing causes; each deserves an accurate analysis. We focused on three specific points that have been insofar not fully discussed in the UK and not very well known outside the British border: clinical governance, access to hospital care or intensive care unit, and implementation of non-pharmaceutical interventions. The considerations herein presented on these fundamental matters will likely contribute to a wider and positive discussion on public health, in the context of an unprecedented crisis

Platelet isoprostane overproduction in diabetic patients treated with aspirin

Aspirin modestly influences cardiovascular events in patients with type 2 diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to determine whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with proaggregating properties derived from arachidonic acid oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate oxidase. A cross-sectional study was performed comparing T2DM patients, treated (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic patients, matched for age, sex, atherosclerosis risk factors, and aspirin treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet recruitment, platelet isoprostane, and NOX2 activation was found in diabetic versus nondiabetic patients and in aspirin-treated diabetic patients versus nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was inhibited in all aspirin-treated patients. In the interventional study, aspirin similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic patients. These findings suggest that in aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane overproduction is associated with enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) inhibition

How do synchronous lung metastases influence the surgical management of children with hepatoblastoma? An update and systematic review of the literature

Approximately 20% of children with hepatoblastoma (HB) have metastatic disease at diagnosis, most frequently in the lungs. In children with HB, lung metastatic disease is associated with poorer prognosis. Its treatment has been approached with a variety of methods that integrate chemotherapy and surgical resection. The timing and feasibility of complete extirpation of lung metastases, by chemotherapy and/or metastasectomy, is crucial for the surgical treatment of the primary liver tumor, which can vary from major hepatic resections to liver transplantation (LT). In children with unresectable HB, which can be surgically treated only by LT, the persistence of unresectable metastases after neoadjuvant chemotherapy excludes the possibility of recurring to LT with consequent negative impact on patients' outcomes. Due to limited evidence and experience, there is no consensus amongst oncologists and surgeons across institutions regarding the surgical treatment for HB with synchronous metastatic lung disease. This narrative review aimed to update the current management of pulmonary metastasis in children with HB and to define its role in the decision-making strategy for the surgical approach to primary liver tumours