Sarcopenia Predicts Major Complications after Resection for Primary Hepatocellular Carcinoma in Compensated Cirrhosis

The burden of post-operative complications of patients undergoing liver resection for hepatocellular carcinoma (HCC) is a cause of morbidity and mortality. Recently, sarcopenia has been reported to influence the outcome of patients with cirrhosis. We aimed to assess factors associated with sarcopenia and its prognostic role in liver surgery candidates. We included all patients with compensated advanced chronic liver disease (cACLD) undergoing liver resection for primary HCC consecutively referred to the University of Bologna from 2014 to 2019 with an available preoperative abdominal CT-scan performed within the previous three months. A total of 159 patients were included. The median age was 68 years, and 80.5% of the patients were male. Sarcopenia was present in 82 patients (51.6%). Age and body mass index (BMI) were associated with the presence of sarcopenia at multivariate analysis. Thirteen (8.2%) patients developed major complications and 14 (8.9%) presented PHLF grade B-C. The model for end-stage liver disease score was associated with the development of major complications, whereas cACLD presence, thrombocytopenia, portal hypertension (PH), Child-Pugh score and Albumin-Bilirubin score were found to be predictors of clinically significative PHLF. The rate of major complications was 11.8% in sarcopenic patients with cACLD compared with no complications (0%) in patients without sarcopenia and cACLD (p = 0.032). The rate of major complications was significantly higher in patients with (16.3%) vs. patients without (0%) sarcopenia (p = 0.012) in patients with PH. In conclusion, sarcopenia, which is associated with age and BMI, may improve the risk stratification of post-hepatectomy major complications in patients with cACLD and PH

Liver collision lesion: inflammatory hepatocellular adenoma within focal nodular hyperplasia

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The impact of preservation fluid culture on graft site arteritis: a systematic review and metanalysis

The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear

Carcinogenesis and Metastasis in Liver: Cell Physiological Basis

Hepatocellular carcinoma (HCC) incidence is rising. This paper summarises the current state of knowledge and recent discoveries in the cellular and physiological mechanisms leading to the development of liver cancer, especially HCC, and liver metastases. After reviewing normal hepatic cytoarchitecture and immunological characteristics, the paper addresses the pathophysiological factors that cause liver damage and predispose to neoplasia. Particular attention is given to chronic liver diseases, metabolic syndrome and the impact of altered gut microbiota, disrupted circadian rhythm and psychological stress. Improved knowledge of the multifactorial aetiology of HCC has important implications for the prevention and treatment of this cancer and of liver metastases in general

Automatically extracted machine learning features from preoperative CT to early predict microvascular invasion in HCC: the role of the Zone of Transition (ZOT)

open12noMicrovascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was developed and validated. Classifier performance was assessed using receiver operating characteristic (ROC) curve analysis and related metrics. Results: The original 89 HCC nodules (32 MVI+ and 57 MVI−) became 169 (62 MVI+ and 107 MVI−) after oversampling. Of the four features within the signature, three are ZOT heterogeneity measures regarding both arterial and venous phases. On the test set (19MVI+ and 33MVI−), the classifier predicts MVI+ with area under the curve of 0.86 (95%CI (0.70–0.93), p∼10^−5), sensitivity = 79% and specificity = 82%. The classifier showed negative and positive predictive values of 87% and 71%, respectively. Conclusions: The classifier showed the highest diagnostic performance in the literature, disclosing the role of ZOT heterogeneity in predicting the MVI+ status.noneMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro BevilacquaMatteo Renzulli, Margherita Mottola, Francesca Coppola, Maria Adriana Cocozza, Silvia Malavasi, Arrigo Cattabriga, Giulio Vara, Matteo Ravaioli, Matteo Cescon, Francesco Vasuri, Rita Golfieri, Alessandro Bevilacqu

Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of > 1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5-year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5-year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients. Copyright © 2004 by the American Association for the Study of Liver Diseases

Impact of the Type of Dialysis on Time to Transplantation: Is It Just a Matter of Immunity?

Background: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies

Tumor-Infiltrating Lymphocytes (TILs) and Risk of a Second Breast Event After a Ductal Carcinoma in situ

Women with a diagnosis of ductal carcinomain situ(DCIS) have a high risk of developing a second breast event (SBE). The immune system might play a role in trying to prevent a SBE. Patients diagnosed with DCIS were identified in the population-based cancer registry of Area Vasta Romagna from 1997 to 2010. Median follow-up is 8.5 years. Tumor-infiltrating lymphocytes (TILs) were evaluated both in index DCIS and in SBE. The main endpoint was to assess the association between TILs' levels in index DCIS and risk of a SBE. Out of 496 DCIS patients, 100 SBEs (20.2%) were identified: 55 ipsilateral (11.1%) and 43 contralateral (8.7%). The distribution of TILs was heterogeneous, but significantly associated with grade, necrosis, screen detection and type of surgery. Patients stratified according to TILs percentage (5%) did not show a statistically significant difference in the 5-year cumulative incidence of SBEs: 14.9% (95% CI 11.3-19.1) and 11.0% (95% CI, 6.9-16.2), respectively (p= 0.147). In the subgroup of patients who did not receive radiotherapy, TILs >5% were associated with a reduced risk of SBE (HR 0.34, 95% CI 0.14-0.82,p= 0.016). Although we did not find any significant association between TILs and SBE, further studies evaluating their role according to radiotherapy are warranted

A Narrative Review of the Applications of Ex-vivo Human Liver Perfusion

Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words “ex-vivo liver or hepatic perfusion”. All relevant studies in English describing experiments using ex-vivo perfusion of human livers between 2016 and 2021, inclusive, were included. Of 21 reviewed studies, 19 used ex-vivo human liver perfusion in the context of allogeneic liver transplantation. The quality and size of the studies varied considerably. Human liver perfusion was almost exclusively limited to whole organs and “split” livers, although one study did describe the successful perfusion of tissue sections following a partial hepatectomy. This review of recent literature involving ex vivo human liver perfusion demonstrates that the technique is not limited to whole liver perfusion. Split liver perfusion is extremely valuable allowing one lobe to act as a control and increasing the number available for research. This review also highlights the present lack of any reports of segmental liver perfusion. The discarded donor liver is a scarce resource, and the successful use of segmental perfusion has the potential to expand the available experimental models to facilitate pre-clinical experimentation

Beyond the Concepts of Elder and Marginal in DCD Liver Transplantation: A Prospective Observational Matched-Cohort Study in the Italian Clinical Setting

Donation after circulatory determination of death (DCD) is a valuable strategy to increase the availability of grafts for liver transplantation (LT). As the average age of populations rises, the donor pool is likely to be affected by a potential increase in DCD donor age in the near future. We conducted a prospective cohort study to evaluate post-transplantation outcomes in recipients of grafts from elderly DCD donors compared with younger DCD donors, and elderly donors after brainstem determination of death (DBD). From August 2020 to May 2022, consecutive recipients of deceased donor liver-only transplants were enrolled in the study. DCD recipients were propensity score matched 1:3 to DBD recipients. One-hundred fifty-seven patients were included, 26 of whom (16.6%) were transplanted with a DCD liver graft. After propensity score matching and stratification, three groups were obtained: 15 recipients of DCD donors & GE;75 years, 11 recipients of DCD donors <75 years, and 28 recipients of DBD donors & GE;75 years. Short-term outcomes, as well as 12 months graft survival rates (93.3%, 100%, and 89.3% respectively), were comparable among the groups. LT involving grafts retrieved from very elderly DCD donors was feasible and safe in an experienced high-volume center, with outcomes comparable to LTs from younger DCD donors and age-matched DBD donors