Combined hepatocellular carcinoma (cHCC-CCA) is an uncommon primary liver lesion in which aspects of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are intimately and unequivocally expressed. Its origin is still a topic of debate, given its heterogenicity, molecular profile, gene mutations but also to the complexities of the microenvironment in which it develops and to the pathways that are triggered in the liver in relation to the phenomena of liver damage. Diagnosis and treatment are still a challenge.

Background: Transarterial chemoembolization (TACE) is the standard treatment for intermediate unresectable hepatocellular carcinoma (HCC); however, reliable prognostic markers are still lacking. Sarcopenia has been proposed as a negative prognostic factor in HCC, but its impact on TACE outcomes remains unclear. Methods: We retrospectively analyzed 48 HCC patients treated with TACE or transarterial embolization (TAE) at our institution (between 2013 and 2020). Sarcopenia was assessed on computed tomography (CT) or magnetic resonance imaging (MRI) scans at baseline, one month, and six months after treatment according to RECIST criteria. Results: At six months, 27 patients (61.4%) achieved complete or partial response, while 17 (38.6%) experienced stable or progressive disease; four patients were excluded due to missing follow-up data. Sarcopenia was more frequent among responders, increasing from 13.5% at baseline to 22.2% in 6 months, while it was initially absent in non-responders. Conversely, non-responders showed a later increase in sarcopenia (0% at baseline to 29.6% at 6 months), suggesting that late sarcopenia might reflect treatment-related metabolic changes. Overall, the prevalence of sarcopenia increased during follow-up. New-onset sarcopenia was more frequent in non-responders and was associated with lower serum creatinine levels , suggesting a possible link between treatment-related muscle loss and poor therapeutic response. Kaplan-Meier showed that smoking status was associated (p = 0.01) with poorer response at 6 months (), while sarcopenia and low creatinine levels showed borderline associations (p = 0.095). Conclusion: In this exploratory study, baseline CT-defined sarcopenia was not significantly associated with short-term response to TACE. However, treatment-related sarcopenia with low creatinine levels may reflect frailty during follow-up, and poorer therapeutic response. Given the small sample size and limited number of sarcopenic patients, these findings should be considered hypothesis-generating and require validation in larger prospective studies.

AIM:The training of medical specialists is a decisive issue for the quality of medical practice. Autonomization in simple procedures and applying the peer education concept seem promising, particularly for general surgery. With this work, we wanted to assess whether there are differences between appendectomy operations performed by differently composed teams with the active involvement of resident doctors at a university centre. METHODS:We retrospectively analyzed the laparotomies and laparoscopic appendicectomies carried out at the Udine Surgery Clinic over a period of 10 years. The interventions were divided into groups according to the experience of the surgical team that performed them: G1 (consultant), G2 (senior resident + consultant), G3 (junior resident + consultant), and G4 (junior resident + senior resident). RESULTS:510 appendectomy procedures were considered for the present analysis. 214 (42.0%) were performed by G1, 139 (27.3%) by G2, 79 (15.5%) by G3 and 78 (15.3%) by G4 group. No difference between the groups was shown in terms of complications, reinterventions, readmissions, length of stay, and duration of surgery. A statistically significant difference was shown in the age of the observed population with respect to the degree of experience of the surgical teams: younger patients were mainly operated on by more experienced teams, and in particular, pediatric laparoscopic appendectomy was performed mainly by consultants. CONCLUSIONS:Appendectomy surgery can be performed by teams with varying levels of experience and is an example of an activity that can be used in Peer Education. It allows for the empowerment of younger residents and the autonomization of older residents in maintaining a medically, ethically, and legally correct standard of safe clinical practice.

Background The need to expand the pool of available organs for transplantation has meant that the use of marginal organs is increasingly widespread. The advent of antiviral therapy for hepatitis C virus (HCV) has made it possible to consider the donation of organs from HCV-positive donors and even from viremic donors. Methods In HCV-positive to HCV-negative antibody donor transplantation, the development of antibodies to HCV is uneven, depending on the organ transplanted and with differences in the time of appearance. Whether the subsequent disappearance is attributed to the development of antibodies or the transmission of immunity between donor and recipient remains unclear. In transplantation from an HCV-infected donor to a HCV-seronegative recipient, the administration of antiviral therapy to the recipient before transplantation or a few days after transplantation achieves sustained response in almost all cases. We wanted to deepen the argument by studying the data in the literature, focusing on kidney transplantation, considering that this could be of interest, particularly for possible long-term renal damage. Results HCV infection both ongoing and previous, as well as the presence of HCV antibodies alone, can be responsible for kidney damage. Conclusions Direct-acting anti-HCV therapy has revolutionized the treatment of HCV disease and the therapeutic possibilities of transplantation. However, we believe it is useful to keep in mind the pathophysiology of HCV-related damage especially in patients with a long life expectancy, using all emerging strategies to minimize the risk of transmission of infection or development of viremia.

The liver is a common site of metastasis for many different tumours due to its anatomical, immunological and metabolic characteristics. For years, metastatic disease, even if oligometastatic, for many tumours was a definite limitation to the surgical option and curative intent. In recent years, the range of therapeutic options for both surgical and ablative and oncological treatment has expanded enormously. New surgical strategies to make what is initially not surgically treatable have emerged in the treatment of metastases, and new innovative medical therapies that rely not only on the local response but also on the systemic response of the patient are outlining exciting future scenarios leading to a complete evolution and revolution of the concept of metastases.

Hepatocellular carcinoma constitutes an ongoing challenge due to its incidence and the high mortality related to it. Metastases and relapses even after treatment with curative intent are frequent. The liver is a common site for metastasis because of anatomical and physiological reasons; its position, the particular cytoarchitecture and cell populations, and its peculiar immunologic properties make it a favorable and tolerogenic environment; the inflammatory state with the alteration of the cytoarchitecture and of the microcirculation associated, and gut permeability and metabolic diseases cause the development of a liable site to progression of hepatocellular carcinoma. The difficulty of always having an early diagnosis and the lack of therapeutic flow charts including the biological behavior of the disease have always posed great difficulties in dealing with it. In the last few years, mechanisms involved in the onset and in the progression of hepatocellular carcinoma are a source of great interest; the discovery of pro-neoplastic and pro-metastatic conditions, of the cross talk between organs and cells, of progression pathways, of mediators contributing to proliferation and metastasis and of modular check points, of miRNAs, all potential therapeutic targets, appear promising for transforming the approach to hepatocarcinoma, offering the possibility of earlier diagnosis, customizable treatments, and better outcome.

Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host’s immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation.

BACKGROUND:Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies.MATERIALS AND METHODS:We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed.RESULTS:The course has been uneventful. In both cases there were no perioperative vascular complications.CONCLUSIONS:The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact.

BACKGROUND Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species–related damage. These mechanisms may improve graft function and survival. OBJECTIVE With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. METHODS This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. RESULTS Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. CONCLUSIONS The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. CLINICALTRIAL ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R INTERNATIONAL REGISTERED REPORT DERR1-10.2196/13922

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.

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.