Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: An Italian liver transplant registry study.

Background & Aims: International consensus has recently introduced a new definition of metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of patients with MASLD and without MASLD waiting for liver transplantation (LT) in Italy. Methods: Using the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT attributable to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was used to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and model for end-stage liver disease (MELD)-sodium values. Results: A total sample of 1,941 patients with MASLD and 11,201 patients without MASLD was considered. A significant increase in the prevalence of MASLD as an indication for LT was observed from 2012 to 2022, for both cohorts with HCC (from 17.7 to 30%) and without HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, whereas it was lower in patients without HCC and without MASLD. Conclusions: Patients with non-HCC MASLD had an increased waitlist mortality and 5-year transplant survival benefit compared with other candidates. Impact and implications: The present research addresses the critical need to understand the evolving landscape of liver transplantation indications, mainly focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) in Italy. Given the significant rise in MASLD cases, these findings highlight that patients with non-HCC MASLD face increased waitlist mortality and benefit more from liver transplantation within 5 years compared with other candidates. The significance of these results lies in their emphasis on the necessity of focusing on patients with MASLD on waiting lists to improve outcomes. By tailoring transplant eligibility criteria and resource allocation, the study provides actionable insights to improve patient survival and optimise liver transplantation practices.

The role of resection in hepatocellular carcinoma BCLC stage B: A multi-institutional patient-level meta-analysis and systematic review.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. METHODS: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. RESULTS: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. CONCLUSION: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies.

Propensity Score-matched Analysis Comparing Robotic Versus Laparoscopic Minor Liver Resections of the Anterolateral Segments: an International Multi-center Study of 10,517 Cases.

OBJECTIVE: To compare the outcomes of robotic minor liver resections (RMLR) versus laparoscopic (L) MLR of the anterolateral segments. BACKGROUND: Robotic liver surgery has been gaining prominence over the years with increasing usage for a myriad of hepatic resections. Robotic liver resections(RLR) has demonstrated non-inferiority to laparoscopic(L)LR while illustrating advantages over conventional laparoscopy especially for technically difficult and major LR. However, the advantage of RMLR for the anterolateral(AL) (segments II, III, IVb, V and VI) segments, has not been clearly demonstrated. METHODS: Between 2008 to 2022, 15,356 of 29,861 patients from 68 international centres underwent robotic(R) or laparoscopic minor liver resections (LMLR) for the AL segments Propensity score matching (PSM) analysis was performed for matched analysis. RESULTS: 10,517 patients met the study criteria of which 1,481 underwent RMLR and 9,036 underwent LMLR. A PSM cohort of 1,401 patients in each group were identified for analysis. Compared to the LMLR cohort, the RMLR cohort demonstrated significantly lower median blood loss (75ml vs. 100ml, P<0.001), decreased blood transfusion (3.1% vs. 5.4%, P=0.003), lower incidence of major morbidity (2.5% vs. 4.6%, P=0.004), lower proportion of open conversion (1.2% vs. 4.5%, P<0.001), shorter post operative stay (4 days vs. 5 days, P<0.001), but higher rate of 30-day readmission (3.5% vs. 2.1%, P=0.042). These results were then validated by a 1:2 PSM analysis. In the subset analysis for 3,614 patients with cirrhosis, RMLR showed lower median blood loss, decreased blood transfusion, lower open conversion and shorter post operative stay than LMLR. CONCLUSION: RMLR demonstrated statistically significant advantages over LMLR even for resections in the AL segments although most of the observed clinical differences were minimal.

Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.

Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.

The Italian experience on liver transplantation for unresectable peri-hilar cholangiocarcinoma: a national survey and future perspectives.

Liver transplantation (LT) was considered an ineffective treatment for perihilar cholangiocarcinoma (pCCA) until the successful experience of the Mayo Clinic, proposing a protocol with strict inclusion criteria and neoadjuvant radio-chemotherapy. Since 2015, pCCA is considered an indication for LT in Italy only in the context of controlled prospective studies. We performed a survey among the 22 Italian Liver Transplant Centers to assess the results of LT for pCCA. Eight centers reported 53 cases from 1986 to 2021 (Bologna 12, Padova 10, Niguarda 10, Milano Tumori 8, Torino 5, Pisa 4, Ancona 2, Modena 2). Patients were divided according to whether they recieved neoadjuvant radio-chemotherapy (Group 1, 25 cases) or not (Group 2, 28 cases). Eleven patients were transplanted without neoadjuvant treatment after 2015. Overall survival at 1, 3 and 5 years was 83.8%, 56.6% and 50.6% in Group 1 and 72.4%, 41.4% and 35.5% in Gropu 2 (p = 0.13). Recurrence-free survival at 1, 3, and 5 years was 91.2%, 61.1% and 47.2% in Group 1 and 58.2%, 42.2%, and 36.1% in Group 2 (p = 0.16). A competing risk regression analysis showed a 5-year risk of cancer-related death of 19% for patients in Group 1 against 62.3% in Group 2, with a hazard ratio of 0.31 (95%CI [0.10-0.98], p 0.047). This survey promoted a discussion about the limitations of the Mayo protocol and set the basis for the adoption of a new nationwide protocol (LITHALICA-NCT06125769), having the same inclusion criteria but proposing standard of care chemotherapy as neoadjuvant regimen.

Full Robotic Whole Graft Liver Transplantation: A Step Into The Future.

OBJECTIVE: To report the first European series of full robotic whole liver transplantation (RLT) with technical details and future perspectives. SUMMARY BACKGROUND DATA: Few cases of liver transplantation with a minimally invasive approach using partial grafts have been reported so far, and no cases of robotic whole liver transplantation have been reported in the scientific literature. METHODS: The adopted technique was full robotic liver hepatectomy, followed by robotic implantation after graft introduction through a small midline incision. Patients presenting with Hepatocellular Carcinoma (HCC) in liver cirrhosis with a small caudate lobe, low degree of portal hypertension, no porto-mesenteric thrombosis, as well as low MELD patients have been considered ideal candidates. RESULTS: Six patients underwent RLT between February and March 2024 at Lisbon and Modena University Liver Transplant Centers. Warm ischemia time during RLT ranged between 55 and 90 min, with a total surgery duration between 440 and 710 min. The median total operative time was 595 (±111,3) minutes. Only one recipient had prolonged hyperbilirubinemia, which was safely treated. The median in-hospital stay was 7.5 days, (±4.8 days). CONCLUSIONS: RLT is a promising technique to further reduce the impact of liver transplantation thanks to smaller incision, gentle tissue manipulation, high magnification and precision for vascular and biliary anastomosis, and reduced postoperative pain. This is the first step toward the demonstration of the feasibility of minimally invasive surgery in liver transplantation, although further selection and technical refinements are needed to improve reproducibility.

Cornerstones and divergencies in the implementation and use of liver hypertrophy techniques: results from a nationwide survey for the set-up of the prospective registry.

BACKGROUND: The aim of this national survey on liver hypertrophy techniques was to track the trends of their use and implementation in Italy and to detect analogies and heterogeneities among centers. METHODS: In December 2022, Italian centers with liver resection activity were specifically contacted and asked to fill an online questionnaire composed of 6 sections including a total of 51 questions. RESULTS: 46 Italian centers filled the questionnaire. The proportion of major/total number of liver resections was 27% and the use of hypertrophy techniques was required in 6,2% of cases. The most frequent reason of drop out was disease progression in 58.5% of cases. Most frequently used techniques were PVE and ALPPS with an increasing use of hepatic venous deprivation (HVD). Heterogeneous answers were provided regarding the cutoff values to indicate the need for hypertrophy techniques. Criteria to allocate a patient to different hypertrophy techniques are not standardized. CONCLUSIONS: The use of hypertrophy techniques is deep-rooted in Italy, documenting the established value of their role in improving resectability rate. While an evolution of techniques is detectable, still significant heterogeneity is perceived in terms of cutoff values, indications and managing protocols.

Robotic Major Hepatectomy in Elderly Patient.

BACKGROUND: the role of minimally invasive liver surgery has been progressively developed, with the practice increasing in safety and feasibility also with respect to major liver resections. The aim of this study was to analyze the feasibility and safety of major liver resection in elderly patients. METHODS: data from a multicentric retrospective database including 1070 consecutive robotic liver resections in nine European hospital centers were analyzed. Among these, 131 were major liver resections. Patients were also divided in two groups (<65 years old and ≥65 years old) and perioperative data were compared between the two groups. RESULTS: a total of 131 patients were included in the study. Operative time was 332 ± 125 min. Postoperative overall complications occurred in 27.1% of patients. Severe complications (Clavien Dindo ≥ 3) were 9.9%. Hospital stay was 6.6 ± 5.3 days. Patients were divided into two groups based on their age: 75 patients < 65 years old and 56 patients ≥ 65 years old. Prolonged pain, lung infection, intensive care stay, and 90-day readmission were worse in the elderly group. The two groups were matched for ASA and Charlson comorbidity score and, after statistical adjustment, postoperative data were similar between two groups. CONCLUSIONS: robotic major liver resection in elderly patients was associated with satisfying short-term outcomes.

Towards a Standardization of Learning Curve Assessment in Minimally Invasive Liver Surgery.

OBJECTIVE: The aim was to analyze the learning curves of minimal invasive liver surgery(MILS) and propose a standardized reporting. SUMMARY BACKGROUND DATA: MILS offers benefits compared to open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization. METHODS: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves, and characterization of different learning phases(competency, proficiency and mastery). RESULTS: 60 articles with 12'241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42) and postoperative complications (n=38). Overall competency, proficiency and mastery were reached after 34 (IQR 19-56), 50 (IQR 24-74), 58 (IQR 24-100) procedures respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: -13%, 2%; blood loss: competency to proficiency to mastery: -33%, 0%; conversion rate (competency to proficiency to mastery; -21%, -29%), whereas postoperative complications improved later (competency to proficiency to mastery: -25%, -41%). CONCLUSIONS: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized three-phase reporting of learning phases (competency, proficiency, mastery) is proposed and should be followed.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Defining Global Benchmarks for Laparoscopic Right Posterior Sectionectomy/H67: An International Multicenter Study.

OBJECTIVE: We aimed to establish global benchmark outcomes indicators for L-RPS/H67. BACKGROUND: Minimally invasive liver resections has seen an increase in uptake in recent years. Over time, challenging procedures as laparoscopic right posterior sectionectomies (L-RPS)/H67 are also increasingly adopted. METHODS: This is a post hoc analysis of a multicenter database of 854 patients undergoing minimally invasive RPS (MI-RPS) in 57 international centers in 4 continents between 2015 and 2021. There were 651 pure L-RPS and 160 robotic RPS (R-RPS). Sixteen outcome indicators of low-risk L-RPS cases were selected to establish benchmark cutoffs. The 75th percentile of individual center medians for a given outcome indicator was set as the benchmark cutoff. RESULTS: There were 573 L-RPS/H67 performed in 43 expert centers, of which 254 L-RPS/H67 (44.3%) cases qualified as low risk benchmark cases. The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, 90-day mortality and textbook outcome after L-RPS were 350.8 minutes, 12.5%, 53.8%, 22.9%, 23.8%, 2.8%, 0% and 4% respectively. CONCLUSIONS: The present study established the first global benchmark values for L-RPS/H6/7. The benchmark provided an up-to-date reference of best achievable outcomes for surgical auditing and benchmarking.

Role of Body Composition in Patients with Resectable Pancreatic Cancer.

This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.

Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

Full robotic versus open ALPPS: a bi-institutional comparison of perioperative outcomes.

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.

Recommendations on Robotic Hepato-Pancreato-Biliary Surgery. The Paris Jury-Based Consensus Conference.

OBJECTIVE: To establish the first consensus guidelines on the safety and indications of robotics in Hepato-Pancreatic-Biliary (HPB) surgery. The secondary aim was to identify priorities for future research. SUMMARY BACKGROUND DATA: HPB robotic surgery is reaching the IDEAL 2b exploration phase for innovative technology. An objective assessment endorsed by the HPB community is timely and needed. METHODS: The ROBOT4HPB conference developed consensus guidelines using the Zurich-Danish model. An impartial and multidisciplinary jury produced unbiased guidelines based on the work of ten expert panels answering predefined key questions and considering the best-quality evidence retrieved after a systematic review. The recommendations conformed with the GRADE and SIGN50 methodologies. RESULTS: Fifty-four experts from 20 countries considered 285 studies, and the conference included an audience of 220 attendees. The jury (n=10) produced recommendations or statements covering five sections of robotic HPB surgery: technology, training and expertise, outcome assessment, and liver and pancreatic procedures. The recommendations supported the feasibility of robotics for most HPB procedures and its potential value in extending minimally invasive indications, emphasizing however the importance of expertise to ensure safety. The concept of expertise was defined broadly, encompassing requirements for credentialing HPB robotics at a given center. The jury prioritized relevant questions for future trials and emphasized the need for prospective registries, including validated outcome metrics for the forthcoming assessment of HPB robotics. CONCLUSION: The ROBOT4HPB consensus represents a collaborative and multidisciplinary initiative, defining state-of-the-art expertise in HPB robotics procedures. It produced the first guidelines to encourage their safe use and promotion.

The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).

Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.

Current role and perspectives of living donor liver transplantation for hepatocellular carcinoma: systematic review of the past 20 years.

Hepatocellular carcinoma (HCC) poses a significant global health challenge, and liver transplantation (LT) remains the best curative option. Living donor liver transplantation (LDLT) emerged as a potential solution to organ scarcity, reducing waitlist times. This comprehensive review explores LDLT practices, focusing on patient selection criteria and oncologic outcomes. A systematic review following PRISMA guidelines included 50 studies (2004-2023) with 8062 patients. Data encompassed baseline characteristics, HCC features, and oncologic outcomes. Further analysis categorized results by geography and publication year. Heterogeneity in patient demographics, tumor burden, and transplant characteristics was observed. Recent LDLT series demonstrated a shift towards refined selection criteria, increased neoadjuvant treatment, and improved oncologic outcomes. Geographic disparities revealed unique challenges in Eastern and Western practices. LDLT proves effective for HCC, addressing donor shortages. Evolving practices highlight the importance of refining inclusion criteria and optimizing tumor management. While geographic differences exist, LDLT, when judiciously applied, offers promising outcomes.

Indications to LDLT: a changing pathway?

Liver transplantation (LT) revolutionized the outlook for cirrhotic patients, offering a potential cure with over 80% life expectancy after 5 years. Cirrhosis, with or without hepatocellular carcinoma (HCC), is the primary LT indication. Living donor LT (LDLT) initially explored as an alternative, declined due to poorer outcomes. Studies on LDLT improved outcomes through precise recipient selection, emphasizing the importance of careful donor/recipient matching. Emerging concepts like left lobe preference and minimally invasive donor approaches enhance LDLT outcomes. The RAPID technique shows promise in both cirrhotic and non-cirrhotic livers. LDLT gains significance in transplant oncology, particularly for liver tumors like colorectal liver metastases (CLM), offering better survival than alternatives. Optimal timing integrates chemotherapy with the transplant. As LT indications evolve, LDLT finds a growing role in oncology, surpassing deceased donor transplants in certain scenarios. The decreasing prevalence of virus-related uncompensated cirrhosis highlights the expanding space for LDLT in liver transplantation.

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: Thirty-six cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), postoperative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, one due to heart failure, one due to septic shock, and three due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated 5 years overall survival was 48% (95% CI: 27-66%), and 5-year cumulative incidence of tumor recurrence was 55% (95% CI: 33-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to nonoperative management, especially in patients affected by intrahepatic cholangiocarcinoma.