Mechanism, Potential, and Concerns of Immunotherapy for Hepatocellular Carcinoma and Liver Transplantation.

In the last decade, immunotherapy (IT) has revolutionized oncology and found indications in many cancers, including hepatocellular carcinoma (HCC). In HCC, IT has become the leading systemic therapy for advanced diseases. At the same time, it carries the promise of being a valuable therapy in other settings, including intermediate-stage and unresectable disease, as a downstaging or conversion modality. More controversial is the role of IT in relationship to liver transplantation (LT): on one side, it could be a helpful tool to control or downstage HCC before LT or to treat tumor recurrence after LT, while on the other, it carries the risk of graft rejection and graft loss. This review aims to cover these concerns in depth and unravel the current literature.

Fairness and pitfalls of the Italian waiting list for elective liver transplantation: The ECALITA registry study.

BACKGROUND: The challenge of transplant waiting-lists is to provide organs for all candidates while maintaining efficiency and equity. AIMS: We investigated the probability of being transplanted or of waiting-list dropout in Italy. METHODS: Data from 12,749 adult patients waitlisted for primary liver-transplantation from January 2012 to December 2022 were collected from the National Transplant-Registry.The cohort was divided into Eras:1 (2012-2014);2 (2015-2018);and 3 (2019-2022). RESULTS: The one-year probability of undergoing transplant increased (67.6 % in Era 1vs73.8 % in Era 3,p < 0001) with a complementary 46 % decrease in waiting-list failures. Patients with hepatocellular-carcinoma were transplanted more often than cirrhotics[at model for end-stage liver-disease (MELD)-15:HR = 1.28,95 %CI:1.21-1.35;at MELD-25:HR = 1.04,95 %CI:0.92-1.19) and those with other indications (at MELD-15:HR = 1.27,95 %CI:1.11-1.46) across all eras. Candidates with Hepatitis-B-virus (HBV)related disease had a greater probability of transplant than those with Hepatitis-C virus-related (HR = 1.13,95 %CI:1.07-1.20), alcohol-related (HR = 1.13,95 %CI:1.05-1.21), and metabolic-related (HR = 1.18,95 %CI:1.09-1.28)disease. Waiting-list failures increased by 27 % every 5 MELD-points and by 14 % for every 5-year increase in recipient-age and decreased by 10 % with each 10-cm increase in stature. Blood-group O patients showed the highest probability of waiting-list failure (HR = 1.28,95 %CI:1.15-1.43). CONCLUSIONS: Liver-transplantation waiting-list success-rates have significantly improved in Italy, with patients with hepatocellular-carcinoma and/or HBV-related diseases being favored. High MELD-score, old-age, short-stature, and blood-group O were significant risk-factors for waiting-list failure. Efforts to improve organ-allocation and prioritization-policies are underway.

Immunosuppression in adult liver transplant recipients: a 2024 update from the Italian Liver Transplant Working Group.

PURPOSE: Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations. METHODS: The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached. RESULTS: A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk. CONCLUSION: The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy.

Cancer mortality after kidney transplantation: A multicenter cohort study in Italy.

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.

Cell transplantation-based regenerative medicine in liver diseases.

This review aims to evaluate the current preclinical state of liver bioengineering, the clinical context for liver cell therapies, the cell sources, the delivery routes, and the results of clinical trials for end-stage liver disease. Different clinical settings, such as inborn errors of metabolism, acute liver failure, chronic liver disease, liver cirrhosis, and acute-on-chronic liver failure, as well as multiple cellular sources were analyzed; namely, hepatocytes, hepatic progenitor cells, biliary tree stem/progenitor cells, mesenchymal stromal cells, and macrophages. The highly heterogeneous clinical scenario of liver disease and the availability of multiple cellular sources endowed with different biological properties make this a multidisciplinary translational research challenge. Data on each individual liver disease and more accurate endpoints are urgently needed, together with a characterization of the regenerative pathways leading to potential therapeutic benefit. Here, we critically review these topics and identify related research needs and perspectives in preclinical and clinical settings.

Outcome of liver transplantation in elderly patients: an Italian multicenter case-control study.

Despite the controversial results of liver transplantation (LT) in elderly recipients, the proportion of patients continues to increase. This study investigated the outcome of LT in elderly patients (≥ 65 years) in an Italian, multicenter cohort. Between January 2014 and December 2019, 693 eligible patients were transplanted, and two groups were compared: recipients ≥ 65 years (n = 174, 25.1%) versus 50-59 years (n = 519, 74.9%). Confounders were balanced using a stabilized inverse probability therapy weighting (IPTW). Elderly patients showed more frequent early allograft dysfunction (23.9 versus 16.8%, p = 0.04). Control patients had longer posttransplant hospital stays (median: 14 versus 13 days; p = 0.02), while no difference was observed for posttransplant complications (p = 0.20). At multivariable analysis, recipient age ≥ 65 years was an independent risk factor for patient death (HR 1.76; p = 0.002) and graft loss (HR 1.63; p = 0.005). The 3-month, 1-year, and 5-year patient survival rates were 82.6, 79.8, and 66.4% versus 91.1, 88.5, and 82.0% in the elderly and control group, respectively (log-rank p = 0.001). The 3-month, 1-year, and 5-year graft survival rates were 81.5, 78.7, and 66.0% versus 90.2, 87.2, and 79.9% in the elderly and control group, respectively (log-rank p = 0.003). Elderly patients with CIT > 420 min showed 3-month, 1-year, and 5-year patient survival rates of 75.7%, 72.8%, and 58.5% versus 90.4%, 86.5%, and 79.4% for controls (log-rank p = 0.001). LT in elderly (≥ 65 years) recipients provides favorable results, but inferior to those achieved in younger patients (50-59), especially when CIT > 7 h. Containment of cold ischemia time seems pivotal for favorable outcomes in this class of patients.

The Enhanced Recovery after Surgery (ERAS) Pathway Is a Safe Journey for Kidney Transplant Recipients during the "Extended Criteria Donor" Era.

Enhanced recovery after surgery (ERAS) protocols are still underused in kidney transplantation (KT) due to recipients' "frailty" and risk of postoperative complications. We aimed to evaluate the feasibility and safety of ERAS in KT during the "extended-criteria donor" era, and to identify the predictive factors of prolonged hospitalization. In 2010−2019, all patients receiving KT were included in ERAS program targeting a discharge home within 5 days of surgery. Recipient, transplant, and outcomes data were analyzed. Of 454 KT [male: 280, 63.9%; age: 57 (19−77) years], 212 (46.7%) recipients were discharged within the ERAS target (≤5 days), while 242 (53.3%) were discharged later. Patients within the ERAS target (≤5 days) had comparable recipient and transplant characteristics to those with longer hospital stays, and they had similar post-operative complications, readmission rates, and 5 year graft/patient survival. In the multivariate analysis, DGF (HR: 2.16, 95% CI: 1.08−4.34, p < 0.030) and in-hospital dialysis (HR: 3.68, 95% CI: 1.73−7.85, p < 0.001) were the only predictive factors for late discharge. The ERAS approach is feasible and safe in all KT candidates, and its failure is primarily related to the postoperative graft function, rather than the recipient's clinical status. ERAS pathways, integrated with strict collaboration with local nephrologists, allow early discharge after KT, with clinical benefits.

Temporal trends of waitlistings for liver transplantation in Italy: The ECALITA (Evolution of IndiCAtion in LIver transplantation in ITAly) registry study.

BACKGROUND: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. AIM: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. METHODS: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004-2011),2(2012-2014) and 3(2015-2020). RESULTS: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. CONCLUSIONS: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.

Pancreatic Adeno-MiNEN, a Rare Newly Defined Entity with Challenging Diagnosis and Treatment: A Case Report with Systematic Literature Review and Pooled Analysis.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are a peculiar entity that can occur throughout the whole gastrointestinal trait, and pancreatic localization is rare. Their main characteristic is the presence of at least a neuroendocrine and an epithelial component, each accounting for at least 30% of the tumour mass. The presence of epithelial ductal component defines adeno-MiNEN. We report a case of a 59-year-old woman affected by pancreatic adeno-MiNEN with challenging diagnosis and successfully treated. A systematic literature review and pooled analysis was also performed, aiming to define the management and outcomes of pancreatic adeno-MiNEN. Out of 190 identified records, 15 studies including 28 patients affected by pancreatic-adeno-MiNEN were included in the analysis. Pancreatic adeno-MiNEN occurred mainly in males (82.8%) and at a mean age of 61.7 (range: 24-82) years. Pre-operative diagnosis was possible only in 14.2% of cases. At presentation, the majority had already advanced disease (TNM stage III (53.8%) and stage IV 19.3%). Adjuvant therapy was performed in 55% of patients, and the tumour recurrence rate was in 30% of cases. Median disease-free survival (DFS) was 12 months (range: 0-216 months) with a 5-year DFS of 16.6%, while the median overall survival (OS) was 12 months (range: 0-288 months) with a 5-year OS of 23.5%. Pancreatic adeno-MiNENs are rare; as they have very heterogenous behaviour, they are rarely diagnosed preoperatively and have poor prognosis. Treatment of localised MiNEN still relies on radical surgical resection, which seems essential to achieve a good oncological prognosis. International registry on MiNEN is necessary to improve the knowledge on this rare tumour and to improve its outcomes.

Graft weight integration in the early allograft dysfunction formula improves the prediction of early graft loss after liver transplantation.

The role of the graft-to-recipient weight ratio (GRWR) in adult liver transplantation (LT) has been poorly investigated so far. The aim is to evaluate the contribution of the GRWR to the well-recognized early allograft dysfunction (EAD) model (i.e., Olthoff model) for the prediction of 90-day graft loss after LT in adults. Three hundred thirty-one consecutive adult patients undergoing LT between 2009 and 2018 at Tor Vergata and Sapienza University in Rome, Italy, served as the Training-Set. The Validation-Set included 123 LTs performed at the Erasmus Medical Center, Rotterdam, the Netherlands. The mEAD model for 90-day graft loss included the following variables: GRWR [Formula: see text] 1.57 = 2.5, GRWR [Formula: see text] 2.13 = 2.5, total bilirubin ≥ 10.0 mg/dL = 2.0, INR ≥ 1.60 = 2.3, and aminotransferase > 2000 IU/L = 2.2. The mEAD model showed an AUC = 0.74 (95%CI = 0.66-0.82; p < 0.001) and AUC = 0.68 (95%CI = 0.58-0.88; p = 0.01) in the Training-Set and Validation-Set, respectively, outperforming conventional EAD in both cohorts (Training-Set: AUC = 0.64, 95%CI = 0.57-0.72; p = 0.001; Validation-Set: AUC = 0.52, 95%CI = 0.35-0.69, p = 0.87). Incorporation of graft weight in a composite multivariate model allowed for better prediction of patients who presented an aminotransferase peak > 2000 IU/L after LT (OR = 2.39, 95%CI = 1.47-3.93, p = 0.0005). The GRWR is important in determining early graft loss after adult LT, and the mEAD model is a useful predictive tool in this perspective, which may assist in improving the graft allocation process.

Prophylactic drains in totally laparoscopic distal gastrectomy: are they always necessary?

Prophylactic drains have always been a useful tool to detect early complications and prevent postoperative fluid collections, particularly in gastrointestinal surgery. Recently, the utilization of such drains has been debated, due to mounting evidence that they could be harmful rather than beneficial. Based on recent published articles, Liu et al reported that the routine use of prophylactic drains in total laparoscopic distal gastrectomy might not be necessary for all patients. Herein, we express our opinion regarding this interesting publication.

High-priority liver transplantation and simultaneous sleeve gastrectomy in MELD 32 end-stage liver disease: a case report with long-term follow-up.

BACKGROUND: Morbid obesity is a worldwide epidemic closely linked to Non-Alcoholic Fatty Liver Disease (NAFLD), an ever more relevant indication for Liver Transplantation (LT). Obesity affects an increasing number of LT recipients, but the ideal management of these patients remain unclear. Bariatric surgery (BS) in LT setting is challenging but feasible, although the debate is still open about the best timing of bariatric surgery. Herein we report a case of high-priority LT and simultaneous sleeve gastrectomy (SG) in an obese young adult. CASE REPORT: A 45 years old man with morbid obesity (BMI 46 kg/m2) and severe NAFLD-related end-stage liver disease (ESLD) underwent simultaneous LT and sleeve gastrectomy (SG) in an emergency setting, due to a MELD score of 32. He had substantial weight loss during long-term follow-up and enjoyed resolution of diabetes and hypertension. At 4 years follow-up, he has normal allograft function with appropriate immunosuppressant blood levels and no ultrasound evidence of steatosis. CONCLUSION: In selected patients, combined LT and SG present several advantages in terms of transplant outcomes, weight loss and resolution of obesity-related comorbidities. In addition, it can be performed in the high-priority setting in case of severe ESLD with good results in the short- and long-term.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

Vascular Involvements in Cholangiocarcinoma: Tips and Tricks.

Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract. To date, surgical treatment remains the only hope for definitive cure of CCA patients. Involvement of major vascular structures was traditionally considered a contraindication for resection. Nowadays, selected cases of CCA with vascular involvement can be successfully approached. Intrahepatic CCA often involves the major hepatic veins or the inferior vena cava and might necessitate complete vascular exclusion, in situ hypothermic perfusion, ex situ surgery and reconstruction with autologous, heterologous or synthetic grafts. Hilar CCA more frequently involves the portal vein and hepatic artery. Resection and reconstruction of the portal vein is now considered a relatively safe and beneficial technique, and it is accepted as a standard option either with direct anastomosis or jump grafts. However, hepatic artery resection remains controversial; despite accumulating positive reports, the procedure remains technically challenging with increased rates of morbidity. When arterial reconstruction is not possible, arterio-portal shunting may offer salvage, while sometimes an efficient collateral system could bypass the need for arterial reconstructions. Keys to achieve success are represented by accurate selection of patients in high-volume referral centres, adequate technical skills and eclectic knowledge of the various possibilities for vascular reconstruction.

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor.

The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.

Global management of a common, underrated surgical task during the COVID-19 pandemic: Gallstone disease - An international survery.

BACKGROUND: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. METHODS: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. RESULTS: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50-75%, 10(27.8%) by 25-50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months.In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. CONCLUSION: In the ongoing COVID-19 emergency, the surgical treatment of GD is postponed, resulting in a huge number of untreated patients who could develop severe morbidity. Updated guidelines and dedicated pathways for patients with benign disease awaiting elective surgery are mandatory to prevent further aggravation of the overloaded healthcare systems.

Feasibility and cost effectiveness of ambulatory laparoscopic cholecystectomy. A retrospective cohort study.

Ambulatory surgery is an efficient, safe and widely performed procedure; this study would shows the advantages of the ambulatory laparoscopic cholecystectomy procedure from the point of view of patients and the Hospital/National Health System. Materials and Methods: Single-center retrospective cohort study including 288 patients who underwent laparoscopic-cholecystectomy at **** from January 2016 to July 2018. Ambulatory LC were compared to well-matched inpatient procedures performed in the same study period. The primary endpoints was the 30-day readmission rate. Secondary endpoints were the discharge rate in the ambulatory group, the post-operative complications rate and cost effectiveness. Results: 120/288 (41.7%) patients underwent ambulatory laparoscopic cholecystectomy. Thirty-two (26.7%) patients who underwent ambulatory laparoscopic cholecystectomy had major preoperative comorbidities and 35 (29.2%) had undergone prior abdominal surgery. The readmission rates for ambulatory patients and inpatients were 0.8% and 1.7% (p = 0.56), respectively; 104 (86.7%) ambulatory patients were discharged successfully on the same day. The two groups showed the same post-operative complication rate (p = 0.40). Ambulatory procedures resulted in related cost savings of more than 300% for the hospital and a remarkable financial benefit for the National Italian Healthcare System, accounting for savings exceeding € 27 000 per year. Conclusions: Ambulatory laparoscopic cholecystectomy is safe and cost effective. Since a third of ambulatory patients showed comorbidity or previous abdominal surgery, we believe that this procedure may be performed safely in a tertiary HPB centre, even in complex patients.