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Background: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. Patients and Methods: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). Results: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). Conclusion: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Perihilar cholangiocarcinoma (pCCA) is one of the most complex challenges for hepatobiliary surgeons. Poor results and high incidence of morbidity after Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for pCCA discouraged this indication. It has been proposed that minimally invasive approach for ALPPS first stage, as well as combination of surgical liver partition and radiologic portal vein embolization (PVE), may improve outcomes reducing interstage morbidity. We report a case of right trisectionectomy with enbloc caudatectomy ALPPS scheduled for pCCA with robotic approach at stage-1, the full video is provided as supplementary material. Due to intraoperative presence of portal vein tumor infiltration during hilar dissection (no evidence in the pre-operative work-up), a radiologic right PVE was performed after stage-1 instead of portal vein ligation, followed by portal vein resection and biductal hepatico-jejunostomy at stage-2 with open approach. The patient was a 74-year-old female diagnosed with 3-cm mass-forming pCCA. The total clean liver volume was 1231 cc, with future liver remnant (FLR) volume of 25.1% (segments II and III). She was discharged in the interstage interval on postoperative day (POD) 4; CT scan on POD 12 showed that FLR increased up to 33% (369 cc) (Fig. 1). ALPPS was completed on POD 17, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 19 after stage-2. Besides the already demonstrated advantages in terms of reduced interstage morbidity, robotic ALPPS represents a promising strategy to expand surgical indication in patients with pCCA. The combination of liver partition and PVE may increase the opportunities to perform radical resections in selected patients with pCCA and portal vein infiltration. Supplementary Information The online version contains supplementary material available at 10.1007/s13304-021-01209-x.

Lymph nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (ICC), but the need to perform lymphadenectomy in clinically node-negative (cN0) patients is still under debate. Aim of this study is to determine whether adequate lymphadenectomy improves long-term outcomes in cN0 patients undergoing liver resection for ICC.Retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 ICC at five tertiary referral Centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weighting (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW-weighted regression.The study includes 706 cN0 patients who underwent curative surgery for intrahepatic cholangiocarcinoma. Four-hundred seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR: 18-77), median overall survival was 39 months (IQR: 23-109) and median recurrence-free survival was 23 months (IQR: 8-74). After stratifying according to nodal status at final pathology, node-positive patients had longer overall survival (28 months vs 23, HR=1.82; 95%CI: 1.14-2.90; p=0.023) and disease free survival (13 months vs 9, HR=1.35; 95%CI: 1.14-1.59; p=0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less advanced tumors (solitary tumors, tumor size5 cm, Ca19.9200 U/mL).Adequate lymphadenectomy provided better survival outcomes for cN0 patients who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 intrahepatic cholangiocarcinoma.Lymphadenectomy (LND) is essential for the surgical staging of intrahepatic cholangiocarcinoma (ICC). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of LND on survival of clinically node-negative (cN0) patients is still under debate. In this large retrospective study on cN0 patients who underwent surgical resection for ICC, we show that performing an adequate LND by retrieving 6 or more lymph nodes significantly improves survival and lowers the risk of tumor recurrence. Lymphadenectomy during surgical resection of ICC is actually underperformed by the surgical community, resulting in inadequate staging and possibly in worse long-term outcomes. The results of this study empower surgeons and clinicians in claiming an adequate lymphadenectomy even in cN0 patients. Since patients with no chronic liver disease and with less advanced tumors are those who receive a significant benefit from LND, our results might guide decision making in patients at high-risk for postoperative complications.

Robotic approach to the liver may allow to perform difficult resections with a minimally invasive strategy in an easier way as compared to standard laparoscopy. The aim of this study is to review our experience with robotic major hepatectomies, reporting technical considerations, and describing the outcomes of patients that underwent either left (LRH) or right robotic hepatectomy (RRH). Our prospectively maintained database was screened to identify all patients that received a major liver resection for benign or malignant disease. Preoperative data and postoperative short-term and long-term outcomes were reported. 261 robotic procedures were performed in our Center between May 2014 and October 2020. 12 patients underwent robotic left hepatectomy (RLH) and 10 patients were treated by robotic right hepatectomy (RRH). In the RLH group, median operative time (OT) was 383 min, median estimated blood loss (EBL) was 300 ml, and median in-hospital stay was of 3 days. In the RRH group, median OT was 490 min, median EBL 725 ml, and median hospital stay was 5 days. Although one of the advantages of minimally invasive surgery is to obtain radical resections with parenchyma sparing strategies, patients that need a major hepatectomy may benefit of a robotic resection with good postoperative outcomes. Team learning curve and growth instead of personal progression is crucial to expand the limits of novel surgical techniques.

ImportanceLong-term oncologic outcomes of robotic surgery remain a hotly debated topic in surgical oncology, but sparse data have been published thus far.ObjectiveTo analyze short- and long-term outcomes of robotic liver resection (RLR) for hepatocellular carcinoma (HCC) from Western high-volume centers to assess the safety, reproducibility, and oncologic efficacy of this technique.Design, Setting, and ParticipantsThis cohort study evaluated the outcomes of patients receiving RLR vs open liver resection (OLR) for HCC between 2010 and 2020 in 5 high-volume centers. After 1:1 propensity score matching, a group of patients who underwent RLR was compared with a validation cohort of OLR patients from a high-volume center that did not perform RLR.Main Outcomes and MeasuresA retrospective analysis was performed of prospectively maintained databases at 2 European and 2 US institutions of patients who underwent RLR for HCC between January 1, 2010, and September 30, 2020. The main outcomes were safety and feasibility of RLR for HCC and its oncologic outcomes compared with a European OLR validation cohort. A 2-sided P ResultsThe study included 398 patients (RLR group: 125 men, 33 women, median [IQR] age, 66 [58-71] years; OLR group: 315 men, 83 women; median [IQR] age, 70 [64-74] years), and 106 RLR patients were compared with 106 OLR patients after propensity score matching. The RLR patients had a significantly longer operative time (median [IQR], 295 [190-370] minutes vs 200 [165-255] minutes, including docking; P P P = .002). Incidence of posthepatectomy liver failure was significantly lower in the RLR group (8 [7.5%] vs 30 [28.3%]; P = .001), with no cases of grade C failure. The 90-day overall survival rate was comparable between the 2 groups (RLR, 99.1% [95% CI, 93.5%-99.9%]; OLR, 97.1% [95% CI, 91.3%-99.1%]), as was the cumulative incidence of death related to tumor recurrence (RLR, 8.8% [95% CI, 3.1%-18.3%]; OLR, 10.2% [95% CI, 4.9%-17.7%]).Conclusions and RelevanceThis study represents the largest Western experience to date of full RLR for HCC. Compared with OLR, RLR performed in tertiary centers represents a safe treatment strategy for patients with HCC and those with compromised liver function while achieving oncologic efficacy.

Background Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree, with morphological variations and occasional invasion. Case summary We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography. Using the SpyGlass DS II technology, we were able to define tumor extension and obtain targeted Spy-byte biopsies. After multidisciplinary evaluation, the patient was scheduled for surgical resection of the tumor, which was radically removed. Conclusion Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

Background & Aims: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. Methods: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. Results: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p

Background: Many patients with Hepatocellular Carcinoma (HCC) present at diagnosis a tumor stage suitable for both Liver Resection (LR) and Liver Transplantation (LT). LR is generally safer, available for all, schedulable at the best timing, but less radical and not able to cure the underlying cirrhosis. Contrarily, LT is much more invasive, unavailable for all the candidates, performed at unpredictable time, but with more extended radicality and able also to cure the underlying cirrhosis. Until now, what is the best candidate for LR or LT upfront is extremely unclear. The aim of the study was to validate a model to predict tumor results after LR or LT for patients eligible for both. Methods: All the 2640 consecutive cases of LR or LT for HCC at the 4 centers involved into the study were collected. After a propensity score matching (PSM), an homogeneous patient’s cohort was selected and compared between LR and LT groups. An intention-to-treat (ITT) analysis with a competing risk model was applied comparing the tumor related deaths of patient groups. Results: Between 2005 and 2015, 551 LRs and 580 LT candidates (LTc) were selected for the study. Of the 580 LTc, 512 were effectively transplanted, whereas 68 (11.7%) were dropped due to tumor progression. After a PSM, 101 high risk patients were, respectively, selected for each groups: LR and LT. Variables considered for the risk assignment were: alfafetoprotein, tumor size, tumor number, AST, MELD, and age at tumor diagnosis. The 3- and 5-years cumulative incidence of tumor related death was, respectively, 23% and 31% vs 5% and 9% for LR and LT group (Pvalue = .002). Conclusions: The high risk patients’ cohort has significantly better ITT tumor-related survival with a LT rather than a LR upfront. The microvascular invasion or HCC satellitosis may significantly increase the risk of tumor related death even in low and intermediate risk patients who have received LR. The ab-initio LT should be considered in these reconverted risk patients.

The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65years and < or ≥80years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow-up of 86months were analysed. The 1-, 3- and 5-year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P&nbsp

September 2020 signed the beginning of the second wave of COVID-19 outbreak in Italy (Supplementary Material-1) (1). Since the dramatic experience learned during the first epidemic wave, a significant decline of liver transplantations (LT) will be expected. Every year, approximatively 1,200 LTs are performed in Italy (2). The majority of these are concentrated within four northern regions (Lombardia, Veneto, Piemonte, Emilia-Romagna, LoVePiER), accounting about more than the half of the overall LT performed per year (749/1,277 LT, 58.6%, in 2019). Nowadays, LoVePiER was the most involved areas by the Covid-19-outbreak, with a total of 75,738 (71.5%) documented cases until March 31st and 10,174 (81.8%) deaths (Supplementary Material-2) (1).

Simple Summary HCC are now emerging as leading causes of morbidity in HIV-infected patients since HAART has made it possible to achieve long life expectation by reducing AIDS-related complications. The results of liver transplantation for HCC in HIV-infected patients are still contradictory. In this paper we demonstrated in a cohort of 32 HIV-infected patients undergoing LT for HCC that the post-LT outcomes are comparable to the controlled cohort of uninfected recipients. Long survival rates were observed for HIV-infected LT patients with HCC. Abstract Background: HIV-infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV-infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post-LT recurrence. Results: Among 1010 LT, 32 were HIV-infected recipients. With an average follow-up of 62 ± 51 months, 5-year overall survival in LT recipients with and without HIV-infection was 71.6% and 69.9%, respectively (p = ns), whereas 5-year graft survival in HIV-infected and HIV-non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83, p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18, p< 0.001), HCC diameter (HR 1.16, p = 0.028), and number of HCC nodules (HR 1.26, p = 0.003) were predictors of recurrence post-LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post-LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64–0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48–0.72] when LI-RADS-5 and LI-RADS-TR-V (P=0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P=0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54–0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P=0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance.

Background and Aims Living Kidney Donor Transplantation (LKDT) is the first therapeutic choice in end stage renal disease (ESRD). Donor safety has to be ensured, throughout an extensive pre operative screening. Venous thromboembolism (VTE) and deep vein thrombosis(DVT) are the most frequent complications after abdominal surgery. Living kidney donation is considered a safe procedure, with a major morbidity rate around 5%, and a not clearly defined incidence of VTE and DVT. We thus proceeded to evaluate the thrombophilic risk among potential kidney donors to define an adequate prophylactic strategy. Method Our Transplant Center introduced thrombophilic screening in all potential donors from 2019. We checked clinical history for previous thrombotic events, active or treated malignacies. Our thombophilic risk panel comprehended: Lupus Anticoagulant (LAC), Factor V -II-VIII, in Protein C and S activity. In case of LAC undetermined results on two consecutive samples, we tested anti-cardiolipin and anti-beta2-glycoprotein 1 antibodies. Nephrectomy was performed by mini-invasive robotic technique; anticoagulation was provided by Enoxaparin 4000U 7-14 days. Results We studied 32 potential donors. No previous thrombotic events were reported. Malignancies were observed in 4 patients (12.5%), 1 before starting the study and 3 were discovered during the evaluation (MGUS, non small cell lung carcinoma). Thrombophilic screening showed uncertain LAC in 3 (9%) patients, an heterozygote mutation in Factor V associated with APC positivity in 1 patient(3%), heterozygote mutation in Factor II in 3(9%) disorder in Protein C S and Factor VIII activity respectively in 4 (12.5%) 3(9%)and 4(12.5%) patients. Among the 9 patients deemed fit for donation: uncertain LAC in 1(11%) patient, heterozygote mutation in Factor II in 1 (9%) patient. No thrombotic event was reported after donation. Conclusion The frequency of coagulation disorders among kidney living donor is low, but not negligible. Appropriate medical history assessment and thrombophilic screening before donation is recommended, as well as an antithrombotic prophylaxis with Enoxaparin from 7 to 14 days after nephrectomy, tailored on each patient risk factors. This strategy allowed to avoid thrombotic events in patients who underwent nephrectomy. More data are necessary to draw more solid conclusions.

Background and Aims Combined liver-kidney transplant is the best treatment for patients with hepatic and renal failure, even though some studies reported a poor patient survival. The aim of our study is to summarize the clinical characteristics of subjects who undergo simultaneous combined liver-kidney transplantation (SLKT) for advanced liver and kidney disease. Furthermore, we evaluated patient and kidney survival of SLKT recipients compared to solitary kidney transplant (KT) recipients. Method We performed a retrospective analysis of all SLKT recipients performed in a single transplant Center (University Hospital of Modena, Italy) from 01/01/2004 to 12/31/2016. All patients were aged more than 18 years. Results 34 SLKT were performed over 16 years of transplant activity. Mean age of recipients was 51.3 ±9.1years. Males accounted for 65% of the population. All patients were of Caucasians origin except one of African origin. Mean BMI was 69.5 ± 13.9 Kg. Hepatitis C Virus (HCV)-related cirrhosis was the main cause (38.1%) of hepatic failure. Other causes of hepatic disease were ADPKD (26.5%), hepatitis B Virus (HBV) (11.8%), alcohol (8.8%), combined HCV-HBV infection (5.9%), Von Gierke Disease (2.9%), primary biliary cirrhosis (2.9%), and autoimmune cirrhosis (2.9%). Six patients developed hepatocellular carcinoma before undergoing SLKT. Renal disease was caused by ADPKD (26.5%), diabetic nephropathy (14.7%), glomerulonephrites (29.4%), hepatorenal syndrome (8.8%) and other renal diseases (20.6%). Overall, 14.7% of patients was affected by Human Immunodeficiency Virus (HIV), 50% by hypertension and 41% by diabetes. Mean MELD at transplantation was 42 (39.2-46.5) and mean serum creatinine value in pre-emptive patients was 3.09 ±1.4 mg/dl. Mean of donors was 46.7±15.3 years and main cause of death was cranial trauma (47.1%), followed by cerebral haemorrhage (41.2%). Mean KDPI was 52% (22-63) and KDRI 1 (0.73-1.1). Mean time on waiting list was 2.8±1.2 years and half of patients was on dialysis maintenance before SLKT. Mean ischemia time were 6.5 ±1.3 and 12.3 ±2.1 hours for liver and kidney, respectively. Only one patient (2.9%) received double kidney transplantation. Primary induction agent was anti-IL2 receptor monoclonal antibodies (82.6%), thymoglobulin (13%) and with methylprednisolone (4.1%). Post SLKT, kidney early complication consisted of 3 delayed graft functions and 1 transplanctectomy in the only double kidney transplant recipient. At the end of the follow-up (8±4.1 years), mean creatinine was 1.44 ± 0.5 mg/dl and kidney survival accounted for 87.9%. Cox regression analysis showed recipient’ age as a protective factor (HR, 0.03; CI95%, 0.8-0.9) for kidney rejection and donor age as a risk factor (HR, 1.13,CI95% 1-1.1) for renal graft loss. Patient survival at 10 years was 91.2%. Two deaths were caused by infections (50%) and 2 by digestive haemorrhages (50%). SLKT recipients were confronted with 304 cadaveric donor KT recipients performed in the same transplant Center from 01/01/2006 to 12/31/2016. Statistical analysis showed that SLKT recipients had shorter waiting list, dialysis vintage and ischemia times. SLKT recipients had a major prevalence of diabetes and HCV infection but a lower prevalence of hypertension. DGF were less common in SLKT. Patient and graft survival a 1, 5 and 10 years did not show statistically significant differences between SLKT and KT. Conclusion Our analysis shows excellent kidney and patient survival in SLKT. SLKT and KT recipients had similar 1, 5 and 10-years patient and graft survival.

Purpose The extent of liver resection for the optimal treatment of hepatocellular carcinoma (HCC) is debated. The purpose of this study was to compare the impact of anatomic resection (AR) vs. parenchyma-sparing resection (PSR) on disease recurrence and patient survival. Methods We retrospectively analyzed patients with HCC who underwent liver resection from January 2001 to August 2015. Patients receiving AR or PSR were compared by a propensity score analysis (PSA) (caliper = 0.1). The primary outcomes were disease-free survival (DFS) and overall survival (OS) rates, and assessed by the Kaplan-Meier method. Results 455 consecutive patients were evaluated. After PSA 354 patient were studied (177 pairs for each group). The median follow-up time was 28.2 months. The median OS was 47.5 months (95% CI: 30.0–65.9) for AR and 56.5 months (95% CI 33.2–79.6) for PSR (p = 0.169). The median DFS was 29.2 months (95% CI 17.6–40.8) for AR and 24.8 months (95% CI: 15.2–34.2) for PSR (p = 0.337). The multivariate regression model showed that cirrhosis (HR 2.85, 95% CI: 1.53–5.32; p = 0.001), BCLC grade B (HR 4.15, 95% CI: 1.33–12.95; p = 0.014), microvascular invasion (HR 1.55, 95% CI: 1.03–2.31; p = 0.033), presence of satellitosis (HR 1.94, 95% CI: 1.25–3.01; p = 0.003), severe complications (HR 6.09, 95% CI: 2.26–16.40; p > 0.001) were independently associated with poor long-term oncologic outcomes. Conclusions The extent of resection did not significantly affect overall and disease-free survival while tumor characteristics and underlying liver function appeared significant determinants.

Background Hepatocellular carcinoma (HCC) is a common indication for associating liver partition with portal vein ligation for staged hepatectomy (ALPPS). Robotic liver resection has been done for HCC, but robotic ALPPS is a rare procedure. Methods To present three cases of totally robotic ALPPS in cirrhotic patients with HCC. Results Three cirrhotic male patients with HCC underwent ALPPS; the mean age was 54.3 years. MELD score was ≤9 and tumour size between 90 and 140 mm. The mean hypertrophy of the future liver remnant after the first stage was 77.5% and no postoperative liver failure was reported. Mean operative time of stage 1 was 7:30 h and of stage 2 was 4:37 h, without blood transfusion. The mean hospital stay for the first stage was 10 days and for the second stage was 9.3 days. No postoperative complication was recorded. Conclusions Robotic ALPPS in cirrhotic patients with HCC is safe and feasible.

Background Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. Methods This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. Results Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. Conclusion Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers’ experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.

BACKGROUND AND AIMS: United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down-staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down-staging by comparing two down-staging groups with (1) tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria and (2) “all-comers” (AC-DS) with initial tumor burden beyond UNOS-DS criteria versus patients always within Milan. APPROACH AND RESULTS: This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n = 3,276), UNOS-DS (n = 422), and AC-DS (n = 121). Median time to LT was 12.8 months in long wait regions, 6.5 months in mid wait regions (MWR), and 2.6 months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC-DS versus 16.9% of UNOS-DS and 14.4% of Milan (P = 0.002). Kaplan-Meier 3-year post-LT survival was 83.2% for Milan, 79.1% for UNOS-DS (P = 0.17 vs. Milan), and 71.4% for AC-DS (P = 0.04 vs. Milan). Within down-staging groups, risk of post-LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P = 0.005) and with alpha-fetoprotein (AFP) ≥ 100 ng/mL at LT (HR, 2.4; P = 0.009). The 3-year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS-DS, and 16.7% for AC-DS (P < 0.001). In down-staging groups, AFP ≥ 100 (HR, 2.6; P = 0.02) was the only independent predictor of HCC recurrence. CONCLUSIONS: Our results validated UNOS-DS criteria based on comparable 3-year survival between UNOS-DS and Milan groups. Additional refinements based on AFP and wait time may further improve post-LT outcomes in down-staging groups, especially given that reported 3-year recurrence was higher than in those always within Milan criteria.

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

Despite gaining wide consensus in the management of hepatocellular carcinoma (HCC), minimally invasive liver surgery (MILS) has been poorly investigated for its role in the setting of salvage liver transplantation (SLT). A multicenter retrospective analysis was carried out in 6 Italian centers on 211 patients with HCC who were initially resected with open (n=167) versus MILS (n=44) and eventually wait-listed for SLT. The secondary endpoint was identification of risk factors for posttransplant death and tumor recurrence. The enrolled patients included 211 HCC patients resected with open surgery (n=167) versus MILS (n=44) and wait-listed for SLT between January 2007 and December 2017. We analyzed the intention-to-treat survival of these patients. MILS was the most important protective factor for the composite risk of delisting, posttransplant patient death, and HCC recurrence (OR, 0.26; 95% confidence interval [CI], 0.11-0.63; P=0.003). MILS was also the only independent protective factor for the risk of post-SLT patient death (OR, 0.29; 95% CI, 0.09-0.93; P=0.04). After propensity score matching, MILS was the only independent protective factor against the risk of delisting, posttransplant death, and HCC recurrence (OR, 0.22; 95% CI, 0.07-0.75; P=0.02). On the basis of the current analysis, MILS seems protective over open surgery for the risk of delisting, posttransplant patient death, and tumor recurrence. Larger prospective studies balancing liver function and tumor stage are strongly favored to better clarify the beneficial effect of MILS for HCC patients eventually referred to SLT.

The performance of biliary reconstruction for restoring bilioenteric continuity after bile duct resection for hepatopancreatobiliary (HPB) tumors or during liver transplantation represents a basic skill for HPB and transplant surgeons. Such reconstruction may involve duct-to-duct anastomosis (or choledochocholedochostomy) or bilioenteric anastomosis, depending on the underlying disease, anatomy and indications. This chapter will describe the techniques of duct-to-duct and bilioenteric anastomoses focusing on their basic principles, techniques and application in oncological HPB surgery and liver transplantation.

The evolution of living donor liver transplantation (LDLT) has spurred advances in complex liver surgery. Refinements in living donor liver surgery along with a better understanding of the liver anatomy and live donor liver volumetry have been applied to resective hepatic surgery, improving outcomes after major liver resection. Likewise, advances in resective hepatic surgery has led to both the split-liver technique and LDLT. The overall result has been the development of innovative techniques, such as two-stage hepatectomy, and the association of liver partition and portal vein ligation, combining aspects of liver resection surgery and partial graft transplantation.

Despite the evolution of the surgical technique, minimizing blood loss during parenchymal transection still remains the major challenge of complex and extended hepatectomies. Total vascular exclusion (TVE) successfully applied in hepatic dissection during liver transplantation is now an accepted and commonly used technique in conventional liver surgery. A better understanding of the concepts related to liver transplantation such as ischemia-reperfusion injury and cold preservation of the liver graft has led to the development of technical improvements such as the combination of hypothermic liver perfusion and standard vascular exclusion. This chapter reviews the surgical and clinical advances in liver surgery using TVE, focusing on the technical progress that will allow further extension and application of these complex surgical procedures.

Minimally invasive surgery (MIS) has been increasingly used in the treatment of gastric cancer (GC). Laparoscopic gastrectomy (LG) has shown several advantages over open surgery in dealing with GC, although it is still considered a demanding procedure. Robotic gastrectomy (RG) is now being employed with increased frequency worldwide and has been reported to overcome some limitations of conventional LG. The aim of this updated meta-analysis is to compare surgical and oncological outcomes of RG versus LG for gastric cancer.A systematic review and meta-analysis was conducted using the PubMed, MEDLINE and Cochrane library database of published studies comparing RG and LG up to March 2020. The evaluated end-points were intra-operative, post-operative and oncological outcomes. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI), and a random-effect model was always applied.Forty retrospective studies describing 17,712 patients met the inclusion criteria. With respect to surgical outcomes, robotic compared with laparoscopic gastrectomy was associated with higher operating time [MD 44.73, (95%CI 36.01, 53.45) p 0.00001] and less intraoperative blood loss [MD -18.24, (95%CI -25.21, -11.26) p 0.00001] and lower rate of surgical complication in terms of Dindo-Clavien ≥ 3 classification [OR 0.66, (95%CI 0.49, 0.88) p = 0.005]. With respect to oncological outcomes, the RG group showed a significantly increased mean number of retrieved lymph nodes [MD 1.84, (95%CI 0.84, 2.84) p = 0.0003], but mean proximal and distal resection margin distance and the recurrence rate were not significantly different between the two approaches.With respect to safety, technical feasibility and oncological adequacy, robotic and laparoscopic groups were comparable, although the robotic approach seems to achieve better short-term surgical outcomes. Moreover, a higher rate of retrieved lymph nodes was observed in the RG group.

Summary Background Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging. Methods We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18–65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov , NCT01387503 . Findings Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4–11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60–85). 5-year tumour event-free survival was 76·8% (95% CI 60·8–96·9) in the transplantation group versus 18·3% (7·1–47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07–0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9–97·1) in the transplantation group versus 31·2% (16·6–58·5) in the control group (HR 0·32, 95% CI 0·11–0·92; p=0·035). The most common registered grade 3–4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation). Interpretation Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria. Funding Italian Ministry of Health.

The management of portosystemic shunts in liver transplant recipients relies on appropriate perioperative study. There are several strategies for shunt handling, ranging from preoperative interventional procedures to intraoperative surgical interruption or embolization. Appropriate management often results in a successful outcome, although wrong decisions could lead to serious consequences. Here, we report a liver transplant recipient with grade 2 portal vein thrombosis associated with 2 large portosystemic shunts (coronary and mesocaval), which were managed intraoperatively via thrombectomy without shunt ligation. Acute portal vein thrombosis developed early after transplant due to portal steal syndrome. The patient underwent a successful endovascular shunt embolization, with prompt restoration of hepatopetal portal flow and resolution of the portal steal. Use of interventional radiology in perioperative management of transplant patients has recently gained wider importance; our case reported here is particularly suggestive of the good outcomes of a multidisciplinary approach to a threatening complication such as postoperative acute portal vein thrombosis.

Machine perfusion (MP), which is re-emerging as an alternative to static cold storage (SCS) for preserving marginal liver grafts, prolongs preservation and promotes the possibility of graft reconditioning and viability testing. MP can be performed at different temperatures, ranging from hypothermia to normothermia. Hypothermic oxygenated perfusion (HOPE) promotes the resynthesis of adenine triphosphate and improves mitochondrial activity, thereby reducing oxidative stress upon reperfusion. However, the current shortage of methods to assess graft function under hypothermic conditions hinders liver selection during HOPE. Normothermic machine perfusion (NMP) reproduces physiologic circulation outside the body, which allows assessment of graft viability by measuring bile production, lactate clearance, and vascular flow. However, the transition from SCS to NMP carries the risk of reperfusion injury, and any system failure during NMP inevitably results in warm ischemia. Subnormothermic machine perfusion (SNMP) could overcome the limitations of HMP and NMP. The interplay between these technologies and hepatobiliary surgery is intriguing, but remains to be tested. Some studies have reported the use of MP during liver splitting and during ex situ liver resections, but further studies are required to clarify the role of MP in these situations.