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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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)., Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking., Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines., Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ )., Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings., Background: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined., Methods: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: (1) minor resections in the anterolateral (2, 3, 4b, 5, and 6) or (2) posterosuperior segments (1, 4a, 7, 8), and (3) major resections (≥3 contiguous segments). Propensity score matching was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+., Results: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After propensity score matching, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs 71.8%, P < 0.001) and TOLS+ (55% vs 50.4%, P = 0.026), less Pringle usage (39.1% vs 47.1%, P < 0.001), blood loss (100 vs 200 milliliters, P < 0.001), transfusions (4.9% vs 7.9%, P = 0.003), conversions (2.7% vs 8.8%, P < 0.001), overall morbidity (19.3% vs 25.7%, P < 0.001), and microscopically irradical resection margins (10.1% vs. 13.8%, P = 0.015), and shorter operative times (190 vs 210 minutes, P = 0.015). In the subgroups, RLS tended to have higher TOLS rates, compared with LLS, for minor resections in the posterosuperior segments (n = 431 per group, 75.9% vs 71.2%, P = 0.184) and major resections (n = 321 per group, 72.9% vs 67.5%, P = 0.086), although these differences did not reach statistical significance., Conclusions: While both produce excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS., Competing Interests: M.A.H. and M.G.B. received grants from Medtronic GmbH, Intuitive Surgical Inc., and Johnson & Johnson Medical GmbH for investigator-initiated studies. S.L.B. reported received fees from Baxter, Olympus, and Johnson & Johnson. M.S. reported received fees from Merck Serono GmbH, Bayer AG, ERBE Elektromedizin GmbH, Amgen Inc., AstraZeneca, Avateramedical GmbH, Johnson & Johnson Medical GmbH, TakedaPharmaceutical Limited, Olympus K.K., Medtronic GmbH, Intuitive Surgical Inc., Corzamedical, Baxter Int Inc. A.A.F. reported speaker’s honoraria from Bayer and Olympus. F.R. reported speakers' honoraria from Olympus. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study was to compare the outcomes of robotic limited liver resections (RLLR) versus laparoscopic limited liver resections (LLLR) of the posterosuperior segments., Background: Both laparoscopic and robotic liver resections have been used for tumors in the posterosuperior liver segments. However, the comparative performance and safety of both approaches have not been well examined in the existing literature., Methods: This is a post hoc analysis of a multicenter database of 5446 patients who underwent RLLR or LLLR of the posterosuperior segments (I, IVa, VII, and VIII) at 60 international centers between 2008 and 2021. Data on baseline demographics, center experience and volume, tumor features, and perioperative characteristics were collected and analyzed. Propensity score-matching (PSM) analysis (in both 1:1 and 1:2 ratios) was performed to minimize selection bias., Results: A total of 3510 cases met the study criteria, of whom 3049 underwent LLLR (87%), and 461 underwent RLLR (13%). After PSM (1:1: and 1:2), RLLR was associated with a lower open conversion rate [10 of 449 (2.2%) vs 54 of 898 (6.0%); P =0.002], less blood loss [100 mL [IQR: 50-200) days vs 150 mL (IQR: 50-350); P <0.001] and a shorter operative time (188 min (IQR: 140-270) vs 222 min (IQR: 158-300); P <0.001]. These improved perioperative outcomes associated with RLLR were similarly seen in a subset analysis of patients with cirrhosis-lower open conversion rate [1 of 136 (0.7%) vs 17 of 272 (6.2%); P =0.009], less blood loss [100 mL (IQR: 48-200) vs 160 mL (IQR: 50-400); P <0.001], and shorter operative time [190 min (IQR: 141-258) vs 230 min (IQR: 160-312); P =0.003]. Postoperative outcomes in terms of readmission, morbidity and mortality were similar between RLLR and LLLR in both the overall PSM cohort and cirrhosis patient subset., Conclusions: RLLR for the posterosuperior segments was associated with superior perioperative outcomes in terms of decreased operative time, blood loss, and open conversion rate when compared with LLLR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy (L-MH)., Background: Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it is unknown whether R-MH is superior to L-MH., Methods: This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience volume, perioperative outcomes, and tumor characteristics were collected and analyzed. Both 1:1 propensity-score matched (PSM) and coarsened-exact matched (CEM) analyses were performed to minimize selection bias between both groups., Results: A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss {PSM:200.0 [interquartile range (IQR):100.0, 450.0] vs 300.0 (IQR:150.0, 500.0) mL; P = 0.012; CEM:170.0 (IQR: 90.0, 400.0) vs 200.0 (IQR:100.0, 400.0) mL; P = 0.006}, lower rates of Pringle maneuver application (PSM: 47.1% vs 63.0%; P < 0.001; CEM: 54.0% vs 65.0%; P = 0.007) and open conversion (PSM: 5.1% vs 11.9%; P < 0.001; CEM: 5.5% vs 10.4%, P = 0.04) compared with L-MH. On subset analysis of 1273 patients with cirrhosis, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs 29.9%; P = 0.02; CEM 10.4% vs 25.5%; P = 0.02) and shorter postoperative stay [PSM: 6.9 (IQR: 5.0, 9.0) days vs 8.0 (IQR: 6.0 11.3) days; P < 0.001; CEM 7.0 (IQR: 5.0, 9.0) days vs 7.0 (IQR: 6.0, 10.0) days; P = 0.047]., Conclusions: This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application, and conversion to open surgery., Competing Interests: B.K.P.G. has received travel grants and honorariums from Johnson and Johnson, Olympus and Transmedic, the local distributor for the Da Vinci Robot. M.V.M. is a consultant for CAVA robotics LLC. J.P. reports a research grant from Intuitive Surgical Deutschland GmbH and personal fees or non-financial support from Johnson and Johnson, Medtronic, AFS Medical, Astellas, CHG Meridian, Chiesi, Falk Foundation, La Fource Group, Merck, Neovii, NOGGO, pharma-consult Peterson, and Promedicis. M. Schmelzle reports personal fees or other support outside of the submitted work from Merck, Bayer, ERBE, Amgen, Johnson and Johnson, Takeda, Olympus, Medtronic, and Intuitive. A.A.F. reports receiving speaker fees from Bayer. F.R. reports speaker fees and support outside the submitted work from Integra, Medtronic, Olympus, Corza, Sirtex, and Johnson and Johnson. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method., Background: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking., Methods: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS., Results: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin., Conclusions: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the effect of a liver transplantation (LT) program on the outcomes of resectable hepatocellular carcinoma (HCC)., Background: Surgical treatment of HCC includes both hepatic resection (HR) and LT. However, the presence of cirrhosis and the possibility of recurrence make the management of this disease complex and probably different according to the presence of a LT program., Methods: Patients undergoing HR for HCC between January 2005 and December 2019 were identified from a national database of HCC. The main study outcomes were major surgical complications according to the Comprehensive Complication Index, posthepatectomy liver failure (PHLF), 90-day mortality, overall survival, and disease-free survival. Secondary outcomes were salvage liver transplantation (SLT) and postrecurrence survival., Results: A total of 3202 patients were included from 25 hospitals over the study period. Three of 25 (12%) had an LT program. The presence of an LT program within a center was associated with a reduced probability of PHLF (odds ratio=0.38) but not with overall survival and disease-free survival. There was an increased probability of SLT when HR was performed in a transplant hospital (odds ratio=12.05). Among transplant-eligible patients, those who underwent LT had a significantly longer postrecurrence survival., Conclusions: This study showed that the presence of a LT program was associated with decreased PHLF rates and an increased probability to receive SLT in case of recurrence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR)., Background: There is limited published data to date on the best achievable outcomes after L-LR., Methods: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs., Results: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively., Conclusions: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves., Competing Interests: B.K.P.G. has received travel grants and honorarium from Johnson and Johnson, Olympus, and Transmedic the local distributor for the Da Vinci Robot. M.V.M. is a consultant for CAVA robotics LLC. J.P. reports a research grant from Intuitive Surgical Deutschland GmbH and personal fees or nonfinancial support from Johnson & Johnson, Medtronic, AFS Medical, Astellas, CHG Meridian, Chiesi, Falk Foundation, La Fource Group, Merck, Neovii, NOGGO, pharma-consult Peterson, and Promedicis. M.S. reports personal fees or other support outside of the submitted work from Merck, Bayer, ERBE, Amgen, Johnson & Johnson, Takeda, Olympus, Medtronic, and Intuitive. A.F. reports receiving speaker fees from Bayer. F.R. reports speaker fees and support outside the submitted work from Integra, Medtronic, Olympus, Corza, Sirtex, and Johnson & Johnson. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Indocyanine green (ICG) fluorescence has proven to be a high potential navigation tool during liver surgery; however, its optimal usage is still far from being standardized., Methods: A systematic review was conducted on MEDLINE/PubMed for English articles that contained the information of dose and timing of ICG administration until February 2021. Successful rates of tumor detection and liver segmentation, as well as tumor/patient background and imaging settings were also reviewed. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN)., Results: Out of initial 311 articles, a total of 72 manuscripts were obtained. The quality assessment of the included studies revealed usually low; only 9 articles got qualified as high quality. Forty articles (55%) focused on open resections, whereas 32 articles (45%) on laparoscopic and robotic liver resections. Thirty-four articles (47%) described tumor detection ability, and 25 articles (35%) did liver segmentation ability, and the others (18%) did both abilities. Negative staining was reported (42%) more than positive staining (32%). For tumor detection, majority used the dose of 0.5 mg/kg within 14 days before the operation day, and an additional administration (0.02-0.5 mg/kg) in case of longer preoperative interval. Tumor detection rate was reported to be 87.4% (range, 43%-100%) with false positive rate reported to be 10.5% (range, 0%-31.3%). For negative staining method, the majority used 2.5 mg/body, ranging from 0.025 to 25 mg/body. For positive staining method, the majority used 0.25 mg/body, ranging from 0.025 to 12.5 mg/body. Successful segmentation rate was 88.0% (range, 53%-100%)., Conclusion: The time point and dose of ICG administration strongly needs to be tailored case by case in daily practice, due to various tumor/patient backgrounds and imaging settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs., Background: The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet., Methods: A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed., Results: Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665-0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671-0.745)., Conclusions: The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study., Methods: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004)., Results: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T., Conclusions: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.

Objective: A novel and easy prognostic score based on the combination of pre-operatively available variables in patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) has been developed from a long waiting time (WT) training set and then validated in a short-WT set., Summary of Background Data: The role of radiological response to loco-regional therapies, alpha-fetoprotein modification, inflammatory markers, and length of WT has been recently shown to be important selection criteria for the risk of intention-to-treat (ITT)-death and recurrence., Methods: The training set consisted of 179 HCC patients listed for LT during the period January 2000 to December 2012 from the UCL Brussels Transplant Centre; the validation set consisted of 110 patients listed during the period January 2005 to December 2014 from the Ancona Liver Centre., Results: The proposed Time-Radiological-response-Alpha-fetoprotein-INflammation (TRAIN) score was the best predictor of microvascular invasion. A TRAIN score ≥1.0 excellently stratified both the investigated populations in terms of ITT and recurrence survivals. When compared with Milan criteria, the proposed score allowed obtaining an increase of potentially transplantable patients (+8.9% in training set and 24.6% in validation set) without additive recurrence risks., Conclusions: The proposed TRAIN score is an easy selection tool based on variables available before LT. This score enables the selection process to be refined in the 2 different scenarios of long and short WT. In case of longer WT, the score is better at predicting risk of death during the WT; in case of short WT, the score is better at identifying risk of post-LT recurrence.

The aim of the study was to evaluate the single-surgeon learning curve (SSLC) in laparoscopic liver surgery over an 11-year period with risk-adjusted (RA) cumulative sum control chart analysis.Laparoscopic liver resection (LLR) is a challenging and highly demanding procedure. No specific data are available for defining the feasibility and reproducibility of the SSLC regarding a consistent and consecutive caseload volume over a specified time period.A total of 319 LLR performed by a single surgeon between June 2003 and May 2014 were retrospectively analyzed. A difficulty scale (DS) ranging from 1 to 10 was created to rate the technical difficulty of each LLR. The risk-adjusted cumulative sum control chart (RA-CUSUM) analysis evaluated conversion rate (CR), operative time (OT) and blood loss (BL). Perioperative morbidity and mortality were also analyzed.The RA-CUSUM analysis of the DS identified 3 different periods: P1 (n = 91 cases), with a mean DS of 3.8; P2 (cases 92-159), with a mean DS of 5.3; and P3 (cases 160-319), with a mean DS of 4.7. P2 presented the highest conversion and morbidity rates with a longer OT, whereas P3 showed the best results (P < 0.001). Fifty cases were needed to achieve a significant decrease in BL. The overall morbidity rate was 13.8%; no perioperative mortality was observed.According to our analysis, at least 160 cases (P3) are needed to complete the SSLC performing safely different types of LLR. A minimum of 50 cases can provide a significant decrease in BL. Based on these findings, a longer learning curve should be anticipated to broaden the indications for LLR., Competing Interests: The authors have no conflicts of interest to disclose.

Background: FT program (FT) is a multimodal approach used to enhance postoperative rehabilitation and accelerate recovery. It was 1st described in open heart surgery, then modified and applied successfully in colorectal surgery. FT program was described in liver resection for the 1st time in 2008. Although the program has become widely accepted, it has not yet been considered the standard of care in liver surgery., Objectives: we performed this systematic review and meta-analysis to evaluate the impact of using the FT program compared to the traditional care (TC), on the main clinical and surgical outcomes for patients who underwent elective liver resection., Methods: PubMed/Medline, Scopus, and Cochran databases were searched to identify eligible articles that compared FT with TC in elective liver resection to be included in this study. Subgroup meta-analysis between laparoscopic and open surgical approaches to liver resection was also conducted. Quality assessment was performed for all the included studies. Odds ratios (ORs) and mean differences (MDs) were considered as a summary measure of evaluating the association in this meta-analysis for dichotomous and continuous data, respectively. A 95% confidence interval (CI) was reported for both measures. I was used to assess the heterogeneity across studies., Results: From 2008 to 2015, 3 randomized controlled trials (RCTs) and 5 cohort studies were identified, including 394 and 416 patients in the FT and TC groups, respectively. The length of hospital stay (LoS) was markedly shortened in both the open and laparoscopic approaches within the FT program (P < 0.00001). The reduced LoS was accompanied by accelerated functional recovery (P = 0.0008) and decreased hospital costs, with no increase in readmission, morbidity, or mortality rates. Moreover, significant results were found within the FT group such as reduced operative time (P = 0.03), lower intensive care unit admission rate (P < 0.00001), early bowel opening (P ≤ 0.00001), and rapid normal diet restoration (P ≤ 0.00001)., Conclusion: FT program is safe, feasible, and can be applied successfully in liver resection. Future RCTs on controversial issues such as multimodal analgesia and adherence rate are needed. Specific FT guidelines should be developed for liver resection.

Background: Tumor recurrence represents the main limitation of liver transplantation in patients with hepatocellular carcinoma (HCC) and can be favored by exposure to calcineurin inhibitors., Methods: We investigated the effect of an immunosuppressant schedule that minimizes the exposure to calcineurin inhibitors on patients transplanted for HCC to ascertain whether this can reduce the tumor recurrence rate. For this purpose, we conducted a matched-cohort study: 31 patients with HCC transplanted between 2004 and 2007 who received sirolimus as part of their immunosuppression (group A) were compared with a control group of 31 patients (group B) transplanted in the same period who had the same prognostic factors but were given standard immunosuppression based on tacrolimus., Results: Three-year recurrence-free survival was 86% in group A and 56% in group B (P=0.04). Although the prevalence of microvascular invasion G3-G4 grading and alpha-fetoprotein more than 200 ng/mL was identical in the two groups, exposure to tacrolimus was significantly higher in patients of group B (median, 8.54; range, 5.5-13.5) in comparison with those of group A (median, 4.6; range, 1.8-9.1) (P=0.0001)., Conclusions: By using sirolimus, exposure to calcineurin inhibitors can be minimized, reducing the risk of HCC recurrence.

Background and Aims: The outcome of hepatic resection in cirrhotic patients has improved remarkably in recent years with improved surgical techniques and perioperative care; however, the role of portal hypertension is still uncertain. The aim of this study was to elucidate surgical outcomes of hepatectomy in patients with portal hypertension., Methods: Data from 241 cirrhotic patients who underwent resection for hepatocellular carcinoma were retrospectively collected and analyzed: patients were divided into 2 groups according to the presence (n = 89) or absence (n = 152) of portal hypertension at the time of surgery. To overcome biases owing to the different distribution of covariates throughout the 2 groups, a one-to-one match was created using propensity score analysis: after match, intraoperative, and postoperative course and survival rates were analyzed., Results: Patients with portal hypertension experienced worse preoperative liver function (mean model for end-stage liver disease [MELD] score, 9.5 +/- 7.8 vs. 8.4 +/- 1.3; P = 0.001) and survival rates (P = 0.008) in comparison to those without portal hypertension: after one-to-one matching, patients with (n = 78) and without portal hypertension (n = 78) had the same preoperative characteristics and showed the same intraoperative course, postoperative occurrence of liver failure, morbidity, length of in-hospital stay and survival rates (P = ns in all cases). The only predictors of postoperative liver failure were MELD score (P = 0.001) and extent of hepatectomy (P = 0.005)., Conclusions: Faced with the same MELD score and extent of hepatectomy planning, presence of portal hypertension should not be considered as a contraindication for hepatic resection in cirrhotic patients.

Background: Split liver transplantation (SLT) for two adult recipients is still considered a challenging procedure, especially when subjected to model for end-stage liver disease (MELD)-based allocation criteria., Methods: Twenty-two SLTs were performed in adult recipients in a European center operating within a MELD-oriented system. Thirteen right-sided grafts and nine left-sided grafts were used. Right-sided grafts included 11 extended right grafts and two full right grafts. Left-sided grafts included six left lateral segment grafts and three full left grafts. Ninety-three percent of donors were allocated based on MELD score. Median graft-to-recipient body weight ratio was 1.53 (range 1.07-2.11) with right-sided grafts and 0.81 (range 0.67-1.11) with left-sided grafts. Liver cirrhosis (46%) and metabolic/genetic disorders (56%) were the main indications for transplant in recipients of right and left grafts, respectively., Results: Overall patient and graft survival were 90% and 86%. Patient survival was 84% in recipients of right grafts and 100% in recipients of left grafts. Graft survival was 84% and 89%, respectively. Vascular and biliary complications occurred in 14% and 4% of cases. Postoperative serum levels of total bilirubin were significantly higher in recipients of left-sided grafts versus right-sided grafts on postoperative days 7 and 14. Prothrombin activity was significantly lower in recipients of left-sided grafts versus right-sided grafts on postoperative days 3 and 7., Conclusions: SLT for two adult recipients can be successfully performed even using left lateral segments by assigning one graft according to MELD score, and with a more liberal allocation of the second graft.

Background: Focal and segmental glomerulosclerosis (FSGS) accounts for more than 10% of all cases of renal diseases leading to renal failure in children. After renal transplantation, 20% to 40% of FSGS relapse, frequently leading to renal loss.Plasmapheresis is considered the first option to treat relapses by several authors but is often ineffective. The anti-CD20 monoclonal antibody rituximab has been proposed as a possible treatment., Methods: We reviewed the effect of rituximab in seven children or young adults with pretransplant FSGS and relapse of proteinuria after transplantation who did not respond to intensive plasmapheresis., Results: After treatment, urine protein disappeared in three patients, was reduced by 70% in one patient and by 50% in one patient. No response was observed in one patient who had a quick deterioration of renal function and reached end-stage renal failure after 3 months. One additional patient developed a severe reaction a few minutes after the start of the first rituximab infusion., Conclusion: Rituximab is a possible option to treat some resistant cases of FSGS with relapsing proteinuria after transplantation. It is important that therapy is started early after evidence of failure of plasmapheresis, before sclerosis develops in the glomeruli. The response to treatment can occur after several months. During the follow-up period, CD19 cells should be monitored carefully, and additional rituximab infusions considered to maintain B-cell depletion.

Objective: We assessed the effect of tacrolimus on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) and compared it with that of the other calcineurin inhibitor, cyclosporine., Introduction: HCC recurrence after LT can be favored by overexposure to cyclosporine. Tacrolimus is now the most widely used main immunosuppressant after LT; its possible effect on HCC recurrence has never been investigated., Materials and Methods: One hundred and thirty nine HCC patients who had LT were reviewed; 60 of them were administered tacrolimus, and 79, cyclosporine. The exposure to the drugs was calculated with the trapezoidal rule in each patient, using blood levels measured after transplantation and compared with HCC recurrence together with several clinical and pathologic risk factors., Results: HCC recurred in 12 of the 60 (20%) patients under tacrolimus in comparison with that in 9 of the 79 (11.4%) patients under cyclosporine; however, the proportion of poorly differentiated and more advanced tumors was significantly higher in the tacrolimus group than in the cyclosporine group. Exposure to tacrolimus was 11.6 +/- 1.5 ng/mL in patients with recurrence and 8.6 +/- 1.7 ng/mL in those without recurrence (P < 0.001). The optimal cut-off values of exposure identified with receiver operating characteristics analysis to categorize the risk of recurrence were 10 ng/mL for tacrolimus (area under the curve (AUC) = 0.913) and 220 ng/mL for cyclosporine (AUC = 0.752). In the tacrolimus group, high drug exposure independently predicted recurrence (P = 0.005). Multivariate analysis, including all patients (tacrolimus + cyclosporine) characterized higher exposure to immunosuppression (P = 0.01), alpha-fetoprotein levels (P = 0.001), tumor grading (P = 0.009), and microvascular invasion (P = 0.04) as independent predictors of HCC recurrence., Conclusions: Just as it is with cyclosporine, overexposure to tacrolimus increases the risk of HCC recurrence after LT. Careful management of calcineurin inhibitors is recommended in HCC patients.

Objective: To examine modifications of acid-base balance of cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Summary Background Data: Acid-base disorders are frequently observed in cirrhotics; however, modifications during hepatectomy and their impact on prognosis have never been investigated., Methods: Two hundred and two hepatectomies for HCC on cirrhosis were reviewed. Arterial blood samples were collected immediately before and at the end of resection. Preresection and postresection acid-base parameters were compared and related to patient characteristics and postoperative course. The accuracy of acid-base parameters in predicting postoperative liver failure, defined as an impairment of liver function after surgery that led to patient death or required transplantation, was assessed using receiver operating characteristic analysis (ROC)., Results: All patients showed a significant reduction in pH, bicarbonate, and base excess at the end of hepatectomy (P < 0.001 in all cases), worsened by intraoperative blood loss (P < 0.010) and preoperative Model for end-stage liver disease score > or =11 (P < 0.010). ROC curve analysis identifies patients with postresection bicarbonate <19.4 mmol/L at high risk for liver failure (50.0%) whereas levels >22.1 mmol/L did not lead to the event (0%; P < 0.001). Postoperative prolongation of prothrombin time and increases in bilirubin, creatinine, and morbidity were also more frequent in patients with lower postresection bicarbonate, resulting in a longer in-hospital stay., Conclusion: In cirrhotic patients, a trend toward a relative acidosis can be expected during surgery and is worsened by the severity of the underlying liver disease and intraoperative blood loss. Postresection bicarbonate level lower than 19.4 mmol/L is an adverse prognostic factor.

Objective: We sought to compare the experience of 2 different surgical units in the treatment of hepatocellular carcinoma (HCC) on cirrhosis with resection or percutaneous radiofrequency ablation (RFA), respectively., Summary Background Data: When allowed by the hepatic functional reserve, surgery is the therapy for HCC on cirrhosis; alternative treatments are proposed because of the high tumor recurrence rate after resection. RFA is being widely adopted to treat HCC., Methods: Over a 4-year period, 79 cirrhotics with HCC underwent resection in 1 surgical unit (group A) and another 79 had RFA at a different unit (group B). Patient selection, operative mortality, hospital stay, and 1- and 3-year overall and disease-free survival were analyzed., Results: Group A (surgery): mean follow-up was 28.9 +/- 17.9 months; operative mortality was 3.8%, mean hospital stay 9 days; 1- and 3-year survival were, respectively, 83 and 65%. One- and 3-year disease-free survival were 79 and 50%. Group B (RFA): mean follow-up was 15.6 +/- 11.7 months. Mean hospital stay was 1 day (range 1-8). One- and 3-year survival were 78 and 33%; 1- and 3-year disease-free survival were 60 and 20%. Overall and disease-free survival were significantly higher in group A (P = 0.002 and 0.001). The advantage of surgery was more evident for Child-Pugh class A patients and for single tumors of more than 3 cm in diameter. Results were similar in 2 groups for Child-Pugh class B patients, Conclusions: RFA has still to be confirmed as an alternative to surgery for potentially-resectable HCCs.

Background: Ganciclovir is a highly effective and relatively safe drug to treat cytomegalovirus (CMV) infection in liver transplant patients; CMV resistance to ganciclovir is progressively emerging due to the extensive use of the drug in transplant and AIDS patients; CMV pp65 antigenemia allows early diagnosis of CMV infection and quantitation of the viral load; preemptive antigenemia-guided therapy of CMV infection can prevent CMV disease but the threshold of antigenemia value above which treatment has to be instituted is unclear., Methods: To demonstrate the safety of abstention from preemptive treatment in the presence of low levels of antigenemia 77 consecutive liver transplant recipients were prospectively evaluated. Antigenemia was tested twice a week from transplantation until discharge, then once a week until the third postoperative month. In absence of risk factors for CMV disease, namely donor positive/recipient negative CMV serology, treatment with antibodies to lymphocytes and retransplantation, only patients with antigenemia of more than 50 or symptoms possibly related to CMV infection had preemptive treatment., Results: A total of 32 patients had at least one positive antigenemia test with a value less than 50; 22 (68.7%) spontaneously cleared the virus, 3 were treated with i.v. ganciclovir for the presence of fever, and the other 7 (21,8%) progressed to values of antigenemia of more than 50 and were treated even if asymptomatic. No CMV disease was observed in these patients., Conclusion: CMV antigenemia less than 50 in liver transplant recipients with low and intermediate risk for CMV disease does not mandate preemptive ganciclovir treatment. Close surveillance with repeated determination of antigenemia until its negativization and careful clinical and laboratory monitoring is advisable.