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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: We analyzed the use of a self-expandable absorbable biliary stent (SEABS) to reduce biliary complications in liver transplant (LT)., Background: Complications related to biliary anastomosis are a still a challenge in LT with a high impact on the patient outcomes and hospital costs., Methods: This non-randomized prospective study was conducted between July 2019 and September 2023 in adult LT patients with duct-to-duct biliary anastomoses. The primary endpoint was to assess early biliary complications at 90 days in LT patients with intraoperative SEABS versus no SEABS. We also compared overall biliary complications, costs and SEABS- adverse effects related., Results: A total of 158 patients were included, 78 with SEABS and 80 no-SEABS (22 T-tube and 58 no-stent). There were no adverse effects related to SEABS. Early biliary complications (23.8 vs 2.6%, P <0.001) and hospital stay (19 vs 15 days, P= 0.001) were higher in no-SEABS. No-SEABS group required 63 ERCPs and 13 surgeries (including 2 LT) versus 35 ERCPs and 2 surgeries in SEABS group. After PSM between SEABS (n=58) vs no-SEABS (n=58), early biliary complications (40% vs 0%, P<.001) were higher in no-SEABS group. T-tube had more early biliary complications (22.7% vs 5%, P=0.23) compared SEABS high-risk biliary anastomosis. SEABS excess cost per patient was lower compared to T-Tube and no-stent (6.988€ vs 17.992€ vs 36.364€, P=0.036 and P=0.002, respectively)., Conclusions: SEABS during biliary anastomosis in LT is feasible with no adverse effects and avoid the T-tube in high-risk biliary anastomoses. It use has been associated with less early biliary complications, hospital costs and reoperations or interventional treatments for biliary complications resolution., Competing Interests: Authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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: To propose to our community a common language about extreme liver surgery., Background: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers., Methods: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages., Results: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery., Conclusion: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy., Competing Interests: Conflicts of interest: The authors declared no conflict of interest. No third-party financial funds or materials were accepted or necessary for execution of this research project., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Background and Aims: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate., Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis., Results: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively)., Conclusions: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 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: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities., Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures., Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient., Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months., Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The author reports no conflicts of interest.

Abstract: This forum summarizes the proceedings of the joint European Surgical Association (ESA)/American Surgical Association (ASA) symposium on Quality and Outcome Assessment for Surgery that took place in Bordeaux, France, as part of the celebrations of the 30th anniversary of the ESA. Three presentations focused on a) the main messages from the Outcome4Medicine Consensus Conference, which took place in Zurich, Switzerland, in June 2022, b) the patient perspective, and c) benchmarking were hold by ESA members and discussed by ASA members in a symposium attended by members of both associations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute., Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics., Results: Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P =0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P =0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P =0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P =0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria., Conclusions: This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies., Background: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown., Methods: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion., Results: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism., Conclusions: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons., Background: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking., Methods: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers., Results: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes., Conclusion: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The potential benefit related to laparoscopic liver surgery (LLS) for colorectal liver metastases outcomes is not well known., Materials and Methods: Serum cytokines associated with Th1 (tumor necrosis factor-α) and Th2 [interleukin (IL)-10 and IL-6] phenotypes were measured in 36 patients operated on for colorectal liver metastases by open liver surgery (OLS) and LLS. Measurements were performed at 3 time points: 1 day before surgery, day 3 postoperative, and 1 month postoperative. We compared the postoperative inflammatory response influence between LLS and OLS on long-term outcomes., Results: In both groups, only IL-6 levels on day 3 postoperative were higher than those measured preoperatively and at 1 month. Comparing the tumor necrosis factor-α levels between the LLS and OLS groups, preoperative (7.28 vs. 2.36), day 3 (7.99 vs. 4.08) and 1 month (7.39 vs. 1.99) postoperative levels were higher in the OLS group (P<0.01, <0.01, and <0.01, respectively). In contrast, IL-10 levels were higher in the LLS group preoperatively (7.51 vs. 4.57) and on day 3 postoperative (13.40 vs. 4.57) (P=0.03 and 0.01, respectively). A cut-off IL-6 level of ≥4.41 in the first month was associated with a higher risk of recurrence (logrank=4.8, P=0.02)., Conclusions: Both LLS and OLS induce an initial increase in IL-6 that normalizes one month after surgery, showing a similar pattern. In addition, a cut-off IL-6 value of 4.41 pg/mL was established, with a higher concentration at 1 month postoperative possibly related to a higher risk or recurrence., Competing Interests: The author declares no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We present a new variant of partial-ALPPS (p-ALPPS) "Tourniquet partial-ALPPS (Tp-ALPPS)", with the aim of reducing aggressiveness during stage 1., Summary Background Data: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) results in liver regeneration in only 9 days. Due to its high initial morbidity and mortality, less aggressive variants were designed., Methods: A new surgical variant of ALPPS was designed consisting in introducing a Kelly forceps from the base of the liver, crossing the liver parenchyma through an avascular area. A 3-mm Vicryl (V152; Ethicon, Somerville, New Jersey, USA) tape is passed, and the tourniquet is then knotted. Six patients operated on by this new Tp-ALPPS surgical technique were compared to 6 patients operated on by Tourniquet ALPPS (T-ALPPS)., Results: There were no differences in volume increase at 10 days. During stage 1, blood losses and transfusion rates tended to be lower in the Tp-ALPPS group, without statistical differences. Surgical time was shorter in the Tp-ALPPS group than in T-ALPPS (90 min versus 135 min) (p < 0.023). In stage 2, blood losses and transfusion were similar in both groups, but surgical time tended to be higher in the Tp-ALPPS group, which could be related to the surgical technique performed. There were no differences in morbidity and mortality., Conclusions: Tp-ALPPS achieved a similar increase in volume as T-ALPPS but with a shorter stage 1 surgical and similar morbidity and mortality., Competing Interests: The authors have nothing to disclose and declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe., Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients., Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers., Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries., Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS., Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking., Methods: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis., Results: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001)., Conclusions: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Introduction: Obesity represents a risk factor in case of major hepatectomy, because the future liver remnant (FLR) must be proportional with body weight. To avoid post-hepatectomy liver failure, and further increase the ratio between FLR and body weight, we performed a bariatric procedure in the first stage of the ALPPS technique., Patient Concerns: Fifty-four-year-old woman, with morbid obesity (BMI 58.5) and type II diabetes mellitus, was scheduled for a major hepatectomy due to multiple colorectal liver metastases DIAGNOSIS:: Six months before, the patient was diagnosed with colorectal cancer and synchronous liver metastases. She was initially treated with sigmoidectomy and chemotherapy. After partial response of the liver metastases, we considered a liver resection but the FLR was very low, especially in relation to her BMI., Intervention: We planned a novel approach and, for the first time, we performed a sleeve gastrectomy during the first stage of Tourniquet ALPPS (T-ALPPS). After achieving an adequate FLR, we successfully completed the major hepatectomy during the second stage of T-ALPPS., Outcome: The association between sleeve gastrectomy and T-ALPPS produced an increase of FLR/body weight ratio up to 0.8 that allowed completing a right trisectionectomy in the second stage of ALPPS. The major hepatectomy was performed without severe complications, and several months after surgery the patient is still alive without any recurrence Conclusion: Despite obesity represents a risk factor involved in the carcinogenesis, the role of the bariatric surgery in the oncological setting is not well established. In this clinical case, we benefited from the weight loss produced by bariatric surgery combined with an effective hypertrophy technique and chemotherapy. These findings suggest that bariatric surgery could be useful for obese patients with liver malignancy and need for extended hepatectomy.

Objective: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been tested in various indications and clinical scenarios, leading to steady improvements in safety. This report presents the current status of ALPPS., Summary Background Data: ALPPS offers improved resectability, but drawbacks are regularly pointed out regarding safety and oncologic benefits., Methods: During the 12th biennial congress of the European African-Hepato-Pancreato-Biliary Association (Mainz, Germany, May 23-26, 2017) an expert meeting "10th anniversary of ALPP" was held to discuss indications, management, mechanisms of regeneration, as well as pitfalls of this novel technique. The aim of the meeting was to make an inventory of what has been achieved and what remains unclear in ALPPS., Results: Precise knowledge of liver anatomy and its variations is paramount for success in ALPPS. Technical modifications, mainly less invasive approaches like partial, mini- or laparoscopic ALPPS, mostly aiming at minimizing the extensiveness of the first-stage procedure, are associated with improved safety. In fibrotic/cirrhotic livers the degree of future liver remnant hypertrophy after ALPPS appears some less than that in noncirrhotic. Recent data from the only prospective randomized controlled trial confirmed significant higher resection rates in ALPPS with similar peri-operative morbidity and mortality rates compared with conventional 2-stage hepatectomy including portal vein embolization. ALPPS is effective reliably even after failure of portal vein embolization., Conclusions: Although ALPPS is now an established 2-stage hepatectomy additional data are warranted to further refine indication and technical aspects. Long-term oncological outcome results are needed to establish the place of ALPPS in patients with initially nonresectable liver tumors.

Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome., Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome., Methods: ALPPS centers of the International ALPPS Registry having performed ≥10 cases over a period of ≥3 years were assessed for 90-day mortality and major interstage complications (≥3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies., Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P < 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers., Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.

Objectives: To create a prediction model identifying futile outcome in ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) before stage 1 and stage 2 surgery., Background: ALPPS is a 2-stage hepatectomy, which incorporates parenchymal transection at stage 1 enabling resection of extensive liver tumors. One of the major criticisms of ALPPS is the associated high mortality rate up to 20%., Methods: Using the International ALPPS Registry, a risk analysis for futile outcome (defined as 90-day or in-hospital mortality) was performed. Futility was modeled using multivariate regression analysis and a futility risk score formula was computed on the basis of the relative size of logistic model regression coefficients., Results: Among 528 ALPPS patients from 38 centers, a futile outcome was observed in 47 patients (9%). The pre-stage 1 model included age 67 years or older [odds ratio (OR) = 5.7], and tumor entity (OR = 3.8 for biliary tumors) as independent predictors of futility from multivariate analysis. For the pre-stage 1 model scores of 0, 1, 2, 3, 4 and 5 were associated with futile risk of 2.7%, 4.9%, 8.6%, 15%, 24%, and 37%. The pre-stage 2 model included major complications (grade ≥ 3b) after stage 1 (OR = 3.4), serum bilirubin (OR = 4.4), serum creatinine (OR = 5.4), and cumulative pre-stage 1 risk score (OR = 1.9). The model predicted futility risk of 5%, 10%, 20%, and 50% for patients with scores of 3.9, 4.7, 5.5, and 6.9, respectively., Conclusions: Both models have an excellent prediction to assess the individual risk of futile outcome after ALPPS surgery and can be used to avoid futile use of ALPPS.

Objectives: The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2., Background Data: ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown., Methods: Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality., Results: Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive., Conclusions: This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.

Objectives: To assess safety and outcomes of the novel 2-stage hepatectomy, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), using an international registry., Background: ALPPS induces accelerated growth of small future liver remnants (FLR) to allow curative resection of liver tumors. There is concern about safety based on reports of higher morbidity and mortality., Methods: A Web-based data entry system was created with password access and data pseudoencryption (NCT01924741). All patients with complete 90-day data were included. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications and mortality and volume growth of the FLR., Results: Complete data were available for 202 patients. A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median starting standardized future liver remnants of 21% increased by 80% within a median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications including mortalities (Clavien-Dindo≥IIIb) occurred in 27% of patients. Independent factors for severe complications were red blood cell transfusion [odds ratio (OR), 5.2), ALPPS stage I operating time greater than 300 minutes (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of Pringle maneuver, and histologic changes led to less volume growth. In patients younger than 60 years with CRLM, 90-day mortality was similar to conventional 2-stage hepatectomies for CRLM., Conclusions: This is the first analysis of the ALPPS registry showing that ALPPS has increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.