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Background Laparoscopic redo resections for colorectal metastases are poorly investigated. This study aims to explore long-term results after second, third, and fourth resections. Material and methods Prospectively updated databases of primary and redo laparoscopic liver resections in six European HPB centers were analyzed. Procedure-related overall survival after first, second, third, and fourth resections were evaluated. Furthermore, patients without liver recurrence after first liver resection were compared to those with one redo, two or three redo, and patients with palliative treatment for liver recurrence after first laparoscopic liver surgery. Survival was calculated both from the date of the first liver resection and from the date of the actual liver resection. In total, 837 laparoscopic primary and redo liver resections performed in 762 patients were included (630 primary, 172 first redo, 29 second redo, and 6 third redo). Patients were bunched into four groups: Group 1—without hepatic recurrence after primary liver resection (n = 441); Group 2—with liver recurrence who underwent only one laparoscopic redo resection (n = 154); Group 3—with liver recurrence who underwent two laparoscopic redo resections (n = 29); Group 4—with liver recurrence who have not been found suitable for redo resections (n = 138). Results No significant difference has been found between the groups in terms of baseline characteristics and surgical outcomes. Rate of positive resection margin was higher in the group with palliative recurrence (group 4). Five-year survival calculated from the first liver resection was 67%, 62%, 84%, and 7% for group 1, 2, 3, and 4, respectively. Procedure-specific 5-year overall survival was 50% after primary laparoscopic liver resection, 52% after the 1st reoperation, 52% after the 2nd, and 40% after the 3rd reoperation made laparoscopic. Conclusions Multiple redo recurrences can be performed laparoscopically with good long-term results. Liver recurrence does not aggravate prognosis as long as the patient is suitable for reoperation.

Objective The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. Background Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. Methods A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. Results Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. Conclusions The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.

Background Pancreatic duct occlusion (PDO) without anastomosis is a technique proposed to mitigate the clinical consequences of postoperative pancreatic fistulas (POPF) after pancreaticoduodenectomy. The aim of this study was to appraise the morbidity following PDO through a systematic review and meta-analysis. Methods A systematic search of MEDLINE, Embase, and Web Of Science identified studies reporting outcomes of PDO following pancreaticoduodenectomy. Pooled prevalence rates of postoperative complications and mortality were computed using random-effect modeling. Meta-regression analyses were performed to examine the impact of moderators on the overall estimates. Results Sixteen studies involving 1000 patients were included. Pooled postoperative mortality was 2.7%. A POPF was reported in 29.7% of the patients. Clinically relevant POPFs occurred in 13.5% of the patients, while intra-abdominal abscess and haemorrhages occurred in 6.7% and 5.5% of the patients, respectively. Re-operation was necessary in 7.6% of the patients. Postoperatively new onset diabetes occurred in 15.8% of patients, more frequently after the use of chemical substances for PDO (p = 0.003). Conclusions PDO is associated with significant morbidity including new onset of post-operative diabetes. The risk of new onset post-operative diabetes is associated with the use of chemical substance for PDO. Further evidence is needed to evaluate the potential benefits of PDO in patients at high risk of POPF.

Background The ideal treatment approach for colorectal cancer (CRC) with synchronous liver metastases (SCRLM) remains debated. We performed a network meta-analysis (NMA) comparing the ‘bowel-first’ approach (BFA), simultaneous resection (SIM), and the ‘liver-first’ approach (LFA). Methods A systematic search of comparative studies in CRC with SCRLM was undertaken using the Embase, PubMed, Web of Science, and CENTRAL databases. Outcome measures included postoperative complications, 30- and 90-day mortality, chemotherapy use, treatment completion rate, 3- and 5-year recurrence-free survival, and 3- and 5-year overall survival (OS). Pairwise and network meta-analysis were performed to compare strategies. Heterogeneity was assessed using the Higgins I2 statistic. Results One prospective and 43 retrospective studies reporting on 10 848 patients were included. Patients undergoing the LFA were more likely to have rectal primaries and a higher metastatic load. The SIM approach resulted in a higher risk of major morbidity and 30-day mortality. Compared to the BFA, the LFA more frequently resulted in failure to complete treatment as planned (34% versus 6%). Pairwise and network meta-analysis showed a similar 5-year OS between LFA and BFA and a more favorable 5-year OS after SIM compared to LFA (odds ratio 0.25–0.90, p = 0.02, I2 = 0%), but not compared to BFA. Conclusion Despite a higher tumor load in LFA compared to BFA patients, survival was similar. A lower rate of treatment completion was observed with LFA. Uncertainty remains substantial due to imprecise estimates of treatment effects. In the absence of prospective trials, treatment of stage IV CRC patients should be individually tailored.

Objective To evaluate the learning curve of an expert liver transplantation surgeon approaching fully laparoscopic living donor left lateral sectionectomy (L-LLS) under proctorship. Background Laparoscopic liver resections necessitate a long learning curve trough a stepwise fulfillment of difficulties. L-LLS requires expertise in both living donor liver transplantation and advanced laparoscopic liver surgery. There is currently no data about the learning curve of L-LLS. Methods A total of 72 pure L-LLS were included in this study. A Broken line model was used to identify the periods of the learning curve. A CUSUM analysis of the operative time was performed to evaluate improvements of outcomes with time. To evaluate the relationship between operative time and progressive number of procedures, a linear regression model was applied. A receiver operating characteristic (ROC) curve was carried out to identify the cutoff for completion of the learning curve. Results Operative time decreased with the progressive increase of procedures. Two cutoffs and 3 different periods were identified: cases 1 to 22, cases 23 to 55, and cases 56 to 72. A significant decrease in blood loss and operative time was noted. The CUSUM analysis showed an increase in operative time in the first period, a stable duration in the second period, and a decrease in the last. Blood loss was significantly associated with an increase in operative time (P = 0.003). According to the ROC curve, the learning curve was completed after 25 procedures. Conclusions L-LLS is a safe procedure that can be standardized and successfully taught to surgeons with large experience in donor hepatectomy through a proctored learning curve.

Background: There is no clear consensus over the optimal width of resection margin for colorectal liver metastases (CRLM), with evolving definitions alongside the advances on the management of the disease. In addition, data on the impact of resection margin after laparoscopic liver resection are still scarce. Methods: Prospectively maintained databases of patients undergoing open or laparoscopic CRLM resection in 7 European tertiary hepatobiliary referral centres were reviewed. After propensity score matching (PSM), the influence of 1mm and wider margins on OS and DFS were evaluated in open and laparoscopic cohorts. Results: After PSM, 648 patients were comparable in each group. The incidence of positive margins (< 1mm) was similar in open and laparoscopic groups (17% vs 13%, p = 0,142). Margins < 1mm were associated with shorter RFS in open (12 vs 26months, p = 0.042) and in laparoscopic group (13 vs 23, p = 0,002). Margins < 1mm were associated with shorter OS in open (36 vs 57months, p = 0.027), but not in laparoscopic group (49 vs 60, p = 0,177). Subgroups with margins ≥ 1mm (1–4mm, 5–9mm, ≥ 10mm) presented similar RFS in open (p = 0,251) or laparoscopic cohorts (p = 0.117), as well as similar OS in open (p = 0.295) or laparoscopic cohorts (p = 0.908). In the presence of liver recurrence, repeat liver resection was performed in 70 (30%) patients in the open group and 88 (48%) in the laparoscopic group (p < 0.001). Conclusions: Our study suggests that a positive resection margin (less than 1mm) width does not impact OS after laparoscopic resection of CRLMs as it does in open liver resection. However, a positive margin continues to affect RFS in open and laparoscopic resection. Wider margins than 1mm do not seem to improve oncological results in open or laparoscopic surgery.

Introduction: A stronger evidence level is needed to confirm the benefits and limits of laparoscopic hemihepatectomies. Methods: Laparoscopic and open hemihepatectomies from nine European referral centers were compared after propensity score matching (right and left hemihepatectomies separately, and benign and malignant diseases sub-analyses). Results: Five hundred and forty-five laparoscopic hemihepatectomies were compared with 545 open. Laparoscopy was associated with reduced blood loss (P < 0.001), postoperative stay (P&nbsp

Background & Aims: Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. Methods: Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. Results: A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count

Objective Evaluating the perioperative outcomes of minimally invasive (MIV) donor hepatectomy for adult live donor liver transplants in a large multi-institutional series from both Eastern and Western centers. Background Laparoscopic liver resection has become standard practice for minor resections in selected patients in whom it provides reduced postoperative morbidity and faster rehabilitation. Laparoscopic approaches in living donor hepatectomy for transplantation, however, remain controversial because of safety concerns. Following the recommendation of the Jury of the Morioka consensus conference to address this, a retrospective study was designed to assess the early postoperative outcomes after laparoscopic donor hepatectomy. The collective experience of 10 mature transplant teams from Eastern and Western countries was reviewed. Methods All centers provided data from prospectively maintained databases. Only left and right hepatectomies performed using a MIV technique were included in this study. Primary outcome was the occurrence of complications using the Clavien-Dindo graded classification and the Comprehensive Complication Index during the first 3 months. Logistic regression analysis was used to identify risk factors for complications. Results In all, 412 MIV donor hepatectomies were recorded including 164 left and 248 right hepatectomies. Surgical technique was either pure laparoscopy in 175 cases or hybrid approach in 237. Conversion into standard laparotomy was necessary in 17 donors (4.1%). None of the donors died. Also, 108 experienced 121 complications including 9.4% of severe (Clavien-Dindo 3-4) complications. Median Comprehensive Complication Index was 5.2. Conclusions This study shows favorable early postoperative outcomes in more than 400 MIV donor hepatectomy from 10 experienced centers. These results are comparable to those of benchmarking series of open standard donor hepatectomy.

Background. There is a growing interest in left lateral sectionectomy for donor hepatectomy. No data are available concerning the safety of the robotic (ROB) approach. Methods. A retrospective comparative study was conducted on 75 consecutive minimally invasive donor hepatectomies. The first 25 ROB procedures performed from November 2018 to July 2019 were compared with our first (LAP1) and last 25 (LAP2) laparoscopic cases performed between May 2013 and October 2018. Short-term donors and recipients' outcomes were analyzed. Results. No conversions were noticed in ROB whereas 2 conversions (8%) were recorded in LAP1 and none in LAP2. Blood loss was significantly less in ROB compared with LAP1 (P ≤ 0.001) but not in LAP2. Warm ischemia time was longer in ROB (P ≤ 0.001) with respect to the other groups. Operative time was similar in the 3 groups (P = 0.080); however, the hospital stay was shorter in ROB (P = 0.048). The trend in operative time in ROB was significantly shorter compared to LAP1 and LAP2: linear R20.478, P≤0.001; R20.012, P = 0.596; R30.004, P = 0.772, respectively. Donor morbidity was nihil in ROB, similar in LAP1 and LAP2 (n=3%-12%; P = 0.196). ROB procedures required less postoperative analgesia (P = 0.002). Recipient complications were similar for all groups (P = 0.274), and no early retransplantations were recorded. Conclusions. Robotic left lateral sectionectomy for donor hepatectomy is a safe procedure with results comparable to the laparoscopy in terms of donor morbidity and overall recipients' outcome when the procedure is performed by experts. Certainly, its use is currently very limited.

Background: When oncologically feasible, avoiding unnecessary splenectomies prevents patients who are undergoing distal pancreatectomy (DP) from facing significant thromboembolic and infective risks. Methods: A systematic search of MEDLINE, Embase, and Web Of Science identified 11 studies reporting outcomes of 323 patients undergoing intended spleen-preserving minimally invasive robotic DP (SP-RADP) and 362 laparoscopic DP (SP-LADP) in order to compare the spleen preservation rates of the two techniques. The risk of bias was evaluated according to the Newcastle–Ottawa Scale. Results: SP-RADP showed superior results over the laparoscopic approach, with an inferior spleen preservation failure risk difference (RD) of 0.24 (95% CI 0.15, 0.33), reduced open conversion rate (RD of −0.05 (95% CI −0.09, −0.01)), reduced blood loss (mean difference of −138 mL (95% CI −205, −71)), and mean difference in hospital length of stay of −1.5 days (95% CI −2.8, −0.2), with similar operative time, clinically relevant postoperative pancreatic fistula (ISGPS grade B/C), and Clavien–Dindo grade ≥3 postoperative complications. Conclusion: Both SP-RADP and SP-LADP proved to be safe and effective procedures, with minimal perioperative mortality and low postoperative morbidity. The robotic approach proved to be superior to the laparoscopic approach in terms of spleen preservation rate, intraoperative blood loss, and hospital length of stay.

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.

Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child–Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child–Pugh B cirrhosis. Methods Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. Results Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child–Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P Conclusion Patients without preoperative portal hypertension and Child–Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Post hepatectomy liver failure (PHLF) could occur even though an adequate liver volume is preserved. Liver function is not strictly related to the volume and the necessity to pre-operatively predict the future liver remnant (FLR) function is emerging, together with the wide spreading of techniques, aiming to optimize the FLR. The aim of this study was to systematically review all the available tests, to pre-operatively assess the liver function and to estimate the risk of PHLF. A systematic literature research of Medline, Embase, Scopus was performed in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, to identify all the studies available for pre-operative liver function tests to assess the risk of PHLF and/or complications. From the 1122 references retrieved, 79 were included in the review. Dynamic functional tests, such as indocyanine green test (ICG), could evaluate only global liver function, with no definition of functional capacity of the remnant. Magnetic resonance imaging (MRI) with liver-specific contrast agents enables both liver function and volume evaluation; the absence of ionizing radiation showed a better patient’s compliance. Nuclear imaging studies as hepatobiliary scintigraphy (HBS) present the unique ability to allow a precise evaluation of the segmental liver function of the remnant liver. Liver volume could overestimate liver function. Several liver function tests are available to evaluate the risk of PHLF in the pre-operative setting. However, no single test alone could accurately predict PHLF. Pre-operative combination between a dynamic quantitative test, such as ICG, with MRI or HBS, should enable a more complete functional evaluation. Functional tests to predict PHLF should be chosen according to patient’s characteristics, disease, and center experience.

The objective of the study was to identify and to evaluate the impact of educational interventions to learn and train liver surgery outside the operating room. A systematic literature search was conducted using PubMed, Web of Science, Embase, and ERIC databases from inception to September 2019 according to the PRISMA guidelines. Studies describing and assessing outcomes of educational interventions in liver surgery, outside the operating room, were included. Neither language nor date of publication restriction was applied. Methodological quality was appraised using NOS-E (Newcastle-Ottawa Scale for Education), and the level of evidence was evaluated based on GRADE (Grades of Recommendation Assessment, Development, and Evaluation) standards. Of the 10,403 screened abstracts, 53 articles were eligible for inclusion, comprising 27 descriptive studies (50.9%), 14 case series assessing any relevant outcome (26.4%), 8 non-randomized controlled trials (15.1%), and 4 randomized controlled studies (7.5%). Almost half (26/53) of the studies did not include any participants, while the remainder of the publications (27/53) involved 1306 learners. The majority of the studies focused on cognitive knowledge (31/53) and/or psychomotor skills training (24/53). Only one publication assessed affective skills. The GRADE score was very low or low in most articles (46/53). Five studies were scored high (5-6) according to NOS-E. Two studies reported data regarding the reliability and validity of employed assessment tools. High-quality studies, particularly well-designed randomized controlled trials that evaluate the effectiveness of simulation-based training on learner behavior and patient outcomes in liver surgery, are still lacking. Forthcoming studies should use robust assessment tools supported by validity evidence.

When the standard arterial reconstruction is not feasible during liver transplantation (LT), aorto-hepatic arterial reconstruction (AHAR) can be the only solution to save the graft. AHAR can be performed on the infrarenal (IR) or supraceliac (SC) tract of the aorta, but the possible effect on outcome of selecting SC versus IR reconstruction is still unclear. One hundred and twenty consecutive patients who underwent liver transplantation with AHAR in six European centres between January 2003 and December 2018 were retrospectively analysed to ascertain whether the incidence of hepatic artery thrombosis (HAT) was influenced by the type of AHAR (IR-AHAR vs. SC-AHAR). In 56/120 (46.6%) cases, an IR anastomosis was performed, always using an interposition arterial conduit. In the other 64/120 (53.4%) cases, an SC anastomosis was performed; an arterial conduit was used in 45/64 (70.3%) cases. Incidence of early (

In the original article Moritz Schmelzle’s last name is spelled wrong. It is correct as reflected here.

Annals of surgical oncology (2020). doi:10.1245/s10434-019-08192-z, Published by Springer, Berlin [u.a.]

BACKGROUND: To assess long-term oncologic outcomes of robotic-assisted liver resection (RLR) for colorectal cancer (CRC) metastases as compared to a propensity-matched cohort of laparoscopic liver resections (LLR). Although safety and short-term outcomes of RLR have been described and previously compared to LLR, long-term and oncologic data are lacking. METHODS: A retrospective study was performed of all patients who underwent RLR and LLR for CRC metastases at six high-volume centers in the USA and Europe between 2002 and 2017. Propensity matching was used to match baseline characteristics between the two groups. Data were analyzed with a focus on postoperative and oncologic outcomes, as well as long-term recurrence and survival. RESULTS: RLR was performed in 115 patients, and 514 patients underwent LLR. Following propensity matching 115 patients in each cohort were compared. Perioperative outcomes including mortality, morbidity, reoperation, readmission, intensive care requirement, length-of-stay and margin status were not statistically different. Both prematching and postmatching analyses demonstrated similar overall survival (OS) and disease-free survival (DFS) between RLR and LLR at 5 years (61 vs. 60% OS, p = 0.87, and 38 vs. 31% DFS, p = 0.25, prematching; 61 vs. 60% OS, p = 0.78, and 38 vs. 44% DFS, p = 0.62, postmatching). CONCLUSIONS: Propensity score matching with a large, multicenter database demonstrates that RLR for colorectal metastases is feasible and safe, with perioperative and long-term oncologic outcomes and survival that are largely comparable to LLR.

Recent studies have indicated that patients with prior bariatric surgery (BS) are at risk for developing alcohol use disorder. We explored patient demographics and impact on liver disease severity in 11 patients with prior BS listed for transplantation due to alcoholic liver disease, and compared these with 177 patients without BS. BS patients were younger with a female predominance and presented with more severe decompensation. The timeframe between diagnosis, listing, and transplantation was significantly shorter in patients with prior BS. The incidence of post-transplant complications and 3-year survival rate was comparable. In conclusion, alcoholic liver disease with rapid decompensation may develop after BS, warranting rapid identification with referral to a transplant center. Attention should be paid to pre-surgery screening for alcohol overuse risk factors.

Background Recent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC. Methods 526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing. Results Overall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence. Conclusions All validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862. ispartof: ANNALS OF SURGERY vol:272 issue:5 pages:855-862 ispartof: location:United States status: published

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.

BACKGROUND: The laparoscopic approach to liver resection has experienced exponential growth in recent years; however, its application is still under debate and objective, evidence-based guidelines for its safe future progression are needed. OBJECTIVE: The aim of this study was to perform a systematic review and meta-analysis comparing the short- and long-term outcomes of laparoscopic and open liver resections for hepatocellular carcinoma (HCC). METHODS: To identify all the comparative manuscripts reporting on laparoscopic and open liver resection for HCC, all published English-language studies with more than 10 cases were screened. In addition to the primary meta-analysis, four specific subgroup analyses were performed on patients with Child-Pugh A cirrhosis, resections for solitary tumors, and those undergoing minor and major resections. The quality of the studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) methodology and the Newcastle-Ottawa Scale. RESULTS: From the initial 361 manuscripts, 28 were included in the meta-analysis. Five of these 28 manuscripts were specific to patients with Child-Pugh A cirrhosis (321 cases), 11 focused on solitary tumors (1003 cases), 16 focused on minor resections (1286 cases), and 3 focused on major resections (164 cases). Three manuscripts compared 1079 cases but could not be assigned to any of the above subanalyses. In general terms, short-term outcomes were favorable when using a laparoscopic approach, especially in minor resections. The only advantage seen with an open approach was reduced operative time during major liver resections. No differences in long-term outcomes were observed between the approaches. CONCLUSIONS: Laparoscopic liver resection for HCC is feasible and offers improved short-term outcomes, with comparable long-term outcomes as the open approach.

Objectives Liver retransplant is considered the only hope for patients with irreversible graft failure after primary transplant. In most Western centers, retransplantis done mainly from deceased donors; so far, only few published studies have reported on outcomes of liver retransplant with living donors. In this study, our aim was to analyze the outcomes of living-donor liver retransplant. Materials and methods Patients who underwent liver retransplant between February 2011 and February 2019 were included in the study. Preoperative, operative, and postoperative data were analyzed. Results from 2 patient groups were compared: liver retransplant with living donors and liver retransplant with deceased donors. Results Thirty-two patients underwent liver retransplant (21 adult and 11 pediatric patients). The most common indications for liver retransplant were hepatic artery thrombosis (28.5%) and primary graft nonfunction (23.8%) in adults and hepatic artery thrombosis (45.5%) and chronic rejection (36.4%) in pediatric patients. Seventeen retransplant patients (53.1%) required early retransplant (within 1 mo), mainly due to hepatic artery thrombosis (52.9%) and primary graft nonfunction (35.3%). Late retransplant was mainly due to chronic rejection (40%) and recurrence of primary disease (26.7%). Seventeen patients (53.1%) underwent living-donor retransplant, and 5 donors underwent robotic right hepatectomy. Graft and patient survival rates at 1, 3, and 5 years were 81.3% for living-donor and 51.4% for deceased-donor liver retransplant recipients (P = .08). On multivariate analyses, we observed significant differences between both groups in pretransplant Model for End-Stage Liver Disease and Pediatric End-Stage Liver Disease scores (P = .05), preoperative international normalized ratio (P = .012), and cold ischemia time (P = .046). Conclusions The use of living donors for liver retransplant, despite its technical demand, was shown to be a safe and feasible option, especially when there is scarcity of deceased donors.

Background In general surgery residency, hepatobiliary training varies significantly across the world. The aim of this study was to establish an international consensus among hepatobiliary surgeons on components of a hepatobiliary curriculum for general surgery residents. Methods A three-round modified Delphi technique was employed. Fifty-two hepatobiliary surgeons involved in general surgery training programs were invited. An initial questionnaire was developed by a group of experts in hepatobiliary and educational research after a systematic literature review. It comprised 90 statements about knowledge, technical skills, attitudes, and postoperative care. Panelists could add or alter items. The survey was delivered electronically and the panel was instructed to score the items based on 5-point Likert scale. Consensus was reached when at least 80% of panelists agreed on a statement with Cronbach's alpha value >0.8. Results Forty-one (79%) experts have participated. Sixteen panelists are based in Asia, 14 in Europe, and 11 in the Americas. Eighty percent of all proposed skills (81/101) were considered fundamental including knowledge (39/43), technical skills (16/32), attitude (15/15), and postoperative care (11/11). Conclusion An international consensus was achieved on components of a hepatobiliary curriculum. Acquiring broad knowledge is fundamental during residency. Advanced liver resection techniques require specialized hepatobiliary training.

Objective. Robotic liver surgery (RLS) has emerged as a feasible alternative to laparoscopic or open resections with comparable perioperative outcomes. Little is known about the oncologic adequacy of RLS. The purpose of this study was to investigate the long-term oncologic outcomes for patients undergoing RLS for primary hepatobiliary malignancies. Methods. We performed an international, multicenter, retrospective study of patients who underwent RLS for hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), or gallbladder cancer (GBC) between 2006 and 2016. Age, gender, histology, resection margin status, extent of surgical resection, disease-free survival (DFS), and overall survival (OS) were retrospectively collected and analyzed. Results. Of the 61 included patients, 34 (56%) had RLS performed for HCC, 16 (26%) for CC, and 11 (18%) for GBC. The majority of resections were nonanatomical or segmental resections (39.3%), followed by central hepatectomy (18%), left-lateral sectionectomy (14.8%), left hepatectomy (13.1%), right hepatectomy (13.1%), and right posterior segmentectomy (1.6%). RO resection was achieved in 94% of HCC, 68% of CC, and 81.8% of GBC patients. Median hospital stay was 5 days, and conversion to open surgery was needed in seven patients (11.5%). Grade III-IV Dindo-Clavien complications occurred in seven patients with no perioperative mortality. Median follow-up was 75 months (95% confidence interval 36-113), and 5-year OS and DFS were 56 and 38%, respectively. When stratified by tumor type, 3-year OS was 90% for HCC, 65% for GBC, and 49% for CC (p = 0.01). Conclusions. RLS can be performed for primary hepatobiliary malignancies with long-term oncologic outcomes comparable to published open and laparoscopic data.

Laparoscopic liver surgery is expanding worldwide, but further evidence is needed to assess safety and efficacy of laparoscopic major hepatectomy. The study analyzes perioperative outcomes of pure laparoscopic versus open major hepatectomies matched by the propensity score method. From 2005 to 2017, 268 major hepatectomies were performed of which 73 were laparoscopic. After a 1:1 propensity score matching, 59 laparoscopic right and left hepatectomies were compared to 59 open. The matching was based on age, gender, year of procedure, BMI, ASA score, underlying liver disease, previous abdominal surgery, type of hepatectomy, preoperative chemotherapy, number, dimension and nature of lesions. An intention-to-treat analysis and a per-protocol analysis were carried out. Mean surgical time was 315 min in the laparoscopic group and 292.5 min in the open group (p = 0.039); conversion rate in laparoscopy was 20.3%; blood loss was 480 ml (50–3000) versus 550 ml (50–2600), respectively, for laparoscopic and open (p = 0.577). Lengths of postoperative analgesia and hospital stay were shorter in the laparoscopic group (p = 0.0001 and 0.024, respectively). Postoperative complications occurred in 11.9% of laparoscopic cases and in 25.4% of open cases (p = 0.098). Median Comprehensive Complication Index was 26.2 (8.7–54.2) in the open group versus 20.9 (8.7–66.2) in open (p = 0.368). Per-protocol analysis showed a better trend in favor of laparoscopy concerning surgical time. Laparoscopic major hepatectomies are safe and feasible procedures allowing a similar complication rate with a shorter hospital stay and diminished postoperative pain with respect to the standard approach.

OBJECTIVE: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery.BACKGROUND: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination.METHODS: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements.RESULTS: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee.CONCLUSION: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

Esophageal cancer (EC) remains an aggressive disease with a poor survival. Management of metastatic EC is limited to palliative chemotherapy (CT). Scientific contributions regarding the role of surgery are scarce and controversial. We analysed outcome of surgically treated metastatic EC patients.We retrospectively identified surgically treated metastatic EC patients from our esophagectomy database. The aim of this study was to evaluate surgical complications, pathological response, oncological outcome and mean survival of these aggressively treated stage IV cancer patients.Twelve stage IV patients with disease presentation limited to outfield lymph node (LN) and/or liver metastasis were treated with an aggressive multimodality treatment including surgery. Mean age was 58 years (75% male, 75% Adenocarcinomas). Median postoperative hospital stay was 15 d. Radiological anastomotic leakage occurred in one patient. In hospital, mortality was nil. Complete resection was achieved in all but one. Metastatic recurrence occurred in 64% of R0 resected patients. At date of censoring, after a median follow-up of 22 months, 50% of the surgical resected patients are still alive and 33% are free of disease recurrence. Kaplan-Meier curves show a possibility to long-term survival after aggressive multimodality therapy including surgery.In selected metastatic EC patients, multimodality treatment including surgery has an acceptable surgical outcome with a potentially long-term survival.

Background: With improvements in living donor liver transplantation (LDLT) techniques and the increased experience of surgeons in laparoscopic major liver resection, laparoscopic donor hepatectomy is performed increasingly. Therefore, expert opinion on this procedure is required. Objective: The study aimed to report the current status and summarize the expert opinion on laparoscopic donor hepatectomy. Methods: An expert consensus meeting was held on September 8, 2016, in Seoul, Korea. Results: Laparoscopic donor left lateral sectionectomy could be considered the standard practice in pediatric LDLT. In adult LDLT, laparoscopy-assisted donor hepatectomy or left hepatectomy is potentially the next need, requiring more evidence for becoming standard practice. Laparoscopic donor right hepatectomy is still in the developmental stage, and more supporting evidence is required. Waving the cost consideration, the robotic approach could be a valid alternative for the suitable approaches of laparoscopy. Conclusions: Laparoscopic donor hepatectomy is increasing its role in both pediatric and adult LDLT. However, for major donor hepatectomy, more evidence is needed.

Background Evidence on the value of laparoscopic liver resections (LLR) for hepatocellular carcinoma (HCC) and severe cirrhosis is still lacking. The aim of this study is to assess surgical and oncological outcomes of LLR in cirrhotic HCC patients. Methods The analysis included 403 LLR for HCC from seven European centres. 333 cirrhotic and 70 non-cirrhotic patients were compared. A matched comparison was performed between 100 Child-Pugh A and 25 Child-Pugh B patients. Results There was no difference in blood loss (250 vs. 250 mL, p 0.465) and morbidity (28.6 vs. 26.4%, p 0.473) between cirrhotics and non-cirrhotics, and liver-specific complications were similar (12.8 vs. 12%, p 0.924). The sub-analysis revealed similar perioperative outcomes in either Child-Pugh A or B patients. Noteworthy, ascitis (11 vs. 12%, p 0.562) and liver failure (3 vs. 4%, p 0.595) were not different. ASA score (OR 1.76, p 0.034) and conversion (OR 2.99, p 0.019) were risk factors for major morbidity. Despite lower recurrence-free survival in cirrhotics (43 vs. 55 months, p 0.034), overall survival was similar to noncirrhotic patients (84 vs. 76.5, p 0.598). Conclusion LLR for HCC appear equally safe in cirrhotic and non-cirrhotic patients, and the advantages can be witnessed in those with advanced cirrhosis. Severe comorbidities and conversion should be considered risk factors for complications-rather than the severity of cirrhosis and portal hypertension-when liver resection is performed laparoscopically. Such results may be of great interest to liver surgeons and hepatologists when deciding on the management of HCC within cirrhosis.

Objectives: The purpose of this study was to evaluate the feedback of participants upon laparoscopic liver surgery (LLS) course on Thiel-embalmed human bodies. Methods: From 2010 to 2017, ten LLS masterclasses have been organized by the Department of Hepatobiliary Surgery at Ghent University Hospital. A 23-question anonymous survey was electronically sent to 119 participants between November 2017 and January 2018, exploring their characteristics and asking for evaluation of the course. The obstacles for implementing LLS in their centers have been assessed. Results: Sixty-four surgeons (53.8%) responded to the survey; 42 (65.6%) were employed at a university hospital; and 39 (60.9%) were in the first decade of their practice as a consultant surgeon. Forty-three (67.2%) surgeons reported an increased percentage of LLS cases afterward. Training on Thiel cadavers was considered superior (49.2%) to other training options including proctoring in the operating room (34.9%), virtual reality (6.3%), video training (4.8%) and practicing on pigs (4.8%). Obstacles identified contained inadequate training, patient’s referral pattern, financial issues, lack of dedicated surgical team and time constrains. Conclusions: This survey revealed that a structured short-time program incorporating interactive discussion, live operations and hands-on training on human bodies under proctorship may enhance efficient training in laparoscopic liver surgery. In a step forward for upcoming courses, the importance of team building has to be addressed.

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 μg), followed by a 2.5 mL/h infusion (somatostatin: 250 μg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

Laparoscopic liver resection demands expertise and a long learning curve. Resection of the posterosuperior segments is challenging, and there are no data on the learning curve. The aim of this study was to evaluate the learning curve for laparoscopic resection of the posterosuperior segments.A cumulative sum (CUSUM) analysis of the difficulty score for resection was undertaken using patient data from four specialized centres. Risk-adjusted CUSUM analysis of duration of operation, blood loss and conversions was performed, adjusting for the difficulty score of the procedures. A receiver operating characteristic (ROC) curve was used to identify the completion of the learning curve.According to the CUSUM analysis of 464 patients, the learning curve showed an initial decrease in the difficulty score followed by an increase and, finally, stabilization. More patients with cirrhosis or previous surgery were operated in the latest phase of the learning curve. A smaller number of wedge resections and a larger number of anatomical resections were performed progressively. Dissection using a Cavitron ultrasonic surgical aspirator and the Pringle manoeuvre were used more frequently with time. Risk-adjusted CUSUM analysis showed a progressive decrease in operating time. Blood loss initially increased slightly, then stabilized and finally decreased over time. A similar trend was found for conversions. The learning curve was estimated to be 40 procedures for wedge and 65 for anatomical resections.The learning curve for laparoscopic liver resection of the posterosuperior segments consists of a stepwise process, during which accurate patient selection is key.La resección hepática laparoscópica exige experiencia y una larga curva de aprendizaje. La resección de los segmentos posterosuperiores (PS) es un reto, y no hay datos acerca de la curva de aprendizaje (learning curve, LC). El objetivo de este estudio fue evaluar la LC de la resección laparoscópica de los segmentos PS. MÉTODOS: Se realizó un análisis CUSUM de la puntuación de dificultad (difficulty score, DS) de la resección en pacientes de 4 centros especializados. La técnica CUSUM se ajustó al riesgo (risk-adjusted CUSUM, RA-CUSUM) para el tiempo operatorio, la pérdida de sangre y las conversiones a cirugía abierta ajustando según la DS de los procedimientos. Se utilizó una curva ROC para identificar el momento en el que se consideró que la LC había sido completada.De acuerdo con el análisis CUSUM de los 464 pacientes incluidos, se observó una DS baja al inicio, que posteriormente se fue incrementando hasta llegar a una estabilización. En la última fase de la LC se operaron más pacientes con cirrosis o cirugía previa. De forma progresiva se fueron reduciendo el número de resecciones hepáticas en cuña y aumentando el de resecciones anatómicas. A lo largo del tiempo se introdujo el CUSA y la maniobra de Pringle con mayor frecuencia. El RA-CUSUM mostró una reducción progresiva del tiempo operatorio. La pérdida de sangre inicialmente aumentó ligeramente, luego se estabilizó y finalmente disminuyó con el tiempo. Una tendencia similar se observó para las conversiones. La LC se estimó en 40 casos para las resecciones en cuña y en 65 casos para las resecciones anatómicas. CONCLUSIÓN: La LC de la resección hepática laparoscópica de los segmentos PS es un proceso paso a paso durante el cual la selección del paciente es clave.

Objective: To compare the learning curves of the self-taught ‘‘pioneers’’ of laparoscopic liver surgery (LLS) with those of the trained ‘‘early adopters’’ in terms of short- and medium-term patient outcomes to establish if the learning curve can be reduced with specific training. Summary of Background Data: It is expected that a wider adoption of a laparoscopic approach to liver surgery will be seen in the next few years. Current guidelines stress the need for an incremental, stepwise progression through the learning curve in order to minimize harm to patients. Previous studies have examined the learning curve in Stage 2 of the IDEAL paradigm of surgical innovation; however, LLS is now in stage 3 with specific training being provided to surgeons. Methods: Using risk-adjusted cumulative sum analysis, the learning curves and short- and medium-term outcomes of 4 ‘‘pioneering’’ surgeons from stage 2 were compared with 4 ‘‘early adapting’’ surgeons from stage 3 who had received specific training for LLS. Results: After 46 procedures, the short- and medium-term outcomes of the ‘‘early adopters’’ were comparable to those achieved by the ‘‘pioneers’’ following 150 procedures in similar cases. Conclusions: With specific training, ‘‘early adapting’’ laparoscopic liver surgeons are able to overcome the learning curve for minor and major liver resections faster than the ‘‘pioneers’’ who were self-taught in LLS. The findings of this study are applicable to all surgical specialties and highlight the importance of specific training in the safe expansion of novel surgical practice.

BACKGROUND: The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. METHODS: This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. DISCUSSION: DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. TRIAL REGISTRATION: The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 . ispartof: BMC GASTROENTEROLOGY vol:19 issue:1 ispartof: location:England status: published