Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation.

BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.

Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

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

Limitations in resectability of colorectal liver metastases 2020 - A systematic approach for clinicians and patients.

Colorectal liver metastases (CRLM) affect over 50 % of all patients with colorectal cancer, which is the second leading cause of cancer in the western world. Resection of CRLM may provide cure and improves survival over chemotherapy alone. However, resectability of CLRM has to be decided in multidisciplinary tumor boards and is based on oncological factors, technical factors and patient factors. The advances of chemotherapy lead to the abolition of contraindications to resection in favor of technical resectability, but somatic mutations and molecular subtyping may improve selection of patients for resection in the future. Technical factors center around anatomy of the lesions, volume of the remnant liver and quality of the liver parenchymal. Multiple strategies have been developed to overcome volume limitations and they are reviewed here. The least investigated topic is how to select the right patients among an elderly and frail patient population for the large variety of technical options specifically for bi-lobar CRLM to keep 90-day mortality as low as possible. The review is an overview over the current state-of-the art and a systematic guide to the topic of resectability of CRLM for both clinicians and patients.

Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients.

BACKGROUND: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. METHODS: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. RESULTS: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. CONCLUSION: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.

Comparative incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients versus kidney or kidney-pancreas waitlisted patients: A single-center study.

BACKGROUND: COVID-19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes. METHODS: In this retrospective cohort study, we assembled kidney or kidney-pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney-pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory-confirmed COVID-19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network. RESULTS: COVID-19 was identified in 62 of 887 kidney or kidney-pancreas transplant recipients and 20 of 434 kidney or kidney-pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID-19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116). CONCLUSIONS: Our study provides single-center data and an informatics approach that can be used to inform the design of multicenter studies.

Simultaneous portal and hepatic vein embolization before major liver resection.

BACKGROUND: Regenerative liver surgery expands the limitations of technical resectability by increasing the future liver remnant (FLR) volume before extended resections in order to avoid posthepatectomy liver failure (PHLF). Portal vein rerouting with ligation of one branch of the portal vein bifurcation (PVL) or embolization (PVE) leads to a moderate liver volume increase over several weeks with a clinical dropout rate of 20-40%, mostly due to tumor progression during the waiting period. Accelerated liver regeneration by the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) was poised to overcome this limitation by reduction of the waiting time, but failed due increased perioperative complications. Simultaneous portal and hepatic vein embolization (PVE/HVE) is a novel minimal invasive way to induce rapid liver growth without the need of two surgeries. PURPOSE: This article summarizes published results of PVE/HVE and analyzes what is known about its efficacy to achieve resection, safety, and the volume changes induced. CONCLUSIONS: PVE/HVE holds promise to induce accelerated liver regeneration in a similar safety profile to PVE. The demonstrated accelerated hypertrophy may increase resectability. Randomized trials will have to compare PVE/HVE and PVE to determine if PVE/HVE is superior to PVE.

Improving the Safety of Major Resection for Hepatobiliary Malignancy: Portal Vein Embolization and Recent Innovations in Liver Regeneration Strategies.

PURPOSE OF REVIEW: For three decades, portal vein embolization (PVE) has been the "gold-standard" strategy to hypertrophy the anticipated future liver remnant (FLR) in advance of major hepatectomy. During this time, CT volumetry was the most common method to preoperatively assess FLR quality and function and used to determine which patients are appropriate surgical candidates. This review provides the most up-to-date methods for preoperatively assessing the anticipated FLR and summarizes data from the currently available strategies used to induce FLR hypertrophy before surgery for hepatobiliary malignancy. RECENT FINDINGS: Functional and physiological imaging is increasingly replacing standard CT volumetry as the method of choice for preoperative FLR assessment. PVE, associating liver partition and portal vein ligation, radiation lobectomy, and liver venous deprivation are all currently available techniques to hypertrophy the FLR. Each strategy has pros and cons based on tumor type, extent of resection, presence or absence of underlying liver disease, age, performance status, complication rates, and other factors. Numerous strategies can lead to FLR hypertrophy and improve the safety of major hepatectomy. Which is best has yet to be determined.

Avoiding postoperative mortality after ALPPS-development of a tumor-specific risk score for colorectal liver metastases.

BACKGROUND: ALPPS is a two-stage hepatectomy that induces more rapid liver growth compared to conventional strategies. This report aims to establish a risk-score to avoid adverse outcomes of ALPPS only for patients with colorectal liver metastases (CRLM) as primary indication for ALPPS. METHODS: All patients with CRLM included in the ALPPS registry were included. Risk score analysis was performed for 90-day mortality after ALPPS, defined as death within 90 days after either stage. Two risk scores were generated i.e. one for application before stage-1, and one for application before stage-2. Logistic regression analysis was performed to establish the risk-score. RESULTS: In total, 486 patients were included, of which 35 (7%) died 90 days after stage-1 or 2. In the stage-1 risk score, age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.9) and total center-volume (OR 2.4) were included. For the stage-2 score age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.8), bilirubin 5 days after stage-1 >50 µmol/L (OR 2.4), and stage-1 morbidity grade IIIA or higher (OR 6.3) were included. CONCLUSIONS: The CRLM risk-score to predict mortality after ALPPS demonstrates that older patients with small remnant livers in inexperienced centers, especially after experiencing morbidity after stage-1 have adverse outcomes. The risk score may be used to restrict ALPPS to low-risk patient populations.

Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a Clinical Trial.

BACKGROUND: Randomized controlled trials (RCTs) data demonstrate that sevoflurane postconditioning improves clinical outcomes of liver resection with inflow occlusion, presumably due to hepatocyte protection from ischemic injury. However, mechanisms remain unclear. This study examines liver biopsy samples obtained in an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane attenuates hepatocyte apoptosis. METHODS: Messenger ribonucleic acid (mRNA) of pro- and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined in hepatic biopsies obtained during the RCT. Hepatic stellate cells (HSCs) and hepatocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to evaluate the effect of sevoflurane postconditioning on apoptosis. The role of HSC as a potential apoptosis trigger in hepatocytes through the production of reactive oxygen species induced by H/R was explored by transferring supernatants from H/R-exposed HSC to hepatocytes as target cells. RESULTS: In patients of the RCT, the Bax/Bcl2 mRNA ratio in liver tissue was markedly decreased in the sevoflurane arm (25% ± 21% reduction; P = .001). In vitro, H/R increased reactive oxygen species production in HSC by 33% ± 16% (P = .025), while it was abolished in the presence of sevoflurane (P < .001). In hepatocytes, caspase was minimally activated by H/R. However, incubation of hepatocytes with supernatants of HSC, previously exposed to H/R, increased caspase activity by 28% ± 13% (P < .001). When exposed to supernatants from HSC undergoing sevoflurane postconditioning, caspase activation in hepatocytes was reduced by 20% ± 9% (P < .001), similarly to the sevoflurane effect on the BAX/Bcl2 mRNA ratio in the liver samples. CONCLUSIONS: The study shows that sevoflurane postconditioning affects apoptosis of hepatocytes after ischemia-reperfusion injury in patients. It also demonstrates that HSC may be the effector cells of sevoflurane protection.

Perioperative surgery- and anaesthesia-related risks of laparoscopic Roux-en-Y gastric bypass - a single centre, retrospective data analysis.

BACKGROUND: Conservative obesity treatment often leads to limited results. Bariatric surgery is highly efficient, but the candidates are at risk of developing perioperative complications. Bariatric outcomes have been well described in the past, but there are only few reports of perioperative outcomes. The aim of this study was to evaluate the incidence of anaesthetic and surgical complications of Roux-en-Y bypass. METHODS: Data of all adult patients, who underwent primary Roux-en-Y gastric bypass surgery between 1/2006 and 12/2013 at the University Hospital Zurich were analysed. Using our clinical database, anaesthetic and surgical complications during the first 30 days after surgery were analysed and risk factors determined by multivariate analysis. RESULTS: Seven hundred eleven patients (72% female, median age 40 years) were analysed. Overall, surgical complications occurred in 34% patient, while complications attributable to anaesthesia occurred in 37%. Post-operative nausea and vomiting (PONV) were observed in 34%, intubation-related complications in 4%, and delayed extubation in 2% of our patients. Within the first 30 days after surgery, 22% of the patients presented with an infection. Gastrointestinal complications were found in 8%, and bleeding complications in 3%. Anaesthesia complications were less common in older patients and in patients anaesthetized with a volatile anaesthetic. Severe complications were more common in patients with a lower body mass index (BMI) and with longer surgery. The risk to develop a postoperative infection was higher in diabetic patients. CONCLUSION: Roux-en-Y bariatric surgery has few anaesthetic complications, the most common is PONV. PONV is more common in younger patients and not more common with volatile anaesthetics. Major complications are overall rare and occur in patients with lower BMI and longer surgery, likely reflecting more difficult procedures.

[Colorectal metastases - Current treatment strategies]. / Kolorektale Metastasen ­ Aktuelle Behandlungskonzepte.

Colorectal metastases - Current treatment strategies Abstract. In the course of their disease, more than 50 % of patients with colorectal cancer develop metastases. They are most frequently localized in the liver, followed by the peritoneum and the lungs. The therapeutic options and prognosis of colorectal metastases have improved markedly in recent years. Modern treatment concepts are multimodal and are customized for the individual patient by interdisciplinary tumour boards that follow widely recognised guidelines and norms. The recommendation of an appropriate treatment option in metastasized patients by an interdisciplinary panel of experts is of paramount importance. Besides technical possibilities, factors such as comorbidities, medical outcomes, quality of processes as well as patient-related outcome are all crucial in the decision-making process. In most patients diagnosed with distant metastases, the prognosis is determined by the extent of the liver burden. Hereby, the resection of the liver metastases is of utmost importance to improve the prognosis of a patient, since only those individuals who have successfully undergone resection have a chance for long-term disease free-survival. Whether liver metastases are resectable depends on sufficient volume and function of the future liver remnant (FLR). Manipulation of the FLR as well as upfront oncological treatment of metastases improves the resectability rates in patients with an advanced tumor load in the liver. Laparoscopic liver resection improves patient outcomes by reducing pain and results in a shortened hospital stay. Lung resection for pulmonary metastases as well as cytoreductive surgery for peritoneal metastases are important mainstays of modern personalized treatment concepts. However, results of ongoing trials are eagerly awaited to help quantify the prognostic effects of those therapies and assess their true therapeutic value.

Transition from open to laparoscopic ALPPS for patients with very small FLR: the initial experience.

BACKGROUND: Laparoscopic ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy) has previously been reported but has been the authors' default option since 2015 in patients with small future liver remnant. METHODS: A retrospective analysis of all consecutive patients undergoing ALPPS at a single referral center was performed using a prospective database from July 2011 to June 2016. Feasibility was studied by assessing conversions. The 90-day mortality and complications were analyzed using a Dindo-Clavien score and the comprehensive complication index. Operative time, blood loss, volumetric growth, and hospital stay were examined. The CUSUM analysis was performed. RESULTS: ALPPS was performed in 30 patients, 10 of whom underwent a laparoscopic approach. There was no mortality and no complication grade ≥3A observed in laparoscopic ALPPS. In open ALPPS, 10 of 20 patients experienced complications grade ≥3A (p = 0.006) and one patient died. Liver failure was not observed after laparoscopic ALPPS, but two patients in the open ALPPS group developed complications that precluded the second stage. The total hospital stay was shorter in the laparoscopic ALPPS group. CONCLUSION: Laparoscopic ALPPS is feasible as the default procedure for patients with very small FLR, and it is not inferior to the open approach. Surgeons experienced with complex laparoscopy should be encouraged to use a laparoscopic approach to ALPPS.

ALPPS as a salvage procedure after insufficient future liver remnant hypertrophy following portal vein occlusion.

BACKGROUND: A minimum future liver remnant (FLR) of 30% is required to avoid post hepatectomy liver failure (PHLF). Portal vein occlusion (PVO) is the main strategy to induce hypertrophy of the FLR, but some patients will not reach sufficient FLR hypertrophy to enable resection. Recently ALPPS has emerged as a "Salvage Procedure" for PVO failure. The aim of this study was to report the short term outcomes of ALPPS following PVO failure. METHODS: A retrospective analysis of patients enrolled within the international ALPPS Registry between October 2012 and November 2015 (NCT01924741) was performed. Patients with documented PVO failure were included. The outcomes reported included feasibility, FLR growth rate and safety of ALPPS. Complications were recorded as per Clavien-Dindo classification. RESULTS: From 510 patients enrolled in the Registry there were 22 patients with previous PVO failure. Two patients were excluded due to missing data and twenty patients were analysed. All of them completed the proposed ALPPS with a medium FLR increase of 88% (23-115%) between two stages and no 90-day mortality. CONCLUSION: In experienced centers, ALPPS following PVO failure is feasible and safe. The FLR hypertrophy was similar to other ALPPS series. ALPPS is a potential rescue strategy after PVO failure.

The many faces of ALPPS: surgical indications and techniques among surgeons collaborating in the international registry.

BACKGROUND: ALPPS was developed to induce accelerated future liver remnant (FLR) hypertrophy in order to increase hepatic tumour resectability and reduce the risk of post-operative liver failure. While early studies demonstrated concerning complication rates, others reported favourable results. This inconsistency may be due to variability in surgical indications and technique. METHODS: A web-based survey was sent to surgeons participating in the International ALPPS Registry in September of 2014. Questions addressed surgeon demographics and training, surgical indications and technique, and clinical management approaches. RESULTS: Fifty six out of 85 surgeons from 78 centers responded (66%) and half (n = 30) had training in liver transplantation. Forty seven (84%) did not reserve ALPPS solely for colorectal liver metastases (CRLM) and 30 (54%) would perform ALPPS for an FLR over 30%. Neoadjuvant chemotherapy for CRLM was recommended by 37 (66%) respondents. Surgical approaches varied considerably, with 30% not preserving outflow to the middle hepatic vein and 39% believing it necessary to skeletonize the hepatoduodenal ligament. Twenty five (45%) surgeons have observed segment 4 necrosis. CONCLUSION: There is considerable variability in how ALPPS is performed internationally. This heterogeneity in practice patterns may explain the current incongruity in published outcomes, and highlights the need for standardization.

Importance of primary indication and liver function between stages: results of a multicenter Italian audit of ALPPS 2012-2014.

BACKGROUND: Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates. METHOD: A national audit was performed to gather information about the safety of the procedure and to better understand the complications. The audit was offered to all high-volume hepatobiliary centers in Italy. RESULTS: Of all Italian centers approached in January 2012, 12 centers with experience in ALPPS enrolled and participated in collection of data. Fifty patients underwent ALPPS between 2012 and 2014. In 48/50 patients completion of hepatectomy was performed successfully. Major morbidity occurred in 54% with a 20% 90-day mortality. Uni- and multivariate analysis showed that ALPPS for cholangiocarcinoma and a peak of bilirubin over 5 mg/dl between stages was associated with increase of 90-day mortality and worse survival. DISCUSSION: It is proposed that a moratorium be introduced for classic ALPPS in cholangiocarcinoma and to abort ALPPS in patients who develop an interstage increase in bilirubin, due to the high risk of liver failure and mortality.