Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

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.

Is an intraoperative liver function assessment possible? Application of the 13C-methacetin-breath-test during major liver resections - a pilot study.

BACKGROUND: As prevention of posthepatectomy-liver-failure is crucial, there is need of dynamic assessment of liver function, even intraoperatively. 13C-methacetin-breath-test estimates the organ's microsomal functional capacity. This is its first intraoperative evaluation in major liver surgery. METHODS: 30 patients planed for resection of ≥3 liver segments, between March-November 2019, were prospectively enrolled in this "single-center", pilot study. Using the 13C-methacetin-breath-test, liver function was assessed four times: preoperatively, intraoperatively before and after resection and postoperatively. The resulted maximum-liver-function-capacity (LiMAx)-values and delta-over-baseline (DOB)-curves were compared, further analyzed and correlated to respective liver volumes. RESULTS: The intraoperative LiMAx-values before resection were mostly lower than the preoperative ones (-11.3% ± 28%). The intraoperative measurements after resection resulted to mostly higher values than the postoperative ones (42.35% ± 46.19%). Pharmacokinetically, an interference between the two intraoperative tests was observed. There was no strong correlation between residual liver volume and function with a percentual residual-LiMAx mostly lower than the percentual residual volume (-17.7% ± 4.1%). CONCLUSIONS: Intraoperative application of the 13C-methacetin-breath-test during major liver resections seems to deliver lower values than the standard preoperative test. As multiple intraoperative tests interfere significantly to each other, a single intraoperative measurement is suggested. Multicentric standardized measurements could define the "normal" range for intraoperative measurements and control their predictive value.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

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.

Liver surgery in the 2020s: ante-situm and in-situ resection are still indicated - A single-center study.

BACKGROUND: Tumor infiltration of the hepatic outflow comprising all three hepatic veins and the inferior vena cava remains a surgical challenge. Liver resection under total vascular exclusion with or without extracorporeal bypass has been described as a therapeutic option for these tumors. Here, we present our experience with these complex surgical methods. METHODS: We searched our database for patients treated with an in-situ or ante-situm liver resection (ISR and ASR, respectively) with extracorporeal bypass. We collected demographic and perioperative data. RESULTS: From January 2010 to December 2021, we performed 2122 liver resections. Nine patients were treated with ASR and five were treated with ISR. Out of these 14 patients, six had colorectal liver metastases, six had cholangiocarcinoma, and two had non-colorectal liver metastases. The median operative time and bypass time in all patients were 536.5 and 150 min, respectively. Compared with ISR, ASR required a longer operative time (ASR 586 min and ISR 495 min) and a longer bypass time (ASR 155 min and ISR 122 min). Morbidity (Clavien-Dindo grade > 3A adverse events) occurred in 78.5% of patients. 90-day postoperative mortality was 7%. Median overall survival was 33 months. Seven patients experienced recurrence. In these patients, median disease-free survival was 9 months. CONCLUSION: Resection of tumors infiltrating the hepatic outflow poses a high risk for patients. However, with rigorous selection and an experienced perioperative team, these patients can be treated surgically with reasonable oncological outcomes.

Sex Disparities in Outcomes Following Major Liver Surgery: New Powers of Estrogen?

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.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

Association of subcellular localization of TEAD transcription factors with outcome and progression in pancreatic ductal adenocarcinoma.

BACKGROUND: Transcriptional enhanced associated domain (TEAD) transcription factors are nuclear effectors of several oncogenic signalling pathways including Hippo, WNT, TGF-ß and EGFR pathways that interact with various cancer genes. The subcellular localization of TEAD regulates the functional output of these pathways affecting tumour progression and patient outcome. However, the impact of the TEAD family on pancreatic ductal adenocarcinoma (PDAC) and its clinical progression remain elusive. METHODS: A cohort of 81 PDAC patients who had undergone surgery was established. Cytoplasmic and nuclear localization of TEAD1, TEAD2, TEAD3 and TEAD4 was evaluated with the immunoreactive score (IRS) by immunohistochemistry (IHC) using paraffin-embedded tissue. Results were correlated with clinicopathological data, disease-free and overall survival. RESULTS: Nuclear staining of all four TEADs was increased in pancreatic cancer tissue. Patients suffering from metastatic disease at time of surgery showed a strong nuclear staining of TEAD2 and TEAD3 (p < 0.05). Furthermore, a nuclear > cytoplasmic ratio of TEAD2 and TEAD3 was associated with a shorter overall survival and TEAD2 emerged as an independent prognostic factor for disease-free survival. CONCLUSION: Our study underlines the importance of TEAD transcription factors in PDAC as a nuclear localization was found to be associated with metastatic disease and an unfavourable prognosis after surgical resection.

Impact of acute kidney injury after extended liver resections.

BACKGROUND: Complex liver resection is a risk factor for the development of AKI, which is associated with increased morbidity and mortality. Aim of this study was to assess risk factors for acute kidney injury (AKI) and its impact on outcome for patients undergoing complex liver surgery. METHODS: AKI was defined according to the KDIGO criteria. Primary endpoint was the occurrence of AKI after liver resection. Secondary endpoints were complications and mortality. RESULTS: Overall, 146 patients undergoing extended liver resection were included in the study. The incidence of AKI was 21%. The incidence of chronic kidney disease (CKD) and hepatocellular carcinoma were significantly higher in patients with AKI. In the AKI group, the proportion of extended right hepatectomies was the highest (53%), followed by ALPPS (43%). Increased intraoperative blood loss, increased postoperative complications and perioperative mortality was associated with AKI. Besides age and CKD, ALPPS was an independent risk factor for postoperative AKI. A small future liver remnant seemed to increase the risk of AKI in patients undergoing ALPPS. CONCLUSION: Following extended liver resection, AKI is associated with an increased morbidity and mortality. ALPPS is a major independent risk factor for the development of AKI and a sufficient future liver remnant could avoid postoperative AKI.

Repeated hepatectomy after ALPPS for recurrence of colorectal liver metastasis: the edge of limits?

BACKGROUND: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described. METHODS: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival. RESULTS: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy. CONCLUSION: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy.

Variation in complications and mortality following ALPPS at early-adopting centers.

BACKGROUND: Various, often conflicting, estimates for post-operative morbidity and mortality following ALPPS have been reported in the literature, suggesting that considerable center-level variation exists. Some of this variation may be related to center volume and experience. METHODS: Using data from seventeen centers who were early adopters of the ALPPS technique, we estimated the variation, by center, in standardized 90-day mortality and comprehensive complication index (CCI) for patients treated between 2012 and 2018. RESULTS: We estimated that center-specific 90-day mortality following treatment with ALPPS varied from 4.2% (95% CI: 0.8, 9.9) to 29.1% (95% CI: 13.9, 50.9), and that center-specific CCI following treatment with ALPPS varied from 17.0 (95% CI: 7.5, 26.5) to 49.8 (95% CI: 38.1, 61.8). Declines in estimated 90-day mortality and CCI were observed over time, and almost all individual centers followed this trend. Patients treated at centers with a higher number of ALPPS cases performed over the prior year had a lower risk of post-operative mortality. CONCLUSION: Despite considerable center-level variation in ALPPS outcomes, perioperative outcomes following ALPPS have improved over time and treatment at higher volume centers results in a lower risk of 90-day mortality. Morbidity and mortality remain concerningly high at some centers.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

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.

A systematic review and meta-analysis of rescue revascularization with arterial conduits in liver transplantation.

Although aortohepatic conduits (AHCs) provide an effective technique for arterialization in liver transplantation (LT) when the native recipient artery is unusable, various publications report higher occlusion rates and impaired outcome compared to conventional anastomoses. This systematic review and meta-analysis investigates the published evidence of outcome and risk of AHCs in LT using bibliographic databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Primary and secondary outcome were artery occlusion as well as graft and patient survival. Twenty-three retrospective studies were identified with a total of 22 113 patients with LT, of whom 1900 patients (9%) received an AHC. An AHC was used in 33% of retransplantations. Early artery occlusion occurred in 7% (3%-16%) of patients with AHCs, compared to 2% (1%-3%) without conduit (OR 3.70; 1.63-8.38; P = .001). The retransplantation rate after occlusion was not significantly different in both groups (OR 1.46; 0.67-3.18; P = .35). Graft (HR 1.38; 1.17-1.63; P < .001) and patient (HR 1.57; 1.12-2.20; P = .009) survival was significantly lower in the AHC compared to the nonconduit group. In contrast, graft survival in retransplantations was comparable (HR 1.00; 0.82-1.22; P = .986). Although AHCs provide an important rescue option, when regular revascularization is not feasible during LT, transplant surgeons should be alert of the potential risk of inferior outcome.

Hepatic artery occlusion in liver transplantation: What counts more, the type of reconstruction or the severity of the recipient's disease?

Although the type of hepatic artery revascularization technique is known to have an impact on patency rates, independent perioperative risk factors on patient outcomes are poorly defined. All consecutive adult patients undergoing cadaveric liver transplantation (n = 361) from July 2007 to June 2016 in a single institution were analyzed. Primary outcomes were early (<30 days) hepatic artery occlusion and primary hepatic artery patency rate. A multivariate model was used to identify independent risk factors for occlusion and the need of arterial conduit, as well as their impact on graft and patient survival. Arterial revascularization without additional reconstruction (end-to-end arterial anastomosis [AA]) was performed in 77% (n = 279), arterial reconstruction (AR) in 15% (n = 53), and aortohepatic conduit (AHC) in 8% (n = 29) of patients. AHC had the highest mean intraoperative flow (275 mL/minute; P = 0.02) compared with AA (250 mL/minute) and AR (200 mL/minute; P = 0.02). There were 43 recipients (12%) who had an occlusive event with successful revascularization in 20 (47%) recipients. One-year primary patency rates of AA, AR, and AHC were 97%, 88%, and 74%, respectively. Aortic calcification had an impact on early occlusion. AR (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.26-10.75; P = 0.02) and AHC (OR, 6.21; 95% CI, 2.02-18.87; P = 0.001) were independent risk factors for early occlusion. Dyslipidemia additionally independently contributed to early occlusion (OR, 2.74; 95% CI, 0.96-7.87; P = 0.06). The 1- and 5-year graft survival rates were 83% and 70% for AA, 75% and 69% for AR, and 59% and 50% for AHC (P = 0.004), respectively. In conclusion, arterial patency is primarily determined by the type of vascular reconstruction rather than patient or disease characteristics. The preoperative lipid status is an independent risk factor for early occlusion, whereas overall occlusion is only based on the performed vascular reconstruction, which is also associated with reduced graft and patient survival. Liver Transplantation 24 790-802 2018 AASLD.

Reductions in post-hepatectomy liver failure and related mortality after implementation of the LiMAx algorithm in preoperative work-up: a single-centre analysis of 1170 hepatectomies of one or more segments.

OBJECTIVES: Post-hepatectomy liver failure has a major impact on patient outcome. This study aims to explore the impact of the integration of a novel patient-centred evaluation, the LiMAx algorithm, on perioperative patient outcome after hepatectomy. METHODS: Trends in perioperative variables and morbidity and mortality rates in 1170 consecutive patients undergoing elective hepatectomy between January 2006 and December 2011 were analysed retrospectively. Propensity score matching was used to compare the effects on morbidity and mortality of the integration of the LiMAx algorithm into clinical practice. RESULTS: Over the study period, the proportion of complex hepatectomies increased from 29.1% in 2006 to 37.7% in 2011 (P = 0.034). Similarly, the proportion of patients with liver cirrhosis selected for hepatic surgery rose from 6.9% in 2006 to 11.3% in 2011 (P = 0.039). Despite these increases, rates of post-hepatectomy liver failure fell from 24.7% in 2006 to 9.0% in 2011 (P < 0.001) and liver failure-related postoperative mortality decreased from 4.0% in 2006 to 0.9% in 2011 (P = 0.014). Propensity score matching was associated with reduced rates of post-hepatectomy liver failure [24.7% (n = 77) versus 11.2% (n = 35); P < 0.001] and related mortality [3.8% (n = 12) versus 1.0% (n = 3); P = 0.035]. CONCLUSIONS: Postoperative liver failure and postoperative liver failure-related mortality decreased in patients undergoing hepatectomy following the implementation of the LiMAx algorithm.

Comparison of the LiMAx test vs. the APRI+ALBI score for clinical utility in preoperative risk assessment in patients undergoing liver surgery - A European multicenter study.

INTRODUCTION: Posthepatectomy liver failure (PHLF) remains the main reason for short-term mortality after liver surgery. APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), score and the liver function maximum capacity test (LiMAx) are both established preoperative (preop) liver function tests. The aim of this study was to compare both tests for their predictive potential for clinically significant PHLF grade B and C (B+C). MATERIALS AND METHODS: 352 patients were included from 4 European centers. Patients had available preop APRI+ALBI scores and LiMAx results. Predictive potential for PHLF, PHLF B+C and 90-day mortality was compared using receiver operating characteristic (ROC) curve analysis and calculation of the area under the curve (AUC). Published cutoffs of ≥ -2.46 for APRI+ALBI and of <315 for LiMAx were assessed using chi-squared test. RESULTS: APRI+ALBI showed superior predictive potential for PHLF B+C (N = 34; AUC = 0.766), PHLF grade C (N = 20; AUC = 0.782) and 90-day mortality (N = 15; AUC = 0.750). When comparing the established cutoffs of both tests, APRI+ALBI outperformed LiMAx in prediction of PHLF B+C (APRI+ALBI ≥2.46: Positive predictive value (PPV) = 19%, negative predictive value (NPV) = 97%; LiMAx <315: PPV = 3%, NPV = 90%) and 90-day mortality (APRI+ALBI ≥2.46: PPV = 12%, NPV = 99%; LiMAx <315: PPV = 0%, NPV = 94%) CONCLUSION: In our analysis, APRI+ALBI outperformed LiMAx measurement in the preop prediction of PHLF B+C and postoperative mortality, at a fraction of the costs, manual labor and invasiveness.

Sarcopenia influences the kinetic growth rate after ALPPS.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy induces rapid and effective hypertrophy of the future liver remnant to prevent postoperative liver failure. The aim of this study was to determine cofactors, including sarcopenia, influencing the kinetic growth rate, and subsequently future liver remnant, in terms of safety, complications, and posthepatectomy liver failure. METHOD: Patients undergoing associating liver partition and portal vein ligation for staged hepatectomy between 2010 and 2020 were included in this study. Kinetic growth rate was defined as the quotient of the degree of hypertrophy and the time interval between the 2 steps. The sarcopenia muscle index was defined as the skeletal muscle area of both psoas major muscles normalized to the patient's height. RESULTS: During the study period, 90 patients underwent associating liver partition and portal vein ligation for staged hepatectomy. The association between kinetic growth rate and posthepatectomy liver failure indicates a significant nonlinear effect (P = .02). The incidence of posthepatectomy liver failure significantly increased at a kinetic growth rate below 7% per week (31%) compared to patients with a kinetic growth rate >7%/wk (7%, P = .02). In patients with a low kinetic growth rate (<7%/wk), the sarcopenia muscle index was significantly lower compared to patients with a high kinetic growth rate (>7%/wk). Furthermore, a low sarcopenia muscle index and a high body mass index turned out to be independent risk factors for a low kinetic growth rate. CONCLUSION: After the first step of the associating liver partition and portal vein ligation for staged hepatectomy procedure, a low kinetic growth rate (<7%/wk) increases the risk of posthepatectomy liver failure. The presence of a low sarcopenia muscle index and a high body mass index are profoundly correlated with clinically substantial impaired liver regeneration, which can result in increased liver dysfunction after associating liver partition and portal vein ligation for staged hepatectomy.

Preoperative leukocytosis is an independent risk factor for morbidity and survival after resection of colorectal liver metastases.

BACKGROUND: Although surgical resection of colorectal liver metastases (CRLM) remains to be the only option for long term survival, traditional surgical concepts have been challenged by the introduction of the liver first approach or neoadjuvant chemotherapy in resectable CRLM and interventional therapies. The aim of this study was to identify prognostic factors for postoperative morbidity and survival and to externally evaluate the recently introduced resection severity index (RSI), in order to optimize patient selection and treatment strategies. METHODS: This is a retrospective single centre analysis of 213 patients undergoing surgery for CRLM in curative intent between January 2010 and December 2018. RESULTS: Median follow up after liver resection was 28.56 (0.01-111.46) months. Severe postoperative complications (Clavien-Dindo ≥ IIIa) were observed in 46 (21.6%) cases. Preoperative leukocytosis (OR: 3.114, CI-95%: 1.089-8.901; p = 0.034) and operation time in minutes (OR: 1.007, CI-95%: 1.002-1.011; p = 0.002) were determined as independent risk factors. Overall survival (OS) was 46.68 months with a 5-year survival rate of 40.5%. Independent prognostic factors were preoperative leukocytosis (HR: 2.358, CI-95%: 1.170-4.752; p = 0.016), major hepatectomy (HR: 1.741, CI-95%: 1.098-2.759; p = 0.018) and low grading of the primary intestinal tumour (HR: 0.392, CI-95%: 0.231-0.667; p < 0.001). The RSI (ASAT (U/l) divided by Quick (%) multiplied by the extent of liver resection in points) was identified as independent risk factor for OS only in patients without neoadjuvant chemotherapy. CONCLUSIONS: Detection of leukocytosis in patients prior resection of CRLM was associated with increased postoperative morbidity and decreased OS and could therefore prove valuable for perioperative risk stratification.

Vascular injury during cholecystectomy: A multicenter critical analysis behind the drama.

BACKGROUND: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery. METHODS: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes. RESULTS: A total of 104 patients were included. Twenty-nine patients underwent vascular repair (27.9%), 13 (12.5%) liver resection, and 1 liver transplant as a first treatment. Eighty-four (80.4%) vascular and biliary injuries occurred in nonspecialized centers and 45 (53.6%) were immediately transferred. Intraoperative diagnosed injuries were rare in referred patients (18% vs 84%, P = .001). The patients managed at the hospital where the injury occurred had a higher number of reoperations (64% vs 20%, P ˂ .001). The need for vascular reconstruction was associated with higher mortality (P = .04). Two of the 4 patients transplanted died. CONCLUSION: Vascular lesions during cholecystectomy are a potentially life-threatening complication. Management of referral to specialized centers to perform multiple complex multidisciplinary procedures should be mandatory. Late vascular repair has not shown to be associated with worse results.