A comparison of the simultaneous, liver-first, and colorectal-first strategies for surgical treatment of synchronous colorectal liver metastases at two major liver-surgery institutions in Sweden.

BACKGROUND: The optimal treatment strategy for patients with synchronous colorectal liver metastases (CRLM) is unclear. The aim of this study was to compare the outcome of the simultaneous, liver-first, and colorectal-first surgical approaches. METHODS: All consecutive patients who had been resected with curative intent for CRLM were included. A Cox regression model was constructed, and an intention-to-treat analysis was performed between the liver-first and the simultaneous approaches, after propensity score matching. RESULTS: 658 patients were included in the analysis. 92 patients had a simultaneous resection, 163 patients had liver-first, and 403 patients had a colorectal-first approach. Overall survival was 54.9 months (95% CI 39.2-70.4) in the liver-first group, 54.5 months (95% CI 46.8-62.3) in colorectal-first group, and 59.6 months (95% CI 42.2-77.0) in the simultaneous group (log-rank p =0.850). In the matched cohort there were no differences in Clavien-Dindo 3a (p = 0.992) or 3b and greater (p = 0.999). Median overall survival was for liver-first group 42.2 months (95% CI 26.3-58.2), and for the simultaneous group 56.2 months (95% CI 47.1-65.4) (stratified log-rank p = 0.455). CONCLUSION: A simultaneous approach was not associated with worse overall survival or morbidity compared to a liver-first approach.

Outcome of ERCP related to case-volume.

BACKGROUND AND AIMS: In some studies, high endoscopic retrograde cholangiopancreatography (ERCP) case-volume has been shown to correlate to high success rate in terms of successful cannulation and fewer adverse events. The aim of this study was to analyze the association between ERCP success and complications, and endoscopist and centre case-volumes. METHODS: Data were obtained from the Swedish National Register for Gallstone Surgery and ERCP (GallRiks) on all ERCPs performed for Common Bile Duct Stone (CBDS) (n = 17,873) and suspected or confirmed malignancy (n = 6152) between 2009 and 2018. Successful cannulation rate, procedure time, intra- and postoperative complication rates and post-ERCP pancreatitis (PEP) rate, were compared with endoscopist and centre ERCP case-volumes during the year preceding the procedure as predictor. RESULTS: In multivariable analyses of the CBDS group adjusting for age, gender and year, a high endoscopist case-volume was associated with higher successful cannulation rate, lower complication and PEP rates, and shorter procedure time (p < 0.05). Centres with a high annual case-volume were associated with high successful cannulation rate and shorter procedure time (p < 0.05), but not lower complication and PEP rates. When indication for ERCP was malignancy, a high endoscopist case-volume was associated with high successful cannulation rate and low PEP rates (p < 0.05), but not shorter procedure time or low complication rate. Centres with high case-volume were associated with high successful cannulation rate and low complication and PEP rates (p < 0.05), but not shorter procedure time. CONCLUSIONS: The results suggest that higher endoscopist and centre case-volumes are associated with safer ERCP and successful outcome.

ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO.

OBJECTIVE: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). BACKGROUND: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. METHODS: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. RESULTS: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). CONCLUSIONS: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.

Cardiovascular complications after common bile duct stone extractions.

BACKGROUND: Common bile duct stone (CBDS) is a common condition the rate of which increases with age. Decision to treat in particular elderly and frail patients with CBDS is often complex and requires careful assessment of the risk for treatment-related cardiovascular complications. The aim of this study was to compare the rate of postoperative cardiovascular events in CBDS patients treated with the following: ERCP only; cholecystectomy only; cholecystectomy followed by delayed ERCP; cholecystectomy together with ERCP; or ERCP followed by delayed cholecystectomy. METHODS: The study was based on data from procedures for gallstone disease registered in the Swedish National Quality Register for Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (GallRiks) 2006-2014. ERCP and cholecystectomy procedures performed for confirmed or suspected CBDS were included. Postoperative events were registered by cross-matching GallRiks with the National Patient Register (NPR). A postoperative cardiovascular event was defined as an ICD-code in the discharge notes indicating myocardial infarct, pulmonary embolism or cerebrovascular disease within 30 days after surgery. In cases where a patient had undergone ERCP and cholecystectomy on separate occasions, the 30-day interval was timed from the first intervention. RESULTS: A total of 23,591 underwent ERCP or cholecystectomy for CBDS during the study period. A postoperative cardiovascular event was registered in 164 patients and death within 30 days in 225 patients. In univariable analysis, adverse cardiovascular event and death within 30 days were more frequent in patients who underwent primary ERCP (p < 0.05). In multivariable analysis, adjusting for history of cardiovascular disease or events, neither risk for cardiovascular complication nor death within 30 days remained statistically significant in the ERCP group. CONCLUSIONS: Primary ERCP as well as cholecystectomy may be performed for CBDS with acceptable safety. More studies are required to provide reliable guidelines for the management of CBDS.

Portal vein embolization with n-butyl-cyanoacrylate before hepatectomy: a single-center retrospective analysis of 46 consecutive patients.

BACKGROUND: Preoperative portal vein embolization (PVE) is performed to induce hypertrophy of the future liver remnant enabling major liver resection in patients with various types of liver tumors. PURPOSE: To evaluate safety and effectiveness of PVE with n-butyl-cyanoacrylate (NBCA). MATERIAL AND METHODS: All consecutive patients referred to our hospital for PVE between July 2006 and July 2017 were retrospectively reviewed. Volumetry was performed on computed tomography images before and after PVE, segmenting the total liver volume and the future liver remnant (FLR), i.e. liver segments I-III. RESULTS: PVE was performed in 46 patients (18 women, 28 men; mean age = 61 years) using local anesthesia. The ipsilateral technique was used in 45 patients. Adverse events were rare. The mean FLR volume increase was 56%, the degree of hypertrophy was 9.7%, and the kinetic growth rate was 2.1%/week. The median ± SD period between PVE and liver surgery was 7 ± 3 weeks. Forty-two patients (91%) had surgery; liver resection was performed in 37 (80%) patients. Three patients (7%) developed transient liver failure after surgery. There was no 90-day post-PVE or postoperative mortality. CONCLUSION: PVE using NBCA through the ipsilateral approach in local anesthesia is safe and effective in inducing hypertrophy of the future liver remnant enabling surgery, and thereby increasing survival in patients with liver tumors.

The prognostic value of C-reactive protein and albumin in patients undergoing resection of colorectal liver metastases. A retrospective cohort study.

BACKGROUND: The systemic inflammation-based Glasgow Prognostic Score (GPS) and modified GPS (mGPS), as measured by preoperative C-reactive protein (CRP) and albumin, correlate with poor survival in several cancers. This study evaluates the prognostic value of these scores in patients with colorectal liver metastases (CRLM). METHODS: This retrospective study assessed the prognostic role of preoperatively measured GPS and mGPS in patients undergoing liver resection because of CRLM. Clinicopathological data were retrieved from local databases. The prognostic value of GPS and mGPS were compared and a Cox regression model was used to find independent predictors of overall survival. RESULTS: In total, 849 consecutive patients between January 2005 and December 2015 were included. Patients with GPS 0 had a median survival of 70 months compared to 49 months in patients with GPS 1, and 27 months in patients with GPS 2. Multivariable analyses showed that GPS 1 (HR = 1.51, 95%CI [1.14-2.01]) and GPS 2 (HR = 2.78, 95%CI [1.79-4.31]), after correction for age >70 years (HR = 1.75 [1.36-2.26]), and extended resection (HR = 2.53, 95%CI[1.79-3.58]), were associated with poor overall survival. CONCLUSION: A preoperative GPS is an independent prognostic factor in patients with CRLM, and appears to be a better prognostic tool than mGPS.

Survival and prognostic factors after transplantation, resection and ablation in a national cohort of early hepatocellular carcinoma.

BACKGROUND: In patients with early hepatocellular cancer (HCC) and preserved liver function, the choice between transplantation, resection and ablation and which factors to consider is not obvious and guidelines differ. In this national cohort study, we aimed to compare posttreatment survival in patients fulfilling predefined criteria, and to analyse preoperative risk factors that could influence decision. METHODS: We used data from HCC-patients registered with primary transplantation, resection or ablation 2008-2016 in the SweLiv-registry. In Child A-subgroups, 18-75 years, we compared survival after transplantation or resection, with different tumour criteria; either corresponding to our transplantation criteria (N = 257) or stricter with single tumours ≤50 mm (N = 159). A subgroup with single tumours ≤30 mm, compared all three treatments (N = 193). RESULTS: We included 1022 HCC-patients; transplantation n = 223, resection n = 438, ablation n = 361. In the transplant criteria subgroup, differences in five-year survival, adjusted for age and gender, were not significant, with 71.2% (CI 62.3-81.3) after transplantation (n = 109) and 63.5% (CI 54.9-73.5) after resection (n = 148). Good liver function (Child 5 vs. 6, Albumin ≥36), increased the risk after transplantation, but decreased the risk after resection and ablation. CONCLUSION: Even within Child A, detailed liver function assessment is important before treatment decision, and for stratifying survival comparisons.

Imbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer.

BACKGROUND & AIMS: Bile duct tumors are rare and have poor prognoses. Natural killer (NK) cells are frequent in human liver and infiltrate these tumors but do not control their progression. Responses of NK cells are regulated by NK immunoglobulin-like receptors (KIRs), which interact with HLA class I ligands. We aimed to characterize the features of the KIR gene loci and their ligands in patients with bile duct cancer (BDC). METHODS: We performed combined multidimensional characterization of genes that encode KIRs and their ligands in blood samples from patients with BDC from Sweden, followed for up to 8 years after diagnosis (n = 148), in 2 geographically matched cohorts of healthy individuals from Northern Europe (n = 204 and n = 900), and in healthy individuals from 6 geographically unrelated populations (n = 2917). We used real-time polymerase chain reaction, RNA sequencing, immunohistochemistry, and flow cytometry to evaluate NK-cell presence, as well as KIR and KIR-ligand expression in bile duct tumors and control tissues. RESULTS: Patients with bile duct tumors had multiple alterations at the KIR gene loci. KIR loci are grouped into genotypes that encode more inhibitory (group A) and more activating (group B) receptors, which can be subdivided into centromeric and telomeric fragments. Patients with BDC had a lower prevalence of KIR2DL3, which was linked to disequilibrium in centromeric A/B and B/B genotypes, compared with control individuals. The associations between KIRs and KIR ligands differed between patients with BDC and control individuals; patients had an altered balance between activating and inhibitory KIRs. KIR-positive NK cells infiltrated biliary tumors that expressed matched KIR ligands. CONCLUSIONS: In a multidimensional analysis of DNA from blood samples of patients with BDC in Europe, we found patients to have multiple alterations at the KIR and HLA gene loci compared with control individuals. These alterations might affect NK-cell tumor surveillance. NK cells from bile duct tumors expressed KIRs and were found in tumors that expressed cognate ligands. This should be considered in development of immune-based therapies for BDC.

ERCP-related perforations: a population-based study of incidence, mortality, and risk factors.

BACKGROUND: Perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare but feared adverse events with highly reported morbidity and mortality rates. The aim was to evaluate the incidence and outcome of ERCP-related perforations and to identify risk factors for death due to perforations in a population-based study. METHODS: Between May 2005 and December 2013, a total of 52,140 ERCPs were registered in GallRiks, a Swedish nationwide, population-based registry. A total of 376 (0.72%) were registered as perforations or extravasation of contrast during ERCP or as perforation in the 30-day follow-up. The patients with perforation were divided into fatal and non-fatal groups and analyzed for mortality risk factors. The case volume of centers and endoscopists were divided into the upper quartile (Q4) and the lower three quartile (Q1-3) groups. Furthermore, fatal group patients' records were reviewed. RESULTS: Death within 90 days after ERCP-related perforations or at the index hospitalization occurred in 20% (75 out of 376) for all perforations and 0.1% (75 out of 52,140) for all ERCPs. The independent risk factors for death after perforation were malignancy (OR 11.2, 95% CI 5.8-21.6), age over 80 years (OR 3.8, 95% CI 2.0-7.4), and sphincterotomy in the pancreatic duct (OR 2.8, 95% CI 1.1-7.5). In Q4 centers, the mortality was similar with or without pancreatic duct sphincterotomy (14% vs. 13%, p = 1.0), but in Q1-3 centers mortality was higher (45% vs. 21%, p = 0.024). CONCLUSIONS: ERCP-related perforations are severe adverse events with low incidence (0.7%) and high mortality rate up to 20%. Malignancy, age over 80 years, and sphincterotomy in the pancreatic duct increase the risk to die after a perforation. The risk of a fatal outcome in perforations after pancreatic duct sphincterotomy was reduced when occurred at a Q4-center. In the case of a complicated perforation a transfer to a Q4-center may be considered.

Postoperative rendezvous endoscopic retrograde cholangiopancreaticography as an option in the management of choledocholithiasis.

BACKGROUND: Rendezvous endoscopic retrograde cholangiopancreaticography (ERCP) is a well-established method for treatment of choledocholithiasis. The primary aim of this study was to determine how different techniques for management of common bile duct stone (CBDS) clearance in patients undergoing cholecystectomy have changed over time at tertiary referral hospitals (TRH) and county/community hospitals (CH). The secondary aim was to see if postoperative rendezvous ERCP is a safe, effective and feasible alternative to intraoperative rendezvous ERCP in the management of CBDS. METHODS: Data were retrieved from the Swedish registry for cholecystectomy and ERCP (GallRiks) 2006-2016. All cholecystectomies, where CBDS were found at intraoperative cholangiography, and with complete 30-day follow-up (n = 10,386) were identified. Data concerning intraoperative and postoperative complications, readmission and reoperation within 30 days were retrieved for patients where intraoperative ERCP (n = 2290) and preparation for postoperative ERCP were performed (n = 2283). RESULTS: Intraoperative ERCP increased (7.5% 2006; 43.1% 2016) whereas preparation for postoperative ERCP decreased (21.2% 2006; 17.2% 2016) during 2006-2016. CBDS management differed between TRHs and CHs. Complications were higher in the postoperative rendezvous ERCP group: Odds Ratio [OR] 1.69 (95% confidence interval [CI] 1.16-2.45) for intraoperative complications and OR 1.50 (CI 1.29-1.75) for postoperative complications. Intraoperative bleeding OR 2.46 (CI 1.17-5.16), postoperative bile leakage OR 1.89 (CI 1.23-2.90) and postoperative infection with abscess OR 1.55 (CI 1.05-2.29) were higher in the postoperative group. Neither post-ERCP pancreatitis, postoperative bleeding, cholangitis, percutaneous drainage, antibiotic treatment, ICU stay, readmission/reoperation within 30 days nor 30-day mortality differed between groups. CONCLUSIONS: Techniques for management of CBDS found at cholecystectomy have changed over time and differ between TRH and CH. Rendezvous ERCP is a safe and effective method. Even though intraoperative rendezvous ERCP is the preferred method, postoperative rendezvous ERCP constitutes an acceptable alternative where ERCP resources are lacking or limited.

Outcomes of Simultaneous Resections and Classical Strategy for Synchronous Colorectal Liver Metastases in Sweden: A Nationwide Study with Special Reference to Major Liver Resections.

BACKGROUND: About 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and surgical resection offers a chance for cure. The aim of the present study was to compare outcomes for patients that underwent simultaneous resection to those that underwent a staged procedure with the bowel-first (classical) strategy by using information from two national registries in Sweden. METHODS: In this prospectively registered cohort study, we analyzed clinical, pathological, and survival outcomes for patients operated in the period 2008-2015 and compared the two strategies. RESULTS: In total, 537 patients constituted the study cohort, where 160 were treated with the simultaneous strategy and 377 with the classical strategy. Patients managed with the simultaneous strategy had less often rectal primary tumors (22% vs. 31%, p = 0.046) and underwent to a lesser extent a major liver resection (16% vs. 41%, p < 0.001), but had a shorter total length of stay (11 vs. 15 days, p < 0.001) and more complications (52% vs. 36%, p < 0.001). No significant 5-year overall survival (p = 0.110) difference was detected. Twenty-five patients had a major liver resection in the simultaneous strategy group and 155 in the classical strategy group without difference in 5-year overall survival (p = 0.198). CONCLUSION: Simultaneous resection of the colorectal primary cancer and liver metastases can possibly have more complications, with no difference in overall survival compared to the classical strategy.

ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis: Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial).

OBJECTIVE: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). BACKGROUND: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. METHODS: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome-RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. RESULTS: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. CONCLUSION: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.

The impact of post-hepatectomy liver failure on mortality: a population-based study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers. AIM: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy. METHOD: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5. RESULTS: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3. CONCLUSION: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.

Serial Assessment of Growth Factors Associated with Liver Regeneration in Patients Operated with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: There is limited knowledge about the mechanisms behind the unparalleled growth of the future liver remnant (FLR) linked to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). In this study, liver regenerative markers were examined in patients subjected to ALPPS. METHODS: Ten patients with colorectal liver metastases treated with neoadjuvant chemotherapy and ALPPS were included. Plasma was sampled at 6 time points and biopsies from both liver lobes were collected at both stages of ALPPS. The levels of interleukin (IL)-6, hepatocyte growth factor (HGF), tumor necrosis factor-α, epidermal growth factor, and vascular endothelial growth factor in plasma were measured at each time point. Expression of mRNA for markers of proliferation and apoptosis was studied in the biopsies from both liver lobes taken at both stages. RESULTS: ALPPS resulted in a peak of IL-6 after stage 1 (p = 0.004), which decreased rapidly and did not increase again after stage 2. HGF also increased after stage 1 (p = 0.048), and the HGF levels correlated significantly with the degree of growth of the FLR before stage 2 (p = 0.02, r2 = 0.47). There was a correlation between peak levels of IL-6 and HGF (p = 0.03, r2 = 0.84). CONCLUSIONS: IL-6 and HGF seem to be early mediators of hypertrophy after stage 1 in the ALPPS procedure. The peak HGF plasma level correlates with the degree of FLR growth in patients subjected to ALPPS.

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

BACKGROUND: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. METHODS: Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. RESULTS: A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. CONCLUSION: The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies.

Rescue ALPPS is efficient and safe after failed portal vein occlusion in patients with colorectal liver metastases.

PURPOSE: The aim of this study was to investigate whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be used as an effective and safe rescue procedure in patients with colorectal liver metastases (CRLM) and insufficient effect on the future liver remnant (FLR) after previous portal vein occlusion (PVO). METHODS: Eleven patients with bilobar CRLM treated with neoadjuvant chemotherapy and previous PVO with insufficient effect on the FLR were analyzed retrospectively from a prospective database. FLR was evaluated with computed tomography volumetry 6 days after stage 1, and stage 2 was performed on day seven. RESULTS: Six days after stage 1, the median increase of the FLR was 209 ml (range 87-314, P < 0.001). This corresponded to a median FLR growth of 61.8 % (range 19.3-120) resulting in an FLR/BW ratio >0.5 % in all patients and successful subsequent removal of the tumor bearing liver (segments IV-VIII) in all patients with no 90-day mortality. No patient had a 3b-complication or more according to Clavien-Dindo. No patient developed severe posthepatectomy liver failure. CONCLUSIONS: The powerful hypertrophy of the FLR associated with ALPPS seems to be maintained in patients with CRLM and previous failed PVO.

Mortality-related risk factors and long-term survival after 4460 liver resections in Sweden-a population-based study.

PURPOSE: The objectives of this study were to analyze the outcome after hepatectomy and to identify contributing factors to mortality and long-term survival in a population-based setting. METHOD: A retrospective, nationwide register study was performed. All patients who underwent hepatectomy in Sweden between 2002 and 2011 were identified in the Swedish Hospital Discharge Registry using their unique personal identification numbers. This cohort was linked to the National Cancer Registry (cancer diagnosis), the National Registry of Causes of Death, and the Migration Registry. Survival analysis by Kaplan-Meier method was performed to assess long-term outcome. A Cox regression model was used to analyze risk factors affecting long-term survival. RESULTS: Overall, 4460 hepatectomies were performed. The 30- and 90-day mortalities were 1.8 and 3.1 %, respectively. The overall 5- and 10-year survival rates for all diagnoses were 45 and 38 %, respectively. Independent risk factors for 5-year mortality were as follows: patient age, comorbidity, male gender, intrahepatic/extrahepatic cholangiocarcinoma, gallbladder cancer, extent of hepatectomy, and hepatectomies performed at non-university hospitals. Re-resection (78.1 % with diagnosis "metastasis") was performed on 374 patients. In these patients, mortality risk decreased by >50 % (HR 0.42; 95 %, CI 0.33-0.53). CONCLUSION: In a population-based analysis, liver resections are done with a low mortality risk and good long-term outcome. Patients who underwent resection at a University Hospital showed a significant better outcome compared to patients resected at non-University Hospitals. These results support further centralization of liver surgery. Re-resection should be performed if feasible.

Changes in gluconeogenesis and intracellular lipid accumulation characterize uremic human hepatocytes ex vivo.

It is well known that reduced glomerular filtration rate (GFR) leads to an increased risk of dyslipidemia, insulin resistance, and cardiovascular mortality. The liver is a central organ for metabolism, but its function in the uremic setting is still poorly characterized. We used human primary hepatocytes isolated from livers of nine donors with normal renal function to investigate perturbations in key metabolic pathways following exposure to uremic (n = 8) or healthy (n = 8) sera, and to serum-free control medium. Both uremic and healthy elicited consistent responses from hepatocytes from multiple donors and compared with serum-free control. However, at physiological insulin concentrations, uremic cells accumulated 56% more intracellular lipids. Also, when comparing uremic with healthy medium after culture, it contained more very-low-density lipoprotein-triglyceride and glucose. These changes were accompanied by decreased phosphorylation of AktS473 mRNA levels of key regulators of gluconeogenesis in uremic sera-treated hepatocytes such as phosphoenolpyruvate carboxykinase 1 and glucose 6-phosphate were elevated. We also found increased expression of 11ß-hydroxysteroid dehydrogenase mRNA in uremic cells, along with high phosphorylation of downstream p53 and phospholipase C-γ1Y783 Thus our ex vivo data suggest that the uremic hepatocytes rapidly develop a glycogenic and lipogenic condition accompanied by perturbations in a large number of signaling networks.