Health Economic Evaluation of Patients With Colorectal Liver Metastases Randomized to ALPPS or TSH: Analysis From the LIGRO Trial.

Objective: This is a preplanned, health economic evaluation from the LIGRO trial. One hundred patients with colorectal liver metastases (CRLM) and standardized future liver remnant <30% were randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or two-staged hepatectomy (TSH). Summary Background Data: TSH, is an established method in advanced CRLM. ALPPS has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health-related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy, and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Nonparametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12,662€, [95% confidence interval (CI): -10,728-36,051; P = 0.283]. Corresponding mean difference in life years and QALYs was 0.1296 (95% CI: -0.12-0.38; P = 0.314) and 0.1285 (95% CI: -0.11-0.36; P = 0.28), respectively. The ICER was 93,186 and 92,414 for QALYs and life years as outcomes, respectively. Conclusions: Based on the 2-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 years is needed.

Portal vein embolization with N-butyl-cyanoacrylate improves liver hypertrophy compared to microparticles - A Swedish multicenter cohort study.

Background: An adequate future liver remnant (FLR) is fundamental for major liver resections. To achieve sufficient FLR, portal vein embolization (PVE) may be used. The most effective material for PVE has yet to be determined. The aim of this study was to investigate the differences in FLR growth between n-butyl-cyanoacrylate glue (NBCA) and microparticles. Material/methodsa: retrospective study was performed at three Swedish hepatobiliary centers and included patients who underwent PVE 2013-2021. Electronic medical records were reviewed, and procedure-related data were collected. Data were analyzed with respect to embolizing material. Results: A total of 265 patients were included: 160 in the NBCA group and 105 in the microparticle group. The NBCA group had a higher degree of hypertrophy (12.1 vs. 9.4 % points, p = 0.003) and a higher resection rate (68 vs. 59 %, p = 0.01) than the microparticle group. Procedure-related data all indicated the superiority of NBCA. No difference in inducing hypertrophy was observed when comparing patients who received chemotherapy before PVE with those who received chemotherapy before and after PVE within the NBCA group. Discussion/conclusion: This retrospective multicenter study supports the superiority of NBCA compared to microparticles in the setting of PVE. Chemotherapy after PVE does not seem to negatively affect hypertrophy.

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. METHODS: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. RESULTS: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. CONCLUSIONS: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.

Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial.

BACKGROUND: Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. METHODS: The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. DISCUSSION: The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT03326791 . Registered on 31 October 2017.

Contributions to Multidisciplinary Team Meetings in Cancer Care: Predictors of Complete Case Information and Comprehensive Case Discussions.

PURPOSE: Multidisciplinary team (MDT) meetings integrate complex information and base recommendations for clinical management on interdisciplinary and multiprofessional decision-making. To support high-quality decision-making and define key performance indicators, we aimed to determine completeness of case information and contributions to MDT case discussions in cancer care. METHODS: In a prospective observational study design, based on three MDTs, we applied the Metric for Observation of Decision-Making (MODe) tool to assess the quality of case presentation and team members' contributions to case discussions. The MDTs handled patients with brain tumors, soft tissue sarcomas and hepatobiliary cancers. The results were correlated to patient and team characteristics and to MDT leadership skills. RESULTS: Data were collected from 349 case discussions during 32 MDT meetings. Information on radiology received the highest scores, followed by case history and information on histopathology. Patient-related information was less frequently mentioned and generally received low scores. Contributions to the case discussions were predominantly by the chair, surgeons, and oncologists with limited contributions from nurses. Leadership skills showed a positive correlation with case presentations scores and failure to reach a treatment recommendation correlated with lower case discussion scores. CONCLUSION: Considerable resources are spent on MDT meetings in cancer care, which motivate initiatives to ensure high-quality and efficient decision-making processes. We identify unbalanced contributions from team members during MDT meetings, demonstrate limited provision of patient-related information and show that leadership skills may positively influence the quality of the case presentations. We suggest that MDTs should consider and develop these aspects to ensure high-quality MDT-based case management and decision-making.

Medical and Nonmedical Information during Multidisciplinary Team Meetings in Cancer Care.

BACKGROUND: Multidisciplinary team (MDT) meetings provide treatment recommendations based on available information and collective decision-making in teams with complementary professions, disciplines and skills. We aimed to map ancillary medical and nonmedical patient information during case presentations and case discussions in MDT meetings in cancer care. METHODS: Through a nonparticipant, observational approach, we mapped verbal information on medical, nonmedical and patient-related characteristics and classified these based on content. Data were collected from 336 case discussions in three MDTs for neuro-oncology, sarcoma and hepato-biliary cancer. RESULTS: Information on physical status was presented in 48.2% of the case discussions, psychological status in 8.9% and comorbidity in 48.5% of the cases. Nonmedical factors, such as family relations, occupation, country of origin and abode were referred to in 3.6-7.7% of the cases, and patient preferences were reported in 4.2%. CONCLUSIONS: Provision of information on comorbidities in half of the cases and on patient characteristics and treatment preferences in <10% of case discussions suggest a need to define data elements and develop reporting standards to support robust MDT decision-making.

How should liver hypertrophy be stimulated? A comparison of upfront associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE) with rescue possibility.

BACKGROUND: The role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in comparison to portal vein embolization (PVE) is debated. The aim of this study was to compare successful resection rates (RR) with upfront ALPPS vs. PVE with rescue ALPPS on demand and to compare the hypertrophy of the liver between ALPPS and PVE plus subsequent rescue ALPPS. METHODS: A retrospective analysis of all patients treated with PVE for colorectal liver metastasis (CRLM) or ALPPS (any diagnosis, rescue ALPPS included) at five Scandinavian university hospitals during the years 2013-2016 was conducted. A Chi-square test and a Mann-Whitney U test were used to assess the difference between the groups. A successful RR was defined as liver resection without a 90-day mortality. RESULTS: A total of 189 patients were included. Successful RR was in 84.5% of the patients with ALPPS upfront and in 73.3% of the patients with PVE and rescue ALPPS on demand (P=0.080). The hypertrophy of the future liver remnants (FLRs) with ALPPS upfront was 71% (48-97%) compared to 96% (82-113%) after PVE and rescue ALPPS (P=0.010). CONCLUSIONS: Upfront ALPPS offers a somewhat higher successful RR than PVE with rescue ALPPS on demand. The sequential combination of PVE and ALPPS leads to a higher overall degree of hypertrophy than upfront ALPPS.

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.

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.

Leadership perspectives in multidisciplinary team meetings; observational assessment based on the ATLAS instrument in cancer care.

OBJECTIVES: High-quality leadership and chairing skills are central components in team performance during multidisciplinary team (MDT) meetings. We hypothesized that the recently developed A Tumor Leadership Assessment inStrument (ATLAS) could provide relevant information to support more detailed insights into MDT chairing and leadership aspects of relevance for team feedback and targeted improvements. MATERIALS AND METHODS: The observational assessment instrument ATLAS rates chairing and leadership skills during MDT meetings in 12 predefined domains that include e.g. time management, case prioritization, team involvement, discussion climate and clarity of treatment recommendations. We used ATLAS to prospectively assess 33 MDT meetings in neuro-oncology, sarcoma and hepatobiliary cancer. RESULTS: The aspects time management, effective case prioritization and provision of clear treatment plans were found to be well-functioning, whereas facilitatation of case discussions, encouragment of team member contributions, keeping the meeting focused and ability to summarize case discussions showed variable and partly weak results. CONCLUSION: We conclude that the ATLAS instrument effectively captures various aspects of MDT leadership and chairing skills. It may thereby provide relevant information to prioritize initiatives that support and develop effective teamwork and decision-making during MDT meetings.

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.

Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease.

BACKGROUND: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. METHODS: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. RESULTS: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95% CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. CONCLUSIONS: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.

A risk score model to predict incidental gallbladder cancer in patients scheduled for cholecystectomy.

BACKGROUND: Gallbladder cancer (GBC) has a poor prognosis. The aim was to develop and validate a preoperative risk score for incidental gallbladder cancer (IGBC) in patients scheduled for cholecystectomy. METHODS: Data registered in the nationwide Swedish Registry for Gallstone Surgery (GallRiks) was analyzed, including the derivation cohort (n = 28915, 2007-2014) and the validation cohort (n = 7851, 2014-2016). An additive risk score model based on odds ratio was created. RESULTS: The scoring model to predict IGBC includes age, female gender, previous cholecystitis, and either jaundice or acute cholecystitis. The calibration by HL test and discrimination by AUROC was 8.27 (P = 0.291) and 0.76 in the derivation cohort (214 IGBC) and 14.28 (P = 0.027) and 0.79 in the validation cohort (35 IGBC). The scoring system was applied to three risk-groups, based on the risk of having IGBC, eg. the high-risk group (>8 points) included 7878 patients, with 154 observed and 148 expected IGBC cases. CONCLUSION: We present the first risk score model to predict IGBC. The model estimates the expected risk for the individual patient and may help to optimize treatment strategies.

Segment 4 occlusion in portal vein embolization increase future liver remnant hypertrophy - A Scandinavian cohort study.

BACKGROUND: The additional value of including segment 4 (S4) portal branches in right portal vein embolization (rPVE) is debated. The aim of the study was to explore this in a large multicenter cohort. MATERIAL AND METHODS: A retrospective cohort study consisting of all patients subjected to rPVE from August 2012 to May 2017 at six Scandinavian university hospitals. PVE technique was essentially the same in all centers, except for the selection of main embolizing agent (particles or glue). All centers used coils or particles to embolize S4 branches. A subgroup analysis was performed after excluding patients with parts of or whole S4 included in the future liver remnant (FLR). RESULTS: 232 patients were included in the study, of which 36 received embolization of the portal branches to S4 in addition to rPVE. The two groups (rPVE vs rPVE + S4) were similar (gender, age, co-morbidity, diagnosis, neoadjuvant chemotherapy, bilirubin levels prior to PVE and embolizing material), except for diabetes mellitus which was more frequent in the rPVE + S4 group (p = 0.02). Pre-PVE FLR was smaller in the S4 group (333 vs 380 ml, p = 0.01). rPVE + S4 resulted in a greater percentage increase of the FLR size compared to rPVE alone (47 vs 38%, p = 0.02). A subgroup analysis, excluding all patients with S4 included in the FLR, was done. There was no longer a difference in pre-PVE FLR between groups (333 vs 325 ml, p = 0.9), but still a greater percentage increase and also absolute increase of the FLR in the rPVE + S4 group (48 vs 38% and 155 vs 112 ml, p = 0.01 and 0.02). CONCLUSION: In this large multicenter cohort study, additional embolization of S4 did demonstrate superior growth of the FLR compared to standard right PVE.

Incidental metastases and lymphoma of the gallbladder - an analysis of ten rare cases identified from a large national database.

Background: The aim was to identify and characterize rare malignancies of the gallbladder, incidentally found at cholecystectomy, and describe the diagnostic work-up, treatment and outcome. Methods: Data from cholecystectomies during 2007-2014 registered in the Swedish Register for Gallstone Surgery (GallRiks) were analyzed for incidental cancer. For completion of the pathology report, data were linked with the Swedish Registry for Cancer in the liver and biliary tract (SweLiv) and/or the Swedish Cancer Registry. Results: From 36,355 patients that underwent cholecystectomy on a benign indication 215 cases of incidental gallbladder cancer (IGBC) were identified. In total seven patients with metastases to the gallbladder from different primary tumors (breast cancer, malignant melanoma, gastric cancer, renal cell carcinoma, upper gastrointestinal cancer, colon cancer and pancreatic cancer) and three patients with lymphoma involvement of the gallbladder were found. Most patients were female with no difference between the groups (8/10 versus 171/215). The median age for the metastasis and lymphoma (MOL) group was equal to the IGBC group, 70 (64-72) years versus 70 (63-78) years. All patients in the MOL group underwent preoperative imaging with ultrasound or computed tomography, on which no metastases were identified. In only two patients a tumor was seen by the surgeon during the perioperative examination of the gallbladder. The median survival was 5.8 months for MOL patients and 23 months for IGBC patients. Conclusion: Metastases and lymphoma of the gallbladder are rare. Traditional imaging methods prior to cholecystectomy may miss gallbladder malignancies. A liberal approach of histopathological analysis of the gallbladder should be applied.