BACKGROUND:Limited research exists on whether post-hepatectomy liver failure (PHLF) impacts recurrence following major hepatectomy for colorectal cancer liver metastases (CRLM). This retrospective study aims to explore this further. METHODS:Data from patients who underwent major hepatectomy for CRLM at Karolinska University Hospital, Sweden, between 2012 and 2020 was analyzed. PHLF definition followed the International Study Group of Liver Surgery criteria. Recurrence risks were estimated with cumulative incidence functions, and Gray's test compared groups. Liver-specific and overall recurrence-free survival (RFS) were assessed using the Fine & Gray subdistribution hazards model, considering competing risks. RESULTS:Of 327 patients, 11 % developed PHLF grade A and 8 % developed PHLF grade B/C. Liver metastasis recurred in 57 % after a median follow-up of 40 months. Three-year cumulative incidences of liver recurrence was not significantly different: no PHLF (56 %), PHLF grade A (50 %), and PHLF grade B/C (48 %). Respectively for overall recurrence: no PHLF (75 %), PHLF grade A (63 %), and PHLF grade B/C (76 %). PHLF did not significantly impact either liver-specific RFS or overall RFS in multivariable analyses. CONCLUSION:Despite its substantial effect on short-term outcomes, PHLF does not appear to be a critical factor for disease recurrence after major hepatectomy for CRLM.

BACKGROUND:This study aimed to investigate whether socioeconomic factors are associated with an improved long-term survival after colorectal cancer liver metastases (LM) resection. METHODS:A retrospective nationwide population-based cohort study. 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 the 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:In total, 2874 liver resections were performed in 2327 patients who were included in the study. In the group, 1362 (59%) were male and the median age was 65 (3-89) years. Patients that had more than one resection, the time was counted from the last resection. The main resection was a local resection that was performed in 60% of patients. The overall 5-year survival rate was 48%. In the univariate analysis, there was a significant association in overall survival for age, comorbidity, sex, income, and education level. In the adjusted multivariate logistic regression analysis, there was a significant relation with (higher OS, for lower age (HR 1.46 (95% CI: 1.23-1.72) and p < 0.001), lower comorbidity (HR 0.78 (95% CI: 0.66-0.92) and p < 0.003), female sex (HR 1.24 (95% CI: 1.05-1.47) and p = 0.01), and higher income (HR 0.84 (95% CI: 0.71-0.99) and p = 0.045)). CONCLUSIONS:Patients that underwent surgery for LM from mainly colorectal disease and who have a low-income experience shorter overall survival. Further findings showed that patients with lower age and comorbidity and female sex had longer overall survival.

Background and aims: Numerous studies have reported superior outcome for patients with hepatocellular carcinoma (HCC) in non-cirrhotic compared to cirrhotic livers. This cohort study aims to describe the clinical presentation, disease course, treatment approaches, and survival differences in a population-based setting. Methods: Data on patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry (SweLiv). Descriptive and survival statistics were applied. Results: Among the 4259 identified patients, 34% had HCC in a non-cirrhotic liver. Cirrhotic patients presented at a younger age (median = 64 vs 74 years, p < 0.001) and with a poorer performance status (Eastern Cooperative Oncology Group (ECOG) = 0–1: 64% vs 69%, p = 0.024). Underlying liver disease was more prevalent among cirrhotic patients (81% vs 19%, p < 0.001). Tumors in non-cirrhotic livers were diagnosed at a more advanced stage (T3–T4: 46% vs 31%) and more frequently with metastatic disease at diagnosis (22% vs 10%, p < 0.001). Tumors were significantly larger in non-cirrhotic livers (median size of largest tumor 7.5 cm) compared to cirrhotic livers (3.5 cm) (p < 0.001). Curative interventions were more commonly intended (45% vs 37%, p < 0.001) and performed (40% vs 31%, p < 0.001) in the cirrhotic vs non-cirrhotic patients. Median survival was 19 months (95% confidence interval (CI) = 18–21 months), in patients with cirrhosis as compared to 13 months in non-cirrhotic patients (95% CI = 11–15) (p < 0.001). In the multivariable Cox regression model, cirrhosis was not an independent predictor of survival, neither among curatively nor palliatively treated patients. Conclusion: These population-based data show that patients with HCC in a cirrhotic liver receive curative treatment to a greater extent and benefit from superior survival compared to those with HCC in a non-cirrhotic liver. The differences in survival are more attributable to patient and tumor characteristics rather than the cirrhotic status itself. Clinical trial registration: not applicable. Patient confidentially: not applicable.

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.

We write to congratulate Dr Engstrand and colleagues for their careful and excellently presented report on treatment intent and outcomes of patients with both liver and lung metastases from colorectal cancer (CRC) [1]. They state “Complete resection resulted in longer survival compared to patients who did not undergo resection of all metastatic sites with median survival of 63 and 27 months, respectively (p < 0.001)”. This seems a bold statement given that this is an observational study of a very complex sample of patients as shown in Table 1.

Background: Heterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact. Methods: A retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses. Results: Out of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p < .001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02-2.78)), right-sided primary tumour (HR 2.01 (1.29-3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06-3.17)). Conclusion: Outcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND:The clinical importance of intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Long-term survival after resection for invasive IPMN (inv-IPMN) compared to conventional pancreatic ductal adenocarcinoma (PDAC) is not thoroughly delineated. OBJECTIVE:This study, based on the Swedish national pancreatic and periampullary cancer registry aims to elucidate the outcome after resection of inv-IPMN compared to PDAC. METHODS:All patients ≥18 years of age resected for inv-IPMN and PDAC in Sweden between 2010 and 2019 were included. Clinicopathological variables were retrieved from the national registry. The effect on death was assessed in two multivariable Cox regression models, one for patients resected 2010-2015, one for patients resected 2016-2019. Median overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS:We included 1909 patients, 293 inv-IPMN and 1616 PDAC. The most important independent predictors of death in multivariable Cox regressions were CA19-9 levels, venous resection, tumour differentiation, as well as T-, N-, M-stage and surgical margin. Tumour type was an independent predictor for death in the 2016-2019 cohort, but not in the 2010-2015 cohort. In Kaplan-Meier survival analysis, inv-IPMN was associated with longer median OS in stage N0-1 and in stage M0 compared to PDAC. However, in stage T2-4 and stage N2 median OS was similar, and in stage M1 even shorter for inv-IPMN compared to PDAC. CONCLUSION:In this population-based nationwide study, outcome after resected inv-IPMN compared to PDAC is more favourable in lower stages, and similar to worse in higher.

Introduction: The variability in chemotherapeutic response between different colorectal liver metastases (CRLM), suggest an impact of physiological and/or biological preconditions. This study aimed to evaluate factors associated with chemotherapeutic response and its impact on outcome in patients with CRLM, receiving neoadjuvant chemotherapy. Methods: A retrospective cohort study was conducted including all patients with CRLM surgically resected at Karolinska University Hospital, Stockholm, Sweden, from 2013-2018. Factors associated with chemotherapeutic response and surgical outcome were analysed with linear regression and survival analyses. Results: Out of 627 surgically treated patients (with 1648 CRLM), 403 patients (with 1312 CRLM), received neoadjuvant chemotherapy. Percentage of viable tumour cells was associated with the occurrence of vascular invasion, oxaliplatin-based chemotherapy, administration of targeted agents, tumour diameter and number of metastases (R2=.12, F(5,642)= 17.38, p<.001). Inferior disease-free survival (DFS) was significantly associated with viable tumour cells>75% (hazard ratio (HR) 1.75(95% CI 1.12-2.73)), CRLM located in central liver segments (HR 1.46(1.00-2.12)), extrahepatic disease (HR 1.89(1.22-2.96)), synchronous CRLM (HR 1.63(1.01-2.62)) and radical resection (HR .63(.43-.93)). The median DFS for patients with CRLM with viable tumour cells>75% was 7 months, compared to 11 months for patients with viable tumour cells<75%, p<.001. Poor overall survival was significantly associated with viable tumour cells>75% (HR 2.30(1.17-4.50)), CRLM diameter (HR 1.02(1.00-1.03)) and right-sided primary tumour (HR 2.56(1.36-4.80)). Conclusion: The impact of chemotherapeutic agents on the viability of treated CRLM in addition to the prognostic importance of the location of the tumour burden suggest that certain physiological and biological preconditions could improve outcome of CRLM.

BACKGROUND:The aim was to assess the likelihood of patients with simultaneously diagnosed liver and lung metastases (SLLM) from colorectal cancer (CRC) to receive the curative treatment decided upon multidisciplinary team meeting (MDT) and to elaborate on the reasons for treatment intention failure and survival outcomes depending on final treatment strategy. METHOD:The study included a retrospective review of all patients discussed at the MDT at a single centre between 2010 and 2018 to identify all patients presenting with SLLM from CRC. Treatment intention, actual treatment outcome and reasons for treatment failure was documented. Descriptive and survival statistics were applied. RESULTS:Of the 160 patients who had SLLM, resection of all metastatic sites was deemed possible in 107 patients (67%) of whom 39 patients (36%) finalized the curative treatment plan. The most common reason for noncompliance with management recommendations was disease progression or recurrence. Complete resection resulted in longer survival compared to patients who did not undergo resection of all metastatic sites with median survival of 63 and 27 months, respectively (p &lt; 0.001). CONCLUSION:A low proportion of patients completed the initially intended curative resections. Simultaneous resection of liver/lung metastases and primary tumour might increase the proportion of fulfilled hepatopulmonary resections.

Background: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort. Methods: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria. Results: The cohort was split into three time periods: pre-MARS period ( n = 192), MARS study period ( n = 207), and post-MARS period ( n = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period ( p = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3–51.7) in the pre-MARS cohort, 57 months (40.7–75.6) in the MARS cohort, and 38.8 months (31.4–51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5–25.9), respectively ( p = 0.138)). Conclusions: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed. The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) with stenting is considered the treatment of choice in bile leakage (BL) after liver surgery. Evidence is lacking on which strategy to choose, distal downstream decompression of the biliary tree or insertion of a longer stent for drainage closer to or bridging the the leakage point. Methods: All ERCPs performed in Sweden are registered in a national quality registry (GallRiks). Data on all ERCPs performed for the indication of BL between 2006-2017 were extracted. Patients who underwent endoscopic intervention for BL following liver resection were compared in two groups: sphincterotomy only or placement of a stent ≤ 7 cm (distal decompression) vs. placement of a stent >7cm (proximal drainage or bridging). The primary outcome was was cessation of BL within 30 days of endoscopic intervention. Results: A total of 2346 ERCPs were performed for BL, of which 259 procedures were in 201 persons following liver resection. Ten patients in whom ERCP could not demonstrate a leak were excluded from the analyses. In 87 patients distal decompression was performed and in 104 patients proximal drainage or bridging. The groups were comparable regarding age, sex and comorbidities. There were no differences in 30-day cessation of BL between the two groups (OR 0.71 (95% CI 0.26-1.98)) and complication rates were comparable (OR 1.30 (95% CI 0.73-2.31). Conclusion: Downstream control seems to be as efficient as the insertion of a proximal or bridging stent in treatment of BL after liver resection.

Abstract Background Several existing scoring systems predict survival of patients with colorectal liver metastases. Many lack validation, rely on old clinical data, and have been found to be less accurate since the introduction of chemotherapy. This study aimed to construct and validate a clinically relevant preoperative prognostic model for patients with colorectal liver metastases. Methods A predictive model with data available before surgery was developed. Survival was analysed by Cox regression analysis, and the quality of the model was assessed using discrimination and calibration. The model was validated using multifold cross-validation. Results The model included 1212 consecutive patients who underwent liver resection for colorectal liver metastases between 2005 and 2015. Prognostic factors for survival included advanced age, raised C-reactive protein level, hypoalbuminaemia, extended liver resection, larger number of metastases, and midgut origin of the primary tumour. A Composite Score was developed based on the prognostic variables. Patients were classified into those at low, medium, and high risk. Survival differences between the groups were significant; median overall survival was 87.4 months in the low-risk group, 50.1 months in the medium-risk group, and 22.6 months in the high-risk group. The discriminative performance, assessed by the concordance index, was 0.71, 0.67, and 0.67 respectively at 1, 3, and 5 years. Calibration, assessed graphically, was close to perfect. A multifold cross-validation of the model confirmed its internal validity (C-index 0.63 versus 0.62). Conclusion The Composite Score categorizes patients into risk strata, and may help identify patients who have a poor prognosis, for whom surgery is questionable.

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.

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 trans-plantation 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 trans-plantation, 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.

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.

Background: Metastatic spread of primary tumors is the most important issue in cancer related mortality. The location of the primary tumor and the presence of synchronous disease both have implications on prognosis. The aim of the study was to determine the prognostic impact of synchronous/metachronous disease and its relation to primary tumor site. Material/Methods: A retrospective, population-based cohort study was conducted, including all patients with resectable colorectal cancer liver metastases (CRCLM) at the Center for Digestive Diseases, Karolinska University Hospital from January 2005, to December 2015. Logistic regression analysis was performed to determine prognostic factors for overall survival (OS) and occurrence of synchronous/metachronous tumors. Results: Out of 794 identified patients, 747 patients (94%) were included in the study. The mean OS was 50 months. OS in patients given perioperative chemotherapy was 53 months compared to 47 months in patients without therapy (p<.001). Poor survival was significantly associated with number of CRCLM (OR 1.092, 95%CI 1.041-2.146), synchronous CRCLM (OR 1.329, 95%CI 1.049-1.683), tumor margin<1mm (OR 1.452, 95%CI 1.151-1.832), perioperative chemotherapy (OR .613, 95%CI .489-.769), recurrence after liver resection (OR 4.508, 95%CI 3.437-5.913) and reresection of CRCLM (OR .326, 95%CI .228-.466). Right-sided carcinomas almost reached a significant association (OR 1.277, 95%CI .988-1.635, p=.052). The occurrence of synchronous CRCLM was significantly associated with age (OR .982, 95%CI .965-1.000), number of CRCLM (OR 1.180, 95%CI 1.063-1.310), right-sided carcinomas (OR 1.691, 95%CI 1.102-2.594), preoperative chemotherapy (OR 3.858, 95%CI 2.631-5.658) and recurrence after liver resection (OR 1.683, 95%CI 1.191-2.377). Conclusion: This study identifies perioperative chemotherapy as a favorable prognostic factor in patients with resectable CRCLM, whereas synchronous disease is associated with worse survival. In addition, we suggest that the poor prognosis in patients with right-sided carcinomas might be associated with the occurrence of synchronous CRCLM.

Objectives Reports on quality-of-life (QoL) after bile duct injury (BDI) show conflicting results. The aim of this cohort study was to evaluate QoL stratified according to type of treatment. Methods QoL assessment using the SF-36 (36-item short form health survey) questionnaire. Patients with post-cholecystectomy BDI needing hepaticojejunostomy (HJ) were compared to all other treatments (BDI repair) and to patients without BDI at cholecystectomy (controls). Results Patients needing a HJ after BDI reported reduced long-term QoL irrespective of time for diagnosis and repair in both the physical (PCS;p < .001) and mental (MCS;p < .001) domain compared to both controls and patients with less severe BDI. QoL was comparable for BDI repair (n = 86) and controls (n = 192) in both PCS (p = .171) and MCS (p = .654). As a group, patients with BDI (n = 155) reported worse QoL than controls, in both the PCS (p < .001) and MCS (p = .012). Patients with a BDI detected intraoperatively (n = 124) reported better QoL than patients with a postoperative diagnosis. Patients with an immediate intraoperative repair (n = 99), including HJ, reported a better long-term QoL compared to patients subjected to a later procedure (n = 54). Conclusions Patients with postoperative diagnosis and patients with BDIs needing biliary reconstruction with HJ both reported reduced long-term QoL.

Background Approximately 25% of patients with colorectal cancer (CRC) will have liver metastases classified as synchronous or metachronous. There is no consensus on the defining time point for synchronous/metachronous, and the prognostic implications thereof remain unclear. The aim of the study was to assess the prognostic value of differential detection at various defining time points in a population-based patient cohort and conduct a literature review of the topic. Methods All patients diagnosed with CRC in the counties of Stockholm and Gotland, Sweden, during 2008 were included in the study and followed for 5 years or until death to identify patients diagnosed with liver metastases. Patients with liver metastases were followed from time of diagnosis of liver metastases for at least 5 years or until death. Different time points defining synchronous/metachronous detection, as reported in the literature and identified in a literature search of databases (PubMed, Embase, Cochrane library), were applied to the cohort, and overall survival was calculated using Kaplan-Meier curves and compared with log-rank test. The influence of synchronously or metachronously detected liver metastases on disease-free and overall survival as reported in articles forthcoming from the literature search was also assessed. Results Liver metastases were diagnosed in 272/1026 patients with CRC (26.5%). No statistically significant difference in overall survival for synchronous vs. metachronous detection at any of the defining time points (CRC diagnosis/surgery and 3, 6 and 12 months post-diagnosis/surgery) was demonstrated for operated or non-operated patients. In the literature search, 41 publications met the inclusion criteria. No clear pattern emerged regarding the prognostic significance of synchronous vs. metachronous detection. Conclusion Synchronous vs. metachronous detection of CRC liver metastases lacks prognostic value. Using primary tumour diagnosis/operation as standardized cut-off point to define synchronous/metachronous detection is semantically correct. In synchronous detection, it defines a clinically relevant group of patients where individualized multimodality treatment protocols will apply.

Background: Bile leakage (BL) after liver resection is an important cause of post-operative morbidity. Percutaneous drainage is the standard therapy but may be prolonged until leak cessation. This study investigates if sphincterotomy and stent reduces duration and significance of BL. Methods: All patients with ISGLS grades A or B BL were eligible for inclusion in this randomized controlled trial. Participants were randomized to standard percutaneous drain or to drain plus sphincterotomy and main bile duct stent. Primary outcome was bilirubin output (drain volume x bilirubin concentration/day) on day 2 after intervention or the corresponding day. Secondary outcomes were BL duration, time of in-hospital stay and complications. Results: 39 patients were included. 20 were randomized to drain and 19 to stent. The groups were similar with respect to patient and surgery characteristics and bilirubin output at inclusion. There was a trend towards reduced BL output in the stent group (median 17 vs 29 μmol/day, p = 0.17), but no significant difference. There were no significant differences in leak duration, time of in-hospital stay or overall morbidity. Conclusion: Sphincterotomy with stent is safe in BL patients. As no significant reduction in BL or clinical benefit was achieved in this study of unselected grade A and B BL patients, we cannot recommend the method for this whole patient group. The trend towards BL reduction implies substantial benefit for some patients and further selection tools are needed.