Hepatocellular carcinoma in cirrhotic versus non-cirrhotic liver: Treatment and survival differences in a nationwide cohort.

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.

Outcome after surgery for invasive intraductal papillary mucinous neoplasia compared to conventional pancreatic ductal adenocarcinoma - A Swedish nationwide register-based study.

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.

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.

Molecular adsorbent recirculating system treatment in patients with post-hepatectomy liver failure: Long-term results of a pilot study.

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).

Treatment intention and outcome in patients with simultaneously diagnosed liver and lung metastases from colorectal cancer.

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 < 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.

Composite Score: prognostic tool to predict survival in patients undergoing surgery for colorectal liver metastases.

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.

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.

Quality-of-life after bile duct injury repaired by hepaticojejunostomy: a national cohort study.

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.

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.

Synchronous and metachronous liver metastases in patients with colorectal cancer-towards a clinically relevant definition.

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.

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.

The molecular adsorbent recirculating system in posthepatectomy liver failure: Results from a prospective phase I study.

Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50:50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5-7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60- and 90-day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60- and 90-day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial. (Hepatology Communications 2018;2:445-454).

Colorectal cancer liver metastases - a population-based study on incidence, management and survival.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-associated deaths with liver metastases developing in 25-30% of those affected. Previous data suggest a survival difference between right- and left-sided liver metastatic CRC, even though left-sided cancer has a higher incidence of liver metastases. The aim of the study was to describe the liver metastatic patterns and survival as a function of the characteristics of the primary tumour and different combinations of metastatic disease. METHODS: A retrospective population-based study was performed on a cohort of patients diagnosed with CRC in the region of Stockholm, Sweden during 2008. Patients were identified through the Swedish National Quality Registry for Colorectal Cancer Treatment (SCRCR) and additional information on intra- and extra-hepatic metastatic pattern and treatment were retrieved from electronic patient records. Patients were followed for 5 years or until death. Factors influencing overall survival (OS) were investigated by means of Cox regression. OS was compared using Kaplan-Meier estimations and the log-rank test. RESULTS: Liver metastases were diagnosed in 272/1026 (26.5%) patients within five years of diagnosis of the primary. Liver and lung metastases were more often diagnosed in left-sided colon cancer compared to right-sided cancer (28.4% versus 22.1%, p = 0.029 and 19.7% versus 13.2%, p = 0.010, respectively) but the extent of liver metastases were more extensive for right-sided cancer as compared to left-sided (p = 0.001). Liver metastatic left-sided cancer, including rectal cancer, was associated with a 44% decreased mortality risk compared to right-sided cancer (HR = 0.56, 95% CI: 0.39-0.79) with a 5-year OS of 16.6% versus 4.3% (p < 0.001). In liver metastatic CRC, the presence of lung metastases did not significantly influence OS as assessed by multivariate analysis (HR = 1.11, 95% CI: 0.80-1.53). CONCLUSION: The worse survival in liver metastatic right-sided colon cancer could possibly be explained by the higher number of metastases, as well as more extensive segmental involvement compared with left-sided colon and rectal cancer, even though the latter had a higher incidence of liver metastases. Detailed population-based data on the metastatic pattern of CRC and survival could assist in more structured and individualized guidelines for follow-up of patients with CRC.

The Impact of a Hepatobiliary Multidisciplinary Team Assessment in Patients with Colorectal Cancer Liver Metastases: A Population-Based Study.

BACKGROUND: Assessing patients with colorectal cancer liver metastases (CRCLM) by a liver multidisciplinary team (MDT) results in higher resection rates and improved survival. The aim of this study was to evaluate the potentially improved resection rate in a defined cohort if all patients with CRCLM were evaluated by a liver MDT. PATIENTS AND METHODS: A retrospective analysis of patients diagnosed with colorectal cancer during 2008 in the greater Stockholm region was conducted. All patients with liver metastases (LM), detected during 5-year follow-up, were re-evaluated at a fictive liver MDT in which previous imaging studies, tumor characteristics, medical history, and patients' own treatment preferences were presented. Treatment decisions for each patient were compared to the original management. Odds ratios (ORs) and 95% confidence intervals were estimated for factors associated with referral to the liver MDT. RESULTS: Of 272 patients diagnosed with LM, 102 patients were discussed at an original liver MDT and 69 patients were eventually resected. At the fictive liver MDT, a further 22 patients were considered as resectable/potentially resectable, none previously assessed by a hepatobiliary surgeon. Factors influencing referral to liver MDT were age (OR 3.12, 1.72-5.65), American Society of Anaesthesiologists (ASA) score (OR 0.34, 0.18-0.63; ASA 2 vs. ASA 3), and number of LM (OR 0.10, 0.04-0.22; 1-5 LM vs. >10 LM), while gender (p = .194) and treatment at a teaching hospital (p = .838) were not. CONCLUSION: A meaningful number of patients with liver metastases are not managed according to best available evidence and the potential for higher resection rates is substantial. IMPLICATIONS FOR PRACTICE: Patients with liver metastatic colorectal cancer who are assessed at a hepatobiliary multidisciplinary meeting achieve higher resection rates and improved survival. Unfortunately, patients who may benefit from resection are not always properly referred. In this study, the potential improved resection rate was assessed by re-evaluating all patients with liver metastases from a population-based cohort, including patients with extrahepatic metastases and accounting for comorbidity and patients' own preferences towards treatment. An additional 12.9% of the patients were found to be potentially resectable. The results highlight the importance of all patients being evaluated in the setting of a hepatobiliary multidisciplinary meeting.

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.

Endoscopic sphincterotomy and risk of cholangiocarcinoma: a population-based cohort study in Finland and Sweden.

Background and study aims: Elevated long-term risk of cholangiocarcinoma is reported after endoscopic sphincterotomy (ES), but in a previous study we found a trend towards a decreased risk. The aim of this study was to evaluate the association in a larger cohort with a longer follow-up. Patients and methods: Data concerning all patients having had an inpatient endoscopic retrograde cholangiopancreatography (ERCP) were collected from the hospital discharge registries of Finland and Sweden. Incident cases of malignancy were identified through linkage to the nationwide Cancer Registries. Patients with a diagnosis of malignancy, before or within 2 years of the ERCP, were excluded. The cohorts were followed until a diagnosis of malignancy, death or emigration, or end of follow-up (end of 2010). The relative risk of malignancy was calculated as standardized incidence ratio (SIR) compared with the general population, inherently adjusting for age, gender, and calendar year of follow-up. Results: A total of 69 925 patients undergoing ERCP from 1976 through 2008 were included in the pooled cohort. ES was performed in 40 193 subjects. The risk of malignancy was elevated in the total cohort (SIR = 2.3; 95 % confidence interval [CI] 2.1 - 2.5) irrespective of whether ES was performed or not. The SIRs diminished with duration of follow-up. Conclusions: We found an elevated risk of malignancy both in the bile ducts alone and in the bile ducts, liver or pancreas together, after ERCP. The risk was the same, regardless of whether ES had been performed or not, so ES was unlikely to be the cause, and a common carcinogenic exposure previous to the ERCP procedure, possibly ductal gallstone disease, was more likely.

Effect of intended intraoperative cholangiography and early detection of bile duct injury on survival after cholecystectomy: population based cohort study.

OBJECTIVES: To determine whether the routine use of intraoperative cholangiography can improve survival from complications related to bile duct injuries. DESIGN: Population based cohort study. SETTING: Prospectively collected data from the Swedish national registry of gallstone surgery and endoscopic retrograde cholangiopancreatography, GallRiks. Multivariate analysis done by Cox regression. POPULATION: All cholecystectomies recorded in GallRiks between 1 May 2005 and 31 December 2010. MAIN OUTCOME MEASURES: Evidence of bile duct injury, rate of intended use of intraoperative cholangiography, and rate of survival after cholecytectomy. RESULTS: During the study, 51,041 cholecystectomies were registered in GallRiks and 747 (1.5%) iatrogenic bile duct injuries identified. Patients with bile duct injuries had an impaired survival compared with those without injury (mortality at one year 3.9% v 1.1%). Kaplan-Meier analysis showed that early detection of a bile duct injury, during the primary operation, improved survival. The intention to use intraoperative cholangiography reduced the risk of death after cholecystectomy by 62% (hazard ratio 0.38 (95% confidence interval 0.31 to 0.46)). CONCLUSIONS: The high incidence of bile duct injury recorded is probably from GallRiks' ability to detect the entire range of injury severities, from minor ductal lesions to complete transections of major ducts. Patients with bile duct injury during cholecystectomy had impaired survival, and early detection of the injury improved survival. The intention to perform an intraoperative cholangiography reduced the risk of death after cholecystectomy.

Possible mortality reduction by endoscopic sphincterotomy during endoscopic retrograde cholangiopancreatography: a population-based case-control study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used for young patients, but ERCP and endoscopic sphincterotomy in particular are reported to be associated with increased complication and mortality rates. This study aimed to calculate mortality and to identify risk factors for death within 90 days after ERCP for nonmalignant disease. METHODS: From the Swedish Hospital Discharge Registry, the authors identified all individuals in Stockholm County who had undergone in-patient ERCP during 1990-2003. Among these individuals, they excluded those recorded in the Swedish Cancer Registry as having a diagnosis of malignancy in the liver, pancreas, or bile ducts. Cases, defined as patients who had died within 90 days after the procedure, were identified by cross-linkage to the causes of death registry. Control subjects were randomly sampled from the same cohort. The medical records were studied to discern risk factors for death after ERCP. RESULTS: The mortality rate was 1.6%. Advanced age, severe comorbidity, high complexity of the procedure, and occurrence of a complication were associated with death within 90 days, whereas a previous cholecystectomy or the simultaneous performance of an endoscopic sphincterotomy reduced the risk. CONCLUSIONS: Old age and comorbidity are the main risk factors for death after ERCP, but a complex procedure or the occurrence of a complication also seems to increase short-term mortality. The performance of a sphincterotomy may reduce the risk of death, possibly by facilitating adequate drainage. A previous cholecystectomy also may decrease the risk of death after ERCP.