Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

The Influence of Hepatic Steatosis and Fibrosis on Postoperative Outcomes After Major Liver Resection of Perihilar Cholangiocarcinoma.

BACKGROUND: Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS: Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS: Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION: In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.

Nationwide treatment and outcomes of intrahepatic cholangiocarcinoma.

BACKGROUND: Most data on the treatment and outcomes of intrahepatic cholangiocarcinoma (iCCA) derives from expert centers. This study aimed to investigate the treatment and outcomes of all patients diagnosed with iCCA in a nationwide cohort. METHODS: Data on all patients diagnosed with iCCA between 2010 and 2018 were obtained from the Netherlands Cancer Registry. RESULTS: In total, 1747 patients diagnosed with iCCA were included. Resection was performed in 292 patients (17%), 548 patients (31%) underwent palliative systemic treatment, and 867 patients (50%) best supportive care (BSC). The OS median and 1-, and 3-year OS were after resection: 37.5 months (31.0-44.0), 79.2%, and 51.6%,; with systemic therapy, 10.0 months (9.2-10.8), 38.4%, and 5.1%, and with BSC 2.2 months (2.0-2.5), 10.4%, and 1.3% respectively. The resection rate for patients who first presented in academic centers was 33% (96/292) compared to 13% (195/1454) in non-academic centers (P < 0.001). DISCUSSION: Half of almost 1750 patients with iCCA over an 8 year period did not receive any treatment with a 1-year OS of 10.4%. Three-year survival was about 50% after resection, while long-term survival was rare after palliative treatment. The resection rate was higher in academic centers compared to non-academic centers.

Multivariable prediction model for both 90-day mortality and long-term survival for individual patients with perihilar cholangiocarcinoma: does the predicted survival justify the surgical risk?

BACKGROUND: The risk of death after surgery for perihilar cholangiocarcinoma is high; nearly one in every five patients dies within 90 days after surgery. When the oncological benefit is limited, a high-risk resection may not be justified. This retrospective cohort study aimed to create two preoperative prognostic models to predict 90-day mortality and overall survival (OS) after major liver resection for perihilar cholangiocarcinoma. METHODS: Separate models were built with factors known before surgery using multivariable regression analysis for 90-day mortality and OS. Patients were categorized in three groups: favourable profile for surgical resection (90-day mortality rate below 10 per cent and predicted OS more than 3 years), unfavourable profile (90-day mortality rate above 25 per cent and/or predicted OS below 1.5 years), and an intermediate group. RESULTS: A total of 1673 patients were included. Independent risk factors for both 90-day mortality and OS included ASA grade III-IV, large tumour diameter, and right-sided hepatectomy. Additional risk factors for 90-day mortality were advanced age and preoperative cholangitis; those for long-term OS were high BMI, preoperative jaundice, Bismuth IV, and hepatic artery involvement. In total, 294 patients (17.6 per cent) had a favourable risk profile for surgery (90-day mortality rate 5.8 per cent and median OS 42 months), 271 patients (16.2 per cent) an unfavourable risk profile (90-day mortality rate 26.8 per cent and median OS 16 months), and 1108 patients (66.2 per cent) an intermediate risk profile (90-day mortality rate 12.5 per cent and median OS 27 months). CONCLUSION: Preoperative risk models for 90-day mortality and OS can help identify patients with resectable perihilar cholangiocarcinoma who are unlikely to benefit from surgical resection. Tailored shared decision-making is particularly essential for the large intermediate group.

Major complications and mortality after resection of intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Evaluation of morbidity and mortality after hepatic resection often lacks stratification by extent of resection or diagnosis. Although a liver resection for different indications may have technical similarities, postoperative outcomes differ. The aim of this systematic review and meta-analysis was to determine the risk of major complications and mortality after resection of intrahepatic cholangiocarcinoma. METHODS: Meta-analysis was performed to assess postoperative mortality (in-hospital, 30-, and 90-day) and major complications (Clavien-Dindo grade ≥III). RESULTS: A total of 32 studies that reported on 19,503 patients were included. Pooled in-hospital, 30-day, and 90-day mortality were 5.9% (95% confidence interval 4.1-8.4); 4.6% (95% confidence interval 4.0-5.2); and 6.1% (95% confidence interval 5.0-7.3), respectively. Pooled proportion of major complications was 22.2% (95% confidence interval 17.7-27.5) for all resections. The pooled 90-day mortality was 3.1% (95% confidence interval 1.8-5.2) for a minor resection, 7.4% (95% confidence interval 5.9-9.3) for all major resections, and 11.4% (95% confidence interval 6.9-18.7) for extended resections (P = .001). Major complications were 38.8% (95% confidence interval 29.5-49) after a major hepatectomy compared to 11.3% (95% confidence interval 5.0-24.0) after a minor hepatectomy (P = .001). Asian studies had a pooled 90-day mortality of 4.4% (95% confidence interval 3.3-5.9) compared to 6.8% (95% confidence interval 5.6-8.2) for Western studies (P = .02). Cohorts with patients included before 2000 had a pooled 90-day mortality of 5.9% (95% confidence interval 4.8-7.3) compared to 6.8% (95% confidence interval 5.1-9.1) after 2000 (P = .44). CONCLUSION: When informing patients or comparing outcomes across hospitals, postoperative mortality rates after liver resection should be reported for 90-days with consideration of the diagnosis and the extent of liver resection.

Actual 10-Year Survival after Resection of Perihilar Cholangiocarcinoma: What Factors Preclude a Chance for Cure?

Complete resection of perihilar cholangiocarcinoma (pCCA) is the only potentially curative treatment. Long-term survival data is rare and prognostic analyses are hindered by the rarity of the disease. This study aimed to determine the cure rate and to identify clinicopathological factors that may preclude cure. All consecutive resections for pathologically confirmed pCCA between 2000 and 2009 in 22 centers worldwide were included in a retrospective cohort study. Each center included its retrospective data series. A total of 460 patients were included with a median follow-up of 10 years for patients alive at last follow-up. Median overall survival (OS) was 29.9 months and 10-year OS was 12.8%. Twenty-nine (6%) patients reached 10-year OS. The observed cure rate was 5%. Factors that virtually precluded cure (i.e., below 1%) according to the mixture cure model included age above 70, Bismuth-Corlette type IV tumors, hepatic artery reconstruction, and positive resection margins. Cure was unlikely (i.e., below 3%) in patients with positive lymph nodes or poor tumor differentiation. These factors need to be considered in patient counseling and long-term follow-up after surgery.

Primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma.

BACKGROUND: The aim of this study was to investigate the incidence and risk factors of primary and secondary liver failure after major liver resection for perihilar cholangiocarcinoma. METHODS: All patients who underwent a major liver resection for presumed perihilar cholangiocarcinoma between 2000 and 2020 at 2 tertiary-referral hospitals were included. Liver failure was defined according to the International Study Group for Liver Surgery criteria, and only grade B/C was considered clinically relevant. Primary liver failure was defined as failure without any underlying postoperative cause, and secondary liver failure was defined as liver failure with an onset after an underlying postoperative complication as a cause. RESULTS: The incidence of liver failure and 90-day mortality were 20.9% and 17.0% in the 253 included patients, respectively. The incidences of primary liver failure was 9.1% and secondary liver failure was 11.9%. Abdominal sepsis, portal vein thrombosis, and arterial thrombosis were the most frequent causes. The absence of preoperative remnant liver assessment and blood loss were independent risk factors for primary liver failure. Independent risk factors for secondary liver failure were Eastern Cooperative Oncology group performance status, percutaneous biliary drainage, and preoperative cholangitis. CONCLUSION: Liver failure after major liver resection for perihilar cholangiocarcinoma occurred in 1 of every 5 patients. The proposed subdivision into primary and secondary liver failure could help to understand differences in outcomes between centers and help to reduce liver failure.

Surgical morbidity in the first year after resection for perihilar cholangiocarcinoma.

BACKGROUND: Surgery for perihilar cholangiocarcinoma (pCCA) is associated with high morbidity and mortality rates. The impact of surgery for pCCA may affect patients after discharge. The aim of this study was to investigate all morbidity and mortality during the first year after surgery for pCCA. METHODS: All consecutive liver resections for suspected pCCA between 2000 and 2019 at two tertiary referral centers were included. All morbidity and mortality until one year after surgery was collected retrospectively, including readmissions and reinterventions. All recurrences within the first year were scored to calculate disease-free survival. RESULTS: In 250 patients, the major morbidity rate was 61% (152/250), in-hospital mortality was 15% (37/250) and 90-day mortality was 16% (40/250). In the 213 discharged patients, 98 patients (46%) suffered 260 surgical complications. These complications required 185 readmissions in 92 patients (43%) and 400 reinterventions in 110 patients (52%), including 330 radiological (83%), 61 endoscopic (15%) and 9 surgical reinterventions (2%). One-year overall survival was 77% and one-year disease-free survival was 70%. Out of the 20 patients who died within the first year after discharge, 15 died of recurrent disease and 3 due to surgery related complications and 2 of unknown causes. CONCLUSION: Readmissions, reinterventions and complications are frequent throughout the first year after surgery for pCCA in tertiary referral hospitals. These adverse events warrants treatment of these complex patients in high expertise centers offering intensive perioperative care and close follow-up of patients after discharge.

Nationwide treatment and outcomes of perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed to analyse the outcomes of patients with pCCA in a nationwide cohort. METHODS: Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival. RESULTS: A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7-5.7) months. Three-hundred-ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti-cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2-34.0), 12.2 (95% CI 11.0-13.3), 14.5 (95%CI 8.2-20.8) and 2.9 (95% CI 2.6-3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non-academic and 32% in academic centres (P < .001), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7-11.7) months in academic centres compared to 4.9 (95% CI 4.3-5.4) months in non-academic centres (P < .001). CONCLUSIONS: In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population-based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients.