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| 2. |
- Choi, Woo Jin, et al.
(författare)
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Optimizing Circulating Tumour DNA Use in the Perioperative Setting for Intrahepatic Cholangiocarcinoma : Diagnosis, Screening, Minimal Residual Disease Detection and Treatment Response Monitoring
- 2023
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 30:6, s. 3849-3863
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Forskningsöversikt (refereegranskat)abstract
- In this review, we present the current evidence and future perspectives on the use of circulating tumour DNA (ctDNA) in the diagnosis, management and understanding the prognosis of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing surgery. Liquid biopsies or ctDNA maybe utilized to: (1) determine the molecular profile of the tumour and therefore guide the selection of molecular targeted therapy in the neoadjuvant setting, (2) form a surveillance tool for the detection of minimal residual disease or cancer recurrence after surgery, and (3) diagnose and screen for early iCCA detection in high-risk populations. The potential for ctDNA can be tumour-informed or -uninformed depending on the goals of its use. Future studies will require ctDNA extraction technique validations, with standardizations of both the platforms and the timing of ctDNA collections.
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| 3. |
- Choi, Woo Jin, et al.
(författare)
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Preoperative neutrophil-to-lymphocyte ratio is prognostic for early recurrence after curative intrahepatic cholangiocarcinoma resection
- 2023
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Ingår i: Annals of Hepato-Biliary-Pancreatic Surgery. - : The Korean Association of Hepato-Biliary-Pancreatic Surgery. - 2508-5778 .- 2508-5859. ; 27:2, s. 158-165
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Tidskriftsartikel (refereegranskat)abstract
- Backgrounds/Aims: Within two years of surgery, 70% of resected intrahepatic cholangiocarcinoma (iCCA) recur. Better biomarkers are needed to identify those at risk of “early recurrence” (ER). In this study, we defined ER and investigated whether preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-inflammatory index were prognostic of both overall relapse and ER after curative hepatectomy for iCCA.Methods: A retrospective cohort of patients who underwent curative-intent hepatectomy for iCCA between 2005 and 2017 were created. The cut-off timepoint for the ER of iCCA was estimated using a piecewise linear regression model. Univariable analyses of recurrence were conducted for the overall, early, and late recurrence periods. For the early and late recurrence periods, multivariable Cox regression with time-varying regression coefficient analysis was used.Results: A total of 113 patients were included in this study. ER was defined as recurrence within 12 months of a curative resection. Among the included patients, 38.1% experienced ER. In the univariable model, a higher preoperative NLR (> 4.3) was significantly associated with an increased risk of recurrence overall and in the first 12 months after curative surgery. In the multivariable model, a higher NLR was associated with a higher recurrence rate overall and in the ER period (≤ 12 months), but not in the late recurrence period.Conclusions: Preoperative NLR was prognostic of both overall recurrence and ER after curative iCCA resection. NLR is easily obtained before and after surgery and should be integrated into ER prediction tools to guide preoperative treatments and intensify postoperative follow-up.
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| 4. |
- Claasen, Marco P. A. W., et al.
(författare)
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An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma
- 2023
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres.Methods: A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents' contemporary decision making process, a hypothetical case study with different tumour size and number combinations was embedded.Results: Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise.Conclusions: Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA.Impact and implications: Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeon vs. oncologist vs. hepatologist/ gastroenterologist), highlighting the urgent need for a standardisation of therapeutic strategies for patients with cHCC-CCA.
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| 5. |
- Ivanics, Tommy, et al.
(författare)
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Long-term outcomes of retransplantation after live donor liver transplantation : A Western experience
- 2023
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Ingår i: Surgery. - : Elsevier. - 0039-6060 .- 1532-7361. ; 173:2, s. 529-536
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated. Method: We aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant. Results: A total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23-1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intentionto-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32; P =.30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54-4.19; P =.40) were equivalent in those who initially received a living donor liver transplant. Conclusion: Patients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes.
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| 6. |
- Ivanics, Tommy, et al.
(författare)
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Machine learning-based mortality prediction models using national liver transplantation registries are feasible but have limited utility across countries
- 2023
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Ingår i: American Journal of Transplantation. - : ELSEVIER SCIENCE INC. - 1600-6135 .- 1600-6143. ; 23:1, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90 post-LT mortality within and across countries. Predictive performance and external validity of each model assessed. Prospectively collected data of adult patients (aged >= 18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined iables in common between the registries [harmonized]). The model performance was evaluated using area the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making future LTs.
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| 7. |
- Ivanics, Tommy, et al.
(författare)
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Outcomes after liver transplantation using deceased after circulatory death donors : A comparison of outcomes in the UK and the US
- 2023
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Ingår i: Liver international. - : Wiley-Blackwell. - 1478-3223 .- 1478-3231. ; 43:5, s. 1107-1119
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight.Methods: Adult (>= 18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0-90 days) and longer-term (90 days-5 years) outcomes.Results: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days-5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49-0.80); graft failure HR: UK: 0.72, 95% CI: 0.58-0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p < .001).Conclusions: For those receiving a DCD LT, longer-term post-transplant outcomes in the UK are superior to the US, however, significant differences in recipient illness, graft quality and access to retransplantation were seen between the two countries.
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| 8. |
- Kitajima, Toshihiro, et al.
(författare)
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Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation
- 2023
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 23:2, s. 248-256
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Tidskriftsartikel (refereegranskat)abstract
- Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/mu L), mid (500-1000/mu L), and high ALC (>1000/mu L). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P =.001; low vs high: P <.001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P <.001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P =.004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P <.001) and cytomegaloviremia (15.2% vs 6.8%; P =.03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P =.001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.
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| 10. |
- Rajendran, Luckshi, et al.
(författare)
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Association of Viral Hepatitis Status and Post-hepatectomy Outcomes in the Era of Direct-Acting Antivirals
- 2023
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Ingår i: Annals of Surgical Oncology. - : Springer. - 1068-9265 .- 1534-4681. ; 30, s. 2793-2802
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of viral hepatitis status in post-hepatectomy outcomes has yet to be delineated. This large, multicentred contemporary study aimed to evaluate the effect of viral hepatitis status on 30-day post-hepatectomy complications in patients treated for hepatocellular carcinoma (HCC).Methods: Patients from the National Surgical Quality Improvement Program (NSQIP) database with known viral hepatitis status, who underwent hepatectomy for HCC between 2014 and 2018, were included. Patients were classified as HBV-only, HCV-only, HBV and HCV co-infection (HBV/HCV), or no viral hepatitis (NV). Multivariable models were used to assess outcomes of interest. The primary outcome was any 30-day post-hepatectomy complication. The secondary outcomes were major complications and post-hepatectomy liver failure (PHLF). Subgroup analyses were performed for cirrhotic and noncirrhotic patients.Results: A total of 3234 patients were included. The 30-day complication rate was 207/663 (31.2%) HBV, 356/1077 (33.1%) HCV, 29/81 (35.8%) HBV/HCV, and 534/1413 (37.8%) NV (p = 0.01). On adjusted analysis, viral hepatitis status was not associated with occurrence of any 30-day post-hepatectomy complications (ref: NV, HBV odds ratio (OR) 0.89 [95% confidence interval (CI): 0.71-1.12]; HCV OR 0.91 [95% CI: 0.75-1.10]; HBV/HCV OR 1.17 [95% CI: 0.71-1.93]). Similar results were found in cirrhotic and noncirrhotic subgroups, and for secondary outcomes: occurrence of any major complications and PHLF.Conclusions: In patients with HCC managed with resection, viral hepatitis status is not associated with 30-day post-hepatectomy complications, major complications, or PHLF compared with NV. This suggests that clinical decisions and prognostication of 30-day outcomes in this population likely should not be made based on viral hepatitis status.
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| 11. |
- Rajendran, Luckshi, et al.
(författare)
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Outcomes of liver transplantation in non-alcoholic steatohepatitis (NASH) versus non-NASH associated hepatocellular carcinoma
- 2023
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Ingår i: HPB. - : Elsevier BV. - 1365-182X .- 1477-2574. ; 25:5, s. 556-567
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is a rising indication for liver transplantation. This unique population, with multiple comorbidities, has po-tential for worse post-transplant outcomes. We compared post-transplant survival of NASH and non-NASH HCC patients using a large cohort.Methods: Adults transplanted for HCC between 2008 and 2018, from United Network for Organ Sharing (UNOS) and University Health Network (UHN) databases were divided into two populations: NASH and non-NASH. Recipient characteristics and post-transplant survival were compared. Subgroup analyses were performed within and beyond Milan criteria.Results: 2071 of 20,672 (10.0%) patients underwent transplantation for NASH HCC, with annual pro-portional increase of 1.2%UHN (p = 0.02) and 1.3%UNOS (p < 0.001). The 1-,3-,5-year post-transplant survival were 90.8%, 83.9%, 76.3% NASH HCC versus 91.9%, 82.1%, 74.9% non-NASH HCC (p = 0.94). No survival differences were observed in populations within or beyond Milan. Competing-risk analysis demonstrated no differences in risk for cardiovascular-related death (HR1.24, 95%CI 0.87-1.55, p = 0.16), or HCC recurrence-related death (HR1.21, 95%CI 0.89-1.65, p = 0.23). NASH HCC patients had lower risk of liver-related deaths (HR0.57, 95%CI 0.34-0.98, p = 0.04).Discussion: NASH HCC is a rising indication for liver transplantation. Despite demographic differences, no post-transplantation survival differences were observed between NASH and non-NASH HCC. This justifies equivalent organ allocation, irrespective of NASH status.
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