Background
Several important changes were made to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the ...prognostic impact of this new tumor staging system compared to the 7th edition.
Methods
A retrospective single‐institution study was performed with 626 patients who underwent R0 resection for ICC over 20‐year period.
Results
Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, carbohydrate antigen 19‐9 >200 U/ml, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For tumor‐node‐metastasis stages in the 7th versus the 8th editions, concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively.
Conclusions
The 8th edition of the AJCC staging system appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition.
Highlight
In this high‐volume single‐center study, Kang and colleagues compared the prognostic impact of the 7th and 8th editions of the AJCC tumor staging system for intrahepatic cholangiocarcinoma. The 8th edition appears to provide high prognostic contrast for most tumor stage categories, but no marked improvement in overall prognostic performance.
T-cell exhaustion, or an impaired capacity to secrete cytokines and proliferate with overexpression of immune checkpoint receptors, occurs during chronic viral infections but has also been observed ...in tumors, including hepatocellular carcinomas (HCCs). We investigated features of exhaustion in CD8+ T cells isolated from HCC specimens.
We obtained HCC specimens, along with adjacent nontumor tissues and blood samples, from 90 patients who underwent surgical resection at Asan Medical Center (Seoul, Korea) from April 2016 through April 2018. Intrahepatic lymphocytes and tumor-infiltrating T cells were analyzed by flow cytometry. Tumor-infiltrating CD8+ T cells were sorted by flow cytometry into populations based on expression level of programmed cell death 1 (PDCD1 or PD1): PD1-high, PD1-intermediate, and PD1-negative. Sorted cells were analyzed by RNA sequencing. Proliferation and production of interferon gamma (IFNG) and tumor necrosis factor (TNF) by CD8+ T cells were measured in response to anti-CD3 and antibodies against immune checkpoint receptors including PD1, hepatitis A virus cellular receptor 2 (HAVCR2 or TIM3), lymphocyte activating 3 (LAG3), or isotype control. Tumor-associated antigen-specific CD8+ T cells were identified using HLA-A*0201 dextramers. PDL1 expression on tumor tissue was assessed by immunohistochemistry.
PD1-high, PD1-intermediate, and PD1-negative CD8+ T cells from HCCs had distinct gene expression profiles. PD1-high cells expressed higher levels of genes that regulate T-cell exhaustion than PD1-intermediate cells. PD1-high cells expressed TIM3 and LAG3, and low proportions of TCF1+, TBEThigh/eomesoderminlow, and CD127+. PD1-high cells produced the lowest amounts of IFNG and TNF upon anti-CD3 stimulation. Differences in the PD1 expression patterns of CD8+ T cells led to the identification of 2 subgroups of HCCs: HCCs with a discrete population of PD1-high cells were more aggressive than HCCs without a discrete population of PD1-high cells. HCCs with a discrete population of PD1-high cells had higher levels of predictive biomarkers of response to anti-PD1 therapy. Incubation of CD8+ T cells from HCCs with a discrete population of PD1-high cells with antibodies against PD1 and TIM3 or LAG3 further restored proliferation and production of IFNG and TNF in response to anti-CD3.
We found HCC specimens to contain CD8+ T cells that express different levels of PD1. HCCs with a discrete population of PD1-high CD8+ T cells express TIM3 and/or LAG3 and produce low levels of IFNG and TNF in response to anti-CD3. Incubation of these cells with antibodies against PD1 and TIM3 or LAG3 further restore proliferation and production of cytokines; HCCs with a discrete population of PD1-high CD8+ T cells might be more susceptible to combined immune checkpoint blockade–based therapies.
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Background
Salvage liver transplantation is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. ADV score is calculated by multiplying α‐fetoprotein and ...des‐γ‐carboxyprothrombin concentrations and tumor volume. Prognostic accuracy of ADV score was assessed in patients undergoing salvage living donor liver transplantation (LDLT) and their outcomes were compared with patients undergoing primary LDLT.
Methods
This study was a retrospective, single‐center, case‐controlled study. Outcomes were compared in 125 patients undergoing salvage LDLT from 2007 to 2018 and in 500 propensity score‐matched patients undergoing primary LDLT.
Results
In patients undergoing salvage LDLT, median intervals between hepatectomy and tumor recurrence, between first HCC diagnosis and salvage LDLT, and between hepatectomy and salvage LDLT were 12.0, 37.2, and 29.3 months, respectively. Disease‐free survival (DFS, P = .98) and overall survival (OS, P = .44) rates did not differ significantly in patients undergoing salvage and primary LDLT. Pretransplant and explant ADV scores were significantly predictive of DFS and OS in patients undergoing salvage and primary LDLT (P < .001). DFS after prior hepatectomy (P = .52) and interval between hepatectomy and LDLT (P = .82) did not affect DFS after salvage LDLT. Milan criteria and ADV score were independently prognostic of DFS and OS following salvage LDLT, and prognosis of patients within and beyond Milan criteria could be further stratified by ADV score.
Conclusions
Risk factors and posttransplant outcomes were similar in patients undergoing salvage and primary LDLT. ADV score is surrogate biomarker for posttransplant prognosis in salvage and primary LDLT recipients. Prognostic model incorporating ADV scores can help determine whether to perform salvage LDLT.
Highlight
Hwang and colleagues developed a prognostic model for hepatocellular carcinoma based on α‐fetoprotein and des‐γ‐carboxyprothrombin concentrations and tumor volume (ADV). The ADV score is a surrogate biomarker for post‐transplant prognosis in salvage and primary liver transplant recipients. Prognostic models incorporating ADV scores can help determine whether to perform salvage liver transplantation.
When timely access to deceased‐donor livers is not feasible, living‐donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary ...objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single‐center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non‐HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post‐LT renal recovery. The HRS group had a higher death rate than the non‐HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post‐LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non‐recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post‐LT sepsis (p < 0.001) and non‐recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre‐LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post‐LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post‐LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post‐LT renal recovery.
When timely access to deceased‐donor livers is not available for candidates with hepatorenal syndrome, expeditious living‐donor liver transplantation can reduce the risk of death or permanent renal failure. Selzner and Wong comment on page 2291
Background
The resection of liver tumors that involve the hepatic veins adjacent to the vena cava or hepatic hilum is technically challenging. We present our surgical techniques and the long‐term ...outcome of five patients with conventionally unresectable tumors.
Methods
Five patients with conventionally unresectable tumors were successfully treated by “ex‐situ liver resection” and “in‐situ and ante‐situm hypothermic liver perfusion” under total vascular exclusion and venovenous bypass.
Results
These approaches allowed complete tumor removal with vascular reconstruction under a bloodless surgical field, while minimizing hepatic ischemic injury and preserving liver function. No perioperative mortalities occurred, and postoperative complications were minimal. The postoperative survival periods were limited due to the advanced malignancies in our patients, but the survival benefit was encouraging. The median postoperative survival time was 29.1 months, with the longest survival period being nearly 10 years. These approaches improved the quality of life and provided an opportunity for additional treatment.
Conclusions
Hypothermic perfusion hepatectomy is a realistic option for achieving surgical cure or significantly improved survival and quality of life in patients with tumors deemed unresectable using conventional normothermic hepatectomy. These approaches can overcome the limitations of the liver's restricted normothermic ischemia tolerance or inaccessible tumor locations.
Highlight
Some liver tumors are conventionally unresectable because of the liver’s limited tolerance to long normothermic ischemia or inaccessible tumor location. Yoon and colleagues present their surgical technique and long‐term outcomes of five cases treated by in‐situ or ante‐situm hypothermic liver perfusion or ex‐situ liver resection under total vascular exclusion and venovenous bypass.
Combined hepatocellular carcinoma–cholangiocarcinoma (cHCC‐CC) is a rare disease. We investigated the clinicopathological features of cHCC‐CC and compared the longterm outcomes following liver ...transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC‐CC through an institutional database search. The HR control group (n = 100) was selected through propensity score‐matching. The incidence of cHCC‐CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC‐CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC‐CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC‐CC is rarely diagnosed following LT, and one‐third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC‐CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330–341 2017 AASLD.
Backgrounds
The anatomy of the left hepatic vein (LHV) is variable; thus, it should be considered for graft hepatic vein (GHV) venoplasty for left lateral section (LLS) and left liver grafts. This ...study assessed the incidence of superficial LHV (sLHV) branches according to LHV anatomy and its usability for GHV venoplasty in pediatric liver transplantation (LT).
Methods
This study consisted of three parts: (1) anatomical classification of LHV variations and the incidence of sLHV branches; (2) morphometric simulative analysis of GHV reconstruction and (3) clinical application based on LHV anatomy.
Results
The LHV anatomy of 248 potential LLS graft donors was classified into four types according to the number and location of GHV openings: one single opening (type 1; n = 186 75.0%), two large openings (type 2; n = 35 14.1%), one large and one small adjacent opening (type 3; n = 14 5.6%), and two large widely‐separated openings (type 4; n = 13 5.2%). An sLHV branch was identified in 87 of 248 (35.1%) donor livers. Morphometric analysis of simulative GHV venoplasty with an sLHV branch increased GHV diameters by 30% in type 1 LLS grafts and 20% in type 2/3 LLS grafts. An analysis of 50 consecutive patients who underwent pediatric LT showed that the 2‐year rates of GHV obstruction were 2.0% with LLS grafts and 0% with left liver grafts.
Conclusions
The GHV orifice can be enlarged through LHV anatomy‐based unification venoplasty. Unification venoplasty with an sLHV branch provided sufficient enlargement of the GHV orifice.
The previously proposed scoring systems are not readily available because of the lack of simplicity for predicting hepatocellular carcinoma (HCC) recurrence. We aimed to develop and validate the new ...score system, which can predict HCC recurrence after living donor liver transplantation (LDLT) by using morphologic and biologic data. Predictors for HCC recurrence after LDLT were developed (n = 627) and validated (n = 806) in 1433 patients for whom we could collect information to date between 2007 and 2016 at Asan Medical center (AMC) to create the SNAPP score (tumor Size and Number, alpha‐fetoprotein AFP, vitamin K absence‐II PIVKA‐II, positron emission tomography PET). On logistic regression based on 3‐year recurrence‐free survival, the SNAPP factors were independently associated with HCC recurrence. The SNAPP score was highly predictive of HCC recurrence (C statistic, 0.920), and 5‐year post‐LT recurrence rates were significantly different between low, intermediate, and high SNAPP score groups. The performance of the SNAPP score (C‐index 95% confidence interval, 0.840 0.801‐0.876) on predicting tumor recurrence after LDLT was better than that of the New York/California, the Risk Estimation of Tumor Recurrence After Transplant (RETREAT), and the Model of Recurrence After Liver Transplant (MoRAL) score. The SNAPP score provides excellent prognostication after LDLT for HCC patients. Hence, we can help voluntary patients’ decisions about whether to undergo LDLT or not.
The authors derive and validate a simple score, based on morphological and biological metrics, that accurately prognosticates hepatocellular carcinoma recurrence after living donor liver transplantation.
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