Sirolimus improves the prognosis of liver recipients with hepatocellular carcinoma: A single-center experience

BackgroundTumor recurrence after liver transplantation (LT) for selective patients diagnosed with hepatocellular carcinoma (HCC) in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients. The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.MethodsThe data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed. These patients were divided into the sirolimus group [patients took sirolimus combined with calcineurin inhibitors (CNIs) (n = 125)] and non-sirolimus group [patients took CNI-based therapy without sirolimus (n = 68)]. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. The prognostic factors and independent risk factors for RFS and OS were further evaluated.ResultsNon-sirolimus was an independent risk factor for RFS (HR = 2.990; 95% CI: 1.050-8.470; P = 0.040) and OS (HR = 3.100; 95% CI: 1.190-8.000; P = 0.020). A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group (69.6% vs. 80.9%, P = 0.030). Compared with the non-sirolimus group, the sirolimus group had significantly better RFS (P < 0.001) and OS (P < 0.001). Further subgroup analysis showed similar results.ConclusionsThis study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.     

Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation

BackgroundLong-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center.MethodsIn total, data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis. The patients were divided into the following three groups: Group 1, within the Milan and Hangzhou criteria (n = 51); Group 2, beyond the Milan but within the Hangzhou criteria (n = 36); and Group 3, beyond the Milan and Hangzhou criteria (n = 112). Survival probabilities for the three groups were calculated using multivariate Cox regression analysis. The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis.ResultsChild-Pugh stage C and hepatitis B virus (HBV) infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria. The overall survival rates of the 199 patients showed statistically significant differences among the three groups (P < 0.001). Moreover, no significant difference was noted in the survival rate between Group 1 and Group 2 (P > 0.05). Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria (OR = 0.478; 95% CI: 0.308–0.741; P = 0.001).ConclusionsChild-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT. The Hangzhou criteria were effective and analogous compared with the Milan criteria. Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.     

The effect of perioperative packed red blood cells transfusion on patient outcomes after liver transplant for hepatocellular carcinoma

BackgroundThe impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC.MethodsPatients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders.ResultsOf the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71–1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71–1.54, p = 0.83).ConclusionPerioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.     

Liver transplantation for hepatocellular carcinoma exceeding the Milan criteria: a single-center experience

Purpose

To establish a prognostic prediction system for patients with hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation (LT).

Methods

A total of 130 patients undergoing LT for HCC exceeding Milan criteria were enrolled into the study. Independent predictors for relapse-free survival (RFS) were adopted to establish a grading system to predict the risk of post-LT tumor recurrence.

Results

Multivariate Cox analysis revealed that tumor size >10 cm [vs. ≤5 cm: relative risk (RR) = 4.214, P < 0.001], preoperative alpha fetoprotein > 400 ng/ml (vs. ≤400 ng/ml: RR = 1.657, P < 0.001), extrahepatic invasion (RR = 2.407, P = 0.005) and vascular invasion (RR = 1.917, P = 0.013) were independent predictors for RFS. The risk index of each patient was defined as the sum of the RR obtained in the Cox analysis for RFS. The risk of tumor recurrence was classified into four grades: grade I—risk index equal to 0, grade II—risk index from 0 to 2, grade III—risk index from 2 to 6 and grade IV—risk index >6. RFS rates of patients with grade I–IV (n = 35, 46, 30 and 19) were 87.5, 57.8, 34.7 and 0 % in 1 year; and 74.4, 41.7, 14.4 and 0 % in 5 years. Both of overall survival (OS) and RFS correlated well with the risk index grade. Patients with grade I achieved comparable prognostic outcomes with the Milan group patients (n = 119) (5-year OS = 73.7 vs. 74.7 %, P = 0.748; 5-year RFS = 74.4 vs. 85.7 %, P = 0.148).

Conclusions

The new grading system was proved to be a promising system in predicting the patient prognosis after LT for HCC exceeding Milan criteria.     

Multicenter validation of a score to predict prognosis after the development of HCC recurrence following liver transplantation

BackgroundHCC recurrence after LT impacts negatively on survival. A recent study detected late recurrence (≥12 months), alpha-fetoprotein (AFP) <100 ng/mL at recurrence and being amenable for curative-intent treatments as good prognostic factors. With these variables a prognostic score was proposed. The objective of this study was to validate the prognostic score for hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT).MethodsData from the University of California, San Francisco, the University Hospital of Birmingham and Instituto Nazionale dei Tumori, Milan including patients with HCC recurrence after LT were analyzed. The previous reported score was applied to this cohort.ResultsFrom June 2002–December 2014, 1328 patients had a confirmed HCC in their explanted liver. The study group comprised 130 patients (9.8%) diagnosed with HCC recurrence after LT. Overall median survival after HCC recurrence was 12.4 (95% CI 10.2–16.3) months. Application of the previously reported score showed a significantly superior survival for the good prognosis group compared to moderate and poor prognosis groups (p < 0.0001).ConclusionThe score continues to identify a group of patients who would benefit from aggressive treatment and experience significant improved survival following recurrent HCC after LT.     

Intraoperative autologous transfusion and oncologic outcomes in liver transplantation for hepatocellular carcinoma: a propensity matched analysis

BackgroundIntraoperative autologous transfusion (IAT) of salvaged blood is a common method of resuscitation during liver transplantation (LT), however concern for recurrence in recipients with hepatocellular carcinoma (HCC) has limited widespread adoption.MethodsA review of patients undergoing LT for HCC between 2008 and 2018 was performed. Clinicopathologic and intraoperative characteristics associated with inferior recurrence-free (RFS) and overall survival (OS) were identified using Kaplan–Meier analysis and uni-/multi-variable Cox proportional hazards modeling. Propensity matching was utilized to derive clinicopathologically similar groups for subgroup analysis.ResultsOne-hundred-eighty-six patients were identified with a median follow up of 65 months. Transplant recipients receiving IAT (n = 131, 70%) also had higher allogenic transfusions (median 5 versus 0 units, P < 0.001). There were 14 recurrences and 46 deaths, yielding an estimated 10-year RFS and OS of 89% and 67%, respectively. IAT was not associated with RFS (HR 0.89/liter, P = 0.60), or OS (HR 0.98/liter, P = 0.83) pre-matching, or with RFS (HR 0.97/liter, P = 0.92) or OS (HR 1.04/liter, P = 0.77) in the matched cohort (n = 49 per group).ConclusionIAT during LT for HCC is not associated with adverse oncologic outcomes. Use of IAT should be encouraged to minimize the volume of allogenic transfusion in patients undergoing LT for HCC.     

Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection

BackgroundWe aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset.MethodsThe database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+.ResultsOut of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients.ConclusionsOur analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.     

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis

BackgroundTo address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT).MethodsAll patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS).ResultsThe LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062).ConclusionThis was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.     

Entecavir and tenofovir reduce hepatitis B virus‐related hepatocellular carcinoma recurrence more effectively than other antivirals

Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high‐potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low‐potency NAs after curative treatment of hepatitis B virus (HBV)‐related HCC. This study included 607 consecutive HBV‐related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low‐potency NA; n = 90) and group C (high‐potency NA; n = 256). The primary end‐point was recurrence‐free survival (RFS). During the duration of follow‐up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log‐rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time‐dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.     

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis

BackgroundDebate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.MethodsPatients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed.Results100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116–9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281–6.589; P=0.011) were independently associated with favorable RFS after HCC resection.ConclusionPreoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.     

Radical antegrade modular pancreatosplenectomy enhances local control of the disease in patients with left-sided pancreatic cancer

BackgroundRadical antegrade modular pancreatosplenectomy (RAMPS) was developed to enhance curability in patients with left-sided pancreatic cancer. However, no evidence is available regarding the prognostic superiority of RAMPS compared with conventional distal pancreatectomy (cDP). Here, we aimed to assess the oncological benefit of RAMPS by comparing surgical outcomes between patients who underwent cDP and RAMPS with propensity score (PS) adjustment.MethodsClinical data of 174 patients undergoing cDP and RAMPS between 2009 and 2016 at two high-volume centers were analyzed with PS matching. Recurrence-free survival (RFS), overall survival (OS), and local recurrence rates were compared between patients who underwent cDP and RAMPS.ResultsThe cDP and RAMPS groups were successfully matched with baseline characteristics. No differences were found in the 3-year RFS and OS rates between the two groups (3-year RFS: cDP 46% vs RAMPS 40%, p = 0.451, 3-year OS: cDP 57% vs RAMPS 53%, p = 0.692). However, the 3-year local recurrence rate was lower in the RAMPS (10%) than that in the cDP group (34%) (hazard ratio 0.275, 95% confidence interval 0.090–0.842, p = 0.02).ConclusionRAMPS is oncologically superior to conventional procedure in achieving local control of the disease in patients with left-sided pancreatic cancer.     

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Background & Aims

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods

A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.

Results

The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.

Conclusion

Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.     

Pathologic complete response to chemoembolization improves survival outcomes after curative surgery for hepatocellular carcinoma: predictive factors of response

BackgroundWe identified the predictive factors and prognostic significance of transarterial chemoembolization (TACE) for achieving pathologic complete response (pCR) before curative surgery for hepatocellular carcinoma (HCC) in hepatitis B–endemic areas.MethodsAmong 753 HCC patients treated with surgery, 124 patients underwent preoperative TACE before liver resection (LR), and 166 before liver transplantation (LT) between 2005 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Pathologic response (PR) was defined as the mean percentage of necrotic area, and pCR was defined as the absence of viable tumor.ResultsA total of 34 (27%) and 38 (23%) patients had pCR before LR and LT, respectively. Alpha-fetoprotein (AFP) < 100 ng/mL and single tumor were significant preoperative predictors of pCR. OS and RFS were significantly improved in patients with pCR or a PR ≥ 90%, but not in patients with PR ≥ 50% after LR and LT. On multivariate analyses, PR ≥ 90% remained an independent predictor of better OS and RFS in LR and LT groups.ConclusionOverall, our data clearly demonstrate that pCR predicts favorable prognosis after curative surgery for HCC, and predictors of pCR are AFP <100 ng/mL and single tumor.     

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

BackgroundEarly singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features.MethodsWe retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models.ResultsOur RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort.ConclusionsCompared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients’ outcomes.     

Angiographic Functional Scoring of Coronary Artery Disease Predicts Mortality in Patients With Severe Aortic Stenosis Undergoing TAVR

Background/purposeCoronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve replacement (TAVR), although its prognostic significance is questionable. Significant CAD stratified using SYNTAX score (SS) has been associated with greater mortality, yet it is unknown whether the functional impact of CAD also impacts outcomes in this cohort. DILEMMA score (DS) is a validated angiographic functional scoring tool that correlates with fractional flow reserve and instantaneous wave-free ratio.This study sought to assess the functional impact of CAD on outcomes in patients undergoing TAVR for severe aortic stenosis (AS).Methods/materials229 patients were included in this analysis. Patients underwent angiographic DS and SS and were classified using predefined values. The primary endpoint was one-year all-cause mortality, with secondary endpoints of 30-day major adverse cardiac and cerebrovascular events (MACCE).ResultsThe mean age was 83.9 ± 0.5 years (55.0% female), with 11.8% all-cause mortality. CAD defined by ≥30% stenosis in any vessel was not associated with adverse outcomes (HR = 1.08, p = 0.84). However, the risk of one-year mortality was greater in patients with either SS > 9 (20.8% vs. 9.4%, HR 2.34, p = 0.03) or DS > 2 (18.4% vs. 8.5%, HR = 2.28, p = 0.03). Both scoring systems were also associated with 30-day MACCE (both p < 0.05). After multivariate adjustment, independent predictors of one-year mortality were DS > 2 (HR = 2.29, p = 0.04), left ventricular ejection fraction <50% (HR 2.66, p = 0.04) and COPD (HR 2.43, p = 0.04).ConclusionOur results demonstrate that angiographic functional scoring is independently predictive of both 12-month mortality and 30-day MACCE following TAVR.     

Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China

BackgroundThe downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging.MethodsWe performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China.ResultsRecipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC.ConclusionsCompared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.     

The combination of systemic inflammation-based marker NLR and circulating regulatory T cells predicts the prognosis of resectable pancreatic cancer patients

BackgroundThe systemic inflammation response and immune impairment are closely related to the development and progression of various tumours, such as pancreatic cancer. In this study, we evaluated circulating inflammation factors and circulating regulatory T cells (Tregs) as markers of immunosuppression in a cohort of Chinese patients with resectable pancreatic cancer.MethodsSamples were retrospectively collected from a series of 195 pathological stage I/II pancreatic cancer patients who underwent potentially curative surgery between June 2010 and April 2014. To examine the prognostic factors, circulating systemic inflammation-based markers and Tregs, detected by flow cytometry, were analysed.ResultsUnivariate analyses revealed that the neutrophil-lymphocyte ratio (NLR), TNM stage, differentiation, chemotherapy, CA19-9 levels and presence of Tregs are significantly associated with overall survival in patients with resectable pancreatic cancers. NLR (p = 0.001, HR = 0.538), TNM stage (p = 0.004, HR = 0.593), differentiation (p = 0.011, HR = 0.46), chemotherapy (p = 0.006, HR = 0.516) and Tregs (p = 0.001, HR = 0.558) are identified as independent prognostic markers by multivariate analyses. Interestingly, we also found that high NLR levels combined with a high proportion of Tregs (p < 0.001, HR = 3.521) correlate strongly with worse survival, with a greater than 3.5–fold increased risk of death compared with those with concurrent low levels of NLR and Tregs.ConclusionsThe preoperative NLR and circulating regulatory T cells are potentially independent prognostic factors for overall survival in resectable pancreatic cancer patients. High NLR levels combined with poor immune state before surgery, as measured by Tregs, are associated with an extremely poor prognosis.     

Characteristics of atypical large well-differentiated hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma?

BackgroundHepatocellular carcinoma (HCC) de-differentiation is thought to correlate with size, therefore well-differentiated HCC ≥3 cm are considered rare and not fully understood.MethodsPatients who underwent hepatectomy for HCC between 1998–2016 were retrospectively analyzed. Patient's characteristics and recurrence-free (RFS) and overall (OS) survival were compared between those with atypical- (well-differentiated-HCC ≥3 cm) and typical-HCC (moderate-to-poorly-differentiated HCC ≥3 cm).ResultsOf 176 patients included in this study, 37 (21%) had atypical-HCC. Patients with atypical-HCC were less likely to be Asian ethnicity (3% vs. 17%, p = 0.062), have lower rate of viral infection (14% vs. 43%, p = 0.003), cirrhosis (8% vs. 27%, p = 0.015). The tumors were less likely to demonstrate vascular invasion (30% vs. 59%, p = 0.002), and were associated with a lower alpha-fetoprotein level (3.5 ng/ml vs. 33.2 ng/ml, p < 0.001). Patients with atypical-HCC had a longer RFS (5-y RFS: 58.3% vs. 35.7%, p = 0.016) and OS (5-y OS: 79.1% vs 53.3%, p = 0.029) as compared to those with typical-HCC following univariate analysis, however this did not appear following multivariate analysis.ConclusionPatients with atypical-HCC have different characteristic in terms of epidemiology, etiology, cirrhosis and vascular invasion as compared to typical-HCC. The etiology of atypical-HCC may be non-alcoholic fatty liver disease-related and/or malignant transformation of hepatocellular adenoma.     

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

BackgroundATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.MethodsOne hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence.ResultsUpregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (High^nucleus/Low^cytosol), moderate risk (High^nucleus/High^cytosol or Low^nucleus/Low^cytosol), and low risk (Low^nucleus/High^cytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015).ConclusionsHigh nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.