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.     

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis

BackgroundMicrovascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR).MethodsThe data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed.Results728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease.ConclusionsPA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.     

Regional lymph node sampling in hepatoma resection: insight into prognosis

BackgroundThe importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis.MethodsPatients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003–2015). Cohort-based clinicopathologic comparisons were made based on completion of regional LNS. Propensity-score matching reduced bias. Overall and disease-specific survival (OS/DSS) were analyzed.ResultsAmong 5395 patients, 835 (15.4%) underwent regional LNS. Patients undergoing LNS had larger tumors (7.0vs4.8 cm) and higher T-stage (30.9 vs. 17.6% T3+, both p < 0.001). Node-positive rate was 12.0%. Median OS (50 months for both) and DSS (28 vs. 29 months) were similar between cohorts, but node-positive patients had decreased OS/DSS (20/16 months, p < 0.01). Matched patients undergoing LNS had equivalent OS (46 vs. 43 months, p = 0.869) and DSS (27 vs. 29 months, p = 0.306) to non-LNS patients. The prognostic impact of node positivity persisted after matching (OS/DSS 24/19 months, p < 0.01). Overall disease-specific mortality were both independently elevated (overall HR 1.71-unmatched, 1.56-matched, p < 0.01; disease-specific HR 1.40-unmatched, p < 0.01, 1.25-matched, p = 0.09).ConclusionRegional LNS is seldom performed during resection for HCC, but it provides useful prognostic information. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional LNS to facilitate optimal multidisciplinary management.     

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.     

Feasibility and safety of liver transplantation or resection after transarterial radioembolization with Yttrium-90 for unresectable hepatocellular carcinoma

BackgroundThe benefit of transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) is increasingly evidenced. However, data on outcome of liver transplantation or resection after TARE remain scarce. This study aimed to assess the safety and feasibility of surgery after TARE in patients with unresectable HCC.MethodsPatients exclusively undergoing TARE followed by either orthotopic liver transplantation (OLT) or liver resection (LR) for HCC between 2012 and 2016 were included. Primary outcomes were postoperative morbidity and mortality. Secondary outcomes were overall survival (OS) and response to TARE.ResultsAmong 349 patients with HCC treated with TARE, 32 (9%) underwent either OLT (n = 22) or LR (n = 10), which represent the study cohort. In this group, TARE induced decreased viable nodules (p < 0.001), an efficient downsizing (p < 0.001) as well as a significant downstaging based on BCLC classification (p < 0.001). Overall, major complications and mortality after surgery occurred in 5 (16%) and 1 (3%) patients, respectively. For the whole study cohort, OS was 47 months while survival rates at 1-, 3- and 5-years reached 97%, 86% and 86%, respectively.DiscussionLiver surgery after TARE is feasible and safe. This strategy allows to offer a curative treatment in a subset of patients with unresectable HCC.     

Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a poorly understood and aggressive malignancy with increasing incidence and mortality. Hepatitis B virus (HBV) infection is recognized as one of the important risk factors of ICC. There are few reports focusing on whether isolated antibody to hepatitis B core antigen (isolated anti-HBc, IAHBc) have prognostic role in ICC, while positive hepatitis B surface antigen (HBsAg) has been reported to be associated with the prognosis of ICC. The aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection, in order to identify those who have the high risk of ICC recurrence in the early stage.MethodsWe divided 209 ICC patients who underwent curative resection into 4 groups: group I (n = 40), HBsAg (-)/antibody to hepatitis B surface antigen (anti-HBs) (-)/anti-HBc (+); group II (n = 70), HBsAg (+)/anti-HBc (-); group III (n = 55), HBsAg (-)/anti-HBs (+)/anti-HBc (+); and group IV (n = 44), HBsAg (-)/anti-HBc (-). We compared the recurrence-free survival (RFS) and overall survival (OS) among these four groups.ResultsThe median follow-up time was 16.93 months (range 1-34.6 months). The 1- and 2-year RFS and OS rates were 60% and 42%, and 78% and 63% respectively in all patients. Compared to the whole non-IAHBc patients (group II + group III + group IV), IAHBc patients (group I) showed significantly lower RFS at 1 year (39.8% vs. 64.4%, P = 0.001) and 2 years (20.7% vs. 46.7%, P = 0.001). When compared to other three individual groups, IAHBc patients (group I) also had the lowest RFS. We did not find significant difference in OS among the four groups. Further multivariate analysis revealed that IAHBc was an independent risk factor of RFS.ConclusionsIAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.     

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group

BackgroundPacked red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection.MethodsA retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan–Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression.ResultsOf 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia.ConclusionPRBC transfusion is associated with worse survival for patients undergoing PNET resection.     

Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5–37 months; 1-year OS rate, 46.8–100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.     

Long-term survival and recurrence after curative resection for hepatocellular carcinoma in patients with chronic hepatitis C virus infection: a multicenter observational study from China

BackgroundHepatocellular carcinoma (HCC) is a recognized sequalae of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. This study aimed to identify long-term survival and prognostic factors after curative resection for HCC among patients with chronic HCV infection.MethodsFrom a Chinese multicenter database, the data of consecutive patients with HCV infection undergoing curative liver resection for initial HCC between 2006 and 2015 were retrospectively reviewed. Postoperative 30-day mortality and morbidity, long-term overall survival (OS) and recurrence-free survival (RFS) were evaluated.ResultsAmong 382 HCC patients with HCV infection, 68 (18%) had concurrent HBV infection and 110 (29%) had portal hypertension. Postoperative 30-day morbidity and mortality rates were 45% and 2.9%, respectively. The 5-year OS and RFS rates were 45% and 34%, respectively. Multivariable Cox-regression analyses identified that concurrent HBV infection, presence of portal hypertension, largest tumor size > 5 cm, and macrovascular and microvascular invasion were independently associated with worse OS and RFS, while postoperative regular anti-HCV therapy was independently associated with better OS.ConclusionLong-term prognosis after HCC resection among patients with HCV infection was worse in those with concurrent HBV infection and concomitant portal hypertension. Postoperative regular anti-HCV therapy was associated with better OS.     

Chronological improvement of pancreatectomy for resectable but advanced pancreatic neuroendocrine neoplasms

BackgroundProgress of non-surgical treatments in the last decade has improved the prognosis of pancreatic neuroendocrine neoplasms (PanNEN). However, the improvement of surgery for advanced PanNEN remains unknown. This study aimed to investigate the chronological changes of the clinical impact of pancreatectomy for PanNEN.MethodsPatients undergoing curative-intent pancreatectomy for PanNEN between 1991 and 2010 were categorized into the earlier period group, and those between 2011 and 2021 were into the later period group.Advanced PanNEN was defined as showing resectable synchronous liver metastases or invasion to portal venous systems or adjacent organs. The recurrence-free survival (RFS) and overall survival (OS) were analyzed among patients with non-advanced and advanced PanNENs. The independent prognostic risk factors were identified using a Cox proportional hazard model.ResultsA total of 189 patients (n = 54 in the earlier period and n = 135 in the later period) were included. The proportion of advanced PanNEN increased from 15% to 30% (P = 0.027). The RFS and OS of non-advanced PanNEN were similar between the periods. Whereas, among patients with advanced PanNEN, the later period group showed improved prognosis; The 5-year RFS of the earlier period vs. the later period was 0% vs. 27%, and the 5-year OS was 38% vs. 82% (p = 0.013).ConclusionsA radical surgical treatment for advanced PanNEN has shown prognostic improvement in this decade. However, more careful perioperative examinations and possibly, additional treatments are required for PanNEN with portal vein invasion.     

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.     

The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study

BackgroundThe resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.MethodsUsing multi-institutional data, the different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed.ResultsIn 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RM & negative MVI, 93.5 and 53.1 months with wide RM & positive MVI, 79.2 and 41.6 months with narrow RM & negative MVI, and 69.2 and 37.5 months with narrow RM & positive MVI (both P < 0.01). On multivariable analyses, narrow RM & positive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11–4.17, and HR 3.15, 95% CI, 2.09–4.67, respectively).ConclusionsConcomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.     

Prediction of post-hepatectomy liver failure and long-term prognosis after curative resection of hepatocellular carcinoma using liver stiffness measurement

Background and study aimsPost-hepatectomy liver failure (PHLF) is the main cause of perioperative death after hepatocellular carcinoma (HCC) resection. PHLF occurrence is related to both the hepatectomy volume and the degree of cirrhosis. Accurate preoperative assessment of the degree of cirrhosis may aid in reducing the incidence of PHLF. Several studies have shown that the liver stiffness measurement (LSM) is well correlated with cirrhosis. This study explored the relationship between LSM and PHLF occurrence after radical HCC resection and the effect on long-term prognosis.Patients and methodsWe retrospectively analyzed the clinical data of 164 patients who underwent radical HCC resection at our center from January 2017 to January 2020. The related postoperative PHLF factors were analyzed. The LSM threshold in postoperative PHLF was calculated through receiver operating characteristic (ROC) curve analysis. Patients were grouped according to different LSM thresholds and survival analysis was performed.ResultsForty-six patients experienced PHLF, of whom 19, 21, and 6 were classified as grades A, B, and C, respectively. Multivariate analysis indicated that LSM was an independent risk factor for PHLF after HCC surgery (OR = 1.174, P < 0.000). LSM (OR = 1.219, P < 0.000) and intraoperative bleeding (OR = 1.001, P = 0.047) were risk factors for grade B-C PHLF. The LSM threshold that predicted PHLF occurrence was 17.9 kPa (AUC = 0.831, P < 0.000) and 24.5 kPa (AUC = 0.867, P < 0.000) for grade B-C PHLF. LSM was correlated with PHLF severity (r = 0.439, P < 0.001). The median survival times were 32 vs 26 months (P = 0.016) for patients with LSM ≤ 17.9 kPa vs those with LSM > 17.9 kPa and 28 vs 24 months (P = 0.004) for patients with LSM ≤ 24.5 kPa vs those with LSM > 24.5 kPa.ConclusionLSM is related to PHLF occurrence in patients undergoing HCC resection; a higher LSM is associated with the occurrence of more severe PHLF after surgery. In addition, LSM may aid in predicting long-term survival after liver resection in patients with HCC.     

Novel biomarker for hepatocellular carcinoma: high tumoral PLK-4 expression is associated with better prognosis in patients without microvascular invasion

BackgroundHepatocellular carcinoma (HCC) recurrence after liver resection (LR) adversely affects prognosis but is difficult to predict. Aberrant expression of Polo-Like Kinase 4 (PLK-4) is implicated in several adult malignancies. We sought to evaluate the prognostic value of PLK-4 expression in HCC after curative-intent LR.MethodsPatients undergoing LR for HCC between July-2015 and November-2017 at our centre were retrospectively identified. PLK-4 expression was measured in tumour and adjacent non-tumour liver tissue using quantitative RT-PCR. Disease-free survival (DFS) was evaluated by Kaplan–Meier and Cox proportional hazard models.ResultsA total of 145 patients were identified. Patients were divided according to PLK-4 expression (high: n = 58, low: n = 87) by generating a receiver operating characteristic curve for recurrence with an area under the curve of 0.72 (95% CI: 0.6–0.8). Recurrence and death rates were similar between groups. In patients without mVI, low PLK-4 expression was associated with worse actuarial DFS (low 1-, 3-, 5-year 83%, 60%, 47% vs. high 91%, 81%, 81%; p = 0.02). In patients without mVI, high PLK-4 expression was an independent predictor of survival (HR 0.3, 95% CI: 0.1–1.0; p = 0.04).ConclusionPLK-4 represents a biomarker for good prognosis in patients with HCC who do not have mVI. This could aid clinical decision making for adjuvant clinical trials.     

Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis

BackgroundOrgan allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT).MethodsThe National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan–Meier survival analyses and log-rank tests were performed.Results1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size.DiscussionHCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.     

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.     

Impact of hepatitis C treatment on long-term outcomes for patients with hepatocellular carcinoma: a United States Safety Net Collaborative Study

BackgroundWidespread HCV treatment for hepatocellular carcinoma (HCC) patients remains limited. Our aim was to evaluate the association of HCV treatment with survival and assess barriers to treatment.MethodsPatients in the U.S. Safety Net Collaborative with HCV and HCC were included. Primary outcome was overall survival (OS). Secondary outcomes were recurrence-free survival (RFS) and barriers to receiving HCV treatment.ResultsOf 941 patients, 57% received care at tertiary referral centers (n=533), 74% did not receive HCV treatment (n=696), 6% underwent resection (n=54), 17% liver transplant (n=163), 50% liver-directed therapy (n=473), and 7% chemotherapy (n=60).HCV treatment was associated with improved OS compared to no HCV treatment (70 vs 21 months, p<0.01), persisting across clinical stages, HCC treatment modalities, and treatment facilities (all p<0.01). Surgical patients who received HCV treatment had improved RFS compared to those who did not (91 vs 80 months, p=0.03). On MVA, HCV treated patients had improved OS and RFS.On MVA, factors associated with failure to receive HCV treatment included Black race, higher MELD, and advanced clinical stage (all p<0.05).ConclusionHCV treatment for HCC patients portends improved survival, regardless of clinical stage, HCC treatment, or facility type. Efforts must address barriers to HCV treatment.     

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus

Introduction and objectivesOptimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial.Materials and methodsA total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type.ResultsResection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort.ConclusionsOur results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.     

Stereotactic radiofrequency ablation of tumors at the hepatic venous confluence

BackgroundRadiofrequency ablation (RFA) is subject to “heat-sink” effects, particularly for treatment of tumors adjacent to major vessels.MethodsIn this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4–8.5) for HCC, 6.4 cm (0.5–11) for ICC and 3.8 cm (0.5–13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival.ResultsThe overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively.ConclusionSRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence.     

Overexpression of CD73 in pancreatic ductal adenocarcinoma is associated with immunosuppressive tumor microenvironment and poor survival

BackgroundCD73, a newly recognized immune checkpoint mediator, is expressed in several types of malignancies. However, CD73 expression and its impact on tumor microenvironment and clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) remain unclear.MethodsThis study included two cohorts: 138 patients from our institution (MDA) and 176 patients from TCGA dataset. CD73 expression, CD4⁺, CD8⁺, CD21⁺ and CD45RO + tumor infiltrating lymphocytes (TILs) were evaluated by immunohistochemistry using tissue microarrays. The results of CD73 expression were correlated with clinicopathologic parameters, survival and TILs.ResultsCD73 overexpression correlated with poor differentiation (P = 0.002) and tumor size (P = 0.049). For CD73-low group, median overall survival (OS) and recurrence-free survival (RFS) were 26.9 ± 3.8 months and 12.6 ± 2.6 months, respectively, compared to 16.9 ± 4.4 months (P = 0.01) and 7.9 ± 1.2 months (P = 0.01), respectively, in CD73-high group. CD73 was an independent predictor for both RFS (P = 0.02) and OS (P = 0.01) by multivariate variate analysis. Similarly, CD73-high tumors had significantly shorter OS than CD73-low tumors in TCGA dataset (P < 0.0001). CD73-high correlated with decreased CD4⁺ TILs in MDA cohort and decreased CD8A and CR2 (CD21) expression in TCGA cohort.ConclusionsCD73 overexpression is associated with poor differentiation, tumor size, and shorter survival, and is an independent prognostic factor in PDAC patients. CD73 overexpression is associated with decreased CD4⁺, CD8⁺ and CD21⁺ TILs. Our data support that CD73 plays an important role in immunosuppressive tumor microenvironment and promote tumor progression in PDAC.