Preoperative Alpha-fetoprotein Level Research Articles

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study

BackgroundThe incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%–40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown. MethodsData of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups. Results489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162–1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922–1.786, P = 0.139). ConclusionHCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.

Preoperative predictors of early recurrence after resection for hepatocellular carcinoma

BackgroundTo assess preoperative image tumor characteristics and alpha-fetoprotein (AFP) levels to predict early recurrence after liver resection (LR) for hepatocellular carcinoma (HCC). MethodsThis retrospective study's enrolled patients underwent LR for newly diagnosed HCC between 2011 and 2018. Multivariate logistic regression analyses using the Akaike information criterion were adopted to construct a nomogram to predict early recurrence (i.e. recurrence within 1 year). The performance of this nomogram was evaluated using calibration plots with bootstrapping. ResultsEarly recurrence was identified in 99 patients (11.2%). Four predictive factors, namely an AFP level of >400 ng/mL; image-diagnosed tumor characteristics, including a tumor size of > 5 cm; vascular invasion; and multiple tumors were adopted in the final model of the early recurrence nomogram, with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions and the actual observations of early recurrence. ConclusionWe have developed a simple nomogram with preoperative image tumor characteristics and AFP levels to predict the early recurrence of HCC after LR.

When is a Seminoma not a Seminoma? The Incidence, Risk Factors and Management of Patients With Testicular Seminoma With Discordant Elevated Serum Alpha-fetoprotein

ObjectiveTo describe the incidence, clinical and demographic factors, and treatment patterns associated with discordant elevated alpha-fetoprotein (AFP) findings in patients with pure seminomatous histology. MethodsWe queried the National Cancer Database to identify patients with testicular germ cell tumors (GCT) diagnosed in 2011-2015. Patients were grouped based on histologic diagnosis and pre-operative serum AFP level. ResultsOf 18,616 patients diagnosed with testicular GCT, 53% (N = 9,849) had pure seminomatous histology, of whom 8.3% (N = 821) had an elevated serum AFP pre-operatively. Non-white patients with seminoma were more likely to have a pre-op elevated AFP (OR 1.42; 95% CI: 1.10-1.83); patients treated at higher volume centers were less likely to have a pre-op elevated AFP (0.66, 95% CI: 0.53-0.83). Patients with seminoma with elevated AFP received adjuvant radiation more frequently than those with NSGCT (Stage I: 15% vs 0.2%, P <.01; Stage II: 21.9% vs 0.1%, P <.01) and less frequently underwent retroperitoneal lymph node dissection (RPLND) (Stage 1: 1.9% vs 11.1% P <.01; Stage II: 8.8% vs 17.4%, P <.01). ConclusionThe detection of elevated serum alpha-fetoprotein (AFP) in patients with pure seminomatous testicular germ cell tumors (GCT) is a discordant finding that implies the presence of occult non-seminomatous GCT (NSGCT) elements. 8% of patients with pure seminomatous GCTs had diagnostically discordant elevated pre-operative AFP levels. Despite recommendations to manage these patients as NSGCT, patients with seminoma and elevated AFP were managed in a fashion comparable to those with seminoma and normal AFP levels.

Establishment, validation and evaluation of predictive model for early relapse after R0 resection in hepatocellular carcinoma patients with microvascular invasion

BackgroundsThis is the first study to build and evaluate a predictive model for early relapse after R0 resection in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).MethodsThe consecutive HCC patients with MVI who underwent hepatectomy in Cancer Hospital of Chinese Academy of Medical Science from Jan 2014 to June 2019 were retrospectively enrolled and randomly allocated into a derivation (N = 286) and validation cohort (N = 120) in a ratio of 7:3. Cox regression and Logistic regression analyses were performed and a predictive model for postoperative early-relapse were developed.ResultsA total of 406 HCC patients with MVI were included in our work. Preoperative blood alpha-fetoprotein (AFP) level, hepatitis B e antigen (HBeAg) status, MVI classification, largest tumor diameter, the status of serosal invasion, number of tumors, and the status of satellite nodules were incorporated to construct a model. The concordance index (C-index) was 0.737 and 0.736 in the derivation and validation cohort, respectively. The calibration curves showed a good agreement between actual observation and nomogram prediction. The C-index of the nomogram was obviously higher than those of the two traditional HCC staging systems.ConclusionWe have developed and validated a prediction model for postoperative early-relapse in HCC patient with MVI after R0 resection.

The ratio of preoperative alpha-fetoprotein level to total tumor volume as a prognostic factor of hepatocellular carcinoma after liver transplantation.

To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation.One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation. Risk factors of early tumor recurrence and poor prognosis of HCC in patients after liver transplantation were studied by multivariate regression analysis. Kaplan-Meier survival analysis was used to compare the tumor-free survival and overall survival between the two groups of patients.In 108 patients, 47 patients have AFP/TTV≤2 while 61 patients have AFP/TTV>2. Patients in AFP/TTV≤2 group have longer tumor-free survival time and overall survival time compared with patients in AFP/TTV>2 group. The age, total bilirubin level, serum AFP level, TTV, portal vein tumor thrombus and AFP/TTV (all P < .05) of patient with HCC are closely related to poor prognosis after liver transplantation. Multivariate regression analysis showed that have portal vein tumor thrombus (hazard ratio [HR] = 2.345, P < .05), TTV≥65.5 cm3 (HR = 2.701, P < .05) and AFP/TTV > 2 (HR = 4.624, P < .05) are independent risk factors for poor prognosis of patients with HCC after liver transplantation while TTV≥65.5 cm3 (HR = 2.451, P < .05) and AFP/TTV > 2 (HR = 4.257, P < 0.05) were independent risk factors for tumor recurrence at the same time.The tumor recurrence and the prognosis of patients with HCC after liver transplantation is affected by many factors. AFP/TTV ratio has important predictive value for the tumor recurrence and the prognosis of patients with HCC after liver transplantation. AFP/TTV>2 is an independent risk factor for both early tumor recurrence and poor prognosis of patients with HCC after liver transplantation.

Glypican-3 and hepatocyte paraffin-1 combined with alpha-fetoprotein as a novel risk scoring model for predicting early recurrence of hepatocellular carcinoma after curative resection.

At present, the predictive model of postsurgical recurrence for hepatocellular carcinoma (HCC) is not well-established. The aim of this study was to develop a novel model for prediction of postsurgical recurrence and survival for HCC. Data from 112 patients who underwent curative liver resection from June 2014 to June 2017 in the First Affiliated Hospital of Kunming Medical University were collected retrospectively. Through the statistical analysis, we combined the results of glypican-3 (GPC3) and hepatocyte paraffin-1 (Heppar1) chemical staining in tumor tissues and preoperative alpha-fetoprotein (AFP) levels, and assigned risk scores to them, respectively, to establish an improved prognostic model for predicting recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 382 ng/ml, area under the curve (AUC) = 0.652, 95% confidence interval (CI) = 0.539-0.765, P < 0.05] and GPC3/Heppar1 expression pattern from 10 putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. At 36 months after liver resection, the recurrence rate of high-risk group in the novel risk scoring model reached 45.6%, which was significantly higher than that of low-risk group (9.1%). In this experiment, the AUC value of the model was 0.741 (95% CI = 0.644-0.839, P < 0.001), which was the highest among all the elements. The novel risk scoring model of combing AFP cut-off value and GPC3/Heppar1 were shown to be effective at predicting early recurrence of HCC after curative resection.

Geriatric nutritional risk index predicts prognosis in hepatocellular carcinoma after hepatectomy: a propensity score matching analysis

The geriatric nutritional risk index (GNRI) is widely used for nutritional assessment in older inpatients and is associated with postoperative complications and cancer prognosis. We investigated the use of GNRI to predict long-term outcomes in hepatocellular carcinoma of all etiologies after hepatectomy. Overall, 346 patients were examined after propensity score matching. We dichotomized the GNRI score into high GNRI (> 98: N = 173) and low GNRI (≤ 98: N = 173) and evaluated recurrence-free survival (RFS) and overall survival (OS) between both groups. Clinicopathological characteristics between the low- and high-GNRI groups were similar after propensity score matching except for the components of the GNRI score (body mass index and serum albumin level), Child–Pugh score (comprising serum albumin level), and preoperative alpha-fetoprotein level (p < 0.0001, p < 0.0001, p = 0.0030, and p = 0.0007, respectively). High GNRI was associated with significantly better RFS and OS (p = 0.0003 and p = 0.0211, respectively; log-rank test). Multivariate analysis revealed that GNRI is an independent prognostic factor of RFS and OS (low vs. high; hazard ratio [HR], 1.8284; 95% confidence interval [CI] 1.3598–2.4586; p < 0.0001, and HR, 1.5452; 95% CI 1.0345–2.3079; p = 0.0335, respectively). GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status and can predict prognosis of hepatocellular carcinoma after hepatectomy.

Clinical Significance of Alpha-Fetoprotein in Alpha-Fetoprotein Negative Hepatocellular Carcinoma Underwent Curative Resection

BackgroundThe clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial.AimsTo investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup.MethodsA total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan–Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC).ResultsEven in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor (P < 0.001), poorer differentiation of tumor cell (P < 0.001), presence of satellite nodules (P < 0.001), and MVI (P = 0.002). Kaplan–Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS (P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system.ConclusionsAFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system.

Multi-institutional validation of novel models for predicting the prognosis of patients with huge hepatocellular carcinoma.

The population of patients with huge hepatocellular carcinoma (H-HCC diameter > 10.0 cm) is an odd group that is not well adjudicated in the current staging systems, whose prognosis after curative resection varies. We aimed to develop novel models to predict the long-term outcomes of patients with H-HCC without portal vein tumor thrombus after hepatectomy. There were 1076 H-HCC patients enrolled who underwent curative liver resection in five institutions in China. In total, 670 patients were recruited from our center and randomly divided into the training cohort (n = 502) and internal validation (n = 168) cohorts. Additionally, 406 patients selected from other four centers as the external validation cohort. Novel models were constructed based on independent preoperative and postoperative predictors of postsurgical recurrence (PSR) and postsurgical mortality (PSM) determined in multivariable cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C index) and calibration curve and compared with five conventional HCC staging systems. PSR model and PSM model were constructed based on tumor number, microscopic vascular invasion, tumor differentiation, preoperative alpha-fetoprotein level, albumin-bilirubin grade, liver segment invasion, neutrophil-to-lymphocyte ratio or platelet-to-neutrophil ratio, and surgical margin or intraoperative blood transfusion. The C-indexes were 0.84 (95% CI, 0.78-0.90) and 0.85 (95% CI, 0.78-0.91) for the PSR and PSM models, respectively, which were substantially higher than those of the five conventional HCC staging systems (0.63-0.75 for PSR; 0.66-0.77 for PSM). The two novel models achieved more accurate prognostic predictions of PSR and PSM for H-HCC patients after curative liver resection.

Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: thoracoscopic versus open approach

BackgroundThe role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method.MethodsA total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients.ResultsDuring the median follow-up period of 33.4 months (range, 1.8–112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142–2.619/1.571–3.963/1.554–4.456; p = 0.010/< 0.001/< 0.001, respectively).ConclusionsMetastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.

Major Hepatectomy for Large Hepatocellular Carcinoma in the Elderly: A Large-Scale Multicenter Study

Background: Due to the increase in life expectancy, more elderly patients with hepatocellular carcinoma (HCC) are considered for hepatectomy, even when the tumor was large. To clarify the impact of age on short-term and long-term outcomes after major hepatectomy (≥3 segments) for large HCC (≥5 cm). Methods: Using a multicenter database, patients who underwent curative-intent major hepatectomy for large HCC between 2006 and 2016 were identified. Postoperative morbidity and mortality, overall survival (OS) and recurrence-free survival (RFS) were compared between the elderly (≥65 years) and the younger (< 65 years). Univariable and multivariable Cox-regression analyses were performed to identify risk factors of OS and RFS in the entire and elderly cohorts, respectively. Results: Of 830 patients, 92 (11.1%) and 738 (88.9%) were elderly and younger aged, respectively. There were no differences in postoperative 30-day mortality and morbidity among elderly versus younger patients (5.4%vs.2.6% and 43.5%vs.38.3%, both P>0.05). The 5-year OS and RFS rates among elderly patients were also comparable to younger patients (35.0%vs.33.2% and 20.0%vs.20.8%, both P>0.05). Multivariable analyses identified that elder age was not independently associated with OS and RFS in the entire cohort, while preoperative alpha-fetoprotein level >400 μg/L, multiple tumors, macrovascular and microvascular invasion were independently associated with decreased OS and RFS in the elderly cohort. Conclusions: Selected elderly patients can benefit from major hepatectomy for large HCC as much as younger patients. Long-term oncologic survival in the elderly was determined by preoperative alpha-fetoprotein level, tumor number and the presence of vascular invasion.

Ideal Surgical Margin to Prevent Early Recurrence After Hepatic Resection for Hepatocellular Carcinoma.

Postoperative early recurrence after hepatic resection for hepatocellular carcinoma (HCC) poses a challenge to surgeons, and the effect of a surgical margin is still controversial. This study aimed to identify an ideal margin to prevent early recurrence. A total of 226 consecutive patients who underwent primary curative hepatic resection for solitary and primary HCC were enrolled. The definition of early recurrence was determined using the minimum P value approach. Logistic regression analysis was used to identify the risk factors of early recurrence. The receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off of the surgical margin and early recurrence. Recurrence within 8months induced the poorest overall survival (P = 2×10-15). ROC analysis showed that the optimal cut-off value of the surgical margin was 7mm. The risk factors of early recurrence (≤ 8-month recurrence) were preoperative alpha-fetoprotein levels ≥ 100ng/ml (Odds ratio [OR] 4.92 [2.28-10.77], P < 0.0001) and a surgical margin < 7mm (OR 3.09 [1.26-8.85], P = 0.01) by multivariable analysis. The probability of early recurrence ranged from 5.0% in the absence of any factors to 43.5% in the presence of both factors. Among patients with alpha-fetoprotein levels ≥ 100ng/ml, non-capsule formation, or microvascular invasion, there was a significant difference in 5-year overall survival between surgical margins of <7 mm and ≥ 7mm. A > 7-mm margin is important to prevent early recurrence. Patients with HCC and alpha-fetoprotein levels > 100ng/ml, non-capsule formation, or microvascular invasion may have a survival benefit from a ≥ 7-mm margin.

Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts.

ObjectivePatient-derived xenograft (PDX) models provide a promising preclinical platform for hepatocellular carcinoma (HCC). However, the molecular features associated with successful engraftment of PDX models have not been revealed.MethodsHCC tumor samples from 76 patients were implanted in immunodeficient mice. The molecular expression was evaluated by immunohistochemistry. Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test. The independent prediction parameters were identified by logistic regression analyses.ResultsThe engraftment rate for PDX models from patients with HCC was 39.47% (30/76). Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates. Tumors with poor differentiation and vascular invasion were related to engraftment success. The positive expression of CK19, CD133, glypican-3 (GPC3), and Ki67 in tumor samples was associated with engraftment success. Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment. Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates, with 71.9% in GPC3+/Ki67+ tumors, 30.8% in GPC3−/Ki67+ tumors, 15.0% in GPC3+/Ki67− tumors, and 0 in GPC3−/Ki67− tumors. ConclusionsSuccessful engraftment of HCC PDXs was significantly related to molecular features. Tumors with the GPC3+/Ki67+ phenotype were the most likely to successfully establish HCC PDXs.

Long-term outcomes of liver resection for multiple hepatocellular carcinomas: Single-institution experience with 187 patients.

Backgrounds/AimsSurgical resection for the treatment of multiple hepatocellular carcinomas (HCCs) is controversial. This study aimed to evaluate the clinical and oncological outcomes after liver resection in patients with multiple HCCs.MethodsClinicopathological and survival data of 187 patients who underwent curative resection for multiple HCCs between June 2004 and December 2016 at Asan Medical Center, Seoul, South Korea were retrospectively reviewed. The prognostic factors for recurrence and survival were identified using univariate and multivariate analyses.ResultsOf the 187 patients, 153 (81.8%) had two nodules, 23 (12.3%) had three nodules, and 11 (5.9%) had more than three nodules. Multiple tumors were located in the ipsilateral lobe in 163 (87.2%) patients. Anatomical resection, non-anatomical resection, and both types of resections were performed in 81.3%, 8.0%, and 10.7% patients, respectively. Recurrence occurred in 133 (71.1%) patients, and the mean time to recurrence after surgery was 34.2 months. Independent risk factors for tumor recurrence in multivariate analyses were indocyanine green retention rate at 15 min ≥15%, preoperative alpha-fetoprotein level ≥400 ng/ml, and total tumor diameter ≥6 cm. The 1-, 3-, 5-, and 10-year disease-free survival rates were 94.1%, 81.7%, 69.7%, and 39.4%, respectively, and the 1-, 3-, 5-, and 10-year survival rates were 93.5%, 74.2%, 64.9%, and 38.8%, respectively.ConclusionsOur experience shows that liver resection can be considered a first-line treatment option for selected patients with multiple HCCs who have well-preserved liver function.

Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis.

Purpose We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). Methods This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. Results Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001). Conclusion In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

Factors influencing early recurrence of hepatocellular carcinoma after curative resection.

ObjectiveTo identify the factors influencing early recurrence in patients with hepatocellular carcinoma (HCC) after curative resection.MethodsClinical data for 99 patients with HCC undergoing curative resection were analyzed. The clinicopathological factors influencing early recurrence were analyzed by Cox regression.ResultsTwenty-five of 99 patients (25.3%) suffered from early recurrence. There were significant differences between patients with and without recurrence in terms of tumor diameter, tumor capsular integrity, and preoperative alpha fetoprotein level. Cox regression analysis revealed that a tumor diameter >2.6 cm and preoperatively increased total bilirubin (TBL) level were risk factors for postoperative recurrence, while tumor capsular integrity had a protective effect on postoperative recurrence. After adjusting for preoperative TBL level and tumor capsular integrity, the risk of HCC recurrence was markedly increased in line with increasing tumor diameter in a non-linear manner.ConclusionTumor diameter >2.6 cm and preoperatively increased TBL level are associated with a higher risk of early recurrence after curative resection in patients with HCC, while tumor capsular integrity is associated with a lower risk of early recurrence.

Major Hepatectomy in Elderly Patients with Large Hepatocellular Carcinoma: A Multicenter Retrospective Observational Study.

BackgroundWith an increase in life expectancy and improvement of surgical safety, more elderly patients with hepatocellular carcinoma (HCC), even with large tumors, are now considered for hepatectomy. This study aimed to clarify the impact of age on short- and long-term outcomes after major hepatectomy (≥3 segments) for large HCC (≥5 cm).Patients and MethodsUsing a multicenter database, patients who underwent curative-intent major hepatectomy for large HCC between 2006 and 2016 were identified. Postoperative morbidity and mortality, overall survival (OS) and recurrence-free survival (RFS) were compared between the elderly (≥65 years) and younger (<65 years) patients. Univariable and multivariable Cox-regression analyses were performed to identify the risk factors of OS and RFS in the entire and elderly cohorts, respectively.ResultsOf 830 patients, 92 (11.1%) and 738 (88.9%) were elderly and younger patients, respectively. There were no significant differences in postoperative 30-day mortality and morbidity between the two groups (5.4% vs 2.6% and 43.5% vs 38.3%, both P>0.05). The 5-year OS and RFS rates in elderly patients were also comparable to younger patients (35.0% vs 33.2% and 20.0% vs 20.8%, both P>0.05). In the entire cohort, multivariable Cox-regression analyses identified that old age was not independently associated with OS and RFS. However, in the elderly cohort, preoperative alpha-fetoprotein level >400 μg/L, multiple tumors, macrovascular invasion and microvascular invasion were independently associated with decreased OS and RFS.ConclusionCarefully selected elderly patients benefited from major hepatectomy for large HCC as much as younger patients, and their long-term prognosis was determined by preoperative alpha-fetoprotein level, tumor number and presence of macro- or micro-vascular invasion.

The impact of tumor localization on prognosis of the patients following liver transplantation for hepatocellular carcinoma

Aim: Hepatocellular carcinoma usually occurs in the setting of liver cirrhosis and therefore, resection is not possible in majority of the cases. Orthotopic liver transplantation (OLS) is a gold standard treatment option in hepatocellular carcinoma. The aim of the present retrospective study was to evaluate the prognosis of hepatocellular carcinoma localized in left or right side of the liver in patients who underwent OLS. Materials and Methods: 120 patients received OLS for hepatocellular carcinoma between 2007 and 2018 in the institute of liver transplantation. Tumors that were centrally located were excluded from the analysis. The remaining 104 patients were divided into two groups; Group 1 (right lobe, n=85 [81.7%]), Group 2 (left lobe, n=19 [18.3%]). The clinical and demographic data of the patients along with preoperative laboratory values such as alpha fetoprotein (AFP), gamma-glutamyl transpeptidase (GGT) and thrombocyte count were retrospectively evaluated. Results: The Median age in Group 1 and 2 were 54 (4-72) and 50.5 (37-68) years, respectively. Preoperative AFP levels in Group 1 and 2 were 9.25 (1-10800) ng/ml and 13 (1.5-317) ng/ml, respectively. The Model for end stage liver disease (MELD) scores in Group 1 and 2 were 12 (6-52) and 9 (6-21), respectively. None of the clinical, demographic and laboratory values along with disease-free survival, early mortality and recurrence were significantly different among the study groups (p>0.05). Conclusions: Although there is a big discrepancy in terms of patient’s numbers in right and left-sided tumors, our data failed to show any survival difference among the groups. Further studies, especially in hepatocellular carcinoma beyond the Milan criteria, are needed to validate our results.

Hepatocellular Carcinoma and Liver Transplantation: A Single-Center Experience

BackgroundLiver transplantation (LT) is the best treatment in selected patients with hepatocellular carcinoma (HCC). Morphologic criteria alone are not sufficient to predict survival. In this study, we investigated the clinical, biochemical, and pathologic factors affecting survival in patients who underwent LT due to HCC. MethodsBetween October 2011 and January 2018, 165 of 749 LT for HCC cases performed at the Memorial Atasehir Hospital were evaluated retrospectively. Survival, demographic characteristics and etiology, preoperative alpha-fetoprotein (AFP) level, Model for End-Stage Liver Disease (MELD) score, prognostic staging, and morphologic and histologic properties were evaluated. ResultsOne hundred and thirty-nine cases of 165 were living donor liver transplantation (LDLT). The mean age was 57.7 ± 7.3 years, the mean follow-up period was 27.8 ± 20 months, and 41 patients (24%) died before follow-up. Recurrence of HCC was detected in 23 (14%) cases. Overall survival was 85%, 71%, and 64% for 1, 3, and 5 years, respectively. In terms of 1-, 3-, and 5-year survival within vs beyond Milan criteria was 90%, 80%, and 76% vs 75%, 66%, and 44%, respectively. In the University of California San Francisco criteria, it was 86%, 76%, and 70% vs 76%, 60%, and 30% compared with 1-, 3-, and 5-year survival. While histopathological poor differentiation and AFP elevation affected the course negatively. Good differentiation did not have a significant effect on survival. It was determined that poor differentiation, lymphovascular invasion, and an increased number of nodules significantly affected survival in both within and beyond cases. ConclusionA transplant decision is controversial in patients with HCC with other than previously defined morphologic criteria. In these cases, AFP level and histologic differentiation determine survival. The results were not satisfactory in both high and/or poorly differentiated cases.

The Role of Preoperative Dynamic Contrast-enhanced 3.0-T MR Imaging in Predicting Early Recurrence in Patients With Early-Stage Hepatocellular Carcinomas After Curative Resection.

Objectives: Liver resection is potentially curative for early-stage hepatocellular carcinoma (eHCC) in patients with well-preserved liver function. The prognosis of these patients after resection is still unsatisfactory because of frequent early recurrence (ER). Therefore, we investigated the role of preoperative dynamic contrast-enhanced 3.0-T MR imaging in predicting ER of eHCC after curative resection.Methods From May 2014 to October 2017, we retrospectively analyzed 82 patients with eHCC who underwent dynamic MR imaging and subsequently underwent curative resection. Liver Imaging Reporting and Data System (LI-RADS) v2018 major and ancillary imaging features, as well as two non-LI-RADS MR imaging features (irregular tumor margin and tumor number), were evaluated. A multivariate Cox regression analysis was used to identify independent predictors, and two models (preoperative and postoperative prediction models) were developed.Results ER was observed in 25 patients (25/82, 30.5%). In the univariate analyses, preoperative alpha-fetoprotein (AFP) level >200 ng/ml, three MR imaging features (multifocal tumors, corona enhancement, and irregular tumor margin), and microvascular invasion (MVI) were associated with ER. In the multivariate analysis, corona enhancement (hazard ratio [HR]: 2.970; p = 0.013) and irregular tumor margin (HR: 2.377; p = 0.048) were independent predictors in the preoperative prediction model, and preoperative AFP level >200 ng/ml (HR: 2.493; p = 0.044) plus corona enhancement (HR: 3.046; p = 0.014) were independent predictors in the postoperative prediction model (microvascular invasion [MVI] was not; p = 0.061). When combined with both predictors, the specificity for ER in the preoperative prediction model was 98.2% (56/57), which was comparable to that of the postoperative prediction model [96.7% (55/57)].Conclusions Our results demonstrated that preoperative MR imaging features (corona enhancement and irregular tumor margin) have the potential to preoperatively identify high-risk ER patients with eHCC, with a specificity >90%.