Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study

Purposes

The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients.

Methods

Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters.

Results

There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group.

Conclusions

Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

Early Viral Suppression Predicts Good Postoperative Survivals in Patients with Hepatocellular Carcinoma with a High Baseline HBV-DNA Load

Purpose

To correlate early HBV-DNA suppression by antiviral treatment with posthepatectomy long-term survivals in patients with HBV-related hepatocellular carcinoma (HCC).

Methods

A retrospective study was conducted on patients with a baseline HBV-DNA load of >2,000 IU/ml. The cumulative rates of HBV-DNA undetectability at weeks 24 and 48, as well as long-term tumor recurrence and overall survivals were determined.

Results

Of 1,040 patients with a high baseline HBV-DNA load, 865 patients received antiviral treatment. At a median follow-up of 42 months, 616 patients (59.2 %) had developed HCC recurrence and 482 patients (46.3 %) had died. The median time to recurrence was 25 months. In patients who received antiviral treatment, the cumulative rates of HBV-DNA undetectability (<200 IU/ml) were 54.3 and 88.1 % at weeks 24 and 48, respectively. There was no significant difference between the two groups of patients who received antiviral treatment or not for disease-free survival. On multivariate analyses, tumor size >5 cm, blood transfusion, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak inflammation score were significant risk factors of HCC recurrence. Also, tumor size >5 cm, surgical margin <1 cm, presence of satellite nodules, presence of portal vein tumor thrombus and high Ishak fibrosis score were significant factors associated with poor postoperative overall survival. On the other hand, an undetectable HBV-DNA level before week 24 was a significant protective factor of disease-free survival and overall survival.

Conclusions

Early HBV-DNA suppression with antiviral treatment improved prognosis of patients with HBV-related HCC.     

The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

Background

The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.

Methods

All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value?>?15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm ? group) within the 90-day postresection period.

Results

Among 271 resected patients, 141 patients (52 %) had a level of serum AFP?≥?15 ng/ml at diagnosis. Five-year OS and median survival were 42 % and 52 months in group norm + versus 20 % and 23 months in the group norm ? (P?=?0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53–16.34]) and microvascular invasion (RR 4.76 [1.42–15.34]).

Conclusion

The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.     

Combination of Morphologic Criteria and α-Fetoprotein in Selection of Patients With Hepatocellular Carcinoma for Liver Transplantation Minimizes the Problem of Posttransplant Tumor Recurrence

Background

Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria.

Methods

This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria.

Results

There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival—significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs.

Conclusions

Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.     

Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Background

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.

Methods

Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models.

Results

Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4–4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30–1.98), disease-free survival (HR = 1.26; 95 % CI 1.10–1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07–1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1–5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7–327,560.0 ng/mL) and Ishak stage 6 cirrhosis.

Conclusions

Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.     

The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

     

Impact of Preoperative α-Fetoprotein Level on Disease-Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Background

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Methods

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10?ng/ml) and increased-level group (>10?ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10–150, 150–500, and ≥500?ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Results

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4?%, respectively, for those with normal AFP; 57 and 10?%, respectively, for those with AFP 10–150?ng/ml; 46 and 24?%, respectively, for those with AFP 150–500?ng/ml; and 28 and 62?%, respectively, for those with AFP ≥500?ng/ml.

Conclusions

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.     

Clinicopathological Features of Recurrence in Patients After 10-year Disease-free Survival Following Curative Hepatic Resection of Hepatocellular Carcinoma

Background

The present study aimed to clarify the clinicopathologic features of long-term disease-fee survival after resection of hepatocellular carcinoma (HCC).

Methods

This retrospective study identified 940 patients who underwent curative resection of HCC between 1991 and 2000 at five university hospitals. Seventy-four patients with 10 years of recurrence-free survival were identified and followed up. They were divided into two groups, 60 recurrence-free and 14 with recurrence after a 10-year recurrence-free period.

Results

Overall survival rates of recurrence and non-recurrence groups were 68 and 91 % at 16 years, and 34 and 91 % at 20 years (p = 0.02), respectively. There were five (36 %), and two deaths (3 %), respectively, after 10 recurrence-free years. A second resection for recurrence was performed in four patients (29 %), and mean survival was 15.3 years after the first hepatectomy. Although three patients in the non-recurrence group (5 %) developed esophageal and/or gastric varices, seven patients in the recurrence group (50 %) developed varices during 10 years (p < 0.0001). In multivariate analysis, preoperative and 10-year platelet count was identified as a favorable independent factor for maintained recurrence-free survival after a 10-year recurrence-free period following curative hepatic resection of HCC.

Conclusions

Recurrence of HCC may occur even after a 10-year recurrence-free period. Long-term follow-up after resection of HCC is important, and should be life-long. Patients with higher preoperative and 10-year platelet counts are more likely to have long-term survival after resection. A low platelet count, related to the degree of liver fibrosis, is a risk factor for recurrence and survival of HCC after curative resection.     

α-Fetoprotein-to-Total Tumor Volume Ratio Predicts Post-operative Tumor Recurrence in Hepatocellular Carcinoma

Background/Aims

Serum α-fetoprotein (AFP) and total tumor volume (TTV) are important factors linked with post-operative tumor recurrence in hepatocellular carcinoma (HCC) patients. We investigated the role of a new prognostic marker, AFP-to-TTV ratio, in predicting HCC recurrence.

Methods

A total of 655 HCC patients undergoing resection were analyzed.

Results

In the multivariate logistic model, serum AFP level [odds ratio (OR) 32.459, p?=?0.012] and TTV (OR 0.006, p?=?0.01) were independently associated with a higher AFT/TTV ratio. The 1-, 3-, and 5-year tumor recurrence rates were 29 %, 55 %, and 68 %, respectively. In the Cox proportional hazards model, alcoholism (hazard ratio [HR], 1.354, p?=?0.028), international normalized ratio of prothrombin time ≥1.01 (HR, 1.349, p?<?0.001), multiple nodules (HR, 1.381, p?=?0.004), main tumor diameter ≥4?cm (HR, 1.535, p?=?0.001), macrovascular invasion (HR, 1.362, p?=?0.016), and AFP/TTV ratio ≥1.5 (HR, 1.49, p?<?0.001) were independently associated with tumor recurrence. In subgroup analysis, a higher AFP/TTV ratio was significantly associated with tumor recurrence in patients characterized by macrovascular invasion, TTV?≥?40 cm³, or main tumor diameter ≥4cm (all p?=?0.001).

Conclusion

The AFP/TTV ratio, a newly proposed marker for predicting post-operative tumor recurrence in HCC, is a feasible surrogate and may be useful in selecting super-high-risk patients for tumor recurrence.     

Predictor for Histological Microvascular Invasion of Hepatocellular Carcinoma: A Lesson from 229 Consecutive Cases of Curative Liver Resection

Background

Microscopic vascular invasion is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. To predict microscopic portal venous invasion, the following two questions were examined retrospectively: Is it possible to detect microvascular invasion preoperatively? What are the characteristics of a group of early HCC recurrences even with no microvascular invasion?

Methods

Study 1 included 229 patients with HCC who underwent curative liver resection between 1991 and 2008; 127 had HCC without microscopic portal venous invasion, and 52 had HCC with microscopic portal venous invasion (MPVI). These two distinct groups were analyzed with regard to various clinicopathologic factors. Subsequently, we specifically investigated if HCCs <5 cm with vascular invasion (n = 32) have some characteristics that would allow detection of latent microvascular invasion. Study 2 included 127 HCC patients without MVPI; 42 had a recurrence within 2 years, and 85 patients were recurrence-free for at least 2 years. These two distinct groups were analyzed with regard to various clinicopathologic factors.

Results

HCC diameter of >5 cm, the macroscopic appearance of HCC, and high levels of preoperative des-γ-carboxyprothrombin are significant prognostic factors in identifying microvascular invasion of HCC. The strongest predictor of early recurrence (within 2 years) was the serum α-fetoprotein level in patients without clear microvascular invasion.

Conclusions

Tumor size, macroscopic appearance, and high tumor marker levels are important elements in identifying the group of patients with a low HCC recurrence rate after curative liver resection.     

Prognostic Significance of Preoperative Peripheral Blood Monocyte Ratio in Patients with Hepatocellular Carcinoma

Background

Leukocyte subsets in peripheral blood, which include neutrophils, lymphocytes, and monocytes, have not been well established as prognostic factors in patients with hepatocellular carcinoma (HCC).

Methods

Consecutive patients who underwent curative hepatic resection for HCC at the National Cancer Center, Republic of Korea, from 2001 to 2008 were enrolled in this retrospective study. Clinicopathologic factors, cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed with respect to preoperative lymphocyte subsets, especially monocyte ratio.

Results

The 603 patients had a median follow-up of 40.0 months and a 5-year overall survival rate of 67.7 %. In univariate analysis of survivals, preoperative lymphocyte ratio ≤35 % and monocyte ratio >7 % were significantly poor prognostic factors. In multivariate analysis, preoperative monocyte ratio >7 %, satellite nodule, and microvascular invasion were independent risk factors for CSS and DFS (hazard ratio of monocyte ratio >7 % = 1.77, p = 0.02 and 1.57, p = 0.006, respectively). Considering monocyte ratio with preoperative α-fetoprotein level, patients with both abnormal α-fetoprotein levels (>12 ng/mL) and monocyte ratio >7 % showed significantly worse CSS and DFS than other groups (p < 0.001). Cirrhotic patients with monocyte ratio >7 % showed significantly poor CSS and DFS compared with non-cirrhotic patients (p = 0.033 and <0.001, respectively).

Conclusions

A preoperative monocyte ratio >7 % of peripheral blood is an independent risk factor for CSS and DFS after hepatic resection for HCC. Preoperative monocyte ratio might be considered as a novel biomarker for HCC.     

Resection of Hepatocellular Carcinoma with Macroscopic Vascular Invasion

Background

Survival for Child’s A patients with hepatocellular cancer (HCC) and macroscopic vascular invasion (MVI) has been reported as approximately 8.1 months with sorafenib. The role of surgery for these patients remains controversial.

Methods

The records of all patients undergoing resection of HCC at a single center were reviewed. Only patients with pathologically proven MVI were included. Inclusion criteria for resection required Child’s A liver disease, no clinical portal hypertension (after 2002), and no extrahepatic disease. The superior mesenteric vein and portal vein branch to the remaining lobe had to be patent.

Results

We identified 165 patients with MVI treated with hepatic resection between June 1992 and March 2010. Median follow-up was 11.9 months with 127 deaths, including 12 (7.3 %) perioperative mortalities. Median and 5-year survivals were 13.1 months and 14 %. Multivariate analysis found α-fetoprotein (AFP) >30 ng/ml (hazard ratio 2.07), tumor size >7 cm (hazard ratio 1.59), and extent of vascular invasion (hazard ratio 1.74) to be independently associated with survival. Those with invasion of hepatic veins or vena cava had a median survival of only 4.7 months.

Conclusions

The results for resection of HCC with MVI remain somewhat disappointing but are better than what is reported with medical therapy in similar patients. Tumor size, AFP, and extent of vascular invasion can help select those that will benefit most from hepatic resection. Resection of patients with hepatic vein or vena cava involvement may not be justified, given such poor results.     

Impact of Spontaneous Hepatocellular Carcinoma Rupture on Recurrence Pattern and Long-term Surgical Outcomes after Partial Hepatectomy

Background

The clinical significance of spontaneous hepatocellular carcinoma (HCC) rupture association with recurrence pattern and long-term surgical outcomes remains under debate. We investigated the impact of spontaneous HCC rupture on recurrence pattern and long-term surgical outcomes after partial hepatectomy.

Methods

From 2000 to 2012, 119 patients with diagnosed ruptured HCC were reviewed. To compare outcomes between staged hepatectomy in spontaneously ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score-matching to adjust for significant differences in patient characteristics. Overall survival, disease-free survival, and recurrence pattern were compared between the matched groups.

Results

Forty-four patients with newly diagnosed ruptured HCC and Child A class were initially treated with transcatheter arterial embolization for hemostasis. Three patients underwent emergency laparotomy, 18 underwent staged hepatectomy, and 23 received transarterial chemoembolization (TACE) alone after transcatheter arterial embolization. Among the 23 patients treated with TACE alone, 10 had resectable tumors. The staged hepatectomy group shows significantly higher overall survival with TACE alone than the resectable tumor group (P < 0.001). After propensity score-matching, overall survival, disease-free survival, and recurrence pattern were not significantly different between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC with hepatectomy group. Peritoneal recurrence rates were similar at 14.3 % versus 10.0 %, respectively (P = 0.632).

Conclusions

Patients with spontaneously ruptured HCC with staged hepatectomy show comparable long-term survival and recurrence pattern as patients with non-ruptured HCC having similar tumor characteristics and liver functional status. Thus, spontaneous HCC rupture may not increase peritoneal recurrence and decrease long-term survival after partial hepatectomy.     

Postoperative Serum Osteopontin Level is a Novel Monitor for Treatment Response and Tumor Recurrence after Resection of Hepatitis B–related Hepatocellular Carcinoma

Background

Presurgery serum osteopontin (OPN) level has been demonstrated to correlate to tumor recurrence and survival of hepatocellular carcinoma (HCC) patients. This study investigated the postoperative dynamic changes of serum OPN level and its clinical significance in HCC patients.

Methods

Presurgery serum OPN levels were measured by enzyme-linked immunosorbent assay in cohort A of 179 HCC patients and were compared with the multiple controls including different kinds of liver diseases and healthy individuals. In cohort B of 110 patients with resectable HCCs, besides preoperative assays, serum OPN was monitored at 1 week, 1, and ≥2 months after operation.

Results

The baseline presurgery serum OPN of HCC patients was significantly higher than that of the patients with the other kinds of liver diseases (p < 0.0001). The prognostic values of presurgery serum OPN level in HCC patients were further confirmed. The postsurgery OPN levels were significantly elevated within 1 week after HCC resection, then decreased at 1 month and reached the nadir later than 2 months after operations. It increased again at the time of tumor recurrence, then declined after the second removal of recurrent HCCs. Moreover, postoperative OPN in α-fetoprotein-negative and -positive HCC patients had the same changing pattern; it only correlated to liver function and C-reactive protein level.

Conclusions

After a transient fluctuation, serum OPN levels significantly decrease after curative resection of HCCs. Postoperative serum OPN could serve as a surrogate serologic biomarker for monitoring treatment response and tumor recurrence after HCC resection, including α-fetoprotein-negative ones.     

Risk Factors for Early Recurrence of Single Lesion Hepatocellular Carcinoma After Curative Resection

Background and objectives

Hepatic resection is established as the treatment for HCC. However, patients sometimes experience early recurrence of HCC (ER HCC) after curative resection.

Methods

A retrospective analysis was conducted for 193 patients with single HCC who underwent curative liver resection in our medical center between April 2000 and March 2013. We divided the cohort into two groups; early recurrence group (ER G) which experienced recurrence within 6 months after resection, and non-early recurrence group (NER G). Risk factors for ER HCC were analyzed.

Results

Thirty-nine out of 193 (20.2 %) patients had ER HCC. Univariate analysis showed Glasgow prognostic score (GPS, p = 0.036), neutrophil to lymphocyte ratio (NLR, p = 0.001), level of PIVKA-II (p = 0.0001), level of AFP (p = 0.0001), amounts of blood loss (p = 0.001), operating time (p = 0.002), tumor size (p = 0.0001), stage III and IV (p = 0.0001), and microvascular invasions (portal vein: p = 0.0001 and hepatic vein: p = 0.001) to be associated with ER HCC. By multivariate analysis, there were significant differences in high NLR (p = 0.029) and high AFP (p = 0.0001) in patients with ER HCC.

Conclusions

Preoperative high AFP (more than 250 ng/ml) and high NLR (more than 1.829) were independent risk factors for ER HCC.

     

HBV DNA and HBsAg Levels as Risk Predictors of Early and Late Recurrence after Curative Resection of HBV-related Hepatocellular Carcinoma

Background

Recent studies have shown that high hepatitis B virus (HBV) load is associated with increased risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). The aim of our study was to investigate the predictive role of HBV DNA and hepatitis B surface antigen (HBsAg) levels in early and late recurrence of HCC after curative resection in patients with HBV-related HCC.

Methods

From January 2008 to December 2010, a total of 248 patients underwent curative resection for HBV-related early-stage HCC (solitary tumor; < 5 cm in diameter or multinodular tumor; number of tumors ≤3 and diameter < 3 cm). We analyzed the predictive factors including HBV DNA and HBsAg levels for early recurrence (within 2 years) and late recurrence (after 2 years) of HCC after curative resection.

Results

The median follow-up duration was 33.3 months. Cumulative recurrence rates after resection at 1, 3, and 5 years were 16.6, 34.0, and 46.7 %, respectively. The multivariate analysis showed that risk factors for early recurrence were the presence of microvascular invasion (hazard ratio [HR] 3.86; p < 0.001), preoperative HBV DNA levels ≥ 20,000 IU/mL (HR 2.77; p < 0.001), and des-γ-carboxy prothrombin level ≥ 40 mAU/mL (HR 1.76; p = 0.045). Although, the risk factors for late recurrence by multivariate analysis were preoperative HBsAg levels ≥ 4,000 IU/mL (HR 2.80; p = 0.023) and age at resection ≥ 50 years (HR 3.22; p = 0.032).

Conclusion

The HBV DNA levels were associated with early recurrence, whereas HBsAg levels were associated with late recurrence after curative resection in HBV-related HCC.     

Complete Necrosis After Transarterial Chemoembolization Could Predict Prolonged Survival in Patients with Recurrent Intrahepatic Hepatocellular Carcinoma After Curative Resection

Background

We explored the predictors of response to transarterial chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular carcinoma (HCC) after hepatectomy and investigated the survival of these patients according to the response to TACE.

Methods

We analyzed data from 199 consecutive HCC patients who underwent curative liver resection and who later received repeat TACE for intrahepatic HCC recurrence.

Results

Of 199 patients, 139 (69.8%) achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At hepatectomy, the CN group showed significantly smaller proportions of tumor capsular invasion, microvascular invasion, and pathologic tumor–node–metastasis stage III or IV HCCs. At first TACE, the CN group showed a significantly greater proportion of patients with time to recurrence ≥ 1 year, Child–Pugh class A, serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary tumors, and nodular tumor types; portal vein invasion were less common than seen in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single tumor at first TACE were independently related to attainment of CN after TACE. Median survival after first TACE was significantly longer in the CN group (48.9 versus 17.0 months). In a Cox regression model, CN after TACE was an independent predictor of favorable survival outcome after first TACE.

Conclusions

CN after repeat TACE for postresection intrahepatic recurrence was attained more commonly in patients with smaller tumor size and lower tumor number at first TACE and favored longer survival in recurrent patients.     

Results of a surgical resection of pulmonary metastasis from hepatocellular carcinoma: prognostic impact of the preoperative serum alpha-fetoprotein level

Purpose

Pulmonary metastasis is the most common type of extrahepatic recurrence of hepatocellular carcinoma (HCC). The outcome of pulmonary metastasectomy of HCC has not yet been thoroughly investigated. The outcomes of surgical treatment of pulmonary metastases from HCC were reviewed in order to analyze the postoperative survival and the relevant prognostic factors.

Methods

This study retrospectively reviewed 20 patients who underwent pulmonary metastasectomy from an HCC between 1990 and 2007 at two institutions. The surgical outcome was evaluated by both the overall survival and cancer-specific survival after pulmonary resection. The association between various clinico-pathological factors and the survival outcome was analyzed.

Results

The overall survival rate after the initial pulmonary metastasectomy was 46.9% at 5?years, and the cancer-specific 5-year survival rate was 63.2%. One patient died of surgery-related events 19?days after the pulmonary resection. The preoperative AFP (alpha-fetoprotein) level was found to be a significant prognostic factor for both overall and cancer-specific survival for patients undergoing pulmonary metastasectomy. Both the overall and cancer-specific survival rates were significantly worse for the patients with AFP?≥?500?ng/ml in comparison to those with AFP?p?Conclusion The serum level of AFP might be a valuable predictor for the outcome of pulmonary metastasectomy required for metastasis of HCC.     

Elevation of Preoperative s-CEA Concentration in Stage IIA Colorectal Cancer Can Also Be a High Risk Factor for Stage II Patients

Purpose

To evaluate stage IIA colorectal cancer in terms of recurrence so as to discover whether high preoperative serum carcinoembryonic antigen (s-CEA) levels indicate that the patient should be included in a high-risk group in stage II colorectal cancer.

Methods

We retrospectively reviewed the records of 1543 patients with stage IIA colorectal cancer who underwent curative surgery between January 2000 and December 2007.

Results

The 5-year disease-free survival and overall survival rates were significantly lower in patients with a higher than normal preoperative s-CEA (90.5 % vs. 82.5 %, P < 0.001, and 92.4 % vs. 87.8 %, P = 0.034, respectively). Multivariate analysis revealed that elevated preoperative s-CEA level, preoperative obstruction, rectal cancer, and dissection of fewer than 12 nodes were independent statistically significant prognostic factors that predicted disease-free survival in patients with stage IIA disease after curative resection.

Conclusions

Elevated preoperative s-CEA concentration is a reliable predictor of recurrence after curative resection in patients with stage IIA colorectal cancer. Patients with stage IIA disease with elevated preoperative s-CEA level do worse than those with normal levels and might constitute a group to evaluate for adjuvant chemotherapy. Further studies on the effect of adjuvant chemotherapy in this group are needed.