Liver resection for hepatocellular carcinoma larger than 10 cm: A multi-institution long-term observational study

BACKGROUNDThe treatment of hepatocellular carcinoma (HCC) ≥ 10 cm remains a challenge. AIMTo consolidate the role of surgical resection for HCC larger than 10 cm.METHODSEligible HCC patients were identified from the Chang Gung Research Database, the largest multi-institution database, which collected medical records of all patients from Chang Gung Memorial Foundation. The surgical outcome of HCC ≥ 10 cm (L-HCC) was compared to that of HCC < 10 cm (S-HCC) (model 1). The survival of L-HCC after either liver resection or transarterial chemoembolization (TACE) was also analyzed (model 2). The long-term risks of all-cause mortality and recurrence were assessed to consolidate the role of surgery for L-HCC.RESULTSFrom January 2004 to July 2015, a total of 32403 HCC patients were identified from the Chang Gung Research Database. Among 3985 patients who received liver resection, 3559 (89.3%) had S-HCC, and 426 had L-HCC. The L-HCC patients had a worse disease-free survival (0.27 for L-HCC vs 0.40 for S-HCC) and overall survival (0.18 for L-HCC vs 0.45 for S-HCC) than the S-HCC after liver resection (both P < 0.001). However, the surgical and long-term outcome of resected L-HCC had improved dramatically in the recent decades. After adjusting for covariates, surgery could provide a better outcome for L-HCC than TACE (adjusted hazard ratio of all-cause mortality: 0.46, 95% confidence interval: 0.38-0.56 for surgery). Subgroup analysis stratified by different stages showed similar trend of survival benefit among L-HCC patients receiving surgery. CONCLUSIONOur study demonstrated an improving surgical outcome for HCC larger than 10 cm. Under selected conditions, surgery is better than TACE in terms of disease control and survival and should be performed. Due to inferior survival, a subclassification within T1 stage should be considered. Future studies are mandatory to confirm our findings.     

Predictors of Long-Term Disease-Free Survival After Resection of Hepatocellular Carcinoma: Two Decades of Experience at Chang Gung Memorial Hospital

Background: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. A high incidence of recurrence after hepatectomy is the most important cause of unsatisfactory results after resection of HCC. This study aimed to determine the clinicopathologic factors for predicting survival >5 years without recurrence in HCC patients treated with hepatectomy.Methods: The clinical features of 46 patients with surgically resected HCC who survived >5 years without recurrence (group A) were reviewed. Also, comparison was made with the clinical features and factors influencing the outcome of 1046 cases of resected HCC who survived <5 years both with and without recurrence and for >5 years with recurrence (group B).Results: Of 1092 cases of surgically resected HCC, 46 (4.5%) survived >5 years without recurrence. Univariate analysis revealed that absence of vascular invasion, satellite lesions, low histological grading of HCC, a lower rate of underlying liver cirrhosis, wider resection margins, and an uneventful postoperative course were frequent in group A patients compared with group B patients. Moreover, multivariate stepwise logistic regression analysis identified an absence of satellite lesions and an uneventful postoperative course as the two main independently significant predictors of HCC patients undergoing hepatectomy with long-term disease-free survival. The 1-, 3-, 5-, and 10-year survival rates of group A patients were 100%, 100%, 100%, and 84.1%, whereas those of group B patients were 73.5%, 47.9%, 29.0%, and 21.2%, respectively.Conclusions: An absence of satellite lesions and an uneventful postoperative course are the two main independent predictors for long-term disease-free survival in HCC patients undergoing hepatic resection.     

Resection of Peritoneal Implantation of Hepatocellular Carcinoma after Hepatic Resection: Risk Factors and Prognostic Analysis

Peritoneal implantation from hepatocellular carcinoma (HCC) after hepatic resection is infrequent, and information on risk factors and long-term survival of such patients is lacking. The clinicopathologic features and risk factors of 16 HCC patients after hepatic resection who developed peritoneal implantation from an HCC and the prognosis after surgical resection of these HCC implants were assessed. The clinical features of 16 HCC patients after hepatic resection undergoing resection of peritoneal HCC implants (P-HCC) from 1986 and 2000 were reviewed. The clinical features and outcomes of 195 HCC patients undergoing hepatectomy without recurrence (NR-HCC) were used for comparison. During 1986 and 2000 a total of 749 HCC patients underwent hepatic resection. Of these 749 patients, 465 (62.1%) had HCC recurrence after hepatic resection during the follow-up period (median 26 months). Of the 465 patients, 26 (5.6%) developed peritoneal implants, and 16 of them underwent resection. Multivariate logistic regression analysis revealed that a high -fetoprotein (AFP) level and capsular invasion by the tumor cells may predispose posthepatectomy patients to peritoneal implantation from their HCCs. The overall survival of the P-HCC patients after peritoneal implant resection was similar to that of the NR-HCC patients. An elevated AFP level might be regarded as a significant prognostic factor for poor overall survival (p = 0.0577) after resection of peritoneal implants from HCCs. Peritoneal implantation occurs infrequently in posthepatectomy patients with an HCC. Elevated AFP values and capsule invasion by tumor cells may predispose posthepatectomy patients to peritoneal implantation from HCCs. Surgical resection of peritoneal implants from HCCs may prolong survival in selected patients. Elevated AFP levels may be regarded as a possibly significant prognostic factor for poor overall survival after resection of peritoneal HCC implants.     

The benefit of curative liver resection with a selective bile duct preserving approach for hepatocellular carcinoma with macroscopic bile duct tumor thrombus

BackgroundHepatocellular carcinoma (HCC) presenting with macroscopic bile duct tumor thrombus (BDTT) is an uncommon event. The role of a curative hepatic resection and associated long-term outcomes remain controversial. In addition the necessity for bile duct resection is still unclear. The aim of this study was to evaluate outcomes of hepatectomy with a selective bile duct preservation approach for HCC with BDTT in comparison to outcomes without BDTT.MethodsA total of 22 HCC with BDTT patients who had undergone curative hepatic resection with a selective bile duct preservation approach at our institute were retrospectively reviewed. These were compared to group of 145 HCC without BDTT patients. The impact of curative surgical resection and BDTT on clinical outcomes and survival after surgical resection were analyzed.ResultsAll HCC with BDTT cases underwent major hepatectomy vs. 32.4% in the comparative group. Bile duct preservation rate was 56.5%. The 1-, 3- and 5-year survival rates of HCC with BDTT patients in comparison to the HCC without BDTT group were 81.8%, 52.8% and 52.8% vs. 73.6%, 55.6% and 40.7% (P=0.804) respectively. Positive resection margin, tumor size ≥5 cm and AFP ≥200 IU/mL were significant risk factors regarding overall survival. However, it is unclear whether presence of a bile duct tumor thrombus has an adverse impact on either recurrence free survival or overall survival.ConclusionsBile duct obstruction from tumor thrombus did not necessarily indicate an advanced form of disease. Tumor size and AFP had greater impact on long-term outcomes than bile duct tumor thrombus. Major liver resection with a selective bile duct preserving approach in HCC with BDTT can achieve favorable outcomes comparable to those of HCC without BDTT in selected patients.     

Pre-operative predictors of post-hepatectomy recurrence of hepatocellular carcinoma: Can we predict earlier?

Backgrounds and purposeTo determine the predictors for recurrence in patients receiving curative hepatectomy for hepatocellular carcinoma (HCC).MethodsFrom January 2001 to July 2007, all patients having hepatectomy for first occurrence HCC with curative intent were identified from a prospectively collected database. Prognostic factors for recurrence and survival after resection were analyzed.ResultsA total of 235 patients were included. With a median follow-up of 50.2 (0.07–125.1) months, the recurrence rate was 57.0%. The 1-, 3-, and 5-year overall survival rates were 83.9%, 66.0%, and 58.1% respectively. Multivariate analysis demonstrated that multi-focal lesions (HR: 2.93, P < 0.001), alpha-fetoprotein (AFP) level greater than 100 ng/ml (HR: 1.74, P = 0.002) and history of tumor rupture (HR: 2.84, P = 0.003) were independent risk factors for recurrence of HCC after hepatectomy.ConclusionsPredictors for HCC recurrence can be identified before operation. These important parameters should be considered before and after contemplating curative resection for HCC patients and for risk stratification in future clinical trials for neoadjuvant or post-resection adjuvant therapy. The possible use of neoadjuvant or adjuvant treatment to improve survival should be addressed by further trials.     

Hepatic Resection for Hepatocellular Carcinoma with Obstructive Jaundice due to Biliary Tumor Thrombi

Hepatocellular carcinoma (HCC) with obstructive jaundice due to biliary tumor thrombi is uncommon, and few studies have examined the outcome of hepatectomy for HCC with this unusual entity. This study examined the clinicopathologic factors influencing the outcomes of 17 HCC patients with obstructive jaundice due to biliary tumor thrombi undergoing hepatectomy. The clinical features of 17 HCC patients with obstructive jaundice due to biliary tumor thrombi (group A) undergoing hepatectomy from 1986 to 1998 were reviewed. The clinical features and factors influencing the outcome of 555 HCC patients without biliary tumor thrombi (group B) undergoing hepatectomy were used for comparison. Of 572 patients with surgically resected HCCs, 17 (3.0%) were classified into group A. Right upper quadrant pain, physical signs of jaundice, low albumin level, elevated bilirubin level, small tumor size, more vascular invasion, and tumor rupture were characteristic of group A patients. Multivariate stepwise logistic regression analysis revealed no independently significant factor differentiating group A patients from group B patients. The disease-free survival was similar between the group A and B patients, although group B patients exhibited significantly better overall survival (p = 0.014). Vascular invasion may adversely influence overall survival in group A patients undergoing hepatic resection (p = 0.0709). When feasible, hepatic resection is the preferred treatment for HCC patients with obstructive jaundice due to biliary tumor thrombi. It can achieve a disease-free survival comparable to that of HCC patients without biliary tumor thrombi. However, HCC patients with biliary tumor thrombi had significantly worse overall survival than did those without biliary tumor thrombi, especially those with concomitant vascular invasion.     

Hepatectomy for hepatocellular carcinoma: the surgeon's role in long-term survival.

HYPOTHESIS: The surgeon can contribute substantially to the long-term survival rate of patients undergoing hepatectomy for hepatocellular carcinoma (HCC). DESIGN: The long-term survival rate of patients with HCC undergoing hepatectomy has improved, but the contribution of the surgeon to the improved survival rate is unknown. We surveyed 211 consecutive patients undergoing hepatectomy for HCC. The clinical, operative, and pathological factors were analyzed to identify factors that were important in affecting long-term survival. SETTING: A tertiary referral center. PATIENTS: From April 1989 to December 1995, 211 consecutive patients with HCC underwent 153 major and 58 minor hepatectomies. MAIN OUTCOME MEASURES: Disease-free and overall cumulative survival rate. RESULTS: The 5-year disease-free survival rate was 27%. By Cox regression analysis, blood transfusion (relative risk [RR], 1.21; 95% confidence interval [CI], 1.05-1.40) and TNM stage (RR, 1.90; 95% CI, 1.47-2.47) were shown to be independent prognostic factors in the 5-year disease-free survival rate. The 5-year overall cumulative survival rate was 37%. By Cox regression analysis, the preoperative indocyanine green retention value at 15 minutes after injection (RR, 1.03; 95% CI, 1.01-1.06), blood transfusion (RR, 1.191; 95% CI, 1.078-1.316), tumor rupture (RR, 1.48; 95% CI, 1.08-2.04), and TNM stage (RR, 1.62; 95% CI, 1.27-2.07) were shown to be significant independent factors that influenced cumulative survival rate. CONCLUSIONS: The long-term survival of patients with HCC after hepatectomy depends on tumor staging, preoperative hepatic functional reserve, history of blood transfusion, and rupture of HCC. Preoperative liver function and tumor staging cannot be altered; however, the surgeon can play an important role in improving the prognosis if blood transfusion and iatrogenic tumor rupture can be avoided and if function of the liver remnant can be preserved.     

The ALBI Grade is a Good Predictive Model for Very Late Recurrence in Patients with Hepatocellular Carcinoma Undergoing Primary Resection

Background

Hepatocellular carcinoma (HCC) patients still have risk for very late recurrence after curative resection. This study assesses prognostic factors in HCC patients with recurrence-free survival (RFS) for 5 years after primary resection.

Methods

We enrolled 383 HCC patients who received primary tumor resection and achieved more than 5 years without recurrence after resection between January 2001 and April 2013. Predictive factors, including albumin-bilirubin (ALBI) grade, for RFS and overall survival (OS) were analyzed.

Results

After a median follow-up of 103 months, 57 patients (14.9%) had recurrent HCC, and 14 (3.7%) died. Independent predictors for HCC recurrence were male sex (p = 0.035), pre-operative liver cirrhosis (LC) (p = 0.025), serum creatinine  > 1.5 mg/dL (p = 0.045), post-operative 5th-year alpha-fetoprotein (AFP) > 15 ng/ml (p < 0.001), LC (p = 0.004), and ALBI grades 2 and 3 (p < 0.001). I ndependent risk factors for poor survival were age >70 years (p = 0.002), post-operative 5th-year AFP > 15 ng/ml (p = 0.003), and ALBI grades 2 and 3 (p = 0.002). Patients whose deteriorated ALBI grades 5 years after resection had adverse RFS outcomes compared to those with constant (p = 0.056) and improved ALBI grades (p = 0.008). In subgroup analysis, patients with post-operative 5th-year ALBI grades 2 and 3 had significantly poorer RFS and OS (both p < 0.001) than those with grade 1 among patients with low post-operative 5th-year AFP (<15 ng/mL).

Conclusion

In HCC patients without recurrence for 5 years after curative resection, post-operative 5th-year ALBI grade is useful for predicting outcomes, even with low AFP during follow-up.

     

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.     

可切除肝细胞癌合并门静脉癌栓的外科治疗

背景与目的 对于肝细胞癌（HCC）合并门静脉癌栓（PVTT）患者而言,手术切除率低,复发率高,预后较差,其治疗方式目前仍有很多争议。笔者总结可切除HCC合并PVTT的外科治疗经验,比较手术与肝动脉化疗栓塞术（TACE）对此类患者的近远期疗效。方法 回顾性分析云南省临沧市人民医院2016年3月—2021年3月收治的39例可切除HCC合并PVTT患者的临床资料,其中23例患者施行手术治疗（手术组）,16例行TACE治疗（TACE组）。比较两组患者的相关临床资料与预后,并分析影响患者预后的因素。结果 手术组除1例肿瘤广泛侵犯仅取材活检,其余均完成手术,无手术死亡;19例示切缘阴性;2例术后肝功能不全,经人工肝及其他支持治疗痊愈出院。TACE组16例肝动脉超选、灌注、栓塞顺利;1例因肝动脉完全栓塞,术后3 d因急性肝衰竭救治无效死亡。手术组8例术后辅助TACE治疗,5例靶向治疗,其中1例I型PVTT患者手术后联合TACE等治疗后仍生存47个月。TACE组13例多次治疗,4例给靶向药物,其中1例II型PVTT患者TACE术后经过7次灌注化疗及栓塞仍然生存25个月。与TACE组比较,手术组住院时间延长、医疗成本增加、术后行TACE的例数更少、术后未做其他治疗的例数以及术后AFP恢复正常的例数更多（均P<0.05）。手术组与TACE组的中位生存期分别为16.2个月与9.5个月;0.5、1、2、3年生存率分别为65.2%、43.5%、34.8%、17.4%与46.7%、33.3.0%、13.3%、0。两组患者中位生存期与累积生存率差异均有统计学意义（均P<0.05）。单因素分析结果显示,PVTT分型、甲胎蛋白（AFP）水平、肿瘤大小、肿瘤数目与患者术后生存时间有关（均P<0.05）;多因素分析结果显示,治疗方式、PVTT分型、肿瘤直径、AFP水平是患者术后生存时间的独立影响因素（均P<0.05）。结论 PVTT分型、肿瘤直径、AFP水平直接影响HCC合并PVTT患者的术后生存,外科手术切除治疗效果明显好于TACE治疗,尤其是对于可切除HCC合并I/II型PVTT的患者,但治疗选择可能受患者意愿、经济因素等的限制。     

AGMA Score: A Novel Prognostic Score for Patients Undergoing Liver Transplant for Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) in cirrhosis represents one of the leading indications for liver transplant. In an effort to expand the listing criteria, a variety of scoring systems have been suggested, mainly based on the tumor number/size criterion. The objective of our study was to evaluate the feasibility of proposing a transplant score for HCC excluding the tumor number/size criterion.Patients and MethodsData corresponding to patients who received transplants because of HCC were reviewed for the purposes of this study. Deceased donor and living donor liver transplants were included. Demographic, clinical and tumor-related parameters were evaluated. Uni- and multivariate regression analyses and survival analysis were performed.ResultsOne hundred patients were included in the study. Fifty-five patients underwent deceased donor liver transplant, and 45 patients received living donor liver transplants. Tumor differentiation (G1/2 vs G3), alpha-fetoprotein levels (AFP), recipient age, and recipient laboratory Model for End-Stage Liver Disease Score (MELD) showed statistical significance. A scoring system was developed, with prognostic points assigned as follows: age 60 years or younger:age older than 60 years = 1:0 points, tumor grading well or moderate:tumor grading poor = 1:0 points, MELD score ≤22:MELD score >22 = 1:0 points, and AFP level ≤400 ng/mL:AFP level >400 ng/mL = 1:0 points. This stratification delineated 3 separate population samples corresponding to patients with scores of 4, 3, and 1 to 2, respectively. The calculated 5-year survival for scores 4, 3, and 1 to 2 was 76%, 47%, and 20%, respectively (P < .001).ConclusionThe AGMA score (age, grading, MELD, AFP) showed prognostic value in this single-center analysis and may find clinical implication avoiding the tumor number/size criterion.     

Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of end-stage liver disease (MELD) score predicts perioperative mortality

Hepatic resection for hepatocellular carcinoma (HCC) in patients with cirrhosis is generally recommended for patients with Child-Turcotte-Pugh (CTP) Class A liver disease and early tumor stage. The Model for End-Stage Liver Disease (MELD) has been shown to accurately predict survival in patients with cirrhosis, but whether MELD is useful for selection of patients with cirrhosis for hepatic resection is unknown. We examined whether MELD was predictive of perioperative mortality and correlated MELD with other potential clinicopathologic factors to overall survival in patients with cirrhosis undergoing hepatic resection for HCC. A retrospective chart review was undertaken of patients with HCC and cirrhosis undergoing hepatic resection between 1993 and 2003. Eighty-two patients (62 men, 20 women; mean age, 62 years) were identified. Forty-five patients had MELD score ≥9 (range, 9–15) and CTP score ranged from 5 to 9 points. Fifty-nine patients underwent minor (<3 segments) hepatic resections (MELD ≤8, n = 29; MELD ≥9, n = 30) and 23 underwent major (≥3 segments) hepatic resections (MELD ≤8, n = 8; MELD ≥9, n = 15). Perioperative mortality rate was 16%. MELD score ≤8 was associated with no perioperative mortality versus 29% for patients with an MELD score ≥9 (P < 0.01). Multivariate analysis demonstrated that MELD score ≥9 (P < 0.01), clinical tumor symptoms (P < 0.01), and ASA score (P = 0.046) are independent predictors of perioperative mortality. Multivariate analysis showed MELD ≥9 (P < 0.01), tumor size >5 cm(P < 0.01), high tumor grade (P = 0.03), and absence of tumor capsule (P < 0.01) as independent predictors of decreased long-term survival. MELD score was a strong predictor of both perioperative mortality and long-term survival in patients with cirrhosis undergoing hepatic resection for HCC. In patients with cirrhosis, hepatic resection (minor or major) for HCC is recommended if the MELD score is ≤8. In patients with MELD score ≥9, other treatment modalities should be considered. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

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.     

Preoperative Alpha-Fetoprotein and Radiological Total Tumor Diameter as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation

BackgroundLiver transplantation is a unique treatment opportunity for patients with chronic liver disease and hepatocellular carcinoma (HCC). Selection of HCC patients for transplantation was revolutionized by Milan-based criteria, but tumor recurrence and shortage of organs are still a major concern. Nowadays, additional preoperative tumor parameters can help to refine the graft allocation process. The objective of this study was to evaluate the prognostic value and cut-off points of pretransplant serum alpha-fetoprotein (AFP) levels and radiological tumor parameters on liver transplantation outcomes.MethodsThis is a single-team retrospective cohort of 162 consecutive deceased donor liver transplants (DDLT) with pathologically confirmed HCC. Pretransplant serum AFP levels and radiological tumor parameters were retrieved from a preoperative follow-up. Receiver-operating characteristics (ROC) curves were used to evaluate cut-off points for each outcome. Multivariate Cox regression model was used to assess the predictors of HCC relapse and recipient mortality.ResultsTwelve recipients (7.4%) had HCC recurrence after transplantation, with median survival time of 5.8 months. Pretransplant AFP ≥30 ng/mL (hazard ratio [HR]: 13.84, P = .003) and radiological total tumor diameter (TTD) ≥5 cm (HR: 12.89, P = .005) were independent predictors for HCC relapse. Moreover, pretransplant AFP ≥150 ng/mL was independently associated with recipient mortality (HR: 4.45, P = .003).ConclusionsPretransplant AFP levels and radiological TTD were independently associated with HCC relapse and recipient mortality after DDLT, with different cut-off points predicting different outcomes. These findings may contribute to improving decision-making in the context of liver transplantation for HCC patients.     

Hepatocellular cancer in the non-cirrhotic liver

Less than 20% of hepatocellular carcinoma (HCC) develops in the non-cirrhotic liver (NCL). The diagnosis of HCC in NCL is suggested by a large hypervascular tumor in a 60-75 year old patient (usually male), particularly if the alpha-fetoprotein (AFP) level is high. But AFP is normal more often than not. Surgical resection is the only curative therapy of HCC; resection is more commonly feasible in HCC in NCL due to the healthy parenchyma of the underlying liver. The prognosis of HCC in NCL is better than that for HCC on cirrhosis with a 5-year survival approaching 50%. Prognosis is best in the patient with a small HCC with no vascular invasion or satellite nodules for whom an R0 resection can be achieved without the need for intra-operative transfusion. While intra-hepatic recurrence occurs frequently, it should be aggressively sought and treated; there is a major role for repeat hepatic resection and a lesser role for hepatic transplantation where results are poorer than those obtained for HCC on cirrhosis.     

Efficacy of Tumor Markers After Liver Transplantation In Patients With Hepatocellular Carcinoma

ObjectiveThe most reliable treatment for hepatocellular carcinoma (HCC) is liver transplantation (LT). Recurrence of HCC after LT is the most serious problem; therefore, early diagnosis of recurrent HCC is very important. This study investigated the efficacy of tumor markers in patients with LT for HCC.Methods and MaterialsFrom January 2008 to December 2016, 242 patients underwent LT for HCC. The operation of LT and immunosuppressive methods were the same as those of general LT patients. All patients were followed up with alpha-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA)-II. The 41 patients (16.9%) recurred during follow-up period.ResultsThe factors associated with recurrence were tumor markers (AFP, PIVKA-II), maximum tumor diameter, number, microvascular invasion, Milan criteria, and Edmondson–Steiner grade. In 41 patients with recurrent HCC, 14 patients (34.15%) were both elevated in 2 markers and 18 patients (43.9%) were elevated in 1 tumor marker. There was no relationship between tumor marker and recurrent site. The survival rate of patients with recurrence in 1, 3, and 5 years were 78.6%, 34.7%, and 23.7%, respectively. Curability of treatment and elevation of tumor marker before treatment were correlated with patient survival after recurrence. When the receiver operating characteristic curve was used, the area under the curve value using the sum of AFP and PIVKA-II before LT was 0.827.ConclusionsIn this study, tumor markers (AFP, PIVKA-II) for HCC were correlated with post-transplant recurrence factors and may be a useful tool for early diagnosis and to predict the prognosis after recurrence.     

Intraoperative Iatrogenic Rupture of Hepatocellular Carcinoma

Intraoperative iatrogenic rupture of hepatocellular carcinoma (HCC), which can occur during hepatic resection when large tumors are being mobilized, may adversely affect the operative outcome. Little information is available in the literature on this serious intraoperative complication. The aim of the present study is to document iatrogenic rupture of HCC as a serious complication during hepatic resection and its effects on the operative and long-term outcomes of patients with this complication. A retrospective study was performed on all patients with intraoperative iatrogenic rupture of HCC during hepatic resection from 1989 to 1997, and the operative and long-term survival outcomes were compared with those of patients without the complication. Among 194 patients who underwent hepatic resection for a large HCC (> or =5 cm) during the study period, 8 (4.1%) had intraoperative iatrogenic rupture of the tumor. When compared with 186 patients with similar clinical parameters but without intraoperative rupture, patients with intraoperative rupture had significantly more intraoperative blood loss (median 5.7 vs. 2.0 L;p = 0.01) and blood transfusion requirement (median 3.1 vs 0.9 L; p = 0.02). On follow-up, patients in the intraoperative rupture group had a significantly higher intraperitoneal extrahepatic recurrence rate (33.3% vs. 2.9%; p =0.02) and significantly shorter survival (median 11.5 vs. 37.9 months,p = 0.04) when compared with patients without the complication. Intraoperative iatrogenic rupture is a serious complication of hepatic resection for HCC because it is associated with increased intraoperative blood loss, increased incidence of intraperitoneal extrahepatic recurrence, and short survival. Extreme care should be taken during mobilization of the tumor, and an alternative operative approach in the presence of a difficult hepatic resection of a large HCC may be required to avoid the complication.     

Development of a machine learning model to predict early recurrence for hepatocellular carcinoma after curative resection

BackgroundEarly recurrence is common for hepatocellular carcinoma (HCC) after surgical resection, being the leading cause of death. Traditionally, the COX proportional hazard (CPH) models based on linearity assumption have been used to predict early recurrence, but predictive performance is limited. Machine learning models offer a novel methodology and have several advantages over CPH models. Hence, the purpose of this study was to compare random survival forests (RSF) model with CPH models in prediction of early recurrence for HCC patients after curative resection.MethodsA total of 4,758 patients undergoing curative resection from two medical centers were included. Fifteen features including age, gender, etiology, platelet count, albumin, total bilirubin, AFP, tumor size, tumor number, microvascular invasion, macrovascular invasion, Edmondson-Steiner grade, tumor capsular, satellite nodules and liver cirrhosis were used to construct the RSF model in training cohort. Discrimination, calibration, clinical usefulness and overall performance were assessed and compared with other models.ResultsFive hundred survival trees were used to generate the RFS model. The five highest Variable Importance (VIMP) were tumor size, macrovascular invasion, microvascular invasion, tumor number and AFP. In training, internal and external validation cohort, the C-index of RSF model were 0.725 [standard errors (SE) =0.005], 0.762 (SE =0.011) and 0.747 (SE =0.016), respectively; the Gönen & Heller’s K of RSF model were 0.684 (SE =0.005), 0.711 (SE =0.008) and 0.697 (SE =0.014), respectively; the time-dependent AUC (2 years) of RSF model were 0.818 (SE =0.008), 0.823 (SE =0.014) and 0.785 (SE =0.025), respectively. The RSF model outperformed early recurrence after surgery for liver tumor (ERASL) model, Korean model, American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) stage, Barcelona Clinic Liver Cancer (BCLC) stage and Chinese stage. The RSF model is capable of stratifying patients into three different risk groups (low-risk, intermediate-risk, high-risk groups) in the training and two validation cohorts (all P<0.0001). A web-based prediction tool was built to facilitate clinical application (https://recurrenceprediction.shinyapps.io/surgery_predict/).ConclusionsThe RSF model is a reliable tool to predict early recurrence for patients with HCC after curative resection because it exhibited superior performance compared with other models. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy.     

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.

     

Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter

BACKGROUND: The role of hepatic resection for large hepatocellular carcinoma (HCC) larger than 10 cm remains unclear. STUDY DESIGN: Perioperative and longterm outcomes of 120 patients with HCC larger than 10 cm who underwent resection (group A) were compared with 368 patients with smaller HCC (group B). The prognostic factors in group A were analyzed. RESULTS: A higher proportion of patients underwent major hepatic resection in group A than in group B (90% versus 57.6%, p = 0.001), but the hospital mortality was similar (5.0% versus 4.6%, p = 0.874). Group A had worse longterm overall survival (median 18.8 months versus 62.8 months, p < 0.001) and disease-free survival (median 5.5 months versus 25.4 months, p < 0.001) than group B. Macroscopic residual tumor, macroscopic venous invasion, and multiple tumors were identified as independent prognostic factors in group A. The median survival of patients with residual tumor and those with curative resection was 7.7 months and 20.8 months, respectively. The median survival of patients with curative resection of solitary HCC larger than 10cm without macroscopic venous invasion was 38.0 months; that of patients with both macroscopic venous invasion and multiple tumors was only 10.5 months. CONCLUSIONS: Hepatic resection is a safe and effective treatment for HCC larger than 10cm when liver function reserve is satisfactory and when curative resection can be expected. Patients with solitary HCC larger than 10cm without macroscopic venous invasion can enjoy longterm survival after surgery, and we propose hepatic resection as a standard treatment for this group of patients.