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.     

Liver Resection with Portal Vein Thrombectomy for Hepatocellular Carcinoma With Vascular Invasion

Introduction  Hepatocellular carcinoma (HCC) tends to invade the intrahepatic vasculature, especially the portal vein.1 The presence of portal vein tumor thrombus (PVTT) in patients with HCC is one of the most significant factors for a poor prognosis.2 ^– 5 The presence of macroscopic PVTT in patients with HCC is also a significant factor for poor prognosis, with a median survival of <3 months without treatment.1 In surgically resected series, in patients with gross PVTT (PVTT in the portal trunk, its first-order branch, or its second-order branch), the 3-year and 5-year survival rates are reportedly 15% to 28% and 0% to 17%, respectively.2 ^– 5 Methods  The patient was a 77-year-old woman with well-compensated hepatitis C virus–related cirrhosis (stage A6 according to Child-Pugh classification) who sought care at our department for vague abdominal discomfort. Triphasic spiral computed tomographic scan confirmed HCC 6 cm in diameter in the left lobe of the liver. In addition, portal vein tumor thrombosis of the left branch that extended to the right portal vein was present. Results  The procedure included left hepatectomy and en-bloc portal vein thrombectomy with clamping of both the common portal vein trunk and the right portal vein. The portal vein was incised at the bifurcation of the right and left portal veins, and the thrombus was extracted from the incision in the portal vein. With this procedure, we were able to examine under direct vision the exact extent of the portal vein thrombus, and we identified whether the tumor thrombus was adherent to the venous wall or was freely floating in the venous lumen. Portal clamping and length of operation were 16 and 330 minutes, respectively. Intraoperative blood loss was 550 mL. The patient was discharged on postoperative day 6, and she was free of disease at 15 months after surgery. Discussion  Liver resection should be considered a valid therapeutic option for HCC with PVTT. Electronic supplementary material  The online version of this article (doi:) contains supplementary video material, which is available to authorized users. Presented to Annual Meeting of the American Hepato-Pancreato-Biliary Association (AHPBA), Miami, Florida, USA, March 9-12, 2006.     

ALPPS for Hepatocellular Carcinoma Is Associated with Decreased Liver Remnant Growth

Background

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been widely described for colorectal liver metastases with insufficient future liver remnant (FLR). However, its role in hepatocellular carcinoma (HCC) remains poorly defined and not widely accepted.

Methods

A retrospective comparison of clinical data, liver volumetry, histological characteristics, and surgical outcomes between nine HCC and four non-HCC patients who underwent ALPPS was performed.

Results

Patients with HCC were more likely to have histological evidence of hepatic fibrosis (HCC vs. non-HCC, 66.7 vs. 0%, p?=?0.049). Baseline demographic and disease characteristics were otherwise comparable between both groups. FLR growth after ALPPS-Stage 1 was significantly less in HCC patients (HCC vs. non-HCC, 154.5 vs. 251.0 ml, p?=?0.012). FLR growth was also significantly decreased in patients with hepatic fibrosis (fibrosis vs. non-fibrosis, 157.5 vs. 247.5 ml, p?=?0.033). There was no difference in post-hepatectomy liver failure (HCC vs. non-HCC, 28.6 vs. 25%, p?=?0.721) or 90-day mortality (HCC vs. non-HCC, 11.1 vs. 0%, p?=?NS).

Discussion

In our study, HCC patients demonstrated significantly less FLR growth after ALPPS-Stage 1 compared to non-HCC patients. Hepatic fibrosis was also found to negatively impact FLR growth. When considering suitability for ALPPS, patients with HCC may benefit from additional pre-operative assessment of fibrosis.

     

New Indication for Reduction Surgery in Patients with Advanced Hepatocellular Carcinoma with Major Vascular Involvement

Background The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly in patients with tumor thrombi (TT) in the major vessels. Patients and Methods From July 1992 to October 2004, 161 patients diagnosed as having advanced HCC with major vascular involvement were seen consecutively at our hospital. Among these patients, 32 (20%) underwent surgical resection [16 complete resection (CR), 16 reductive resection (RR)]. Eighteen patients (11%) received radiotherapy (RT), 73 (45%) underwent transcatheter arterial chemoembolization (TACE) or transcatheter arterial infusion chemotherapy (TAI), 8 (5%) with distant metastases received systemic chemotherapy, and 30 (19%) received palliative therapy. Results Excluding the CR group, the patients in the RR group had a higher 1-year survival rate than the other treatment groups. However, there was no significant difference in the overall survival rates of the RR, RT, and TACE/TAI groups. When we evaluated prognostic factors to clarify the indications for RR in the multidisciplinary treatment of patients with advanced HCC with TT, prothrombin activity (PA) was identified as a significant independent preoperative factor for overall survival in the RR group. The survival rate in patients with PA of ≤78% was significantly lower than that of patients with PA of >78% (P = 0.0004). The median survival time of patients with serum PA of >78% who underwent RR was 13.9 months and that of patients who underwent CR was 9.1 months, with no survival difference between the groups. Conclusion In advanced HCC with major vascular involvement, patients who had RR with PA of greater 78% achieved a similar survival to those who had CR. The surgeon should still proceed with RR in those patients with serum PA of >78% if CR does not seem feasible on preoperative evaluation.     

Preoperative Microvascular Invasion Prediction to Assist in Surgical Plan for Single Hepatocellular Carcinoma: Better Together with Radiomics

Annals of Surgical Oncology - Prediction models with or without radiomic analysis for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) have been reported, but the potential for...     

肝细胞癌侵犯肝内主要管道结构的螺旋CT表现

目的 探讨原发性肝细胞癌(HCC)侵犯肝内主要管道结构(门静脉、肝静脉和胆管)的多排螺旋CT(MDCT)表现特征。方法 收集68例侵犯肝内主要管道结构的HCC患者MDCT双期增强扫描资料，进行回顾性分析。着重观察和记录肝内门静脉血管、肝静脉及下腔静脉肝内段、胆道系统以及肝实质等结构在肝动脉期和门静脉期的形态学改变。结果 68例HCC中侵犯门静脉系统并继发癌栓病例47例，侵犯肝静脉及下腔静脉肝内段12例，侵犯胆管并继发胆管内癌栓者9例。肝内静脉血管受侵的直接CT征象有：①受累静脉扩张或增粗，伴管腔内软组织密度样“充盈缺损”；②静脉内癌栓在动脉期出现强化．呈现静脉的动脉化现象等。间接征象包括：①动脉-静脉瘘形成；②癌旁肝实质在动脉期出现异常强化；③门静脉海绵样变等。HCC侵犯胆管征象为：①病灶周围胆管或近端胆管扩张；②胆管腔内软组织密度结节或肿块影。结论 HCC侵犯肝内主要管道结构可出现相应的MDCT征象。MDCT增强双期扫描结合图像重建技术可以更好地评价肝内管道结构的受侵情况。     

A Gene Expression Profile for Vascular Invasion can Predict the Recurrence After Resection of Hepatocellular Carcinoma: a Microarray Approach

Background Recurrence after hepatocellular carcinoma (HCC) resection is the major obstacle to improved survival. The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor for HCC recurrence. Though some VI-related genes have been reported, their association with recurrence-free survival is not known. We hypothesized that a gene expression profile for VI can predict the recurrence of HCC after liver resection.Methods Eighteen patients receiving complete HCC resection were included as a “training group”. Genome-wide gene expression profile was obtained for each tumor using a microarray technique. Datasets were subjected to clustering analysis supervised by the presence or absence of VI to obtain 14 discriminative genes. We then applied those genes to execute pattern recognition using the k-Nearest Neighbor (KNN) classification method, and the best model for this VI gene signature to predict recurrence-free survival in the training group was obtained. The resulting model was then tested in an independent “test group” of 35 patients.Results A 14-gene profile was extracted which could accurately separate ten patients with VI and eight patients without VI in the “training group”. In the “test group”, significant difference in disease-free survival was found between patients predicted to have and not to have recurrence (P = .02823). In patients with stage_I disease, this model can also predict outcomes (P = .000205).Conclusions Using the 14-gene expression profile extracted from microarrays based on the presence of VI can effectively predict recurrence after HCC resection. This approach might facilitate “personalized medicine” for HCC patients after surgical resection.Po-Huang Lee and Fon-Jou Hsieh share correspondence     

Referrals for Surgical Therapy in Patients with Hepatocellular Carcinoma: A Community Experience

The treatment of hepatocellular carcinoma (HCC) is notoriously difficult. Either because of oncogenic behavior or the frequent association of cirrhosis, successful therapy is elusive, particularly in cirrhotic patients. Surgical removal has been the only modality that has produced long-term, disease-free survival. In a large series of patients from specialty institutions, median survival in those who underwent resection of HCC lesions has ranged from 30 to 70 months. Similarly, liver transplantation has been shown to be an effective treatment when HCC is favorable (limited in size and number), producing long-term survival in greater than 70% of patients. However, less information is known about community-based treatment of HCC. Reports from referral centers may not accurately reflect the community experience. We have retrospectively reviewed patients with HCC seen in surgical referral from three teaching hospitals in a medium-size urban community from 1995 to 2004 who were not felt to be candidates for liver transplantation and who were not sent to referral centers. We sought to examine their suitability for operation and resection. The study group comprised 61 patients, whose ages ranged from 35 to 83 years old. There were 44 patients (72%) with cirrhosis (Childs A, B, and C in 27, 15, and 2 patients, respectively), 21 from hepatitic C virus (HCV) infection. Three recognized staging systems were used that incorporated the estimation of hepatic reserve and tumor burden. Seven patients (11%) were deemed nonoperable (five advanced disease by imaging, two comorbidities). Of the 54 patients who underwent surgical procedures, 32 underwent resection (28 patients) or cryoablation (4 patients). The reasons for unresectability were unrecognized multifocality (ten patients), poor risk for major hepatectomy (five patients), portal vein/hepatic vein involvement (three patients), metastatic disease (two patients), and excessive blood loss prior to hepatectomy (two patients). Eleven of 17 (65%) noncirrhotic patients and 21 of 44 (48%) cirrhotic patients were resectable or ablatable. There were ten postoperative deaths: six following resection, two following cryoablation, and two following exploratory celiotomy. All deaths were in cirrhotic patients (Childs A in four patients, B in five patients, and C in one patient), 10 of 44 patients (23%); 3 of 11 (27%) patients died following segmentectomy and 3 of 9 (33%) following major hepatectomy. Seven deaths that occurred were in patients with HCV; (P = NS). From this series, the difficulty in surgically treating cirrhotic patients in an urban practice is evident. From 39 to 73% of patients had advanced local disease. Less than half were resectable and, for cirrhotic patients, the postoperative mortality was high, even after “minor” hepatectomies. Noncirrhotic patients fared somewhat better. While HCC in community practice can be treated surgically in the majority of noncirrhotic patients, cirrhotic patients are less likely candidates, and surgical treatment is associated with significant postoperative mortality. This frequently reflected advanced disease and HCV but may be associated with access to preventative and surveillance measures. Only those with optimum hepatic reserve and small tumor burden should be considered for surgical resection. Presented at the 2006 Spring Meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, FL, March 9–12, 2006 (poster of distinction).     

Estimating Surgical Outcomes for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

The Significance of Classifying Microvascular Invasion in Patients with Hepatocellular Carcinoma

Background

Microvascular invasion (MVI) has been recognized as a risk factor for outcome following curative resection in hepatocellular carcinoma (HCC). Because MVI can range from few to many invaded vessels, we evaluated the significance of MVI classification in this study.

Methods

Between January 1995 and December 2010, 207 consecutive patients who underwent curative resection for HCC within Milan criteria were included in this retrospective study. Patients were classified into mild and severe MVI groups based on the number of vessels invaded. This study evaluated whether MVI classification can help to predict recurrence and survival after curative resection.

Results

Of the total 207 patients, 103 (50 %) patients had no detectable MVI, whereas 59 (28 %) had mild MVI, and 45 (22 %) had severe MVI. Recurrence-free survival rates at 2 years for patients without MVI, with mild MVI, and severe MVI were 75.9, 47.2, and 32.7 %, respectively. Patients with severe MVI experienced a high frequency of fatal recurrence, such as multiple tumors, macroscopic vascular invasion, and extrahepatic metastasis after curative resection. Multivariate analysis revealed age, number of tumors, mild MVI, and severe MVI as independent predictors of recurrence-free survival. Disease-specific survival rates at 5 years for patients without MVI, with mild MVI, and severe MVI were 91.5, 70.4, and 51.4, respectively. Multivariate analysis also revealed cirrhosis, tumor size, mild MVI, and severe MVI as independent predictors of disease-specific survival.

Conclusions

We demonstrated that MVI classification can stratify HCC patients by different patterns of recurrence and risk of survival after curative resection.     

Clinicopathologic Characteristics of Hepatocellular Carcinoma with Bile Duct Invasion

To clarify the characteristics of hepatocellular carcinoma (HCC) with bile duct invasion, we retrospectively analyzed clinical features and surgical outcome of HCC with bile duct invasion (b⁺ group, n = 15) compared to those without bile duct invasion (b⁻ group, n = 256). In the b⁺ group, four patients (27%) showed obstructive jaundice, and a diagnosis of bile duct invasion was obtained preoperatively in seven patients (47%). The levels of serum bilirubin and carbohydrate antigen 19–9 were significantly higher in the b⁺ group. Macroscopically, confluent multinodular type and infiltrative type were predominant in the b⁺ group (P = 0.002). Microscopically, capsule infiltration (P = 0.040) and intrahepatic metastasis (P = 0.013) were predominant in the b⁺ group. Portal vein invasion was associated significantly with the b⁺ group (P = 0.004); however, the frequency of hepatic vein invasion was similar (P = 0.096). The median survival after resection was significantly shorter in the b⁺ group than in the b⁻ group (11.4 vs. 56.1 months, P = 0.002), and eight of 11 intrahepatic recurrences in the b⁺ group occurred within 3 months after surgery. HCC with bile duct invasion has an infiltrative nature and a high risk of intrahepatic recurrence, resulting in poor prognosis.     

原发性肝癌合并脾功能亢进的外科治疗

目的 探讨原发性肝癌合并脾功能亢进的合理治疗方法。方法 1994年1月至2004年12月我院收治67例原发性肝癌合并脾功能亢进患者，17例行肝切除联合脾切除，7例行单纯肝切除，43例行肝动脉栓塞化疗联合脾动脉栓塞。结果 肝切除联合脾切除组术后30d患者脾功能亢进症状消失，外周血细胞恢复正常。单纯肝切除组术后脾功能亢进症状加重，其中6例于术后3～7个月分别行脾动脉栓塞治疗。肝动脉栓塞化疗联合脾动脉栓塞组治疗后30 d 79％（34／43）的病例脾功能亢进症状改善，外周血细胞恢复正常。结论 原发性肝癌合并脾功能亢进的处理应争取行肝切除联合脾切除治疗，如肝癌不能切除，则应争取行肝动脉栓塞化疗联合脾动脉栓塞治疗。     

肝癌解剖性肝切除的初步经验

目的总结行解剖性肝切除的经验及结果。方法2004年1月至2005年6月期间,我们对93例肝细胞癌患者进行解剖性肝切除,对相应外科技术进行改进以减少术中出血、输血及术后并发症。切肝采用血管钳钳夹肝组织,暴露肝内管道后再结扎,选择性阻断出、入肝血流;对13例巨大肿瘤行半肝切除时采用肝脏悬吊法,切肝时采用间断Pringle法阻断肝门。结果93例肝癌患者中82例(88%)伴有不同程度的肝硬变,平均出血量300ml(100~6000ml),71%(66/93)病例不需输血。术后并发症发生率为34%(32/93),膈下积液多发,共8例。术后30d内无手术死亡。结论解剖性肝切除可能提高手术疗效。     

Adjuvant Hepatic Arterial Infusion Chemotherapy after Hepatic Resection of Hepatocellular Carcinoma With Macroscopic Vascular Invasion

Background

The prognosis of hepatocellular carcinoma (HCC) with macroscopic vascular invasion is extremely poor even after hepatic resection. We aimed to clarify the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with vascular invasion.

Methods

A total of 73 HCC patients with macroscopic vascular invasion were divided into two groups: 38 with hepatectomy with HAI (HAI group) and 35 with hepatectomy alone (non-HAI group). From 1997 to 2007, HAI was performed via an implanted injection port. The treatment comprised three courses of weekly infusion of HAI, which comprised cisplatin (10 mg daily on days 1–5) followed by 5-fluorouracil (5-FU; 250 mg daily on days 1–5) infusion. From 2007, cisplatin (60 mg/m²), 5-FU (600 mg/m²), and a mixture of mitomycin C (3 mg/m²) and degradable starch microspheres were administered for two courses.

Results

Overall, 92 % of patients completed adjuvant HAI. In the HAI and non-HAI groups, the 5-year disease-free survival (DFS) rates were 33.1 % and 11.8 %, respectively (p = 0.029), and the 5-year overall survival (OS) rates were 46.7 % and 32.7 %, respectively (p = 0.318). Among the patients with Vp3/4 or Vv3 (n = 32) in the HAI group, the 3-year DFS and OS rates were 33.7 % and 56.8 %, respectively (p = 0.049). Those in the non-HAI group were 8.3 % and 12.0 %, respectively (p = 0.023). Cox proportional multivariate analysis for DFS revealed that HAI was an independent favorable prognostic factor in all 73 patients (hazard ratio 0.536; p = 0.029).

Conclusions

Adjuvant HAI for HCC patients with vascular invasion might reduce the risk of recurrence.     

A Systematic Review of Microvascular Invasion in Hepatocellular Carcinoma: Diagnostic and Prognostic Variability

Selected patients with hepatocellular carcinoma are candidates to receive potentially curative treatments, such as hepatic resection or liver transplantation, but nevertheless there is a high risk of tumor recurrence. Microvascular invasion is a histological feature of hepatocellular carcinoma related to aggressive biological behavior. We systematically reviewed 20 observational studies that addressed the prognostic impact of microvascular invasion, either after liver transplantation or resection. Outcomes were disease-free survival and overall survival. In liver transplantation, the presence of microvascular invasion shortened disease-free survival at 3 years (relative risk (RR) = 3.41 [2.05–5.7]; five studies, n = 651) and overall survival both at 3 years (RR = 2.41 [1.72–3.37]; five studies, n = 1,938) and 5 years (RR = 2.29 [1.85–2.83]; six studies, n = 2,003). After liver resection, microvascular invasion impacted disease-free survival at 3 and 5 years (RR = 1.82 [1.61–2.07] and RR = 1.51 [1.29–1.77]; four studies, n = 1,501 for both comparisons). However inter/intraobserver variability in reporting and the lack of definition and grading of microvascular invasion has led to great heterogeneity in evaluating this histological feature in hepatocellular carcinoma. Thus, there is an urgent need to clarify this issue, because determining prognosis and response to therapy have become important in the current management of hepatocellular carcinoma. In this systematic review, we summarize the diagnostic and prognostic data concerning microvascular invasion in hepatocellular carcinoma and present a basis for consensus on its definition.     

血管硬化性病变与肝癌自发性破裂的关系

目的 探讨血管壁弹性变化与肝癌自发性破裂的相关关系。方法 选用肝癌破裂及未破裂患者的肝癌组织标本各30例，采用免疫组化ABC法及电子显微镜检测其与血管病变有关的因素：第八因子相关抗原因子(vWF因子)、弹性硬蛋白、弹性蛋白酶(中性粒细胞性)。结果与未破裂组相比，肝癌破裂患者中血管内皮vWF因子表达量明显下降，小动脉壁中弹性蛋白酶分布异常、弹性硬蛋白增生过度、弹力膜断裂。vWF因子为血管受损指标之一，并参与凝血过程。上述病变的结果，导致患者小动脉壁脆性增加及凝血功能下降，稍遇外力的作用即易发生血管破裂，进而可导致肿瘤组织的破裂。结论肝癌患者体内的血管壁硬变可能与肝癌肿瘤破裂有关。     

Surgical Outcomes for the Ruptured Hepatocellular Carcinoma: Multicenter Analysis with a Case-Controlled Study

Background

While spontaneously ruptured hepatocellular carcinoma (HCC) has a poor prognosis, the true impact of a rupture on survival after hepatic resection is unclear.

Methods

Fifty-eight patients with ruptured HCC and 1922 with non-ruptured HCC underwent hepatic resection between 2000 and 2013. To correct the difference in the clinicopathological factors between the two groups, propensity score matching (PSM) was used at a 1:1 ratio, resulting in a comparison of 42 patients/group. We investigated outcomes in all patients with ruptured HCC and compared outcomes between the two matched groups.

Results

Of the 58 patients with ruptured HCC, 7 patients (13 %) died postoperatively. Overall survival (OS) rate at 5 years after hepatic resection was 37 %. Emergency hepatic resection was an independent risk factor for in-hospital death and Child-Pugh class B for unfavorable OS in multivariate analysis. Clinicopathological variables were well-balanced between the two groups after PSM. No significant differences were noted in incidence of in-hospital death (ruptured HCC 12 % vs non-ruptured HCC 2 %, p?=?0.202) or OS rate (5/10-year; 42 %/38 % vs 67 %/30 %, p?=?0.115).

Conclusion

Emergency hepatic resection should be avoided for ruptured HCC in Child-Pugh class B patients. Rupture itself was not a risk for unfavorable surgical outcomes.

     

Microvascular Invasion in Patients with Hepatocellular Carcinoma and Its Predictable Clinicopathological Factors

Background Macroscopic vascular invasion is known to be a poor prognostic factor in hepatocellular carcinoma (HCC). The aim of this study was to determine the outcomes and predictive factors after hepatic resection for HCC with microvascular invasion (MVI). Methods One hundred ten patients who underwent curative resection for HCC without macroscopic vascular invasion were included in this retrospective study. The risk factors of these patients for recurrence-free and disease-specific survival were investigated, and the clinicopathological factors predicting the presence of MVI were also determined. Results Of the 110 resected specimens, 49 (45%) had evidence of MVI. By univariate analysis, MVI was found to be statistically significantly associated with greater tumor size, gross classification, histological grade, and intrahepatic micrometastasis. Gross classification proved to be the only independent predictive factor for MVI by multiple logistic regression analysis. By multivariate analysis, cirrhosis and MVI were identified as independent risk factors for recurrence-free survival. The 5-year recurrence-free survival rates for patients with and without MVI were 20.8% and 52.6%, respectively. By multivariate analysis, the number of tumors, presence of MVI, and intrahepatic micrometastasis were identified as independent predictors of disease-specific survival. The 5-year disease-specific survival rates for patients with and without MVI were 59.3% and 92.0%, respectively. Conclusions The presence of MVI was the most important risk factor affecting recurrence and survival in HCC patients after curative resection. Furthermore, this study showed that gross classification of HCC can be very helpful in predicting the presence of MVI.