Partial Hepatectomy For Hepatocellular Carcinoma Research Articles

Liver Resection for Hepatocellular Carcinoma in a Hepatitis B Endemic Area

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Treatment options include liver resection, tumor ablation, and liver transplantation. We report the results of all patients undergoing partial hepatectomy for HCC with curative intent from a center where all major treatment modalities were available. A series of 53 patients were identified, of whom 72% had underlying liver disease, mostly chronic hepatitis B infection. Altogether, 57% of patients underwent major resections, of whom 43% had histologically proven cirrhosis. Postoperative morbidity and mortality occurred in 41.5% and 7.5%, respectively. After a median follow-up of 34 months, the survival probabilities at 1, 3, and 5 years were 74.1%, 54.1%, and 42.6%, respectively. A total of 47% developed recurrent disease over the study period with a median disease-free survival of 13.8 months. The probabilities of recurrence at 1, 3, and 5 years were 35.2%, 49.4%, and 55.9%, respectively. Among those who developed recurrence, 76% died, with a median time to death from the time the recurrence was diagnosed of 7.8 months. There was a good association between the CLIP score and survival following liver resection. Multivariate analysis showed that only tumor recurrence and the presence of cirrhosis was a significant determinant of the risk of tumor-related death. These findings confirm that with careful patient selection liver resection for HCC can achieve good long-term patient survival and acceptable risks.

The role of partial hepatectomy for hepatocellular carcinoma after prior renal transplantation (RE: Cheng et al., J Surg Oncol 2006;93:273–278)

The role of partial hepatectomy for hepatocellular carcinoma after prior renal transplantation (RE: Cheng et al., J Surg Oncol 2006;93:273–278)

Surgically Resected Hepatocellular Carcinoma: Protean Yet Predictable

In this issue of the Annals of Surgical Oncology, Ramacciato et al. report the results of a study in which they evaluated the new (6th edition) American Joint Committee on Cancer and International Union Against Cancer (AJCC/UICC) staging system for hepatocellular carcinoma (HCC) in a series of 112 patients undergoing resection for HCC. The authors report a homogeneous group of patients (90% had cirrhosis, and 55% had cirrhosis induced by hepatitis C) with small (median tumor size, 4 cm) and solitary HCC (82% of patients). Microscopic vascular invasion was present in only 23 patients (21%). The authors conclude that the 6th edition AJCC/UICC staging system is superior to the preceding one because of its simplicity and more accurate stratification of patients into homogeneous subsets with similar prognosis. In agreement with the evaluation by Poon and Fan, the authors found no improved prognosis for tumors measuring 2 cm or smaller. Furthermore, in multivariate analysis, when the stage was analyzed with other prognostic factors determined in univariate analysis (cirrhosis of viral origin, multiple nodules, and microscopic vascular invasion), stage was the only independent predictor of prognosis. The new staging system for HCC is one of the many staging systems updated in the 6th edition of the AJCC cancer staging manual. In this edition, the staging systems for upper gastrointestinal tract cancers, including HCC, were revised such that stage IV disease is uniformly defined as metastatic disease. The staging system for HCC, which was formerly based on the complex classification of the Liver Cancer Study Group of Japan, was simplified on the basis of a large multicenter multivariate analysis of more than 500 patients undergoing partial hepatectomy for HCC in the United States, Japan, and France. This study included a complete pathologic review of the tumor and underlying liver characteristics that account for the protean presentation of HCC. The T-categories in the new HCC staging system are based on the presence or absence and severity of vascular invasion (T1, solitary tumor without vascular invasion; T2, solitary tumor with vascular invasion or multiple tumors smaller than 5 cm; T3, any tumor with major vascular invasion or multiple tumors larger than 5 cm). Vascular invasion is important because it predicts prognosis after resection or transplantation. A substantial addition to the new system is the provision of a fibrosis factor to reflect the severity of underlying fibrosis (F0, no or moderate fibrosis; F1, severe fibrosis or cirrhosis). Each T-category of the new staging system is affected by the severity of the underlying fibrosis. Thus, the new system recommends that a fibrosis score (F0 or F1), similar to the Edmondson-Steiner nuclear grade (G1 to G4), be added to the tumor stage. What is the relevance of the new AJCC/UICC staging system with regard to other existing staging systems for HCC, such as the Barcelona Cancer Liver Clinic staging system, the Cancer of the Liver Italian Program (CLIP) score, the Okuda staging system, and the Chinese University Prognostic Index? In contrast to those, the AJCC/UICC staging system for HCC is based on a pathologic review of surgical specimens. Received December 9, 2004; accepted January 10, 2005; published online March 14, 2005. Address correspondence and reprint requests to: Jean-Nicolas Vauthey, MD; E-mail: jvauthey@mdanderson.org.

Effects of Human Hepatocyte Growth Factor on the Proliferation of Human Hepatocytes and Hepatocellular Carcinoma Cell Lines

Background: Hepatocyte growth factor (HGF) has been suggested to initiate both hepatocyte and tumor cell proliferation after partial hepatectomy, thereby supporting local tumor recurrence. The aim of this study was to clarify the role of HGF in the regeneration of human hepatocyte and the growth of residual hepatocellular carcinoma cells after liver resection. Patients/Methods: 36 patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) or living liver donation have been analyzed for HGF serum levels at day –1 through day 5 following surgery using an enzyme-linked immunosorbent assay. Isolated human hepatocytes and HCC cell lines (Hep 3B, Hep G2) were treated either with recombinant human (rh)-HGF, or sera from the 36 patients in the presence or absence of anti-HGF in order to measure their proliferative capacity using ³H-thymidine incorporation. Results: Basal HGF levels were significantly higher in HCC than in healthy patients (1,573 ± 131 vs. 778 ± 64 pg/ml; p < 0.001), however, the postoperative rise of HGF in healthy patients was higher (9,608 ± 3111 vs. 2,060 ± 148 pg/ml) than in HCC patients. Incubation of human hepatocytes and Hep 3B cells with rh-HGF revealed a dose-dependent increase in DNA synthesis, while anti-HGF partially abolished this effect. Sera from normal and resected HCC patients stimulated DNA synthesis only in human hepatocytes, whereas it was inhibited in HCC cell lines. Conclusion: HGF plays an important role in hepatocyte proliferation but contrary to in vitro results, HGF does not play a major role for the progression of hepatocarcinoma cells in vivo.

Computed tomographic features of hepatocellular carcinoma predict long-term survival after hepatic resection

Aim: To evaluate the potential of computed tomographic features of hepatocellular carcinoma as prognostic factors. Methods: Medical records for 112 patients who had undergone a partial hepatectomy for hepatocellular carcinoma were retrospectively analyzed. The largest hepatic tumour in each patient was classified by pre-operative computed tomographic features as lobular configurations with indentations showing an acute angle, or non-lobular configuration without such indentations. Results: Twenty-six tumours were lobular and 86 were non-lobular. The outcome after hepatectomy was significantly worse in patients with lobular tumours (cumulative 5-year survival rate of 19.9%) than with non-lobular ones (that of 75.2%) (P<0.001). Cox's proportional hazards model showed computed tomographic features (P=0.0025), cirrhosis (P=0.0033), and tumour size (P=0.0412) to be independent prognostic factors. A lobular configuration was associated with satellite nodules (P<0.001), portal vein invasion (P=0.021), and extrahepatic tumour relapse (P=0.006). Conclusions: Computed tomographic features represent a strong prognostic factor in patients undergoing partial hepatectomy for hepatocellular carcinoma, and are likely to accurately reflect the tumour biology. Configuration, size of the hepatic tumour and presence of cirrhosis are the most important prognostic imaging findings in these patients.

Increased expression of transforming growth factor-α in a patient with recurrent hepatocellular carcinoma following partial hepatectomy

A 45-year-old woman with chronic hepatitis B underwent partial hepatectomy for hepatocellular carcinoma (HCC). However, the HCC recurred 2 months after surgery and rapid progression of the disease resulted in her death. Immunohistochemistry showed that transforming growth factor-alpha (TGFalpha) was barely expressed in the liver specimens obtained at hepatic resection, whereas autopsy specimens were strongly stained with anti-TGFalpha antibody in the cytoplasm of both non-tumourous and tumourous liver cells. A higher level of Ki67 expression, a proliferating marker, was observed in the recurrent HCC, similar to that of TGFalpha. Thus, we speculate that the partial hepatectomy increased the level of TGFalpha leading to recurrence and progression of HCC through an autocrine/paracrine mechanism.

肝癌に合併した胆管肺ろうの１症例

肝癌手術後に, 胆管肺瘻を合併した症例に対し, 経胸的に瘻孔を閉鎖し良好な結果を得た.患者は肝癌で肝部分切除術をうけ, その後数回に渡り, 肝動脈塞栓術を施行された.術後1年4ヵ月目に突然大量の胆汁を喀出し呼吸困難に陥った.呼吸管理のため気管内挿管を行ったが, この際持続的陽圧呼吸が胆汁喀出の抑制に対して有効であった.肝癌の再発, 浸潤による胆管肺瘻と診断したが, 開腹術では病巣への到達が困難であると判断して, 開胸手術で気道と胆道の交通を遮断した.病理組織学検査では, 胸腔内に癌組織は証明されず, 初回手術後の横隔膜下の感染が原因で胆管肺瘻を形成したものと考えられた.

Recurrent hepatocellular carcinoma: Usefulness of ultrasonography compared with computed tomography and AFP assay

Follow-up studies using monitoring with alpha1-feto protein (AFP), ultrasonography (US), and computed tomography (CT) were carried out in 75 patients who had prior partial hepatectomy for hepatocellular carcinoma (HCC). Recurrence in the remaining liver was confirmed in 31 patients (41.3%) during the 4 month to 3 years 7 month period. Ultrasonography detected recurrence in 29 cases (sensitivity: 93.5%), CT in 26 (83.9%), and AFP assay in 12 (38.7%). In 4 patients, ultrasonography detected four recurrent nodules that CT missed. In 1 patient, two subphrenic nodules were detected with CT but not with ultrasonography. The specificity of US, CT, and AFP assay was 90.9%, 95.5%, and 93.2% respectively. Frequent follow-up study with ultrasonography in combination with CT and AFP assay should be recommended for the early detection of recurrent HCC. Ultrasonography is mandatory for the follow-up of patients with a prior hepatectomy for HCC.

FACTORS INFLUENCING ERALY HEPATIC FAILURE FOLLOWING PARTIAL HEPATECTOMY FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CIRRHOSIS

In 137 patients with cirrhosis undergoing partial hepatectomy for hepatocellular carcinoma, the relationship of early postoperative hepatic failure to preoperative hepatic function, the extent of hepatectomy, and a blood loss during operation was studied.Thirteen cases developed hepatic failure within one month after operation, in which the preoperative KICGextent of hepatectomy, and blood loss during operation were related to the onset of hepatic failure. The incidence of hepatic failure was high when the preoperative KICG was 0.1 or less, then two or more regions of the liver were resected, and when operative blood loss was 3, 000 ml or more. When all these three factors were scored, the sum was useful as an index for predicting postoperative occurrence of hepatic failure and for determining the surgical indications and techniques.

Elevation of alpha-fetoprotein level without evidence of recurrence after hepatectomy for hepatocellular carcinoma

Seven Japanese patients showed a gradual rise in serum alpha-fetoprotein (AFP) levels for periods of 4 to 14 weeks after partial hepatectomy for hepatocellular carcinoma. These levels then gradually decreased, but not always to a normal level, and various procedures after surgery failed to detect tumor recurrence. All the cases were complicated with liver cirrhosis. It is suggested that the postoperative elevation in the AFP level may have been caused by hepatic regeneration as a result of the intervention chemotherapy and/or surgery, but it does not exclude the possibility of a tumor recurrence.