Trimethadione tolerance test for the quantitative assessment of liver function in rats

The quantitative estimation of the hepatic functional volume in rats was attempted using the serum dimethadione (DMO)/trimethadione (TMO) ratio in a single blood sampling after oral administration of TMO, which we call the TMO tolerance test, in order to develop a means of pre-operatively assessing hepatic resectability. Serum DMO/TMO ratios correlated well with the total amount of the hepatic microsomal TMO-N-demethylase activity (enzyme activity) and with the remnant liver weight after 37% and 68% partial hepatectomy. These ratios increased after partial hepatectomy in parallel with the changes in the enzyme activity and the remnant liver weight. The results suggest that the quantitative functional changes of the remnant liver after hepatectomy in both CCl4-treated and untreated rats can be estimated pre-operatively by the TMO tolerance test.     

Current status of hepatic resection for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. For this disease, a variety of therapeutic measures have been applied, including hepatic resections, total hepatectomy followed by allografting, transarterial chemoembolization, and percutaneous tumor ablative therapy by ethanol, microwave coagulation, and radiofrequency ablation. This article focuses on the current status of hepatic resections for HCC.     

Assessment of safety in hepatic resection for hepatocellular carcinoma focusing on indirect hyperbilirubinemia

Background/purpose

The indications for hepatic resection for hepatocellular carcinoma (HCC) patients with total bilirubin (T-Bil) equal to or higher than 1.2 mg/dl remain controversial. The aim of this study was to investigate the safety of hepatic resection for HCC patients who showed high T-Bil (≥1.2 mg/dl) with low direct bilirubin (D-Bil ≤ 0.5 mg/dl).

Methods

Thirty-four HCC patients showing high T-Bil with low D-Bil were treated with mono- to tri-segmentectomy between January 2000 and December 2010. The perioperative clinical parameters and prognosis of the high T-Bil/low D-Bil patients were compared with those of 253 HCC patients showing normal T-Bil. In addition, complication rates of the patients with high T-Bil/high D-Bil (n = 4) were analyzed.

Results

The prothrombin time activity, indocyanine green clearance test, asialo-scintigraphy, and platelet count were similar in the two groups. The mean serum albumin in high T-Bil/low D-Bil patients was significantly higher than that of normal T-Bil patients (4.2 ± 0.5 vs. 4.0 ± 0.4 g/dl, P = 0.004). There were no significant differences in operation time, intraoperative bleeding, red cell concentrate transfusion rate, postoperative complication rate, and disease-free and overall survivals between the two groups. Postoperative hyperbilirubinemia (T-Bil >5 mg/dl) with ascites was observed in one of four high T-Bil/high D-Bil patients (25 %).

Conclusions

Mono- to tri-segmentectomy can be performed in patients with low D-Bil (≤0.5 mg/dl) similarly to patients with low T-Bil (<1.2 mg/dl), even in HCC patients showing high T-Bil (≥1.2 mg/dl).     

A long-term survivor of ruptured hepatocellular carcinoma after hepatic resection

Abstract We treated a patient who had previously undergone a hepatic resection for ruptured hepatocellular carcinoma (HCC) but developed a solitary peritoneal recurrence at the site of the incision 8 years and 9 months later. Since no other recurrence was evident, we resected the tumour. The primary tumour was 2.5 cm in size and histological examination revealed HCC without any histological risk factors for intrahepatic recurrence. The peritoneal tumour consisted of less differentiated cancer cells than those found in the primary tumour. The positive rates of Ki-67 were 10% in the primary tumour and 23.3% in the peritoneal recurrence. The DNA indexes in both tumours were considered to be identical.
The comparison between the primary and peritoneal tumours suggested that the histological differentiation and proliferation activity can change after recurrence, in spite of consistent DNA ploidy contents. Clinically, a patient who undergoes a hepatic resection for ruptured HCC can survive for a long time, such as 10 years, if they have good liver function and small HCC without any histological risk factors for intrahepatic recurrence. However, since late recurrence is possible, a follow up for as long as 10 years is recommended.     

Redox tolerance test: An indicator of preoperative hepatic functional reserve in liver diseases

Changes in the arterial ketone body ratio during oral glucose loading were observed preoperatively in 134 patients with liver disease, and these data were correlated with the pathology findings of liver tissue and the postoperative clinical course. It was found that the redox tolerance index (RTI) could serve as a quantitive indicator of the severity of the underlying chronic hepatic disease in patients with liver disease, and as a reliable indicator of preoperative hepatic functional reserve. When the RTI was 0.70 or more, the underlying hepatic disease was slight and there was good hepatic functional reserve; these patients could tolerate any type of hepatic resection. When the RTI was less than 0.70 and more than 0.5, the underlying hepatic disease was moderate and hepatic functional reserve was poor; if the RTI was less than 0.50, major hepatic resection could not be tolerated.     

Feasibility and validity of hepatic vein reconstruction in hepatectomy for hepatocellular carcinoma

The majority of hepatocellular carcinomas are complicated by liver cirrhosis. Cirrhotic patients with a tumor located in segments 7 and 8 cannot tolerate right lobectomy. To perform curative resection without causing liver failure in such patients, resection of segments 7 and 8, together with resection of the right hepatic vein, is recommended. Nine patients underwent such resection. In four patients, the right hepatic vein was not reconstructed. One patient died of liver failure and the other two patients had postoperative liver dysfunction. Based on this experience, the right hepatic vein was reconstructed in the remaining five patients; the defect was repaired by transplanting a vein graft in three patients, and a patch graft was carried out in two. In one patient who underwent reconstruction with vein graft, veno-venous bypass was performed between the remnant hepatic vein and inferior vena cava. This procedure decompressed the remnant liver and facilitated secure anastomosis in reconstruction of the hepatic vein. There were no complications or deaths. The reconstructed veins were patent 2–3 years postoperatively. This procedure is feasible and valid, and should be widely practiced in patients with a diminished liver function reserve.     

Right hepatic lobectomy with removal of tumor thrombus from the portal vein for hepatocellular carcinoma

Hepatocellular carcinoma with tumor thrombus in the portal trunk and collateral veins in the hepatoduodenal ligament is usually considered to be unresectable. To resect the tumor, it is necessary to handle the portal trunk and bile duct after the hepatic artery and liver parenchyma have been transected without dissection of the hepatoduodenal ligament. In this way, we were able to perform right lobectomy with removal of the tumor thrombus in the portal trunk, avoiding profuse bleeding due to transection of the collateral veins. Our procedure is associated with certain problems, one being whether the tumor thrombus can be separated from the endothelium of the portal vein, and another being related to the radical extent of this operation. The major issue is the radical nature of this procedure. It is presumed that the collateral veins can be extirpated to achieve a curative operation.     

Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with extensive tumour thrombus through the hepatic vein

BACKGROUND AND AIMS: Advanced hepatocellular carcinoma (HCC) with extensive tumour growth through the hepatic vein still has an extremely poor prognosis, even after cancer chemotherapy and/or transarterial embolization. Although aggressive surgical treatments using extracorporeal circulation and liver transplantation have been performed by some authors, the reported results were still unsatisfactory. In this study, we report the favourable result of hepatic artery chemoembolization and subsequent surgical resection in three patients with advanced HCC with extensive tumour thrombus through the hepatic vein. METHODS AND RESULTS: Three irresectable patients with HCC with extensive tumour thrombus through the hepatic vein underwent hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam. After the reduction of tumour extent with hepatic artery chemoembolization, two of the three patients underwent surgical resection. These two patients are still alive at 59 and 21 postoperative months, respectively. In the other case, the extent of the tumour and functional reserve of the liver prevented us from performing surgical resection, but the patient is doing well 62 months after the initial treatment. CONCLUSIONS: Hepatic artery chemoembolization with aclarubicin, mitomycin C, lipiodol and/or Gelfoam might be an effective treatment for irresectable advanced HCC with extensive tumour thrombus into the inferior vena cava or the right atrium through the hepatic vein. Radical surgical resection might be applicable for selected patients without high surgical risk after reducing tumour extent by hepatic artery chemoembolization.     

Factors affecting prognosis of small hepatocellular carcinoma in Taiwanese patients following hepatic resection

BACKGROUND:

Small hepatocellular carcinoma (HCC) affects millions of individuals worldwide. Surveillance of high-risk patients increases the early detection of small HCC.

OBJECTIVE:

To identify prognostic factors affecting the overall survival (OS) and recurrence-free survival (RFS) of patients with small HCC.

METHODS:

The present prospective study enrolled 140 Taiwanese patients with stage I or stage II small HCC. Clinical parameters of interest included operation type, tumour size, tumour histology, Child-Pugh class, presence of hepatitis B surface antigen and liver cirrhosis, hepatitis C status, alpha-fetoprotein, total bilirubin and serum albumin levels, and administration of antiviral and salvage therapies.

RESULTS:

Tumour size correlated significantly with poorer OS in patients with stage I small HCC (P=0.014); however, patients with stage II small HCC experienced a significantly poorer RFS (P=0.033). OS rates did not differ significantly between patients with stage I and stage II small HCC. Tumour margins, tumour histology and cirrhosis did not significantly affect OS or RFS (P>0.05).

DISCUSSION:

Increasing tumour size has generally been associated with poorer prognoses in cases of HCC. The present study verified the relationship between small HCC tumour size and OS; however, a reduction in OS with increasing tumour size was demonstrated for patients with stage I – but not for stage II – small HCC.

CONCLUSION:

Patients with stage II small HCC may benefit from aggressive surveillance for tumour recurrence and appropriate salvage treatment. Further studies are needed for additional stratification of stage I patients to identify those at increased risk of death.     

Hepatic resection for elderly patients with hepatocellular carcinoma: a systematic review of more than 17,000 patients

ABSTRACT

Background: With the aging population and increasing incidence of hepatic malignancies in elderly patients, establishing the safety and efficacy of hepatic resection for elderly patients with hepatocellular carcinoma (HCC) is crucial. The present systematic review investigates postoperative morbidity, hospital mortality, median survival time, overall and disease-free survival in elderly patients with undergoing hepatic resection.

Methods: Some databases were systematically searched for prospective or retrospective studies to reveal the safety and efficacy of hepatic resection for elderly patients with primary HCC.

Results: Fifty studies involving 4,169 elderly patients and 13,158 young patients with HCC were included into analyses. Elderly group patients had similar rate of median postoperative morbidity (28.2% vs. 29.6%) but higher mortality (3.0% vs. 1.2%) with young group patients. Moreover, elderly group patients had slightly lower median survival time (55 vs. 58 months), 5-years overall survival (51% vs. 56%) and 5-years disease-free survival (27% vs. 28%) than young group patients. There was an upward trend in 5-years overall and disease-free survival in either elderly or young group.

Conclusion: Though old age may increase the risk of hospital mortality for patients with HCC after hepatic resection, elderly patients can obtain acceptable long-term prognoses from hepatic resection.     

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy

Background The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC).Methods Forty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics.Results Of all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables—the Child-Pugh score (P = 0.013, P = 0.018), -fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors.Conclusions Patients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.     

Assessment of liver function for successful hepatectomy in patients with hepatocellular carcinoma with impaired hepatic function

Background/Purpose

This study aimed to construct a formula for assessing liver function in order to prevent post-hepatectomy liver failure.

Methods

A formula was constructed by analyzing data from 28 patients with hepatocellular carcinoma (HCC) with liver cirrhosis operated on between 1981 and 1984. Next, we evaluated the validity of this formula in 207 hepatectomy patients operated on from 1985 to 1999. For 145 hepatectomy patients operated on from 2000 to 2006, this formula was calculated before surgery in order to assess their risk of hepatectomy.

Results

The formula for liver functional evaluation, constructed from preoperative hepatic function parameters, was: liver failure score = 164.8 ? 0.58 × Alb ? 1.07 × HPT + 0.062 × GOT ? 685 × K. ICG ? 3.57 × OGTT. LI + 0.074 × RW, where Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, glutamate oxaloacetate transaminase (U/l); K. ICG, K value of indocyanine green clearance test; OGTT. LI, 60-min/120-min glucose level in 75-g oral glucose tolerance test. linearity index of OGTT; and RW, weight of resected liver (g). We decided that a score below 25 would be safe for hepatectomy.

Conclusions

The mortality rate decreased from 3.9% in 1985–1999 to 1.3% in 2000–2006. This finding allows us to conclude that the formula is valid for assessing the risk of post-hepatectomy liver failure.