To investigate the trend of the posthepatectomy survival outcomes of hepatocellular carcinoma (HCC) patients by analysis of a prospective cohort of 1198 patients over a 20-year period.
The hospital ...mortality rate of hepatectomy for HCC has improved but the long-term survival rate remains unsatisfactory. We reported an improvement of survival results 10 years ago. It was not known whether there has been further improvement of results in recent years.
The patients were categorized into two 10-year periods: period 1, before 1999 (group 1, n = 390) and period 2, after 1999 (group 2, n = 808). Patients in group 2 were managed according to a modified protocol and technique established in previous years.
The patients in group 2 were older and had a higher incidence of comorbid illness and cirrhosis. They had a lower hospital mortality rate (3.1% vs 6.2%, P = 0.012) and longer 5-year overall survival (54.8% vs 42.1%, P < 0.001) and disease-free survival rates (34.8% vs 24%, P = 0.0024). An improvement in the overall survival rate was observed in patients with cirrhosis, those undergoing major hepatectomy, and those with tumors of tumor-node-metastasis stages II, IIIA, and IVA. A significant increase in the survival rates was also seen in patients whose tumors were considered transplantable by the Milan criteria (72.5% vs 62.7%, P = 0.0237). Multivariate analysis showed a significantly more favorable patient survival for hepatectomy in period 2.
A continuous improvement of survival outcomes after hepatectomy for HCC was achieved in the past 20 years even in patients with advanced diseases. Hepatectomy remains the treatment of choice for resectable HCC in a predominantly hepatitis B virus-based Asian population.
This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable ...hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%;
P = .002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81;
P = .006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment. (H
EPATOLOGY 2002;35:1164-1171.)
To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special ...reference to the implications for a strategy of salvage transplantation.
Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation.
From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC.
Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients.
For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.
The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for ...hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate.
In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997.
Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome.
Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate.
With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated.
Liver transplantation for hepatocellular carcinoma (HCC) is restricted by the scarcity of cadaver grafts. Living donor liver transplantation (LDLT) may potentially increase the applicability but its ...role and limitation are not clear. We studied the outcome of a cohort of 51 patients with unresectable HCC who were accepted on list for both options of deceased donor liver transplantation (DDLT) and LDLT. Twenty‐five of 51 (49%) patients had voluntary living donors (group 1) and 26 did not (group 2). Patients in group 1 were younger, and more often had a MELD score more than 20 or blood group other than O. Twenty‐one patients of group 1 underwent LDLT after a median waiting time of 24 days (range, 2–126 days), but 4 did not because the donors were not suitable (HBsAg‐positive, 2; ABO‐incompatible, 1; liver dysfunction, 1). Of the 30 patients who remained on list, only 6 underwent DDLT after a median waiting time of 344 days (range, 22–1359 days, P < .005). Nineteen died before transplantation and 2 were alive but taken off the list because of disease progression (drop‐out rate, 70%). One patient was alive on list and 2 had undergone transplantation outside Hong Kong. The 1‐, 2‐, 3‐, and 4‐year intention‐to‐treat survival rates were 88%, 76%, 66%, and 66%, respectively, for group 1 and 72%, 46%, 38%, and 31%, respectively, for group 2 (relative risk of death for group 1, 0.35; 95% CI, 0.14 to 0.90; P = .029). In conclusion, although complicated factors such as donor voluntarism and selection criteria limit the role of LDLT for HCC, LDLT allows more patients to undergo early transplantation and results in a better outcome. (Liver Transpl 2004;10:440–447.)
To evaluate the safety of donors who have donated the middle hepatic vein in right lobe live donor liver transplantation (LDLT) and to determine whether such inclusion is necessary for optimum graft ...function.
The necessity to include the middle hepatic vein in a right lobe graft in adult-to-adult LDLT is controversial. Inclusion of the middle hepatic vein in the graft provides uniform hepatic venous drainage but may lead to congestion of segment IV in the donor.
From 1996 to 2002, 93 right-lobe LDLTs were performed. All right-lobe grafts except 1 contained the middle hepatic vein. In the donor operation, attention was paid to preserve the segment IV hepatic artery and to avoid prolonged rotation of the right lobe. The middle hepatic vein was transected proximal to a major segment IVb hepatic vein whereas possible to preserve the venous drainage in the liver remnant.
There was no donor death. Two donors had intraoperative complications (accidental left hepatic vein occlusion and portal vein thrombosis) and were well after immediate rectification. Twenty-four donors (26%) had postoperative complications, mostly minor wound infection. The postoperative international normalized ratio on day 1 was better in the donors with preservation of segment IVb hepatic vein than those without the preservation, but, in all donors, the liver function was largely normal by postoperative day 7. The first recipient had severe graft congestion as the middle hepatic vein was not reconstructed before reperfusion. In 7 other recipients, the middle hepatic vein was found occluded intraoperatively owing to technical errors. The postoperative hepatic and renal function of the recipients with an occluded or absent middle hepatic vein was worse than those with a patent middle hepatic vein. The hospital mortality rate was also higher in those with an occluded middle hepatic vein (3/9 vs. 5/84, P = 0.028).
Inclusion of the middle hepatic vein in right-lobe LDLT is safe and is essential for optimum graft function and patient survival.
To identify the possible reasons of failure of biliary reconstruction in right lobe live donor liver transplantation (LDLT) and to devise the best method of reconstruction and treatment strategy for ...the complications.
Right lobe LDLT was associated with a high biliary complication rate (15-64%) in the reported series. The causes of failure were not completely understood and the best treatment strategy has not been defined.
From 1996 to 2001, 74 patients received right lobe LDLT. The operative procedures of the first 37 patients were critically reviewed to identify the possible reasons of leakage or stenosis from the anastomosis. The causes included right hepatic duct ischemia, double or triple hepaticojejunostomies, unrecognized branch of right hepatic duct, jejunal opening smaller than the size of right hepatic duct, and ductal plasty without division of newly created septum. The second 37 patients had biliary reconstruction by a modified technique that preserved blood supply to the right hepatic duct and aimed at avoidance of risk factors.
The overall complication rate decreased from 43% in the first 37 patients to 8% in the second 37 patients. There was no leakage from the anastomosis in the second group of patients. Percutaneous transhepatic biliary drainage (PTBD) for the biliary complications resulted in right portal vein and hepatic artery injury in four patients and accounted for mortality in three of them. To avoid complications from PTBD, three patients in the second group developing stenosis of hepaticojejunostomy had repeated hepaticojejunostomy without preoperative PTBD and recovered.
With identification of risk factors and modification of the surgical technique, the complication rate of biliary reconstruction of right lobe LDLT could be reduced. Repeated hepaticojejunostomy without preoperative PTBD is the preferred approach once a complication develops.
To evaluate whether major right hepatectomy using the anterior approach technique for large hepatocellular carcinoma (HCC) results in better operative and long-term survival outcomes when compared ...with the conventional approach technique.
The anterior approach technique has been advocated recently for large right liver tumors. However, its beneficial effects on the operative and survival outcomes of the patients have not been evaluated prospectively.
A prospective randomized controlled study was performed on 120 patients who had large (> or =5 cm) right liver HCC and underwent curative major right hepatic resection during a 57-month period. The patients were randomized to undergo resection of the tumor using the anterior approach technique (AA group, n = 60) or the conventional approach technique (CA group, n = 60). The anterior approach technique involved initial vascular inflow control, completion of parenchymal transection, and complete venous outflow control before the right liver was mobilized. Operative and long-term survival outcomes of the two groups were analyzed. Quantitative assessments of markers of circulating tumor cells at various stages of surgery of the two techniques were also assessed by plasma albumin-mRNA.
The overall operative blood loss, morbidity, and duration of hospital stay were comparable in both groups. Major operative blood loss of > or =2 L occurred less frequently in the AA group (8.3% vs. 28.3%, P = 0.005). As a result, blood transfusion requirement and number of patients requiring blood transfusion were significantly lower in the AA group. Hospital mortality occurred in 1 patient in the AA group and 6 patients in the CA group (P = 0.114). Median disease-free survival was 15.5 months in the AA group and 13.9 months in the CA group (P = 0.882). Overall survival was significantly better in the AA group (median >68.1 months) than in the CA group (median = 22.6 months, P = 0.006). The survival benefit appeared more obvious in patients with stage II disease and patients with lymphovascular permeation of the tumor. The anterior approach was also found to associate with significantly lower plasma albumin-mRNA levels at various stages of surgery compared with the CA technique. On multivariate analysis, tumor staging, anterior approach hepatic resection, and resection margin involved by the tumor were independent factors affecting overall survival.
The anterior approach results in better operative and survival outcomes compared with the conventional approach. It is the preferred technique for major right hepatic resection for large HCC.
We conducted a randomized controlled trial of adjuvant interferon therapy in patients with predominantly hepatitis B-related hepatocellular carcinoma (HCC) to investigate whether the prognosis after ...hepatic resection could be improved.
Recurrence is common after hepatic resection for HCC. Interferon possesses antiviral, immunomodulatory, antiproliferative, and antiangiogenic effects and may be an effective form of adjuvant therapy.
Since February 1999, patients with no residual disease after hepatic resection for HCC were randomly assigned with stratification by pTNM stage to receive no treatment (control group), interferon alpha-2b 10 MIU/m (IFN-I group) or 30 MIU/m (IFN-II group) thrice weekly for 16 weeks. Enrollment to the IFN-II group was terminated from January 2000 because adverse effects resulted in treatment discontinuation in the first 6 patients. By June 2002, 40 patients each had been enrolled into the control group and IFN-I group. The baseline clinical, laboratory, and tumor characteristics of both groups were comparable.
The 1- and 5-year survival rates were 85% and 61%, respectively, for the control group and 97% and 79%, respectively, for the IFN-I group (P = 0.137). After adjusting for the confounding prognostic factors in a Cox model, the relative risk of death for interferon treatment was 0.42 (95% CI, 0.17-1.05; P = 0.063). Exploratory subset analysis showed that adjuvant interferon had no survival benefit for pTNM stage I/II tumor (5-year survival 90% in both groups; P = 0.917) but prevented early recurrence and improved the 5-year survival of patients with stage III/IVA tumor from 24% to 68% (P = 0.038).
In a group of patients with predominantly hepatitis B-related HCC, adjuvant interferon therapy showed a trend for survival benefit, primarily in those with pTNM stage III/IVA tumors. Further larger randomized trials stratified for stage are needed.
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