Partial hepatic resection for hepatocellular carcinoma

This review summarizes the efficacy of the most common therapeutic option for hepatocellular carcinoma (HCC), partial hepatic resection, taking into account not only its antitumoural effect, but also its consequences on survival. Partial hepatic resection results in 5 year survival rates as high as 45% in more favourable subgroups having: small tumours, well-differentiated tumours, unifocal tumours, a lack of vascular invasions, an absence of cirrhosis, and the fibrolamellar variant. Resection has been limited primarily by low resectability rates and recurrent disease. However, surgical resection in the form of partial hepatectomy is the preferred treatment for HCC. The early detection of tumours by screening high-risk populations is crucial. During the 12 year period between 1983 and 1994, hepatic resections were carried out in 382 patients with HCC. One hundred and fifty-three (40%) had HCC smaller than 5 cm in diameter. There were 294 male and 88 female patients, with an average age of 52.3 years. Among them, 45% had liver cirrhosis and 73% were positive for hepatitis B surface antigen. Two hundred and eighteen (57%) were positive for hepatitis C virus circulating antibodies (since 1991). Operative mortality was 3.9%. The overall survival rates at 1, 3 and 5 years were 71, 52 and 46%, respectively. Sex, cirrhosis, Child's staging, surgical procedure, blood loss, pathological pattern, presence of capsule, surgical margin and DNA ploidy appeared to be factors not related to prognosis. However, alpha-fetoprotein level, size (whether less than or greater than 5 cm), and vascular invasion were factors which significantly affect survival.     

Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma

BACKGROUND/AIMS: Experimental and clinical studies have found a relationship between blood transfusion and altered immune function. We estimated the risk of transfusions for shorter survival on patients with hepatocellular carcinoma who underwent hepatic resection. METHODOLOGY: The impact of perioperative blood transfusions on 235 patients with hepatocellular carcinoma who had resections from January 1981 to December 1988 was retrospectively examined. All patients underwent hepatic resection and received no additional chemotherapy. RESULTS: Using the Cox proportional hazard model, the number of perioperative blood transfusions was found to be a significant prognostic factor for patient outcome (p = 0.03). Overall, patients who received less than 12 transfused units had a significantly better 5-year survival rate than those who received more than 13 transfused units (46.3% vs. 24.5%, p < 0.001). This result was also seen when the patients were subdivided by stage: 5-year survival in the early stage group (57.2% vs. 35.5%, p < 0.01) and in the advanced stage group (30.0% vs. 18.2%, p < 0.05). The number of perioperative blood transfusions also influenced the survival of patients who underwent a curative resection (66.2% vs. 38.5%, p < 0.01), but did not affect the survival of those who received a non-curative resection (7.9% vs. 7.4%). CONCLUSION: This study suggests that the number of perioperative blood transfusions is a significant prognostic factor in patients with hepatocellular carcinoma who undergo hepatic resection.     

Prognostic factors after hepatic resection for hepatocellular carcinoma associated with Child-Turcotte class B and C cirrhosis

OBJECTIVE: To evaluate prognostic factors after resection of hepatocellular carcinoma (HCC) in patients with Child-Turcotte class B and C cirrhosis. SUMMARY BACKGROUND DATA: Although hepatic resection remains the mainstay in the treatment of HCC and can be performed with low morbidity and mortality rates in patients without cirrhosis, its role is poorly defined for patients with severe cirrhosis. METHODS: From 1986 to 1996, partial hepatectomy was performed for HCC in 63 patients with Child-Turcotte class B (n = 46) and C (n = 17) cirrhosis. There were 46 men and 17 women, with an average age of 61.2 years (range 35 to 79 years). Associated conditions were diabetes mellitus in 45, esophageal varices in 32, severe hypersplenism in 26, cholelithiasis in 13, gastroduodenal ulcer in 6, and hiatal hernia, gastric lymphoma, splenic abscess, and pancreatic cyst each in 1. Concomitant surgical procedures were performed for most of these conditions. RESULTS: Major complications occurred in 17 patients (27%), six (9.5%) of whom died within 1 month after surgery. The overall in-hospital death rate was 14.3%. Liver failure and intraabdominal sepsis were mostly fatal complications. The overall and disease-free survival rates, respectively, were 70.2% and 64.5% at 1 year, 43.5% and 23.8% at 3 years, and 21.4% and 14.9% at 5 years. Multivariate analysis with the Cox regression model revealed that favorable factors for survival were Child class B, no transcatheter arterial embolization before surgery, young age, and low alanine aminotransferase (ALT) level before surgery. CONCLUSIONS: Hepatic resection can provide a favorable result in young patients with HCC complicating Child class B cirrhosis with low hepatitis activity, but transcatheter arterial embolization before surgery should be avoided in such patients.     

Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy

BACKGROUND: Postoperative hepatic failure is the leading cause of hospital mortality following hepatectomy for hepatocellular carcinoma (HCC). This prospective study was performed to identify the best test for assessment of the adequacy of hepatic functional reserve in patients with HCC before hepatectomy. METHODS: Between April 1989 and June 1993, 127 patients with HCC underwent hepatectomy. Each patient was evaluated before operation with the indocyanine green (ICG) clearance test, the aminopyrine breath test and the amino acid clearance test. RESULTS: Fourteen patients (11 per cent) died after hepatectomy. ICG retention at 15 min showed significant differences between patients who survived or died. By discriminant analysis, the safety limit of ICG retention at 15 min for major hepatectomy was 14 per cent and the relative risk of hospital mortality was 3. CONCLUSION: The ICG clearance test, expressed as the percentage of ICG retained at 15 min, is the best discriminating preoperative test for evaluating hepatic functional reserve in patients with HCC before hepatectomy.     

Clinicopathologic features of submucosal carcinoma of the stomach

A retrospective study of 155 patients with submucosal gastric carcinoma compared the clinicopathologic features with mucosal and muscularis proprial gastric carcinoma. Fifty-seven percent of the patients presented with gastrointestinal symptoms, whereas 36.1% had been detected by mass screening. The incidence of curative resection, lymph node metastasis, and complications were 96.1, 20.6, and 14.8%, respectively. Two patients died of sepsis and pulmonary infarction 30 days post-operatively. Five patients died of recurrent gastric cancer 1-5 years postresection. The overall 5-year survival rate was 90.2%. Recurrence patterns, histologic type, lymph node metastasis, lymphatic and venous infiltration, and growth pattern were similar to those of muscularis proprial carcinoma rather than mucosal carcinoma. Therefore, curative gastrectomy with extended lymphadenectomy (D2) may be feasible for submucosal carcinoma of the stomach.     

Clinicopathologic features of retinoblastoma after primary chemoreduction

BACKGROUND: Cytotoxic T cells can induce target cell lysis and apoptosis by different pathways. The interactions of CD95 antigen (Fas) with its ligand (CD95L) and of tumor necrosis factor (TNF)-alpha with its receptor (TNF-R1) lead to apoptotic cell death. Recently, conflicting studies have been published concerning the expression and the role of CD95L in allograft rejection and tolerance. METHODS: In this study, the intragraft expression of CD95/CD95L and TNF-alpha and the frequency and distribution of apoptotic cells were compared in a model of heterotopic cardiac allograft in the rat in which recipients were either not treated (acute rejection) or pretreated with donor-specific blood transfusion (tolerant). RESULTS: In the acutely rejected allografts, a peak in the expression of CD95L and TNF-alpha and in the number of apoptotic cells was observed during the first week after transplantation; apoptotic cells were confined to graft-infiltrating cells. In the tolerated allografts, however, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower. The expression of Fas was constitutive and was not modulated during acute rejection or tolerance. CONCLUSION: This down-regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing pathways in acute allograft rejection.     

Androgen and oestrogen receptors in hepatocellular carcinoma and surrounding liver parenchyma: impact on intrahepatic recurrence after hepatic resection

Seventy-eight patients in whom androgen or oestrogen receptors, or both, were assayed in hepatocellular carcinoma (HCC) and the surrounding liver were discharged from hospital after curative resection of the tumour. Intrahepatic recurrence was evaluated retrospectively after 28-128 months follow-up to determine the association with receptor status. Androgen and oestrogen receptors in HCC significantly influenced the intrahepatic recurrence rate. The recurrence-free 5-year survival rate was 55 per cent for patients who had androgen receptor-negative tumours, 24 per cent for oestrogen receptor-negative, 10 per cent for oestrogen receptor-positive and 0 for androgen receptor-positive (P = 0.0322). Recurrence-free 5-year survival in 57 patients who had both receptor assays was 75 per cent for patients who had androgen receptor-negative, oestrogen receptor-negative tumours, 50 per cent for androgen receptor-negative, oestrogen receptor-positive, but 0 for androgen receptor-positive, oestrogen receptor-positive and androgen receptor-positive, oestrogen receptor-negative (P = 0.0104). The presence or absence of androgen or oestrogen receptor in the liver, however, was not associated with intrahepatic recurrence (P = 0.7534). Thus, androgen receptors are strongly associated with intrahepatic recurrence of HCC, while oestrogen receptors are weakly associated. Receptor status in the normal liver was not related to intrahepatic recurrence.     

Long-term results after resection of hepatocellular carcinoma: experience of 480 cases

We have investigated the use of dU excision by uracil N-glycosylase (UDG) to create cohesive ends on PCR fragments "mimicking" those generated by restriction enzymes. The feasibility of this approach for directional and nondirectional cloning using cohesive ends mimicking SacI or PstI ends is demonstrated by the subcloning of a 383 to 388-bp fragment of bovine basic fibroblast growth factor into restriction enzyme-linearized pT7T318U. UDG-mediated cohesive ends imperfectly matched to PstI-generated vector ends gave reasonable cloning efficiency and accuracy, suggesting that the approach may be extended to mimicry of other restriction enzymes producing 3' overhangs. The rapid and specific excision of dU by UDG (within 30 min at 37 degrees C) has several potential advantages over the use of restriction site-modified primers, including the avoidance of restriction cleavage at internal sites within the PCR product. Also, following ligation, the approach described may be used to prevent subsequent cleavage of the joined DNA segments by the restriction enzyme, that is, by not recreating the restriction enzyme recognition sequence at the junction, which may find application in gene engineering. By adapting the approach to use dU-containing linkers or "vectorettes," the approach may be used for cloning unknown sequences (e.g., by cDNA or genomic library construction) or for mimicking 5' overhang cohesive ends on PCR fragments.     

The long-term results of percutaneous isolated hepatic perfusion for patients with advanced hepatocellular carcinoma

We studied the long-term outcome of percutaneous isolated hepatic perfusion (PIHP) for patients with hepatocellular carcinoma. This study included 31 patients with Stage IVA and 5 with IVB disease treated by PIHP until December, 1997. The mean age and tumor diameter were 55 and 7.7 cm, respectively. Twenty-two had portal vein invasion, 13 had hepatic vein invasion, and all patients had multiple intrahepatic metastases of more than 5 tumor foci. The PIHP with adriamycin or cisplatin was undertaken in a total of 50 treatments in these 36 patients. CR was observed in 6 and PR in 13 with an overall response rate of 59%, excluding 4 patients who were not evaluable. Five of 6 patients with CR remain free of disease at 7 to 54 months after the first treatment. The overall survival rate was 67% at 1 year and 32% at 5 years. The survival rates of Stage IVA patients (1-year = 71%, 5-year = 36%) were higher than Stage IVB patients (1-year = 20%, 5-year = 0%). The 5-year survival rates of patients with vascular invasion (Vp1-3 = 23%, Vv1-3 = 8%) were lower than those without it (Vp0 = 47%, Vv0 = 51%). These results indicated that PIHP achieved a 5-year survival rate of approximately 40% in patients with multiple advanced hepatocellular carcinoma in the absence of distant organ metastases and marked vascular invasion, and yielded complete long-term remission in some of these patients.     

Improved survival with resection after transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma

Three patients with malignant blue nevus are reported-one on the right side of the body, one on the right arm, and one on the face. The criteria and difficulty of histopathological diagnosis are considered as well as the differential diagnoses for this tumor. The therapy is described, and the possible relations between malignant blue nevus and certain other tumors (e.g., atypical or locally aggressive cellular blue nevus) are explored. A review of the literature reveals that there is current disagreement about the exact prognosis for these tumors and indicates the need to collect data for all patients observed.     

Topical cooling-assisted hepatic segmentectomy for cirrhotic liver with hepatocellular carcinoma

BACKGROUND: A safe limit for normothermic consecutive portal triad occlusion in hepatectomy for the cirrhotic liver was believed to be around 30 minutes. Possibly, the occlusion time can be prolonged by cooling the ischemic liver in vivo. We describe the technique of segmentectomy assisted by topical cooling and its usefulness in prolonging the hepatic inflow occlusion time for cirrhotic livers without causing further ischemic injury. STUDY DESIGN: Fifty patients with hepatocellular carcinoma and chronic hepatic disease who underwent right-sided segmentectomy under hemihepatic inflow occlusion were divided into two groups: normothermic (n = 27), and hypothermic with hemihepatic topical cooling using ice slush (n = 23). Segmentectomies were carried out in the same way in both groups, guided by initial enbloc ligation of the corresponding portal pedicles. RESULTS: The mean right hepatic inflow occlusion time was significantly longer in the hypothermic group than in the normothermic group (53 +/- 22 minutes compared with 17 +/- 9.3 minutes). Despite the significant difference in occlusion time, no differences were found in the recovery of hepatic functions and the incidence of postoperative complications between the groups. Intraoperative blood loss was significantly less in the hypothermic group. CONCLUSIONS: The hepatic right-sided partial inflow occlusion time can safely be prolonged to 60 to 90 minutes in the presence of cirrhosis without causing another injury from ischemia and intermittent reperfusion.     

A valid new approach in treating solitary new lesions after resection of hepatocellular carcinoma

Recent studies have suggested that the appearance of solitary new lesions after a curative resection of hepatocellular carcinoma (HCC) may be closely related to the metachronous multicentric development of HCC. It is therefore extremely important to investigate the histological characteristics of solitary new nodular lesions confirmed to be HCC by an ultrasound (US)-guided needle biopsy. Thirty-five patients with small HCC, < or = 3 cm in diameter, who underwent a curative hepatic resection between 1987 and 1992, were observed for possible recurrence over a period of > or = 1 year. Solitary new lesions confirmed to be HCC were noted in 7 (20.0%) out of 35 cases 10-65 months after operation. All solitary new lesions underwent US-guided needle biopsy, and a histological examination of the biopsy specimen was performed. All seven solitary new lesions were then classified into the following two groups according to the histologic differentiation of biopsy specimens and were found to consist of five well-differentiated HCCs (71.4%) and two moderately differentiated HCCs (28.6%). Three of the five well-differentiated HCCs were accompanied by varying degrees of fatty changes. These morphologic observations suggest that approximately 70% of the solitary new lesions confirmed to be HCC after a curative resection of small HCC may thus be related to the metachronous multicentric origin of HCC. However, it is difficult to estimate the exact incidence of such cases. As a result, curative treatment may sometimes be feasible, even when treating solitary new lesions after resection of HCC. Therefore, we can better evaluate such solitary new nodular lesions after a resection of HCC by means of a histologic evaluation using US-guided needle biopsy.     

Female sex hormone receptor status in advanced hepatocellular carcinoma and outcome after surgical resection

BACKGROUND: There is a limited amount of data regarding the estrogen receptor (ER) and progesterone receptor (PgR) status of hepatocellular carcinomas (HGCs), and the relationship between receptor status and clinicopathologic features of tumors has not been reported. METHODS: Between April 1992 and December 1993, cancerous tissues for cytosolic preparation and receptor quantification in a monoclonal solid-phase enzyme immunoassay were obtained from 28 patients undergoing resection, three patients with total hepatectomy and subsequent liver transplantation, and two patients suffering from nonresectable HCC. RESULTS: ER and PgR were detected in the HCCs of 13 (39%) and 6 patients (18%), respectively. A lower age was observed among the female patients whose receptor status was negative for ER or PgR or both, as compared with the respective receptor-positive groups. No significant differences with respect to tumor stage and grading could be observed. There was one perioperative death (3%). In patients undergoing curative resection, 1-year survival in the ER(+) group was significantly lower than in the ER(-) group (40% versus 79%, p < 0.05). The 2-year survival rates in the ER(+) and ER(-) groups were 40% and 71%, respectively. A comparable trend did not become evident for PgR(+) and PgR(-) patients. CONCLUSIONS: Our data suggest a negative effect of an ER(+) tumor on patient survival after curative resection of advanced HCC.     

Fibrolamellar hepatocellular carcinoma: results of partial liver resection

AIM: To assess the results of partial hepatic resection in the treatment of fibrolamellar hepatocellular carcinoma. PATIENTS AND RESULTS: We present six cases of Fibrolamellar hepatocellular carcinoma treated by partial hepatic resection. There were five females and one male with a mean age of 20 (2.6) yr. Five patients were stage IVA and 1 IVB based on the Union International Against Cancer Classification. Two patients, due to recurrent disease, needed further pulmonary resection and a hilar lymphadenectomy. All six cases underwent major resection, three with vascular reconstruction. No operative mortality was recorded; half of the patients displayed some degree of morbidity. One patient died six months after the operation and the rest are alive at 78, 41, 24, 12 and 9 months. We believe that even in advanced cases, an aggressive surgical policy even with vascular reconstruction is justified in patients with fibrolamellar hepatocellular carcinoma.     

Synchronous hepatocellular carcinoma or metastatic hepatic tumor with primary gastric cancer

BACKGROUND/AIMS: When a solitary hepatic tumor occurs synchronously with gastric cancer, it is usually presumed to be metastatic. However, this may not be true in a place like Taiwan, where hepatocellular carcinoma (HCC) is prevalent. This study was conducted to examine the clinicopathological factors of both conditions. METHODOLOGY: A retrospective analysis of 14 patients who underwent a synchronous hepatectomy in combination with radical gastrectomy over the past 15 years was performed. RESULTS: Seven patients had metastatic gastric cancer, and seven had concomitant gastric and hepatic cancer. Serosal invasion and lymph node metastasis were the major features in the patients with metastatic gastric cancer. Early gastric cancer was found in three of the patients with the coexisting primary cancers. No patient with solitary metastatic cancer survived more than one year, but long-term survival of more than two years was achieved in two patients with the two forms of cancer. CONCLUSIONS: Double cancer of the stomach and liver should be kept in mind in patients with gastric cancer concomitant with a solitary hepatic tumor, in order to provide optimal treatment.     

Hepatic embolization through extrahepatic collateral pathways after hepatic arterial embolization for the hepatocellular carcinoma

Extrahepatic collateral pathways developing after repeated transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) make therapeutic arterial embolization for recurrent lesions extremely difficult. TAE was performed through the collateral pathways using a sophisticated micro-catheter with good trackability and pushability and a coaxial system. Twenty-three TAEs were undertaken through the collateral pathways in 13 patients with recurrent HCC who had extrahepatic collateral pathways after the previous hepatic arterial TAE. There were 69 extrahepatic collateral pathways, with partially obstructed hepatic arteries. On the average, three feeding arteries were seen in the liver. The main extrahepatic collateral pathways were the inferior phrenic artery and epicholedocal artery, 18 vessels and 29 vessels, respectively, accounting for about 80% of the total collateral pathways. TAEs were successful in all cases and the number of embolized vessels was 2.1 on average. The average time of the first collateral TAE after the initial conventional hepatic arterial TAE was 2.3 years. Excellent prognosis was observed with a one-year survival rate of 77% and 3-year survival rate of 38% after the collateral TAE. We consider that collateral TAE for recurrent HCC with obstruction of the hepatic artery is the procedure of choice, is technically feasible, and provides better prognosis for the patients.     

The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment

To determine whether serum hepatitis C virus (HCV) RNA disappearance after interferon (IFN) treatment prevents development of hepatocellular carcinoma (HCC), we evaluated retrospectively the incidence of HCC in patients with chronic hepatitis C. A total of 213 patients were monitored for more than 6 months after completion of IFN treatment. Sixty-three of the 213 patients (29.6%) achieved a complete response (CR) to treatment and 150 (70.4%) had no response (NR). HCC developed in 12 (5.6%), all of whom were NR. Logistic analysis showed age, alpha -fetoprotein, and staging of histological finding before IFN treatment were independent factors to development of HCC. The fact that there was no HCC development from CR provides a basis for IFN treatment in chronic HCV infection.     

A case report of multiple hepatic hilar cyst associated with hepatocellular carcinoma

Two types of cDNA encoding gonadotropin beta subunits (GTH beta) were isolated from a cDNA library prepared from pituitary gland of Baikal omul (Coregonus autumnalis migratorius Georgi). The nucleotide sequences of cDNA were determined. The CTHI beta and GTHII beta cDNAs code for polypeptides of 137 and 142 amino acids, respectively. Both of them include a putative signal peptide of 24 amino acids. The predicted amino acid structures of omul gonadotropins were compared with those of other vertebrate species.