Operative manipulation during hepatic resection (HR) causes tumor cell shedding which is a factor in disease recurrence. Radiofrequency ablation (RFA) causes coagulative necrosis and was used to destroy the tumor before HR. We evaluated tumor necrosis and recurrence of hepatic malignancies treated by sequential RFA/HR. A retrospective review of patients treated with sequential RFA/HR from April 1999 to January 2002 was performed. A Radionics 500-kW RF generator was used to ablate lesions via H2O-cooled electrodes under ultrasound guidance. Segmental HR was performed after RFA. Resected specimens were reviewed with hematoxylin and eosin staining and for apoptosis. Patient follow-up ranged from 10 to 33 months with evaluation of salient clinical, radiologic, and laboratory parameters. Seven patients (four male and three female) ages 62.1 +/- 10.3 years had sequential RFA/HR. Four patients had hepatocellular carcinoma (HCC) and three had colorectal metastases (CRm). The tumors were unifocal right-lobe lesions measuring 4.1 +/- 0.9 cm with a resection margin of 0.4 to 2.5 cm. Extensive necrosis was noted but intact nests of tumor cells occurred in all specimens with minimal apoptosis. Three of seven patients (two HCC and one CRm) developed pulmonary metastases at 3 to 20 months with one HCC patient developing concurrent liver metastases. Two deaths occurred in the HCC group. Sequential RFA/HR may minimize local recurrence; however, the high incidence of pulmonary metastases raises concern of transvenous migration. The histologic findings demonstrate foci of intact tumor cells after RFA. Controlled study of additional patients with long-term follow-up is necessary to better understand these findings.

BACKGROUND Historically, surgical correction has been the treatment of choice for benign biliary strictures (BBS). Self-expandable metallic stents (MSs) have been useful for inoperable malignant biliary strictures; however, their use for BBS is controversial and their natural history unknown. HYPOTHESIS To test our hypothesis that MSs provide only short-term benefit, we examined the long-term outcome of MSs for the treatment of BBS. Our goal was to develop a rational approach for treating BBS. DATA EXTRACTION Between July 1990 and December 1995, 15 patients had MSs placed for BBS and have been followed up for a mean of 86.3 months (range, 55-120 months). The mean age of the patients was 66.6 years and 12 were women. Stents were placed for surgical injury in 5 patients and underlying disease in 10 patients (lithiasis, 7; pancreatitis, 2; and primary sclerosing cholangitis, 1). One or more MSs (Gianturco-Rosch "Z" for 4 patients and Wallstents for 11 patients) were placed by percutaneous, endoscopic, or combined approaches. We considered patients to have a good clinical outcome if the stent remained patent, they required 2 or fewer invasive interventions, and they had no biliary dilation on subsequent imaging. DATA SYNTHESIS Metallic stents were successfully placed in all 15 patients, and the mean patency rate was 30.6 months (range, 7-120 months). Five patients (33%) had a good clinical result with stent patency from 55 to 120 months. Ten patients (67%) required more than 2 radiologic and/or endoscopic procedures for recurrent cholangitis and/or obstruction (range, 7-120 months). Five of the 10 patients developed complete stent obstruction at 8, 9, 10, 15, and 120 months and underwent surgical removal of the stent and bilioenteric anastomosis. Four of these 5 patients had strictures from surgical injuries. The patient who had surgical removal 10 years after MS placement developed cholangiocarcinoma. CONCLUSIONS Surgical repair remains the treatment of choice for BBS. Metallic stents should only be considered for poor surgical candidates, intrahepatic biliary strictures, or failed attempts at surgical repair. Most patients with MSs will develop recurrent cholangitis or stent obstruction and require intervention. Chronic inflammation and obstruction may predispose the patient to cholangiocarcinoma.

An 82-year-old black woman with a history of hepatocellular carcinoma presented with gastrointestinal bleeding. Barium enema and fibrocolonoscopy revealed a 4-cm polypoid mass at the level of the ascending colon with evidence of active bleeding. Biopsies of the lesion proved it to be metastatic hepatocellular carcinoma. Exploratory laparotomy revealed no further dissemination of the tumor, and the patient underwent an ileocolectomy. The serosal side of the colonic lesion was free from tumor, and there was no peritoneal implantation, direct extension, or lymph node involvement. This case represents an extremely rare presentation of metastatic hepatocellular carcinoma.

Acute liver failure has been reported as a frequent complication of transarterial chemoembolization (TACE). We prospectively evaluated the adverse effects and biochemical changes of TACE. From 10/95 to 9/96, 35 patients with hepatic malignancies were evaluated for TACE. Fifteen patients (9 male and 6 female) received 23 treatments. Ten of 15 patients had hepatocellular carcinoma, and 5 had metastatic tumors. Treatment exclusion criteria included advanced liver disease, hepatic vascular thrombosis, and severe comorbidity. TACE consisted of intra-arterial infusion of a mixture of doxorubicin, cisplatin, and mitomycin followed by embolization. Clinical symptoms and laboratory studies were monitored following treatment. Technical success was achieved in all patients. Adverse symptoms were transient, and most resolved within 1 week. Changes in hepatic, renal, and hematologic function were temporary and returned to pre-TACE levels by 1 month. None developed acute liver failure. The mean hospital stay was 3 days. Ten of 13 patients had a significant decrease in baseline tumor markers. The actual survival was 93 per cent with a median follow-up of 10 months. TACE can be performed safely in patients with hepatic tumors. The adverse effects can be anticipated and easily managed.

Two case reports of hepatic angiomyolipoma, both originating in the caudate lobe, are reported with a review of the literature. The liver is the second most common site of angiomyolipoma, an uncommon benign tumor of mixed mesenchymal origin. It is commonly diagnosed following abdominal pain or as an asymptomatic mass discovered on abdominal ultrasound or computed tomography scan. Of 74 cases reported, the lesions ranged from 0.3 to 36 cm in diameter and are noted between the first and eighth decade, with predominant female predilection. The right lobe is the most common site, with lesions arising in the caudate lobe comprising only five cases. The natural history of the hepatic lesion is unknown. Malignant invasion or metastatic disease has not been documented. Hepatic and renal angiomyolipoma can occur concurrently (13 of 60 cases), although the majority are not biopsy proven. Multicentric hepatic disease occurs. The correlation between tuberous sclerosis and hepatic angiomyolipoma is not confirmed histologically and occurs rarely. These lesions have a characteristic radiographic appearance due to high fat content. Histologically, angiomyolipoma are characterized by an admixture of adipose tissue, blood vessels, and smooth muscle cells. These lesions cannot reliably be differentiated from a malignant lesion based on clinical history, radiologic examination, and/or pathologic interpretation. If clinical suspicion for malignancy is low, then careful observation with serial radiologic follow-up is performed. The treatment for a symptomatic or suspicious lesion is resection, if feasible. Liver transplantation may be considered for large or centrally located lesions not amenable to resection.

We evaluated the effect of Liqui‐E, a water‐soluble vitamin E preparation, on cyclosporin A (CyA) whole blood concentration in liver transplant recipients, and its impact on the cost of CyA. Patients were 26 liver transplant recipients (19 adults, 7 children) who were unable to achieve and maintain therapeutic CyA whole blood concentrations with the standard recommended oral daily dose in the early post‐transplant period. Liqui‐E 6.25 IU/kg orally was administered with CyA every 12 hours (median time of starting Liqui‐E day 14.5). With Liqui‐E, the daily oral CyA requirements (mean ± SD) were decreased in adults from 22.6 ± 8.9 to 16.2 ± 7.3 mg/kg/day (p<0.001) and in children from 78.6 ± 34.1 to 53.7 ± 35.0 mg/kg/day (pl0.02); intravenous administration of CyA was unnecessary. The CyA trough concentrations (mean ± SD) before and after Liqui‐E were 670 ± 186 and 1012 ± 216 ng/ml, respectively, in adults (pl0.001) and 732 ± 187 and 1052 ± 166 ng/ml, respectively, in children (pl0.01). When given with Liqui‐E, the daily cost of CyA decreased by 26% in both adults and children. No clinical or biochemical evidence of Liqui‐E toxicity was observed. Thus its administration in the early post‐transplantation period can enhance CyA absorption in adults and children who are unable to achieve adequate whole blood concentrations with the usual recommended oral dosages. In addition, a significant cost saving can be realized by coadministration.

Variceal bleeding (VB) and ascites refractory to diuretics (RA) represent a significant cause of morbidity and mortality in patients with portal hypertension. Transjugular intrahepatic portosystemic shunts (TIPS) have been used effectively in patients with these complications, especially those individuals awaiting orthotopic liver transplantation (OLT). From April 1992 to July 1995, 41 adult patients underwent an attempt at TIPS placement for refractory VB or ascites at Cedars-Sinai Medical Center. Technical success was achieved in 37 of 41 cases (90.3%) with only two technical complications. Immediate control of hemorrhage and significant improvement of ascites was obtained in 91.9% and 83.5% of the patients, respectively. Six patients (16.2%) died within a week of TIPS placement due to uncontrollable ascites and multiorgan failure. Four of 31 patients (12.9%) developed mild to moderate grades of hepatic encephalopathy that was controlled with lactulose. Rebleeding from recurrent portal hypertension was noted in 5 of 31 cases (16.1%). Shunt stenosis or occlusion was seen in 7 of 31 cases (22.6%) at an average of 6.3 months following TIPS placement. Six patients underwent OLT within an average of 87 days after TIPS. These results indicate that TIPS appears to be an effective method for treatment of refractory VB and RA, especially for patients who are poor candidates for a surgical shunt or awaiting OLT. However, TIPS may not be considered a definitive solution for all patients with portal hypertension because of its current rate of shunt occlusion or stenosis.

Although elderly patients are accounted for in all large series of major hepatic resections, the role of age as a determinant of outcome remains unclear. At Cedars-Sinai Medical Center, we review a series of 20 major hepatectomies for neoplasia performed in patients older than 66 years of age (4 of them > or = 80 years old) over a 5-year period. A retrospective comparison was conducted with a group of 22 hepatectomies for malignancy performed in 20 patients younger than 59 years of age during the same time period. The younger group had a significantly greater degree of liver resected (12 trisegmentectomies vs 3). Although one operative death (5% mortality) was observed in the elderly group, no statistically significant difference was noted, when compared to the younger group (Chi-square, P = 0.48). Likewise, no significant difference in the complication rate (20% vs 33%) was noticed (Chi-square, P = 0.8). Severe postoperative liver dysfunction was present in 2 cases (10%) in the elderly group and one (4%) in the younger group. These patients underwent a right trisegmentectomy (TS). Nine patients from each group were resected without red blood cell transfusion. We conclude that major hepatic resection in elderly patients without severe comorbid disease is a safe procedure that is not associated with an increased perioperative morbidity or mortality rate.

Liver regeneration occurs as a result of hepatic tissue loss or injury. The process of liver regeneration is carefully regulated in a controlled biologic scheme with closely interactive relationships between hormones, free neurotransmitters, and nutrients; protooncogenes; and polypeptide and glycolipid growth factors. These relationships are now being studied at the molecular and cellular levels and attempts are being made to reconstruct the complete intricate process. Although significant breakthroughs have occurred in understanding the effects and regulation of several subsystems (such as insulin and its receptors; TGF-alpha and TGF-beta; HGF and its receptors), the integral process remains a mystery. Improved comprehension of the regeneration process will lead to rational treatment algorithms for now dreaded hepatic diseases.