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NCI CANCERLIT^® Search: Therapy of Primary Liver Cancer - September 2002

National Cancer Institute^®

Hepatoprotective drugs for the treatment of virus-induced chronic hepatitis: from hypercarcinogenic state to hypocarcinogenic state.
Liver transplantation in the therapy of hepatocellular carcinoma: a revision of our series.
Post-treatment malignant liver lesions. MR imaging.
Novel drug delivery device may improve liver cancer outcomes.
Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the liver surface.
Resection of hepatocellular carcinoma without preoperative tumor biopsy.
Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes.
[Extrahepatic arterial blood supply of hepatocellular carcinoma and interventional treatment]
[The effect of postoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for
Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced versus mangafodipir trisodium-enhanced MR imaging.
Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma.
Prioritization of patients with liver cancer within the MELD system.
Remission and survival following monthly intraarterial cisplatinum in nonresectable hepatoma.
Prospective assessment of the safety and benefit of laparoscopic liver resections.
Radiofrequency ablation of hepatocellular carcinoma.
Finite-element analysis of hepatic multiple probe radio-frequency ablation.
IkappaBalpha gene therapy in tumor necrosis factor-alpha- and chemotherapy-mediated apoptosis of hepatocellular carcinomas.
Management of spontaneous bleeding due to hepatocellular carcinoma.
Main characteristics of hepatocellular carcinoma and cirrhosis and therapeutic approaches.
Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.
Effect of the presence of hepatitis B e antigen on prognosis after liver resection for hepatocellular carcinoma in patients with chronic
Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy.
Radiofrequency thermal ablation versus other interventions for hepatocellular carcinoma.
Transcatheter arterial chemoembolization for hepatocellular carcinomas in patients with celiac axis occlusion.
Dose-response relationship in local radiotherapy for hepatocellular carcinoma.
Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric
Resection of liver tumors: technical aspects.
A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma.
[Benign hepatic tumors: diagnostic management and therapeutic outcome]
Safety of liver transection before mobilization.
Demographic, clinical, and virological characteristics of hepatocellular carcinoma in Asia: survey of 414 patients from four countries.
Hepatitis B immunization and hepatocellular carcinoma: The Gambia Hepatitis Intervention Study.
[Interventional methods in the treatment of malignant conditions of the liver]
Molecular targets for prevention of hepatocellular carcinoma.

1
UI - 11885965
AU - Okamoto T; Kajino K; Hino O
TI - Hepatoprotective drugs for the treatment of virus-induced chronic hepatitis: from hypercarcinogenic state to hypocarcinogenic state.
SO - Jpn J Pharmacol 2001 Nov;87(3):177-80
AD - Research Laboratories, Nippon Chemiphar Co, Ltd, Saitama, Japan.
Interferon (IFN)-based therapy is a standard treatment for chronic hepatitis caused by hepatitis C virus (HCV) infection. This treatment is effective in approximately 30-40% of the patients and using ribavirin in combination with IFN increases the rate of sustained virologic clearance. For the remaining patients, glycyrrhizin is often used. Glycyrrhizin is known to prevent the development of hepatocellular carcinoma (HCC), but glycyrrhizin is usually administered intravenously. Drugs that are effective by oral administration are convenient for patients for long-term administration, and development of more effective drugs than glycyrrhizin is preferable. However, studies on drugs for the treatment of hepatitis are not actively conducted, and promotion of the study of drugs in this area is encouraging. For that reason, we show our approach to study drugs for the treatment of hepatitis. We analyzed the effect of glycyrrhizin on hepatitis as a standard chemical using the mouse liver injury model. Based on this, we screened drugs and found that a coumarin derivative seems to be one of model chemicals for the treatment of hepatitis.

2
UI - 11959274
AU - Lucena de la Poza JL; Turrion VS; Alvira LG; Garrido MJ; Arana RU;
TI - Sanmartin JA Liver transplantation in the therapy of hepatocellular carcinoma: a revision of our series.
SO - Transplant Proc 2002 Feb;34(1):260-1
AD - Liver Transplantation Unit, Clinica Puerta de Hierro, Universidad Autonoma, Madrid, Spain.

3
UI - 11998575
AU - Braga L; Semelka RC; Pedro MS; de Barros N
TI - Post-treatment malignant liver lesions. MR imaging.
SO - Magn Reson Imaging Clin N Am 2002 Feb;10(1):53-73
AD - Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
MR imaging is very accurate in the diagnosis and staging of tumors and in surgical planning. MR imaging is also an excellent method for evaluation of the liver after surgical resection, systemic or local tumor therapies, and liver transplantation. It permits early recognition of complications and the presence of recurrent tumor, providing an opportunity to repeat treatment or use alternative treatment. Surgical resection remains the standard therapy for treating liver metastases. The relatively small number of patients who are candidates for curative resection have provided impetus for the implementation and improvement of other techniques. The variety of techniques and the sensitivity for contrast enhancement have made MR imaging an ideal method to follow the response of tumors to various treatment approaches. The appearance of tumor recurrence and the response to treatment are relatively consistently shown on MR images; however, the time course of change in lesion appearance has not been fully elucidated, particularly in the setting of chemotherapy. Evaluating the response to chemotherapy is rendered complex because of the longer duration of the therapy, the types of response that various chemotherapeutic agents engender, the method of action of this therapy and the time of imaging in relation to therapy. The various local therapies share some general principles of action, and many have similar MR imaging findings. Some local therapies are effective only with certain malignancies (e.g., alcohol therapy and HCC), whereas other therapies are more limited because of the size of the tumor kill zone (e.g., interstitial laser therapy). We are in the early stages of using MR imaging to guide local therapies and to monitor response during treatment in real time. This appears to be an important future direction for MR imaging. The role of MR imaging in liver transplantation involves pre- and postoperative investigation of both donors (in the case of living-related transplantation) and recipients. These issues are described further in the section on MR imaging of liver transplantation.

4
UI - 12147418
AU - Reidenbach F
TI - Novel drug delivery device may improve liver cancer outcomes.
SO - Lancet Oncol 2002 Aug;3(8):450

5
UI - 11007264
AU - Ohmoto K; Yamamoto S
TI - Percutaneous microwave coagulation therapy for superficial hepatocellular carcinoma on the liver surface.
SO - Am J Gastroenterol 2000 Sep;95(9):2401-3

6
UI - 11505066
AU - Levy I; Greig PD; Gallinger S; Langer B; Sherman M
TI - Resection of hepatocellular carcinoma without preoperative tumor biopsy.
SO - Ann Surg 2001 Aug;234(2):206-9
AD - Department of Medicine, Toronto General Hospital, Toronto, Canada.
OBJECTIVE: To evaluate the need for a preoperative tumor biopsy of liver lesions suspicious for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: With advances in liver imaging, the results of recent studies have suggested a very high accuracy of preoperative evaluation of liver masses suspicious of HCC, making preoperative tumor biopsy unnecessary. METHODS: A retrospective analysis was conducted of all liver resections for HCC at the Toronto General and Mt. Sinai Hospitals, underwent 65 liver resections without a preoperative liver biopsy. The median age was 61 years. Sixty percent of the patients had cirrhosis and 38.5% had noncirrhotic chronic hepatitis. HCC was confirmed histologically in the surgical specimen in 63 of the 65 cases (96.9%). Both patients without HCC had a significant risk factor for HCC (chronic hepatitis C and alcohol in one and chronic hepatitis B and previous resection for HCC in the other). The lesions were 2 cm and 2.7 cm in diameter, and the alpha-fetoprotein level was low (<5 and 22 ng/mL, respectively). In such patients, with tumor 3 cm or smaller and an alpha-fetoprotein level less than 100 ng/mL (10 patients), the false-positive rate for the preoperative diagnosis was 2/10 (20%). CONCLUSIONS: Preoperative diagnosis of HCC was highly accurate in lesions larger than 3 cm. Tumor biopsy is unnecessary in these patients. However, in a subgroup of patients with lesions less than 3 cm, particularly those with alpha-fetoprotein levels less than 100 ng/mL, there is a higher false-positive diagnostic rate, and tumor biopsy should be considered.

7
UI - 11584966
AU - Weber SM; Jarnagin WR; Klimstra D; DeMatteo RP; Fong Y; Blumgart LH
TI - Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes.
SO - J Am Coll Surg 2001 Oct;193(4):384-91
AD - Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Intrahepatic cholangiocarcinoma (IHC) is a rare primary hepatic tumor of bile duct origin for which resection is the most effective treatment. But resectability, outcomes after resection, and recurrence patterns have not been well described. Patients with IHC were identified from a prospective database. Demographic data, tumor characteristics, and with hepatic tumors underwent exploration and were found to have pure IHC on pathologic analysis. Patients with mixed hepatocellular and cholangiocarcinoma tumors were excluded. At exploration, 20 patients were unresectable for an overall resectability rate of 62% (33 of 53). Median survival for patients submitted to resection was 37.4 months versus 11.6 months for patients undergoing biopsy only (p = 0.006; median followup for surviving patients, 15.6 months). Actuarial 3-year survival was 55% versus 21%, respectively. Factors predictive of poor survival after resection included vascular invasion (p = 0.0007), histologically positive margin (p = 0.009), or multiple tumors (p = 0.003). After resection, 20 of 33 patients (61%) recurred at a median of 12.4 months. Sites of recurrence included the liver (14), retroperitoneal or hilar nodes (4), lung (4), and bone (2). The median disease-free survival was 19.4 months, with a 3-year disease-free survival rate of 22%. Factors predictive of recurrence were multiple tumors (p = 0.0002), tumor size (p = 0.001), and vascular invasion (p = 0.01). About two-thirds of patients who appeared resectable on preoperative imaging were amenable to curative resection at the time of operation. Although complete resection improved survival, recurrence was common. The majority of recurrences were local or regional, which may help guide future adjuvant therapy strategies.

8
UI - 12015039
AU - Li C; Guo Y; Tian G; Shi Z; Liu D; Zeng H; Jiang W; Li H; Zhou C
TI - [Extrahepatic arterial blood supply of hepatocellular carcinoma and interventional treatment]
SO - Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):163-6
AD - Department of Diagnostic Radiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To study the pattern extrahepatic arteriy supply to hepatocellular carcinoma and catheterization technique for interventional therapy. METHODS: Routine celiac and superior mesenteric artery angiography was done before transcatheter arterial chemoembolization (TACE) for 78 collateral arterial pathways of 62 hepatocellular carcinoma patients. Super selective catheterization and transcatheter dual arterial chemoembolization (TDACE) to extrahepatic arterial and hepatic arteries were performed. RESULTS: Extrahepatic blood supply was found in 43.1% of hepatocellular carcinoma patients. There was close correlation between extrahepatic arterial blood supply and location of tumor. Success rate of super selective extrahepatic artery catheterization was 71.8% by the combined use of RH, Cobra and SP catheters. Follow-up studies revealed reduction of tumor and complete dense deposition of lipiodol. CONCLUSION: Ample extrahepatic arterial blood supply is found in hepatocellular carcinoma. Transcatherdual arterial chemoembolization is effective, necessary and feasible for hepatocellular carcinoma with extrahepatic arterial blood supply.

9
UI - 12133334
AU - Zhang Z; Wu M; Chen H; Yang J; Yang G; Shen F; He J
TI - [The effect of postoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma]
SO - Zhonghua Wai Ke Za Zhi 2002 May;40(5):329-31
AD - Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
OBJECTIVE: To evaluate postoperative transcatheter hepatic arterial chemoembolization (TACE) for improving the disease-free survival of HCC patients after hepatectomy. METHODS: 1 725 HCC patients were followed up after hepatectomy retrospectively. Of 1 457 patients who were followed-up completely, 209 had postoperative TACE. The 1 457 patients were divided into ten groups according to tumor thrombus, small HCC, capsular invasion, vascular invasion and cirrhosis. The disease-free survival was analyzed between subgroups of weather postoperative TACE was performed in every group. Software SAS 6.12 and EGRET package were used. Kaplan-Meier estimation was used to calculate the disease-free survival rates. RESULTS: There were no difference of the disease-free survival between the subgroups in no capsular invasion and in no hepatic cirrhosis groups. CONCLUSION: Postoperative TACE is helpful in improving the disease-free survival of HCC patients after hepatectomy except those with integrated tumor envelope or no hepatocirrhosis. It is important to prolong the long-term results of operation.

11
UI - 11965574
AU - Cheng SJ; Freeman RB Jr; Wong JB
TI - Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma.
SO - Liver Transpl 2002 Apr;8(4):323-8
AD - Department of Medicine, Division of Clinical Decision Making, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Allocation of cadaveric livers to patients based on such objective medical urgency data as the Model for End-Stage Liver Disease (MELD) score may not benefit patients with small hepatocellular carcinomas (HCCs). To ensure that these patients have a fair opportunity of receiving a cadaveric organ, the risk for death caused by HCC and tumor progression beyond 5 cm should be considered. Using a Markov model, two hypothetical cohorts of patients with small hepatomas were assumed to have either (1) Gompertzian tumor growth, in which initial exponential growth decreases as tumor size increases; or (2) rapid exponential growth. The model tracked the number of patients who either died or had tumor progression beyond 5 cm. These results were used to back-calculate an equivalent MELD score for patients with small HCCs. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. The Gompertzian growth model predicted that patients with a 1- and 4-cm tumor have 1-year progression-free survival rates of 70% (HCC-specific MELD score 6) and 66% (HCC-specific MELD score 8), respectively. When assuming rapid exponential growth, patients with a 1- and 4-cm tumor have progression-free survival rates of 69% (HCC-specific MELD score 6) and 12% (HCC-specific MELD score 24), respectively. Our model predicted that the risk for death caused by HCC or tumor progression beyond 5 cm should increase with larger initial tumor size in patients with small hepatomas. To ensure that these patients have a fair opportunity to receive a cadaveric organ, HCC-specific scores predicted by our model could be added to MELD scores of patients with HCC.

12
UI - 11965575
AU - Roberts JP
TI - Prioritization of patients with liver cancer within the MELD system.
SO - Liver Transpl 2002 Apr;8(4):329-30

13
UI - 12197216
AU - Court WS; Order SE; Siegel JA; Johnson E; DeNittis AS; Principato R;
TI - Martz K; Zeiger LS Remission and survival following monthly intraarterial cisplatinum in nonresectable hepatoma.
SO - Cancer Invest 2002;20(5-6):613-25
AD - Center for Molecular Medicine, 700 Stewart Avenue, Garden City, NY 11530, USA. drcourt@molecularoncology.com
PRECIS: Intraarterial delivery of 50 mg/m2 cisplatinum on a monthly basis is a well-tolerated regimen for patients with nonresectable hepatoma. The selective uptake of cisplatinum delivered intraarterially suggests other selective intraarterial protocols would be of use in regional cancers treated with cisplatinum. BACKGROUND: Sixty-seven patients with nonresectable hepatoma were treated with hepatic artery infusions (HAI) of 50 mg/m2 cisplatinum on a monthly basis. METHODS: Forty-eight patients received an initial course of whole liver external radiation with intravenous (i.v.) cisplatinum 50 mg/m2. Nineteen patients did not receive radiation and received HAI cisplatinum only. All patients then received HAI cisplatinum at 50 mg/m2 on a monthly basis. Six patients were given a tracer dose of radioactive 195m cisplatinum for quantitation by the HAI and i.v. routes. RESULTS: Monthly HAI cisplatinum was well tolerated and could be repeated indefinitely. Median survival for primarily treated nonresectable hepatomas was 12 months [alpha fetoprotein (AFP) elevated] and 17.5 months (AFP negative). Radioactive cisplatinum given by HAI yielded 34-55% tumor uptake of cisplatinum vs. < 5% by i.v. delivery. CONCLUSIONS: Hepatic intraarterial cisplatinum at 50 mg/m2 is a well-tolerated monthly regimen for patients with nonresectable hepatoma.

14
UI - 12140614
AU - Farges O; Jagot P; Kirstetter P; Marty J; Belghiti J
TI - Prospective assessment of the safety and benefit of laparoscopic liver resections.
SO - J Hepatobiliary Pancreat Surg 2002;9(2):242-8
AD - Department of Digestive Surgery and Liver Transplantation, Beaujon Hospital, 92118 Clichy cedex, France.
BACKGROUND/PURPOSE: Laparoscopy represents an alternative to open surgery for virtually all digestive surgery procedures, with the anticipated short-term advantage of reduced esthetic prejudice, postoperative pain, and duration of in-hospital stay. In this study, we investigated the safety and benefits of laparoscopic liver resections in patients with benign solid liver tumors. METHODS: Laparoscopic liver resection of up to two segments for benign liver tumor was performed under continuous carbon dioxide (CO(2)) pneumoperitoneum in 21 patients with no underlying chronic liver disease. The risk of gas embolism was assessed by end-tidal CO(2) and O(2) saturation, and the hemodynamic variations were monitored by a Swan-Ganz catheter. The postoperative course was compared with that following open surgery by matched-pair analysis. RESULTS: No patient experienced gas embolism or was converted, and clamping of the hepatic pedicle resulted in hemodynamic variations comparable to those observed during open surgery. Duration of surgery (177 vs 156 min.), intraoperative blood loss (218 vs 285 ml), modifications of postoperative liver function tests, and incidence of postoperative complications (10% vs 10%) were comparable to those after open surgery. Laparoscopic resection was associated with a 50% reduction (15.5 vs 31.6 mg) in morphine consumption during the first postoperative days, a reduction of the delay to oral intake of 0.8 days, and a reduction of in-hospital stay of 1.4 days. CONCLUSIONS: Liver resections of up to two segments can be performed by laparoscopy using the same technique as that used during open surgery. However, the benefits observed compared with open surgery appear to be limited.

15
UI - 11941292
AU - Curley SA; Izzo F
TI - Radiofrequency ablation of hepatocellular carcinoma.
SO - Minerva Chir 2002 Apr;57(2):165-76
AD - M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA. scurley@mdanderson.org
The majority of patients with primary or metastatic hepatic tumors are not candidates for resection because of tumor size, location near major intrahepatic blood vessels precluding a margin-negative resection, multifocality, or inadequate hepatic function related to coexistent cirrhosis. Radiofrequency ablation (RFA) is an evolving technology being used to treat patients with unresectable primary and metastatic hepatic cancers. RFA produces coagulative necrosis of tumor through local tissue heating. Liver tumors are treated percutaneously, laparoscopically, or during laparotomy using ultrasonography to identify tumors and to guide placement of the RFA needle electrode. For tumors smaller than 2.0 cm in diameter, one or two deployments of the monopolar multiple array needle electrode is sufficient to produce complete coagulative necrosis of the tumor. However, with increasing size of the tumor, there is a concomitant increase in the number of deployments of the needle electrode and the overall time necessary to produce complete coagulative necrosis of the tumor. In general, RFA is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies less than 6.0 cm in diameter. Effective treatment of larger tumors awaits the development of more powerful, larger array monopolar and bipolar RFA technologies.

16
UI - 12148822
AU - Haemmerich D; Tungjitkusolmun S; Staelin ST; Lee FT Jr; Mahvi DM;
TI - Webster JG Finite-element analysis of hepatic multiple probe radio-frequency ablation.
SO - IEEE Trans Biomed Eng 2002 Aug;49(8):836-42
AD - Department of Surgery, University of Wisconsin, Madison 53792, USA.
Radio-frequency (RF) ablation is an important means of treatment of nonresectable primary and metastatic liver tumors. RF ablation, unlike cryoablation (a method of tumor destruction that utilizes cold rather than heat), must be performed with a single probe placed serially. The ablation of any but the smallest tumor requires the use of multiple overlapping treatment zones. We evaluated the performance of a configuration incorporating two hooked probes (RITA model 30). The probes were lined up along the same axis in parallel 20 mm apart. Three different modes applied voltage to the probes. The first mode applied energy in monopolar mode (current flows from both probes to a dispersive electrode). The second mode applied the energy to the probes in bipolar mode (current flows from one probe to the other). The third method applied the energy sequentially in monopolar mode (in 2-s intervals switched between the probes). We used the finite-element method (FEM) and analyzed the electric potential profile and the temperature distribution at the end of simulation of a 12-min ablation. The alternating monopolar mode allowed precise independent control of the amount of energy deposited at each probe. The bipolar mode created the highest temperature in the area between the probes in the configuration we examined. The monopolar mode showed the worst performance since the two probes in close vicinity create a disadvantageous electric field configuration. We, thus, conclude that alternating monopolar RF ablation is superior to the other two methods.

17
UI - 11059688
AU - Tietze MK; Wuestefeld T; Paul Y; Zender L; Trautwein C; Manns MP;
TI - Kubicka S IkappaBalpha gene therapy in tumor necrosis factor-alpha- and chemotherapy-mediated apoptosis of hepatocellular carcinomas.
SO - Cancer Gene Ther 2000 Oct;7(10):1315-23
AD - Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Germany.
The transcription factor nuclear factor kappaB (NFkappaB) is an essential antagonist of apoptosis during liver regeneration and embryonal development of hepatocytes. Several reports have indicated that NFkappaB may also inhibit the programmed cell death induced by cytokines, ionizing radiation, or cytotoxic drugs in some cancer cell lines. Because hepatocellular carcinomas (HCCs) are one of the most resistant tumors to systemic chemotherapy, we investigated the activation of NFkappaB and the consequence of its inhibition by an IkappaBalpha-super repressor during tumor necrosis factor alpha (TNFalpha)- and chemotherapy-induced apoptosis in HCC cell lines. We demonstrate that both TNFalpha and adriamycin activate NFkappaB in hepatoma cells. Activation of NFkappaB could be blocked through an adenoviral vector expressing the IkappaBalpha super repressor, regardless of the activating agent. Inhibition of NFkappaB enhanced the apoptosis induced by TNFalpha, whereas IkappaBalpha had an anti-apoptotic effect on chemotherapy-induced programmed cell death. A strong inhibition of chemotherapy- and TNFalpha-induced apoptosis by dominant-negative Fas-associated death domain indicated an essential contribution of death receptor-mediated apoptosis. To elucidate the different role of NFkappaB in chemotherapy-induced apoptosis, we investigated the expression of Fas (CD95) and Fas ligand (CD95 ligand), which have been described as important mediators of chemotherapy-induced cell death and as target genes of NFkappaB. However, our investigations demonstrated that in hepatoma cells, the chemotherapy-induced up-regulation of Fas (CD95) and Fas ligand (CD95 ligand) is not transcriptionally mediated through NFkappaB. Thus, other molecular mechanisms must account for the anti-apoptotic effect of IkappaBalpha in adriamycin-induced death of hepatoma cells. In summary, our investigations indicate that the activation of NFkappaB in response to cytotoxic drugs, in contrast to TNFalpha, exerts a pro-apoptotic stimulus rather than an anti-apoptotic function, which has implications for therapy of HCCs.

18
UI - 12029230
AU - Recordare A; Bonariol L; Caratozzolo E; Callegari F; Bruno G; Di Paola
TI - F; Bassi N Management of spontaneous bleeding due to hepatocellular carcinoma.
SO - Minerva Chir 2002 Jun;57(3):347-56
AD - IV Divisione di Chirurgia, Centro Regionale Specializzato di Chirurgia epato-bilio-pancreatica, Ospedale Regionale di Treviso, Italy.
BACKGROUND: Spontaneous rupture is a life-threatening complication of HCC, occurring in 4.8-26% of cases. Liver failure is the main cause of death. Debates still remain on the most appropriate treatment in such patients because of the high operative mortality of emergency surgery and the high risk of rebleeding and less satisfying mid- and long-term results of nonoperative procedures like angiographic embolization. Early and long-term results of a surgically oriented treatment, based on prompt evaluation of the functional liver reserve and tumor (11.86 years) were treated for ruptured HCC, in 10 cases involving a cirrhotic liver. Seven patients underwent emergency surgery and 4 patients transcutaneous arterial embolization (TAE). Liver resection was performed in patients with preserved liver function, after ultrasonography and/or CT scan demonstrated hemoperitoneum and a single resectable liver tumour (5 cases). In one patient with cirrhosis, ultrasonography showed only hemoperitoneum. A bleeding nodule was discovered intraoperatively and resected in a liver with a multinodular HCC. Another patient under-went emergency resection after referral at our Unit with a surgical packing. In 4 cases with poor liver function and/or unresectable tumour TAE of the neoplasm was performed, in one case after surgical packing. Mortality, morbidity and patients survival after treatment were analyzed. All patients had at least 1 year follow-up. RESULTS: All patients underwent minor resection; 2 left lobectomies, 1 segmentectomy (VII), 1 bisegmentectomy (VII-VIII), and 3 wedge resections. Postoperative course was complicated by ascites in 5 cases and subphrenic abscess in one case. Four patients died 3, 4, 6 and 62 months after surgery; 3 patients are actually alive 22, 25, and 89 months after surgery. Four patients were submitted to TAE: all patients died within 6 months. CONCLUSIONS: When ruptured HCC is suspected, preserved liver function (Child A-B7) and a resectable hepatic tumour are considered clear indications to surgery. Emergency liver resection achieved good early and long-term results. In cases of advanced liver disease or multinodular HCC a non-operative approach, like TAE, must be attempted. Surgical direct hemostasis or hepatic artery ligation must be reserved for patients with uncontrollable o recurrent bleeding after TAE.

19
UI - 11945147
AU - Elba S; Buongiorno GP; Caruso ML; Noviello MR; Manghisi OG
TI - Main characteristics of hepatocellular carcinoma and cirrhosis and therapeutic approaches.
SO - Curr Pharm Des 2002;8(11):1007-11
AD - Div. di Gastroenterologia, Serv. di Anatomia Patologica, I.R.C.C.S. S. De Bellis , Castellana Grotte, Italy.
Between 1995 and 1997 we studied 100 patients with hepatocarcinoma (HCC) and cirrhosis. Of these 74 were males and 26 females with a mean age of 66 years. 13% patients were only HbsAg positive, 75% only anti-HCV positive, 6% HbsAg and anti-HCV and the etiology in 6% of cases was alcoholic. Alpha-foetoprotein was >400 ng/ml in only 18% of cases and portal thrombosis was present in 12%. Mononodular HCC was observed in 63% of cases (small HCC in only 38%) and in 79% was localized to the right lobe. Of the mononodular types, 70% were shown by echography to be hypoechoic, 6% hysoechoic, 6% hyperechoic and 17% mixed patterns. Histologically, 49% were well-differentiated, 45% moderately-differentiated and 6% poorly-differentiated. No correlation was found between histologic pattern and number of nodules. Well-differentiated HCC was found in 51% of mononodular types and in 46% of multinodular types. Moderately-differentiated HCC was detected in 46% and 43% respectively and poorly-differentiated HCC in 3% and 11% respectively. No correlation was found between number of nodules and the degree of Edmonson.

20
UI - 11945148
AU - Perrone F; Gallo C; Daniele B; Gaeta GB; Izzo F; Capuano G; Adinolfi LE;
TI - Mazzanti R; Farinati F; Elba S; Piai G; Calandra M; Stanzione M; Mattera D; Aiello A; De Sio I; Castiglione F; Russo M; Persico M; Felder M; Manghisi OG; De Maio E; Di Maio M; Pignata S; Cancer of Liver Italian Program (CLIP) Investigators Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.
SO - Curr Pharm Des 2002;8(11):1013-9
AD - CLIP secretariat, Ufficio Sperimentazioni Cliniche Controllate, Istituto Nazionale Tumori, Via Mariano Semmola, Napoli, 80131, Italy. fr.perrone@agora.it
BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

21
UI - 12098045
AU - Kubo S; Hirohashi K; Yamazaki O; Matsuyama M; Tanaka H; Horii K; Shuto
TI - T; Yamamoto T; Kawai S; Wakasa K; Nishiguchi S; Kinoshita H Effect of the presence of hepatitis B e antigen on prognosis after liver resection for hepatocellular carcinoma in patients with chronic hepatitis B.
SO - World J Surg 2002 May;26(5):555-60
AD - Second Department of Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. m7696493@msic.med.osaka-cu.jp
We examineded the clinical effects of serum hepatitis B e antigen (HBeAg) positivity on clinicopathologic findings and prognosis after liver resection for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. A series of 56 patients who underwent curative resection were divided into two groups: 25 HBeAg-positive patients (group 1) and 31 HBeAg-negative patients (group 2). The mean age was significantly lower in group 1 than in group 2 (p = 0.0021), and the proportion of patients with symptoms was significantly higher in group 1 than in group 2 (p = 0.037). There were no significant differences in other clinical findings between the two groups, including laboratory test results, coexisting medical conditions, and operative methods. Although tumor size, degree of differentiation of the main tumor, and the prevalence of vascular invasion did not differ between the groups, the prevalence of intrahepatic metastasis and the proportion of patients with active hepatitis were significantly higher in group 1 than in group 2 (p = 0.009 and p = 0.043, respectively). Tumor-free and cumulative survival rates were significantly lower in group 1 than in group 2 (p = 0.022 and p = 0.0001, respectively). Multivariate analysis of various possible risk factors demonstrated serum HBeAg positivity to be an independent risk factor for recurrence [risk ratio (RR) 2.49; 95% confidence interval (CI) 1.12-5.49; p = 0.032] and an independent unfavorable factor for the survival time (RR 7.58; 95% CI 2.10-27.8; p = 0.0020). We concluded that the prognosis after liver resection for HCC is worse for HBeAg-positive patients than for HBeAg-negative patients.

22
UI - 12209726
AU - Teratani T; Ishikawa T; Shiratori Y; Shiina S; Yoshida H; Imamura M; Obi
TI - S; Sato S; Hamamura K; Omata M Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy.
SO - Cancer 2002 Aug 15;95(4):816-23
AD - Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Japan. teratani-2im@h.u-tokyo.ac.jp
BACKGROUND: The age of patients with hepatocellular carcinoma (HCC) has been increasing worldwide. The objective of this study was to assess the efficacy and safety of percutaneous ethanol injection therapy (PEIT) in elderly patients with HCC. METHODS: The authors retrospectively analyzed 653 patients who were treated with PEIT between 1985 and 1997. One hundred thirty-seven patients were age > or = 70 years, 90 of 137 patients (66%) were male, and 106 of 137 patients (77%) were positive for hepatitis C virus antibodies. Both survival rates and standardized mortality ratios (SMRs) related to the causes of death were compared between patients age > or = 70 years and patients age < 70 years. RESULTS: With the exception of greater maximum tumor size in elderly patients age > or = 70 years, the clinical features of tumors and underlying liver disease were similar to those of patients age < 70 years The survival rates after PEIT in patients age > or = 70 years were 83%, 52%, and 27% at 1 year, 3 years, and 5 years, respectively. These results were comparable to the rates for patients age < 70 years (1 year, 90%; 3 years, 65%; and 5 years, 40%). In addition, there was no difference in mortality from extrahepatic disease between the two groups (9.8% for patients age > or = 70 years vs. 9.4% for patients age < 70 years; P > 0.999). The SMR of patients age > or = 70 years who died of causes related to extrahepatic disease (SMR, 0.56; 95% confidence interval [95%CI], 0.18-1.30) was lower compared with the SMR of patients age < 70 years (SMR, 1.75; 95%CI, 1.07-2.71). The SMR of patients age > or = 70 years who died of causes related to liver disease (SMR, 115; 95%CI, 84.1-153.0) was similar to that of patients age < 70 years (SMR, 120; 95%CI, 103.0-138.0). CONCLUSIONS: These results provide support for the treatment of patients with HCC age > or = 70 years by tumor ablation using PEIT. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10735

23
UI - 12137670
AU - Galandi D; Antes G
TI - Radiofrequency thermal ablation versus other interventions for hepatocellular carcinoma.
SO - Cochrane Database Syst Rev 2002;(3):CD003046
AD - Department for Gastroenterology and Hepatology, University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, Germany. galandi@cochrane.de
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. The only possibly curative therapeutic option is surgical resection. Due to impaired liver function and/or anatomical reasons only a low percentage of patients can be treated surgically. For the remainder, several non-surgical treatment approaches have been developed. In addition to percutaneous ethanol injection, transarterial interventions, and several medical interventions, radiofrequency thermal ablation has been investigated in coagulating HCC lesions. OBJECTIVES: To evaluate the effects of radiofrequency thermal ablation in HCC patients with respect to clinically relevant outcomes (mortality, rate of recurrences, adverse events, quality of life, and duration of hospital stay). SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE, Current Contents, EMBASE, and Reference lists of the identified articles were checked for further trials. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials investigating radiofrequency thermal ablation versus placebo, no intervention, or any other therapeutic approach were considered for inclusion, regardless of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information. MAIN RESULTS: One randomised trial which is still ongoing and only published as an interim analysis was identified. This trial compared radiofrequency thermal ablation versus percutaneous ethanol injection in 102 patients with small HCC. With respect to mortality the trial showed no significant difference between the two treatments (relative risk = 0.19, 95% confidence interval 0.02 to 1.59). Concerning the recurrence free survival the trial demonstrated no significant superiority of radiofrequency thermal ablation versus percutaneous ethanol injection (relative risk = 0.70, 95% confidence interval 0.46 -1.04). REVIEWER'S CONCLUSIONS: At present, radiofrequency thermal ablation is an insufficiently studied intervention for HCC.

24
UI - 12119327
AU - Kwon JW; Chung JW; Song SY; Lim HG; Myung JS; Choi YH; Park JH
TI - Transcatheter arterial chemoembolization for hepatocellular carcinomas in patients with celiac axis occlusion.
SO - J Vasc Interv Radiol 2002 Jul;13(7):689-94
AD - Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
PURPOSE: To verify the hypothesis that most instances of celiac axis occlusion in patients with hepatocellular carcinoma (HCC) are caused by diaphragmatic compression and, therefore, transcatheter arterial chemoembolization (TACE) can be performed through the compressed lumen of the celiac axis. MATERIALS AND METHODS: The authors attempted to perform TACE in 36 consecutive patients with HCC and celiac axis occlusion. Spiral computed tomographic (CT) images were available in 26 patients. Initially, catheterization of the hepatic arteries was attempted through the occluded celiac axis. If it failed, catheterization was performed through the pancreaticoduodenal arcades. The causes of celiac axis occlusion were evaluated based on spiral CT and angiographic findings, access routes, technical success rates, and related complications in superselective catheterization of hepatic arteries. RESULTS: Among the 26 patients who underwent spiral CT, diaphragmatic compression of the celiac axis was demonstrated in 23. Selective catheterization of hepatic arteries was possible through the occluded celiac axis in 23 patients (64%). In nine (25%) of the remaining 13 patients, TACE was performed through the dilated pancreaticoduodenal arcades from the superior mesenteric artery. As a procedure-related complication, celiac axis dissection occurred in one patient (3%). CONCLUSION: Most patients with celiac axis occlusion had arcuate ligament compression. In TACE, the celiac artery occlusion could be traversed directly and this should be the initial approach.

25
UI - 12182985
AU - Park HC; Seong J; Han KH; Chon CY; Moon YM; Suh CO
TI - Dose-response relationship in local radiotherapy for hepatocellular carcinoma.
SO - Int J Radiat Oncol Biol Phys 2002 Sep 1;54(1):150-5
AD - Department of Radiation Oncology, Brain Korea 21 Project for Medical Science, Seoul, South Korea.
PURPOSE: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC). METHODS AND MATERIALS: One hundred fifty-eight patients The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4-8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated. RESULTS: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses <40 Gy, 40-50 Gy, and >50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses <40 Gy, 40-50 Gy, and >50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively. CONCLUSIONS: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D-CRT can theoretically be used for treating primary HCC.

26
UI - 12182986
AU - Cheng JC; Wu JK; Huang CM; Liu HS; Huang DY; Cheng SH; Tsai SY; Jian JJ;
TI - Lin YM; Cheng TI; Horng CF; Huang AT Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and implication.
SO - Int J Radiat Oncol Biol Phys 2002 Sep 1;54(1):156-62
AD - Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, No. 125 Lih-Der Road, Pei-Tou District, Taipei 112, Taiwan. jasoncheng@mail.kfcc.org.tw
PURPOSE: To analyze the correlation of radiation-induced liver disease (RILD) with patient-related and treatment-related dose-volume factors and to describe the probability of RILD by a normal tissue complication probability (NTCP) model for patients with hepatocellular carcinoma (HCC) treated with three-dimensional conformal radiotherapy (3D-CRT). patients with intrahepatic malignancies were treated with 3D-CRT at our institution. Sixty-eight patients who were diagnosed with HCC and had complete 3D dose-volume data were included in this study. Of the 68 patients, 50 had chronic viral hepatitis before treatment, either type B or type C. According to the Child-Pugh classification for liver cirrhosis, 53 patients were in class A and 15 in class B. Fifty-two patients underwent transcatheter arterial chemoembolization with an interval of at least 1 month between transcatheter arterial chemoembolization and 3D-CRT to allow adequate recovery of hepatic function. The mean dose of radiation to the isocenter was 50.2 +/- 5.9 Gy, in daily fractions of 1.8-2Gy. No patient received whole liver irradiation. RILD was defined as Grade 3 or 4 hepatic toxicity according to the Common Toxicity Criteria of the National Cancer Institute. All patients were evaluated for RILD within 4 months of RT completion. Three-dimensional treatment planning with dose-volume histogram analysis of the normal liver was used to compare the dosimetric difference between patients with and without RILD. Maximal likelihood analysis was conducted to obtain the best estimates of parameters of the Lyman NTCP model. Confidence intervals of the fitted parameters were estimated by the profile likelihood method. RESULTS: Twelve of the 68 patients developed RILD after 3D-CRT. None of the patient-related variables were significantly associated with RILD. No difference was found in tumor volume (780 cm(3) vs. 737 cm(3), p = 0.86), normal liver volume (1210 cm(3) vs. 1153 cm(3), p = 0.64), percentage of normal liver volume with radiation dose >30 Gy (V(30 Gy); 42% vs. 33%, p = 0.05), and percentage of normal liver volume with >50% of the isocenter dose (V(50%); 45% vs. 36%, p = 0.06) between patients with and without RILD. The mean hepatic dose was significantly higher in patients with RILD (2504 cGy vs. 1965 cGy, p = 0.02). The probability of RILD in patients could be expressed as follows: probability = 1/[1 + exp(-(0.12 x mean dose - 4.29))], with coefficients significantly different from 0. The best estimates of the parameters in the Lyman NTCP model were the volume effect parameter of 0.40, curve steepness parameter of 0.26, and 50% tolerance dose for uniform irradiation of whole liver [TD(50)(1)] of 43 Gy. Patients with RILD had a significantly higher NTCP than did those with no RILD (26.2% vs. 15.8%; p = 0.006), using the best-estimated parameters. CONCLUSION: Dose-volume histogram analysis can be effectively used to quantify the tolerance of the liver to RT. Patients with RILD had received a significantly higher mean dose to the liver and a significantly higher NTCP. The fitted volume effect parameter of the Lyman NTCP model was close to that from the literature, but much lower in our patients with HCC and prevalent chronic viral hepatitis than that reported in other series with patients with normal liver function. Additional efforts should be made to test other models to describe the radiation tolerance of the liver for Asian patients with HCC and preexisting compromised hepatic reserve.

27
UI - 12020669
AU - Fan MH; Chang AE
TI - Resection of liver tumors: technical aspects.
SO - Surg Oncol 2002 May;10(4):139-52
AD - Division of Surgical Oncology, 3302 Cancer Center, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor 48109, USA.
The resection of primary and secondary liver tumors has become accepted as the only curative therapy that can be offered to patients with these cancers. Techn

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