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

National Cancer Institute^®

Percutaneous radiofrequency thermal ablation of liver malignancies: techniques, indications, imaging findings, and clinical results.
Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns.
Transplantation for liver tumors: current status.
CT-guided transthoracic percutaneous ethanol injection for hepatocellular carcinoma not detectable with US.
Hepatocellular carcinoma: diagnosis and treatment.
Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter.
Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the
Three-dimensional conformal radiation therapy and periodic irradiation with the deep insipration breath-hold technique for hepatocellular
Hepatocellular carcinoma.
[Prevention of liver neoplasms]
Hepatocellular carcinoma: a prime indication for living donor liver transplantation.
Cryosurgery after chemoembolization for hepatocellular carcinoma in patients with cirrhosis.
Liver resection for cancer.
[Departmental review of surgical cases in the last 17 years: Liver neoplasms]
Comparison of techniques for image-guided ablation of focal liver tumors.
Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy.
[When is resection indicated in primary liver tumors?]
Mediation of transcatheter arterial chemoembolization induced gastric slow-wave dysrhythmia by endogenous prostaglandin.
Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization.
Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised
[Arsenic trioxide for the treatment of medium and advanced primary liver cancer]
An increase in body temperature during radiofrequency ablation of liver tumors.
Hepatic vein reconstruction for resection of hepatic tumors.
Treatment of hepatocellular carcinoma with radiofrequency ablation: radiologic-histologic correlation during follow-up periods.
Transplantation of liver grafts from living donors into adults.
Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation.
Local, intrahepatic, and systemic recurrence patterns after radiofrequency ablation of hepatic malignancies.
Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells.
Advances in the treatment of liver tumors.
Cytologic changes in small hepatocellular carcinomas after radiofrequency ablation.
Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?
Unresectable hepatocellular carcinoma: the need for an individualized multidisciplinary approach.
Candidates for liver transplantation for cancer: physical, psychological, and social conditions.
Ultra-low-dose interleukin-2 in unresectable hepatocellular carcinoma.
[Catheter placement in the right gastroepiploic artery without fixation using a W spiral catheter for implantable reservoir therapy of malignant

1
UI - 11441546
AU - Lencioni R; Cioni D; Bartolozzi C
TI - Percutaneous radiofrequency thermal ablation of liver malignancies: techniques, indications, imaging findings, and clinical results.
SO - Abdom Imaging 2001 Jul-Aug;26(4):345-60
AD - Division of Diagnostic and Interventional Radiology, Department of Oncology, Transplants, and Advanced Technologies in Medicine, University of Pisa, Via Roma 67, I-56125 Pisa, Italy.

2
UI - 11441549
AU - Catalano O; Lobianco R; Esposito M; Siani A
TI - Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns.
SO - Abdom Imaging 2001 Jul-Aug;26(4):375-83
AD - Department of Radiology, S. Maria delle Grazie Hospital, via Domitiana Loc. La Schiana, Pozzuoli, Naples I-80078, Italy.
BACKGROUND: To categorize the helical computed tomographic (CT) intrahepatic recurrence patterns of hepatocellular carcinoma (HCC) after treatment with percutaneous ablation procedures. METHODS: Double-phase helical CT studies of 67 patients with HCC recurrence were reviewed. The study population had undergone percutaneous ablation therapy procedures (multisession or single-session ethanol injection therapy, radiofrequency thermal ablation therapy, and interstitial laser photocoagulation therapy) for 120 HCC nodules. RESULTS: Four patterns were defined. (A) Enhancing tissue within the edge of the ablated nodule on arterial phase images (ingrowth): this pattern was seen in five treated lesions (4.2% of all treated nodules) in five patients (7.5% of all patients with recurrence) 3-7 months after treatment (mean = 4 months). (B) Enhancing tissue around the treated nodule but continuously to its border on arterial-phase images (outgrowth): this pattern was found in 12 (10%) treated lesions in 12 patients (18%) 3-6 months after ablation (mean = 4 months). (C) Enhancing tissue within the same segment of the treated nodule on arterial phase images (spread): this pattern was detected in 10 (8%) treated lesions in 10 patients (15%) 3-6 months after treatment (mean = 5 months). (D) Enhancing tissue within different segments from the treated nodule on arterial phase images (progression): this pattern was identified in 34 patients (51%) with 53 (44%) treated tumors 5-22 months after ablation (mean = 8 months). A mixed pattern was found in six subjects (9%) with seven (6%) treated nodules. Among the 61 patients with a nonmixed pattern, there were 85 treated nodules with persistent necrosis, 17 treated nodules with local recurrence (pattern A or B), and 107 new nodules due to nonlocal recurrence (pattern C or D). Portal phase enhanced images and especially unenhanced images showed a lower detection rate and a lower lesion-to-liver conspicuity score (for all patterns but mainly for pattern C). CONCLUSION: Four patterns of recurrence after percutaneous ablation procedures can be categorized on double-phase helical CT and are best depicted on arterial phase images. Knowledge of these patterns is relevant for early detection and may be helpful in understanding the recurrence mechanism.

3
UI - 11906612
AU - Ringe B
TI - Transplantation for liver tumors: current status.
SO - Liver 2002 Feb;22(1):1-7
AD - Klinik fur Transplantationschirurgie, Georg-August Universitat Gottingen, Gottingen, Germany. bringe@med.uni-gottingen.de
The question of liver transplantation for hepatobiliary malignancy has continued to generate controversial discussion. As shown by single-center studies and large databases, there is a clear indication for total hepatectomy and liver replacement under the premises of appropriate selection of suitable patients as well as of favorable type and stage of tumors. Future improvement of tumor-free patient survival can be expected from better understanding of tumor biology, including prevention and earlier detection of cancer, and effective multimodality treatment strategies.

4
UI - 11930055
AU - Shibata T; Iimuro Y; Yamamoto Y; Ikai I; Itoh K; Maetani Y; Ametani F;
TI - Kubo T; Konishi J CT-guided transthoracic percutaneous ethanol injection for hepatocellular carcinoma not detectable with US.
SO - Radiology 2002 Apr;223(1):115-20
AD - Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Shogoin, Sakyoku, Kyoto 606-8507, Japan.
PURPOSE: To evaluate the safety and effectiveness of computed tomography (CT)-guided percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) not detectable with ultrasonography (US). with 57 HCC nodules not detectable with US underwent CT-guided transthoracic PEI. Complications associated with the transthoracic approach, effectiveness of transthoracic PEI, and prognosis of the patients were evaluated. RESULTS: Seventy-one PEI sessions were performed for 57 nodules. Complications included pneumothorax in 21 sessions (30%) for 19 nodules (33%), moderate pleural effusion in four sessions (6%) for four nodules (7%), and hemoptysis in three sessions (4%) for two nodules (4%). A chest tube was required for pneumothorax in five sessions (7%) for five nodules (9%), and pleural effusion drainage was performed in two sessions (3%) for two nodules (4%). Apparent tumor necrosis was noted at CT in 51 nodules (89%). During follow-up (range, 3 months to 5(1/2) years; mean, 29 months +/- 18 [SD]), local recurrence was seen in seven nodules (12%), three of which received repeat treatment with transthoracic PEI. Twenty-six patients survived, and 25 patients died of multiple tumors, hepatic failure, or rupture of esophageal varices. CONCLUSION: Transthoracic PEI seems to be relatively safe and effective for the treatment of HCC not detectable with US.

6
UI - 12022599
AU - Poon RT; Fan ST; Wong J
TI - Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter.
SO - J Am Coll Surg 2002 May;194(5):592-602
AD - Centre for the Study of Liver Disease and the Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, China.
BACKGROUND: The role of hepatic resection for large hepatocellular carcinoma (HCC) larger than 10 cm remains unclear. STUDY DESIGN: Perioperative and longterm outcomes of 120 patients with HCC larger than 10 cm who underwent resection (group A) were compared with 368 patients with smaller HCC (group B). The prognostic factors in group A were analyzed. RESULTS: A higher proportion of patients underwent major hepatic resection in group A than in group B (90% versus 57.6%, p = 0.001), but the hospital mortality was similar (5.0% versus 4.6%, p = 0.874). Group A had worse longterm overall survival (median 18.8 months versus 62.8 months, p < 0.001) and disease-free survival (median 5.5 months versus 25.4 months, p < 0.001) than group B. Macroscopic residual tumor, macroscopic venous invasion, and multiple tumors were identified as independent prognostic factors in group A. The median survival of patients with residual tumor and those with curative resection was 7.7 months and 20.8 months, respectively. The median survival of patients with curative resection of solitary HCC larger than 10cm without macroscopic venous invasion was 38.0 months; that of patients with both macroscopic venous invasion and multiple tumors was only 10.5 months. CONCLUSIONS: Hepatic resection is a safe and effective treatment for HCC larger than 10cm when liver function reserve is satisfactory and when curative resection can be expected. Patients with solitary HCC larger than 10cm without macroscopic venous invasion can enjoy longterm survival after surgery, and we propose hepatic resection as a standard treatment for this group of patients.

7
UI - 12014732
AU - Huang YS; Chiang JH; Wu JC; Chang FY; Lee SD
TI - Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test.
SO - Am J Gastroenterol 2002 May;97(5):1223-7
AD - Department of Medicine, Taipei Veterans General Hospital, Taiwan.
OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. METHODS: One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide oncentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. RESULTS: Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7+/-5.8 vs 43.9+/-13.2 ng/ml), Child-Pugh score (6.9+/-0.6 vs 6.0+/-0.7), indocyanine green retention ratio at 15 min (32.4+/-6.5% vs 15.7+/-5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07-2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. CONCLUSIONS: As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.

8
UI - 11999815
AU - Pattaranutaporn P; Chansilpa Y; Ieumwananonthachai N; Kakanaporn C;
TI - Onnomdee K; Mungkung N; Santisiri R Three-dimensional conformal radiation therapy and periodic irradiation with the deep insipration breath-hold technique for hepatocellular carcinoma.
SO - J Med Assoc Thai 2001 Dec;84(12):1692-700
AD - Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol Univesity, Bangkok, Thailand.
Nine cases of primary hepatocellular carcinoma were treated with 3D-conformal radiation therapy using computerized planning system. This technique permits the precise delivery of a high dose of radiation to the target while sparing most of the normal liver tissue. In order to decrease the effect of organ movement related to respiration, periodical irradiation was combined with the deep inspiration breath-hold technique. The radiation dose was equivalent to conventional radiation with a total dose of 50-70 Gy with 2 Gy, 5 times a week. Irradiation was given in 1-10 fractions which encompassed the target with 90 per cent isodose line. The patients tolerated the treatment procedure well without any complications inherent to the technique. The tumors were decreased in size, the pain symptom and abdominal discomfort were relieved for 3-20 months. This technique is an effective and safe treatment for palliation in hepatocellular carcinoma especially in locally advanced stages with large or multiple lesions. However, long term follow-up should be done to evaluate the late radiation effect and clinical outcome.

9
UI - 11889672
AU - Desjardins LA
TI - Hepatocellular carcinoma.
SO - Clin J Oncol Nurs 2002 Mar-Apr;6(2):107-8
AD - LDesjardins@NYC.RR.com
Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a disease of multifactorial etiology. Strong correlations exist between the prevalence of the hepatitis B and C viruses and HCC incidence. HCC treatment may involve surgical resection, liver transplantation, locoregional treatments, and chemotherapy. Prevention of virus-related HCC is contingent upon control of hepatitis types B and C. Universal vaccination against hepatitis B could eliminate hepatitis B-related HCC; however, hepatitis C-related HCC still could occur because a vaccine for hepatitis C currently is not available. Individuals at risk for HCC should be screened for the disease. Early detection could result in improved prognosis and survival.

10
UI - 11989264
AU - Moriwaki H
TI - [Prevention of liver neoplasms]
SO - Nippon Naika Gakkai Zasshi 2002 Mar 20;91 Suppl():63-6

11
UI - 11986025
AU - Gondolesi G; Munoz L; Matsumoto C; Fishbein T; Sheiner P; Emre S; Miller
TI - C; Schwartz ME Hepatocellular carcinoma: a prime indication for living donor liver transplantation.
SO - J Gastrointest Surg 2002 Jan-Feb;6(1):102-7
AD - Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY 10029, USA.
Cadaveric liver transplantation for hepatocellular carcinoma (HCC) is limited by donor organ availability. This report reviews our initial experience with living donor liver transplantation (LDLT) for HCC. Since Underlying diagnoses included hepatitis C in 17, hepatitis B in eight, cryptogenic cirrhosis in one, and primary biliary cirrhosis in one. Four patients had recurrent HCC after resection. Patients with tumors measuring 5 cm or larger received a single dose of intravenous doxorubicin intraoperatively and six cycles of doxorubicin at 3-week intervals beginning 6 weeks postoperatively. All HCC patients are followed with CT scans and alpha-fetoprotein measurements every 3 months during the first 2 years after transplant. Mean waiting time to transplant for patients with HCC was 83 days, compared to 414 (P = 0.001) days for 50 patients with HCC who were transplanted with cadaveric organs during this period. At median follow-up of 236 days, there have been four deaths due to non-tumor-related causes and one death from recurrence; recurrence has been observed in one other patient. LDLT permits expeditious transplantation in patients with early HCC, and provides access to transplantation for patients with HCC exceeding the United Network of Organ Sharing criteria for prioritization who are, in effect, barred from receiving cadaveric organs.

12
UI - 11986024
AU - Clavien PA; Kang KJ; Selzner N; Morse MA; Suhocki PV
TI - Cryosurgery after chemoembolization for hepatocellular carcinoma in patients with cirrhosis.
SO - J Gastrointest Surg 2002 Jan-Feb;6(1):95-101
AD - Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Duke University Medical Center, Durham, NC, USA. clavien@chi.unizh.ch
Most cirrhotic patients with hepatocellular carcinoma (HCC) are not candidates for resection. Transarterial chemoembolization (TACE) may ablate a significant portion of the tumor but has a high rate of recurrence. Cryosurgery may permit successful ablation of hepatic tumors but can be complicated by postoperative hemorrhage and is also associated with a significant risk of recurrence. The combination of the two techniques might be beneficial. We evaluated in a prospective study the safety and efficacy of this combination in cirrhotic patients with unresectable HCC. Fifteen patients were included in this study. All but one patient underwent one or several sessions of TACE before cryosurgery. Cryoablation was successfully performed in each patient. The patient who did not undergo preoperative TACE required reoperation for hemorrhage. Another patient with Child-Pugh class B cirrhosis died postoperatively of hepatic and multiorgan failure. At a mean follow-up of 2.5 years, three patients had recurrence of disease, and 13 of 15 patients were alive with the longest survival time being 5 years. The actuarial survival rate at 5 years was 79%. Cryosurgery after TACE is feasible in cirrhotic livers with HCC and can increase the cure rate in large tumors. TACE may reduce the risk of hemorrhage after cryosurgery but can increase the risk of hepatic failure in patients with poor hepatic function.

13
UI - 11854897
AU - Parks RW; Garden OJ
TI - Liver resection for cancer.
SO - World J Gastroenterol 2001 Dec;7(6):766-71
AD - Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary of Edinburgh, UK. r.w.parks@ed.ac.uk

14
UI - 11989235
AU - Shimada M; Shirabe T; Tanaka S; Maeda T; Yamashita Y; Rikimaru T;
TI - Tsujita H; Maehara S; Harimoto N; Ikeda Y; Ashidate H; Utsunomiya T; Esaki T; Furuta T; Sonoda T; Matsumata T; Takenaka K; Kanematsu T [Departmental review of surgical cases in the last 17 years: Liver neoplasms]
SO - Fukuoka Igaku Zasshi 2002 Mar;93(3 Suppl):16-9

15
UI - 11997528
AU - Goldberg SN
TI - Comparison of techniques for image-guided ablation of focal liver tumors.
SO - Radiology 2002 May;223(2):304-7

16
UI - 11997534
AU - Shibata T; Iimuro Y; Yamamoto Y; Maetani Y; Ametani F; Itoh K; Konishi J
TI - Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy.
SO - Radiology 2002 May;223(2):331-7
AD - Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54-Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan. ksj@kuhp.kyoto-u.ac.jp
PURPOSE: To evaluate the effectiveness of radio-frequency (RF) ablation and percutaneous microwave coagulation (PMC) for treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy-two patients with 94 HCC nodules were randomly assigned to RF ablation and PMC groups. Thirty-six patients with 48 nodules were treated with RF ablation, and 36 patients with 46 nodules were treated with PMC. Therapeutic effect, residual foci of untreated disease, and complications of RF ablation and PMC were prospectively evaluated with statistical analyses. RESULTS: The number of treatment sessions per nodule was significantly lower in the RF ablation group than in the PMC group (1.1 vs 2.4; P <.001). Complete therapeutic effect was achieved in 46 (96%) of 48 nodules treated with RF ablation and in 41 (89%) of 46 nodules treated with PMC (P =.26). Major complications occurred in one patient treated with RF ablation and in four patients treated with PMC (P =.36). During follow-up (range, 6-27 months), residual foci of untreated disease were seen in four of 48 nodules treated with RF ablation and in eight of 46 nodules treated with PMC. No significant difference in rates of residual foci of untreated disease was noted (P =.20, log-rank test). CONCLUSION: RF ablation and PMC thus far have had equivalent therapeutic effects, complication rates, and rates of residual foci of untreated disease. However, RF tumor ablation can be achieved with fewer sessions. Copyright RSNA, 2002

17
UI - 12030052
AU - Vyhnanek F; Denemark L; Duchac V; Cap F
TI - [When is resection indicated in primary liver tumors?]
SO - Rozhl Chir 2002 Apr;81(4):196-200
AD - Chirurgicka klinika 3, LF UK, Praha.
The development of hepatic surgery involved also definition of indications for resection in primary liver tumours. Based on an analysis of a group of 76 patients with primary liver tumours operated in 1978-2001 (up to the end of October) the authors evaluated the indication criteria for resection of primary hepatic tumours. As to benign tumours most frequently haemangiomas were resected (in 35 patients) and follicular nodular hyperplasia in 10 patients. Indication for resection was the symptomatology of the tumour (40x), signs of progression during a check-up examination (13x) or doubts as regards preoperative ruling out of malignity (16x). Hepatocellular adenoma was resected in 8 patients, incl. 7 where the preoperative diagnosis was assessed by bioptic examination. The extent of resection depended on the size and site of the tumour, in haemangiomas and follicular nodular hyperplasia non-anatomical resections predominated (in 27 patients). On account of hepatocellular carcinoma resections were made in 18 patients, incl. 8 who suffered also from cirrhosis which limited the extent of resection. In patients without cirrhosis with carcinoma in one of the lobes an anatomical resection was implemented. Postoperative complications developed in 14 patients (18%), two died (3%) from hepatic failure and pulmonary embolism.

18
UI - 11895552
AU - Chang CS; Yang SS; Yeh HZ; Ko CW; Lien HC; Chen GH
TI - Mediation of transcatheter arterial chemoembolization induced gastric slow-wave dysrhythmia by endogenous prostaglandin.
SO - J Gastroenterol Hepatol 2002 Jan;17(1):46-51
AD - Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan. changcs.vghtc.vghtc.gov.tw
BACKGROUND AND AIMS: In recent years, gastric slow-wave dysrhythmias induced by transcatheter arterial chemoembolization (TACE) have been observed. Enhanced endogenous prostaglandin may be a possible mechanism for the myoelectrical changes. The aim of this study was to evaluate whether the gastric slow-wave dysrhythmias induced by TACE may be mediated by ketoprofen, a prostaglandin synthesis inhibitor. METHODS: Twenty-three patients with hepatocellular carcinoma (HCC) admitted for TACE were enrolled. A follow-up TACE was scheduled to take place 2 months later. During the next admission for TACE, 50 mg of ketoprofen was given intramuscularly 12 h for 3 days, beginning 48 h before TACE, as premedication. Cutaneous electrogastrography (EGG) was performed before and within 24 h after TACE. RESULTS: The results showed that the change in the fasting EGG parameters after TACE without premedication was not statistically significant. However, the postprandial EGG parameters, including the dominant frequency (DF); the percentages of DF in the normal, bradygastric and tachygastric range; along with the dominant frequency instability coefficient, deteriorated significantly after the procedure (P < 0.01). After the follow-up TACE with ketoprofen premedication, neither the fasting nor postprandial EGG parameters in the control group changed significantly. CONCLUSIONS: Gastric slow-wave dysrhythmias induced by TACE may be mediated by ketoprofen, a prostaglandin synthesis inhibitor, in HCC patients. However, the improvement in the gastric myoelectrical activity does not eliminate the degree of nausea/vomiting after TACE.

19
UI - 11895553
AU - Lee JK; Chung YH; Song BC; Shin JW; Choi WB; Yang SH; Yoon HK; Sung KB;
TI - Lee YS; Suh DJ Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization.
SO - J Gastroenterol Hepatol 2002 Jan;17(1):52-8
AD - Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
BACKGROUND AND AIMS: The aim of this study was: (i) to define the characteristics of hepatocellular carcinoma (HCC) associated with recurrences following initial remission by transcatheter arterial chemoembolization (TACE); (ii) to evaluate the patterns of recurrences; and (iii) find a better surveillance method of detecting recurrent HCC. METHODS: Out of 230 consecutive HCC patients who underwent TACE, 77 with initial remission were followed prospectively for at least 12 months. We compared the recurrence rates according to the characteristics of the tumors and analyzed the locations of the recurrent HCC. The diagnostic efficacies of CT scans with serum AFP, angiography and Lipiodol CT scan in detecting recurrent HCC were also evaluated. RESULTS: Recurrent HCC was detected in 40 patients during a median period of 27 months. The recurrence rate of multinodular HCC was higher than the single nodular type. All six patients with portal vein thrombosis recurred. Even though 45% of recurrences were adjacent to original tumors, 63% were separated from them (8% at both). Hepatocellular carcinoma with heterogeneous Lipiodol uptake tended to recur at the site adjacent to the original tumors more frequently than HCC with homogeneous Lipiodol uptake. Only 18 of 40 recurrent HCC were initially detected by serum alpha-fetoprotein (AFP) and CT scans: 19 by angiography and three only by Lipiodol CT scan. CONCLUSION: Our data indicated that HCC of the multinodular type and with portal vein thrombosis recur more frequently following initial remission by TACE. It is also suggested that regular angiography in addition to serum AFP and CT scan may be valuable in detecting recurrent HCC. Other treatment modalities may need to be combined to ablate tumors completely and to therefore reduce recurrences, especially in HCC with heterogeneous Lipiodol uptake.

20
UI - 12049862
AU - Llovet JM; Real MI; Montana X; Planas R; Coll S; Aponte J; Ayuso C; Sala
TI - M; Muchart J; Sola R; Rodes J; Bruix J; Barcelona Liver Cancer Group Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial.
SO - Lancet 2002 May 18;359(9319):1734-9
AD - Liver Unit, Digestive Disease Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.
BACKGROUND: There is no standard treatment for unresectable hepatocellular carcinoma. Arterial embolisation is widely used, but evidence of survival benefits is lacking. METHODS: We did a randomised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment, of Child-Pugh class A or B and Okuda stage I or II, to assess the survival benefits of regularly repeated arterial embolisation (gelatin sponge) or chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative treatment. 903 patients were assessed, and 112 (12%) patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat. FINDINGS: The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation, and 63% and 27% for control (chemoembolisation vs control p=0.009). Chemoembolisation induced objective responses sustained for at least 6 months in 35% (14)of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81], p=0.02). INTERPRETATION: Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma.

21
UI - 11856508
AU - Qian J; Qin S; He Z; Wang L; Chen Y; Shao Z; Liu X
TI - [Arsenic trioxide for the treatment of medium and advanced primary liver cancer]
SO - Zhonghua Gan Zang Bing Za Zhi 2002 Feb;10(1):63
AD - PLA Cancer Center of the 81st hospital, Nanjing 210002, China.

22
UI - 12031998
AU - Sawada M; Watanabe S; Tsuda H; Kano T
TI - An increase in body temperature during radiofrequency ablation of liver tumors.
SO - Anesth Analg 2002 Jun;94(6):1416-20, table of contents
AD - Department of Anesthesiology, Kurume University School of Medicine, Asahimachi 67, Kurume, Fukuoka 830-0011, Japan. mmss416@hotmail.com
Radiofrequency ablation (RFA) therapy using an active needle electrode inserted into liver tumors has been used clinically. To avoid hyperthermia, we investigated the relationship between the total output energy of the applied radiofrequency wave and changes in body temperature (BT) in patients receiving RFA. Fifteen patients undergoing RFA of liver tumors with general anesthesia were enrolled. The total output energy of radiofrequency waves was calculated from the power and duration of RFA. Changes in rectal (T(rect)) and tympanic temperatures were measured throughout the study. The mean number of liver tumors per patient was 1.7 +/- 1.3. The mean RFA time was 30.0 +/- 26.3 min. The mean total output energy was 125,935 +/- 114,506 J. The mean value of T(rect) increased from 36.3 degrees C +/- 0.5 degrees C to 37.0 degrees C +/- 1.0 degrees C (P < 0.01). A linear correlation was obtained between the total output energy and the changes in T(rect), indicating that T(rect) increased approximately by 1 degrees C for every 3000 J/kg of total output energy. The increase in BT during RFA of liver tumors under general anesthesia is predictable. Close observation of total output energy delivered and BT are required, and preparation of cooling measures is important, in RFA of liver tumors. IMPLICATIONS: The increase in body temperature (BT) is predictable during radiofrequency ablation (RFA) of liver tumors under general anesthesia. Close observation of total output energy delivered and BT are required, and preparation of cooling measures is important, in RFA of liver tumors.

23
UI - 12035042
AU - Hemming AW; Reed AI; Langham MR; Fujita S; van der Werf WJ; Howard RJ
TI - Hepatic vein reconstruction for resection of hepatic tumors.
SO - Ann Surg 2002 Jun;235(6):850-8
AD - Department of Surgery, Center for Hepatobiliary Disease, University of Florida, Gainesville 32610, USA. hemmiaw@surgery.ufl.edu
SUMMARY BACKGROUND DATA: Involvement of the hepatic veins requiring reconstruction has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis poor. Recent advances in liver surgery gleaned from split and live donor liver transplantation that necessitate hepatic vein reconstruction can be applied to hepatic resection in some cases. METHODS: Sixteen patients who underwent hepatic resection requiring hepatic vein reconstruction from 1996-2001 were reviewed. The mean age was 43 years (range 2-61). Nine patients were resected for hepatocellular carcinoma (HCC), five patients for colorectal metastases, and one patient each for hepatoblastoma and cholangiocarcinoma. In six patients with HCC and cirrhosis, the right hepatic vein was reconstructed to provide venous outflow to liver segments not adequately drained by a remaining major hepatic vein. Four of these six patients required the use of Gore-Tex (W. L. Gore & Associates, Inc., Newark, DE) interposition grafts. In the 10 other cases the entire venous outflow from the remnant liver was reconstructed or reimplanted into the inferior vena cava primarily (n = 8) or using segments of the portal vein from the resected side of the liver as a graft (n = 2). Ex-vivo procedures with the use of veno-venous bypass were required in two cases and in-situ cold perfusion of the liver was used in one case. RESULTS: There were two perioperative deaths (12%). One patient died of liver failure 3 weeks after right trisegmentectomy with reconstruction of the left hepatic vein and one patient died at 3 months after resection due to sepsis from a segment of small bowel that perforated into a diaphragmatic hernia. Four patients had evidence of postoperative liver failure that resolved with supportive management and one patient required temporary dialysis. All vascular reconstructions were patent at last followup. With median followup of 23 months, 3 patients have died of recurrent malignancy at 14, 18 and 30 months, while an additional patient went on to die of progressive liver failure at 22 months. Actuarial 1 and 3 year survival was 88% and 50% respectively. CONCLUSION: Hepatic vein involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the hepatic veins can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.

24
UI - 12029632
AU - Morimoto M; Sugimori K; Shirato K; Kokawa A; Tomita N; Saito T; Tanaka
TI - N; Nozawa A; Hara M; Sekihara H; Shimada H; Imada T; Tanaka K Treatment of hepatocellular carcinoma with radiofrequency ablation: radiologic-histologic correlation during follow-up periods.
SO - Hepatology 2002 Jun;35(6):1467-75
AD - Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
To determine whether radiographic images after radiofrequency (RF)-induced coagulation necrosis are correlated with the pathologic effects, we evaluated the morphology and histologic characteristics of RF ablation lesions over a 6-month follow-up period and compared the results with those of radiologic studies. Thirty-three hepatocellular carcinoma (HCC) tumors with a maximum diameter of 3 cm or less were treated percutaneously by using RF ablation in 26 patients. Six treated tumors were resected 4 weeks after ablation; the remaining 27 treated tumors underwent a biopsy procedure by using an 18-gauge fine needle 3 days, 4 weeks, and 24 weeks after ablation. The excised or biopsied lesions were examined by using histologic methods; the findings were then compared with those of contrast-enhanced computed tomography (CT). Three days after ablation, a core of hypoattenuation surrounded by an enhanced/hemorrhagic rim was observed on the contrast-enhanced CT images. Hematoxylin-eosin-stained specimens were inconclusive as to whether or not cellular viability remained; however, cell viability as determined by the presence of histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and the reduced form of nicotinamide-adenine dinucleotide phosphate [NADPH]-diaphorase) stains was absent, suggesting 100% cellular destruction in the ablated lesion. Four and 24 weeks after ablation, the sizes of the ablated lesions were progressively smaller on the CT images; the histochemical stains remained superior to the hematoxylin-eosin stains for obtaining a definite diagnosis of cell death. We conclude that irreversible cellular destruction, as determined by the absence of positive histochemical staining patterns, was useful for evaluating the pathologic thermal effect of RF ablation. These pathologic findings can be correlated with those of contrast-enhanced CT.

25
UI - 11565532
AU - Shaked A; Lucey MR
TI - Transplantation of liver grafts from living donors into adults.
SO - N Engl J Med 2001 Sep 20;345(12):923-4

27
UI - 11992812
AU - Kosari K; Gomes M; Hunter D; Hess DJ; Greeno E; Sielaff TD
TI - Local, intrahepatic, and systemic recurrence patterns after radiofrequency ablation of hepatic malignancies.
SO - J Gastrointest Surg 2002 Mar-Apr;6(2):255-63
AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
The objective of this study was to describe the recurrence patterns in patients with unresectable hepatic malignancies treated with radiofrequency ablation (RFA). As RFA is applied more widely to patients with hepatic tumors, a better understanding of the biologic behavior of these tumors and the risk of recurrence, both in the liver and systemically, is needed. A multidisciplinary team evaluated patients referred for RFA and followed them prospectively to assess local, intrahepatic, and extrahepatic disease recurrence and complication rates. Forty-five patients with 143 lesions and a minimum follow-up of 6 months (median 19.5 months) were treated. Overall, 7.7% of treated lesions had local recurrence. New intrahepatic disease was seen in 49% of patients, and 24% had evidence of new systemic tumor progression. Patients with colorectal metastatic lesions > or =4 cm at the time of the first RFA were more likely to present with local recurrence (P = 0.048). Complications occurred in 27% of patients. Although RFA has a satisfactory local failure rate and safety profile, the patient population being treated is at high risk of developing new disease. Multimodality adjuvant therapy will be necessary to realize the full potential of hepatic malignancy control with RFA.

28
UI - 12017300
AU - Liu JJ; Wang JY; Hertervig E; Nilsson A; Duan RD
TI - Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells.
SO - Anticancer Res 2002 Jan-Feb;22(1A):263-6
AD - Cell Biology B, Biomedical Center, University of Lund, Sweden.
BACKGROUND: It has recently been reported that sulindac has an apoptotic effect on KYN-2 cells, an undifferentiated hepatoma cell line. The present work investigates whether sulindac also has an apoptotic effect on well-differentiated hepatoma cells and what its potential mechanism might be. MATERIALS AND METHODS: Hep G2 cells were treated with sulindac at different concentrations. Apoptosis rate, cell proliferation and 3H-thymidine incorporation were measured. The activities of caspase-3, acid and neutral sphingomyelinase and the changes of sphingomyelin content were also assayed. RESULTS: Sulindac dose-dependently induced apoptosis in Hep G2 cells; both sulindac sulfone and sulfide had similar effects. The apoptosis was accompanied by an increase of caspase-3 activity and a decrease of cell proliferation and 3H-thymidine incorporation. No significant change could be observed for the activity of sphingomyelinase and sphingomyelin content. CONCLUSION: Sulindac induces apoptosis and inhibits proliferation in Hep G2 cells. The effect may be mediated by a pathway related to caspase-3 activation but independent of sphingomyelin metabolism

29
UI - 12019420
AU - Curley SA; Cusack JC Jr; Tanabe KK; Ellis LM
TI - Advances in the treatment of liver tumors.
SO - Curr Probl Surg 2002 May;39(5):449-571
AD - The University of Texas M.D. Anderson Cancer Center, Houston, USA.

30
UI - 12040642
AU - Lin SM; Shen CH; Lin DY; Kuo SH; Lin CJ; Hsu CW; Chung HJ; Peng CY
TI - Cytologic changes in small hepatocellular carcinomas after radiofrequency ablation.
SO - Acta Cytol 2002 May-Jun;46(3):490-4
AD - Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
OBJECTIVE: To illustrate the cytologic changes in hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). STUDY DESIGN: The study included 20 patients with 23 HCC who had undergone RFA under ultrasound guidance. Baseline cytomorphology of HCC was evaluated by fine needle aspiration (FNA) in all cases. Triphasic helical computed tomography (CT) and FNA cytology were done to evaluate the efficacy of the treatment within two weeks after RFA. The cytologic specimens were stained with Riu's method (Romanowsky stain). RESULTS: A range of cytologic findings after RFA was found, including granular and amorphous debris with artefactual aggregation, degenerated cells or necrotic material, and dyshesive, degenerated cells in a necrotic background. The cytologic patterns included necrotic cells and debris in 14 tumors and fine, granular necrosis in 9. Helical CT showed no enhancement in any of the tumors after RFA. CONCLUSION: The cell patterns indicated complete necrosis in HCC after RFA.

31
UI - 11319307
AU - Trevisani F; De Notariis S; Rossi C; Bernardi M
TI - Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies?
SO - J Clin Gastroenterol 2001 May-Jun;32(5):383-9
AD - Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Universita di Bologna, Bologna, Italy.
Hepatocellular carcinoma (HCC) generally occurs in patients with cirrhosis. Curative options, such as liver transplantation, hepatic resection, and percutaneous alcohol injection, are applicable to a minority of cases. Because systemic chemotherapy and radiation therapy provide dismal results, transarterial chemoembolization (TACE) remains the sole approach to antagonizing the cancer growth in most patients. Although most tumors show an extensive necrosis after TACE, the beneficial effect on survival has not been properly substantiated, so that its application still remains a matter of debate. This review analyzes the results of randomized clinical trials on TACE. In most studies, TACE did not increase the survival of patients as compared with the palliative treatment. However, several methodologic and technical pitfalls may have adversely affected the results of these trials, such as inadequate patient selection and statistical power of the study design, a nonoptimal procedure, and treatment repetition not tailored to the cancer response and patient tolerance. Nonetheless, the literature will hardly be enriched by new trials including untreated patients because, wrong or right, TACE is currently considered the standard treatment of unresectable HCC. It seems more realistic to expect randomized studies comparing different techniques and time schedules of treatment, as well as TACE alone versus combined procedures.

32
UI - 11500603
AU - Levy AE; Kowdley KV
TI - Unresectable hepatocellular carcinoma: the need for an individualized multidisciplinary approach.
SO - J Clin Gastroenterol 2001 Sep;33(3):180-2

33
UI - 12042651
AU - Gangeri L; Tamburini M; Borreani C; Brunelli C; Miccinesi G; Murru L;
TI - Boeri P; Mazzaferro V Candidates for liver transplantation for cancer: physical, psychological, and social conditions.
SO - Transplantation 2002 May 27;73(10):1627-35
AD - Psychology and Liver Surgery and Transplantation Units, National Cancer Institute, 20133 Milan, Italy. gangeri@istitutotumori.mi.it
BACKGROUND: There is little knowledge of the psychological and social conditions of candidates for liver transplantation and the meaning that these patients attribute to those conditions. METHODS: The research has been conducted with quantitative and qualitative methods. For the quantitative study, 80 patients were assessed with four evaluation instruments: the Interdisciplinary Group for Cancer Care Evaluation in Italy (GIVIO) questionnaire for quality of life, the Needs Evaluation Questionnaire (NEQ) for psychosocial needs, the Minnesota Multiphasic Personality Inventory (MMPI) personality test, and a questionnaire for the family's reactions to the illness. The qualitative evaluation was conducted to better understand the meaning of the transplantation as expressed by the patients, the integration of the new organ, and the symbolic relationship with the donor with particular attention to the different levels of patients' awareness. RESULTS: The quantitative evaluation showed a good level of quality of life assessed by GIVIO and

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