National Cancer Institute®
Last Modified: April 1, 2002
UI - 11593513
AU - Cao X; He N; Sun J; Tan J; Zhang C; Yang J; Lu T; Li J
TI - Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of primary liver cancer.
SO - Chin Med J (Engl) 1999 May;112(5):430-2
AD - Department of Radiology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
OBJECTIVE: To study the clinical results of hepatic radioembolization with Yttrium-90 (90Y) glass microspheres in the treatment of primary liver cancer. METHODS: Seventeen patients with liver cancer were treated radioembolization with 90Y and lipiodol-ultrafluid was used. Percutaneous port-catheter system (PCS) implantations via femoral artery were performed in 12 patients. RESULTS: In the 17 patients, their mean ratio of absorbed doses between tumor and normal liver was 2.4:1. CT showed a significant reduction in tumor size in 11 of the 17 patients. Average survival was 19.5 months. The indwelling catheters of all the 12 patients were patent and no catheter tip locations were found. CONCLUSIONS: 90Y glass microsphere is one of the best radioisotopes. Not only good responses to the therapy of 90Y glass microspheres can be achieved in patients with metastatic liver cancer, but also in those with primary liver cancer, specially the localized or hypervascular mass. The patients with massive arterioportal shunt should not be limited to this form of radiation therapy. The percutaneous PCS implantation via the femoral artery is a new passageway for the treatment of primary liver cancer with 90Y glass microspheres and other interventional therapy.
UI - 11780473
AU - Ho S; Lau WY; Leung WT
TI - Comments on "Hepatic radioembolization with yttrium-90 glass microspheres for treatment of primary liver cancer" by Cao et al, Chin Med J 1999; 112: 430-432.
SO - Chin Med J (Engl) 2001 Apr;114(4):433-4
UI - 11862430
AU - Ueno H; Okada S; Okusaka T; Ikeda M; Kuriyama H
TI - Phase I and pharmacokinetic study of 5-fluorouracil administered by 5-day continuous infusion in patients with hepatocellular carcinoma.
SO - Cancer Chemother Pharmacol 2002 Feb;49(2):155-60
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. email@example.com
PURPOSE: In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated. METHODS: Patients with hepatocellular carcinoma no longer amenable to established forms of treatment were eligible for the study. The starting dose of 5-fluorouracil was 300 mg/m(2) per day and doses were escalated in 50 mg/m(2) per day increments in successive cohorts of three new patients if tolerated. Pharmacokinetic studies were performed at the time of the first course of therapy. RESULTS: Enrolled in the study were 20 patients. The maximum tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity was stomatitis. Other toxicities were mild and well tolerated. Age, gender and associated liver cirrhosis were significant factors influencing 5-fluorouracil clearance. With regard to biochemical parameters, serum alanine aminotransferase and cholesterol levels were correlated with 5-fluorouracil clearance. CONCLUSIONS: The maximum tolerated dose for 5-day continuous infusion of 5-fluorouracil in hepatocellular carcinoma patients was 500 mg/m(2) per day. The recommended dose for phase II studies using this schedule is 450 mg/m(2) per day. Furthermore, the pharmacokinetic data obtained in this study may be useful in determining chemotherapy dosage adjustments for reduction of toxicity.
UI - 11247073
AU - Penchev R
TI - [Two-year experience with the jet dissector "Parenchymotome 01" in clinical practice]
SO - Khirurgiia (Sofiia) 1998;53(6):52-6
AD - Military Medical Academy, Clinic of General Surgery, Sofia, Bulgaria.
UI - 11672831
AU - Colombo M
TI - Treatment of hepatocellular carcinoma.
SO - Antiviral Res 2001 Nov;52(2):209-15
AD - Department of Hepatology, IRCCS Maggiore Hospital, University of Milan, Via Pace No. 9, 20122 Milan, Italy. firstname.lastname@example.org
Treatment options have largely been selected according to empirical criteria, such as the presence or absence of cirrhosis, number and size of tumors, and degree of hepatic deterioration and taking into account the local technological and economic resources. There are virtually no controlled studies comparing the efficacy of the available treatments, and the substantial heterogeneity of survival between control groups does not allow us to obtain therapeutic evaluation by comparing results of separate trials. The reassessment of treatment outcomes on the basis of intention-to-treat analysis yielded less encouraging figures. Hepatic resection is the primary option for the few patients with a hepatocellular carcinoma arising in a normal liver with well-preserved hepatic function and for patients with a single tumor, compensated cirrhosis and low portal hypertension who are not candidable to liver transplantation. The latter is the best treatment modality for patients with a solitary tumor <5 cm in diameter or patients with less than three tumors <3 cm, resulting in a 5-year survival of 75%. Locoregional ablative treatments are curative options for patients with a "resectable" tumor who cannot be offered transplantation or hepatic resection. The 5-year survival is approximately 50% but it copes with a high risk of tumor recurrence. Patients with advanced tumor disease cannot be offered curative treatments but only symptomatic treatments.
UI - 11905412
AU - Leung TW; Tang AM; Zee B; Yu SC; Lai PB; Lau WY; Johnson PJ
TI - Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy.
SO - Cancer 2002 Jan 15;94(2):421-7
AD - Department of Clinical Oncology, The Chinese University of Hong Kong, SAR. email@example.com
BACKGROUND: The objective of the current study was to identify patient and disease related factors that influence response and survival for patients with unresectable hepatocellular carcinoma (HCC) who received a systemic combination chemotherapy consisting of cisplatin, alpha-interferon, doxorubicin, and 5-fluorouracil (PIAF). METHODS: From treated with PIAF: cisplatin (20mg/m2 intravenously, Days 1-4), doxorubicin (40mg/m2 intravenously, Day 1), 5-fluorouracil (400mg/m2 intravenously, Days 1-4), and alpha-interferon (5MU/m2 subcutaneously, Days 1-4), once every 3 weeks up to a maximum of six cycles. Univariate and multivariate analyses of patient and disease characteristics were used to identify factors predicting response and survival. RESULTS: The objective response rate according to conventional criteria was 16.8% (complete response in 3 out of 149 patients, or 2%, 95% confidence interval [CI] 0-4.3%; partial response in 22 out of 149 patients, or 14.8%, 95% CI 9-20%). The median survival time was 30.9 weeks (95% CI 22.1 to 40). Significant independent predictors of an objective response were: absence of cirrhosis (P = 0.006), low bilirubin level (P = 0.006), and positive hepatitis C serology (P = 0.025). The following factors were related to a shorter survival time: high Okuda stage (P = 0.001), vascular involvement (P = 0.018), and cirrhosis (P = 0.008). Good risk patients (absence of cirrhosis and total bilirubin < or = 0.6mg/dL) had an objective response rate of 50%. CONCLUSIONS. Patients with unresectable HCC who also have normal total bilirubin and non-cirrhotic livers have a better chance of response and prolonged survival after treatment with systemic PIAF.
UI - 11900230
AU - Wood BJ; Ramkaransingh JR; Fojo T; Walther MM; Libutti SK
TI - Percutaneous tumor ablation with radiofrequency.
SO - Cancer 2002 Jan 15;94(2):443-51
AD - Diagnostic Radiology Department, Special Procedures Division, National Institutes of Health Clinical Center, Bethesda, Maryland 20892, USA. firstname.lastname@example.org
BACKGROUND: Radiofrequency thermal ablation (RFA) is a new minimally invasive treatment for localized cancer. Minimally invasive surgical options require less resources, time, recovery, and cost, and often offer reduced morbidity and mortality, compared with more invasive methods. To be useful, image-guided, minimally invasive, local treatments will have to meet those expectations without sacrificing efficacy. METHODS: Image-guided, local cancer treatment relies on the assumption that local disease control may improve survival. Recent developments in ablative techniques are being applied to patients with inoperable, small, or solitary liver tumors, recurrent metachronous hereditary renal cell carcinoma, and neoplasms in the bone, lung, breast, and adrenal gland. RESULTS: Recent refinements in ablation technology enable large tumor volumes to be treated with image-guided needle placement, either percutaneously, laparoscopically, or with open surgery. Local disease control potentially could result in improved survival, or enhanced operability. CONCLUSIONS: Consensus indications in oncology are ill-defined, despite widespread proliferation of the technology. A brief review is presented of the current status of image-guided tumor ablation therapy. More rigorous scientific review, long-term follow-up, and randomized prospective trials are needed to help define the role of RFA in oncology.
UI - 11865373
AU - Liu CL; Fan ST; Lo CM; Ng IO; Poon RT; Wong J
TI - Intraoperative iatrogenic rupture of hepatocellular carcinoma.
SO - World J Surg 2002 Mar;26(3):348-52
AD - Department of Surgery, Centre of Liver Diseases, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. email@example.com
Intraoperative iatrogenic rupture of hepatocellular carcinoma (HCC), which can occur during hepatic resection when large tumors are being mobilized, may adversely affect the operative outcome. Little information is available in the literature on this serious intraoperative complication. The aim of the present study is to document iatrogenic rupture of HCC as a serious complication during hepatic resection and its effects on the operative and long-term outcomes of patients with this complication. A retrospective study was performed on all patients with intraoperative iatrogenic rupture of HCC during hepatic resection from 1989 to 1997, and the operative and long-term survival outcomes were compared with those of patients without the complication. Among 194 patients who underwent hepatic resection for a large HCC (> or =5 cm) during the study period, 8 (4.1%) had intraoperative iatrogenic rupture of the tumor. When compared with 186 patients with similar clinical parameters but without intraoperative rupture, patients with intraoperative rupture had significantly more intraoperative blood loss (median 5.7 vs. 2.0 L;p = 0.01) and blood transfusion requirement (median 3.1 vs 0.9 L; p = 0.02). On follow-up, patients in the intraoperative rupture group had a significantly higher intraperitoneal extrahepatic recurrence rate (33.3% vs. 2.9%; p =0.02) and significantly shorter survival (median 11.5 vs. 37.9 months,p = 0.04) when compared with patients without the complication. Intraoperative iatrogenic rupture is a serious complication of hepatic resection for HCC because it is associated with increased intraoperative blood loss, increased incidence of intraperitoneal extrahepatic recurrence, and short survival. Extreme care should be taken during mobilization of the tumor, and an alternative operative approach in the presence of a difficult hepatic resection of a large HCC may be required to avoid the complication.
UI - 11920537
AU - Chan AO; Yuen MF; Hui CK; Tso WK; Lai CL
TI - A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma.
SO - Cancer 2002 Mar 15;94(6):1747-52
AD - Department of Medicine, Queen Mary Hospital, the University of Hong Kong, Hong Kong.
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of cancer death throughout the world. The majority of patients are not suitable for curative resection either because of the advanced stage of the disease at the time of presentation or because of underlying cirrhosis. Transcatheter intraarterial lipiodol chemoembolization (TACE) has been reported to be one of the most effective palliative measures for HCC. However, its severe side effects continue to make its use controversial. METHODS: In the current study, the authors prospectively evaluated 197 sessions of TACE performed in 59 patients with HCC. RESULTS: Acute hepatic decompensation occurred in 20% of the 197 sessions with 3% of cases being irreversible. Significant elevation of bilirubin was associated with the dosage of cisplatin used (P = 0.0001), basal bilirubin level (P = 0.0001), basal prothrombin time (P =0.004), basal aspartate aminotransferase (AST) level (P = 0.013), and stage of cirrhosis (P < 0.0001). Patients with irreversible hepatic decompensation were more likely to have higher pre-TACE bilirubin levels (P = 0.009), more prolonged prothrombin time (P = 0.015), received a higher dose of cisplatin (P = 0.033), and more advanced cirrhosis (P < 0.0001). The majority of the other side effects were self-limiting with the exception of one patient who died of liver and splenic abscesses. Approximately 36% of the patients achieved a tumor response, 39% achieved stable disease, and 29% developed progressive disease. CONCLUSIONS: The results of the current study identified factors that appeared to predispose patients to irreversible hepatic decompensation after TACE. Despite the high percentage of patients who developed hepatic decompensation after TACE, irreversible damage occurred in only a minority. Copyright 2002 American Cancer Society.
UI - 11100351
AU - Okano A; Hajiro K; Takakuwa H; Nishio A; Matsusue S; Sano A; Kobashi Y
TI - Diffuse intrahepatic recurrence after resection of hepatocellular carcinoma.
SO - Hepatogastroenterology 2000 Sep-Oct;47(35):1356-9
AD - Department of Gastroenterology, Tenri Hospital, Nara, Japan.
BACKGROUND/AIMS: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients. RESULTS: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.
UI - 11767865
AU - Harris M; Gibbs P; Cebon J; Jones R; Sewell R; Schelleman T; Angus P
TI - Hepatocellular carcinoma and chemoembolization.
SO - Intern Med J 2001 Dec;31(9):517-22
AD - Department of Medical Oncology, Austin & Repatriation Medical Centre, Melbourne, Victoria, Australia. firstname.lastname@example.org
BACKGROUND: Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting. AIMS: To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively 1999 in a teaching hospital and liver transplant centre in Victoria. METHODS: Selective catheterization of the right or left hepatic arteries was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1-3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival. RESULTS: CT response rates: partial response 19% (n = 7), median duration 11 months (range 2+ to 37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+); stable disease 42% (n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% (n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0-37+). Median overall survival was 15 months (range 6-50+). CONCLUSION: Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour.
UI - 11882759
AU - Poon RT; Fan ST; Lo CM; Liu CL; Wong J
TI - Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation.
SO - Ann Surg 2002 Mar;235(3):373-82
AD - Centre for the Study of Liver Disease & Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China. email@example.com
OBJECTIVE: To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. SUMMARY BACKGROUND DATA: Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. METHODS: From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. RESULTS: Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. CONCLUSIONS: For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.
UI - 11920482
AU - Schnater JM; Aronson DC; Plaschkes J; Perilongo G; Brown J; Otte JB;
TI - Brugieres L; Czauderna P; MacKinlay G; Vos A Surgical view of the treatment of patients with hepatoblastoma: results from the first prospective trial of the International Society of Pediatric Oncology Liver Tumor Study Group.
SO - Cancer 2002 Feb 15;94(4):1111-20
AD - Pediatric Surgical Center Amsterdam (EKZ-AMC/VUmc), Amsterdam, The Netherlands.
BACKGROUND: Surgical resection is the cornerstone of treatment for patients with hepatoblastoma (HB). The Society of Pediatric Oncology Liver Tumor Study Group launched its first prospective trial (SIOPEL-1) with the intention to treat all patients with preoperative chemotherapy and delayed surgical resection. The objective of this article was to assess the assumed surgical advantages of primary chemotherapy. METHODS: Between 1990 and 1994, 154 patients age < 16 years with HB were registered on SIOPEL-1. The pretreatment extent of disease was assessed, and, after undergoing biopsy, patients were treated with cisplatin 80 mg/m(2) intravenously over 24 hours and doxorubicin 60 mg/m(2) intravenously over 48 hours by continuous infusion (PLADO). Generally, tumors were resected after four of a total of six courses of PLADO. RESULTS: One hundred twenty eight patients underwent surgical resection (13 patients underwent primary surgery, and 115 patients underwent delayed surgery after PLADO). A pretreatment surgical biopsy was performed in 96 of 128 patients (75%). Biopsy complications occurred in 7 of 96 patients (7%). Twenty-two patients showed pulmonary metastases at the time of diagnosis, and 7 patients underwent thoracotomy. Operative morbidity and mortality were 18% and 5%, respectively. Complete macroscopic surgical resection was achieved in 106 patients (92%), including 6 patients who underwent orthotopic liver transplantation. The actuarial 5-year event free survival (EFS) rate for all 154 patients in the study was 66%, and the overall survival (OS) rate was 75%. For the 115 patients who were included in the surgical analysis that followed the exact protocol, the EFS and OS rates were 75% and 85%, respectively. CONCLUSIONS: Biopsy is a safe procedure and should be performed routinely. Preoperative chemotherapy seems to make tumor resection easier. Reresection of a positive resection margin does not necessarily have to be performed, because postoperative chemotherapy showed good results. Resection of lung metastases can be curative if there is local control of the primary tumor; however, results showed that the patient's prognosis was worse. Surgical morbidity or mortality rates were not necessarily higher in large multicenter studies. More importantly, countries of lesser economic status also can contribute effectively to these trials. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10282
UI - 11872055
AU - Lee WC; Jeng LB; Chen MF
TI - Estimation of prognosis after hepatectomy for hepatocellular carcinoma.
SO - Br J Surg 2002 Mar;89(3):311-6
AD - Department of General Surgery, Chang-Gung Memorial Hospital, 5 Fu Hsing Street, Kwei-Shan Hsiang, Taoyuan Hsien, Taiwan. firstname.lastname@example.org
BACKGROUND: The preferred means of treatment for hepatocellular carcinoma is surgical resection. However, the tumour recurrence rate is high. Accurate estimation of the risk of tumour recurrence after hepatectomy may facilitate the administration of adjuvant therapy after hepatectomy to patients with a high likelihood of tumour recurrence. METHODS: The clinical and pathological profiles of 176 patients were used to analyse univariate prognostic factors. The Cox proportional hazard model was used for multivariate analysis. Disease-free and overall cumulative survival rates were estimated with respect to the number of prognostic factors. RESULTS: Independent factors associated with a lower disease-free survival included the presence of venous infiltration, presence of daughter tumours, absence of tumour encapsulation and tumour size exceeding 5 cm. Factors decreasing the overall survival rate included the presence of venous infiltration, absence of tumour encapsulation and surgical resection margin less than 1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e. 5.6) to 14.0(8.5) per cent when the number of risk factors present increased from zero to three. The 5-year survival rate decreased from 60.2(11.7) per cent to zero when the number of risk factors increased from zero to three. CONCLUSION: The deterioration of disease-free or overall survival of patients with hepatocellular carcinoma after hepatectomy correlates with increasing number of risk factors. The number of risk factors can be employed to accurately estimate disease-free and overall survival.
UI - 11896118
AU - Seymour LW; Ferry DR; Anderson D; Hesslewood S; Julyan PJ; Poyner R;
TI - Doran J; Young AM; Burtles S; Kerr DJ; Cancer Research Campaign Phase I/II Clinical Trials committee Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.
SO - J Clin Oncol 2002 Mar 15;20(6):1668-76
AD - Cancer Research UK Institute for Cancer Studies, University of Birmingham, United Kingdom.
PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver. The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2. PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide copolymers bearing galactosamine. Targeting, toxicity, and efficacy were evaluated in 31 patients with primary (n = 25) or metastatic (n = 6) liver cancer. Body distribution of the radiolabelled polymer conjugate was assessed using gamma-camera imaging and single-photon emission computed tomography. RESULTS: The polymer was administered by intravenous (i.v.) infusion over 1 hour, repeated every 3 weeks. Dose escalation proceeded from 20 to 160 mg/m(2) (doxorubicin equivalents), the maximum-tolerated dose, which was associated with severe fatigue, grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after administration, 16.9% +/- 3.9% of the administered dose of doxorubicin targeted to the liver and 3.3% +/- 5.6% of dose was delivered to tumor. Doxorubicin-polymer conjugate without galactosamine showed no targeting. Three hepatoma patients showed partial responses, with one in continuing partial remission 47 months after therapy. CONCLUSION: The recommended PK2 dose is 120 mg/m(2), administered every 3 weeks by IV infusion. Liver-specific doxorubicin delivery is achievable using galactosamine-modified polymers, and targeting is also seen in primary hepatocellular tumors.
UI - 11896125
AU - Tan SB; Machin D; Cheung YB; Chung YF; Tai BC; Machin D
TI - Following a trial that stopped early: what next for adjuvant hepatic intra-arterial iodine-131 lipiodol in resectable hepatocellular carcinoma?
SO - J Clin Oncol 2002 Mar 15;20(6):1709
UI - 11915031
AU - Ijichi M; Takayama T; Matsumura M; Shiratori Y; Omata M; Makuuchi M
TI - alpha-Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: a prospective study.
SO - Hepatology 2002 Apr;35(4):853-60
AD - Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
alpha-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC. Peripheral blood samples were taken from 87 patients before and after surgery to determine the presence of AFP mRNA by use of a reverse-transcription polymerase chain reaction. A primary endpoint was recurrence-free interval. AFP mRNA was detectable preoperatively in 31 patients (36%) and postoperatively in 30 patients (34%). With a median follow-up period of 28 months (range, 3-41 months), HCC recurred in 46 patients (53%). Among 4 groups separated according to preoperative and postoperative AFP mRNA status, patients with consistent positivity of AFP mRNA showed the highest recurrence rate (85%) and trend to distant or multiple recurrence. The recurrence-free interval was significantly shorter in patients with postoperative positivity of AFP mRNA than in those without (53% [95% CI, 36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60% [95% CI, 46-75] at 2 years; P =.014), whereas the preoperative positivity of AFP mRNA provided no significance (P =.100). Cox's proportional-hazards model identified the postoperative positivity of AFP mRNA as an independent prognostic factor for HCC recurrence (relative risk, 2.33; 95% CI, 1.26-4.34; P =.007). In conclusion, postsurgical recurrence of HCC can be predicted by detecting AFP mRNA-expressing cells in peripheral blood.
UI - 11894035
AU - Fukuda S; Okuda K; Imamura M; Imamura I; Eriguchi N; Aoyagi S
TI - Surgical resection combined with chemotherapy for advanced hepatocellular carcinoma with tumor thrombus: report of 19 cases.
SO - Surgery 2002 Mar;131(3):300-10
AD - Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan.
BACKGROUND: Prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPV), inferior vena cava (IVC), or extrahepatic bile duct (EBD) treated by conventional therapies has been considered poor. This study aimed to evaluate the efficacy of hepatic arterial infusion chemotherapy after surgical resection as an adjuvant therapy or as a treatment for intrahepatic recurrence of HCC with tumor thrombus in MPV, IVC, or EBD. METHODS: Nineteen patients with HCC and tumor thrombus in the MPV, IVC, or EBD who underwent hepatectomy with thrombectomy were reviewed retrospectively. RESULTS: The overall 3-year survival rate was 48.5%. Two patients with postoperative residual tumor thrombus died within 6 months owing to rapid progression of the residual tumor thrombus. Five patients survived more than 5 years after their operations. Tumors disappeared completely in 3 patients after hepatic arterial infusion chemotherapy with a combination of cisplatinum and 5-fluorouracil, and the longest survival period was 17 years and 11 months in a patient with EBD thrombus. CONCLUSIONS: If hepatic reserve is satisfactory, an aggressive surgical approach combined with chemotherapy seems to be of benefit for patients having HCC with tumor thrombus in the MPV, IVC, or EBD.
UI - 11894036
AU - Regimbeau JM; Kianmanesh R; Farges O; Dondero F; Sauvanet A; Belghiti J
TI - Extent of liver resection influences the outcome in patients with cirrhosis and small hepatocellular carcinoma.
SO - Surgery 2002 Mar;131(3):311-7
AD - Department of Hepatobiliary and Digestive Surgery, Beaujon Hospital, University of Paris VII, Clichy, France.
BACKGROUND: The long-term outcome after resection of hepatocellular carcinoma (HCC) is influenced by parameters related to the tumor and the underlying liver disease. However, the extent of the resection, which can be limited or anatomical (including the tumor and its portal territory), is controversial. METHODS: Among 64 Child-Pugh A patients with cirrhosis who underwent curative liver resection for small HCC (< or = 4 cm) between 1990 and 1996, 34 patients underwent limited resection with a margin width of at least 1 cm, and 30 patients underwent anatomic resection of at least 1 liver segment with complete removal of the portal area containing the tumor. The 2 groups were comparable in terms of epidemiologic and pathologic parameters. The major end points were: (1) in-hospital mortality and morbidity; (2) overall and disease-free survival; and (3) rate and topography of recurrence. RESULTS: The 30-day mortality (6% vs 7%) and morbidity (52% vs 47%) rates after limited and anatomic liver resection were not statistically different. The 5- and 8-year overall survival rates after limited versus anatomic resection were, respectively, 35% versus 54% (P <.05) and 6% versus 45% (P <.05). The 5- and 8-year disease-free survival rates were, respectively, 26% versus 45% and 0% versus 21% (P <.05). Local recurrence was more frequently observed after limited resections than after anatomic resections (50% vs 10%, P <.05). CONCLUSIONS: In patients with cirrhosis and a small HCC, anatomic resection achieves better disease-free survival than limited resection without increasing the postoperative risk. Therefore, anatomical resection should be the treatment of choice and considered as the reference surgical treatment compared with other treatments.
UI - 9679583
AU - Beppu T; Ogawa M; Yamanaka T; Egami H; Ohara C; Masuda Y; Kudo S;
TI - Kuramoto M; Doi K; Matsuda T [Clinical evaluation of Azasetron Hydrochloride: a new selective 5-HT3 receptor antagonist--antiemetic profile and plasma concentration in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma]
SO - Gan To Kagaku Ryoho 1998 Jul;25(8):1197-202
AD - Dept. of Surgery II, Kumamoto University Medical School.
We performed a clinical evaluation on the antiemetic profile and the plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3 receptor antagonist), in transcatheter arterial chemoembolization using CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were examined in 32 patients in the serotone group (administration of serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the control group (administration of metoclopramide 20-30 mg + methylprednisolone 500 mg). The response rate and the CR ratio in serotone group was 97% and 66%, respectively. These results were statistically higher than in the control group. Although all patients had chronic liver diseases, no side effects and complications related to administration of serotone were observed. The average area under the concentration (AUC) curve of plasma serotone in five patients with liver cirrhosis was 531 ng.h/ml, which was greater than that of a healthy volunteer. In conclusion, serotone is a new, safe and useful antiemetic drug in TACE therapy for hepatocellular carcinoma.
UI - 11408926
AU - De Ledinghen V; Monvoisin A; Neaud V; Krisa S; Payrastre B; Bedin C;
TI - Desmouliere A; Bioulac-Sage P; Rosenbaum J Trans-resveratrol, a grapevine-derived polyphenol, blocks hepatocyte growth factor-induced invasion of hepatocellular carcinoma cells.
SO - Int J Oncol 2001 Jul;19(1):83-8
AD - Groupe de Recherches pour l'Etude du Foie, INSERM E9917, Universite Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France.
We have shown that liver myofibroblasts stimulate in vitro invasion of hepatocellular carcinoma cell lines through a hepatocyte growth factor/urokinase-dependent mechanism. Resveratrol, a grapevine-derived polyphenol, has been shown to inhibit cellular events associated with tumor initiation, promotion and progression. The aim of this study was to evaluate the effects of trans-resveratrol on invasion of the human hepatoma cell line HepG2. Cell invasion was assessed using a Boyden chamber assay. Activation of the HGF signal transduction pathways was evaluated by Western blot with phospho-specific antibodies. Urokinase expression was measured by RT-PCR and zymography. Trans-resveratrol decreased hepatocyte growth factor-induced cell scattering and invasion. It also decreased cell proliferation without evidence for cytotoxicity or apoptosis. Trans-resveratrol did not decrease the level of the hepatocyte growth factor receptor c-met and did not impede the hepatocyte growth factor-induced increase in c-met precursor synthesis. Moreover, trans-resveratrol did not decrease hepatocyte growth factor-induced c-met autophosphorylation, or Akt-1 or extracellular-regulated kinases-1 and -2 activation. Finally, it did not decrease urokinase expression and did not block the catalytic activity of urokinase. In conclusion, our results demonstrate that trans-resveratrol decreases hepatocyte growth factor-induced HepG2 cell invasion by an as yet unidentified post-receptor mechanism.
UI - 11926943
AU - Antonetti MC; Killelea B; Orlando R 3rd
TI - Hand-assisted laparoscopic liver surgery.
SO - Arch Surg 2002 Apr;137(4):407-11; discussion 412
AD - Department of Surgery, Hartford Hospital and University of Connecticut School of Medicine, Hartford, CT, USA.
HYPOTHESIS: The hand-assisted laparoscopic technique may be applied to the treatment of liver tumors. DESIGN: A case series with mean follow-up of 13 months. SETTING: University-affiliated tertiary care center. PATIENTS: A total of 15 patients with hepatic neoplasms underwent screening tests, including appropriate tumor marker analyses, abdominal sonography, and computed tomographic scan and, in most cases, magnetic resonance imaging to determine operability. Contraindications included extrahepatic disease, more than 5 liver lesions, coagulopathy, and ascites. INTERVENTION: Between March 1, 1998, and April 30, 2001, 15 patients underwent 16 hand-assisted diagnostic laparoscopic operations to rule out extrahepatic disease. Four patients had extrahepatic disease. In the 11 patients without evidence of extrahepatic disease, intraoperative ultrasound was used to establish the number and location of liver lesions. Operative strategies included resection, cryoablation, or both. MAIN OUTCOME MEASURES: Operative time, conversion to open procedure, length of stay, complications, and recurrence of disease. RESULTS: Of the 15 patients with liver tumors, 6 patients had more extensive disease than was detected by either preoperative imaging or laparoscopic exploration They included extrahepatic disease (3), additional liver lesion (2), or both (1). Hand-assisted management included resection only (3), cryoablation only (5), and a combination of the 2 (3). A total of 9 lesions were resected and 10 lesions were cryoablated. The mean operative time was 197 minutes with a mean length of stay of 4.5 days. There were no conversions to open procedures. One patient experienced minor postoperative bleeding but required no treatment. All treated patients are alive, and 5 have had recurrence of disease. CONCLUSIONS: Hand-assisted technique can be applied safely and effectively to laparoscopic liver surgery and may identify presence of otherwise undetectable disease.
UI - 11926946
AU - Iannitti DA; Dupuy DE; Mayo-Smith WW; Murphy B
TI - Hepatic radiofrequency ablation.
SO - Arch Surg 2002 Apr;137(4):422-6; discussion 427
AD - Department of Surgery, Brown University School of Medicine, Rhode Island Hospital, Providence, RI, USA. Diannitti@usasurg.org
HYPOTHESIS: Hepatic radiofrequency ablation (RFA) is effective in treating patients with unresectable hepatic malignancies. DESIGN: Case series of 123 patients with unresectable hepatic tumors or tumors with histological findings not traditionally treated by means of hepatic resection were considered for hepatic RFA. Median follow-up was 20 months. SETTING: Tertiary referral center. PATIENTS: The 123 patents underwent 168 RFA sessions from January 1, 1998, through September 30, 2001. Sixty-nine patients were male and 54, female; average age was 65 years (range, 1-89 years). Fifty-two patients had metastatic colorectal cancer; 30, hepatocellular carcinoma; and 41, cancers with other histological findings. INTERVENTIONS: A 200-W, cooled-tip RF probe system was used for all cases. Probe placement and ablation were monitored by means of real-time ultrasonography or fluoroscopic computed tomography. Final tissue temperature of greater than 50 degrees C was achieved in all cases. RESULTS: Initial treatment sessions were percutaneous in 87 patients, open operations in 33, and laparoscopic in 3. Repeated sessions were percutaneous in all but 2 patients. The mean number of lesions treated per session was 2.7 (range, 1-24). Mean tumor size was 5.2 cm (range, 0.5-15.0 cm). One death occurred within 30 days of a procedure. No hepatic bleeds, bile leaks, or adult respiratory distress syndrome occurred. Overall morbidity was 7.1%. Complications included hepatic abscesses in 4 patients, transient liver insufficiency in 3, segmental hepatic infarcts in 2, diaphragm paralysis in 1, hepatic artery-to-portal vein fistula in 1, and systemic hemolysis in 1. CONCLUSIONS: Hepatic RFA is an effective treatment option for patients with unresectable hepatic malignancies. Careful patient selection based on tumor size, location, and number and on patient clinical status should determine the choice of treatment. Further controlled trials are needed to determine the effect of hepatic RFA on long-term survival.
UI - 11819207
AU - Pimpalwar AP; Sharif K; Ramani P; Stevens M; Grundy R; Morland B; Lloyd
TI - C; Kelly DA; Buckles JA; de Ville De Goyet J Strategy for hepatoblastoma management: Transplant versus nontransplant surgery.
SO - J Pediatr Surg 2002 Feb;37(2):240-5
AD - Birmingham, England.
BACKGROUND: Liver transplantation now is proposed for managing selected hepatoblastoma cases. Indications are not yet well defined. METHODS: The case records of 34 children with hepatoblastoma treated over a period of 10 years (1991 to 2000) were reviewed retrospectively. RESULTS: All patients benefited from preoperative chemotherapy. Twenty patients underwent major hepatic resections. Twelve patients, in absence of residual metastasis, underwent liver transplant because the tumour remained unresectable after chemotherapy. Two patients who presented with recurrence after a right hepatectomy, benefited from transplant as a second option. Two other patients did not undergo surgery because of widespread disease or resistance to chemotherapy. Disease-free survival rates were 95% after surgical resection, 100% when primary transplant was performed in patients with good response to chemotherapy, 60% after transplantation in patients with poor response to chemotherapy, 50% in patients with transplant as second option, and 0% in patients not undergoing surgery. CONCLUSIONS: Transplantation is a potentially curative option for unresectable hepatoblastoma when chemosensitive (decrease in alpha-fetoprotein and decrease in tumour size). In this context, also favourable cases with good response but difficult resections with doubtful margins of resection may best be proposed for primary transplantation. Patients with recurrent or resistant disease are not good candidates.
UI - 11933628
AU - Biertho L; Waage A; Gagner M
TI - [Laparoscopic hepatectomy]
SO - Ann Chir 2002 Mar;127(3):164-70
AD - Mount Sinai School of Medicine, Department of Surgery, Minimally Invasive Surgery Center, New York, NY, USA.
AIM: To report the current indications and techniques of laparoscopic liver resections, and assess the results of this technique by reviewing international literature. REVIEW OF THE LITERATURE: About 200 laparoscopic hepatectomies have been reported from 1991 to 2001. 102 resections were performed for malignant tumours, and 84 for benign tumours. Global conversion rate was 7% (13/186). Morbidity rate was 16.1% with two cases of possible gas embolisms (1.1%). Mortality rate was 0.54% (1/186 patients). Mean hospital stay was 7.7 days. CONCLUSION: Laparoscopic hepatectomy is feasible, with a morbidity and mortality rate comparable to open procedures according to a careful selection of patients. However, prospective randomized trials are still needed to confirm those results, especially for resection of metastasis or malignant tumors. Evolution of laparoscopic hepatectomies will probably depend on the development of new techniques and instrumentations.
UI - 11037997
AU - Dancey JE; Shepherd FA; Paul K; Sniderman KW; Houle S; Gabrys J; Hendler
TI - AL; Goin JE Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres.
SO - J Nucl Med 2000 Oct;41(10):1673-81
AD - Department of Radiology, The Toronto General Hospital, University of Toronto, Ontario, Canada.
Treatment for nonresectable hepatocellular carcinoma (HCC) is palliative. The relatively greater arteriolar density of hepatic tumors compared with normal liver suggests that intrahepatic arterial administration of 90Y-microspheres can be selectively deposited in tumor nodules and results in significantly greater radiation exposure to the tumor than external irradiation. The purpose of this study was to determine the proportion (frequency) and duration of response, survival, and toxicity after intrahepatic arterial injection of 90Y-microspheres in patients with HCC. METHODS: Patients with documented HCC, Eastern Cooperative Oncology Group performance status 0-3, adequate bone marrow, and hepatic and pulmonary function were eligible for study. Patients who had significant shunting of blood to the lungs or gastrointestinal (GI) tract or who could not undergo cannulation of the hepatic artery were excluded. Patients received a planned dose of 100 Gy through a catheter placed into the hepatic artery. RESULTS: Twenty-two patients were treated with 90Y-microspheres; 20 of the treated patients (median age, 62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda stage I, and 11 were Okuda stage II. The median dose delivered was 104 Gy (range, 46-145 Gy). All 22 treated patients experienced at least 1 adverse event. Of the 31 (15%) serious adverse events, the most common were elevations in liver enzymes and bilirubin and upper GI ulceration. The response rate was 20%. The median duration of response was 127 wk; the median survival was 54 wk. Multivariable analysis suggested that a dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P = 0.06), and Okuda stage I (P = 0.07) were associated with longer survival. CONCLUSION: Significantly higher doses of radiation can be delivered to a HCC tumor by intrahepatic arterial administration of 90Y-microspheres than by external beam radiation. This treatment appears to be beneficial in nonresectable HCC with acceptable toxicity.