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1. Patiutko IuI, Chuchuev ES, Kotel'nikov AG, Sagaĭdak IV, Badalian KhV: [Synchronous operations in metastatic cancer of the liver]. Khirurgiia (Mosk); 2006;(5):14-7
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  • [Title] [Synchronous operations in metastatic cancer of the liver].
  • The resection of the liver has been performed in 661 patients including 154 (23.3%) cases of synchronous metastatic cancer of the liver.
  • Among the latter patients primary tumor was removed in one stage with liver resection in 56% cases.
  • Elderly age of the patients, multiple bilobular foci in the liver, size of the foci more than 10 cm, traumatic operations on the primary focus were not contraindications to synchronous operations.
  • Surgical treatment for colorectal cancer should be supplemented with adjuvant chemotherapy.
  • The long-term results demonstrate better survival after synchronous operations for colorectal cancer.
  • [MeSH-major] Liver Neoplasms / secondary. Liver Neoplasms / surgery. Surgical Procedures, Operative / methods
  • [MeSH-minor] Adult. Aged. Female. Gastrointestinal Neoplasms / pathology. Gastrointestinal Neoplasms / surgery. Humans. Male. Middle Aged. Stomach Neoplasms / pathology. Stomach Neoplasms / surgery


2. Nakamura H, Kawata S, Takamura M, Osuga K, Murakami T: [Transcatheter arterial embolization for advanced hepatocellular carcinoma--indications and limitations]. Gan To Kagaku Ryoho; 2000 Sep;27(10):1509-15
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  • [Title] [Transcatheter arterial embolization for advanced hepatocellular carcinoma--indications and limitations].
  • Many patients with advanced hepatocellular carcinoma (HCC) in stage IV have no surgical indications.
  • Transcatheter methods such as transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy play a main role of the treatment for advanced HCC.
  • Conventional TAE (from proper hepatic artery) is performed for patients without liver dysfunction.
  • Patients with severe liver dysfunction could not in the past be treated with TAE, but lately it has become possible to treat them with the method of segmental TAE or subsegmental TAE due to the development of a microcatheter and advances in equipment.
  • [MeSH-major] Carcinoma, Hepatocellular / therapy. Embolization, Therapeutic. Liver Neoplasms / therapy
  • [MeSH-minor] Antibiotics, Antineoplastic / administration & dosage. Antineoplastic Agents / administration & dosage. Doxorubicin / administration & dosage. Epirubicin / administration & dosage. Hepatic Artery. Humans. Infusions, Intra-Arterial. Iodized Oil / administration & dosage

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  • (PMID = 11015994.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] JAPAN
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Antineoplastic Agents; 3Z8479ZZ5X / Epirubicin; 8001-40-9 / Iodized Oil; 80168379AG / Doxorubicin
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3. Lee GY, Kim BS, Seo YT, Choi SH, Kim HJ, Choi DS, Ko JY, Yang SH, Byun JH: Phase II study to topotecan and cisplatin in advanced hepatocellular carcinoma. Korean J Intern Med; 2003 Jun;18(2):104-8
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  • [Title] Phase II study to topotecan and cisplatin in advanced hepatocellular carcinoma.
  • BACKGROUND: Hepatocellular carcinoma remains a highly chemoresistant neoplasm and is a common malignancy with poor prognosis in Korea.
  • We performed a phase II study to evaluate the efficacy and toxicities of topotecan and cisplatin combination chemotherapy for advanced hepatocellular carcinoma.
  • METHODS: Between November 1999 and May 2001, ten patients with histologically proven hepatocellular carcinoma were enrolled in this study.
  • Six patients demonstrated stage IV, 1 stage IIIC, 2 stage IIIB and 1 stage IIIA.
  • The treatment regimen consisted of topotecan 1.25 mg/m2 and cisplatin 20 mg/m2 for 5 days.
  • The treatment was repeated every 4 weeks.
  • In non-hematologic toxicity, diarrhea and hepatoxicity of grade 3 occurred in 1 and 2 patients, respectively.
  • But there was no treatment-related death.
  • CONCLUSION: When used in this dose and schedule, topotecan and cisplatin combination chemotherapy does not seem to be effective for patients with advanced hepatocellular carcinoma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Cisplatin / administration & dosage. Liver Neoplasms / drug therapy. Topotecan / administration & dosage
  • [MeSH-minor] Aged. Humans. Male. Middle Aged. Treatment Outcome

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  • (PMID = 12872448.001).
  • [ISSN] 1226-3303
  • [Journal-full-title] The Korean journal of internal medicine
  • [ISO-abbreviation] Korean J. Intern. Med.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 7M7YKX2N15 / Topotecan; Q20Q21Q62J / Cisplatin
  • [Other-IDs] NLM/ PMC4531618
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4. Huang GW, Yang LY: Metallothionein expression in hepatocellular carcinoma. World J Gastroenterol; 2002 Aug;8(4):650-3
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  • [Title] Metallothionein expression in hepatocellular carcinoma.
  • AIM: To investigate the expression of metallothioneins (MTs), which were recently thought to have close relationship with tumors, in human hepatocellular carcinoma.
  • METHODS: Histological specimens of 35 cases of primary human hepatocellular carcinoma with para-neoplastic liver tissue and 5 cases of normal liver were stained for MTs with monoclonal mouse anti-MTs serum (E9) by the immunohistochemical ABC technique.
  • But MTs were stained strongly positive in all the five cases of normal liver and 35 cases of para-neoplastic liver tissue.
  • The differences of MTs expression between HCC and normal liver tissue or para-neoplastic liver tissue were highly significant (P<0.01).
  • The rate of MTs expression in HCC grade I was 100 percent, higher than that in grade II(81 %) and grade III and IV (78 %).
  • But the differences were not significant (P>0.05).
  • No obvious correlations between MTs expression in HCC and tumor size, clinical stage or serum alpha fetoprotein concentration were found (P>0.05).
  • We can choose the anticancer agents according to the MTs concentration in HCC, which may improve the results of chemotherapy for HCC.
  • [MeSH-major] Carcinoma, Hepatocellular / enzymology. Liver Neoplasms / enzymology. Metallothionein / metabolism
  • [MeSH-minor] Adult. Aged. Female. Humans. Immunohistochemistry. Liver / enzymology. Male. Middle Aged

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  • (PMID = 12174372.001).
  • [ISSN] 1007-9327
  • [Journal-full-title] World journal of gastroenterology
  • [ISO-abbreviation] World J. Gastroenterol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 9038-94-2 / Metallothionein
  • [Other-IDs] NLM/ PMC4656314
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5. Knox JJ, Gill S, Synold TW, Biagi JJ, Major P, Feld R, Cripps C, Wainman N, Eisenhauer E, Seymour L: A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168). Invest New Drugs; 2008 Jun;26(3):265-72
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  • [Title] A phase II and pharmacokinetic study of SB-715992, in patients with metastatic hepatocellular carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG IND.168).
  • Hepatocellular carcinoma (HCC) remains a lethal treatment-resistant cancer with a median survival of <6 months in patients not considered candidates for radical surgical treatments.
  • A non-randomized, non-blinded multicentre two-stage phase II study was completed examining the efficacy, toxicity, and pharmacokinetics of SB-715992 at 18 mg/m2 IV q 3 weeks, in patients with measurable locally advanced, metastatic or recurrent HCC.
  • The predictive value of KSP in archival tumour was assessed.
  • The most common grade 3+ toxicities were granulocytopenia, leukocytopenia, diarrhea and liver transaminase rise.
  • Seven (46%) patients had a best response of stable disease at the 8-week evaluation (median duration 3.9 months) Median time to progression was 1.61 months (95%CI = 1.31-3.94 months) SB-715992 plasma concentrations were comparable to those observed in the phase I studies.
  • Among these patients with preserved hepatic function and good performance status, SB-715992 was generally well tolerated.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Benzamides / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Liver Neoplasms / drug therapy. Quinazolines / therapeutic use
  • [MeSH-minor] Adult. Aged. Disease Progression. Female. Gene Expression. Humans. Infusions, Intravenous. Kinesin / antagonists & inhibitors. Male. Middle Aged. Neoplasm Metastasis / drug therapy. Treatment Outcome

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  • (PMID = 18196204.001).
  • [ISSN] 0167-6997
  • [Journal-full-title] Investigational new drugs
  • [ISO-abbreviation] Invest New Drugs
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / KIF11 protein, human; 0 / Quinazolines; BKT5F9C2NI / ispinesib; EC 3.6.4.4 / Kinesin
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6. Kawarada Y, Yamagiwa K: [Up to date of multidisciplinary treatments centering around hepatectomy for advanced liver cancer in stage IV-A]. Gan To Kagaku Ryoho; 2000 Sep;27(10):1489-95
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  • [Title] [Up to date of multidisciplinary treatments centering around hepatectomy for advanced liver cancer in stage IV-A].
  • Patients with advanced Stage IV-A primary liver cancer, hepatocellular carcinoma (HCC) can be divided into subgroups: those with involvement of a major branch of the portal (Vp3) or hepatic (Vv2, Vv3) veins and those having multiple tumors in both lobes without Vp3 or Vv2, Vv3.
  • The prognosis of Stage IV-A patients with Vv2 or Vv3 may be improved by extended hepatectomy with resection and reconstruction of hepatic veins or IVC.
  • In those with Vp3, multidisciplinary treatments consisting of extended hepatectomy and adjuvant chemotherapy, i.e. intra-arterial injection or TACE, are thought to be feasible at the present, but the outcomes are still poor.
  • On the other hand, there are some Stage IV-A patients with multi-centrical tumors who have multiple tumors in both lobes without major vascular invasion, and their prognoses are improved by partial resection of each tumor.
  • However, when there are multiple tumors caused by intrahepatic metastases, multidisciplinary treatments consisting of reduction surgery, microwave ablation, ethanol injection, and intra-arterial chemotherapy might be useful at present.
  • [MeSH-major] Hepatectomy. Liver Neoplasms / surgery
  • [MeSH-minor] Aged. Combined Modality Therapy. Female. Humans. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Proportional Hazards Models. Survival Rate

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  • (PMID = 11015991.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] JAPAN
  • [Number-of-references] 8
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7. Rizzetto M: Hepatocellular carcinoma: screening and therapy. Minerva Gastroenterol Dietol; 2000 Sep;46(3):143-7
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  • [Title] Hepatocellular carcinoma: screening and therapy.
  • Treatment of the liver cancer (LC) patient is often problematic as the tumour is identified at an advanced stage: the frequent coexistence of cirrhosis limits the use of surgical resection, there is no efficacious chemotherapy, and in patients treatable with liver transplant, indication is rendered uncertain from the point of view of cost-effectiveness and the high risk of recurrence of the tumour and hepatitis infection.
  • Surgical resection appears to be the treatment of choice in patients with a liver tumour in a ''healthy'' liver.
  • Instead, orthotopic liver transplant is the most valid indication for patients with cirrhosis and tumours of dimensions smaller than 2-3 cm.
  • Nevertheless, due to the lack of organs palliative treatments, like surgical resection, PEI and TACE are the most indicated in patients with advanced neoplastic disease, in practice patients with TNM III and IV; radiotherapy with protons and the coagulation of the tumour by microwaves or laser fibres are also used in the attempt to slow down the progress of the neoplastic process.
  • In some patients the most effective approach may be the combined use of various therapies, such as TACE, PEI and surgery.

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  • (PMID = 16498375.001).
  • [ISSN] 1121-421X
  • [Journal-full-title] Minerva gastroenterologica e dietologica
  • [ISO-abbreviation] Minerva Gastroenterol Dietol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
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8. Castaldo ET, Pinson CW: Liver transplantation for non-hepatocellular carcinoma malignancy. HPB (Oxford); 2007;9(2):98-103
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  • [Title] Liver transplantation for non-hepatocellular carcinoma malignancy.
  • Liver transplantation (LT) for hepatocellular carcinoma is effective for selected patients.
  • LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and neuroendocrine tumors (NET) is being defined.
  • For CCA, series that did not emphasize highly selected early stage disease and neoadjuvant or adjuvant chemoradiation had an average 5-year survival of 10%.
  • However, emphasizing neoadjuvant radiation and chemosensitization in operatively confirmed stage I or II hilar CCA has led to improved 5-year survival, up to 82%.
  • LT is indicated under strict research protocols at selected centers, for patients with early stage CCA and anatomically unresectable (Bismuth type IV) lesions.
  • HB is typically sensitive to cisplatin-based chemotherapy.
  • LT plays a role as primary surgical therapy for those individuals in whom tumors remain unresectable after chemotherapy or as rescue therapy for those who are incompletely resected, recur after resection, or develop hepatic insufficiency after chemotherapy and/or resection.
  • HEHE is a multifocal tumor that lies somewhere between benign hemangiomas and malignant AS.
  • However, AS is an aggressive tumor and LT is contraindicated.
  • For NET, resection of the primary tumor and all gross metastatic disease is reported to provide 5-year survival of 70-85%.
  • LT has been employed for some patients for unresectable tumors or for palliation of medically uncontrollable symptoms with 5-year survival reported between 36% and 80%.

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  • (PMID = 18333123.001).
  • [ISSN] 1365-182X
  • [Journal-full-title] HPB : the official journal of the International Hepato Pancreato Biliary Association
  • [ISO-abbreviation] HPB (Oxford)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2020792
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9. Pham TH, Iqbal CW, Grams JM, Zarroug AE, Wall JC, Ishitani MB, Nagorney DM, Moir C: Outcomes of primary liver cancer in children: an appraisal of experience. J Pediatr Surg; 2007 May;42(5):834-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Outcomes of primary liver cancer in children: an appraisal of experience.
  • INTRODUCTION: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary liver cancers in children.
  • Recent advances in management of pediatric liver cancer have improved disease-specific survival (DSS).
  • This is a review of our experience with childhood liver malignancy over the past 3 decades.
  • MATERIALS AND METHODS: A retrospective chart review from 1975 to 2005 identified patients who were 18 years old or younger with a histologically confirmed diagnosis of primary liver cancer.
  • Patients were staged according to the Children's Cancer Group and Pediatric Oncology Group (CCG/POG) system.
  • RESULTS: Fifty-two patients were confirmed to have primary liver cancers, where 24 (46%) patients had HB, 22 (42%) had HCC, 3 (6%) had sarcomas, and 3 (6%) had other histologies.
  • Most patients underwent major liver resection (n = 45, 87%), including: lobectomy (n = 25, 48%), and trisegmentectomy (n = 11, 21%).
  • Three patients underwent liver transplantation (n = 3, 6%) for advanced local disease.
  • Forty-five (87%) received primary or neoadjuvant and/or adjuvant chemotherapy.
  • Patients had the following CCG/POG stages: I (n = 31, 60%), II (n = 6, 11.5%), III (n = 9, 17%), and IV (n = 6, 11.5%).
  • Complete gross resection (stage I and II) was achieved in 37 (71%) patients.
  • CONCLUSION: Complete resection of the pediatric primary liver tumors remains the cornerstone of treatment to achieve cure.
  • Major liver resection can be performed with minimal perioperative mortality and morbidity.
  • Liver transplantation in conjunction with chemotherapy may have an increasing role in the management of locally advanced primary liver cancers.
  • [MeSH-major] Carcinoma, Hepatocellular / therapy. Hepatoblastoma / therapy. Liver Neoplasms / therapy
  • [MeSH-minor] Adolescent. Analysis of Variance. Child. Child, Preschool. Combined Modality Therapy. Hepatectomy. Humans. Liver Transplantation. Registries. Retrospective Studies. Survival Rate. Treatment Outcome

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  • (PMID = 17502194.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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10. Tanisaka Y, Seike H, Matsumoto T, Tanaka Y, Tsubouchi E, Miyauchi S, Iwakawa K, Ichikawa M: [A case of advanced hepatocarcinoma responding to combination therapy of S-1 and PEG-IFN]. Gan To Kagaku Ryoho; 2009 Oct;36(10):1761-3
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  • [Title] [A case of advanced hepatocarcinoma responding to combination therapy of S-1 and PEG-IFN].
  • He was hospitalized because many venereal diseases had been pointed out in the liver by abdomen ultrasonography.
  • Results of close examination revealed stage IV B with bone metastases, and pulmonary metastases was diagnosed.
  • After consultation, whole-body chemotherapy combining S-1 and PEG-IFN was attempted as of June 26, 2007.
  • S-1 (80 mg/day) was then administered every day for two weeks with drug withdrawal for one week.
  • The liver tumor was markedly reduced, and the pulmonary metastases were also reduced at the completion of 5 courses.
  • The therapeutic effectiveness of this chemotherapy was confirmed by imaging test.
  • The course was favorable, and whole-body chemotherapy was discontinued on January 29, 2008.
  • This treatment method is a promising choice for whole-body chemotherapy for advanced hepatocarcinoma in the future.
  • We have added some review of the literature, and the S-1+PEG-IFN combination chemotherapy is reported.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Interferon-alpha / therapeutic use. Liver Neoplasms / drug therapy. Oxonic Acid / therapeutic use. Polyethylene Glycols / therapeutic use. Tegafur / therapeutic use
  • [MeSH-minor] Angiography. Bone Neoplasms / drug therapy. Bone Neoplasms / radiography. Bone Neoplasms / secondary. Drug Combinations. Hepatitis C, Chronic / complications. Humans. Lung Neoplasms / drug therapy. Lung Neoplasms / radiography. Lung Neoplasms / secondary. Male. Middle Aged. Neoplasm Staging. Recombinant Proteins. Tomography, X-Ray Computed

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  • (PMID = 19838044.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Drug Combinations; 0 / Interferon-alpha; 0 / Recombinant Proteins; 0 / peginterferon alfa-2a; 150863-82-4 / S 1 (combination); 1548R74NSZ / Tegafur; 30IQX730WE / Polyethylene Glycols; 5VT6420TIG / Oxonic Acid; 76543-88-9 / interferon alfa-2a
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11. Chia WK, Ong S, Toh HC, Hee SW, Choo SP, Poon DY, Tay MH, Tan CK, Koo WH, Foo KF: Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma. Ann Acad Med Singapore; 2008 Jul;37(7):554-8
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  • [Title] Phase II trial of gemcitabine in combination with cisplatin in inoperable or advanced hepatocellular carcinoma.
  • INTRODUCTION: Advanced hepatocellular carcinoma (HCC) has a dismal prognosis and is notoriously chemo-resistant.
  • We conducted a Phase II prospective study to evaluate the activity and tolerability of gemcitabine and cisplatin in chemo-naïve advanced hepatocellular carcinoma.
  • Utilising a Simon's minimax two-stage design with a type I error of 0.05 and power of 80%, 25 subjects would be required.
  • Fifteen patients would be needed in stage 1 and if fewer than 2 responses were observed, the trial would be stopped and lack of efficacy claimed.
  • Assessment of response based on computer tomography was performed after every 2 cycles of chemotherapy.
  • Two patients had Child C liver cirrhosis, 5 patients had Child B cirrhosis, and the remaining 8 patients had Child A cirrhosis.
  • This regime was well tolerated and there was only 1 patient who experienced grade IV toxicities.
  • A further 3 patients experienced stable disease and 11 patients progressed on chemotherapy.
  • The median time to progression was 6 weeks.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Liver Neoplasms / drug therapy
  • [MeSH-minor] Adult. Cisplatin / administration & dosage. Deoxycytidine / administration & dosage. Deoxycytidine / analogs & derivatives. Disease-Free Survival. Female. Humans. Male. Middle Aged. Prospective Studies. Time Factors. Treatment Outcome

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  • (PMID = 18695766.001).
  • [ISSN] 0304-4602
  • [Journal-full-title] Annals of the Academy of Medicine, Singapore
  • [ISO-abbreviation] Ann. Acad. Med. Singap.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article
  • [Publication-country] Singapore
  • [Chemical-registry-number] 0W860991D6 / Deoxycytidine; B76N6SBZ8R / gemcitabine; Q20Q21Q62J / Cisplatin
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12. Ochiai T, Sonoyama T, Ikoma H, Kuriu Y, Nakanishi M, Kubota T, Kikuchi S, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Kokuba Y, Otsuji E: Salvage surgery for uncontrollable hepatocellular carcinoma treated with repeated non-surgical therapies. Hepatogastroenterology; 2010 Jul-Aug;57(101):858-64
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  • [Title] Salvage surgery for uncontrollable hepatocellular carcinoma treated with repeated non-surgical therapies.
  • BACKGROUND/AIMS: Some hepatocellular carcinoma (HCC) cases undergo surgery because tumor progression cannot be controlled by various non-surgical therapies.
  • METHODOLOGY: Among cases with solitary small HCCs (< or = 3.0cm at the time of detection), the clinicopathologic features of 7 patients who had undergone hepatectomy after various non-surgical therapies (Salvage (S) group) were analyzed and compared with those of 30 patients who received hepatectomy as the initial treatment (Control (C) group).
  • RESULTS: In S group, the serum alpha-fetoprotein level was higher (p = 0.045) and macroscopic ductal invasion was more common (p = 0.028) at the time of the operation.
  • Lobectomy was more commonly performed (p = 0.034) and curability B (No residual cancer, but Stage III or IV) was more frequent (p = 0.011).
  • The survival time after the initial treatment (post-initial treatment survival) was worse (p = 0.028).
  • Univariate analyses revealed that those with maximum tumor sizes of > 3.0 cm at the time of the operation were significantly worse compared with the other patients (p = 0.012).
  • CONCLUSIONS: The timing for changing from a non-surgical treatment to a surgical treatment is important.
  • [MeSH-major] Carcinoma, Hepatocellular / surgery. Hepatectomy. Liver Neoplasms / surgery. Salvage Therapy
  • [MeSH-minor] Aged. Catheter Ablation. Chemoembolization, Therapeutic. Disease Progression. Female. Hepatic Duct, Common / pathology. Humans. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Recurrence, Local / pathology. Neoplasm Staging. Prognosis. Retrospective Studies. Survival Analysis. Treatment Failure

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  • (PMID = 21033242.001).
  • [ISSN] 0172-6390
  • [Journal-full-title] Hepato-gastroenterology
  • [ISO-abbreviation] Hepatogastroenterology
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
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13. Gervain J: [Symptoms of hepatocellular carcinoma. Laboratory tests used for its diagnosis and screening]. Orv Hetil; 2010 Aug 29;151(35):1415-7
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  • [Title] [Symptoms of hepatocellular carcinoma. Laboratory tests used for its diagnosis and screening].
  • Early stage hepatocellular carcinoma is a symptom-free disease.
  • Local and general symptoms occur due to the growth of the tumor tissue and the infiltration of the surrounding blood vessels.
  • Illness progression is indicated by the development of abdominal discomfort, cachexia, therapy-resistant decompensation of previously compensated cirrhosis and in severe cases, the thrombosis of the portal vein or the hepatic veins.
  • Characteristic laboratory findings are the quickly deteriorating blood and liver function tests results, the occurrence of haemostatic disorders and occasional hypoglycemia and/or hypercalcemia.
  • To clarify the etiology and to identify high risk patients, we need to differentiate alcohol-, drug- or chemical-induced hepatic disorders, viral hepatitis B, C and Delta, metabolic disorders and non-alcoholic steatohepatitis.
  • In the case of focal hepatic lesions, persistently elevated alfa fetoprotein levels have a high diagnostic value.
  • At levels over 200 ng/ml, the positive predictive value is >90%.
  • Other, less commonly measured biomarkers are the glycosilated alfa fetoprotein-L3 and the vitamin K-deficiency induced des-gamma-carboxy prothrombin.
  • The risk of tumor occurrence is multiple in patients with HbeAg positive chronic hepatitis B if the virus is of genotype C with mutations in the 1762 and 1764 locations of the core promoter region.
  • Abdominal ultrasound and measurement of alfa fetoprotein is recommended every 6 months for high risk individuals, or every 3-4 months over an 18-24 months period for patients with hepatic lesions of <1cm and of unknown malignancy.
  • [MeSH-major] Biomarkers, Tumor / blood. Carcinoma, Hepatocellular / diagnosis. Carcinoma, Hepatocellular / prevention & control. Liver Neoplasms / diagnosis. Liver Neoplasms / prevention & control. Mass Screening / methods
  • [MeSH-minor] Alcohol Drinking / adverse effects. Biomarkers / blood. Drug-Induced Liver Injury / complications. Early Detection of Cancer. Fatty Liver / complications. Hepatitis, Viral, Human / complications. Humans. Protein Precursors / blood. Prothrombin. alpha-Fetoproteins / metabolism

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  • (PMID = 20719715.001).
  • [ISSN] 0030-6002
  • [Journal-full-title] Orvosi hetilap
  • [ISO-abbreviation] Orv Hetil
  • [Language] hun
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Hungary
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Biomarkers, Tumor; 0 / Protein Precursors; 0 / alpha-Fetoproteins; 53230-14-1 / acarboxyprothrombin; 9001-26-7 / Prothrombin
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14. Zhang Z, Fan S: [Liver transplantation for hepatocellular carcinoma: a report of 8 patients]. Zhonghua Wai Ke Za Zhi; 2000 Jun;38(6):415-7
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  • [Title] [Liver transplantation for hepatocellular carcinoma: a report of 8 patients].
  • OBJECTIVE: To evaluate the feasibility of liver transplantation as a treatment for hepatocellular carcinoma (HCC).
  • METHODS: From July 1995 to October 1998, eight liver cancer patients with cirrhosis underwent liver transplantation in Queen Mary Hospital.
  • The liver grafts were obtained from 6 brainstem dead donors and 2 living donors.
  • Five patients had known HCC and 3 had incidental tumor identified in the explanted liver.
  • TNM staging: stage II (5 cases), stage III (2 cases) and stage IV a (1 case).
  • After liver transplantation, the patients were followed up prospectively for a median of 36 months.
  • Except for one patient who had preoperative chemotherapy, no anticancer treatment was given before and after transplantation.
  • RESULTS: Three patients had acute rejection, 5 developed complication in early post transplantation.
  • CONCLUSIONS: Liver transplantation is a feasible method for treatment of HCC in selected patients.
  • Living donor liver transplantation can overcome the problems of donor shortage and tumor growth while waiting for liver transplantation.
  • [MeSH-major] Liver Neoplasms / surgery. Liver Transplantation
  • [MeSH-minor] Adult. Female. Follow-Up Studies. Humans. Liver Cirrhosis / complications. Male. Middle Aged. Tissue Donors. Treatment Outcome

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  • (PMID = 11832071.001).
  • [ISSN] 0529-5815
  • [Journal-full-title] Zhonghua wai ke za zhi [Chinese journal of surgery]
  • [ISO-abbreviation] Zhonghua Wai Ke Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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15. Katzenstein HM, Krailo MD, Malogolowkin MH, Ortega JA, Liu-Mares W, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Newman K, Finegold MJ, Haas JE, Sensel MG, Castleberry RP, Bowman LC: Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study. J Clin Oncol; 2002 Jun 15;20(12):2789-97
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  • [Title] Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study.
  • PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B).
  • PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children's Cancer Group (CCG) 8881).
  • After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26).
  • Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively.
  • Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy.
  • CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy.
  • Outcome was uniformly poor for children with advanced-stage disease treated with either regimen.
  • New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Carcinoma, Hepatocellular / surgery. Liver Neoplasms / drug therapy. Liver Neoplasms / surgery
  • [MeSH-minor] Adolescent. Chemotherapy, Adjuvant. Child. Child, Preschool. Cisplatin / administration & dosage. Disease-Free Survival. Doxorubicin / administration & dosage. Female. Fluorouracil / administration & dosage. Humans. Infant. Infant, Newborn. Infusions, Intravenous. Male. Neoplasm Staging. Prognosis. Treatment Outcome. Vincristine / administration & dosage

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  • (PMID = 12065555.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R25 CA092049
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil
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16. Das UN: Occlusion of infusion vessels on gamma-linolenic acid infusion. Prostaglandins Leukot Essent Fatty Acids; 2004 Jan;70(1):23-32
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  • In this study, the effect of lithium salt of GLA conjugated to iodized lymphographic oil (LGIOC) was injected intra-arterially close to the origin of tumor-feeding vessel(s) was studied.
  • Four patients with stage 4 cancer disease (2 with hepatocellular carcinoma, 1 with giant cell tumor of the bone, and one with renal cell carcinoma), were selected for the study.
  • Angiography, radiography and computed axial tomography were performed prior to and immediately after the injection of LGIOC and at periodic intervals.
  • All four patients tolerated the treatment well.
  • The most significant observation was the complete occlusion of the tumor-feeding vessels after LGIOC injection.
  • Follow-up angiograms performed in all the patients showed occlusion of the tumor-feeding vessels is more or less permanent.
  • A significant reduction in the size of the tumor was also observed in these patients.
  • LGIOC showed occlusion of tumor-feeding vessels after infusion, and further studies are needed to confirm these preliminary results.
  • [MeSH-major] Neoplasms / drug therapy. gamma-Linolenic Acid / administration & dosage. gamma-Linolenic Acid / pharmacology
  • [MeSH-minor] Adult. Aged. Carcinoma, Hepatocellular / drug therapy. Carcinoma, Hepatocellular / pathology. Carcinoma, Hepatocellular / radiography. Carcinoma, Renal Cell / drug therapy. Carcinoma, Renal Cell / pathology. Carcinoma, Renal Cell / radiography. Giant Cell Tumor of Bone / drug therapy. Giant Cell Tumor of Bone / pathology. Giant Cell Tumor of Bone / radiography. Humans. Male. Middle Aged

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  • (PMID = 14643176.001).
  • [ISSN] 0952-3278
  • [Journal-full-title] Prostaglandins, leukotrienes, and essential fatty acids
  • [ISO-abbreviation] Prostaglandins Leukot. Essent. Fatty Acids
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Scotland
  • [Chemical-registry-number] 78YC2MAX4O / gamma-Linolenic Acid
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17. Zaydfudim V, Whiteside MA, Griffin MR, Feurer ID, Wright JK, Pinson CW: Health insurance status affects staging and influences treatment strategies in patients with hepatocellular carcinoma. Ann Surg Oncol; 2010 Dec;17(12):3104-11
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Health insurance status affects staging and influences treatment strategies in patients with hepatocellular carcinoma.
  • BACKGROUND: Lack of health insurance is associated with poorer outcomes for patients with cancers amenable to early detection.
  • The effect of insurance status on hepatocellular carcinoma (HCC) presentation stage and treatment outcomes has not been examined.
  • We examined the effect of health insurance status on stage of presentation, treatment strategies, and survival in patients with HCC.
  • METHODS: The Tennessee Cancer Registry was queried for patients treated for HCC between January 2004 and December 2006.
  • (2) government insurance (non-Medicaid);.
  • Logistic, Kaplan-Meier, and Cox models tested the effects of demographic and clinical covariates on the likelihood of having surgical or chemotherapeutic treatments and survival.
  • The uninsured were more likely to present with stage IV disease (P = 0.005).
  • After adjusting for demographics and tumor stage, Medicaid and uninsured patients were less likely to receive surgical treatment (both P < 0.01) but were just as likely to be treated with chemotherapy (P ≥ 0.243).
  • Survival was significantly better in privately insured patients and in those treated with surgery or chemotherapy (all P < 0.01).
  • CONCLUSIONS: Uninsured patients with HCC are more likely to present with late-stage disease.
  • Although insurance status did not affect chemotherapy utilization, Medicaid and uninsured patients were less likely to receive surgical treatment.
  • [MeSH-major] Antineoplastic Agents / economics. Carcinoma, Hepatocellular / economics. Catheter Ablation / economics. Hepatectomy / economics. Insurance, Health. Liver Neoplasms / economics. Liver Transplantation / economics
  • [MeSH-minor] Combined Modality Therapy. Female. Humans. Insurance Coverage. Male. Middle Aged. Neoplasm Staging. Registries. Retrospective Studies. Risk Factors. Survival Rate. Treatment Outcome

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  • (PMID = 20585872.001).
  • [ISSN] 1534-4681
  • [Journal-full-title] Annals of surgical oncology
  • [ISO-abbreviation] Ann. Surg. Oncol.
  • [Language] eng
  • [Grant] United States / AHRQ HHS / HS / T32 HS 013833
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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18. Kamiyama T, Nakagawa T, Nakanishi K, Kurauchi N, Kamachi H, Matsushita M, Todo S: [Postoperative adjuvant intraarterial chemotherapy of combined cisplatin and 5-FU for advanced hepatocellular carcinoma]. Gan To Kagaku Ryoho; 2003 Oct;30(11):1618-20
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  • [Title] [Postoperative adjuvant intraarterial chemotherapy of combined cisplatin and 5-FU for advanced hepatocellular carcinoma].
  • Postoperative adjuvant intraarterial infusion chemotherapy was performed for 22 hepatectomized patients with Stage III and Stage IV-A hepatocellular carcinoma from July, 1997, to December, 1999.
  • One course of this chemotherapy consisted of cisplatin (10 mg/body/day on days 1-5) followed by 5-FU (250 mg/body/day on days 1-5).
  • One hundred forty-eight patients of Stage III and Stage IV-A underwent hepatectomy from 1992 to 2001 and were enrolled as historical control.
  • There were 9 Stage III cases treated with this adjuvant chemotherapy, and there were 7 or 6 Stage IV-A cases with and without main portal thrombosis, respectively.
  • Survival and disease-free survival curves were not improved compared to historical control by this adjuvant chemotherapy.
  • The number of recurrences in the remnant liver of 2 Stage IV-A cases with main portal thrombosis was limited to 3.
  • Those cases treated with rehepatectomy and transarterial chemoembolization survived about 1,200 days without tumor recurrence.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Hepatectomy. Liver Neoplasms / drug therapy
  • [MeSH-minor] Chemotherapy, Adjuvant. Cisplatin / administration & dosage. Fluorouracil / administration & dosage. Humans. Infusions, Intra-Arterial. Neoplasm Staging. Postoperative Care. Prognosis

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  • (PMID = 14619478.001).
  • [ISSN] 0385-0684
  • [Journal-full-title] Gan to kagaku ryoho. Cancer & chemotherapy
  • [ISO-abbreviation] Gan To Kagaku Ryoho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] Q20Q21Q62J / Cisplatin; U3P01618RT / Fluorouracil; CF regimen
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19. Lin AY, Fisher GA, So S, Tang C, Levitt L: Phase II study of imatinib in unresectable hepatocellular carcinoma. Am J Clin Oncol; 2008 Feb;31(1):84-8
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  • [Title] Phase II study of imatinib in unresectable hepatocellular carcinoma.
  • BACKGROUND: The expression of platelet-derived growth factor, a potent mitogen, and its receptor both in tissue and serum correlate with the severity of liver cirrhosis.
  • Over-expression of platelet-derived growth factor has been demonstrated in human hepatocellular carcinoma (HCC) tumors and cell lines.
  • METHODS: Eligibility criteria consisted of HCC patient over the age of 18 with reasonable organ function, unresectable but measurable disease, not candidates for chemoinfusion, and a performance status of 0 to 2.
  • Metastatic disease (American Joint Committee on Cancer stage IV) was noted in 13 patients and locally advanced (stage III) in the remainder.
  • The median dose-level of imatinib was 500 mg/d.
  • No grade 3 or 4 hematologic toxicity was observed.
  • Two patients had grade 3 elevated liver function tests during treatment; otherwise, there was no other grade 3 or 4 nonhematologic toxicity noted.
  • CONCLUSION: Although toxicities were tolerable, imatinib as a monotherapy for the treatment of unresectable HCC has little, if any, significant efficacy.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma, Hepatocellular / drug therapy. Liver Neoplasms / drug therapy. Piperazines / therapeutic use. Pyrimidines / therapeutic use
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Benzamides. Bone Neoplasms / drug therapy. Bone Neoplasms / secondary. Bone Neoplasms / surgery. Female. Heart Neoplasms / drug therapy. Heart Neoplasms / secondary. Heart Neoplasms / surgery. Humans. Imatinib Mesylate. Lung Neoplasms / drug therapy. Lung Neoplasms / secondary. Lung Neoplasms / surgery. Male. Middle Aged. Prognosis. Protein-Tyrosine Kinases / antagonists & inhibitors. Survival Rate. Treatment Outcome

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  • (PMID = 18376233.001).
  • [ISSN] 1537-453X
  • [Journal-full-title] American journal of clinical oncology
  • [ISO-abbreviation] Am. J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate; EC 2.7.10.1 / Protein-Tyrosine Kinases
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20. Sasaki F, Matsunaga T, Iwafuchi M, Hayashi Y, Ohkawa H, Ohira M, Okamatsu T, Sugito T, Tsuchida Y, Toyosaka A, Nagahara N, Nishihira H, Hata Y, Uchino J, Misugi K, Ohnuma N, (Japanese Study Group for Pediatric Liver Tumor): Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: A report from the Japanese Study Group for Pediatric Liver Tumor. J Pediatr Surg; 2002 Jun;37(6):851-6
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  • [Title] Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: A report from the Japanese Study Group for Pediatric Liver Tumor.
  • PURPOSE: Hepatoblastoma is the most common malignant liver tumor in childhood.
  • This report reviews the results of the Japanese Study Group for Pediatric Liver Tumor Protocol-1 (JPLT-1) and compares its outcomes with published reports of other studies.
  • METHODS: From March 1991 to December 1999, 154 patients with malignant liver tumor including 145 cases of hepatoblastomas were enrolled in the JPLT study.
  • JPLT-1 protocol 91A was used for patients with stage I or II hepatoblastoma.
  • The chemotherapy regimen consisted of repeated courses of cisplatin (CDDP), 40 mg/m(2), and tetrahydropyranyl (THP)-Adriamycin, 30 mg/m(2).
  • JPLT-1 protocol 91B was administered to patients with stage IIIA, IIIB, or IV hepatoblastoma.
  • The chemotherapy regimen consisted of repeated courses of CDDP, 80 mg/m(2), and THP-Adriamycin, 30 mg/m(2)/day for 2 days.
  • RESULTS: Seven patients died of chemotherapy-related side effects.
  • Six of them died of sepsis caused by leukopenia and 1 case of liver failure.
  • Overall survival rate (3-year/6-year) was 100%/100% for stage I (n = 9), 100%/95.7% for stage II (n = 32), 76.6%/73.8% for stage IIIA (n = 48), 50.3%/50.3% for stage IIIB (n = 25), 64.8%/38.9% for stage IV (n = 20), and 77.8%/73.4% overall.
  • For stage IIIA and B disease, intravenous chemotherapy was better than intraarterial chemotherapy (66.4% v 38.1% for event-free survival and 69.3% v. 57.1% for overall survival).
  • Patients less than 1 year of age had a better prognosis than older patients, but age was not a significant prognostic factor by multivariate analysis.
  • The event-free survival rate at 3 years for stage IIIB and IV disease was under 50%.
  • New treatment strategies are needed for patients with advanced hepatoblastoma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Doxorubicin / analogs & derivatives. Hepatoblastoma / drug therapy. Liver Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Age Factors. Chemotherapy, Adjuvant. Child. Child, Preschool. Cisplatin / administration & dosage. Female. Humans. Infant. Infant, Newborn. Injections, Intra-Arterial. Injections, Intravenous. Male. Neoplasm Staging. Survival Rate. Treatment Outcome

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  • [Copyright] Copyright 2002, Elsevier Science (USA). All rights reserved.
  • (PMID = 12037748.001).
  • [ISSN] 1531-5037
  • [Journal-full-title] Journal of pediatric surgery
  • [ISO-abbreviation] J. Pediatr. Surg.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 80168379AG / Doxorubicin; D58G680W0G / pirarubicin; Q20Q21Q62J / Cisplatin
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21. Bhagat V, Javle M, Yu J, Agrawal A, Gibbs JF, Kuvshinoff B, Nava E, Iyer R: Combined hepatocholangiocarcinoma: case-series and review of literature. Int J Gastrointest Cancer; 2006;37(1):27-34
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • BACKGROUND AND AIM: Combined hepatocholangiocarcinoma (CHCC) is an infrequent primary hepatic malignancy with no clearly defined diagnostic criteria, poorly studied natural history, and no guidelines regarding therapy.
  • Eight cases were identified; histological and immunohistochemical criteria used for diagnosis were defined.
  • Abdominal pain (n = 6), hepatomegaly (n = 4), and elevated CA 19-9 >40 U/mL (n = 4/5) were frequent.
  • Early TNM stage (I and II) compared with advanced disease (III and IV) correlated with higher overall survival on univariate analyses [37 and 6 mo respectively (p = 0.011)].
  • Median overall survival was significantly higher in patients who underwent potentially curative resection (23 mo, range 4-48+) compared with patients who underwent non-surgical therapies such as transcatheter arterial chemoembolization and chemotherapy (2 mo, range 1-8) (p = 0.0357, one-sided exact log-rank test).
  • Surgical resection and early stage at diagnosis predict longer survival.
  • [MeSH-major] Carcinoma, Hepatocellular / complications. Cholangiocarcinoma / complications. Liver Neoplasms / complications
  • [MeSH-minor] Aged. Aged, 80 and over. CA-19-9 Antigen / blood. Cholelithiasis / epidemiology. Female. Hepatitis B, Chronic / epidemiology. Humans. Male. Middle Aged. Retrospective Studies. Risk Factors

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  • (PMID = 17290078.001).
  • [ISSN] 1537-3649
  • [Journal-full-title] International journal of gastrointestinal cancer
  • [ISO-abbreviation] Int J Gastrointest Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / CA-19-9 Antigen
  • [Number-of-references] 37
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