Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisantrene (NSC-337766) was administered to five patients with cancer of the liver (one case of hepatocellular carcinoma, two of metastatic carcinoma of unknown primary, two of metastatic colorectal carcinoma). Under fluoroscopic guidance, percutaneous hepatic venous catheters were placed in five patients and percutaneous hepatic arterial catheters in four. A fifth patient's hepatic arterial catheter was implanted at laparotomy. Hepatic plasma flow was estimated by the Fick principle using peripheral vein indocyanine green infusion. On the first day of treatment, patients received a 2- or 4 h hepatic arterial infusion of bisantrene (130 mg/m2); peripheral venous, hepatic arterial, and hepatic venous timed blood samples were drawn during and for 18 h after drug infusion. On the second day of treatment, 2- or 4 h peripheral vein infusion of bisantrene (130 mg/m2) was followed by the same blood sampling schedule. Patients were followed weekly for toxicity. Four patients received only one course of treatment, while a fifth received two courses. All patients experienced leukopenia (median nadir 2400/mm3; range 1400-2700/mm3). Two patients developed fever after drug infusion. No antitumor responses were observed. Plasma bisantrene concentrations were measured by HPLC. Pharmacokinetic analyses are reported for four patients. The hepatic extraction ratio ranged from 15% to 49%, hepatic plasma clearances were 0.029-0.353 1/min/m2; peripheral vein areas under the concentration-time curve during hepatic arterial infusion ranged from 35% to 50% of peripheral vein areas under the curve during peripheral vein infusion. We conclude that hepatic arterial bisantrene infusion offers only modest pharmacokinetic advantage to the target organ or to the systemic circulation over peripheral vein infusion.
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PMID:A phase I and pharmacokinetic comparison of hepatic arterial and peripheral vein infusions of bisantrene for liver cancer. 401 63

Extended schedules of oral etoposide have been evaluated in many types of advanced cancer. In addition to their use in the common solid tumours, extended schedules have been employed in Kaposi's sarcoma (both AIDS-related and endemic types), medulloblastoma, glioma, and hepatocellular carcinoma. Single agent activity was demonstrated in all of these tumour subtypes. For patients with carcinoma of unknown primary site, we have recently incorporated a 10-day oral etoposide schedule into a combination regimen that also includes paclitaxel and carboplatin. With this regimen we achieved a 47% response rate in a group of 53 evaluable patients, with a median survival of 13.4 months. Patients with adenocarcinoma and poorly differentiated carcinoma of unknown primary site had comparable response rates and survival. According to a large number of clinical trials and pharmacokinetic data, a daily oral etoposide dose of 50 mg/m2 consistently produces serum concentrations >1 mg/L for several hours each day. Lower doses fail to consistently produce this serum concentration, which is considered necessary for optimum tumoricidal activity. Optimal dose duration is 10 to 14 days, particularly when combination regimens are being employed. Oral etoposide has an established role as a single agent in patients with low grade non-Hodgkin's lymphoma, Kaposi's sarcoma, and testicular cancer (if residual carcinoma is resected after first-line treatment). The optimal use of extended-schedule etoposide in combination regimens is not defined but is being evaluated in a number of etoposide-sensitive malignancies.
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PMID:Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues. 1071 42

Carcinoma of unknown primary (CUP) is not uncommon and poses both diagnostic and therapeutic challenges. Recent developments in immunohistochemical (IHS) stains in diagnostic pathology help resolve many of these clinical dilemmas. Antibodies against Thyroid Transcription Factor (TTF-1), a relatively new and organ specific marker that stains lung and thyroid malignancies, are commonly included in the first battery of stains when dealing with a CUP. The usual pattern of staining for TTF-1 is purely nuclear. However, it was recently noticed that TTF-1 stains the mitochondria of benign hepatocytes and tumor cells in hepatocellular carcinoma. We would like to report two cases where the clue to the hepatic origin of CUP was the presence of cytoplasmic staining for TTF-1. Description of both cases with pertinent literature review will be offered. Two patients were seen at the James H. Quillen Veterans Administration Medical Center (VAMC), where one had a right chest wall mass with previous history of prostatic carcinoma and the other was found to have a lytic rib lesion with a previous history of lung squamous cell carcinoma. FNA and core biopsies were performed on both lesions where the initial pathological interpretations were nonsmall cell carcinoma. IHS revealed positivity for cytokeratin-7 and granular cytoplasmic staining for TTF-1. Further workup using stains for Alpha Fetoprotein, Hepatocyte Paraffin (Hep Par 1) and CEA confirmed the diagnosis of metastatic hepatocellular carcinoma (HCC). Paying attention to cytoplasmic staining for TTF-1 in any CUP should prompt further pathological and clinical evaluation to rule out hepatocellular carcinoma.
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PMID:Carcinoma of unknown primary: check the liver... thanks to TTF-1. 2235 93

The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.
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PMID:Hepatocellular Carcinoma with Cervical Spine and Pelvic Bone Metastases Presenting as Unknown Primary Neoplasm. 2619 30

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.
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PMID:Systemic therapies for intrahepatic cholangiocarcinoma. 3195 97