Hepatobiliary Tumors Research Articles

Relationship between anal occult blood and hepatobiliary pancreatic carcinoma screening.

Cotton swab anal smear instead of stool occult blood test can not only be used as a mass screening method for colorectal cancer, but is an auxiliary way to screen hepatobiliary pancreatic carcinoma. Two hundred and twenty-three cases of hepatobiliary pancreatic carcinoma patients received anal occult blood test, of which 121 were positive (54.3%). The screening test was performed in 14,645 healthy people aged 40-60 years; 511 persons (3.4%) were positive for anal blood. Among these, six cases of digestive tract cancer were found (one oesophageal carcinoma, one gastric cardia carcinoma, two gastric carcinomas, two liver carcinomas). This suggests that when anal occult blood is positive, the patient should be scanned by ultrasonic means to rule out hepatobiliary pancreatic tumour.

Pancreatic and hepatobiliary cancers: Problems in staging of pancreatic and hepatobiliary tumours

Pancreatic and hepatobiliary cancers: Problems in staging of pancreatic and hepatobiliary tumours

Genes and viruses in hepatobiliary neoplasia.

Hepatobiliary neoplasms comprise a significant portion of the worldwide cancer burden. Advances in basic science research have led to rapid progress in our understanding of the molecular events responsible for these dreaded diseases. The genetic changes associated with hepatocellular carcinoma (HCC) have received the most attention. Aflatoxin B1 exposure leads to mutations in the p53 tumor suppressor gene, most commonly a transversion in codon 249 that leads to a substitution of serine for arginine in the p53 protein. Numerous other tumor suppressor genes, oncogenes, and tumor gene pathways are altered in HCC. Hepatitis B virus (HBV) infection is strongly associated with HCC. HBV may cause HCC either directly via the HBV X protein, or indirectly by causing liver inflammation and cirrhosis. Hepatitis C virus (HCV) infection is also associated with HCC. Recent evidence suggests that the HCV core protein may play a role in hepatocarcinogenesis. Several inherited metabolic diseases are associated with HCC. It is likely that these diseases cause HCC indirectly by causing cirrhosis. The molecular pathogenesis of cholangiocarcinoma and gallbladder cancer has not been well defined. However, multiple tumor suppressor genes and oncogenes, including p53 and K-ras, are altered in these tumors. Further molecular characterization of hepatobiliary tumors may lead to earlier diagnosis, better staging, improved treatment planning, and the development of more effective therapies.

Diagnostic imaging approaches and relationship to hepatobiliary cancer staging and therapy.

Diagnostic imaging plays an essential role in management of hepatobiliary tumors. High resolution images provided by computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) allow detection of tumor within the liver. CT arterial portography remains the standard for detection of small lesions in the range of 1.5 cm, but noninvasive techniques such as contrast-enhanced helical CT and MR hold promise for comparable lesion detection. MRI provides lesion characterization for differentiation of benign and malignant tumors. Lesion characterization has been further improved by faster CT and MR techniques that allow imaging in both arterial and portal venous phases for characterization of lesions based on the rate and pattern of enhancement. Functional imaging such as 2-fluoro-2-deoxy-D-glucose-positron-emission tomography (FDG-PET) is increasingly utilized for detection of intrahepatic tumor and extrahepatic disease. Accuracy of FDG-PET for extrahepatic disease is better than conventional imaging and has been shown to change management in a significant number of patients. Imaging is also invaluable for surgical planning. Segmental anatomy is well shown by CT, MRI, and US. CT or MR angiography with newer 3D techniques delineate vascular variants and areas of encasement or occlusion by tumor. Biliary involvement at the hilus may be shown by US and MR cholangiography. Imaging detection of vascular involvement, bile duct extension, and lobar atrophy may alter the surgical approach.

CT portography by direct intrasplenic contrast injection: a new technique.

The evaluation of percutaneous contrast injection into splenic parenchyma as an alternative technique for computed tomographic (CT) portography in the preoperative assessment of primary hepatobiliary tumors. Thirty-two patients underwent a nonenhanced CT scan of the liver, after which a 19-gauge, 10-cm-long needle was introduced into the splenic parenchyma under CT guidance. One hundred forty milliliters of contrast medium (200 mgI/mL; 28 g/I) were injected through this needle: first, a 20-mL bolus (in 5 s) and then 2 mL/s for 60 s. At the end of the bolus injection (5 s), 8-mm-thick contiguous axial scans of the liver were obtained. The success rate of the procedure was 93.7% (30/32; two technical failures). The average time required for the entire study was 13 min and 50 s (range = 7 min 53 s to 25 min 17 s). Hepatic parenchymal enhancement was good in 24/30 (80%), moderate in 3/30 (10%), and unsatisfactory in caudal sections of the liver in 3/30 (10%). Artifactual perfusion defects were seen in 4/30 (13%) due to inadvertant injection of small quantities of air. Intrasplenic subcapsular contrast accumulation occurred in 56.2% (18/32; minimal 15, moderate 3), extrasplenic contrast leakage in 12. 5% (4/32), and left shoulder pain in 18.7% (6/32). No major complications were observed. Direct intrasplenic contrast injection for CT portography is a simple, effective, and safe technique with a high success rate and requires significantly less time and lower doses of contrast medium; it also eliminates angiography, indwelling arterial catheters, and patient transfers from angiography to the CT area.

Imaging of Hepatobiliary Neoplasms

Improvements in imaging have markedly improved the ability to detect hepatobiliary masses. The radiologic features of a lesion when considered in the context of the medical history, physical findings, and laboratory data can often provide a diagnosis. Investigative modalities can accurately stage hepatobiliary tumors and determine their resectability so that the patient may be offered appropriate therapeutic interventions. This article summarizes the essential imaging techniques and their application to common hepatobiliary neoplasms.

Clinical Experience with Cryosurgery for Advanced Hepatobiliary Tumors

Introduction.There have been reports that suggest cryosurgical techniques may be a useful adjunct to surgical resection or even a viable alternative treatment for hepatobiliary malignancies. Our objective was to evaluate the clinical results following cryoablation in conjunction with surgical resection for advanced hepatic tumors.Materials and methods.Thirty-two consecutive procedures in 31 patients with advanced liver tumors treated with cryosurgical ablation were evaluated. Cryosurgery was applied: (1) to achieve a >1-cm tumor-free margin when standard surgical margins were close (2) with or without standard surgical resection to manage multiple tumors (3) with hepatic arterial portocath placement to increase tumor response. Cryoablation was applied to 47 of 105 lesions—independently in 4 patients and in combination with hepatic resection in 28 procedures.Results.Cryoablation was used in 11 procedures because of close surgical margins. In 21 operations cryosurgery was used for primary ablation. In 17 of these 21 patients both cryosurgery and resection were used for different lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes, PT, PTT, and platelets were at maximum on Postoperative Days 1–3. Surgical mortality and morbidity rates were 6 and 60%, respectively. Coagulation abnormalities were common: at least 30% reduction in platelets occurred in all patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty patients had a PT >15 s and 6 of these 20 also had a platelet count <50,000. Associated complications included one wound hematoma, two GI hemorrhages, one intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site. The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36 months, respectively.Conclusions.This report helps define the risks and results of cryosurgical ablation as a complement to surgical resection for advanced hepatobiliary tumors. Management of lesions contiguous to major blood vessels may include either the Pringle maneuver or total vascular isolation. Since these procedures can have significant morbidity, we urge cautious application of cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable patients.

A Phase I trial of hepatic arterial bromodeoxyuridine and conformal radiation therapy for patients with primary hepatobiliary cancers or colorectal liver metastases

We have previously found that conformal radiation therapy (RT) and hepatic arterial fluorodeoxyuridine was associated with durable responses and long-term survival for patients treated for nondiffuse primary hepatobiliary tumors and colorectal liver metastases. Further improvements in hepatic control may result from the addition of selective radiosensitization using bromodeoxyuridine (BrdU) infused through the hepatic artery (HA) concurrently with RT. This is a Phase I study of escalating doses of HA BrdU combined with our standard hepatic RT. Patients with unresectable primary hepatobiliary cancer or colorectal liver metastases were treated with concurrent HA BrdU and conformal RT (1.5 Gy per fraction, twice a day). Three-dimensional treatment planning was used to define both the target and normal liver volumes. The total dose of RT (24, 48, or 66 Gy) was determined by the fractional volume of normal liver excluded from the high dose volume. HA BrdU was escalated in standard Phase I fashion with at least three patients receiving each combination of RT dose and BrdU dose. The starting dose of HA BrdU was 10 mg/kg/day, with two potential escalations to a maximum of 25 mg/kg/day (the maximum tolerable dose of HA BrdU when given alone on this same schedule). Grade > or = 3 toxicity was considered dose limiting. Patients receiving 24 Gy had one cycle of HA BrdU, while those receiving either 48 or 66 Gy had two cycles. Patients were followed for toxicity, complications, and response (when evaluable). A total of 41 patients (18 with colorectal liver metastases, 16 with cholangiocarcinoma and 7 with hepatoma) were treated. Five patients were removed from the protocol (three had HA catheter complications, one developed atrial fibrillation, and one was removed due to recurrent Grade 4 toxicity), although all five are included for toxicity purposes. Dose-limiting toxicity was primarily thrombocytopenia and there was no obvious relationship with the RT dose. Only 2 of 17 cycles given at 25 mg/kg/day had Grade > or = 3 toxicity. Complications developed in four patients, including one patient with radiation-induced liver disease. Response rates were not improved compared to our previous experience. The appropriate dose of HA BrdU for Phase II evaluation is 25 mg/kg/day. Neither the hepatic parenchyma nor the gastrointestinal mucosa appeared to be sensitized by this method of BrdU administration. It is anticipated that these, or still newer methods of therapy, can improve treatment results in the near future.

Indications and Role of Liver Transplantation for Malignant Tumors

PURPOSE: The indication for liver transplantation in malignant liver tumors has been controversial due to disappointing results and shortage of donor organs. The authors evaluated the experience and results of a single center in order to define present indications and selection criteria in hepatobiliary malignancy. PATIENTS AND METHODS: Retrospective analysis of 212 patients who underwent liver transplantation for malignant tumors between 1972 and 1995: Primary hepatobiliary tumors: hepatocellular carcinoma, n = 124 (with underlying cirrhosis, n = 86; fibrolamellar subtype, n = 8); intrahepatic bile duct (cholangiocellular) carcinoma, n = 24; proximal bile duct carcinoma, n = 29; other uncommon entities (n = 15); secondary liver tumors: neuroendocrine, n = 11, and nonendocrine, n = 9. RESULTS: Survival rates in primary liver cancer were correlated to International Union Against Cancer (UICC) tumor stage. For hepatocellular and proximal bile duct carcinoma significantly better outcome was found in UICC-tumor stage I and II versus III and IV. No long-term survival was found after transplantation for intrahepatic bile duct carcinoma, hemangiosarcoma and nonendocrine liver metastases. Comparison of transplant and resected patients with hepatocellular carcinoma stage I and II with underlying cirrhosis showed better survival after transplantation: 1-, 3-, 5-year survival rate of 83.3% versus 76.9%, 75.8% versus 44.0%, 60.6% versus 44.0%, and median survival 96.5 versus 23.2 months. Although this difference was not significant, no patient died from tumor recurrence in the transplant group versus three in the resection group. DISCUSSION AND CONCLUSIONS: Patients with malignant tumors can be selected for transplantation with predictable likelihood for long-term survival. According to the present data, liver transplantation can be considered in unresectable UICC-stage II hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epitheliod hemangioendothelioma and hepatoblastoma as well as liver metastases from neuroendocrine tumors. UICC-stage II and IV hepatocellular carcinoma as well as intrahepatic bile duct carcinoma, hemangiosarcoma and metastases from nonendocrine tumors should be excluded from transplantation alone. For hepatocellular carcinoma, multimodality treatment protocols have had a proven impact on the prevention of early recurrence and prolongation of survival. There is evidence that liver transplantation in still resectable hepatocellular carcinoma with underlying cirrhosis might be more appropriate in order to cure the cancer-bearing disease.

Preoperative risk assessment of hepatic resection for malignant disease.

Clinical, laboratory, functional, and volumetric data of 340 consecutive patients undergoing hepatic resection for malignant disease between November 1990 and June 1995 were analyzed. The operative mortality was 3.3% (8/244 patients). Among 178 patients with liver metastases and 66 with primary hepatobiliary tumors the hospital mortality was 4.1% (10/244 patients) and morbidity 22.0% (54/244 patients). Survival after hepatectomy was strongly influenced by the extent of resection quantified by the parenchymal hepatic resection rate. The prediction of fatal postoperative complications can be improved for patients with hepatic metastases by calculating the liver resection index (sensitivity 75%, specificity 83%).

Rapid production of interleukin-2-secreting tumor cells by herpes simplex virus-mediated gene transfer: implications for autologous vaccine production.

Production of autologous tumor vaccines would be facilitated by the development of a rapid and efficient method for the transfer of genes into freshly isolated cells. To evaluate the potential of replication defective herpes simplex viral (HSV) amplicon vectors as gene transfer vehicles for tumor vaccine generation, a vector that expresses the human interleukin-2 (IL-2) gene (HSV-IL2) and one that expresses Escherichia coli beta-galactosidase (HSVlac) were tested in hepatoma cells of both murine and human origin. Gene transfer into murine hepatoma cells (HEPA 1-6) was both rapid and highly efficient: greater than 50% of cells expressed beta-Gal when infected at a multiplicity of infection (m.o.i.) of 1 with an exposure period of 20 min. Moreover, gene transfer was as efficient in tumor cells after irradiation with 10,000 rads as in nonirradiated tumor cells. Irradiated HEPA 1-6 cells infected with HSV-IL2 for 20 min secreted IL-2 at a rate of 1,200 +/- 160 ng/10(6) cells per day. C57B1/6J mice immunized with irradiated, HSV-IL-2-transduced tumor cells produced in this way demonstrated specific tumor immunity by in vitro splenocyte tumoricidal activity and by in vivo protection against tumor challenge. Human hepatobiliary tumor specimens harvested at the time of operation, irradiated, and infected with HSV-IL-2 also produced nanogram quantities of IL-2/10(6) cells per 24 hr. These results indicate that the HSV amplicon vector is a good candidate vehicle for gene transfer in the production of autologous tumor vaccines. By allowing rapid gene transfer to freshly harvested tumor specimens, these vectors bypass the requirement for cell culture and make feasible reinfusion of genetically modified and irradiated autologous cells within hours of tumor harvest.

Epirubicin, cisplatin and infusional 5-fluorouracil (5-FU) (ECF) in hepatobiliary tumours

Hepatobiliary tumours are rare, often present late and have a poor prognosis, with no current effective systemic therapy available. This study aimed to evaluate the activity and toxicity of epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) in patients with these tumours. From March 1991 to November 1993, 25 patients with advanced biliary tumours and 7 with hepatoma were treated with epirubicin 50 mg/m2 and cisplatin 60 mg/m2 intravenously (i.v.) day 1, each given every 21 days and 5-FU 200 mg/m2/day given as a continuous 24 h i.v. infusion throughout the treatment course. 8 of the 20 (40%) evaluable patients with biliary tumours responded. Median duration of response was 10 months. 2 of the 7 (29%) patients with hepatoma responded. The regimen was well tolerated with minimal haematological and non-haematological toxicity. This novel regimen is active in advanced hepatobiliary tumours.

Three-dimensional treatment planning and conformal radiation therapy: preliminary evaluation

Preliminary clinical results are presented for 209 patients with cancer who had treatment planned on our three-dimensional radiation treatment planning (3-D RTP) system and were treated with external beam conformal radiation therapy. Average times (min) for CT volumetric simulation were: 74 without or 84 with contrast material; 36 for contouring of tumor/target volume and 44 for normal anatomy; 78 for treatment planning; 53 for plan evaluation/optimization; and 58 for verification simulation. Average time of daily treatment sessions with 3-D conformal therapy or standard techniques was comparable for brain, head and neck, thoracic, and hepatobiliary tumors (11.8–14 min and 11.5–12.1, respectively). For prostate cancer patients treated with 3-D conformal technique and Cerrobend blocks, mean treatment time was 19 min; with multileaf collimation it was 14 min and with bilateral arc rotation, 9.8 min. Acute toxicity was comparable to or lower than with standard techniques. Sophisticated 3-D RTP and conformal irradiation can be performed in a significant number of patients at a reasonable cost. Further efforts, including dose-escalation studies, are necessary to develop more versatile and efficient 3-D RTP systems and to enhance the cost benefit of this technology in treatment of patients with cancer.

Analysis of genomic instability in hepatobiliary tract tumors: [formula omitted], P. Yeaton, J. Sato, S.P. Cherian, and C.R. Boland. Univ. of Michigan Medical Center, Ann Arbor, MI, Univ. of Virginia Health Science Center, Charlottesville, VA, and Univ. of Tsukuba, Tsukuba City, Japan

Analysis of genomic instability in hepatobiliary tract tumors: [formula omitted], P. Yeaton, J. Sato, S.P. Cherian, and C.R. Boland. Univ. of Michigan Medical Center, Ann Arbor, MI, Univ. of Virginia Health Science Center, Charlottesville, VA, and Univ. of Tsukuba, Tsukuba City, Japan

Mortality in patients with epilepsy: a study of patients in long term residential care.

The causes of death in a group of patients with severe epilepsy in long term residential care over a period of 11 years were assessed and the standardised mortality rate (SMR) determined. A total of 3392 patient-years were surveyed. One hundred and thirteen deaths were recorded in the period and this represents an overall mortality rate which is almost twice the expected rate for this population (SMR = 1.9; 95% CI 1.6-2.3; p < 0.01). Most deaths were due to cancer (26%), bronchopneumonia (25%), circulatory diseases (24%), were seizure-related (12%) or due to sudden unexpected death (6%). The highest SMRs in the neoplasm sub-group were due to cancers of the pancreas (SMR = 6.2) and hepatobiliary tumours (SMR = 17.6). Twenty per cent of patients died of epilepsy or epilepsy related causes (that is accidents, during seizures, status or sudden unexpected death). One in every 480 patients died due to a sudden unexpected death. This study in a highly selected population seems to confirm suggestions that mortality rates are higher in patients with epilepsy than in the general population, but prospective studies are warranted to ascertain underlying mechanisms.

Experimental and nonexperimental studies: methodological, ethical, and practical implications in the context of hepatobiliary tumors.

Experimental and nonexperimental studies: methodological, ethical, and practical implications in the context of hepatobiliary tumors.

Portal vein resection with a new antithrombogenic catheter.

Curative resection of pancreatic and hepatobiliary tumors is rarely possible because of local invasion, especially into the portal vein. We developed a new antithrombogenic catheter using a heparinized hydrophilic polymer to allow portal vein bypass during resection of tumors invading the portal vein. Pancreatectomy or hepatectomy accompanied by portal vein resection was performed for pancreatic or hepatobiliary cancer, with an intraoperative shunt from the superior mesenteric vein to the femoral vein or from the superior mesenteric vein to the intrahepatic portal vein through the umbilical vein or the hepatic hilar portal vein. Use of the shunt prevented stasis in the superior mesenteric vein and hepatic ischemia even during prolonged occlusion of the portal vein, and portal vein resection was performed in 81 patients with hepatobiliary and pancreatic disease with greater safety and ease.

Pathogenesis of skin and liver neoplasms in white suckers from industrially polluted areas in Lake Ontario

Increased prevalences of epidermal and hepatobiliary neoplasms in white suckers (Catostomu commersoni) and brown bullheads (Ictalurus nebulosus) in the Western region of Lake Ontario have been associated with industrial pollution, but the identity and causative role of environmental carcinogens have not yet been established. Most epidermal tumors of lip and body skin are benign focal proliferations that occur in fish from the polluted Hamilton region, and also in fish from less polluted sites in the Great Lakes. These skin tumors in white suckers do not have consistent alterations in cellular glutathione S-transferase (GST), suggesting that growth of skin tumors is not promoted by chemicals normally detoxified by GST. However, elevated levels of glutathione peroxidase (GPO) and glutathione reductase (GR) in skin papillomas are indicative of promotional peroxidative tissue injury, either caused directly by xenobiotics or indirectly by chemical-induced inflammation. Liver tumors in white suckers from Lake Ontario include preneoplastic, benign, and malignant populations of the hepatocellular and biliary cells, all of which are more prevalent in fish from polluted sites. These liver tumors are consistently associated with chronic cholangiohepatitis and segmental cholangiofibrosis, but these conditions also occur in white suckers in non-industrial locations. Thus, the natural occurrence of biliary disease, not attributable to industrial pollution, may have some influence on the development of liver tumors. Some preneoplastic lesions and the majority of neoplastic hepatocellular and biliary lesions in white suckers have low levels of total GST, indicating that these liver neoplasms are not promoted by xenobiotics normally detoxified by hepatic GSTs. These studies suggest that an understanding of the biochemical changes and pathogenesis of tumors in white suckers can serve as a basis for identifying the chemicals involved in the initiation, promotion, and progression of these skin and hepatic neoplasms.

Surgical Treatment of Metastatic Tumors of the Spine

Metastatic tumors involving the spine cause severe pain and paraplegia. Vertebral body collapse results in spinal collapse results in spinal instability. In order to promote stability and improve pain, anterior fusion with bone cement and posterior fusion with instruments were used. Retrospective study was carried out of 16 cases of the metastatic tumor of the spine in Ewha Womans University Hospital Orthopedic Surgical dept. from Jan. 1982 to Dec. 1988. We have analyzed the results of treatment and obtained following conclusions.The results were as follows :1) Of the 16 patients, the ratio of men to women approximately 3:5 and the high incidence was over 5th. decades.2) According to tumor classification, reproductive tract tumor was in 4 cases(25%), gastric, lung and hepato-biliary tumors in 2 cases each(12%), thyroid tumor in 1 case(7%) unknown origin in 5 cases(31%).3) The thoracic spine commonly involved in 12 cases(75%).4) Anterior fusion with bone cement was in 11 cases and posterior fusion with instrument in 4 cases. Both anterior and posterior fusion was in 1 case.5) In functional results, the ambulation was achieved in 14 cases postoperatively, in 12 cases at 6 months, and 10 cases finally.6) The surgical treatment was valuable, because the good results were appeared in 62.5% finally with loss of pain.

Hepatobiliary Cystadenoma with Mesenchymal Stroma

In a detailed review of cystic hepatobiliary neoplasms, we identified a subset of 50 cases in which tumors were characterized by the presence of a mesenchymal cell layer interposed between an inner epithelial lining and an outer connective tissue layer. We have recently seen three such patients, making a total of 53 patients reported in the English literature. All of the patients were female, 44 of whom, with an average age of 41 years, had benign tumors. The average age of the remaining nine patients was 57 years and these patients had malignant tumors. In seven patients, the malignancy arose from the epithelial layer, but in two patients sarcomatous changes were identified in the mesenchymal tissues. The older age of the patients with malignant tumors with adequate serial biopsies in two cases supported the thesis that malignant transformation may occur in the benign tumors. Moreover the location of the tumor in one of our patients in whom the resected tumor was associated with anomalous right hepatic ducts and portal veins supported the theory that these tumors develop embryologically from nests of primitive hepatobiliary endodermal and mesodermal cells. Although surgical treatment was performed in all patients, 25% of the patients with benign hepatobiliary cystadenoma with mesenchymal stroma (CMS), and 33% of the patients with malignant CMS had tumor recurrence after primary resection. Ninety per cent of these patients had an incomplete resection at the time of their initial operations. Forty-four per cent of the patients with malignant CMS died after a mean follow-up of 17 months. We conclude that CMS (Edmonson's tumor) occurs uniquely in young female patients, develops from nests of primitive embryonal cells, has the potential for malignant transformation, and should be completely resected at primary operation to avoid recurrence.