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Biomedical subjects

K E Hobbs

Publications and source records attributed to K E Hobbs.

At least 19 recordsLinked to original sources
PubMed1999

In vitro assessment of Lipiodol-targeted radiotherapy for liver and colorectal cancer cell lines.

Intra-arterial Lipiodol has been used to deliver targeted therapies to primary, and some metastatic, liver cancers. Targeted radiotherapy has been used by substituting the iodine in Lipiodol with 131Iodine (131I). Early clinical results are encouraging, but the variable response may partly depend on local pharmacokinetics. This study evaluated the in vitro cytotoxic effects of 131I-Lipiodol on human hepatocellular carcinoma (Hep-G2), human colorectal metastatic cancer (SW620), human colorectal hepatic cancer (LoVo) and human umbilical vein endothelial cells (HUVEC) cell lines. The cell cultures were exposed to 131I-Lipiodol for 48 h, following which cell counts and viability were assessed by haemocytometer, S-Rhodamine uptake and radioactivity assay. The effect of exposure to control Lipiodol, 131I-Lipiodol and 131I alone was evaluated. 131I-Lipiodol was cytotoxic against all the cancer cell lines but not against the non-malignant (HUVEC) cell line. The cytotoxicity effects were very similar in all the cancer cell lines. There were no cytotoxic effects following exposure to plain 131I in any of the cell lines (malignant and non-malignant). A similar trend was seen with radioactivity counts using a gamma counter. The cytotoxic effect of 131I-Lipiodol had a graded effect with an increase in cytotoxicity following the increase in the radioactive dose. This study showed that there was a marked cytotoxic effect by 131I-Lipiodol on all the cancer cell lines. There was no difference between the controls and the 131Iodine. This suggests that effective 131I-Lipiodol targeted therapy is dependent on the uptake and retention of Lipiodol by malignant cells.

Cell Division↗
PubMed1996

Human liver cancer cells and endothelial cells incorporate iodised oil.

Iodised oil (lipiodol) administered via the hepatic artery localises selectively in primary liver cell cancers (hepatocellular carcinomas or HCCs) for prolonged periods and has been used as a vehicle for cytotoxic agents. Despite clinical use, the mechanism of lipiodol retention by tumours has remained unclear, embolisation of oil droplets in the tumour vasculature being the prevailing hypothesis. We have investigated the role of tumour and endothelial cells in lipiodol retention. Human liver tumour (Hep G2) cells and human umbilical vein endothelial cells in culture were exposed to lipiodol. Light microscopy using selective silver impregnation stains and transmission electron microscopy revealed lipiodol incorporation by both cell types, probably by pinocytosis. This was not associated with cellular injury in terms of cell lysis, cell replication or radio-labelled leucine uptake. Histological analysis of 24 HCCs either surgically resected or discovered incidentally at liver transplantation (with prior arterial injection of lipiodol) revealed vesicles of lipiodol in the cytoplasm of tumour cells and endothelial cells lining tumour vessels. Thus, lipiodol is likely to deliver cytotoxic agents directly into tumour cells and endothelial cells, both in vitro and in vivo. This may also apply to other lipids and to other human tumours. These findings have significant therapeutic implications.

Carcinoma, Hepatocellular↗
PubMed1995

Epirubicin-Lipiodol chemotherapy versus 131iodine-Lipiodol radiotherapy in the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: Arterially administered iodized oil (Lipiodol) is selectively retained by hepatocellular carcinomas (HCCs), and has been used as a vehicle for delivery of therapeutic agents to these tumors. This study compared the efficacy of Lipiodol-targeted epirubicin chemotherapy with Lipiodol-131I radiotherapy. METHODS: Ninety-five patients with unresectable HCC confined to the liver were administered either Lipiodol-epirubicin emulsion (n = 69; 61 cirrhotics; Okuda tumor Stage I, 14; II, 37; III, 18; epirubicin dose, 75 mg/m2) or Lipiodol-131I (131I) (n = 26; 18 cirrhotics; Okuda tumor Stage I, 6; II, 19; III, 1; dose 750-1050 MBq). The last 28 patients (17 epirubicin, 11 131I) were treated within a prospective randomized trial. Bolus drug or isotope was injected into the hepatic artery by transfemoral cannulation. Lipiodol and 131I uptake were gauged by 10th day computed tomography and 48-hour scintiscan. Treatments were repeated two-monthly when indicated. RESULTS: Tumor size at 2 months remained static or diminished partially in 21 of 38 epirubicin recipients (55%) and 15/22 131I recipients (68%). Actuarial survival at 6, 12, and 24 months was 40%, 25%, and 6% with epirubicin, and 58%, 25%, and 0% with 131I; 30-day mortality was 11% and 15%, respectively. Comparison with historic controls indicated survival benefit in Stages I and II. Similar findings were recorded in the 28 patients in the randomized trial. CONCLUSIONS: Patients with unresectable HCC receiving Lipiodol-epirubicin or Lipiodol-131I show good tumor localization, acceptable toxicity, and comparable survival benefit at 6 and 12 months with either modality.

Actuarial Analysis↗
PubMed1995

Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis.

Hepatocellular carcinoma arising in a patient with genetic haemachromatosis, without cirrhosis, has only been described once previously. We present a patient with a 15 year history of genetic haemachromatosis who underwent resection of a hepatocellular carcinoma in a liver with normal architecture.

Aged↗
PubMed1994

Iodized oil in the treatment of hepatocellular carcinoma.

When injected into the hepatic artery the contrast agent Lipiodol (iodized poppy seed oil) is selectively retained by hepatocellular carcinoma (HCC) for a prolonged period of time. Liver computed tomography (CT) performed after Lipiodol angiography is more sensitive than ordinary CT at imaging HCC. Arterial administration of cytotoxic drugs and radioisotopes conjugated to Lipiodol has been shown to be reasonably safe in patients with irresectable HCC. These therapies, often combined with embolization, provide effective palliation, better tumour response and improved survival compared with other available treatments. Their use as a preoperative adjunct to surgical resection of HCC is controversial.

Animals↗
PubMed1994

Validation of volume blood flow measurements using three-dimensional distance-concentration functions derived from digital x-ray angiograms.

RATIONALE AND OBJECTIVES: The authors present phantom validation of a method for computing pulsatile flow waveforms in arterial vessels from high-frame-rate biplane x-ray angiograms. METHODS: The three-dimensional course of a blood vessel is constructed from biplane digital x-ray angiograms. A parametric image of contrast mass versus time and true three-dimensional path length is generated. Adjacent contrast mass-distance profiles are matched to compute instantaneous velocity, which is multiplied by cross-sectional area to yield volume flow. An electromagnetic flowmeter was used to validate flow estimates in a phantom consisting of 150-mm tubes 3, 4, and 6 mm in diameter, orientated 15 degrees, 30 degrees, and 35 degrees to the imaging plane, with flow rates and waveforms expected in vivo. RESULTS: Mean and peak flows were accurate to within 9% and 10%, respectively, for velocities of less than 1 meter/second at a frame rate of 25 frames per second. CONCLUSIONS: A practical method for computing highly pulsatile flow waveforms in vivo in tortuous vessels is presented.

Algorithms↗
PubMed1994

Abdominal wall haematoma complicating laparoscopic cholecystectomy.

Of 61 consecutive patients undergoing laparoscopic cholecystectomy, 4 (6.25%) developed abdominal wall haematomas. This complication of laparoscopic cholecystectomy may occur more commonly than existing literature suggests, and manifests in the post-operative period (days 2 to 6) by visible bruising, excessive pain or an asymptomatic drop in haematocrit. It is readily confirmed by ultrasonography. While no specific treatment is necessary apart from replacement of significant blood loss, the patient requires reassurance that this apparently alarming complication will rapidly resolve.

Abdominal Muscles↗
PubMed1994

Selective radionuclide localisation in primary liver tumours (pilot study).

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellular carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I-Lipiodol can deliver highly selective internal irradiation to foci of HCC with evidence of objective response and may be the treatment of choice for patients with cirrhosis and a small tumour.

Adult↗
PubMed1994

Case report: localization of lipiodol-radioiodine in hepatic metastases from renal cell carcinoma.

Lipiodol, an iodinated derivative of poppyseed oil, is selectively retained in hepatocellular carcinoma and has been used as a vehicle to deliver localized doses of chemotherapeutic and radioactive agents to such tumours, thereby reducing the problems of external beam irradiation and the systemic toxicity of chemotherapy. We describe the first reported case where Lipiodol-targeted radiotherapy has been administered to a patient with secondary renal cell carcinoma in the liver. Localization was good and there were no complications. This case suggests that in future such patients may benefit from this therapy for unresectable lesions.

Carcinoma, Renal Cell↗
PubMed1993

A prospective study of biliary cytology in 100 patients with bile duct strictures.

In patients with obstructive jaundice due to biliary tract stricture a tissue diagnosis is essential because of the varied treatment options available. Radiological imaging of a biliary stricture may suggest that it is malignant, but only a tissue diagnosis can be conclusive. The difficulty of obtaining biopsy tissue has encouraged the use of cytology in this field. This study prospectively analyzed the diagnostic value of exfoliative bile and brush cytology methods. One hundred consecutive patients with biliary strictures diagnosed at endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography (60 men and 40 women; median age = 71 yr, range = 31 to 91 yr) underwent biliary cytology and were divided into two groups. Group 1 comprised the first 47 patients, who were studied by means of bile cytology alone; and group 2 comprised the subsequent 46 patients, who were studied by means of bile and brush cytology techniques. Seven patients were excluded from analysis because of inadequate follow-up information. A single experienced cytologist examined all samples to determine whether they were neoplastic. Eighty-one patients had malignant strictures and 12 had benign strictures. Combined bile and brush cytology (group 2) was more sensitive than bile cytology alone (group 1) (69% [27 of 39] vs. 33% [16 of 42], p < 0.01). In the patients studied by means of bile and brush cytology methods (group 2), cytologic study of brushings was more sensitive (69% vs. 26%, p < 0.01). No false-positive results were reported in either group (specificity = 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Treatment of small hepatocellular carcinomas.

There is growing interest in screening to detect symptomless hepatocellular carcinoma (HCC), which should be easier to treat than symptomatic tumours. Combined alpha-fetoprotein and ultrasound monitoring can detect HCCs of 1 cm, and Lipiodol retention can be detected in tumours smaller than 1 cm. A number of treatment options are available. Surgical resection may be curative in selected patients with a single small tumour, but the cirrhotic patient is left with a diseased liver and the risk of tumour recurrence or death from underlying liver dysfunction. Orthotopic liver transplantation is a rational treatment for patients with decompensating cirrhosis and a small HCC, but it is expensive and necessitates immunosuppression. A variety of targeted or local therapies, either individually or in combination, can be used to treat HCC. These include percutaneous alcohol injection into an HCC, which may be an alternative to surgical resection. Tumour necrosis can be seen after targeted Lipiodol chemotherapy or radiotherapy. Transcatheter arterial embolisation selectively embolises the feeding artery, and can be combined with Lipiodol chemotherapy. Small tumours are thus amenable to treatment, even in patients who cannot have surgery. Screening and treatment for symptomless HCC seems justified, unless controlled trials teach us differently.

Antineoplastic Agents↗