Kenneth R. Stokes

Hepatic Arterial Chemoembolization for Metastatic Neuroendocrine Tumors

PURPOSE OF THE STUDY To evaluate the effectiveness of chemoembolization of the liver with doxorubicin and iopamidol emulsified in ethiodized oil for the treatment of metastatic neuroendocrine tumors. PATIENTS AND METHODS Twenty patients with hepatic islet cell or carcinoid metastases were treated with selected hepatic arterial embolization consisting of an emulsion of doxorubicin and iopamidol emulsified in ethiodol followed by Gelfoam powder embolization. Fifteen patients had failed intravenous chemotherapy. Two of the patients with carcinoid tumors had three embolizations over 4 and one 6 years earlier with gelatin sponge only. RESULTS In 14 patients with hormonally active tumors, hormones secretion decreased 90% (range 69-98%) in 10 days with relief of symptoms in all patients. Average tumor size decrease was 84%. Average hospital stay was 8 days. Six patients are alive and asymptomatic at 14-33 months postembolization. Fourteen patients have died 2-16 months postembolization. Ten patients died 2-37 months postembolization from progressive liver disease. One of these patients was 103 months post-Gelfoam embolization and 13 months postchemoembolization. In 8 patients, the pancreas was the primary site: 5 were nonfunctioning islet cell carcinomas, 1 glucagonoma, 1 gastrinoma and 1 carcinoid. The primary site in 1 patient with carcinoid was the bronchus, and the primary site was unknown in 1 patient with gastrinoma. The remaining 4 patients died with liver disease under control from renal failure, peritonitis, carcinoid heart failure and generalized bone metastases. The response rate was 95% with median duration of response 8.5 months. The median survival was 24 months. CONCLUSION Chemoembolization with doxorubicin and iopamidol emulsified in ethiodized oil is less morbid than embolization with particulate matter alone, is more convenient and less costly, and it is less morbid than the effects of systemic chemotherapy. The median survival, duration and response compare favorably with other reported therapies.

In Vivo and in Vitro Analysis of the Effectiveness of Doxorubicin Combined with Temporary Arterial Occlusion in Liver Tumors

PURPOSE The authors evaluated the effects of daunomycin (daunorubicin)--an analogue of doxorubicin--ethiodized oil, and arterial occlusion on an in vitro hepatoma analogue and on in vivo rat liver tumors. MATERIALS AND METHODS A human Sk hepatoma cell monolayer sandwich system was used to determine uptake of 3H-daunomycin under normoxic/hypoxic conditions with use of autoradiography. Fluorescence microscopy was used to evaluate the biodistribution of doxorubicin in cell cultures (human Sk hepatoma and colon carcinoma). Microvascular flow adjacent to and within liver tumors and the intrahepatic effects of doxorubicin and ethiodized oil were studied with in vivo video microscopy on exteriorized rat livers containing peripheral hepatomas. RESULTS Increased uptake of 3H-daunomycin by hepatoma cells occurred under hypoxic conditions. Intrahepatic arterial administration of ethiodized oil caused temporary occlusion of peripheral sinusoids following passage through arterioportal anastomoses. Tumors received portal venous and neovascular blood supply and ethiodized oil occluded but did not enter the narrow neovasculature perfusing the tumors. CONCLUSION Hypoxia increases uptake of 3H-daunomycin by human Sk hepatoma and colon carcinoma cell cultures. Selective hepatic arterial occlusion (and perhaps the resultant hypoxia) may facilitate increased uptake of doxorubicin analogues into liver tumors. Hepatomas receive both arterial and portal venous blood supply, and ethiodized oil reaches the tumor via arterioportal anastomoses that perfuse the tumor periphery.

Hepatic Arterial Chemoembolization for Metastatic Endocrine Tumors

PURPOSE In patients with hepatic metastases from endocrine tumors, the safety and effectiveness of chemoembolization with ethiodized oil was determined and compared with those of embolization with particulate matter alone. PATIENTS AND METHODS Twenty patients with hepatic islet cell or carcinoid tumor metastases were treated with selective hepatic artery injection of doxorubicin and iopamidol emulsified in ethiodized oil, followed by gelatin foam powder embolization. RESULTS In 16 patients with hormonally active tumors, hormone secretion decreased 90% (range, 69%-98%) in 10 days, with relief of symptoms in all patients. Average tumor size decrease was 84%; average hospitalization was 8 days. Seventeen patients are alive 6-27 months after embolization, and all are asymptomatic. Three patients died within 1 year after embolization of progressive disease outside the liver. CONCLUSION Chemoembolization with doxorubicin emulsified in ethiodized oil and iopamidol is effective in the treatment of hepatic metastases from endocrine tumors. This technique appears to result in less morbidity than particulate embolization alone.

Percutaneous Intraarterial Thrombolysis: Analysis of Factors Affecting Outcome

PURPOSE The authors report results of high-dose thrombolytic therapy in native arteries and vein grafts and discuss the various factors affecting outcome. PATIENTS AND METHODS In a retrospective study, the outcome of 82 high-dose urokinase infusions in 76 patients was examined. Comorbid risk factors as they relate to outcome were studied extensively with log-linear analysis. Positive thrombolytic outcome (PTO) is defined as complete thrombolysis of a previously occluded segment with restoration of antegrade flow augmented by angioplasty or operative intervention to clear symptoms for 30 days. RESULTS The procedure resulted in a PTO in 63 of 82 instances (77%). The treatment was with urokinase alone in 39 cases (47%) and urokinase followed by surgery in 34 (41%), by angioplasty in four (5%), and by angioplasty in the proximal artery and peripheral vein grafting in five (6%). All stenoses associated with grafts were treated surgically. None of the following affected thrombolytic outcome: age of occlusion, heparin dose, catheter type, length or location of graft, or artery versus graft occlusion. The 30-day mortality was 6.1%, with a procedure-related mortality rate of 2.4%. Overall amputation rate was 18% (74% for patients in whom lysis failed by 30 days). CONCLUSION The presence of at least one runoff vessel was the most important factor affecting outcome (PTO, 95%; P = .00001, chi 2). The most important comorbid risk factor for failed thrombolysis was coronary artery disease (P = .03, chi 2).

Chemoembolization for Hepatocellular Carcinoma: Epinephrine Followed by a Doxorubicin–Ethiodized Oil Emulsion and Gelatin Sponge Powder☆

PURPOSE This study evaluates chemoembolization (CE) of the liver with minimal vasoconstriction followed by selective intraarterial delivery of an emulsion of iopamidol, doxorubicin, and ethiodized oil and temporary occlusion of hepatic artery with gelatin sponge powder in patients with hepatocellular carcinoma. PATIENTS AND METHODS Since 1988, 30 patients with nonresectable hepatocellular carcinoma underwent CE with the above protocol. Intraarterial epinephrine (0.5-1 microgram diluted in 10 mL of saline) was rapidly injected directly into the proper hepatic artery or selectively into the right or left hepatic arteries and was followed by 40-60 mg of doxorubicin dissolved in 10 mL of iopamidol and emulsified in 20 mL of ethiodized oil. The chemoembolic mixture was injected at the rate of arterial flow. Liver function and clotting parameters were monitored three times a day until there was a downward trend toward preembolic levels. Computed tomography (CT) was performed immediately after embolization and at 1-3-month intervals. Embolization was repeated when CT demonstrated recurrent or progressive disease. RESULTS Disease recurred or progressed in 11 patients at 2-17 months after embolization. CE was repeated in four patients; one individual underwent three embolizations. Re-embolization was performed up to 14 months after initial embolization (median, 10 months). Five patients (16.7%) died within 1 month of embolization. Ten patients died at 3-33 months after CE. Two of these patients died of cirrhosis at 6 and 14 months, without evidence of recurrent tumor. Fifteen patients remain alive 5-28 months after CE. Kaplan-Meier estimation of probability of survival curves demonstrates a median survival of 14 months. Sixty-one percent of patients were alive at 1 year and 36% at 2 years after the procedure. CONCLUSION CE with use of the above technique is effective for palliating inoperable hepatocellular carcinoma. It causes a significant prolongation of survival over the expected 18-24 weeks in untreated patients; this may occur because high doses of chemotherapeutic agents are delivered and come in contact with the tumor for a longer period, followed by ischemia brought about by temporary arterial occlusion.

Biliary duct stones: Percutaneous transhepatic removal

Percutaneous transhepatic removal of common bile duct stones was performed 57 times in 53 patients with a success rate of 93%. All patients had contraindications to surgery or had undergone unsuccessful attempts at endoscopic retrograde cholangiopancreatography and papillotomy. A modified Dormia basket was inserted through a percutaneous transhepatic approach and the stones or fragments were advanced into the duodenum. Monooctanoin (26 patients) or methyl tertiary butyl ether (4 patients) was infused to reduce stone size or remove residual debris. The average time for complete stone removal was 8.5 days. Morbidity was 12% and mortality was 4%, results which compare favorably with those of surgery.

Magnetic resonance angiography in transjugular intrahepatic portosystemic stenting: comparison with contrast hepatic and portal venography.

In order to highlight the role of magnetic resonance angiography [MRA] in the assessment of patients pre-transjugular intrahepatic portosystemic shunt (TIPS) stenting, the MRA images of portal and hepatic veins of 21 patients were compared with the images from contrast portal and hepatic venograms performed on the same patients at the time of TIPS stenting (20 patients). MRA enabled accurate, non-invasive, multiplanar imaging of portal and systemic venous anatomy in each of the patients studied. MRA facilitated accurate determination of vessel patency and flow direction, images correlating exactly with contrast venograms of hepatic and portal veins in each case. In one patient, identification of occult hepatocellular carcinoma extending to the portal vein lead to the postponement of the TIPS procedure.