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

PURPOSE: 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. METHODS AND MATERIALS: 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). RESULTS: 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. CONCLUSIONS: 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.

Intravascular ultrasound imaging of vascular responsiveness in isolated perfused canine arteries.

We investigated the feasibility of using intravascular ultrasound imaging to analyze vascular physiology in various arterial beds. Canine superficial femoral, external iliac, and common carotid arteries were harvested and suspended and perfused in a bath of oxygenated, heated, physiologic salt solution. A 6-Fr, 20-MHz ultrasound imaging catheter was inserted into the lumen of the arteries and serial images were acquired after bolus injections of either serotonin or normal saline into the extravascular bathing medium. Serotonin resulted in a significant time- and dose-dependent decrease in cross-sectional area in muscular femoral arteries (P less than .001): -5.2% with 10(-8) M serotonin, -15% with 10(-7) M, and -28% with 10(-6) M. Histologically transitional iliac arteries demonstrated less marked changes, while elastic carotid arteries demonstrated no significant changes. Our results indicate that intravascular ultrasound may be used to quantify and differentiate responses to vasoconstrictive agents in different vascular beds.

Gadolinium-enhanced magnetic resonance venography of the portal venous system prior to transjugular intrahepatic portosystemic shunts and liver transplantation. Original investigation.

RATIONALE AND OBJECTIVES: The accuracy of gadolinium-enhanced magnetic resonance venography (GdMRV) in identifying visceral venous abnormalities was assessed in patients before they underwent transjugular intrahepatic portosystemic shunt (TIPS) or orthotopic liver transplantation (OLT). METHODS: Twenty-seven patients with portal hypertension underwent GdMRV and transcatheter venography prior to OLT or TIPS. The gadolinium dose was 0.5 mL/kg (0.25 mmol/kg), administered by rapid hand injection. Coronal 3D spoiled gradient-echo GdMRV was performed in a single breath-hold. Four blinded reviewers retrospectively evaluated coronal maximum intensity projection (MIP) images, while two reviewers evaluated the MIPs and multiplanar reconstructions. Abnormalities that could affect transjugular intrahepatic portosystemic shunt or transplantation were noted and compared with the results of corresponding catheter venograms read by a separate blinded reviewer. RESULTS: Abnormalities were identified by GdMRV with a sensitivity and specificity of 83% and 97% for the right hepatic vein, 86% and 100% for the main portal vein (MPV), 42% and 99% for the right portal vein, 54% and 94% for the left portal vein, 61% and 96% for the superior mesenteric vein, and 74% and 91% for the splenic vein. Varices and shunts were correctly identified with a sensitivity of 96%. Multiplanar reconstruction increased MPV sensitivity to 100%. CONCLUSION: Vascular abnormalities that affect TIPS and OLT can be identified by GdMRV. Multiplanar reconstruction increased the accuracy to 100% for the MPV.

Evaluation of a new percutaneous stainless steel Greenfield filter by intravascular ultrasonography.

The standard stainless steel Greenfield filter was modified by extending the limbs at the apex to permit loading into a 12F carrier for percutaneous insertion. This model was tested for fixation and resolution of experimental embolism in dogs (six filters in four dogs) and sheep (eight suprarenal filters in eight sheep). Serial radiographs and venacavography at 2 and 4 weeks allowed measurement of migration and suspected caval penetration, confirmed by direct examination at autopsy. Caval penetration was graded according to visibility of point (0), hook (1+), or limb (2+) for each limb of the filter. Oxidized cellulose-induced thrombi were injected and trapped in two dogs and four sheep without proximal filter displacement or thrombus propagation. Thrombi showed incomplete resolution during 4 weeks' observation by interval venacavography and subsequent autopsy but no tendency for proximal propagation. Distal migration occurred in four of six filters in dogs, and caval wall penetration was seen (score 1.8/filter). Less migration was seen in sheep (2/8), but there was evidence of hook penetration in four animals (score 0.88/filter). Intravascular ultrasonography, 20 MHz, with a 6.5 F catheter assembly successfully visualized all 10 filters in which it was attempted and showed thrombi attached to the filter or caval wall, all of which were confirmed at explant. No thrombi were missed; however, intravascular ultrasonography was limited in assessment of caval wall penetration by lack of position control and reverberation artifact. Although it performs well as a filter, the elasticity of the percutaneous stainless steel greenfield filter allows distal migration and caval penetration comparable to the titanium Greenfield filter and will require further modification of hook design to improve performance.

Cholescintigraphy in the critically ill.

Critical review of cholescintigraphy in critically ill patients suggests the examination will not conclusively prove or disprove the diagnosis of acute cholecystitis. Of 17 scans performed in critically ill patients with clinical evidence of acute cholecystitis, 7 were true-negative, 1 was false-negative, 6 were false-positive, and 3 were nondiagnostic. Cholestasis and hepatocyte dysfunction, common in the critically ill, result in abnormal clearance of hepatobiliary radionuclide imaging agents, decreasing the usefulness of cholescintigraphy in this patient population. Diagnosing acute cholecystitis in a critically ill patient remains difficult.

The estimation of occupational effective dose in diagnostic radiology with two dosimeters.

Annual effective dose limits have been proposed by national and international radiation protection committees. Radiation protection agencies must decide upon a method of converting the radiation dose measured from dosimeters to an estimate of effective dose. A proposed method for the estimation of effective dose from the radiation dose to two dosimeters is presented. Correction factors are applied to an over-apron collar dose and an under-apron dose to estimate the effective dose. Correction factors are suggested for two cases, both with and without a thyroid shield. Effective dose may be estimated by the under-apron dose plus 6% of the over-collar dose if a thyroid shield is not worn or plus 2% of the over-collar dose if a thyroid shield is worn. This method provides a reasonable estimate of effective dose that is independent of lead apron thickness and accounts for the use of a thyroid shield.

The use of intra-arterial urokinase in the management of hand ischemia secondary to palmar and digital arterial occlusion.

Impending gangrene of the hand or digits secondary to palmar or digital artery occlusion can be a devastating complication of upper extremity thromboembolic or atheroembolic disease. Over the past 7 years, 9 patients with severe unilateral hand ischemia and impending tissue loss secondary to distal forearm, palmar arch, and digital artery occlusion were managed with intra-arterial urokinase (UK) infusion. The etiology of the ischemia was thromboembolism in 3 patients, atheroembolism in 2, and traumatic ulnar artery occlusion ("hypothenar hammer syndrome") in the remaining 4 patients. Initial high-dose UK was administered in 3 patients (240,000 U per hour for 2 hours) and all 9 patients were maintained on 80,000 to 120,000 U per hour until clot lysis occurred or until a minimum dose of 600,000 U had been given without clinical improvement. Following UK therapy, the 3 patients with thromboemboli had angiographic demonstration of clot lysis as well as complete resolution of ischemia. The 2 patients with atheroemboli showed no angiographic or clinical improvement, and both required surgical intervention. Angiographic improvement was demonstrated in only 1 patient with traumatic ulnar artery occlusion, although 3 of the 4 patients were clinically improved. A pericatheter thrombosis due to insufficient heparinization and a subcutaneous abscess at the femoral artery puncture site were the only complications of UK infusion. No hemorrhagic complications occurred and no adverse effects of lytic therapy were documented in patients who subsequently required surgery. UK is an effective treatment for recent thromboembolism, because it lyses unorganized thrombi. It is ineffective for treatment of organized thrombi or atheroemboli. Because the etiology of acute hand ischemia is not always obvious at the time of presentation, a trial of UK infusion is warranted, because it is relatively safe and its use may obviate the need for complex microsurgical reconstruction.

Cholecystojejunostomy varices demonstrated by enteroclysis.

Varices in unusual sites constitute a minor but significant cause of gastrointestinal bleeding in patients with liver disease. We report a case of varices across the anastomotic line between the jejunum and gallbladder after cholecystojejunostomy. Although such varices have been demonstrated by angiography, to our knowledge they have never been demonstrated by small bowel enema (enteroclysis). We report a case and describe the findings on enteroclysis.

Interventional radiologists: occupational radiation doses and risks.

Interventional radiologists receive nonuniform occupational radiation doses, with relatively high doses to the head and extremities and low doses to the trunk, which is protected by a lead apron. Twenty-eight interventional radiologists from 17 institutions wore thermoluminescent dosimeters over their collars and under their aprons for a 2-month period. The estimated annual radiation dose was converted to effective dose as suggested by the International Commission on Radiological Protection. Effective dose is used to relate the risk associated with nonuniform dose to that associated with an equivalent uniform whole-body dose. The mean annual effective dose was 3.16 mSv (316 mrem), with a range of 0.37-10.1 mSv. The mean annual effective dose is approximately equal to the mean natural background dose of 3 mSv per year from radon and other natural sources and is only 6% of the National Council on Radiation Protection and Measurements' recommended effective dose equivalent limit of 50 mSv per year. The annual radiation risk of fatal cancer would be less than one per 10,000 for almost the entire career of an interventional radiologist.

Occupational radiation exposure to interventional radiologists: a prospective study.

This study investigates the occupational radiation dose to interventional radiologists and the operator-controlled factors that may affect dose. Thirty interventional radiologists wore radiation badges over and under lead aprons for 2 months and answered a questionnaire. The relationships between dose and caseload, case mix, experience, optional fluoroscopy features, lead apron type, and additional lead shielding were evaluated. Mean projected yearly dose (PYD) over lead was 49.1 mSv (1 mSv = 100 mrem) but was 66.6 mSv for persons performing 1,000 or more cases per year (P = .027). Mean PYD under lead was 0.9 mSv but was 1.3 mSv for persons with 0.5-mm lead coverage and 0.4 mSv for those with 1.0-mm lead coverage (P = .002). No other significant correlation was found. Conclusions are that caseload and apron thickness are the primary determinants of total body dose, that over-lead dose is high enough to warrant additional lead shielding for the head and neck, and that a double-thickness apron lowers under-lead dose by two-thirds. The large difference between under-lead and over-lead doses suggests that use of a collar badge alone for monitoring purposes is not predictive of total-body effective dose for this group of radiation workers.

Role of percutaneous intracorporeal electrohydraulic lithotripsy in the treatment of biliary tract calculi. Work in progress.

Although surgery is the treatment of choice for symptomatic gallstones, most bile duct calculi can be successfully treated with the use of routine percutaneous or endoscopic methods. Failure of these methods is most often associated with stones larger than 1.5 cm. The authors used percutaneous intracorporeal electrohydraulic lithotripsy (EHL) to treat 11 patients with calculi in the bile ducts (n = 10) or gallbladder (n = 1) in whom the use of other percutaneous or endoscopic methods failed. The stones in all 11 patients were successfully fragmented and removed. There were no complications. Intracorporeal EHL is an effective alternative therapy for the treatment of biliary tract calculi when standard methods fail.

Chronic intestinal obstruction: value of percutaneous gastrostomy tube placement.

Percutaneous gastrostomy tubes were placed in six patients for treatment of nausea and vomiting associated with chronic intestinal obstruction. There were no complications related to the tubes, and in all patient, symptoms were relieved. For the patient, the advantages of gastrostomy over nasogastric drainage include improved comfort, increased mobility, and a decreased risk of pulmonary aspiration. Percutaneous gastrostomy is a safe procedure and provides excellent palliation for intractable nausea and vomiting in patients with chronic intestinal obstruction.

Creation of reentry tears in aortic dissection by means of percutaneous balloon fenestration: gross anatomic and histologic considerations.

PURPOSE: To study the safety and efficacy of percutaneous fenestration in aortic dissection, transmural tears in canine and human aortae were created with conventional angioplasty balloons. MATERIALS AND METHODS: Tears created in the aortae of five living dogs were compared with tears created in postmortem specimens. Percutaneous fenestration was performed in a woman with acute type I dissection and ischemic hepatitis who died in multisystem failure, and the balloon tear was documented at autopsy. Additional tears in the human aorta were studied in necropsy specimens of normal, Marfanoid, atherosclerotic, and acutely and chronically dissected thoracic and abdominal aortae. RESULTS: In the canine aorta, transmural balloon tears resulted in rapid death of all five animals, and the tears were approximately 10% longer than tears created post mortem with the same balloon. In human aortic specimens, most transmural and all transseptal tears were linear and were oriented nearly perpendicular to the longitudinal axis of the aorta. Tears that were initiated near calcified plaques or large aortic branches extended in unpredictable directions. The transverse orientation of the tears coincided with the long axis of smooth muscle cells in the media of the intact aorta or the dissection septum. CONCLUSION: Percutaneous balloon fenestration, when performed in areas of the aorta relatively free of atherosclerosis, results in transverse tears in the aortic dissection septum. Percutaneous fenestration of the aortic dissection septum appears feasible and should be considered as a treatment option in carefully selected cases of aortic dissection with ischemic complications. A final conclusion regarding the safety and efficacy of percutaneous fenestration undertaken to relieve organ ischemia requires further clinical experience.

Evaluation of the inferior vena cava with intravascular US after Greenfield filter placement.

An animal model was used to evaluate the utility of intravascular ultrasound (US) imaging of the inferior vena cava (IVC) following Greenfield filter placement. Ten Greenfield filters were placed in the IVCs of five sheep and three dogs. Experimentally induced thrombi were injected into four filters at the time of placement. Intravascular US and cavography were performed 4 weeks after filter implant. The imaging studies were evaluated for demonstration of filter position, orientation, and leg distribution, as well as prediction of caval wall penetration by filter hooks. Experimentally induced and spontaneous intrafilter thrombi were also imaged. Findings were compared with those of postmortem examination. Exact filter position and orientation were most simply and accurately demonstrated on radiographs. Filter leg distribution and extent of intrafilter thrombus were best evaluated on intravascular US images. The prevalence of caval wall penetration was underestimated with both studies. The results of this animal study suggest that the information about the IVC provided at cavography and intravascular US following Greenfield filter placement may be complementary.

Massive arterial hemorrhage from the stomach and lower esophagus: impact of embolotherapy on survival.

The authors retrospectively reviewed the clinical courses in 36 patients referred for angiographic evaluation of massive arterial hemorrhage from the stomach, gastroesophageal junction, and lower esophagus. Twenty-four patients underwent embolotherapy, and 12 were treated with nontranscatheter therapy such as surgery, Sengstaken-Blakemore tube placement, endoscopic submucosal injection of epinephrine, or supportive medical therapy. Bleeding was controlled completely in 15 (62%) and partially in three (13%) of the patients who underwent embolotherapy. In nine of the patients treated with nontranscatheter therapy (75%), bleeding control was complete. Sixteen patients died, including seven of 28 in whom bleeding was controlled. There was no significant difference in the mortality rates of patients treated with nontranscatheter therapy (46% and 42%, respectively). Survival correlated with the clinical condition at the time of intervention. All patients with multiorgan failure died, while 87% of the other patients, even those with serious cardiovascular compromise, survived. The results imply that massive gastric hemorrhage should be treated aggressively, before it results in multiorgan failure.

Percutaneous cholecystolithotomy: preliminary experience and technical considerations.

Surgical cholecystectomy is associated with a high morbidity and mortality in elderly patients with acute calculous cholecystitis and underlying cardiac or pulmonary disease. Currently there are few alternatives for treating these patients. The authors have used percutaneous cholecystolithotomy in 11 such high-risk patients for definitive treatment of gallbladder calculi. In all 11 patients all stones were successfully removed from the gallbladder and cystic duct. The entire procedure--from initial tube placement to final tube removal--lasted 17-40 days (mean, 21 days). There were two complications: one minor--local wound infection--and one major--bile peritonitis with eventual death. Percutaneous cholecystolithotomy is an effective alternative therapy for acute calculous cholecystitis in elderly, debilitated patients.

Severe skin reactions from interventional fluoroscopy: case report and review of the literature.

Some patients with certain preexisting health conditions may be at elevated risk for unusually intense radiation-induced skin reactions and late tissue damage from high-dose interventional procedures. The authors present a case report of a patient with mixed connective tissue disease and non-insulin-dependent diabetes mellitus who developed an unusual complication after placement of a transjugular intrahepatic portosystemic shunt. On the basis of a review of the literature, the following experiences may help identify patients at increased risk: previous high-dose procedures, connective tissue disease, diabetes mellitus, and homozygosity for ataxia telangiectasia.

Fluoroscopically guided percutaneous gastrostomy and gastroenterostomy: analysis of 158 consecutive cases.

We reviewed our experience with 158 consecutive patients who underwent either percutaneous gastrostomy or percutaneous gastroenterostomy during a 2-year period. The catheters used included Foley catheters (36), Cope-type gastric catheters (86), or Carey-Alzate-Coons gastrojejunostomy catheters (36). Gastrojejunostomy tubes were placed in patients with gastroesophageal reflux or aspiration, gastric atony, or partial gastric obstruction. Ninety percent of the tubes were placed for feeding purposes. The technical success rate was 100%. Thirty-day follow-up was obtained in 89%. Thirty-day mortality was 26%, reflecting the substantial number of debilitated patients. No deaths were directly related to tube placement. Major morbidity was 6% and included hemorrhage, peritonitis, tube migration, and sepsis. Minor morbidity was 12%. There was no difference in 30-day mortality or feeding tolerance between the tube types (p less than .05). Patients with Foley catheters had more complications necessitating surgical intervention and an increased incidence of tube changes required within 30 days. These were the only statistically significant differences between the tubes (p less than .05). Our results show that percutaneous gastrostomy is a safe and effective means of gastroenteric feeding or decompression. Because of the fewer complications and ease of insertion, the Cope type of gastrostomy tube has become our preferred catheter for percutaneous feeding or decompression.