Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma.

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).

Fetal tachycardia and intramyocardial tumors.

The two-dimensional echocardiographic diagnosis of multiple cardiac rhabdomyomas and evaluation of tachycardia in a fetus are presented. Prenatal echocardiographic examination defined the extent of tumor involvement and mechanism of the tachycardia and demonstrated the lack of fetal hemodynamic compromise. Perinatal, clinical and therapeutic implications are discussed.

Use of radiologic modalities in coccidioidal meningitis.

The diagnostic utility of pentetate indium trisodium in 111 CSF studies, technetium Tc 99m brain scans, and computerized tomographic (CT) scans was evaluated in eight patients in whom coccidioidal meningitis developed following a dust storm in the Central Valley of California. The 111In flow studies and the CT scans demonstrated hydrocephalus in five patients with clinical findings suggesting this complication. Ventriculitis has not previously been diagnosed before death in patients with coccidioidal meningitis; however, it was demonstrated in two patients by the technetium Tc 99m brain scan. Basal meningitis, which is indicative of fungal infection, is also detectable on contrast-enhanced CT scan. The finding that communicating hydrocephalus occurs early in meningitis and interferes with CSF flow into infected basilar regions has important therapeutic implications in that antifungal agents injected into the lumbar subarachnoid space may not reach these regions.

Pancreatic pleuropericardial effusions. Fistulous tracts demonstrated by computed tomography.

Demonstration of the fistulous tract linking pancreatic pseudocysts to the mediastinum and pleural cavity has diagnostic and therapeutic implications. In four cases, pseudocyst drainage through the esophageal and aortic diaphragmatic crus into the mediastinum and pleural cavity was delineated by computed tomography. In two cases, significant pericardial effusions were demonstrated. Computed tomography offers an effective diagnostic method when treatment is dependent on anatomic localization of the disrupted pseudocyst and its intrathoracic drainage tract.

A new method for thermocholecystectomy. Initial experience and comparison with other techniques.

RATIONALE AND OBJECTIVES: The authors tested the feasibility of thermocholecystectomy for gallbladder ablation in an animal model. METHODS: Thermal treatment of the cystic duct followed by heating of the saline-filled gallbladder using a separately designed heater/expander was performed in 13 pigs (group I). In four animals, heating of the gallbladder alone was performed (group II). Two animals served as controls (group III). All animals were killed 12 weeks after treatment. RESULTS: There was cystic duct occlusion in 10 (77%) of 13 of group I animals. In 6 (60%) of 10 of these animals with cystic duct occlusion, there was complete ablation of the gallbladder mucosa and complete obliteration of the gallbladder lumen. In group II animals, all cystic ducts were intact with an unchanged gallbladder volume in all four animals (100%), and normal gallbladder mucosa were intact in three (75%) of four animals. The gallbladders and cystic ducts in group III animals were normal. CONCLUSIONS: This study demonstrates many technical difficulties with thermal cholecystectomy. However, under ideal conditions, permanent gallbladder ablation is feasible in our animal model using a specially designed heating system.

Assessment of cerebral blood flow in man by video dilution technique: a preliminary report.

Video dilution technique (VDT) is currently performed in conjunction with routine cerebral angiography to determine carotid blood flow in humans. Preliminary results indicate that the blood flows (as a percentage of cardial output) of the common, internal, and external carotid arteries are 8.5%, 5.5%, and 3.0%, respectively (SD less than 1%). In contradistinction to previous techniques, VDT provides a safe and highly accurate method of determining carotid blood flow in human subjects. The usefulness of this technique in normal and pathologic states is discussed.

Refinement of a technique for thermocholecystectomy in an animal model.

RATIONALE AND OBJECTIVES: A modification of a thermal ablation system was tested for improved cystic duct occlusion and gallbladder mucosa ablation in an animal model. METHODS: Fourteen domestic swine were included in group 1 with thermal treatment of the cystic duct to 75 degrees C for 15 minutes, followed by heating of the gallbladder lumen with a catheter/heating device to 54 degrees C for 30 minutes. One swine served as a control (group 2). A ligature was placed around the cystic duct without thermal treatment of the cystic duct and with the catheter/heating device placed into the gallbladder for 30 minutes without thermal treatment. All animals were killed after 3 weeks with histologic examination of the gallbladder, cystic duct, and surrounding organs. RESULTS: In group 1, technical failure due to catheter clogging occurred in the first three animals, which were killed immediately. Eleven animals were treated with a redesigned catheter system. Three weeks after treatment, 10 of the 11 animals had complete cystic duct occlusion and complete obliteration of the cystic duct mucosa. One of the 11 animals experienced partial cystic duct ablation. Nine of the 11 treated animals experienced complete mucosal ablation of the gallbladder. Five of the 11 animals had no residual lumen, whereas 6 of the 11 had a luminal volume that averaged 4 mL compared to 35 mL before treatment. In group 2, the control subject had a gallbladder volume of 50 mL and normal gallbladder and cystic duct mucosa. CONCLUSIONS: This study demonstrates improvement in both cystic duct occlusion and gallbladder mucosa ablation with standardization of the technique for thermocholecystectomy in an animal model. However, a better system is required to promote complete obliteration of the gallbladder lumen.

Dissolution of gallstones using methyl tertiary-butyl ether in an animal model.

Human gallstones were surgically implanted in the gallbladders of six pigs. Through cholecystostomy catheters, methyl tertiary-butyl ether (MTBE) was infused from 3 to 5 days. MTBE successfully dissolved 19 of the 20 cholesterol stones and partially dissolved one mixed cholesterol-bilirubin stone. Gross and microscopic examination of abdominal organs revealed mild superficial ulcerations of the gallbladder and mild to moderate chronic inflammatory changes in the gallbladder of animals treated with MTBE infusion. There were no other significant changes within other abdominal organs except for mild inflammation of the duodenum in one animal and of the common bile duct in another. Because of its efficacy and limited deleterious effects, MTBE may be a good solvent when dissolving pure cholesterol gallstones in the gallbladder.

Dissolution of gallstones using cholecystostomy tube in the pig.

Cholecystostomy catheters and human cholesterol gallstones were implanted surgically in the gallbladders of eight pigs. Through the catheters, mono-octanoin or sterile water (H2O) was infused from two to seven days. The mono-octanoin dissolved pure cholesterol gallstones smaller than 200 g. There was no stone dissolution with infusion of sterile water and only one stone larger than 250 g was dissolved with mono-octanoin. Side effects included moderate-to-severe inflammation and ulceration of the gallbladder with mono-octanoin instillation, which precludes its widespread use with the present treatment regimen. Infusion of water caused little gallbladder irritation.

Carotid blood flow in man determined by video dilution technique: 1. Theory, procedure, and normal values.

The blood flows in the common, internal, and external carotid arteries were determined as a percentage of the cardiac output by video dilution technique in 20 normal subjects during routine angiography. Nine women and 11 men, ages 19-63 years, displayed a mean flow in the common carotid of 8.5% (SD +/- 0.9%; n = 40); internal carotid, 5.3% (SD +/- 1.0%; n = 24); and external carotid, 3.2% (SD +/- 0.4%; n = 24). Relative flow is calculated by a modification of the Stewart-Hamilton principle. The technique is fast, simple, highly accurate, and avoids the errors connected with previous videodensitometric mean transit time techniques. The method can be used in routine angiography without prolonging the catheterization procedure or adding to the patient's risk or cost.

Carotid blood flow in man determined by video dilution technique: II. Vascular abnormalities.

Carotid blood flows were evaluated in 31 individuals with vascular abnormalities using the video dilution technique. In patients with stenoses, angiographically estimated at 70%, blood flow was usually, but not always, measured less than normal. The technique proved to be useful in the evaluation of the efficiency of collateral arterial pathways and in the evaluation of superficial temporal-middle cerebral arterial bypass grafts. It was also helpful in estimating contralateral increase in arterial flows with cross compression techniques for the preoperative evaluation of patients subjected to carotid sacrifice. In a limited number of patients video dilution flows correlated with the degree or proximal arterial spasm and were useful in the preoperative study of these patients. The demonstration of flow abnormalities in patient with seizure disorders may be useful in the medical and surgical management of these individuals.

Carotid blood flow response to Conray-60: diagnostic implications.

The vasoactive effect of the angiographic contrast medium Conray-60 (iothalamate meglumine 60%) on carotid blood flow was studied by the video dilution technique in 26 subjects during routine neuroangiography. After a test series of 1 ml injections of contrast material into the carotid arteries at designated time intervals, an increase in carotid blood flow was found in normal controls at 30 sec, while a significant decrease in flow was observed in patients with atheromatous disease and avascular intracranial masses (p less than 0.01). Test responses in patients with intracranial aneurysm, neoplasm, and granulomatous vasculitis are also reported. The differential effect of contrast material on the cerebral circulation correlates well with several pathologic states of the central nervous system and may be used as a simple test to diagnose and evaluate a variety of vascular disorders.

Monte Carlo assessment of computed tomography dose to tissue adjacent to the scanned volume.

The assessment of the radiation dose to internal organs or to an embryo or fetus is required on occasion for risk assessment or for comparing imaging studies. Limited resources hinder the ability to accurately assess the radiation dose received to locations outside the tissue volume actually scanned during computed tomography (CT). The purpose of this study was to assess peripheral doses and provide tabular data for dose evaluation. Validated Monte Carlo simulation techniques were used to compute the dose distribution along the length of water-equivalent cylindrical phantoms, 16 and 32 cm in diameter. For further validation, comparisons between physically measured and Monte Carlo-derived air kerma profiles were performed and showed excellent (1% to 2%) agreement. Polyenergetic x-ray spectra at 80, 100, 120, and 140 kVp with beam shaping filters were studied. Using 10(8) simulated photons input to the cylinders perpendicular to their long axis, line spread functions (LSF) of the dose distribution were determined at three depths in the cylinders (center, mid-depth, and surface). The LSF data were then used with appropriate mathematics to compute dose distributions along the long axis of the cylinder. The dose distributions resulting from helical (pitch = 1.0) scans and axial scans were approximately equivalent. Beyond about 3 cm from the edge of the CT scanned tissue volume, the fall-off of radiation dose was exponential. A series of tables normalized at 100 milliampere seconds (mAs) were produced which allow the straight-forward assessment of dose within and peripheral to the CT scanned volume. The tables should be useful for medical physicists and radiologists in the estimation of dose to sites beyond the edge of the CT scanned volume.

The evaluation of seizure disorders by computerized tomography.

A series of 150 patients with seizure disorders was analyzed in detail. Older individuals (over the age of 65 years) with a short duration of seizure activity at the time of computerized tomography (CT) examination (less than 6 months), associated with specific neurological findings and focal seizures secondarily generalized, produced the highest number of intracranial CT abnormalities. Relationships between CT, electroencephalography (EEG), and other diagnostic procedures and pertinent historical and neurological findings are discussed.

Comparison of ultrasonography, computerized tomography, and radionuclide imaging in the diagnosis of acute and chronic cholecystitis.

Seventy-five patients with abdominal pain in the right upper quadrant who were subsequently confirmed operatively and histologically to have acute or chronic cholecystitis underwent radionuclide imaging of the biliary tree, ultrasonography, and/or computerized tomography before operation. fifty-eight of the patients had acute cholecystitis and 17 had chronic cholecystitis and cholelithiasis. Analysis of our data indicates that ultrasonography is an accurate and better screening test than cholescintigraphy in the diagnosis of chronic cholecystitis and cholelithiasis, but it is less accurate in the detection of acute cholecystitis. On the other hand, radionuclide imaging is highly sensitive and specific in the early diagnosis of acute cholecystitis, but it is poor in the diagnosis of chronic cholecystitis and cholelithiasis unless the cystic duct is obstructed. CT scanning is more expensive than ultrasonography but may be extremely helpful in problematic cases such as the diagnosis of the cause in biliary obstruction or in imaging of the pancreas.

Treatment of a patient with B cell lymphoma by I-131 LYM-1 monoclonal antibodies.

A patient with Richter's syndrome, a malignant lymphomatous transformation of chronic lymphocytic leukemia, had become moribund with rapidly enlarging masses, granulocytopenia and thrombocytopenia despite the use of conventional chemotherapy and radiotherapy. Greater than ten percent of a test dose of I-131 Lym-1, a murine monoclonal antibody produced against Burkitt's African B cell lymphoma, was accumulated by her tumor. The patient was subsequently treated with a series of injections of I-131 Lym-1 with dramatic clinical response, reduction of tumor volume by x-ray computerized tomography and progression of circulating cellular elements toward normality. Her course over the next ten months was not like that to be expected for Richter's syndrome, which has an average survival of four months. This mode of treatment appears promising.

Deep-vein thrombosis after fracture of the pelvis: assessment with serial duplex-ultrasound screening.

Sixty patients who had had a major fracture of the pelvis and were in stable condition on the orthopaedic ward three to five days after the injury were tested serially with duplex ultrasound, beginning approximately seven days after the injury, in order to determine the incidence of deep-vein thrombosis. Contrast venography was performed to confirm all positive non-invasive studies. Deep-vein thrombosis developed in eight patients (approximately 15 per cent). The thrombosis was in the popliteal or a more proximal vein in six of the eight patients, whereas in two it was distal to the popliteal vein. In four patients, evidence of thrombosis developed after one or more normal duplex-ultrasound studies. In one patient, symptoms that were suggestive of deep-vein thrombosis developed fifty-two days after the injury (four days after the fourth normal duplex-ultrasound examination), and ascending venography was entirely normal. Another patient had a pulmonary embolus fifteen days after the injury, and on the same day a duplex-ultrasound study was positive for thrombosis. During six weeks of follow-up after discharge from the hospital, symptoms of deep-vein thrombosis or pulmonary embolism did not develop in any patient in whom serial duplex-ultrasound studies had been negative.

Low-dose, fractionated radioimmunotherapy for B-cell malignancies using 131I-Lym-1 antibody.

PURPOSE: This trial was conducted to assess the toxicity and efficacy of 131I-Lym-1 in patients with either malignant B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) using low-dose, fractionated radioimmunotherapy (RIT). MATERIALS AND METHODS: Thirty adult patients who had advanced B-cell malignancies (25 NHL and 5 CLL) had progressed despite standard therapy; 12 patients entered the trial with Karnofsky performance status (KPS) of equal to or greater than 60. Patients were treated with a series of intravenous doses of 131I-Lym-1 with a goal of reaching a cumulative dose in each patient of at least 300 mCi. All patients were Lym-1 reactive. Clinical responses and immediate toxicity were evaluable in all 30 patients and delayed toxicity in 26. RESULTS: Toxicity to Lym-1 antibody occurred with 28% of the 176 doses and was transient. Human antimouse antibodies (HAMA) were generated in 30% after a mean of 4 doses, but interrupted therapy in only 10% of the patients. Thrombocytopenia was dose-limiting; there were no deaths due to toxicity. Tumor regression occurred in 25 (83%) of the patients and was great enough, and durable enough, in 17 (57%) to qualify them as responders; 13 NHL patients and 4 CLL patients. Advanced disease often interrupted therapy prematurely. However, 18 patients received at least 180 mCi of 131I-Lym-1; 17 (94%) of these responded to the therapy. CONCLUSION: Although advanced disease often interrupted therapy prematurely, the results from 131I-Lym-1 therapy are clearly promising and warrant additional trials.

Percutaneous ultrasound-guided radiofrequency electrocautery ablation of prostate tissue in dogs.

RATIONALE AND OBJECTIVES: We investigated the feasibility of percutaneous radiofrequency (RF) electrocautery in ablation of prostate tissue in dogs. METHODS: We used six dogs in whom a specially designed needle was placed percutaneously into the prostate. RF electrocautery was applied to the needle and treatment was monitored with ultrasound. Animals were sacrificed and gross examination of the prostate and surrounding tissues was performed. Histopathologic examinations of the prostate were also performed. RESULTS: The treatment zone appeared as an elliptical echogenic focus on ultrasound that increased in size with the application of current. Gross and histopathologic correlation demonstrated that the treatment area included a central area of char with a surrounding area of coagulation. There were no deleterious effects to surrounding tissues. CONCLUSION: Our results demonstrate the feasibility of percutaneous ultrasound-guided RF electrocautery ablation of canine prostate tissue.

Hepatic ablation using bipolar radiofrequency electrocautery.

RATIONALE AND OBJECTIVES: Percutaneous methods have been used to treat primary and secondary hepatic neoplasms. In the current study, we evaluated the potential of bipolar radiofrequency (RF) electrocautery to increase in vitro liver tissue destruction when compared with monopolar RF electrocautery. METHODS: Two needles (electrodes) were placed into fresh bovine liver tissue for use with bipolar electrocautery. Needle tip exposure was kept constant at 3 cm while other parameters, including treatment time, power (wattage), interneedle distance, and needle tip temperature, were changed. Pathologic and histologic correlation was performed, and tissue necrosis was weighed in grams for individual parameters. RESULTS: There was a minimal threshold of approximately 45 degrees C where tissue coagulation occurred. Tissue coagulation increased the longer treatment went on. Increasing temperature, wattage, or both increased tissue coagulation such that necrosis was too rapid and char formation occurred, which prevented further coagulation. For all wattages and temperatures, there was increasing tissue necrosis with increasing needle separation, until a point at which further needle separation produced less tissue necrosis. Optimizing parameters allowed tissue coagulation of greater than 30 g. CONCLUSION: Bipolar RF electrocautery shows promise for increasing the tissue coagulation in fresh bovine liver compared with the previously described monopolar technique.