Increased effectiveness of interferon alfa-2b following active specific immunotherapy for melanoma.

PURPOSE: To determine whether interferon alfa-2b (IFN-alfa; intron-A, Schering Corp, Kenilworth, NJ) can induce a remission in patients previously treated with active specific immunotherapy (therapeutic melanoma vaccine) without response. PATIENTS AND METHODS: Eighteen patients with disseminated melanoma who had failed to respond to at least five injections of Melacine therapeutic melanoma vaccine (Ribi ImmunoChem Research, Inc, Hamilton, MT) were then treated IFN-alfa after a 4-week interval. IFN-alfa 5 or 6 x 10(6) U/m2 was self-administered three times a week subcutaneously by melanoma patients for at least 2 months. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging of the brain were performed within 4 weeks before treatment as a baseline, and then at 2-month intervals during treatment to evaluate response. All 18 patients were HLA-typed before treatment. The frequency of cytolytic T-cell precursors (pCTL) in the blood had been measured weekly in 13 of the patients during treatment with Melacine. RESULTS: Eight of 18 patients (44.4%) had a major objective clinical response induced by IFN-alfa, including site-specific complete remissions in five. Responses lasted a median of 11 months. The median survival duration of the responders has not been reached, and exceeds 32 months. The group as a whole had a median survival duration of 10.1 months, and nonresponders lived 7.3 months. Cytolytic T-cell precursors had been increased by immunization in all five responding patients tested, but also in five of eight nonresponders. There was no association of response to IFN-alfa with specific HLA phenotypes, in contrast to our previous results with melanoma theraccine alone. CONCLUSION: These data suggest an additive effect of active specific immunotherapy and IFN-alfa on the objective response rate, perhaps through upregulation of HLA molecules and tumor-associated antigens on the tumor cell by IFN-alfa, after immunization of the patient by Melacine. This treatment may have improved survival over that expected in metastatic melanoma.

Budd-Chiari syndrome: detection with color Doppler sonography.

The value of color Doppler sonography in evaluating newly diagnosed Budd-Chiari syndrome in five patients was studied. Hepatic venous findings included absence of vessels (one patient), flow reversal (two patients), narrowing (four patients), and tortuosity (three patients). Detected collaterals included hepatic venous to hepatic venous (four patients), hepatic venous to subcapsular systemic venous (two patients), and portosystemic (three patients). Hepatic venous spectral Doppler waveforms were flat and essentially aphasic in four patients, indicative of distal hepatic venous compression. The inferior vena cava was markedly compressed in two patients and slightly compressed in one. Color Doppler sonography allowed more reliable and confident identification of irregular, compressed, or otherwise abnormal hepatic veins than did conventional sonography. Color Doppler sonography also showed collateral vessels that were undetected with conventional sonography or other imaging techniques. Our results suggest that color Doppler sonography may be a valuable tool in the initial diagnosis and evaluation of suspected Budd-Chiari syndrome.

Magnetic resonance of the inferior vena cava.

MRI was performed in 54 patients with abnormalities of the inferior vena cava (IVC). These included 16 patients with extrinsic IVC compression, 32 patients with intrinsic IVC abnormalities, and 6 patients with IVC dilatation. All patients had spin-echo imaging, and 21 had MR angiography. While presaturated spin-echo images showed intrinsic lesions to advantage, collateral vessels were best appreciated with MR angiography. The IVC is well evaluated with MRI techniques.

Computed tomography of lymphogranuloma venereum mimicking cervical cancer.

A case of lymphogranuloma venereum involving the cervix as a primary site is discussed. The patient's clinical presentation and findings on tomography were suggestive of carcinoma of the cervix. The differential diagnosis of retroperitoneal pelvic lymphadenopathy is discussed.

Cardiac MRI cine and color Doppler in valvular disease: correlative imaging.

Cardiac cine field echo MRI and color Doppler were performed in 13 patients with aortic regurgitation (n = 4) or multiple valvular diseases (n = 9). The size, shape, and direction of regurgitation jets correlated well. Color Doppler was better able to follow flow jets in oblique planes. Cine MRI was better able to evaluate patients with marked cardiac dilatation.

Spinal MR imaging in suspected metastases: correlation with skeletal scintigraphy.

Bone scintigraphy (RN) and magnetic resonance imaging (MR) were prospectively and retrospectively correlated in 64 patients with suspected spinal metastatic disease and possible spinal cord compression. Images were retrospectively interpreted and compared with the prospective official RN and MR reports to help decide relative prospective lesion conspicuity. Spinal lesions were confirmed by radiography, computed tomography, myelography or MR and RN follow-up in 56 patients (88%). Prospectively, MR detected 11 lesions not reported on RN while RN detected two lesions not reported on MR. Retrospective review of RN detected six lesions previously not reported. Retrospectively MR showed all lesions. Those lesions seen only in retrospect by RN were rather subtle and would be difficult to detect prospectively. In general, lesions not well seen on RN had relatively more bone marrow abnormality and less cortical bone involvement. In some cases, MR imaging shows spinal marrow lesions not well seen on planar RN.

Cardiac calcifications: difficult MRI diagnosis.

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed in 40 patients with a variety of cardiovascular diseases. These imaging modalities were compared to investigate their relative value in the assessment of cardiovascular diseases. Of these 40 patients, 7 were found by CT to have detectable cardiovascular calcifications. These patients included one calcified mitral stenosis, one calcified coronary artery, one calcified type B aortic dissection, two calcified myocardial infarctions, and two patients with calcific pericarditis. In several cases, MRI was misleading because of difficulty in detecting calcifications. We present a series of cases illustrating a limitation of MRI in identifying diagnostically and clinically important cardiovascular calcifications.

Fine needle aspiration of pancreatic fluid collections.

The complications of pancreatitis remain diagnostic and therapeutic challenges. Patients with simple pancreatitis, pancreatic necrosis, pseudocyst, noninfected fluid collection or abscess may all have similar clinical pictures. During the last decade computerized tomography (CT)-guided needle aspiration of peripancreatic fluid collections has been increasingly used as a diagnostic tool for pancreatic abscesses. This study reviewed the effectiveness of CT-guided needle aspiration of peripancreatic fluid collections at our institution in terms of diagnostic accuracy, correlation with eventual outcome, and safety. Charts of patients who underwent needle aspiration of de novo peripancreatic fluid collections over the past 2 years were reviewed. Thirty-five patients underwent 50 aspirations. Eleven patients (31%) had a positive aspirate culture; seven of these had a positive Gram's stain. There were no false positive Gram's stains but four false negatives. Twenty-four (69%) patients had negative aspirate Gram's stains and cultures. Patients with positive aspirate cultures were treated with antibiotics only (2), CT-guided drain placement (7), or surgical drainage (3). The mortality related to each of these therapeutic modalities was 50 per cent, 0 per cent, and 33 per cent, respectively. Of the 24 patients with negative aspirate cultures, five had no further treatment, 12 received antibiotics, and six underwent CT drain placement. All these patients survived. There was one false negative aspirate culture. This patient underwent delayed surgical drainage but expired. There were no major complications from CT-guided aspiration. CT-guided aspiration appears to be a safe and reliable method of diagnosing infection in peripancreatic fluid collections.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography in endobronchial neoplasms.

Computed tomography (CT) was performed in 86 patients with bronchoscopically proven endobronchial neoplasms. There were 76 primary and 10 metastatic lesions. CT correctly identified the abnormal airway in 95% of cases (82/86) by demonstrating either nodule, mass, or stricture. A discrete endobronchial nodule was seen in 55% (47/86). There was good morphological correlation of CT with bronchoscopic findings (89% for discrete nodule, 80% overall). Appropriate atelectasis was noted in 80% (69/86) of cases. CT is sensitive in detecting and localizing endobronchial neoplasms and correlates well with bronchoscopic findings.

Color Doppler sonography of portocaval shunts.

Nine patients who had undergone end-to-side portocaval shunts were assessed using a sector real-time color Doppler sonography system. Shunt patency was demonstrated in 8 of 9 patients by detection of color-coded flow within the portal vein, in the anastomotic region, and in the inferior vena cava adjacent to the shunt. Color flow could not be detected in 1 patient. This patient had no evidence of shunt compromise. Spectral Doppler studies were also performed in these patients and flow was demonstrated in all 8. In these instances, information available with color Doppler imaging allowed visualization of the shunt even when it had not been apparent on preliminary real-time grey-scale imaging. This study, which does not assess accuracy, nevertheless suggests that color flow Doppler sonography may prove useful in assessing patients with portocaval shunts.

Active-specific immunotherapy for melanoma.

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.

Magnetic resonance imaging features in melanoma.

T1 and T2 relaxation time shortening secondary to paramagnetic compounds has been described in melanoma. The purpose of this paper is to evaluate the signal behavior of melanoma involved in various body areas using short TR, TE and long TR, TE sequences. Twenty-seven sites of melanoma were evaluated with MR using T1 weighted and T2-weighted techniques. Using fat and muscle signal intensities as references tissues, lesions were graded into high, low or intermediate intensity categories for each of the sequences. Four signal patterns emerged. The typical pattern characterized by high signal on T1-weighted images and low signal on T2-weighted images reflected T1 and T2 shortening. The other pattern categories comprised of lesions demonstrating low signal T1-weighted images and high signal on T2-weighted images, high signal on both T1- and T2-weighted images and lesions showing intermediate signal on either T1- or T2-weighted images. We observed a tendency away from the typical signal pattern in extraocular melanoma cases with only one of 14 demonstrating this pattern. Moreover, only seven of thirteen ocular melanomas exhibited such behavior. Possible explanations for this findings as well as the existence of a variety of MR appearances to melanoma are offered. We conclude that while signal patterns showing T1 and T2 shortening are typical of melanoma, the absence of these does not exclude the diagnosis.

MRI evaluation of AIDS-related encephalopathy: toxoplasmosis vs. lymphoma.

The spectrum of cranial MRI findings was evaluated in 113 patients with the acquired immunodeficiency syndrome, assessing lesion number, size, location, and configuration in association with the autopsy and/or biopsy results. Correlation of cranial MRI and CT was performed in 32 patients. MRI was shown to be superior in sensitivity of lesion detection demonstrating more lesions than CT in 14 studies (44%) and equivalent information in 18 studies (56%). In no case did CT demonstrate lesions not detected on MRI. We conclude that MRI should be the study of choice in evaluating AIDS-related encephalopathy. Multiple lesions that involve both deep gray matter and white matter suggest the possibility of CNS lymphoma. The "target" appearance on MRI is not helpful in distinguishing toxoplasmosis from lymphoma.

Sonographically guided arthrocentesis of the hip.

High-resolution real-time sonography not only provides a noninvasive means of diagnosing hip effusions, but also provides easy access for arthrocentesis. Nineteen sonographically guided hip arthrocentesis were performed in 18 patients. In 13 of 19 patients aspirated, capsular distension was present. In 10 of 19 patients, fluid could be aspirated from the joint space (volume varying from 1 to 9 mL). Saline lavage was performed in 12 of the 19 joints needled. Intra-articular location was confirmed by observation during distension on real-time images or by successful aspiration. Sonographically guided arthrocentesis has potential advantages over conventional fluoroscopic techniques. These include a lack of ionizing radiation, superior visualization of needle location within the joint capsule, and the ability to diagnose soft tissue and periarticular abnormalities generally not seen fluoroscopically.

Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma.

We have studied the effects of low-dose recombinant interleukin-2 preceded by low-dose cyclophosphamide on malignant melanoma. Thirty eight outpatients aged from 25 to 75 years were treated with interleukin-2, 3.6 million Cetus units/m2 i.v. daily for five days on two successive weeks beginning three days after 350 mg/m2 of intravenous cyclophosphamide. This schedule was repeated at least twice more with a one-week interval between cycles, usually at the same dosage level. Ten of the 38 patients (26.3%) had clinically significant remissions: two complete (5.3%), seven partial (18.4%), and one ongoing, long-term (greater than 18 mo) "minor" response (2.6%). Four others (10.5%) had shorter minor responses and four (10.5%) a mixed response. One patient with disease restricted to the skin had a complete remission, while the other patient with a complete remission had had three lung nodules and an enlarged hilar lymph node. It was gratifying that one of the major sites of disease responding to treatment was the liver. Two complete and two partial remissions (i.e., greater than 50% regressions for greater than four weeks at this site) were obtained in 10 patients with liver involvement. Lung metastases also responded in four of 16 patients (one complete and three partial remissions). Subcutaneous nodules responded in seven of 21 patients (two complete, five partial remissions), while lymph node metastases diminished significantly in four of 14 patients (one complete, three partial remissions). The median duration of response was nine months (range, 1.5-20 months), with four patients treated for more than one year. Toxicity was moderate and controllable, and only two patients required hospitalization, both overnight. Lymphokine activated killer cell activation was induced in 24 of 38 patients, including all nine of the major responders. Conversely, none of 14 patients without lymphokine activated killer cell activation had a significant clinical remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of lymphokine activated killer cells, and was more tolerable than therapy with high doses of interleukin-2.

Pulsed Doppler sonography of the hepatoduodenal ligament: efficacy and ease of performance.

A prospective analysis of the hepatoduodenal ligament (HDL) in 205 patients with abdominal pulsed Doppler sonography supports the conclusion that Doppler ultrasound is a useful adjunct to routine scanning in this area. Abdominal pulsed Doppler sonography allows reliable differentiation among the HDL structures by identifying and characterizing flow in the portal vein and hepatic arterial structures, while demonstrating no flow in the bile ducts. Proper hepatic arterial signal was obtained in 190 (92.7%) patients. Portal venous signal was obtained in virtually all (203 of 205-99%) patients. Abdominal Doppler sonography shows promise in its ability to provide definitive diagnostic information in situations where images alone may prove misleading. Doppler sonography can differentiate similarly sized bile ducts and arteries and detect dilated arterial and venous structures simulating dilated bile ducts.

FM sonography in gallbladder disease: efficacy and comparison with conventional sonography.

A new type of ultrasound signal processing ("FM sonography") appears to be beneficial compared to conventional ultrasound ("AM sonography") in some applications (e.g., diffuse liver disease and prostatic carcinoma). Despite these possible advantages, it is doubtful FM sonography will be widely used unless it is at least as useful as conventional (AM) sonography in all common applications. Fifty-five patients with suspected gallbladder disease were independently evaluated with both AM and FM sonography. The two modalities were blindly and prospectively compared for accuracy in detecting gallstones and for image quality. No statistically significant difference was found between images produced by FM and conventional signal processing. FM had an accuracy of detecting gallstones of 98.1%, compared to 96.2% for AM. Overall, FM accuracy was 97.7%, while AM had an overall accuracy of 97.3%. Other useful sonographic signs were evaluated (gallbladder wall thickness, diameter of common duct). No AM/FM difference was noted. Our data suggest that FM-only imaging could be performed in patients with suspected gallbladder disease without loss of accuracy.

The motion artifact suppression technique (MAST) in magnetic resonance imaging: clinical results.

The Motion Artifact Suppression Technique (MAST) is a method which uses a series of gradient echos that are computed to cancel velocity, acceleration and pulsatility components of involuntary motion in MR imaging. A total of 916 patient studies were performed over a nine month period using MAST sequences with a TE 40, 60, 80, 100, 120, and 26/112. There was considerable improvement in long TR, long TE images. Cerebrospinal fluid flow artifacts were reduced. Body and spine images had reduced flow and respiratory artifacts. Spin rephasing in blood vessels caused increase intraluminal signal. This might be useful for cardiovascular imaging.

Magnetic resonance imaging of bone after radiation.

Magnetic resonance imaging (MRI) was performed in 22 patients at various times (0-3) years) following radiation therapy to the spine. T1 and T2 weighted images were obtained at 0.5 Tesla. Increased signal was seen after 800-6000 rads (8-60 Gy). Marrow effects corresponded to radiation ports. Recurrent tumor was clearly separated from fatty replacement. This was much better seen on T1 weighted images. Five patients that had MRI during their course of radiotherapy (XRT) did not have increased signal on T1 images of the bone marrow. The earliest fatty marrow change was seen nine days following completion of 3000 rads (30 Gy) XRT over one month's duration. One patient who received 800 rads (8 Gy) to the upper thoracic spine for eosinophilic granuloma had no radiation effects on MRI when imaged 16 days following completion of XRT given over five days. Fatty marrow change was seen in this patient on MRI six months later. MRI was particularly useful in defining the extent of prior radiation effects when repeat therapy was needed.