Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a Research on Adverse Drug Events and Reports (RADAR) report.

OBJECTIVE: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. METHODS: The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. RESULTS: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. CONCLUSION: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. ADVANCES IN KNOWLEDGE: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization.

Chemoembolization and other ablative therapies are routinely utilized in downstaging from United Network for Organ Sharing (UNOS) T3 to T2, thus potentially making patients transplant candidates under the UNOS model for end-stage liver disease (MELD) upgrade for hepatocellular carcinoma (HCC). This study was undertaken to compare the downstaging efficacy of transarterial chemoembolization (TACE) versus transarterial radioembolization. Eighty-six patients were treated with either TACE (n = 43) or transarterial radioembolization with Yttrium-90 microspheres (TARE-Y90; n = 43). Median tumor size was similar (TACE: 5.7 cm, TARE-Y90: 5.6 cm). Partial response rates favored TARE-Y90 versus TACE (61% vs. 37%). Downstaging to UNOS T2 was achieved in 31% of TACE and 58% of TARE-Y90 patients. Time to progression according to UNOS criteria was similar for both groups (18.2 months for TACE vs. 33.3 months for TARE-Y90, p = 0.098). Event-free survival was significantly greater for TARE-Y90 than TACE (17.7 vs. 7.1 months, p = 0.0017). Overall survival favored TARE-Y90 compared to TACE (censored 35.7/18.7 months; p = 0.18; uncensored 41.6/19.2 months; p = 0.008). In conclusion, TARE-Y90 appears to outperform TACE for downstaging HCC from UNOS T3 to T2.

Cryptogenic liver disease in HIV-seropositive men.

OBJECTIVES: In the era of highly active antiretroviral therapy (HAART), liver disease has become a leading cause of morbidity and mortality in HIV-seropositive individuals. Although liver disease is commonly caused by viral co-infection, it has also been described in patients without viral hepatitis. In this study, we determined clinical factors associated with the development of cryptogenic liver disease in HIV-infected individuals. METHODS: HIV-seropositive and -seronegative patients undergoing evaluation for liver transplantation were selected if they met clinical criteria for cryptogenic liver disease. Clinical data were collected retrospectively, and radiological and histological data were reviewed separately. RESULTS: Nine HIV-seropositive individuals were compared with 41 HIV-seronegative patients with cryptogenic liver disease. Only one HIV-seropositive patient (11%) had cirrhosis, compared to 39 HIV-seronegative patients (93%) (P<0.001). Three HIV-infected patients (33%) had histological evidence of nodular regenerative hyperplasia. HIV-seropositive patients had significantly lower body mass indices, and lower Child-Pugh-Turcotte and Model for Endstage Liver Disease scores than HIV-seronegative patients (P<0.05). CONCLUSIONS: Advanced cryptogenic liver disease in HIV-infected patients is infrequently caused by cirrhosis, and more frequently by nodular regenerative hyperplasia. This disease entity may become more common in the HAART era, and may contribute to an increased morbidity in HIV-infected individuals.

Gastrointestinal infection in the immunocompromised (AIDS) patient.

In the past two decades acquired immunodeficiency syndrome (AIDS) has become one of the most devastating illnesses in human history. As the epidemic continues to spread increasingly, AIDS patients are no longer confined to a few specialized AIDS hospitals and are now seen in general hospitals and clinics everywhere. Radiologists need to recognize the appearances, to understand how-safely-to care for patients with this disease, and to know enough about the illness to be able to counsel their patients. This article presents a review of current knowledge about the wide range of gastrointestinal hepatic, splenic, biliary, and retroperitoneal manifestations in AIDS, and how the role of modern medical imaging techniques and diagnosis and treatment can be applied. The imaging aspects (conventional double-contrast gastrointestinal studies, ultrasound, CT, and MR) of the diseases of the luminal gastrointestinal tract, liver, spleen, biliary tract, and retroperitoneum will be systematically discussed. Candidiasis, herpes, cytomegalovirus, cryptosporidiosis, histoplasmosis, isosporiasis, salmonellosis, toxoplasmosis, unusual mycobacteria, and viral infections account for the majority of non-neoplastic disorders.

Imaging features of enterohemorrhagic Escherichia coli colitis.

OBJECTIVE: The purpose of this article is to define and illustrate the radiologic findings in patients with enterohemorrhagic Escherichia coli colitis. CONCLUSION: Although not definitive, imaging studies in conjunction with an appropriate clinical history can aid in the early diagnosis of E. coli colitis and exclude surgical conditions. CT is more sensitive than conventional radiography for detection. Contiguous involvement, including the transverse colon, was seen in all patients. Because CT is becoming routine in the initial workup of patients with acute abdominal pain, it is important for the radiologist to suggest E. coli colitis in the proper setting.

Total splenic infarct due to Aspergillus and AIDS.

Invasive aspergillosis is a rare but important cause of morbidity and mortality in patients with AIDS. In the majority of patients, invasive aspergillosis involves the lungs. Extrapulmonary involvement with total splenic infarction has not been previously described. We illustrate a patient who developed total splenic infarction and septic emboli to the brain from Aspergillus.

Staging of colorectal cancer.

CT, MR, and TRUS play complementary roles in staging CRC. Further improvements in these techniques will improve the accuracy of preoperative staging and thereby help optimize patient treatment and outcome.

Total splenic infarct due to Aspergillus and AIDS.

Invasive aspergillosis is a rare but important cause of morbidity and mortality in patients with AIDS. In the majority of patients, invasive aspergillosis involves the lungs. Extrapulmonary involvement with total splenic infarction has not been previously described. We illustrate a patient who developed total splenic infarction and septic emboli to the brain from Aspergillus.

Detection of bleeding due to small bowel cholesterol emboli using helical CT examination in gastrointestinal bleeding of obscure origin.

Chronic, intermittent GI bleeding is defined as obscure when routine diagnostic examinations of the GI tract, including barium and endoscopic studies, fail to reveal the cause of bleeding. Our patient had significant bleeding and extensive evaluation including upper endoscopy, small bowel enteroscopy, enteroclysis, colonoscopy, and provocative angiography with urokinase, without the source of bleeding detected. This report describes a noninvasive novel approach using helical CT scanning with water as oral contrast and rapid injection of intravenous iodinated contrast material and thin slices obtained to diagnose the site of recurrent, obscure GI bleeding related to cholesterol crystal embolization to the small intestine.

Comparison of endoscopic retrograde cholangiopancreatography with MR cholangiopancreatography in patients with pancreatitis.

PURPOSE: To assess the usefulness of magnetic resonance (MR) cholangiopancreatography (MRCP) in the evaluation of disease in patients with acute or chronic pancreatitis. MATERIALS AND METHODS: MR imaging was performed at 1.5 T in 39 patients with chronic (n = 30) or acute (n = 9) pancreatitis. The patients underwent a pancreas MR imaging protocol that included an MRCP sequence. Comparison was made with findings at endoscopic retrograde cholangiopancreatography (ERCP), performed within 30 days. Three blinded readers used a scoring system to evaluate nine segments of the pancreatic and biliary ducts as depicted on the ERCP and MRCP images. MRCP image quality was also evaluated. RESULTS: Of 196 segments analyzed, 17 were not seen at MRCP (sensitivity, 91%). Of the segments visualized at MRCP, 14 were incorrectly characterized (accuracy, 92%). At MRCP, segments not detected or mischaracterized were either normal, slightly dilated, or narrowed. At ERCP, 42 segments in 19 patients were not visualized. MRCP findings were considered useful in all those cases. MRCP image quality was not interpretable in two cases due to artifacts. CONCLUSION: Very good correlation between ERCP and MRCP findings was demonstrated. Both modalities failed to depict pathologic conditions depicted by the alternative method. MRCP may obviate ERCP, particularly in patients who cannot undergo ERCP or in whom ERCP has been unsuccessful.

Seminomas complicating undescended intraabdominal testes in patients with prior negative findings from surgical exploration.

OBJECTIVE: This paper describes the clinical and imaging characteristics of seminoma complicating intraabdominal testes in three patients who had a history of negative findings from surgical exploration of the inguinal canal and scrotum. CONCLUSION: Because inguinal surgery for cryptorchidism may fail to disclose intraabdominal testes, surgery that has negative findings should be followed up by a close examination of the abdomen. Seminomas arising from an intraabdominal testis can be large and asymptomatic or may simulate other diseases. Torsion may occur and occasionally appear as acute abdomen. The imaging features can be nonspecific, and the history of cryptorchidism may not be provided. Awareness of the clinical and imaging features of neoplasms involving undescended intraabdominal testes is important for appropriate diagnosis and therapy.

Medical malpractice implications of alternative medicine.

Although use of alternative therapies in the United States is widespread and growing, little is known about the malpractice experience of practitioners who deliver these therapies or about the legal principles that govern the relationship between conventional and alternative medicine. Using data from malpractice insurers, we analyzed the claims experience of chiropractors, massage therapists, and acupuncturists for 1990 through 1996. We found that claims against these practitioners occurred less frequently and typically involved injury that was less severe than claims against physicians during the same period. Physicians who may be concerned about their own exposure to liability for referral of patients for alternative treatments can draw some comfort from these findings. However, liability for referral is possible in certain situations and should be taken seriously. Therefore, we review relevant legal principles and case law to understand how malpractice law is likely to develop in this area. We conclude by suggesting some questions for physicians to ask themselves before referring their patients to alternative medicine practitioners.

Using triphasic helical CT to detect focal hepatic lesions in patients with neoplasms.

OBJECTIVE: Our purpose was to determine the value of triphasic helical CT (unenhanced, hepatic arterial, and portal venous phases) in the detection and characterization of focal hepatic lesions due to hepatomas or metastases. MATERIALS AND METHODS: One hundred two patients with known or suspected hepatomas or liver metastases underwent triphasic CT. The number and conspicuity of lesions were evaluated on each phase. RESULTS: Five hundred eighty-four lesions were detected in 102 patients. Patients with hypovascular malignancies had more lesions detected on the portal venous phase with increased conspicuity than on the other phases. Patients with hypervascular malignancies had lesions best detected on the hepatic arterial phase, which revealed small lesions that were not seen on the other phases in seven (21%) of the 33 patients with hypervascular metastases and hepatomas. No lesions were detected on the unenhanced phase that were not seen on the other phases. However, arterial phase images introduced new diagnostic dilemmas because not all lesions seen on the arterial phase alone were caused by hepatomas or metastases, even in patients with known malignancies; several lesions represented benign abnormalities that included focal nodular hyperplasia. CONCLUSION: The unenhanced phase is not routinely necessary for the detection of metastases or hepatomas. Hypovascular malignancies are best evaluated during the portal venous phase. Small lesions due to hypervascular metastases and hepatomas are best evaluated and may be detected only during the hepatic arterial phase, which should be used routinely in these patients. New dilemmas may develop from the increased sensitivity of the hepatic arterial phase for lesions. However, the hepatic arterial phase is of limited value with hypovascular malignancies.

Benign and malignant ovarian masses: selection of the most discriminating gray-scale and Doppler sonographic features.

PURPOSE: To determine the gray-scale and Doppler sonographic features that best enable discrimination between malignant and benign ovarian masses and develop a scoring system for accurate diagnosis with these features. MATERIALS AND METHODS: Gray-scale and Doppler sonographic features of 211 adnexal masses were correlated with the final diagnosis; the most discriminating features for malignancy were selected with stepwise logistic regression. RESULTS: Twenty-eight masses were malignant and 183 benign. All masses with a markedly hyperechoic solid component or no solid component were benign. For masses with a nonhyperechoic solid component, additional features that allowed statistically significant discrimination of benignity from malignancy were, in decreasing order of importance, (a) location of flow at conventional color Doppler imaging, (b) amount of free intraperitoneal fluid, and (c) presence and thickness of septations. A scoring formula that made use of values based on the logistic regression equation had an area under the receiver operating characteristic curve of 0.98 +/- 0.01. The cutoff score with the highest accuracy had a sensitivity of 93% and specificity of 93%. CONCLUSION: A solid component is the most statistically significant predictor of a malignant ovarian mass. A multiparameter scoring system that uses three gray-scale and one Doppler feature, developed by means of stepwise logistic regression, has high sensitivity and specificity for predicting malignancy.