Edgardo J. Angtuaco

Magnetic Resonance Imaging in Multiple Myeloma: Diagnostic and Clinical Implications

PURPOSE Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs). PATIENTS AND METHODS Both baseline MBS and MRI were available in 611 of 668 myeloma patients who were treated uniformly with a tandem autologous transplantation-based protocol and were evaluated to determine their respective merits for disease staging, response assessment, and outcome prediction. RESULTS MRI detected focal lesions (FLs) in 74% and MBS in 56% of imaged anatomic sites; 52% of 267 patients with normal MBS results and 20% of 160 with normal MRI results had FL on MRI and MBS, respectively. MRI- but not MBS-defined FL independently affected survival. Cytogenetic abnormalities (CAs) and more than seven FLs on MRI (MRI-FLs) distinguished three risk groups: 5-year survival was 76% in the absence of both more than seven MRI-FLs and CA (n = 276), 61% in the presence of one MRI-FL (n = 262), and 37% in the presence of both unfavorable parameters (n = 67). MRI-FL correlated with low albumin and elevated levels of C-reactive protein, lactate dehydrogenase, and creatinine, but did not correlate with age, beta-2-microglobulin, and CA. Resolution of MRI-FL, occurring in 60% of cases and not seen with MBS-defined FL, conferred superior survival. CONCLUSION MRI is a more powerful tool for detection of FLs than is MBS. MRI-FL number had independent prognostic implications; additionally, MRI-FL resolution identified a subgroup with superior survival. We therefore recommend that, in addition to MBS, MRI be used routinely for staging, prognosis, and response assessment in myeloma.

F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma

F18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a powerful tool to investigate the role of tumor metabolic activity and its suppression by therapy for cancer survival. As part of Total Therapy 3 for newly diagnosed multiple myeloma, metastatic bone survey, magnetic resonance imaging, and FDG-PET scanning were evaluated in 239 untreated patients. All 3 imaging techniques showed correlations with prognostically relevant baseline parameters: the number of focal lesions (FLs), especially when FDG-avid by PET-computed tomography, was positively linked to high levels of beta-2-microglobulin, C-reactive protein, and lactate dehydrogenase; among gene expression profiling parameters, high-risk and proliferation-related parameters were positively and low-bone-disease molecular subtype inversely correlated with FL. The presence of more than 3 FDG-avid FLs, related to fundamental features of myeloma biology and genomics, was the leading independent parameter associated with inferior overall and event-free survival. Complete FDG suppression in FL before first transplantation conferred significantly better outcomes and was only opposed by gene expression profiling-defined high-risk status, which together accounted for approximately 50% of survival variability (R(2) test). Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy.

Myeloma of the central nervous system: association with high-risk chromosomal abnormalities, plasmablastic morphology and extramedullary manifestations.

Summary.  Involvement of the central nervous system (CNS) by multiple myeloma, as defined by the detection of malignant plasma cells in the cerebrospinal fluid in the presence of suggestive symptoms, is considered extremely rare. We report on the characteristics of 18 such patients diagnosed and treated at the University of Arkansas over the last 10 years for an overall incidence of approximately 1%. Their evaluation revealed association of CNS involvement with unfavourable cytogenetic abnormalities (especially translocations and deletion of the chromosome 13), high tumour mass, plasmablastic morphology, additional extramedullary myeloma manifestations and circulating plasma cells. The presence of these features should alert clinicians to the possibility of CNS involvement. The outcome of these patients was extremely poor despite the use of aggressive local and systemic treatment including autologous stem cell transplants. Given this universally poor prognosis, the application of allogeneic transplants should be studied in this clinical setting.

Intracranial aneurysms in infants and children

Background. The diagnosis and imaging of pediatric aneurysms has changed since the advent of MR and MRA. Objective. To update the literature on pediatric aneurysms and better define the appropriate work-up of childhood aneurysms in 1997. Materials and methods. Retrospective review of 21 children (12 boys, 9 girls) with 25 aneurysms from three institutions over a 20-year period was performed. Imaging studies were mixed and included CT (19 patients), MR (11 patients), MRA (6 patients) and angiography (18 patients). Results. Eighteen of 25 aneurysms were congenital saccular, 6 were mycotic, and 1 was post-traumatic. Of these, 44 % were in the posterior circulation. Nine aneurysms arose from distal arterial branches. Forty percent were large (between 1–2.5 cm) and 16 % were giant (> 2.5 cm). CT and MR showed hemorrhage, and frequently revealed the aneurysms as a focal mass with or without enhancement and flow void. Six children had MRA which revealed aneurysms in four patients. All patients with MRA had corresponding conventional angiography. Conclusion. Characteristics of pediatric aneurysms include diversity of type, increased incidence in the posterior fossa, peripheral location, and large size. CT, MR and MRA are useful in the diagnosis with conventional angiography essential for preoperative planning.

A combined microsurgical skull-base and endovascular approach to giant and large paraclinoid aneurysms

Abstract BACKGROUND The treatment of giant and large paraclinoid aneurysms remains challenging. To improve exposure, facilitate the dissection of aneurysms, assure vascular control, reduce brain retraction and temporary occlusion time, enable simultaneous treatment of associated lesions, and achieve more successful treatment of “difficult” (atherosclerotic and calcified) aneurysms, we combined the skull-base approach with endovascular balloon occlusion of the internal carotid artery (ICA) and suction decompression of the aneurysm. METHODS Sixteen female patients were treated, eight with giant aneurysms and eight with large aneurysms. Eight aneurysms occurred on the right side and eight on the left. Eight patients had an additional aneurysm; five were clipped during the same procedure. Three patients had infundibular arterial dilation. One patient had an associated hemangioma of the ipsilateral cavernous sinus. The cranio-orbital-zygomatic approach was used for all patients. The anterior clinoid was drilled, and the optic nerve was decompressed, dissected, and mobilized. Transfemoral temporary balloon occlusion of the ICA in the neck was followed by placement of a temporary clip proximal to the posterior communicating artery. Suction decompression was then applied. All aneurysms were then successfully clipped, except one that had a calcified neck and wall that could not be collapsed. Intraoperative angiography performed in 13 of 15 patients with clipped aneurysms confirmed obliteration of the aneurysm and patency of the blood vessels. RESULTS Postoperative results were good in 14 patients. One patient had right-sided hemiplegia and expressive aphasia, which improved after rehabilitation. One patient with an additional basilar tip aneurysm clipped simultaneously died on the fifth postoperative day because of intraventricular hemorrhage. The origin of bleeding could not be determined on autopsy. Surgical difficulties and morbidity stemmed mainly from a severely calcified or atherosclerotic aneurysmal neck. CONCLUSION The combination of skull-base approaches and endovascular balloon occlusion coupled with suction decompression is a successful option for the treatment of these challenging aneurysms.

Avascular Necrosis of Femoral and/or Humeral Heads in Multiple Myeloma: Results of a Prospective Study of Patients Treated With Dexamethasone-Based Regimens and High-Dose Chemotherapy

PURPOSE To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. PATIENTS AND METHODS A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. RESULTS With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. CONCLUSION AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data

Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (n=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling–defined high risk, and the proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling–defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling–risk designation. (Clinicaltrials.gov identifier: NCT00081939)

Dural arteriovenous malformations of the transverse/sigmoid sinus acquired from dominant sinus occlusion by a tumor: report of two cases.

OBJECTIVE AND IMPORTANCE Debate continues regarding the pathogenesis of dural arteriovenous malformations (dAVMs). The prevailing theory is that dAVMs are acquired lesions that occur after thrombosis of the dural venous sinus. CLINICAL PRESENTATION We report unique cases of two patients having different tumors (one meningioma and one glomus jugulare paraganglioma) that occluded the ipsilateral transverse and sigmoid sinuses, respectively, and were associated with dAVMs. In each patient, the occluded venous sinus was the dominant sinus. CONCLUSION Our experience with these patients supports the hypothesis that dAVMs are acquired and induced lesions that may occur after sinus occlusion. We suggest that the occlusion of the dominant transverse/ sigmoid sinus is a major contributing factor to the development of dAVMs because of the inability of the contralateral (nondominant) sinus to handle the venous flow from the obstructed (dominant) side.

Computed tomographic discography in the evaluation of extreme lateral disc herniation.

Thin section, high resolution computed tomographic (CT) scans of the lumbar spine produce images that can show herniated intervertebral discs without intravenous or intrathecal contrast enhancement. With this technique, the diagnosis of posterolateral and midline herniation has been greatly facilitated. This communication reports the use of CT discography in the preoperative evaluation of two patients who were shown at discography and proven at operation to have extreme lateral disc herniations.

Ocular Involvement in Mycotic Sinusitis Caused by Bipolaris

We examined two patients with unilateral ophthalmologic findings secondary to pansinusitis caused by Bipolaris. Both patients were healthy young men. One patient had a gradual visual loss, whereas the other showed proptosis. Surgical debridement was the primary treatment in both patients. One patient received antifungal therapy, whereas the other was cured with surgery alone.