A phase II study of bortezomib in patients with MALT lymphoma.

We have performed a phase II study to evaluate bortezomib in patients with MALT-lymphoma. Sixteen patients entered the trial, 4 had gastric MALT-lymphoma, 7 of the ocular adnexa, one of the colon, and 2 of the parotid, and one patient each the lung and the breast. Bortezomib was given at 1.5 mg/m(2) days 1, 4, 8 and 11; repeated every 21 days. The overall response rate was 80% (13/16); 7 patients achieved complete remission (43%), 6 partial response (37%) and 3 stable disease. After a median follow-up of 23 months (range; 8-26), all patients are alive and 4 have relapsed. Fifteen patients required dose reductions due to either neuropathy (7 patients) or diarrhea (8 patients). Bortezomib appears to be active in patients with MALT-lymphoma. However, an unexpectedly high rate of toxicities was seen, warranting assessment of combination schedules with bortezomib at a lower dose than given in our study.

Assessment of the role of hepatitis C, Helicobacter pylori and autoimmunity in MALT lymphoma of the ocular adnexa in 45 Austrian patients.

INTRODUCTION: A recent series from Italy has suggested a pathogenic link between hepatitis C virus and MALT lymphoma of the ocular adnexa. The hypothesis of our study was to prove this concept in Austrian patients with MALT lymphoma of the ocular adnexa. MATERIALS AND METHODS: A total of 45 patients presenting with MALT lymphoma of the ocular adnexa were assessed for the presence of infection with hepatitis A, B and C. Furthermore, extensive staging to evaluate the extent of disease along with analysis of Helicobacter pylori-infection, the presence or absence of autoimmune diseases (AD) and assessment of MALT-lymphoma specific genetic changes was performed. RESULTS: Only 2/45 (4%) patients were tested positive for hepatitis C, while 10/45 (22%) had an underlying AD and 15/39 (38%) had HP infection. Chromosomal aberrations were detected in 19 (54%) of 35 patients analyzed. Disseminated disease was a significant risk factor for relapse (p=0.014). DISCUSSION: Our series suggests that infection with hepatitis C is not a significant contributor to the pathogenesis of ocular adnexal MALT lymphoma in the Austrian population, while a substantial proportion of these patients suffer from autoimmune conditions.

Orbital scintigraphy with the somatostatin receptor tracer 99mTc-P829 in patients with Graves' disease.

UNLABELLED: Receptors for somatostatin (SST) (SSTR) are expressed on various tumor cells as well as on activated lymphocytes. Previous data have shown that (99m)Tc-P829 binds with high affinity to many different types of tumor cells as well as to leukocytes via the human hSSTR2, hSSTR3, and hSSTR5 target receptors. Consequently, (99m)Tc-P829 was successfully introduced as a peptide tracer for tumor imaging. In this study, we evaluated the orbital uptake of (99m)Tc-P829 in patients with active and inactive thyroid-associated orbitopathy (TAO), accompanied by lymphocyte infiltration in the acute stage and by muscle fibrosis in the chronic stage of the disease. METHODS: To evaluate its clinical usefulness in Graves' disease, (99m)Tc-P829 scintigraphy (approximately equal to 740 MBq) was performed in 44 patients with TAO (median duration, 19 mo; range, 1-360 mo). The clinical activity of the orbital disease was graded by the NOSPECS (no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) classification of the American Thyroid Association, the clinical activity score (CAS), and the superonasal index (SNI). SPECT (360 degrees ) and planar studies were completed within 3 h after injection. Orbital (O) regions of interest (ROIs) were compared with temporoparietal and occipital (OCC) ROIs. Orbital uptake ratios in Graves' disease were compared with data obtained from lung cancer patients with no eye disease (n = 22). RESULTS: Overall, (99m)Tc-P829 biokinetics were the same in Graves' disease patients as in lung cancer patients, showing a rapid blood clearance and visualization of the facial bones within minutes of injection. In all control patients, the orbit appeared as a "cold area," whereas visual orbital accumulation of (99m)Tc-P829 was found in patients with active TAO (O/OCC ratios: 1.26 +/- 0.04 vs. 1.69 +/- 0.04; P < 0.01, respectively). Patients with active eye disease (n = 25) presented with an increased orbital uptake of (99m)Tc-P829 compared with patients with inactive disease (n = 19; O/OCC ratio: 1.12 +/- 0.05; P < 0.01). A statistically significant correlation was found between CAS and the orbital uptake (O/OCC ratio) values (r = 0.90), whereas no correlation could be documented regarding the NOSPECS classification as well as the SNI. CONCLUSION: In TAO, (99m)Tc-P829 yields high orbital binding with good clinical correlation. The better image quality due to the high energy of technetium, the lower radiation dose for patients and personnel, and the short acquisition protocol favor SSTR scintigraphy with (99m)Tc-P829 over (111)In-labeled compounds. The in-house availability of the radiotracer and cost-effectiveness are further advantages.

Surgery in unilateral congenital cataract caused by persistent fetal vasculature or minimal fetal vascular remnants: age-related findings and management challenges.

PURPOSE: To document in detail the surgical management challenges over the wide spectrum of persistent fetal vasculature syndrome (PFVS). SETTING: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. METHODS: As part of an ongoing prospective clinical trial of the treatment and etiology of pediatric cataract, a subgroup of 31 children with unilateral cataract was defined. Standard surgical techniques were used based on age. Group 1 comprised infants between 0 and 1.5 years; Group 2, preschool children between 1.6 and 5.9 years; and Group 3, school-aged children between 6 and 16 years. Additional surgical procedures were used based on the degree of PFVS. RESULTS: All 31 eyes with unilateral cataract showed signs of PFVS. Characteristic features were found in 75% of eyes in Group 1, 8% of eyes in Group 2, and 67% of eyes in Group 3. Minimal fetal vascular remnants were found in 92%, 25%, and 33%, respectively. Correct diagnosis of PFVS was made preoperatively in 56% of eyes in Group 1, 8% in Group 2, and 67% in Group 3. Surgical procedures in addition to standard age-related techniques were necessary in all eyes with unilateral cataract. CONCLUSIONS: Results indicate that varying degrees of PFVS are a frequent cause of unilateral congenital cataract. Most severe cases were in infants, and preschool children were usually mildly affected. Vitreoretinal complications may lead to challenges in the surgical management in infants. In preschool children, cataract surgery must be performed in a guarded fashion because of the high risk for preexisting posterior capsule breaks due to minimal fetal vascular remnants.

CT-MR image data fusion for computer-assisted navigated surgery of orbital tumors.

PURPOSE: To demonstrate the value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative assessment of orbital tumors, and to present, particularly, CT and MR image data fusion for surgical planning and performance in computer-assisted navigated surgery of orbital tumors. MATERIALS AND METHODS: In this retrospective case series, 10 patients with orbital tumors and associated complaints underwent MDCT and MRI of the orbit. MDCT was performed at high resolution, with a bone window level setting in the axial plane. MRI was performed with an axial 3D T1-weighted (w) gradient-echo (GE) contrast-enhanced sequence, in addition to a standard MRI protocol. First, MDCT and MR images were used to diagnose tumorous lesions compared to histology as a standard of reference. Then, the image data sets from CT and 3D T1-w GE sequences were merged on a workstation to create CT-MR fusion images that were used for interventional planning and intraoperative image guidance. The intraoperative accuracy of the navigation unit was measured, defined as the deviation between the same landmark in the navigation image and the patient. Furthermore, the clinical preoperative status was compared to the patients' postoperative outcome. RESULTS: Radiological and histological diagnosis, which revealed 7 benign and 3 malignant tumors, were concordant in 7 of 10 cases (70%). The CT-MR fusion images supported the surgeon in the preoperative planning and improved the surgical performance. The mean intraoperative accuracy of the navigation unit was 1.35mm. Postoperatively, orbital complaints showed complete regression in 6 cases, were ameliorated notably in 3 cases, and remained unchanged in 1 case. CONCLUSION: CT and MRI are essential for the preoperative assessment of orbital tumors. CT-MR image data fusion is an accurate tool for planning the correct surgical procedure, and can improve surgical results in computer-assisted navigated surgery of orbital tumors.

Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience.

PURPOSE: Molecular data and preliminary clinical findings have suggested mucosa-associated lymphoid tissue (MALT) lymphoma as a multifocal disease in a high percentage of patients. We report our findings with an extensive staging routine applied in patients diagnosed with MALT lymphoma at our institution. PATIENTS AND METHODS: A total of 140 consecutive patients (61 with gastric and 79 with extragastric MALT lymphoma) underwent staging according to a standardized protocol. Staging included gastroscopy with multiple biopsies, endosonography of the upper GI tract, computed tomography of thorax and abdomen, lymph node sonography, colonoscopy with multiple biopsies, otorhinolaryngologic assessment, magnetic resonance imaging of salivary and lacrimal glands, and bone marrow biopsy. All lesions suggestive of lymphoma involvement were subjected to biopsy, if accessible, and biopsies were evaluated for MALT lymphoma-specific genetic aberrations by means of reverse transcriptase polymerase chain reaction and/or fluorescent in situ hybridization. RESULTS: Fifteen (25%) of 61 patients with gastric MALT lymphoma had multiorgan involvement, with dissemination beyond the GI tract in six patients. By contrast, significantly more patients with extragastric MALT lymphoma had dissemination to another MALT organ (37 of 79 patients, 46%; P = .045). Nine of these 37 patients had dissemination to the stomach. Only three (2%) of 140 patients had bone marrow involvement. Multifocality was significantly associated with t(11;18)(q21;q21) in gastric lymphomas (P = .045) and with trisomy 18 in extragastric lymphomas (P = .011). CONCLUSION: Our findings suggest that MALT lymphoma frequently presents as a multifocal disease. Extragastric MALT lymphomas are significantly more prone to dissemination than gastric MALT lymphomas.

Biometry and refractive outcome of eyes filled with silicone oil by standardized echography and partial coherence interferometry.

BACKGROUND: We evaluated the validity of calculations for refractive outcome in cataract surgery in silicone oil-filled eyes. The retrosilicone space (RSS) was included in these calculations. METHODS: In a prospective study the axial length (AL) of silicone oil-filled eyes was measured. with standardized A-scan echography (SAE) and partial coherence interferometry (PCI). Meldrum's formula was used to transform the velocity of ultrasound within the vitreous cavity. To investigate whether refractive outcome can be calculated accurately, we assessed the difference between precalculated and final refractive outcome. Furthermore, we determined the advantages and disadvantages of SAE and PCI. A minor aim was to assess whether the AL of the two eyes differed significantly. RESULTS: In 85% of 117 eyes the difference between precalculated and postsurgical refraction was smaller than 1 diopter spherical and statistically not significant (p>0.2). The mean AL was 24.1 mm (range 20.0-31.4 mm). The difference in outcome between the two methods was without statistical significance: the AL difference was 0.4 (+/-2.6) mm on measurement with SAE and 0.04 (+/-0.46) mm with PCI. PCI has the advantage that it can be performed more easily, without contact, while echography is advantageous in the presence of advanced cataracts. In supine position an oil-free fluid space behind the silicone oil was detected with echography. The mean dimension of this space was 1.9 (+/-0.67) mm and it was taken into consideration for IOL calculation. The mean AL difference between the two eyes was 0.4 mm, but the difference was greater than 1 mm in 26% of the patients. CONCLUSION: The AL of eyes filled with silicone oil can be measured reliably with SAE and PCI. In supine position the RSS has to be considered to obtain more accurate IOL calculations.