Diagnosis and management of central nervous system metastases from breast cancer.
(73/795)
The brain, cranial nerves, leptomeninges, spinal cord, and eye compose the central nervous system (CNS) and are at risk for the development of metastases from breast cancer. Such metastases are diagnosed on the basis of clinical suspicion and substantiated by neuroimaging, resection when indicated, and sampling of cerebrospinal fluid when leptomeningeal metastasis (LM) is suspected. Treatment is aimed at palliation of symptoms and preservation of neurologic function. Historically, conventional radiation therapy has been the mainstay of palliative treatment for brain, cranial nerve, spinal cord, and ocular metastases. However, additional treatment options for brain metastases have been brought about by technological advances in surgery to resect brain metastases, and stereotactic radiosurgery (SRS) to focally irradiate metastases, both of which have been substantiated by data from randomized trials. Ongoing research is aimed at refining criteria to select which patients with brain metastases should undergo surgery and SRS and how these focal therapies should be optimally integrated with whole-brain radiotherapy. Therapy for LM must carefully balance the potential risks and perceived benefits associated with CNS-directed therapies. Despite advances in neuroimaging, surgery, and radiation therapy, novel treatments are needed to improve the effectiveness of treatments for CNS metastases, especially LM, while reducing attendant neurotoxicity. (+info)
Malignancy of eye melanomas originating in the retinal pigment epithelium of transgenic mice after genetic ablation of choroidal melanocytes.
(74/795)
Eye tumors of the retinal pigment epithelium (RPE) have been thought generally to be benign, whereas choroidal ones are malignant. To test this assumption in mice, the W/Wv (Kit) mutant genotype was introduced into melanoma-prone transgenic mice whose recombinant simian virus 40 transforming sequences are specifically expressed in pigment cells. W/Wv causes programmed death of neural crest-derived pigment cells, including choroidal ones, but leaves intact the brain-derived pigment cells, such as those in the RPE. Dysplastic cells arose in the RPE, contiguous with frank melanotic neoplasms. Invasion of the optic nerve, and tumor growth outside the orbit, attested to the malignancy of these RPE-derived melanomas. The widespread melanosis previously seen in mice with this transgene was absent when W/Wv was added, thus validating its chief origin from neural crest cells. (+info)
Prolapsed intraocular aspergilloma masquerading as malignant melanoma.
(75/795)
We describe an aspergilloma that masqueraded as an intraocular malignant melanoma in an elderly male patient. (+info)
Characterization of vitreous B-cell infiltrates in patients with primary ocular lymphoma, using CDR3 size polymorphism analysis of antibody transcripts.
(76/795)
PURPOSE: Histopathology usually cannot be performed and cytology is unfortunately frequently insufficient to confirm a suspicion of primary intraocular lymphoma (PIOL). The purpose of this study was to evaluate the Immunoscope technique for the identification of ocular B-cell monoclonal infiltrates in patients with malignant or immune conditions. METHODS: Polymorphism analysis of the size of the third complementarity-determining region (CDR3) of heavy chain antibody transcripts was used to differentiate between a polyclonal infiltrate and a monoclonal infiltrate within a clinical vitreous sample of two groups of patients. PIOL was confirmed in all patients of the first group (n = 6). Five patients with autoimmune uveitis or immune-recovery uveitis associated with AIDS were included in the control group. The level of IL-10 in the vitreous was determined in all patients. RESULTS: In five cases of severe PIOL, CDR3 polymorphism analysis confirmed the presence of a dominant B-cell clone within the eye. In one case of confirmed PIOL presenting with mild vitritis, CDR3 polymorphism analysis was consistent with the existence of a polyclonal profile in the ocular sample studied. Conversely, it was shown that the detection of an intraocular monoclonal B-cell population does not necessarily imply ocular lymphoma. A clonal expansion was detected in a control patient who exhibited merely a nonmalignant response associated with immune-recovery uveitis. CONCLUSIONS: This PCR-based technique can make an important contribution to the characterization of intraocular B cells, but it alone cannot confirm or exclude the existence of a malignant lymphocyte proliferation. In the evaluation of a patient with intraocular inflammation in whom PIOL is suspected, CDR3 polymorphism analysis is recommended to confirm clonality. In general, the information about lymphocyte diversity provided by this technology opens up new possibilities for the analysis of ocular infiltrates. (+info)
A pilot study in ophthalmology of inter-rater reliability in classifying diagnostic errors: an underinvestigated area of medical error.
(77/795)
BACKGROUND: Misdiagnosis is the least studied form of medical error. Before effective strategies to reduce misdiagnosis can be developed, there needs to be a better understanding of the factors that lead to these errors. AIM: To evaluate the applicability and reliability of three classification systems for misdiagnosis. DESIGN: Retrospective independent analysis of five cases by clinical experts. PARTICIPANTS: Three ophthalmologists trained in ocular oncology who devote at least 75% of their practice to ocular oncology. MAIN OUTCOME MEASURES: Percentage agreement in determining cause of misdiagnosis. RESULTS: Participants agreed a misdiagnosis occurred in all cases and the error was graded as serious 14 of 15 times (93%). Inter-rater agreement for root cause varied among the three classification systems from 47% to zero. CONCLUSIONS: Although there was excellent agreement among clinical experts of what constitutes serious misdiagnosis under idealized conditions, there is not a reliable method for categorizing the primary or root cause for these errors. The origins of misdiagnosis are complex, often multifactorial, and more difficult to categorize than other types of medical error. Misdiagnosis is a professional and public healthcare challenge that will require novel strategies to enable it to be successfully studied. (+info)
Prolonged survival after complete resection of metastases from intraocular melanoma.
(78/795)
BACKGROUND: The median survival time is only 2-6 months after a diagnosis of metastases from intraocular melanoma. Because complete resection of metastatic melanoma from a cutaneous primary tumor can prolong survival, the authors hypothesized that resection also might benefit patients with metastases from an intraocular site. METHODS: From 1971 to 1999, 112 patients with metastatic melanoma from an intraocular site were enrolled in various treatment protocols after informed consent was obtained. Prospectively recorded clinical variables and follow-up information were retrieved from the patient database. Survival curves were estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. Propensity score analysis was used to reduce the imbalance between subgroups and to assess treatment effect. RESULTS: Seventy-eight patients (70%) presented with liver involvement. Twenty-four patients (21%) underwent resection of metastatic lesions. At a median follow-up time of 11 months (range, 1-97 months; > 36 months for survivors), the median survival period was 11 months and the 5-year survival rate was 7%. Univariate analysis showed that surgical resection, site of metastases, number of metastatic lesions, and disease-free interval were correlated significantly with survival (P < 0.001, P < 0.001, P < 0.001, and P = 0.031, respectively). Multivariate analysis showed that surgical resection was significant (P = 0.008) but that the site of metastases was not (P = 0.146). The median survival and the 5-year survival rate were 38 months and 39%, respectively, for surgical patients, versus 9 months and 0%, respectively, for nonsurgical patients. After adjusting for covariate imbalance by propensity score analysis, surgery remained significant (P = 0.021) on multivariate analysis. CONCLUSIONS: Complete resection may prolong survival in certain patients with distant metastases from intraocular primary melanoma. However, the overall unfavorable prognosis indicates an urgent need for more effective nonsurgical interventions. (+info)
Mitomycin C as an adjunct in the treatment of localised ocular surface squamous neoplasia.
(79/795)
AIM: To report the outcome of topical mitomycin C (MMC) used as adjunctive treatment following primary excision of ocular surface squamous neoplasia (OSSN). METHOD: Prospective, non-comparative interventional case series of 27 primary OSSN lesions from 26 patients treated in a single ocular oncology centre over a 4 year period. RESULT: 27 cases of OSSN received a treatment regimen of surgical excision, followed by topical MMC. Mean follow up of 27 (SD 12) months (range 12-50, median 25 months) revealed zero recurrences. CONCLUSION: MMC treatment following surgical excision decreases the recurrence rate of primary ocular surface neoplasia and should be considered as adjunctive therapy in primary treatment. (+info)
Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver.
(80/795)
PURPOSE: Liver metastases are the sole or life-limiting component of disease in the majority of patients with ocular melanoma who recur. Because median survival after diagnosis of liver metastases is short and no satisfactory treatment options exist, we have conducted clinical trials evaluating isolated hepatic perfusion (IHP) for patients afflicted with this condition. EXPERIMENTAL DESIGN: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP using 1.5 mg/kg of melphalan (mean total dose 105 mg). Via laparotomy, perfusion inflow was established with a cannula in the gastroduodenal artery and outflow via a cannula positioned in an isolated segment of the retrohepatic inferior vena cava. Portal and infra-renal inferior vena cava blood flow was shunted externally to the axillary vein using a veno-veno bypass circuit. Patients were assessed for toxicity, radiographic response, and survival. RESULTS: There was no treatment related mortality and transient grade 3/4 hepatic toxicity was observed in 19 patients (65%). Mean length of operation and hospital stay was 8.3 h and 10 days, respectively. There were 3 (10%) complete responses (duration: 12, 14+, 15 months) and 15 partial responses (52%; mean duration: 10 months). The initial site of disease progression included liver in 17 of 25 patients (68%) who recurred. At a median follow-up of 30.7 months the median actuarial progression-free and overall survivals were 8 and 12.1 months, respectively. CONCLUSIONS: IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly in liver, continued clinical evaluation of hepatic directed therapy in this patient population is justified. (+info)