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Biomedical subjects

R P Dinapoli

Publications and source records attributed to R P Dinapoli.

At least 19 recordsLinked to original sources

Paraneoplastic and metastatic neurologic complications of Merkel cell carcinoma.

Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is locally aggressive and frequently accompanied by distant metastases. Neurologic complications of Merkel cell carcinoma are rare. We describe a 69-year-old man who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel cell carcinoma. The paraneoplastic syndrome improved with initial treatment of the malignancy. He subsequently developed a solitary brain metastasis and died of leptomeningeal carcinomatosis.

Aged↗

Recurring brachial plexus neuropathy in a diabetic patient after shoulder surgery and continuous interscalene block.

IMPLICATIONS: The performance of regional blockade on a patient with a preexisting neurologic condition or a history of neurologic complications after regional anesthesia is controversial. We present a case of recurring brachial plexus neuropathy in a diabetic patient after two shoulder procedures performed 4 mo apart. In both cases, the patient underwent intensive physical therapy with continuous postoperative interscalene analgesia.

Adult↗

Phase II North Central Cancer Treatment Group study of 2-cholorodeoxyadenosine in patients with recurrent glioma.

There is no standard treatment for patients with recurrent gliomas, and their prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has significant activity in many low-grade lymphoproliferative disorders. The authors conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in patients with recurrent gliomas. Patients with a histologically confirmed primary brain tumor with evidence of progression after radiation therapy were eligible. Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on days 1 through 5 every 28 days. For those with a history of prior nitrosourea therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1 through 5. Treatment was continued until progression or a maximum of 12 cycles. Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades were entered in the study. Treatment was well tolerated. Major toxicities were myelosuppression and neurotoxicity. No responses were seen. The authors conclude that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity in patients with recurrent gliomas was established.

Adult↗

Central nervous system histoplasmosis mimicking a brain tumor: difficulties in diagnosis and treatment.

Neurologic involvement occurs in 10% to 20% of patients with disseminated histoplasmosis. We describe a 20-year-old woman who had headache and diplopia but no evidence of systemic infection. Magnetic resonance imaging showed an enhancing mass in the thalamomesencephalic and third ventricular region. After subtotal resection of what was presumed to be a glioma, the patient had symptoms and signs of meningitis. Subsequent pathological review demonstrated noncaseating granulomas, and serologic tests and cultures confirmed the diagnosis of histoplasmosis. Initiation of antifungal therapy and removal of an infected shunt system resulted in clinical improvement. Clinicians should maintain a high index of suspicion in patients who are from any area endemic for histoplasmosis.

Adult↗

Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high-grade glioma.

PURPOSE: A Phase I study to determine the safety, toxicity, and maximum tolerated dose (MTD) of carmustine (BCNU) and interferon alpha-2a (IFN-a) when combined with radiation as initial therapy in high-grade glioma. METHODS AND MATERIALS: Patients with newly diagnosed Grade 3 or 4 astrocytoma, oligoastrocytoma, or gliosarcoma were enrolled after surgery. All received radiation therapy to the brain (64.8 Gy/36 fractions), combined with a single dose of BCNU (200 mg/m2) at the start of radiation. Chemotherapy after completing radiation consisted of BCNU 150 mg/m2 once every 7 weeks, and IFN-a 12 x 10(6) units/m2 subcutaneously Days 1-3 each week of a 7-week cycle. Subsequent dose modification was based on constitutional symptoms for IFN-a and on myelosuppression for BCNU. RESULTS: Fifteen patients were entered on the study. Four were excluded because they did not receive IFN-a (3 refused treatment and 1 patient left the study due to multiple medical problems). Eleven were evaluable for toxicity and efficacy. Nonhematological toxicity, mainly lethargy and flu-like symptoms, were dose-limiting for IFN-a. After the first 6 patients were treated per the initial protocol, the frequency of IFN-a administration was decreased to Days 1-3 on weeks 1, 3, and 5 of the 7-week cycle for 5 additional patients. Lethargy, fever, chills, myalgias, alopecia, and anorexia occurred in all patients. Other toxicities included nausea and vomiting (91%), central-nervous-system depression or mood changes (64%), headaches (55%), and elevation of liver enzymes (36%). Grade 3-4 leukopenia occurred in 4 (45%) of 11 patients, and Grade 3-4 thrombocytopenia in 3 (27%) of 11 patients. Due to myelosuppressive effects, BCNU dose was not escalated. Median survival of the cohort was 44 months. Objective responses occurred in 5 (56%) of 9 patients and median duration of response was 33 months. The MTD of this combination after radiation therapy is IFN-a 12 x 10(6) units/m2 Days 1-3, on Weeks 1, 3, and 5 of a 7-week cycle and BCNU 150 mg/m2 Day 1, every 7 weeks. CONCLUSIONS: Treatment with radiation, IFN-a, and BCNU is feasible and effective in patients with high-grade gliomas, although constitutional symptoms from IFN-a are substantial.

Adult↗

Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.

PURPOSE: The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS: We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS: The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION: In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.

Adolescent↗

Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.

PURPOSE: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS: Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS: Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION: This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.

Adult↗

Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results.

OBJECT: Gliosarcoma, a rare malignancy of the central nervous system, consists of gliomatous and sarcomatous elements. There are conflicting reports regarding its aggressiveness and cell line of origin compared with those of glioblastoma multiforme (GBM). The goal of this study was to compare clinicopathological features such as disease-free survival time and actual survival time in patients with gliosarcoma with a matched group of patients with GBM as well as with the entire group of patients with GBM. METHODS: The authors report on 18 cases of gliosarcoma derived from a series of 748 Grade 4 astrocytoma cases that were part of four consecutive randomized Phase III trials conducted between 1979 and 1996. In this series the gliosarcoma group represented only 2.4% of all GBMs and included 11 men and seven women with a median age of 61.5 years (range 31-81 years). The median tumor size was 5 cm (range 2-8 cm). The locations, all supratentorial, included temporal in 44%, parietal in 28%, frontal in 17%, and occipital in 11%. The 18 patients with gliosarcomas, all Grade 4 (World Health Organization classification), were compared with the entire group of 730 patients with GBM and a control group of 18 patients with GBM matched for known prognostic factors including patient age, randomization date, performance status, extent of resection, and protocol number. Patients in all treatment groups received radiation and nitrosourea-based chemotherapy. The median time to progression and the median survival times for the patients with gliosarcoma were 28.0 and 35.1 weeks as compared with 24.7 and 41.6 weeks for the entire group of patients with GBM (log rank test, p = 0.94 and 0.27, respectively) and 16.7 and 34.4 weeks in the control group (p = 0.20 and 0.84, respectively). In previous molecular cytogenetic analyses of gliosarcoma these authors have shown similar genetic changes in the gliomatous and sarcomatous components. CONCLUSIONS: The data obtained in this study support the conclusion that gliosarcoma shares significant clinical and genetic similarities with GBM and that the same principles should be applied for patient enrollment in research protocols and treatment for these two kinds of tumor.

Adult↗

Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT plus BCNU in high grade astrocytoma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and DBD with RT and BCNU in patients with high-grade astrocytoma. METHODS: A total of 238 patients with supratentorial grade 3 and grade 4 astrocytoma were studied. Patients were stratified by age, extent of surgery, tumor grade, and performance score and randomly assigned to receive RT 55-60 Gy and either DBD, 200 mg/m2 orally on Days 1-10 every five weeks or BCNU, 200 mg/m2 intravenously every seven weeks. Median age was 60 years; 62% were 55 years or older. Eighty-three percent had subtotal resection, 58% had grade 4 tumors, and 83% had performance scores of 0-2. RESULTS: Survival distributions for all patients in the two arms were similar, with median survival of 41 weeks in each arm. Time to progression distributions were virtually identical, with medians of 22 weeks. BCNU produced significantly greater hematologic toxicity; median leukocyte and platelet nadirs on the first cycle were 3.6 vs. 4.7 (P = 0.0001) and 117 vs. 162 (P < 0.0001), and overall platelet nadirs were 80.5 vs. 114 (P = 0.0019). Non-hematologic toxicities were also significantly greater with BCNU, including nausea (57% vs. 31%; P < 0.0001) and vomiting (45% vs. 17%; P < 0.0001). CONCLUSION: This trial found no evidence of differences in treatment efficacy when either DBD or BCNU is combined with radiation therapy for patients with high-grade astrocytoma.

Algorithms↗

Occult systemic non-Hodgkin's lymphoma (NHL) in patients initially diagnosed as primary central nervous system lymphoma (PCNSL): how much staging is enough?

OBJECTIVE: To demonstrate the extent of staging necessary to exclude occult systemic stage IV NHL before making a diagnosis of stage I AE PCNSL. BACKGROUND: The diagnosis of PCNSL requires the demonstration of malignant lymphocytes within the CNS (usually by biopsy) and finding no evidence of systemic NHL. Different staging approaches have been recommended, ranging from extensive systemic evaluation (including bone marrow examination) to a more focused approach (abdominal and pelvic CT) to no systemic evaluation. We have employed a staging regimen that included: ophthalmologic evaluation (including slit lamp examination); CT of chest, abdomen, and pelvis; bilateral iliac crest aspirate and biopsy; flow cytometry of circulating lymphocytes; and, in men, testicular ultrasound. DESIGN/METHODS: We carried out a retrospective review of 128 patients entered into the Mayo Lymphoma Project data bank (1975-1994). RESULTS: Between the years 1975 and 1994, five patients (3.9%) were identified who fulfilled criteria for the diagnosis of PCNSL (typical clinical history, pathognomonic neuro-imaging, and histologic proof of NHL in brain tissue) but who had occult systemic NHL on staging (bone marrow 1, abdominal lymph nodes 3), or at autopsy (colon 1). Case histories are presented. CONCLUSIONS: Patients with apparent PCNSL may have systemic NHL. Complete staging is essential to the initial management of patients presenting as PCNSL to exclude systemic stage IV disease.

Aged↗

Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful?

Fifty-one patients with supratentorial glioma treated with external beam radiotherapy (median dose 59.5 Gy) who then demonstrated clinical or radiographic evidence of disease progression underwent stereotactic biopsy to differentiate tumor recurrence from radiation necrosis. The original tumor histological type was diffuse or fibrillary astrocytoma in 21 patients (41%), oligodendroglioma in 13 (26%), and oligoastrocytoma in 17 (33%); 40 tumors (78%) were low-grade (Kernohan Grade 1 or 2). The median time to suspected disease progression was 28 months. Stereotactic biopsy showed tumor recurrence in 30 patients (59%), radiation necrosis in three (6%), and a mixture of both in 17 (33%); one patient (2%) had a parenchymal radiation-induced chondroblastic osteosarcoma. The tumor type at stereotactic biopsy was similar to the original tumor type and was astrocytoma in 24 patients (47%), oligodendroglioma in eight (16%), oligoastrocytoma in 16 (31%), unclassifiable in two (4%), and chondroblastic osteosarcoma in one patient (2%). At biopsy, however, only 19 tumors (37%) were low grade (Kernohan Grade 1 or 2). Subsequent surgery confirmed the stereotactic biopsy histological findings in eight patients. Follow-up examination showed 14 patients alive with a median survival of 1 year for the entire group. Median survival times after biopsy were 0.83 year for patients with tumor recurrence and 1.86 years for patients with both tumor recurrence and radionecrosis; these findings were significantly different (p = 0.008, log-rank test). No patient with radiation necrosis alone died. Other factors associated with reduced survival were a high proportion of residual tumor (p = 0.024), a low proportion of radionecrosis (p < 0.001), and a Kernohan Grade of 3 or 4 (p = 0.005). In conclusion, in patients with previously irradiated supratentorial gliomas in whom radionecrosis or tumor recurrence was clinically or radiographically suspected, results of stereotactic biopsy could be used to differentiate tumor recurrence, radiation necrosis, a mixture of both lesions, or radiation-induced neoplasm. In addition, biopsy results could predict survival rates.

Adult↗

Brain metastatic lesions.

OBJECTIVE: To describe current concepts in the diagnosis and treatment of brain metastases. RESULTS: More than 25% of all autopsy-proven brain metastases have a pulmonary source. Most brain metastases manifest with a combination of focal and generalized symptoms and signs. Typically, patients have subacute, progressive symptoms. In most situations, a computed tomographic scan of the head provides sufficient neuroimaging and allows one to monitor the effects of therapy. Magnetic resonance imaging has become increasingly useful in the diagnosis and management of brain metastases. It can detect computed tomographic occult metastases, identify associated leptomeningeal disease, and reveal early therapeutic complications. CONCLUSION: Treatment options for patients with brain metastases include corticosteroids, whole-brain radiation therapy (WBRT), surgical intervention, stereotactic radiosurgical techniques, and chemotherapy. Corticosteroids produce prompt improvement in most patients; however, prolonged use is associated with considerable risks. For most patients, WBRT is the preferred treatment. Nonetheless, it has associated nonneurologic and neurologic complications, some of which are serious. In patients with a single metastasis, surgical removal should be considered. Recent studies have suggested that resection of a single metastatic lesion followed by radiation therapy offers better survival than does radiation therapy alone. The subsequent administration of WBRT after radiosurgical treatment has become standard practice. The role of chemotherapy is uncertain.

Brain Neoplasms↗

Thromboembolism in patients with high-grade glioma.

OBJECTIVE: To identify factors related to increased or decreased risk of thromboembolism (TE) in patients with high-grade glioma. DESIGN: We performed a retrospective analysis of 64 patients enrolled in two prospective clinical trials of chemotherapy and radiation therapy for newly diagnosed high-grade glioma. MATERIAL AND METHODS: The 64 patients were 18 years of age or older and had histologically confirmed grade 3 or 4 astrocytoma, mixed astrocytoma-oligodendroglioma, or gliosarcoma. The diagnosis of TE was confirmed by impedance plethysmography, venography, duplex ultrasonography, ventilation-perfusion lung scanning, or pulmonary angiography. For statistical analysis, the study group was divided into those with and those without TE. RESULTS: TE developed in 18 of the 64 patients (28%). Of the 18 patients, 11 had deep venous thrombosis of a lower extremity, 5 had pulmonary emboli, and 2 had superficial thrombophlebitis. A paretic arm (P = 0.017), a paretic leg (P = 0.026), or a history of TE before the diagnosis of glioma (P = 0.076) was more common in patients with TE than in those without TE. Ten patients in the group without TE were using aspirin preoperatively in comparison with no patient in the TE group (P = 0.05). No significant differences were noted in duration of survival (median, 39.4 weeks and 46 weeks for the TE and non-TE groups, respectively). One patient with apparently excessive anticoagulation had a fatal intracerebral hemorrhage. CONCLUSION: This study suggests that TE in patients with newly diagnosed high-grade glioma might be associated with a history of TE or with a paretic extremity; however, no evidence of worse survival was noted in the TE group. Treatment with heparin followed by warfarin sodium was associated with infrequent bleeding complications. An intriguing finding was that the use of aspirin before operation was associated with a decreased risk of TE. Thus, a prospective study with use of aspirin in patients with high-grade glioma at risk for TE would be reasonable.

Adolescent↗

Rapidly progressive aphasic dementia and motor neuron disease.

Articulatory and language impairment heralded rapidly progressive motor neuron disease in 7 patients aged 54 to 77 years. One patient had a family history of a similar disorder. Severe nonfluent aphasia developed in all 7 patients and 4 were anarthric within a year. Other cognitive domains were impaired, yet 2 patients lived alone until 1 month before their deaths. Four died within 2 years. Abnormalities were found on electromyography, computed tomography, magnetic resonance imaging, single-photon emission computed tomography, and electroencephalography. Neuropathological examination in 3 patients showed bilateral hemispheric atrophy with neuronal loss and gliosis predominantly of superficial cortical layers. Pigmented and hypoglossal nuclei were relatively preserved. At all spinal levels there was degeneration of corticospinal tracts and loss of anterior horn cells with gliosis. Rapidly progressive aphasic dementia and motor neuron disease are a distinctive clinical entity whose nosology is poorly understood.

Aphasia↗

Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS: A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS: The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION: PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.

Adult↗

Cranial nerve lesions due to base of the skull metastases in prostate carcinoma.

We studied 11 patients with prostate cancer metastatic to the base of skull that caused cranial nerve deficits. Patients with occipital condyle, jugular foramen, middle fossa, parasellar, and orbital syndromes are described. Other patients had combinations of these syndromes or other cranial nerve involvements. Two patients had 6th nerve palsies secondary to prepontine cistern and clivus lesions. The median survival time from the diagnosis of cranial nerve involvement was 4 months. Two patients had cranial nerve involvement and, on subsequent investigation, were found to have carcinoma of the prostate. Interestingly, these patients are still alive at 42 and 84 months after diagnosis.

Aged↗