Radiosurgical management of meningiomas

The management of residual, recurrent, or small skull base meningiomas is controversial. Stereotactic radiosurgery has emerged as an alternative treatment. We report our experience from September 1991 to August 1994 of treatment of 20 such patients [18 females -age 19-82 years, followed for 6-36 months (mean 15.5 months)] with the Leksell Gamma Knife. Nine patients were treated either with recurrent (2 patients-2 operations each) or residual tumor. Twelve patients had skull base, 3 optic nerve, 3 parasagittal, and 1 residual torcular tumor. Mean volume/diameter was 9.172 mm3/25 mm.     

Risk analysis of linear accelerator radiosurgery

PURPOSE: To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS: Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS: Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS: These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.     

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.     

Interrelationship between beta-amyloid deposition and complement-activated oligodendroglia

PURPOSE: To assess the reliability of the size-overestimation ratio obtained from spiral CT arterial portography (CTAP) and spiral equilibrium-phase CT (EPCT) in distinguishing malignant focal hepatic lesions from benign ones. METHODS: The CTAP images and EPCT images obtained five minutes after CTAP in 39 patients with focal hepatic lesions were retrospectively analyzed. Fifty-eight lesions (hepatocellular carcinoma [HCC], 33; metastasis, 10; liver cyst, 10; cavernous hemangioma, 2; adenomatous hyperplasia [AH], 2; focal nodular hyperplasia [FNH], 1) had their sizes measured on CTAP and EPCT images using the calipers on the CT console. RESULTS: The size-overestimation ratios (CTAP/EPCT) were 1.24+/-0.15 in HCC, 1.28+/-0.26 in metastasis, 1.02+/-0.23 in liver cyst, 0.98+/-0.34 in cavernous hemangioma, 0.94+/-0.39 in AH, and 1.00 in FNH. Mean size-overestimation ratios for benign- and malignant-lesion groups were 1.00+/-0.37 and 1.25+/-0.18, respectively (p < 0.0001). When a cutoff level was set at 1.05, sensitivity and specificity for malignancy were 91% and 93%, respectively. CONCLUSIONS: In comparison with EPCT, CTAP significantly overestimates the size of malignant hepatic tumors. This phenomenon may be an indicator of hepatic malignancy.     

Stereotactic radiosurgery for tentorial meningiomas

Radical microsurgical resection is the procedure of choice for tentorial meningiomas. Despite advances in microsurgery, tentorial meningiomas continue to challenge surgeons and patients. To evaluate the response of tentorial meningiomas, we evaluated 41 patients who had Gamma knife stereotactic radiosurgery during a 9 year period. Patient age varied from 32 to 79 years. Headache, trigeminal neuralgia, or facial paraesthesia were the most common presenting symptoms. Sensory deficits in the distribution of the trigeminal nerve were the most common finding. Eighteen patients (44%) had undergone between 1 and 5 (mean, 1.9) resections prior to radiosurgery; 23 had tumors diagnosed by neuroimaging. The average tumor diameter in this series was 20 mm. The maximum tumor dose varied from 24 to 40 Gy (mean, 30.5 Gy), and the tumor margin dose varied from 12 to 20 Gy (mean, 15.3 Gy). During the average follow-up interval of 3 years (range, 1-8 years), 19 patients had clinical improvement, 20 remained stable, and 2 patients deteriorated. Follow-up imaging showed a reduction in tumor size in 18 patients, no further tumor growth in 22, and an increase in tumor size in one (overall tumor control rate of 98%). Stereotactic radiosurgery using the Gamma Knife was a safe and effective primary or adjuvant treatment for patients with tentorial meningiomas.     

Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study

Although overexpression of GLUT-1 glucose transporter has already been reported in human cancers, the mechanism of glucose entry into pancreatic cancers remains unknown. To evaluate the relationship between GLUT glucose transporters and FDG uptake, FDG-PET was performed in 34 preoperative patients (mean age, 60.9 yr) with suspected pancreatic tumors, including 28 malignant and 6 benign tumors. METHODS: FDG uptake at 50 min after injection of 185 MBq of [18F]FDG with >5 hr of fasting was semiquantitatively analyzed as standardized uptake values (SUVs). The GLUT expression was studied by immunohistochemistry of paraffin sections from these tumors after operation using anti-GLUT-1, -2, -3, -4 and -5 antibodies to obtain immunohistochemical grading ("strong," "weak" and "negative") by three experienced physicians. RESULTS: Of 26 malignant tumors proved by histological examination, 23 (88%) tumors were positive for the expression of GLUT-1 glucose transporter, and 17 (61%) showed strong expression. On the other hand, 13 (46%), 0 (0%), 9 (36%) and 13 (46%) malignant tumors were positive for the expression of GLUT-2, -3, -4 and -5 glucose transporters, respectively. Three of six benign tumors showed strong GLUT-1 expression. Concerning GLUT-2, -3, -4 and -5, only one benign tumor showed positive GLUT-5 expression. Thus, GLUT-1 showed relatively high sensitivity but low specificity (50%) for detecting malignant tumors, whereas GLUT-2, -3, -4 and -5 had lower sensitivities but higher specificities. Correlations between SUVs and grading of GLUT immunoreactivity were significant in GLUT-1 (strong, 4.49 +/- 2.95; weak, 3.42 +/- 1.21; negative, 2.52 +/- 0.84) (p < 0.05) but not in the remaining four GLUT transporters. CONCLUSION: These data indicate that GLUT-1 has a significant role in the malignant glucose metabolism and may contribute to the increased uptake of FDG in PET imaging in patients with pancreatic tumor.     

Stereotactic radiosurgery for recurrent malignant gliomas

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.     

Regulation of ion channel expression by cytoplasmic subunits

The present phase II trial was undertaken to assess the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line chemotherapy in patients with metastatic transitional cell carcinoma of the urothelium. Twenty patients (age range 50-79 years; inclusion criteria: WHO performance status 0-2, no previous cytotoxic treatment) with metastatic transitional cell carcinoma of the urothelium were recruited and received cytotoxic treatment with paclitaxel at a dosage of 175 mg m(-2) administered over a 3-h infusion and carboplatin given at an AUC of 5 mg ml(-1) min (according to creatinine clearance) administered every 21 days. A total of 65% of patients achieved remissions (CR+PR), with CR occurring in 40% of patients. A further 15% of patients experienced stable disease. Remissions occurred after 2.4 +/- 0.8 (mean +/- standard deviation; range two to four) treatment cycles. The mean duration of responses (CR+PR) was 8.5 +/- 5.5 months. After a mean observation period of 11.4 +/- 4.8 months, 16 patients (80%) are alive. Toxicity included alopecia of WHO grade 3 in all patients, leucopenia of WHO grades 1 and 2 in ten patients, grade 3 in eight and grade 4 in two patients and, finally, severe thrombocytopenia grade 3 in only three patients. Non-haematological toxicity consisted of polyneuropathy of WHO grade 1 in 13 patients and grade 2 in five patients. We thus conclude that a combination of paclitaxel and carboplatin at the given dosage and schedule constitutes an active, well-tolerated first-line cytotoxic treatment for patients with metastatic urothelial cancer.     

Biochemical modulation of doxorubicin by high-dose tamoxifen in the treatment of advanced hepatocellular carcinoma

BACKGROUND/AIMS: In vitro data have indicated that tamoxifen (> 2.5 uM) significantly enhances the cytotoxic effect of doxorubicin in hepatocellular carcinoma (HCC) cells. This clinical study was conducted to examine whether tamoxifen, at a dose sufficient to result in a plasma concentration of more than 2.5 uM, may improve the therapeutic efficacy of doxorubicin in patients with advanced HCC. METHODOLOGY: A prospective phase II study was conducted. Eligible patients had unresectable and non-embolizable HCC, objectively measurable tumors, adequate neogram with absolute granulocyte count > 2,000/mm3 and platelet count > 1 x 10/mm3, total serum bilirubin < 3.0 mg/dl, age > or = 75 year, and a Karnofsky performance status < or = 50%. The treatment included oral tamoxifen 40 mg/m2, q.i.d, Day 1 to 7, and intravenous doxorubicin 60 mg/m2, Day 4, repeated every 3 weeks. RESULTS: Between May 1994 and December 1996, a total of 38 patients were enrolled in the study. Thirty-six patients were evaluable for tumor response and treatment-related toxicities. There were 32 men and 4 women, with a median age of 49 years. They received an average of 3.8 (range:1-12) courses of chemotherapy. ECOG (Eastern Cooperative Oncology Group) Grade 3-4 leucopenia and Grade 3-4 thrombocytopenia developed in 27.2% and 12.5% courses given, respectively. Gastrointestinal toxicity was generally mild. Three patients developed symptomatic cardiac toxicity. Twelve patients (33.3%, 95% confidence interval 17-51%) had achieved a partial remission (PR), with a median progression-free survival of 7 months. Median survivals of the responders and non-responders were 10 and 3 months, respectively (p<0.05). The median Karnofsky performance status of the responders improved from 74.0+/-6.3% to a post-chemotherapy value of 93.2+/-4.6% (p<0.05) CONCLUSIONS: High dose tamoxifen appears to be an effective biochemical modulator of doxorubicin in the treatment of HCC. Prospective randomized phase III studies comparing doxorubicin alone versus doxorubicin plus high-dose tamoxifen are needed.     

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.     

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.     

Indications for, contraindications to, and interruption of craniofacial procedures

In spite of increasing experience with skull base surgery, some of the guidelines for indications for operations may vary according to the institution. One-hundred two patients underwent craniofacial oncologic resections at our institution from 1982 to 1995. A retrospective analysis of the indications for and contraindications to these procedures was undertaken. The main indications for malignant tumors were skin lesions with direct invasion of the anterior or lateral skull base (69%) and nasal-paranasal sinus tumors (21%). The main indications for benign tumors were glomus lesions (26%), menigiomas (22%), and fibro-osseous lesions of the anterior skull base (19%). The main contraindications were extensive invasion of the central nervous system, invasion of the cavernous sinus and/or internal carotid artery by aggressive malignancies, and bilateral orbital invasion in a nonblind patient. Also, 6 patients had their procedures interrupted during craniotomy for several reasons - extensive central nervous system invasion (2 cases), bilateral orbital invasion (1), lack of brain retraction (1), lack of histologic diagnosis during the operation (1), and purulent discharge at the frontal sinus (1). Craniofacial oncologic operations are extensive surgical procedures that have to be properly indicated in order to obtain low levels of morbidity and mortality. The selection of cases is of paramount importance. In some instances, it seems advisable even to interrupt these operations in the first phase.     

Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure

BACKGROUND: The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. METHODS AND RESULTS: Thirty-six men (mean age+/-SD, 55+/-8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4+/-4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], -13.9% [-16.0% to -11.7%]), pulmonary artery mean (-12.9% [-17. 4% to -8.3%]) and capillary wedge (-14.5% [-20.5% to -8.5%]) pressures, and right atrial pressure (-20.2% [-29.4% to -11.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (-24.2% [-28.1% to -20.3%]) and pulmonary (-19.9% [-28.4% to -11.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15. 2% [10.8% to 19.6%]) and systemic (-9.3% [-12.3% to -6.4%]) and pulmonary (-9.7% [-16.3% to -3.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged. CONCLUSIONS: Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.     

Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

PURPOSE: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND MATERIALS: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. RESULTS: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0     

Flow cytometric analysis of peripheral blood and bone marrow for tumor cells in patients with neuroblastoma

PURPOSE: To report initial clinical experience with a novel high-precision stereotactic radiotherapy system. METHODS AND MATERIALS: Sixty patients ranging in age from 2 to 82 years received a total of 1426 treatments with the University of Florida frameless stereotactic radiotherapy system. Of the total, 39 (65%) were treated with stereotactic radiotherapy (SRT) alone, and 21 (35%) received SRT as a component of radiotherapy. Pathologic diagnoses included meningiomas (15 patients), low-grade astrocytomas (11 patients), germinomas (9 patients), and craniopharyngiomas (5 patients). The technique was used as means of dose escalation in 11 patients (18%) with aggressive tumors. Treatment reproducibility was measured by comparing bite plate positioning registered by infrared light-emitting diodes (IRLEDs) with the stereotactic radiosurgery reference system, and with measurements from each treatment arc for the 1426 daily treatments (5808 positions). We chose 0.3 mm vector translation error and 0.3 degrees rotation about each axis as the maximum tolerated misalignment before treating each arc. RESULTS: With a mean follow-up of 11 months, 3 patients had recurrence of malignant disease. Acute side effects were minimal. Of 11 patients with low grade astrocytomas, 4 (36%) had cerebral edema and increased enhancement on MR scans in the first year, and 2 required steroids. All had resolution and marked tumor involution on follow-up imaging. Bite plate reproducibility was as follows. Translational errors: anterior-posterior, 0.01 +/- 0.10; lateral, 0.02 +/- 0.07; axial, 0.01 +/- 0.10. Rotational errors (degrees): anterior-posterior, 0.00 +/- 0.03; lateral, 0.00 +/- 0.06; axial, 0.01 +/- 0.04. No patient treatment was delivered beyond the maximum tolerated misalignment. Daily treatment was delivered in approximately 15 min per patient. CONCLUSION: Our initial experience with stereotactic radiotherapy using the infrared camera guidance system was good. Patient selection and treatment strategies are evolving rapidly. Treatment accuracy was the best reported, and the treatment approach was practical.     

Cleveland Clinic experience with adrenal Cushing's syndrome

PURPOSE: Cushing's syndrome due to adrenal adenoma or adrenocortical carcinoma is rare. To understand better the clinical and biochemical presentation of this disorder, as well as therapy efficacy and patient survival, we conducted a retrospective review. MATERIALS AND METHODS: Between August 1971 and April 1994, 40 patients presented to our institution with adrenal Cushing's syndrome (27 adenomas and 13 carcinomas). These groups were analyzed with respect to clinical signs and symptoms preoperatively and postoperatively, biochemical analysis, length of postoperative steroid replacement therapy, disease recurrence and patient survival. Followup was obtained by chart review and telephone interviews and averaged 59.6 +/- 66.4 and 47.6 +/- 56.2 months for adenoma and carcinoma patients, respectively. RESULTS: Women predominated in both groups (26 of 27 adenomas, 11 of 13 carcinomas), and tumors affected the left adrenal gland more frequently (19 of 27 adenomas, 9 of 13 carcinomas). Adenoma patients were younger than carcinoma patients (39.6 +/- 14.4 versus 51.5 +/- 16.6 years, p = 0.026) and presented with smaller tumors (3.3 +/- 1.0 versus 8.6 +/- 4.5 cm., p = 0.001). There was a trend toward increased incidence of glucose intolerance among carcinoma patients but no significant differences in clinical signs or symptoms between adenoma and carcinoma patients could be made. Similarly, while there was no significant difference in biochemical evaluation of adenoma versus carcinoma patients, 24-hour urinary free cortisol and serum lactate dehydrogenase levels tended to be higher among carcinoma patients. In addition 17-ketosteroid and dehydroepiandrosterone sulfate levels were more elevated in carcinoma than in adenoma patients, and several adenoma patients actually had subnormal levels. Among adenoma patients mean length of steroid replacement therapy was 16.8 +/- 9.1 months. However, 7 adenoma patients (25.9%) required greater than 24 months of exogenous steroids, and only 1 of these patients was subsequently weaned off steroid replacement. There were no recurrences among adenoma patients, although there was 1 perioperative death due to hypoglycemia. Ten (76.9%) carcinoma patients had recurrences at a mean followup of 33 months. The 3 and 5-year survival rates were 41.5 and 31.2%, respectively. CONCLUSIONS: While presenting signs and symptoms and hormonal analysis may suggest benign or malignant disease, only tumor size and patient age are reliable preoperative indicators of adrenal adenoma versus adrenocortical carcinoma among patients with adrenal Cushing's syndrome. Surgery is curative for adenoma patients, but lifelong steroid replacement may be required. Survival remains poor among carcinoma patients.     

Long-term results after liver transplantation for primary hepatic epithelioid hemangioendothelioma

BACKGROUND: Hepatic epithelioid hemangioendothelioma (PHEHE) is a multifocal, low-grade malignant neoplasia characterized by its epithelial-like appearance and vascular endothelial histogenesis. The outcome of 16 patients treated with orthotopic liver transplantation (OLT) is the subject of this report. METHODS: A retrospective study of 16 patients with HEHE (7 men, 9 women) with ages ranging from 24 to 58 years (mean 37 +/- 10.6 years). Follow-up intervals ranged from 1 to 15 years (median of 4.5 years). RESULTS: Actual patient survival at 1, 3, and 5 years was 100, 87.5, and 71.3%, respectively. Disease-free survival at 1, 3, and 5 years was 81.3, 68.8, and 60.2%, respectively. The 90-day operative mortality was 0. Involvement of the hilar lymph nodes or vascular invasion did not affect survival. The 5-year survival of HEHE compares favorably with that of hepatocellular carcinoma at the same stage (stage 4A): 71.3 versus 9.8% (p = 0.001) CONCLUSIONS: The long-term survival obtained in this series justifies OLT for these tumors even in the presence of limited extrahepatic disease.     

Role of provocation poliomyelitis in vaccine-associated poliomyelitis

BACKGROUND: Laparoscopic gastrostomy as an alternative to open gastrostomy was introduced with various technical variants 5 years ago. However, long-term results of these new methods are still lacking. METHODS: From 4/1993 to 2/1996, laparoscopic gastrostomies were performed on 42 patients (50.9 +/- 15.6 [24-71] years) with esophageal stenosis in locally advanced hypopharyngeal (17 patients) or oropharyngeal (nine patients) carcinoma, incurable esophageal carcinoma (13 patients) and cerebral dyspagia (three patients). Operating time was 38 +/- 11 min [15-65 min]. Procedure-related mortality was 0%. Major complications occurred in 2/42 (4.7%) patients; minor complications were found in 4/42 (9.4%) patients. During a total usage time of 427 months, 14 stoma infections occurred (0.11 infections/100 days). CONCLUSION: Laparoscopic gastrostomy allows a safe, fast, and cheap reestablishment of enteral nutrition. The procedure is minimally invasive and can also be performed under local anesthesia. It has become our method of choice in patients with malignant, nonresectable subtotal stenosis of the hypopharynx or esophagus.     

Preventive effects of an antiallergic drug, pemirolast potassium, on restenosis after percutaneous transluminal coronary angioplasty

PURPOSE: Radiosurgery is an effective treatment for cerebral arteriovenous malformations. We conducted the present study to investigate the feasibility and efficacy of gamma knife radiosurgery for dural arteriovenous fistulas (DAVFs) of the cavernous sinus. METHODS: Eighteen patients (12 women and six men; 29-75 years old [mean age, 55 years]) with DAVFs of the cavernous sinus (Barrow's type B:1, C:7, and D:10) treated by gamma knife radiosurgery were enrolled in the study. DAVFs were bilateral in six patients and unilateral in 12. Stereotactic X-ray angiography and MR imaging were performed for targeting the radiosurgery. Areas of arteriovenous communication targeted for irradiation were first outlined on the X-ray angiograms. The target regions were then transferred to and displayed on the MR images. Dose planning was based on findings on the integrated images. Prescribed maximum target doses were 22 to 38 Gy (mean, 28 Gy). The targets were covered by 50% to 90% isodose levels. Radiation doses to the surrounding optic apparatus were kept to less than 8 Gy. The patients were followed up with color Doppler sonography and MR imaging. When noninvasive imaging suggested obliteration, X-ray angiography was performed to verify the results. RESULTS: The DAVFs were totally obliterated in 12 (80%) of the 15 patients. In the other three, one was almost completely obliterated at 14 months and two were partially obliterated at 19 and 27 months, respectively, after radiosurgery. No complications or symptom worsening occurred during the follow-up period. CONCLUSION: Gamma knife radiosurgery is a feasible, effective, and safe treatment for DAVFs of the cavernous sinus. Integration of stereotactic X-ray angiography and MR imaging not only aids treatment efficacy but also protects the relevant vital structures, especially the optic apparatus, from the hazards of radiation.     

Rheumatic fever in the Kimberley region of Western Australia

BACKGROUND: Effusions in patients with renal cell carcinoma are rare; the clinicopathologic features of these patients have not been described fully. METHODS: All effusions from patients with renal cell carcinoma obtained between 1986 and 1997 at the study institution were reviewed. RESULTS: Twelve effusions from 9 patients were benign, and 8 effusions from 7 patients were malignant. Patients with sarcomatoid tumors presented early with benign effusions, and patients with papillary tumors presented later with malignant effusions. Patients with clear cell tumors were intermediate. The majority of patients who developed malignant effusions had tumors that were classified as T3 or higher (according to the American Joint Committee on Cancer) at the time of resection. Tumor cells had abundant clear to vacuolated cytoplasm, large nuclei, and prominent nucleoli. Cells from clear cell and papillary tumors could not be distinguished in effusion specimens unless papillae were present. At last follow-up 13 of 15 patients were dead of disease within 2 years of the onset of effusion (median 24 weeks; range, 1-93 weeks), including 7 of 9 patients with benign effusions. CONCLUSIONS: Malignant effusions due to renal cell carcinoma most commonly occur in patients with papillary and clear cell tumors. Malignant effusions from these two tumor types are difficult to distinguish unless papillae are present. Effusions associated with renal cell carcinoma confer a poor prognosis.