Stereotactic radiosurgery for intracranial malignancies

Stereotactic radiosurgery has historically been used for arteriovenous malformations and benign tumors but has rather recently been used as a tool in the multimodality management of intracranial malignancies. Radiosurgery has been shown to be highly effective in the management of small metastatic brain tumors and has proven effective in controlling small brain metastases that progress after prior fractionated radiotherapy. The technique is also a reasonable, low morbidity alternative to surgical resection in the initial management of patients with solitary brain metastasis. In selected patients with small, relatively spherical, high-grade gliomas, radiosurgery appears to produce tumor control, survival, and toxicity similar to that of brachytherapy. However, compared with brachytherapy, radiosurgery has the advantage of lower initial morbidity, reduced hospital stay, reduced radiation exposure to personnel, and lower costs. Future clinical trials should further define dose-response relationships and the optimum role for radiosurgery in the management of malignant intracranial neoplasms.     

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.     

p53 protein expression in benign and malignant breast lesions

OBJECTIVE: To investigate p53 protein expression in imprints from benign and ductal breast carcinoma cases in relation to the histologic grade of malignancy and clinical stage. STUDY DESIGN: The study group consisted of 60 cases of primary ductal breast carcinomas and 20 benign lesions. For the demonstration of p53 protein expression, an immunocytochemical avidin-extravidin complex technique was applied. Monoclonal antibody p53 was used as the primary antibody, diaminobenzidine as the chromogen and hematoxylin as the counterstain. RESULTS: Forty-five percent of breast cancer cases showed positive expression of p53. A statistically significant difference in p53 protein expression was observed between grade 1, 2 and 3 carcinomas and stage I, II and III cases. All benign lesions were negative for p53 protein expression. CONCLUSION: Immunocytochemical p53 protein expression in cytologic material is a simple method that can be applied in routine cytologic laboratories for the identification of genetic alterations in primary ductal breast cancer.     

Endoscopic sonography of the stomach: findings in benign and malignant lesions

Endoscopic sonography combines direct visualization of the luminal surface of the gut with sonographic examination of the gut wall and surrounding structures. Lesions arising from different layers of the wall can be identified, staged, and in some cases characterized. Endoscopic sonography is complementary to endoscopy, barium studies, transabdominal sonography, and CT examination of gastrointestinal lesions. A thorough examination with endoscopic sonography may determine the layer of origin, size, echogenicity, and extent of gastric lesions and allows differentiation of lesions arising in the stomach from lesions arising outside the stomach. The purpose of this essay is to illustrate the findings from endoscopic sonography of a variety of benign and malignant lesions of the stomach.     

Evaluation of benign vs malignant hepatic lesions with positron emission tomography

BACKGROUND: In most malignant cells, the relatively low level of glucose-6-phosphatase leads to accumulation and trapping of [18F]fluorodeoxyglucose (FDG) intracellularly, allowing the visualization of increased uptake compared with normal cells. OBJECTIVES: To assess the value of FDG positron emission tomography (PET) to differentiate benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. DESIGN: Prospective blinded-comparison clinical cohort study. SETTING: Tertiary care university hospital and clinic. PATIENTS: One hundred ten consecutive referred patients with hepatic lesions 1 cm or larger on screening computed tomographic (CT) images who were seen for evaluation and potential resection underwent PET imaging. There were 60 men and 50 women with a mean (+/-SD) age of 59 +/- 14 years. Follow-up was 100%. INTERVENTIONS: A PET scan using static imaging was performed on all patients. The PET scan imaging and biopsy, surgery, or both were performed, providing pathological samples within 2 months of PET imaging. All PET images were correlated with CT scan to localize the lesion. However, PET investigators were unaware of any previous interpretation of the CT scan. MAIN OUTCOME MEASURES: Visual interpretation, lesion-to-normal liver background (L/B) ratio of radioactivity, and standard uptake value (SUV) were correlated with pathological diagnosis. RESULTS: All (100%) liver metastases from adenocarcinoma and sarcoma primaries in 66 patients and all cholangiocarcinomas in 8 patients had increased uptake values, L/B ratios greater than 2, and an SUV greater than 3.5. Hepatocellular carcinoma had increased FDG uptake in 16 of 23 patients and poor uptake in 7 patients. All benign hepatic lesions (n = 23), including adenoma and fibronodular hyperplasia, had poor uptake, an L/B ratio of less than 2, and an SUV less than 3.5, except for 1 of 3 abscesses that had definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful to differentiate malignant from benign lesions in the liver. Limitations include false-positive results in a minority of abscesses and false-negative results in a minority of hepatocellular carcinoma. The PET technique was useful in tumor staging and detection of recurrence, as well as monitoring response to therapy for all adenocarcinomas and sarcomas and most hepatocellular carcinomas. Therefore, pretherapy PET imaging is recommended to help assess new hepatic lesions.     

Serial MR imaging of intracranial metastases after radiosurgery

PURPOSE: To evaluate the spatiotemporal evolution of radiosurgical induced changes both in metastases and in normal brain tissue adjacent to the lesions by serial magnetic resonance (MR) imaging. METHODS AND MATERIALS: Thirty-five intracranial metastases of different primaries were treated in 25 patients by single high-dose radiosurgery. MR images acquired before radiosurgery were available in all patients. Sixty-three follow-up MR studies were performed in these patients including T2- and contrast-enhanced T1-weighted MR images. The average follow-up time was 9 +/- 5 months (mean +/- standard deviation [SD]). Based on contrast-enhanced T1-weighted MR images, tumor response was radiologically classified in the following four groups: stable disease was assumed if the average tumor diameter after treatment did not show a tumor shrinkage of more than 50% and an increase of more than 25%, partial remission as a shrinkage of tumor size of more than 50%, a disappearance of contrast-enhancing tumor as a complete remission, and an increase of tumor diameter of more than 25% as tumor progress. Moreover, we analysed signal changes on T2-weighted images in brain parenchyma adjacent to the enhancing metastases. RESULTS: The overall mean survival time was 10.5 +/- 7 months, with a 1-year actuarial survival rate of 40%. Stable disease, partial or complete remission of the metastatic tumor was observed in 22 patients (88%). Central or homogeneous loss of contrast enhancement appeared to be a good prognostic sign for stable disease or partial remission. This association was statistically significant (p < 0.05). Three patients (12%) suffered from tumor progression. In eight patients (32%) with stable disease or partial remission, signal changes on T2-weighted images were observed in tissue adjacent to the contrast enhancing lesions. A progression of the high signal on T2-weighted images was seen in seven of the eight patients between 3 and 6 months after therapy, followed by a signal regression 6-18 months after irradiation. CONCLUSION: MR imaging is a sensitive imaging tool to evaluate tumor response as well as the presence or absence of adjacent parenchymal changes following radiosurgery. Loss of homogeneous or central contrast enhancement on Gd-enhanced MR images appeared to be a good prognostic sign for tumor response. Tumor shrinkage seems not to be dependent on time. In addition, most cases of radiation induced changes in normal brain parenchyma observed on T2-weighted images seem to be self limited.     

Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience

OBJECTIVE: Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment. METHODS: All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr). RESULTS: Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery). CONCLUSION: Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.     

Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions

BACKGROUND: The 13C-urea breath (13C-UBT) test value is (semi-)quantitatively related to Helicobacter pylori density in the gastric antrum, and the value correlates with the grade of gastritis. The aim of this study was to assess variation of the 13C-urea breath test value by sociodemographic factors in H. pylori-positive children. METHODS: The analysis was performed on 127 asymptomatic children (aged 5-7 years) who were identified as H. pylori-positive with the 13C-UBT test in a large population-based epidemiologic study in the city of Ulm (southern Germany). The parents of the children were asked to fill out a standardized questionnaire about sociodemographic data. RESULTS: Forty-two infected children (33.1%) were of German nationality, 47 children (37.0%) were of Turkish and 38 children (29.9%) were of another nationality. Turkish children had a significantly higher 13C-UBT value (geometric mean = 27.2%) than German children (16.7%) or children with another nationality (19.3%) (P < 0.001). Girls had a trend towards higher values than boys (P = 0.058 after adjustment for nationality). Body mass index, education of the parents, and prior use of antibiotics were unrelated to the extent of the 13C-UBT. CONCLUSIONS: This study identified significant variation in the extent of the 13C value by nationality among H. pylori-infected children. Further studies are needed to elucidate the causes and potential consequences of these variations.     

Comparing neural networks in the discrimination of benign from malignant lower urinary tract lesions

BACKGROUND: Angiocentric cutaneous T-cell lymphomas of childhood (ACTCLC) are an unusual type of T-cell lymphomas that present with a vesiculopapular eruption mimicking hydroa vacciniforme. Most patients have been children from Asia and Latin America. OBJECTIVE: The purpose of this study was to describe four cases of ACTCLC; to discuss its clinical, histopathologic, and immunohistochemical features; to consider its possible relationship to the Epstein-Barr virus (EBV); and to clarify its classification within the spectrum of angiocentric lymphomas. METHODS: The clinical, histopathologic, and immunohistochemical features of four cases of ACTCLC were identified and analyzed. In addition in situ hybridization for EBV was performed in all cases. RESULTS: The clinical features were similar to previous cases reported under different names, such as hydroa-like lymphomas, edematous, scarring vasculitic panniculitis. Histologically, all showed angiocentric infiltrates composed mainly of T cells. In all cases there were variable numbers of CD30+ cells. The EBV was present in three of the cases. CONCLUSION: ACTCLC is a distinct type of T-cell lymphoma. It affects mainly children, and the EBV appears to play a role in the pathogenesis of this disease.     

Hepatic lesions: discrimination of nonsolid, benign lesions from solid, malignant lesions with heavily T2-weighted fast spin-echo MR imaging

PURPOSE: To determine whether the combined use of heavily and moderately T2-weighted fast spin-echo magnetic resonance (MR) images improves differentiation of non-solid, benign hepatic lesions from solid malignancies. MATERIALS AND METHODS: Three radiologists reviewed moderately (n = 133) and heavily (n = 133) T2-weighted and multiphasic dynamic contrast material-enhanced (n = 93) MR images in 133 patients with proved focal hepatic lesions (95 benign, 38 malignant). The radiologists used a five-point scale to rate their confidence in determination of malignancy. RESULTS: All three reviewers were statistically significantly better able to differentiate small (diameter less than 3 cm; n = 84) benignancies from small malignancies with the combination of moderately and heavily T2-weighted images (area under the receiver operating characteristic curve, 0.99 for each reader) than with moderately T2-weighted images alone (area, 0.88-0.90; P < .05). Confident diagnoses were rendered in 69 (82%) patients, with 100% accuracy for the combined use of moderately and heavily T2-weighted images. For larger lesions (diameter 3 cm or larger; n = 49), accurate differentiation was possible with moderately T2-weighted images alone. Additional use of multiphasic images did not improve the sensitivity, specificity, or accuracy of image interpretation. CONCLUSION: The combined use of moderately and heavily T2-weighted fast spin-echo MR images improves differentiation of small benign hepatic lesions from small malignant lesions.     

Renal lesions in Von Hippel-Lindau disease: the benign, the malignant, the unknown

This study analysed the frequency of distress at induction (DAI) in 2122 paediatric patients. The data were analysed to assess predictors of DAI and to examine associations between predictors of DAI and recovery characteristics. Patient age, preoperative behaviour, premedication (oral midazolam, n = 480) and venue for anaesthesia induction were associated with changes in the incidence of DAI. Distressed preoperative behaviour was a good predictor of DAI in all age groups. Premedication reduced the incidence of DAI in children aged 0.5-2 years old, and in older children who were distressed preoperatively. Induction in the Day Surgery Unit was associated with a reduction of the incidence of DAI in younger children. Children with DAI were more likely to suffer from distress at arousal (P = 0.001). Average early recovery time was prolonged 4.4 minutes and average discharge time in day patients was delayed 36 minutes by the use of oral midazolam premedication. Premedication was not significantly associated with arousal distress. We conclude that a policy of optimizing nonpharmacological approaches for minimizing induction distress, combined with selective premedication with oral midazolam, can produce a low incidence of induction distress and adverse effects.     

Care of a patient requiring intracranial pressure monitoring

The use of a Codman bolt is described in a 14-year-old head-injured boy. The benefits of the Codman bolt in permitting titration of nursing actions against rises in intracranial pressure are highlighted. Arguments for retaining head injury patients in a general ICU with intracranial pressure monitoring are weighed against the dangers of transfer.     

Metal stents for benign and malignant bile duct strictures stents for benign and malignant bile duct strictures

Self-expanding metal stents provide a much larger diameter--up to 30 Fr--in comparison with plastic stents, which have a maximum diameter of 12 Fr. Although they have consequently been found to be far superior to plastic prostheses, they are not removable, and in benign strictures metal stents should therefore be used only in exceptional situations. Metal stents are the preferred mode of treatment for malignant strictures, provided the patient has a sufficient life expectancy although this is hard to predict in individual cases. Metal stents also seem to be superior in hilar malignancy, but the data here are limited. Future developments may include the use of covered metal stents and self-expanding stents (made of plastic or other materials) that are removable or self-dissolving.     

Stereotactic volumetric radiofrequency lesioning of intracranial structures for control of intractable seizures

Computed tomography (CT) scans provide three-dimensional information about intracranial structures, which can be used to place stereotactically guided radiofrequency (RF) lesions and destroy a targeted volume of tissue. This technique was used for lesioning of the corpus callosum (CC) or the amygdala-hippocampus complex (AHC) in 9 patients with intractable seizures. The procedures were monitored by intraoperative CT scans. Lesions were made in the AHC in 7 patients and the CC in 2 patients. In addition, multiple subpial transection (MST) was performed in 6 patients. The longest follow-up is 29 months with a median of 19 months. Five patients (56%) are free of seizures, 3 patients (33%) have greater than 90% reduction in seizure activity and 1 patient (11%) has greater than 50% but at most 90% reduction in seizure activity. There were no complications except for temporary hemiparesis following MST in 1 patient. The results suggest that stereotactic volumetric RF lesioning of the AHC and the CC may be safe and effective in controlling intractable seizures.