Pure Necrosis Research Articles

Redo craniotomy or bevacizumab for symptomatic steroid-refractory true or pseudoprogression following IMRT for glioblastoma.

There is minimal evidence to support decision making for symptomatic steroid-refractory pseudoprogression or true progression occurring after intensity-modulated radiation therapy (IMRT) for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM. Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database. Patients with symptomatic steroid-refractory mass effect within 6 months of IMRT managed with either RedoSx or BEV were identified for analysis. For the primary endpoint of median overall survival (OS) postintervention, outcome was analyzed in regards to potential prognostic factors, and differences between groups were assessed by log-rank analyses. Of the 399 patients managed with the EORTC-NCIC Protocol, 78 required an intervention within 6 months of IMRT completion for either true or pseudoprogression (49 with RedoSx and 29 with BEV). Subsequently, 20 of the 43 patients managed with RedoSx when BEV was clinically available, required salvage with BEV within 6 months after RedoSx. Median OS postintervention was 8.7 months (95% CI: 7.84-11.61) for the total group; and 8.7 months (95% CI: 6.8-13.1) for RedoSx and 9.4 months (95% CI: 7.8-13.6) for BEV (P = .38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (P = .10). Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki-67% reduction correlated with survival. The presence of pure necrosis and residual tumor cells only had improved survival compared with the presence of gross tumor (P < .001). At time of symptomatic steroid-refractory true or pseudoprogression following IMRT for GBM, BEV was equivalent to RedoSx in terms of OS. Pseudoprogression with residual cells at RedoSx was not associated with worse outcome compared to pure necrosis.

Head and Neck Cancer Soft Tissue Radiation Necrosis—Diagnostic Challenge

A 53-year-old man with T4aN2cM0 tongue base squamous cell carcinoma received definitive chemoradiation. FDG PET/CT at 6 weeks showed partial metabolic response with soft tissue air indicating radiation necrosis at primary site and complete response in the neck. At 9 weeks, contrasted CT showed worsening but nonenhancing ulceration, area biopsied demonstrating a minute carcinoma focus with treatment effect. At 12 weeks, PET/CT showed increased primary site uptake interpreted as disease progression; however, no viable tumor was found at salvage surgery. Because nonenhancing ulceration predicts pure radiation necrosis with no viable tumor, contrasted CT may guide treatment selection in challenging cases.

Contribution of Myocardial Perfusion’s Tomoscintigraphy in the Management of Coronarian Disease in Senegal: About 42 Cases

The aim of the study was to evaluate the contribution to moscintigraphy of myocardial perfusion (TSMP) with 99mTc-sestamibi in the management of suspected or known coronary patients’s population. It included 42 patients with an average age of 57.02 ± 9.77 years with extremes ranging from 36 to 77 years. The pre-test probability in 38 patients was high in 7 patients (18.42%), intermediate in 29 patients (76.31%) and low in 2 patients (5.26%). Patients with a high pre-test probability had a positive scintigraphy. Among the 26 patients who underwent transthoracic ultrasound (TTU), 10 with normal kinetics on trans-thoracic ultrasound (TTU) had positive scintigraphy. For 16 patients with TTU abnormalities, 6 had negative scintigraphy and 10 had positive scintigraphy. The TSMP was positive for 28 patients (66.66%). Among these patients, 16 had pure ischemia, 57.14% (16/28), 7 pure necrosis (25%), and 5 both necrosis and ischemia. Myocardial perfusion scintigraphy remains a very contributory consideration in the management of coronary disease. This is synchronized with the electrocardiogram (ECG) and is an important diagnostic and prognostic tool for coronary artery disease. It also provides a good indication of coronary angiography.

OS3 - 187 Differentiating Radionecrosis from Tumor Progression Using IVIM perfusion Fraction in Brain Metastases Treated with Radiosurgery

Radiation necrosis occurs in 5-25% of patients who undergo stereotactic radiosurgery (SRS) for brain metastases. Intravoxel incoherent motion (IVIM) uses MRI diffusion-weighted imaging (DWI) to assess regional perfusion. We investigated the utility of IVIM to differentiate recurrent tumor from radionecrosis after SRS. Patients who had SRS and subsequent surgical resection of what was thought to be either tumor progression or necrosis were included. ROIs were contoured on the pre-operative post-Gd T1-weighted images and transferred to DWI images using automated co-registration. The perfusion fraction (f) was calculated using asymptotic fitting and the mean f (fmean), 90th percentile for f (f90), mean ADC (ADCmean) and 10th percentile for ADC (ADC10) were calculated. Pathology reports were used to identify the predominant feature (necrosis versus tumor). Nine patients with ten lesions were included. One lesion exhibited pure necrosis while the other nine were mixed; three were predominantly (&gt;75%) tumor, three predominantly necrosis, and three were equal parts of both. The perfusion fraction was significantly higher in cases with predominantly tumor compared to those with predominantly necrosis (fmean 0.10±0.01 vs 0.08±0.01, p=0.02 and f90 0.22±0.01 vs 0.14±0.02, p&lt;0.001). ADC did not differentiate tumor from necrosis (ADCmean 0.97±0.23 vs 1.02±0.36, p=0.8 and ADC10 0.53±0.29 vs 0.76±0.29, p=0.33). The IVIM perfusion fraction is useful in differentiating recurrent tumor from radionecrosis in brain metastases treated with SRS. This is the first study to evaluate IVIM against the gold standard (histopathology).

Management and outcomes of pituitary apoplexy

This study was undertaken to analyze the predisposing factors, clinical presentation, therapeutic management, and clinical recovery in patients with pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and functional outcomes. The authors performed a retrospective analysis of consecutive cases involving patients treated at Mayo Clinic between 1992 and 2013. Patients were included in the study only if they had 1) abrupt onset of severe headache or visual disturbance in the presence of a pituitary adenoma and 2) radiological or surgical confirmation of a pituitary mass. The primary endpoints of analysis were the visual (ocular motility, visual fields, and visual acuity), endocrine, and functional outcomes (using the modified Rankin Scale). Eighty-seven patients were identified (57 males and 30 females, mean age 50.9 years, range 15-91 years). Twenty-two patients (25.3%) had a known pituitary adenoma. Hypertension was the most common associated factor (39%). Headache was the most frequent presenting symptom (89.7%), followed by visual abnormalities (47.1%). Cranial nerve palsies were present in 39% and visual field defects in 34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by CT scan. Sixty-one patients (70.1%) underwent surgery during acute hospitalization (median time from apoplexy 5 days, IQR 3-10 days), 8 (9.2%) had delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4 (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization. The average duration of follow-up was 44.2 ± 43.8 months. All survivors were independent and had complete resolution or substantial improvement in eye movements and visual fields at the last follow-up. Many patients needed long-term hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily desmopressin was needed in 23% of all surgical patients at 3 months (versus none of the medically treated) and this requirement decreased slightly over time. Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no statistically significant differences in any of the outcome measures across the treatment groups. The outcome of most patients with pituitary apoplexy is excellent. Selected patients can be managed conservatively, and patients with severe neuro-ophthalmological deficits treated with early surgery can achieve an excellent recovery.

Different clinical models of CD34 + cells mobilization in patients with cardiovascular disease

To test the role of necrosis, ischemia or both in bone marrow cells (BMC) mobilization in patients with cardiovascular disease. We studied three groups of patients: group 1, Iatrogenic Necrosis, with pure necrosis (28 patients undergoing transcatheter radiofrequency ablation); group 2, Ischemic Necrosis (30 patients with myocardial infarction); group 3, Pure Ischemia (24 patients with unstable angina). As control groups, we studied 27 patients with stable coronary artery disease (CAD), and 20 patients without CAD undergoing angiography for valvular diseases or cardiomiopathy. CD34 + cells and cytokines were evaluated at: T(0) (baseline), 48 h and 5, 7, 10, 14 days thereafter. We observed a significant increase of CD34 + cells at T(3) and T(4) only in Iatrogenic Necrosis and Ischemic Necrosis group. The peak of mobilization was observed ten days after the necrotic event (2.8 ± 1.4 vs. 5.9 ± 1.9 in the group 1, P = 0.03; and 3 ± 1.5 vs. 5.6 ± 2 in the group 2, P = 0.04; respectively). We found a good correlation between CD34 + and vascular endothelial growth factor (VEGF) and stromal derived factor (SDF-1α) peak values (r = 0.77 and r = 0.63, respectively). At multivariable analysis, myocardial necrosis (OR 3.5, 95%CI 2.2-4.2, P < 0.01), VEGF (OR 2, 95%CI 1.1-3, P = 0.01 as above versus below median value), and SDF-1α (OR 1.6, 95%CI 1.1-2.5, P = 0.02 as above versus below median value) emerged as independent predictors of C34 + cells increase. Myocardial necrosis with simultaneous elevation of VEGF and SDF-1α causes a significant CD34 + cells mobilization in patients with cardiovascular disease.

Oncolytic adenoviral mutants induce a novel mode of programmed cell death in ovarian cancer

Oncolytic adenoviral mutants have considerable activity in ovarian cancer. However, the mechanisms by which they induce cell death remain uncertain. dl922-947, which contains a 24 bp deletion in E1A CR2, is more potent than both E1A wild-type adenoviruses and the E1B-55K deletion mutant dl1520 (Onyx-015). We investigated the mode of death induced by three E1A CR2-deleted replicating adenoviruses in models of ovarian cancer and also the importance of E3 11.6 (adenovirus death protein) in determining this mode of death. Ovarian cancer cells were infected with dl922-947 (E3 11.6+) and dlCR2 (E3 11.6-). We also generated dlCR2 tSmac, which also encodes the gene for processed Smac/DIABLO. Classical apoptosis does not occur in adenoviral cell death and there is no role for mitochondria. Expression of Smac/DIABLO does not enhance cytotoxicity nor increase apoptotic features. A role for cathepsins and lysosomal membrane permeability was excluded. Autophagy is induced, but is not the mode of death and may act as a cell survival mechanism. There is no evidence of pure necrosis, while the presence of E3 11.6 does not modulate the mode or extent of cell death. Thus, E1A CR2-deleted oncolytic adenoviral cytotoxicity in ovarian cancer may define a novel mode of programmed cell death.

Manifestations osseuses des anémies de l'enfant

Radiological signs are important aspects of anemia in children, malignant diseases being excluded. Among these signs, osseous manifestations may be a diagnostic clue in haemoglobin disorders such as sickle-cell disease or thalassemia. In both, medullar expansion may be observed, with cortical thinning related to medullar hyperplasia. In case of homozygoteous thalassemia, extra-medullar haematopoiesis mainly in the mediastinum can be also observed. In sickle-cell disease the images are partly related to medullar hyperplasia but also to thrombosis and bone infarcts. The location of these signs follows the process of conversion from red marrow to fatty marrow. So it will start at the extremities to involve in adolescents the spine and the proximal epiphysis of the limbs. The main complication is a superimposed infection of the infarcted areas. The differential diagnosis between infection and pure necrosis is very difficult in such patients.

Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis.

The differentiation of tumor recurrence from radiation necrosis in patients with malignant gliomas who have been treated previously remains a challenge. Magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography cannot provide definitive histopathological insight. Multivoxel proton magnetic resonance spectroscopic imaging ((1)H MRSI) may be reliable in guiding the clinical management of untreated patients; however, its value in managing previously treated patients remains unclear. Twenty-seven patients who had been treated previously with surgery, radiotherapy, and chemotherapy and reoperated for clinical and/or radiographic signs that caused suspicion for recurrent disease were studied. Tissues were categorized into four groups: spectroscopically normal, pure tumor, mixed tumor and radiation necrosis, and pure radiation necrosis. Spectral data for choline (Cho), lipid-lactate (Lip-Lac), N-acetylaspartate, and creatine (Cr) were analyzed as Cho/normal Cr (nCr), Lip-Lac/Cho, Lip-Lac/nCr, N-acetylaspartate/Cho, N-acetylaspartate/nCr, and Cho/normal Cho (nCho). Stereotactic biopsies were obtained within 48 hours of (1)H MRSI and were directly correlated digitally with (1)H MRSI data. Logistic regression analysis was performed on the basis of data obtained from 99 (1)H MRSI observations to determine whether the (1)H MRSI ratios varied according to tissue category. (1)H MRSI ratios were found to distinguish pure tumor from pure necrosis. The odds of a biopsy's being pure tumor and having either a Cho/nCr value greater than 1.79 or a Lip-Lac/Cho value less than 0.75 are seven times the odds of that biopsy's being pure necrosis (odds ratio, 7.00; P = 0.0136). The odds of a biopsy's being pure necrosis and having either a Cho/nCr value less than 0.89 or a Cho/nCho value less than 0.66 are six times the odds of that biopsy's being pure tumor (odds ratio, 5.71; P = 0.0329). The odds of a biopsy's being pure necrosis and having either a Lip-Lac/Cho value greater than 1.36 or a Lip-Lac/nCr value greater than 2.84 are more than five times the odds of the biopsy's being pure tumor (odds ratio, 5.25; P = 0.0322). In addition, although only marginally significant, Lip-Lac/Cho and Lip-Lac/nCr ratios distinguish pure tumor from pure necrosis. No values suggested that mixed specimens could be distinguished in a statistically significant way from either pure tumor or pure necrosis. The data that we gathered suggest that metabolite ratios derived on the basis of (1)H MRSI spectral patterns do allow reliable differential diagnostic statements to be made when the tissues are composed of either pure tumor or pure necrosis, but the spectral patterns are less definitive when tissues composed of varying degrees of mixed tumor and necrosis are examined.

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Correlation between dynamic MRI and outcome in patients with malignant gliomas

We assessed the correlation between dynamic MRI results and clinical outcomes in patients with malignant gliomas. Rapid serial MRIs were obtained after bolus injection of gadolinium that resulted in an initial fast uptake followed by a slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake were correlated with survival and prognostic covariates such as age and histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity units per second or greater, were associated with shorter survival (p = 0.0066). The correlation of delayed rate of uptake with survival was less significant. After adjusting for age, histology, and Karnofsky performance score, the maximum rate of uptake remained more significantly correlated with survival than the delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis (p = 0.022). No correlation between delayed rate of uptake and histology was seen in this group of patients. Our results suggest that the maximum rate of uptake in dynamic MRI can be a prognostic measure for patients with malignant gliomas. Further prospective study is needed to assess the utility of this technique for evaluating brain tumors.