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Local Control of Newly Diagnosed and Distally Recurrent, Low-Volume Brain Metastases Using Fixed Dose (20 Gy) Gamma Knife Radiosurgery

Elliott RE; Rush SC; Morsi A; Mehta N; Spriet J; Narayana A; Donahue B; Parker EC; Golfinos JG
BACKGROUND:: Metastases to the brain occur in 20-30% of patients with cancer and have been identified on autopsy in as many as 50% of patients. OBJECTIVE:: To analyze the efficacy of 20 Gy gamma knife radiosurgery (GKR) as initial treatment in patients with 1 to 3 brain metastases </= 2 cm in greatest diameter. METHODS:: A retrospective analysis of 114 consecutive adults with KPS >/= 60 who received GKR for 1 to 3 brain metastases </= 2 cm in size was performed. Five patients lacked detailed follow-up and were excluded, leaving 109 for outcome analysis (34 males/75 females; median age: 61.2 years). All metastases received 20 Gy to the 50%-isodose line. RESULTS:: One hundred-nine patients underwent treatment of 164 metastases at initial GKR. Twenty-six patients (23.9%) were alive at last follow-up (median time: 29.9 months; range: 6.6 months to 7.8 years). The median overall survival was 13.8 months (range: 1 day to 7.6 years). Among the 52 patients with distant failure, 33 patients received 20 Gy to 95 new lesions. A total of 259 metastases received 20 Gy and 4 patients lacked imaging follow-up secondary to death prior to post-treatment imaging. Local failure occurred in 17 of 255 treated lesions (6.7%), yielding an overall local control rate of 93.3%. Actuarial local control at 6-, 12-, 24-, and 36-months was 96%, 93%, 89%, and 88%, respectively. Permanent neurological complications occurred in 3 patients (2.8%). CONCLUSION:: Among patients with 1 to 3 brain metastases </= 2 cm in size who have not received whole-brain radiation therapy, GKR with 20 Gy provides high rates of local control with low morbidity and excellent neurological symptom-free survival
PMID: 21221034
ISSN: 1524-4040
CID: 124087

Taking advantage of behavioral changes during development and training to assess sensory coding mechanisms

Sarro, Emma C; Rosen, Merri J; Sanes, Dan H
The relationship between behavioral and neural performance has been explored in adult animals, but rarely during the developmental period when perceptual abilities emerge. We used these naturally occurring changes in auditory perception to evaluate underlying encoding mechanisms. Performance of juvenile and adult gerbils on an amplitude modulation (AM) detection task was compared with response properties from auditory cortex of age-matched animals. When tested with an identical behavioral procedure, juveniles display poorer AM detection thresholds than adults. Two neurometric analyses indicate that the most sensitive juvenile and adult neurons have equivalent AM thresholds. However, a pooling neurometric revealed that adult cortex encodes smaller AM depths. By each measure, neural sensitivity was superior to psychometric thresholds. However, juvenile training improved adult behavioral thresholds, such that they verged on the best sensitivity of adult neurons. Thus, periods of training may allow an animal to use the encoded information already present in cortex.
PMID: 21535001
ISSN: 0077-8923
CID: 163878

19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells

Hitchens, T Kevin; Ye, Qing; Eytan, Danielle F; Janjic, Jelena M; Ahrens, Eric T; Ho, Chien
Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron-oxide labeled immune-cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T 2*-weighted images. In this study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine-19 ((19) F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro-15-crown-5-ether, we observed (19) F-signal intensity in the organs experiencing rejection by (19) F MRI, and conventional (1) H MRI was used for anatomical context. Immunofluorescence and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, (19) F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients.
PMCID:3135171
PMID: 21305593
ISSN: 1522-2594
CID: 5005432

Quantification of benign lesion regression as a function of 532-nm pulsed potassium titanyl phosphate laser parameter selection

Mallur, Pavan S; Tajudeen, Bobby A; Aaronson, Nicole; Branski, Ryan C; Amin, Milan R
OBJECTIVES/HYPOTHESIS: Although the potassium titanyl phosphate (KTP) laser is versatile, the variability in laser parameters for laryngeal pathologies and the lack of clinical efficacy data remain problematic. We provide preliminary data regarding these parameters for benign lesion regression. In addition, we describe a novel method for the quantification of the effects of the KTP laser on vocal fold (VF) lesions. STUDY DESIGN: Retrospective chart review. METHODS: Images were captured from examinations before and after in-office KTP treatment in patients with a range of benign lesions. Laser settings were noted for each patient. Imaging software was then used to calculate a ratio of lesion area to VF length. Ten percent of images were requantified to determine inter-rater reliability. RESULTS: Thirty-two patients underwent 47 procedures for lesions including hemorrhagic polyp, nonhemorrhagic polyp, vocal process granuloma, Reinke's edema, cyst/pseudocyst, leukoplakia, and squamous cell carcinoma in situ. No statistically significant differences were observed with regard to the laser parameters used as a function of lesion type. Regardless, by 1 month following treatment, all lesions had significantly decreased in size, except nonhemorrhagic polyps. Similar data were obtained at 2-month follow-up. We then compared the pre-KTP lesion size with the smallest lesion size quantified during the 1-year follow-up period. All lesions were significantly smaller, with the exception of Reinke's edema. Inter-rater reliability was quite good. CONCLUSIONS: KTP laser effectively reduced VF lesion size, irrespective of the laser parameters used. In addition, our quantification method for lesion size appeared to be both viable and reliable. Laryngoscope, 2011
PMID: 21298636
ISSN: 1531-4995
CID: 124097

Lateral arm free flap for oral tongue reconstruction: an analysis of surgical details, morbidity, and functional and aesthetic outcome

Thankappan, Krishnakumar; Kuriakose, Moni A; Chatni, Shilpa S; Sharan, Rajeev; Trivedi, Nirav P; Vijayaraghavan, Sundeep; Sharma, Mohit; Iyer, Subramania
The purpose of this study was to report the effectiveness of the lateral arm free flap (LAFF) in the reconstruction of oral tongue defects, the subsite in which it may have advantage over the other donor sites. This is a retrospective analysis of 48 consecutive cases of LAFF used for the reconstruction of partial glossectomy defects for squamous cell carcinoma of the oral tongue. Primary defect and donor-site morbidity and the functional and aesthetic outcomes were assessed in 37 evaluable patients, with a minimum of 6 months follow-up. Patient-reported Visual Analog Scale score from 0 (minimum satisfaction) to 10 (maximum satisfaction) was used to evaluate the aesthetic outcome. The follow-up was for 6 to 52 months (mean, 24 months). The flap was successful in 45 (93.8%) patients. The commonest observed donor-site morbidity was a broad scar, but it did not cause much patient dissatisfaction because it could be covered with appropriate dressing. Speech was normal or near-normal in all patients. Poor functional outcome was associated with adjuvant postoperative radiotherapy. The visual analog scale score for the aesthetic satisfaction (mean [standard deviation]) was 6.58 (1.82) for primary site and 7.13 (1.99) for the donor site. LAFF is an excellent option for the reconstruction of partial glossectomy defects of oral tongue without significant involvement of the floor of mouth and base of tongue.
PMID: 20948419
ISSN: 0148-7043
CID: 831942

The angry face syndrome

Pastorek, Norman J; White, W Matthew
PMID: 21422448
ISSN: 1538-3660
CID: 134146

Development of t(8;21) and RUNX1-RUNX1T1 in the Philadelphia-positive clone of a patient with chronic myelogenous leukemia: additional evidence for multiple steps involved in disease progression [Case Report]

Najfeld, Vesna; Wisch, Nathaniel; Mascarenhas, John; Issa, Leonard; Tripodi, Joseph; Sidhu, Manpreet; Hoffman, Ronald
A 65-year-old patient with a high hemoglobin and hematocrit was treated for 14 months with therapeutic phlebotomy when cytogenetics of bone marrow revealed 100% cells with the Ph chromosome and 45% of the Ph+ cells contained trisomy 8. Treatment with tyrosine kinase inhibitors did not reduce the BCR-ABL1 fusion positive clone. Instead, the Ph positive cells acquired further the t(8;21)/RUNX1-RUNX1T1, del(4q) and trisomy 15 chromosomal abnormalities which were resistant to further treatment. Literature review revealed eight other patients who either had t(9;22) and t(8;21) simultaneously or developed t(8;21) in the Ph positive clone. We conclude that there are rare patients with CML who either present in blast crisis with coexistence of t(9;22) and t(8;21) with or without +8, or progress to blast crisis with acquiring RUNX1-RUNX1T1 in the BCR-ABL1 clone which may or may not be therapy related and represent a later event in a multistep pathogenesis.
PMID: 21504717
ISSN: 2210-7762
CID: 177505

Metastatic balloon cell malignant melanoma: a case report and literature review

Lee, Lili; Zhou, Fang; Simms, Anthony; Wieczorek, Rosemary; Fang, Yanan; Subietas-Mayol, Antonio; Wang, Beverly; Heller, Patricia; Huang, Hongying; Pei, Zhiheng; Osman, Iman; Meehan, Shane; Lee, Peng
A case of metastatic balloon cell malignant melanoma (BCMM) is presented. The balloon melanoma cells (BMC) were absent in the shave biopsy of the primary lesion and present as a minor component in the wide and deep excision. A subsequent right neck lymph node metastasis showed complete replacement of the lymph node by large, foamy cells. Though the tumor was amelanocytic and Fontana-Masson stain failed to reveal melanin, it stained positively for S-100, HMB-45, and Melan-A. Ultrastructurally, the foamy cells were characterized by cytoplasmic vacuolization and a lack of melanosomes. The differential diagnosis of metastatic balloon cell malignant melanoma is broad, and clinicopathologic correlation may play a critical role in achieving the correct diagnosis
PMCID:3071665
PMID: 21487528
ISSN: 1936-2625
CID: 133175

Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma

Sethi, Rajni; Allen, Jeffrey; Donahue, Bernadine; Karajannis, Matthias; Gardner, Sharon; Wisoff, Jeffrey; Kunnakkat, Saroj; Mathew, Jeena; Zagzag, David; Newman, Kia; Narayana, Ashwatha
Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 +/- 1.2 months), and 13 patients have died (median survival 9.0 +/- 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 +/- 3.3 months without LD and 8.0 +/- 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 +/- 3.9 months without LD and 3.0 +/- 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials
PMID: 20623246
ISSN: 1573-7373
CID: 138150

Intraoperative transillumination to determine the extent of frontal sinus in subcranial approach to anterior skull base

Sharan, Rajeev; Thankappan, Krishnakumar; Iyer, Subramania; Panicker, Dilip; Kuriakose, Moni Abraham
We sought to determine the extent of the frontal sinus by intraoperative transillumination through the superomedial orbital wall in a subcranial approach to the anterior skull base. After raising a bicoronal flap, the frontal sinus was transilluminated through the superomedial orbital wall with a fiber-optic light source, delineating the extent of the frontal sinus. The frontal sinus boundary was marked with a marker pen. A frontal sinus anterior wall osteotomy was performed with a sagittal saw, staying within the confines of the frontal sinus marking. A bone flap was removed, and the posterior wall was drilled out. The remaining procedure was performed in a standard fashion. At the end of the procedure, the bone flap was fixed with a titanium plate. A total of 58 patients had undergone craniofacial resection from January 2004 to December 2007. In 13 patients, a subcranial approach was employed using the transillumination technique. Transillumination was successful in delineating the frontal sinus periphery in all 13 patients. Intraoperative transillumination of the frontal sinus through the superomedial orbital wall is a simple and effective method to delineate the frontal sinus periphery in a subcranial approach to the anterior skull base.
PMCID:3312596
PMID: 22451803
ISSN: 1531-5010
CID: 831712