Evisceration With Injectable Hydrogel Implant in a Rabbit Model.

PURPOSE: To determine the safety, durability, and biocompatibility of 2.5% polyacrylamide hydrogel (Aquamid, Specialty European Pharma, Ltd., London, UK) as an injectable viscoelastic implant following evisceration in a rabbit model. METHODS: The protocol was reviewed and approved by the Wake Forest Institutional Animal Care and Use Committee. Adult New Zealand rabbits underwent cornea-sparing evisceration of the right eye with injection of 2.5% polyacrylamide hydrogel implant. The rabbits were sacrificed after 2 weeks (n = 1), 5 weeks (n = 2), 12 weeks (n = 3), 25 weeks (n = 3), and 1 year (n = 3) to evaluate the implant volume and host reaction to the implant. Both eyes were enucleated and their diameters were measured. The eviscerated eyes were fixed in formalin and processed using routine histopathologic methods to assess inflammatory reaction and vascularization. RESULTS: The implant material was well tolerated with a moderate giant cell reaction seen at 6 weeks that improved over time. Extensive vascularization of the implant was noted starting at 6 weeks. There was excellent maintenance of globe volume that did not diminish over time. The relative diameters of the eviscerated eyes compared with control were 89 ± 6% (mean% ± SD) at 12 weeks (n = 3), 94 ± 2% at 25 weeks (n = 3), and 93 ± 4% at 1 year (n = 3). CONCLUSION: With further study, injectable 2.5% polyacrylamide hydrogel may provide an excellent alternative to solid orbital implants. The implant material was universally well tolerated and maintained appropriate volume in the orbit for the study period of 1 year. Extensive vascularization of the implant was noted indicating biointegration.

Ultrasonographic Tinel sign.

High-resolution ultrasound has become increasingly useful in the evaluation of peripheral nerves. As we have gained experience, clinically helpful ultrasonographic signs have been detected. One of these is the ultrasonographic Tinel sign, in which paresthesias are produced when the transducer compresses a nerve lesion. This sign has not been previously described. We present a case in which the ultrasonographic Tinel sign helped accurately guide a nerve biopsy in a woman with mononeuritis multiplex.

Interleukin-13 receptor alpha 2, EphA2, and Fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy.

PURPOSE: We investigated the expression of interleukin-13 receptor alpha2 (IL-13R alpha 2), EphA2, and Fos-related antigen 1 (Fra-1) in astrocytomas and normal brain. We sought to document whether the expression of the three factors changed with progression to higher grade malignancy and whether two or three targets in combination might be sufficient to target all patients with high-grade astrocytomas. EXPERIMENTAL DESIGN: Immunohistochemistry was done for IL-13R alpha 2, EphA2, and Fra-1 using human brain tumor tissue microarrays containing 30 specimens of WHO grades II and III astrocytomas, 46 glioblastoma multiformes (GBM), and 9 normal brain samples. Sections were scored based on frequency and intensity of expression. Western blotting was done for all three markers using GBM tumor specimens and xenograft cell lines. Two cytotoxins, IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, which target IL-13R alpha 2 or EphA2, respectively, were tested for cytotoxicity against human GBM primary explant cells and established cells. RESULTS: Expression of all three proteins was significantly higher in GBM compared with normal brain, low-grade, and anaplastic astrocytomas. Greater than 95% of GBM overexpressed at least two of the three markers. Importantly, every GBM overexpressed at least one marker. Human GBM primary explant cells and cell lines were potently killed by IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, in accordance with their level of expression of IL-13R alpha 2 and EphA2, respectively. CONCLUSIONS: IL-13R alpha 2, EphA2, and Fra-1 are attractive therapeutic targets representing molecular denominators of high-grade astrocytomas. One hundred percent of GBM tumors overexpress at least one of these proteins, providing the basis for rational combinatorial targeted therapies/diagnostics suitable for all patients with this disease.

EphA2 as a novel molecular marker and target in glioblastoma multiforme.

We investigated the presence of EphA2, and its ligand, ephrinA1, in glioblastoma multiforme (GBM), a malignant neoplasm of glial cells, and normal brain. We also initially examined the functional importance of the interaction between EphA2 and ephrinA1 in glioma cells. Expression and localization of EphA2 and ephrinA1 in human GBM and normal brain were examined using Western blotting, immunofluorescence, and immunohistochemistry. A functional role for EphA2 was investigated by assessing the activation status of the receptor and the effect of ephrinA1 on the anchorage-independent growth and invasiveness of GBM cells. We found EphA2 to be elevated in approximately 90% of GBM specimens and cell lines but not in normal brain, whereas ephrinA1 was present at consistently low levels in both GBM and normal brain. EphA2 was activated and phosphorylated by ephrinA1 in GBM cells. Furthermore, ephrinA1 induced a prominent, dose-dependent inhibitory effect on the anchorage-independent growth and invasiveness of GBM cells highly overexpressing EphA2, which was not seen in cells expressing low levels of the receptor. Thus, EphA2 is both specifically overexpressed in GBM and expressed differentially with respect to its ligand, ephrinA1, which may reflect on the oncogenic processes of malignant glioma cells. EphA2 seems to be functionally important in GBM cells and thus may play an important role in GBM pathogenesis. Hence, EphA2 represents a new marker and novel target for the development of molecular therapeutics against GBM.

Current controversies in the radiotherapeutic management of adult low-grade glioma.

Over the last decade, the results of four prospective clinical trials of supratentorial low-grade glioma (LGG) in adults have been published. The data from the nearly 1,000 patients treated on these studies are summarized in this presentation, addressing the following three current controversies in the radiotherapeutic management of these patients: (1) optimum timing of radiation therapy (RT); (2) optimum RT dose; and (3) addition of chemotherapy to RT. The 5-year overall survival (OS) and progression-free survival (PFS) rates in these four studies ranged from 58% to 72% and from 37% to 55%, respectively. Significant prognostic factors included extent of surgical resection, histology, tumor size, and age. The European Organization for Research and Treatment of Cancer (EORTC) study 22845 randomized 311 adults to postoperative observation or RT. There was no difference in the 5-year OS rate between the two arms, but the irradiated patients had a significantly improved 5-year PFS rate. EORTC study 22844 randomized 379 adults to low- versus high-dose RT. Similarly, an intergroup study conducted by the North Central Cancer Treatment Group (NCCTG), Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Group (ECOG) randomized 211 adults to low- versus high-dose RT. There was no difference in the 5-year OS or PFS rates between the two dose groups in either study. A Southwest Oncology Group (SWOG) study randomized 60 adults with incompletely resected LGG to RT alone or RT plus lomustine (CCNU) chemotherapy. There was no difference in outcome between the two treatment arms. Further prospective clinical trials are needed to define the optimal management strategy for adults with supratentorial LGG. The schemata from recently completed and ongoing LGG studies will be presented.

Intussusception secondary to metastasis from a low-grade retroperitoneal liposarcoma.

Liposarcomas are the most prevalent soft tissue sarcomas in adults. Low-grade liposarcomas are the most frequent and least aggressive and are noted as having a low risk of metastasis. We present a case of low-grade myxoid liposarcoma that metastasized to the small bowel resulting in intussusception. This case involves a 44-year-old woman with a recurrent retroperitoneal liposarcoma. Approximately 30 months after initial diagnosis, the patient was found to have a solitary metastasis to the small bowel that presented as a jejunal intussusception. Interestingly, there was no indication of a round cell component in either the metastasis or recurrent tumor, although the original tumor did contain a small round cell component. This is the first report in the English literature of liposarcoma metastasizing to the small bowel. We suggest that atypical presentations of liposarcoma metastases should always be considered in the management of patients with a history of liposarcoma.

Rare intraparenchymal choroid plexus carcinoma resembling atypical teratoid/rhabdoid tumor diagnosed by immunostaining for INI1 protein.

The authors present the case of a rare extraventricular, intraparenchymal choroid plexus carcinoma (CPC). This 6-year-old girl presented to the emergency department with a 1-week history of headaches, nausea, and vomiting. Imaging studies revealed an intraaxial cystic and solid mass located in the right frontal lobe with central nodular enhancement and minimally enhancing cyst walls. Gross-total resection was accomplished via craniotomy without complications. The initial pathological diagnosis was atypical teratoid/rhabdoid tumor (AT/RT); however, immunostaining for INI1 protein (using the BAF47/SNF5 antibody) showed retention of nuclear staining in the tumor cells, resulting in a change in the diagnosis to CPC. There was no evidence of recurrence at the last follow-up 2.5 years after treatment, which supports the diagnosis of CPC over AT/RT. This case emphasizes the importance of immunostaining for INI1 protein for distinguishing CPC from AT/RT in cases with atypical or indeterminate features.

Primary neuroendocrine tumor of the orbit progressing to neoplastic meningitis.

A 60-year-old man presented with multiple cranial neuropathies and an identifiable left orbital lesion along the course of the supraorbital nerve. The pathologic features of the excised orbital lesion were consistent with a poorly differentiated primary neuroendocrine carcinoma. Four years after his diagnosis, the patient succumbed to neoplastic meningitis. No other primary tumor site was identified or clinically apparent during his illness.

Injectable hydroxyapatite paste as an option for ocular implantation after evisceration.

OBJECTIVE: To investigate the feasibility of small incision evisceration with an injectable ocular implant that is biocompatible and preserves globe size. DESIGN: Experimental animal study. METHODS: The axial length of the eyes of 12 rabbits was determined by ultrasound before surgery. Subsequently, 12 eyes of 12 separate rabbits were eviscerated and injected with hydroxyapatite (HA) paste (BoneSource; Stryker Leibinger, Kalamazoo, MI). Three rabbits each were killed at 2 weeks, 6 weeks, 3 months, and 6 months after evisceration, and measurements of globe size were compared with measurements of the fellow eye. Histologic examination of the eviscerated eyes was performed. MAIN OUTCOME MEASURES: The axial length and lateral globe measurements of the eviscerated eye were compared with the fellow eye. The eviscerated eye was examined histologically and the degree of inflammation, vascularization, and ossification was noted for each period of observation. RESULTS: The mean preoperative difference in axial length between the control (fellow eyes) and the subsequently eviscerated eyes was 0.15 +/- 0.04 mm (mean +/- standard error of mean). The average axial and lateral globe measurements of the operated eye were 0.8 +/- 0.4 mm less than the fellow eye 2 weeks after surgery, and this difference increased to 3.1 +/- 0.7 mm 6 months after surgery. Histologic examination showed a decrease in granulomatous inflammation and an increase in vascularization of the implanted HA over the time of observation with early osseous metaplasia. CONCLUSIONS: Small incision evisceration is possible with ocular volume replacement with an injectable orbital implant. Injectable HA paste shows promise as an option for implantation after eye evisceration; however, further studies are required to establish the stability of this material for this application.

Soft tissue amyloidoma of the extremities: a case report and review of the literature.

The deposition of amyloid as a distinct, clinically apparent mass is uncommon, particularly in soft tissues. Among reported sites of soft tissue amyloidomas, the extremities are quite rare. Amyloid tumors can mimic malignant neoplasms both clinically and radiologically. We report a case of AA amyloidoma presenting in the deltoid region with radiological features suggesting sarcoma. Cytomorphology from fine-needle aspiration material, tissue histology, and appearance by magnetic resonance imaging are described. The literature on soft tissue amyloidoma is reviewed.