The magnetic resonance characteristics of sinonasal rhabdomyosarcoma in adults: analysis of 27 cases and comparison with pathological subtypes.

BACKGROUND: Sinonasal rhabdomyosarcoma (RMS) in adults is extremely rare, and early diagnosis and treatment are crucial to improve the patient's prognosis. The purpose of this study was to evaluate the magnetic resonance imaging (MRI) findings of sinonasal RMS in adults and analyze the correlations between the imaging features and pathological subtypes. METHODS: We reviewed 27 patients with pathologically proven RMS of the nasal cavity and paranasal sinuses, including embryonal RMS (ERMS) in 14 patients, alveolar RMS (ARMS) in seven patients, and mixed-type RMS in six patients. Conventional MRI was performed in all 27 patients, and high-resolution diffusion-weighted imaging was conducted in 25 patients. The tumor location, size, morphological features, signal intensity, texture, contrast enhancement characteristics, lymph node metastases, apparent diffusion coefficients (ADCs), and involvement of local soft tissues were independently assessed by two authors. RESULTS: On MR imaging, sinonasal RMS appeared isointense on T1-weighted imaging in 21 cases (77.8%) and heterogeneously hyperintense on T2-weighted imaging in 18 patients (66.7%). After enhancement, the tumors were heterogeneously enhanced in 24 cases (88.9%). Botryoid enhancement with multiple small rings resembling bunches of grapes was found in 15 cases (55.6%). Mucosal invasion of the maxillary sinus was identified in 51.9% patients. Skull and orbit involvement were found in 55.6% and 81.5% patients, respectively. Lymph node metastasis was seen in 18 cases (66.7%). There were significant differences in botryoid enhancement (P = 0.044) and skull involvement (P = 0.044) among different histological subtypes. The mean ADC value of RMS was 0.73 ± 0.082 × 10-3 mm2/s, and there was no significant difference among different histological subtypes. CONCLUSIONS: Some characteristic MRI findings such as botryoid enhancement in the ethmoid sinus, involvement of the orbit and skull, and a lower ADC value can provide important clues for preoperative diagnosis of sinonasal RMS in adults. Further, botryoid enhancement was more common in ERMS, while skull involvement was more common in ARMS.

Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection.

Purpose: Bevacizumab-bvzr (Zirabev®), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Methods: Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.25 mg/eye/dose once every 2 weeks (3 doses total) for 1 month by bilateral IVT injection, followed by a 4-week recovery phase to evaluate the reversibility of any findings. Local and systemic safety was assessed. Ocular safety assessments included in-life ophthalmic examinations, tonometry (intraocular pressure, IOP), electroretinograms (ERGs), and histopathology. In addition, concentrations of bevacizumab-bvzr were measured in serum and in ocular tissues (vitreous humor, retina, and choroid/retinal pigment epithelium) and ocular concentration-time profiles and serum TKs were evaluated. Results: Bevacizumab-bvzr was tolerated locally and systemically, with an ocular safety profile comparable to the saline or vehicle control group. Bevacizumab-bvzr was observed in both serum and in the evaluated ocular tissues. There were no bevacizumab-bvzr-related microscopic changes or effects on IOP or ERGs. Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase. Conclusions: Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control.

Middle Ear Teratoma: Clinical and Imaging Features.

BACKGROUND: Teratoma is a true neoplasm composed of a number of different types of tissue derived from the three germinal layers but rarely occurs in the middle ear (ME). The features of middle ear teratomas (MET) have not been well described. OBJECTIVE: The objective of this study is to explore the clinical and imaging features of MET, and report 2 rare cases of MET with ear malformation that have never been reported. MATERIALS AND METHODS: The clinical, CT and MRI data of 8 patients with a pathological diagnosis of MET were collected and retrospectively mined, and 14 patients with MET reported in previous literature were also reviewed. RESULTS: ① Female, left ear predominance in MET, and the most common symptoms were otorrhea and hearing loss. ② On CT and MRI, the MET presented as an irregular soft tissue mass that was heterogeneous, with fatty tissue and involved multiple sites, and the ET and tympanum were correspondingly expanded and locally destroyed. ③ Mictotia with MET in two patients was presented, which was the first report. CONCLUSION: MET has female sex and left ear predominance. CT and MRI can be used to diagnose MET and display its extent and its relationship to the carotid canal in detail. Complete surgical excision is the definitive treatment.

Behavioral, Histopathologic, and Molecular Biological Responses of Nanoparticle- and Solution-Based Formulations of Vincristine in Mice.

Clinical use of the chemotherapeutic agent vincristine (VCR) is limited by chemotherapy-induced peripheral neuropathy (CiPN). A new formulation of VCR encapsulated by nanoparticles has been proposed and developed to alleviate CiPN. We hypothesized in nonclinical animals that the nanoparticle drug would be less neurotoxic due to different absorption and distribution properties to the peripheral nerve from the unencapsulated free drug. Here, we assessed whether VCR encapsulation in nanoparticles alleviates CiPN using behavioral gait analysis (CatWalk), histopathologic and molecular biological (RT-qPCR) approaches. Adult male C57BL/6 mice were assigned to 3 groups (empty nanoparticle, nano-VCR, solution-based VCR, each n = 8). After 15 days of dosing, animals were euthanized for tissue collection. It was shown that intraperitoneal administration of nano-VCR (0.15 mg/kg, every other day) and the empty nanoparticle resulted in no changes in gait parameters; whereas, injection of solution-based VCR resulted in decreased run speed and increased step cycle and stance (P < 0.05). There were no differences in incidence and severity of degeneration in the sciatic nerves between the nano-VCR-dosed and solution-based VCR-dosed animals. Likewise, decreased levels of a nervous tissue-enriched microRNA-183 in circulating blood did not show a significant difference between the nano- and solution-based VCR groups (P > 0.05). Empty nanoparticle administration did not cause any behavioral, microRNA, or structural changes. In conclusion, this study suggests that the nano-VCR formulation may alleviate behavioral changes in CiPN, but it does not improve the structural changes of CiPN in peripheral nerve. Nanoparticle properties may need to be optimized to improve biological observations.

Assessment of Cochlea Endolymphatic Hydrops Using 3-D FLAIR and 3-D Real IR Sequence in Guinea Pigs via 3T MRI After Intratympanic Gadolinium: A Histopathological Comparison.

OBJECTIVE: We assessed whether the three-dimensional fluid-attenuated inversion-recovery (3-D FLAIR) and three-dimensional inversion-recovery with real reconstruction (3-D real IR) sequences can be used to detect cochlea endolymphatic hydrops (EHs) in guinea pigs using 3 Tesla magnetic resonance imaging (3T MRI). The results of 3-D real IR imaging were compared with histopathological outcomes. MATERIALS AND METHODS: Fourteen healthy men and women albino guinea pigs were used in this study. Their right ears received procedures that promoted EHs, and their left ears were used as untreated controls. High-resolution 3T MRI, combined with the intratympanic injection of gadolinium (Gd) in both ears, was performed 8 to 12 weeks after surgery. Both sides of the cochlea midmodiolar sections were observed under a light microscope and saved as the histopathological images. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) between the T2-weighted 3-D FLAIR and T2-weighted 3-D real IR sequences were compared. The appearance of EHs in the basal, second, third, and apical turns of the cochlea was further evaluated using 3-D FLAIR, 3-D real IR, and the histopathological images. Moreover, the maximum scala media area ratios (SMRs) on the histopathological sections were compared with the grading of the EHs on the 3-D real IR sequence with regard to each turn of the cochlea. RESULTS: Significant differences were found between the 3-D FLAIR and 3-D-real IR sequences with regard to the SNRs and CNRs (p < 0.05): the 3-D FLAIR sequence exhibited higher SNRs (SNRROI: 347.95 ±â€Š105.01; SNRB: 103.28 ±â€Š17.61) compared with the 3-D real IR sequence (SNRROI: 86.71 ±â€Š30.11; SNRB: 11.11 ±â€Š3.45), whereas the 3-D real IR sequence showed higher CNRs (2.78 ±â€Š0.58) compared with the 3-D FLAIR sequence (2.18 ±â€Š0.55). Various degrees of EHs were observed in each turn of the cochlea in the experimental ears on the basis of the histopathological images. Thirteen, 10, 4, and 0 EHs were observed in the basal, second, third, and apical turns of the cochlear using 3-D FLAIR images, respectively, whereas 14, 14, 14, and 13 EHs were found using 3-D real IR images, respectively. Significant differences were found between the two sequences when evaluating the second, third, and apical turns of the cochlear but not with regard to the basal turn (p < 0.05). The SMRs were proportional to the extent of the EHs on 3-D real IR imaging in each turn of the cochlea. CONCLUSIONS: 3-D real IR images are clearer than 3-D FLAIR images, and they can display cochlea EHs more precisely using 3T MRI in guinea pigs. The extent of the EHs on 3-D real IR imaging was more consistent with the histopathological observations in each turn of the cochlea.

Identification and Evaluation of Novel MicroRNA Biomarkers in Plasma and Feces Associated with Drug-induced Intestinal Toxicity.

Gastrointestinal toxicity is dose limiting with many therapeutic and anticancer agents. Real-time, noninvasive detection of markers of toxicity in biofluids is advantageous. Ongoing research has revealed microRNAs as potential diagnostic and predictive biomarkers for the detection of select organ toxicities. To study the potential utility of microRNA biomarkers of intestinal injury in a preclinical toxicology species, we evaluated 3 rodent models of drug-induced intestinal toxicity, each with a distinct mechanism of toxicity. MiR-215 and miR-194 were identified as putative intestinal toxicity biomarkers. Both were evaluated in plasma and feces and compared to plasma citrulline, an established intestinal injury biomarker. Following intestinal toxicant dosing, microRNA changes in feces and plasma were detected noninvasively and correlated with histologic evidence of intestinal injury. Fecal miR-215 and miR-194 levels increased, and plasma miR-215 decreased in a dose- and time-dependent manner. Dose-dependent decreases in plasma miR-215 levels also preceded and correlated positively with plasma citrulline modulation, suggesting miR-215 is a more sensitive biomarker. Moreover, during the drug-free recovery phase, plasma miR-215 returned to predose levels, supporting a corresponding recovery of histologic lesions. Despite limitations, this study provides preliminary evidence that select microRNAs have the potential to act as noninvasive, sensitive, and quantitative biomarkers of intestinal injury.

Validation of Cross-Species Reactivity of the VEGF-A/PDGFRß Bifunctional Antibody PF-06653157.

PURPOSE: PF-06653157 is a bifunctional antagonist monoclonal antibody (mAb) that targets human VEGF-A ligand and PDGF-Rß. With the advent of PF-06653157 as an angiogenesis inhibitor and potential treatment for angiogenesis deregulation diseases, a relevant toxicology species is needed for toxicity and efficacy studies. Investigative studies were conducted to validate the mAb dual antagonist properties in a human system and determine its cross-reactive pharmacology in nonhuman cells. METHODS: Sequence alignment was used to determine percent sequence identity of VEGF and PDGF receptors and ligands; qualitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the presence of PDGF-Rß on cells of interest. The functional activity of PF-06653157 antibody was assessed in human, dog, porcine, rabbit, rat, mouse, and cynomolgus monkey cells treated with VEGF and PDGF ligands through cell proliferation assays and western blot analysis of AKT and p44/p42 (ERK1/2) protein phosphorylation and enzyme-linked immunosorbent assay. RESULTS: PF-06653157 attenuated phosphorylation of AKT and p44/p42 proteins in human and cynomolgus monkey cells. The antibody did not attenuate AKT nor p44/p42 phosphorylation in any other species tested. PDGFR signaling could not be activated with human PDGF ligand in the porcine cells, so PF-06653157 activity in porcine remains inconclusive. CONCLUSION: The PF-06653157 mAb cross-reacts with cynomolgus monkey cells in a similar manner to human cells. Therefore, cynomolgus monkeys are considered the appropriate species for efficacy and regulatory toxicology studies in PF-06653157 development.

Toxicity of hydroxyurea in rats and dogs.

The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr.

[Imaging evaluation of the cases with tympanicum and pulsatile tinnitus].

OBJECTIVE: To analyze the CT and MRI features of glomus tympanicum tumors accompanied with tympanitis and evaluate the diagnostic value of CT and MRI in order to improve the cognition for the disease. METHODS: The clinical materials and images of 8 patients with the symptoms of pulsatile tinnitus and hearing loss in whom glomus tympanicum tumors with tympanitis surgically and pathologically confirmed were retrospectively reviewed. The characteristics and diagnostic value of CT and MR imaging were summarized. RESULTS: By CT examination the lesions in middle ear and mastoid were preoperatively diagnosed as tympanitis in five cases and only in three cases the glomus tympanicum tumors were suspected. In six patients underwent MR examination the lesions were all preoperatively diagnosed as glomus tympanicum tumors accompanied with tympanitis. HRCT scanning of the temporal bone in all patients showed the soft tissue lesions in the tympanic cavity and mastoid, and the caritas tympanic were mostly (n = 3) or completely (n = 5) occupied by soft tissue lesions, but the auditory ossicles were all without destruction. Contrast-enhanced axial CT scanning performed in five cases showed less soft tissue mass on the cochlear promontory, and the size of mass was less than that observed in MR imaging. MR T(1)-weighted imaging showed the presence of isointense lesions in middle ear and isointense (n = 3) or hyperintense (n = 3) lesions in mastoid. On T(2)-weighted imaging the lesions with slight hyperintense were viewed in the middle ear and the lesions with hyperintense in mastoid. T(1)-weighted gadolinium-enhanced MRI showed the masses in tympanum were markedly increased enhancement, but the lesions in mastoid without enhancement. MRI and CT imaging revealed the masses in six cases of eight extending to the eustachian tube. CONCLUSION: When the glomus tympanicum tumor was accompanied with tympanitis the tumor could be misdiagnosed or missed only by CT examination. The patients with pulsatile tinnitus should be taken seriously. MRI with contrast-enhancement is superior to CT in the preoperative diagnosis and accurately evaluation for the glomus tympanicum tumors with tympanitis.

Role of magnetic resonance diffusion-weighted imaging in differentiating lacrimal masses.

PURPOSE: To evaluate the role of magnetic resonance (MR) diffusion-weighted imaging (DWI) in discriminating lacrimal masses, including neoplastic and nonneoplastic entities. MATERIALS AND METHODS: Forty-four patients with lacrimal masses underwent conventional MRI and DWI. The apparent diffusion coefficient (ADC) values of each mass and the ipsilateral temporal lobe were measured and the ratios of the lesion to temporal lobe ADC were calculated. RESULTS: Pleomorphic adenomas had significantly higher ADC values (1.37 ± 0.22 × 10(-3) mm(2) /sec) and ADC ratios (1.85 ± 0.34) than malignant tumors (1.03 ± 0.19 × 10(-3) mm(2) /sec, 1.37 ± 0.27) (P < 0.001), inflammatory pseudotumors (0.9 ± 0.08 × 10(-3) mm(2) /sec, 1.19 ± 0.07) (P < 0.01), reactive lymphoid hyperplasias (RLHs) (0.6 ± 0.06 × 10(-3) mm(2) /sec, 0.79 ± 0.07) (P < 0.001), and lymphomas (0.55 ± 0.06 × 10(-3) mm(2) /sec, 0.74 ± 0.08) (P < 0.001). RLHs and lymphomas had significantly lower ADC values and ADC ratios than malignant tumors (P < 0.05) and inflammatory pseudotumors (P < 0.05). An ADC value of less than 1.14 × 10(-3) mm(2) /sec and an ADC ratio of less than 1.6 were optimal for differentiating malignant tumors from benign tumors (sensitivity: 80 and 90%, specificity: 100 and 88.9%, respectively). An ADC value of less than 0.76 × 10(-3) mm(2) /sec and an ADC ratio of less than 1.0 were optimal for distinguishing lymphoproliferative disorders from inflammatory pseudotumors (sensitivity: 100%, specificity: 100% for both). CONCLUSION: DWI can help differentiate lacrimal masses and provides a potential clinical tool for noninvasive tissue characterization.

[Imaging diagnosis of masses in temporal bone associated with pulsatile tinnitus].

OBJECTIVE: To improve the imaging diagnosis accuracy on masses of temporal bone associated with pulsatile tinnitus. METHODS: The CT and MRI features of masses in temporal bone associated with pulsatile tinnitus in 32 cases, confirmed by pathology, were retrospectively analyzed. RESULTS: They were grouped into two according to the jugular bulb involved or not. In the group involving the jugular bulb, there were 5 cases with glomus jugular, 2 cases of them presented the feature of "salt-pepper". There were 5 cases with middle ear carcinoma, which presented the masses in the tympanic cavity and antrum, extended to the external auditory canal and eroded the eustachian tube and jugular bulb. There were 3 cases with endolymphatic sac tumors, which presented multiple bony spicules on CT images and high signal on T1-weighted images. There was 1 case with metastatic tumor, which extensively eroded temporal and occipital bone, involved the jugular bulb, presented intermediate signal on T1-weighted images and intermediate or high signal on T2-weighted images, moderately enhanced following contrast administration. In the group not involving the jugular bulb, there were 15 cases with tympanic glomus, without ossicles and tympanic erosion, 7 cases of them limited to the promontory, 7 cases of them filled the tympanic cavity and antrum and 5 cases extended deep into the external auditory canals, 1 case extended to the mastoid, 12 cases intensely enhanced with gadolinium. There were 2 cases with cholesterol granulomas of the middle ear, which presented the masses in the tympanic cavity and antrum and high T1-weighted and T2-weighted signal. There was 1 case with facial nerve hemangioma, which presented the enlargement and mass of the geniculate fossa involving the tympanic segment of facial nerve with the erosion and displacement of ossicles. On MR images, the mass was intensely enhanced after contrast administration. CONCLUSION: Among the masses of temporal bone associated with pulsatile tinnitus, the paragangliomas are the most common and easy to be diagnosed by their imaging features. While the other masses of temporal bone are uncommon, they could also be diagnosed accurately by clinical and imaging characteristics.

Labyrinthine sequestrum: four case studies.

Labyrinthine sequestrum, a rare form of labyrinthitis, is highly distinct from the more commonly encountered labyrinthitis ossificans based on its unique clinical, radiologic, and histologic characteristics. The study included 4 such patients who had undergone clinical and laboratory investigations, computed tomography (CT), and magnetic resonance imaging (MRI) assessments followed by surgical procedures and pathological evaluation. Their major symptoms were otorrhea, otalgia, tinnitus, and profound hearing loss. Imaging studies showed an osteolytic soft mass with calcified debris in the inner ear, and the bony labyrinth was eroded partly or completely by granulation mass, with loss of bony morphology. Further pathological examination was coincident with inflammatory granulation tissue with some calcification or osseous tissue. The disease process is attributed to chronic osteomyelitis due to the presence of osteonecrosis. Prompt CT and MRI examinations and optimal therapeutic management facilitate definitive diagnosis and protect against fatal complications.

3D image of the middle ear ossicles: three protocols of post-processing based on multislice computed tomography.

The aim of this study was to examine and assess the comparative values of HRCT-based multiplanar reformation (MPR), volume rendering (VR) and virtual endoscope built on three-dimensional shaded-surface display (SSD-based CTVE) for evaluations of the ossicular chain. The normal pure tone audiograms, type-A tympanogram, and normal HRCT characteristics of 32 human ears of 18 patients were reviewed, whose ossicular chains were reconstructed with the three aforementioned protocols and assessed via the 3-point scoring system. The HRCT-based protocols could demonstrate a 3D image of the ossicular chain, except that of the footplate on the SSD-based CTVE. On the qualitative assessment, the efficacy of the MPR and VR, which were both superior to the SSD-based CTVE (P < 0.05), presented no statistical significance among the major and/or hyperdense structures (P > 0.05). As regards the lateral process of the malleus, VR was found to be significantly superior to the MPR and SSD-based CTVE (P < 0.05), both of which, however, showed no significant comparative differences (P > 0.05). Moreover, the three protocols in terms of efficacy were comparatively different in their representations of the anterior crus and footplates of the stapes, respectively (P < 0.05). On the MPR images, not all the images of the lenticular process were ideal; 20 of 32 cases were detected, but not defined. VR could be the more valuable protocol for the 3D reconstruction of the ossicular chain and ought to be more employed in future, especially for the education.

Corneal neovascularization and ocular irritancy responses in dogs following topical ocular administration of an EP4-prostaglandin E2 agonist.

Prostaglandin receptor agonists have intraocular pressure-lowering effects in humans and are of interest in the treatment of glaucoma. The prostanoid receptor agonist PF-04475270 is a potent and selective agonist of the prostaglandin E(2) receptor EP4. This paper characterizes the toxicity associated with topical ocular administration of PF-04475270 in beagles. Dogs were given PF-04475270 topically to the eye on a consecutive daily dosing schedule for one or four weeks followed by a one-or four-week reversal period, respectively. Clinical observations, ophthalmic, and laboratory parameters were recorded. Necropsies were conducted at the end of the dosing and recovery phases, and histologic examinations performed. Corneal neovascularization that was considered adverse was observed at doses of >or=1.0 microg/eye and was not reversed by the end of the recovery phase. Dogs dosed with >or=0.25 microg/eye developed a dose-related conjunctival hyperemia that persisted throughout the reversal period. Corneal neovascular cells stained positive with EP4 and the endothelial biomarker Factor VIII-vWF. Other histopathology findings observed at doses of >or=1.0 microg included single-cell necrosis and neutrophils in the cornea, inflammatory cell infiltrates in the iris/ciliary body, and iridal endothelial cell hypertrophy. A resolving acute to subacute inflammation in the iris/ciliary body was observed after the four-week recovery period.

PD0325901, a mitogen-activated protein kinase kinase inhibitor, produces ocular toxicity in a rabbit animal model of retinal vein occlusion.

OBJECTIVE: PD0325901, a selective inhibitor of mitogen-activated protein kinase kinase (MEK), was associated with the occurrence of ocular retinal vein occlusion (RVO) during clinical trials in patients with solid tumors. As previous animal safety studies in rats and dogs did not identify the eye as a target organ of toxicity, this work was conducted to develop a rabbit model of ocular toxicity with PD0325901. METHODS: Dutch-Belted rabbits were administered a single intravitreal injection of PD0325901 (0.5 or 1 mg/eye) or saline control, and ophthalmic examinations and retinal angiography were conducted over a 2-week period post-dose. In addition, mechanism of ocular toxicity was further explored in rat with microarray analysis. RESULTS: PD0325901 treatment produced RVO with retinal vasculature leakage and hemorrhage within 48-h postinjection in Dutch-Belted rabbits. Subsequent retinal detachment and degeneration were also detected on day 8 postinjection. To evaluate the potential mechanism(s) of PD0325901-mediated RVO, male Brown Norway rats were orally administered PD0325901 (45 mg/kg/day) up to 5 days and retinal tissue was collected for gene array analysis. Although PD0325901 did not produce clinical evidence of RVO in rats, retinal gene expression suggested an increased oxidative stress and inflammatory response, endothelium and blood-retinal barrier damage, and prothrombotic effects. Moreover, soluble endothelial protein C receptor (sEPCR), a biomarker for RVO, was elevated in human umbilical vascular endothelial cells (HUVECs) cultured with PD0325901. CONCLUSIONS: This work has developed a rabbit model of PD0325901-induced RVO that may be used to characterize the cellular and molecular mechanisms of this effect in humans.

Surgery for endolymphatic sac tumor: whether and when to keep hearing?

CONCLUSION: Endolymphatic sac tumors (ELSTs) are locally invasive, osteolytic, and hypervascular tumors. If the labyrinth has not been invaded, the hearing should be preserved in operation. OBJECTIVE: To summarize three cases of ELST and discuss whether to keep hearing in the surgical treatment of ELST. SUBJECTS AND METHODS: Complete otorhinolaryngological examinations with audiologic, vestibular, and neurologic evaluations were performed. CT and MRI scans were carried out before operation and in the course of follow-up. The patients underwent radical removal of the tumor through a transmastoid approach and accepted postoperative radiotherapy. In two of them, the structure of the labyrinth and facial nerve were preserved in operation. RESULTS: Histopathologic examinations agreed with features of an ELST. Patients suffered transitory vertigo shortly after operation, and so far, they are alive and well without further cranial nerve involvement. Case 3 patient has good hearing and facial nerve function now. No residual or recurrent tumor was detected on the postoperative MRI images.