Combined chemoradiotherapy showed improved outcome with early-stage HPV-positive oropharyngeal cancers.

BACKGROUND: The revised 8th Edition American Joint Committee on Cancer (AJCC) Head and Neck Staging Manual distinguishes HPV-mediated from non-HPV-mediated oropharyngeal cancer (OpSCC). The objective was to analyze OpSCC treatment modalities and outcomes. METHODS: A retrospective study of OpSCC patients treated with radiotherapy or chemoradiotherapy between January 1st, 2000, and December 31st, 2008, as identified from the BC Cancer Registry. All patients received treatment at cancer clinics and had at least 5 years follow-up post-treatment. A total of 1259 OpSCC patients were identified. After initial chart reviews, 288 patients were excluded from further analysis and the majority (n = 198) was due to not receiving curative treatment. Based on the availability of formalin-fixed, paraffin-embedded (FFPE) tissue, patients were divided into two cohorts: Study Cohort (FFPE available, n = 244) and General Cohort (FFPE unavailable, n = 727). The Study Cohort was restaged according to AJCC 8th Edition based on p16 immunohistochemistry status. Kaplan-Meier analysis was used to estimate the 5-year overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival (LFS). RESULTS: Among 971 patients, OpSCC age-adjusted incidence rate was observed to have increased from 2.1 to 3.5 per 100,000 between 2000 and 2008. The General Cohort was relatively older than the Study Cohort (60.1 ± 10.5 vs. 57.3 ± 9.4), but both cohorts were predominantly males (78.3% vs. 76.2%). Amongst the Study Cohort, 77.5% were p16-positive, of whom 98.4% were down staged in the 8th Edition. These early-stage patients showed OS improvement for those treated with chemoradiation, compared to radiation alone (85.8% vs. 73.1%, p = 0.05). CONCLUSIONS: OpSCC incidence is increasing in BC. The addition of chemotherapy to radiotherapy may portend a benefit in OS even for early-stage p16-positive OpSCC. Additional research is necessary to assess the safety of treatment de-escalation even among early-stage disease.

Imaging-Based 3-Dimensional Printing for Improved Maxillofacial Presurgical Planning: A Single Center Case Series.

PURPOSE: 3-D printing is an increasingly widespread technology that allows physical models to be constructed based on cross-sectional medical imaging data. We sought to develop a pipeline for production of 3-dimensional (3-D) models for presurgical planning and assess the value of these models for surgeons and patients. METHODS: In this institutional review board-approved, single-center case series, participating surgeons identified cases for 3-D model printing, and after obtaining patient consent, a 3-D model was produced for each of the 7 participating patients based on preoperative cross-sectional imaging. Each model was given to the surgeon to use during the surgical consent discussion and preoperative planning. Patients and surgeons completed questionnaires evaluating the quality and usefulness of the models. RESULTS: The 3-D models improved surgeon confidence in their operative approach, influencing the choice of operative approach in the majority of cases. Patients and surgeons reported that the model improved patient comprehension of the surgery during the consent discussion, including risks and benefits of the surgery. Model production time was as little as 4 days, and the average per-model cost was $350. CONCLUSIONS: 3-D printed models are useful presurgical tools from both surgeon and patient perspectives. Development of local hospital-based 3-D printing capabilities enables model production with rapid turnaround and modest cost, representing a value-added service for radiologists to offer their surgical colleagues.

Plain radiograph assessment of spinal hardware.

The frequency and variety of spinal instrumentation has increased tremendously over the past 100 years, and imaging plays an important role in evaluating the postoperative spine. Although assessment of spinal hardware often involves a multimodality approach, plain radiographs are the most commonly used modality, given accessibility, cost, relatively low radiation dose compared with computed tomography, and provision of positional information. An approach to assessment of plain radiographs of the postoperative spine is discussed, and examples of common postoperative complications are provided, including infection, hardware failure, incomplete fusion, and junctional failure.

Imaging in adult scoliosis: preoperative assessment and postoperative complications.

Adult scoliosis rates range from 2 to 32%. Surgery for scoliosis is common. Accurate and surgically relevant information should be provided to the referring surgeon from pre- and postoperative imaging. There are various methods to correct scoliosis surgically with the end points correction of the curve and relief of symptoms. This is achieved through the placement of spinal instrumentation with a goal of osseous fusion across the instrumented levels. There are many potential postoperative complications. The initial and postoperative imaging, types of surgery, and hardware are reviewed along with the common early and late complications with relevant illustrations.

Arterial Onyx embolisation of intracranial DAVFs with cortical venous drainage.

PURPOSE: To present our experience with the endovascular management of intracranial dural arteriovenous fistulas with direct cortical venous drainage by trans-arterial embolisation using Onyx. MATERIALS & METHODS: Between January 2004 and April 2008, 12 consecutive high grade intracranial dural arteriovenous fistulas (Cognard type III (eight patients) or IV (three patients)) were treated by trans-arterial embolisation with Onyx. The majority of cases were treated by Onyx embolisation alone. One case had additional embolisation with n-butyl-2-cyanoacrylate at the same session. Imaging follow-up was obtained in all but one patient (mean 3.6 months). RESULTS: Nine patients had a technical success at the end of the embolisation procedure with complete angiographic exclusion of the fistula. Two patients had a small residual fistula at the end of embolisation, one of which had residual mild cortical venous drainage. Both were stable at follow-up angiography. One patient had a residual fistula supplied by the ophthalmic artery, which was thought to be unsafe to embolise and was sent for surgery, which was curative. In one patient the microcatheter ruptured, with a fragment of the distal microcatheter left in the occipital artery. No clinical complications were observed in this series at clinical follow-up (mean 3.3 months). Two patients were noted to have significant radiation dose. CONCLUSION: Endovascular management of intracranial dural arteriovenous fistulas with direct venous cortical drainage by trans-arterial Onyx embolisation is a safe and effective treatment according to our experience. Fluoroscopy times and radiation dose may be a concern.

Iatrogenic embolization following cardiac intervention: postmortem analysis of 110 cases.

INTRODUCTION: Iatrogenic embolization following cardiac investigative procedures may result from hydrophilic polymer emboli (HPE) from catheter valve and vessel wall calcifications, and air embolism from open heart surgery. This retrospective clinical pathologic analysis was undertaken to ascertain the frequency and extent of these potentially fatal complications. METHODS: This retrospective clinical pathologic autopsy analysis with premortem diagnostic imaging correlation identified 110 individuals who had undergone endovascular procedures between 2010 and 2016 within 90 days of death and followed by hospital autopsy. Clinical outcomes, radiologic studies, and autopsy materials were reviewed. RESULTS: Iatrogenic emboli were assessed as causing death in 9/110 autopsy cases (8.2%) and 9/34 (26.5%) cases with proven iatrogenic emboli. Iatrogenic emboli caused strokes in 10/110 (9.1%) autopsy cases including calcified emboli (CE, n=6), HPE (n=2), cardiac valvular tissue (n=1), and air embolism (n=1). Seven cases of calcified emboli complicating endovascular procedures were identified: four of the CE were thought to be the cause of death due to fatal strokes (n=2) and fatal myocardial (n=1) and colonic infarction (n=1). The CE likely originated from calcified aortic valves and atherosclerotic aortic plaques. Histologic evidence of HPE was found in 23% (25/110) of cases; 54% (26/48) showed evidence of infarction in postprocedural imaging, with radiologic evidence of infarction in 32% (8/25) of cases with HPE histology. Endovascular aortic repair was associated with the greatest density/distribution of HPE. HPE material showed degradation with time and was often associated with an inflammatory response. HPE directly contributed to death in three cases. One fatal air embolism followed open heart surgery, and one cardiac tissue embolus resulted in a major stroke. CONCLUSIONS: We advocate for greater awareness of these underrecognized and occasionally fatal complications of endovascular procedures. Targeted postprocedural imaging has a role in the identification of iatrogenic embolic infarcts.

Histopathologic features of multiple myeloma involving the optic nerves.

We report a case of optic nerve involvement by multiple myeloma in which progressive visual loss heralded leukemic transformation and intracranial involvement. Imaging showed enhancing nodules in the intracranial segments of both optic nerves posterior to the optic canals and in the anterior optic tract, optic chiasm, and basal leptomeninges. Postmortem histopathologic examination disclosed malignant plasma cells in the subarachnoid spaces around the optic nerves and in the optic nerves. Infarctions were present in both optic nerves near their junction with the globes. Microscopic examination also showed malignant plasma cell infiltration of the leptomeninges of the cerebrum, brain stem, optic chiasm, pituitary gland, cranial bone marrow, and subarachnoid blood vessels. This is the first reported histopathologic examination in conjunction with MRI of multiple myeloma involving the anterior visual pathway. The mechanism of optic neuropathy in this case is probably related to infiltration of the optic nerve meninges by malignant plasma cells and impaired vascular supply caused by aggregated intraluminal plasma cells and monoclonal hypergammaglobulinemia.

Case of Primary Central Nervous System Lymphoma Arising at Site of Remote Herpes Encephalitis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that usually arises in the context of severe immunosuppression but has incompletely understood etiology, limiting effective treatments. CASE DESCRIPTION: We present the case of an 81-year-old immunocompetent man who developed a PCNSL in the right temporal lobe, at the site of a remote episode of herpes simplex virus (HSV) encephalitis 8 years prior. There are numerous viruses with known oncogenic associations; however, to our knowledge, this is the first reported case of PCNSL with an antecedent HSV infection. CONCLUSIONS: We discuss this case in the context of our current understandings of the pathogenesis of HSV encephalitis and PCNSL and postulate mechanisms through which the 2 could be associated.

Ipsilateral Motor Innervation Discovered Incidentally on Intraoperative Monitoring: A Case Report.

Background and importance: Lesions in the corticospinal tract above the decussation at the medullary pyramids almost universally produce contralateral deficits. Rare cases of supratentorial lesions causing ipsilateral motor deficits have been reported previously, but only ever found secondary to stroke or congenital pyramidal tract malformations. Clinical presentation: Herein, we report a case of ipsilateral corticospinal tract innervation discovered incidentally with intraoperative monitoring during a microsurgical resection of a vestibular schwannoma. Intraoperative monitoring with electrical transcranial stimulation of the frontal scalp triggered motor-evoked potentials in the ipsilateral arms. The uncrossed pathways were later confirmed with MRI tractography using diffusion tensor imaging. Conclusion: To the best of our knowledge, this is the first case of isolated ipsilateral motor innervation of the corticospinal tract discovered incidentally during a neurosurgical procedure. Given the increasing use of intraoperative monitoring, this case underscores the importance of cautious interpretation of seemingly discordant neurophysiological findings. Once technical issues have been ruled out, ipsilateral motor innervation may be considered as a possible explanation and neurosurgeons should be aware of the existence of this rare anatomic variant.

Lymphocytic infiltration and enlargement of the lacrimal glands: a new subtype of primary Sjögren's syndrome?

PURPOSE: To review the clinical, radiologic, serologic, histopathologic, immunohistochemical, and molecular genetic features of patients having Sjögren's syndrome (SS) with lacrimal gland enlargement. DESIGN: Retrospective case series review. PARTICIPANTS: Fourteen patients histopathologically diagnosed with SS with lacrimal enlargement. Twenty-three age- and gender-matched controls were used for comparison on radiologic analysis. METHODS: Clinical and serologic data were determined directly or by chart review. Computed tomography images from patients were compared with those from the control group. Histopathologic sections were reviewed and graded using the Chisholm-Mason scale, and quantitative immunohistochemical analysis was applied. MAIN OUTCOME MEASURES: Clinically, patients were assessed for age, gender, onset, symptoms and signs, systemic features, treatment, and outcome. Existing histologic specimens were reviewed according to the Chisholm-Mason scale, and then the percentages of plasma cells containing immunoglobulin (Ig) A, IgG, and IgM were determined. Imaging was assessed for lacrimal gland thickness, prolapse, density, and margin contour; extraocular muscle size; orbital tissue displacement; and proptosis. RESULTS: Clinical and histopathological data fulfilled the revised American-European criteria for primary SS in 79% of patients. Compared with other large series of primary SS patients, similarities were found with age, xerophthalmia, parotidomegaly, and articular involvement. Differences included a lower incidence of autoantibodies, xerostomia, and extraglandular features and a higher male-to-female ratio. In almost all patients (93%), the percentage of plasma cells positive for IgA was less than 70%, consistent with SS. Compared with controls, the lacrimal glands were enlarged significantly (P<0.0001) and prolapsed (P<0.001). Involved glands had blurred margins (P<0.007), caused displacement of adjacent tissues (P = 0.03), and were associated with hyperdense fat (P = 0.007). Lymphocytic infiltration of orbital fat was present in all patients for whom fat biopsy results were available. Three patients had monoclonal infiltrates, and 1 patient experienced subsequent extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, 4 years after presentation. CONCLUSIONS: The criteria used to diagnose primary SS are controversial, but both diagnostic and quantitative immunohistochemical criteria suggest that these patients, with lacrimal gland enlargement resulting from lymphocytic infiltration, represent a new subtype of primary SS. This is clinically important in view of the increased risk of lymphoma associated with SS, compared with idiopathic nonspecific lacrimal inflammation.

High-content, high-throughput analysis of cell cycle perturbations induced by the HSP90 inhibitor XL888.

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations.

Accuracy of DXA scanning of the thoracic spine: cadaveric studies comparing BMC, areal BMD and geometric estimates of volumetric BMD against ash weight and CT measures of bone volume.

Biomechanical studies of the thoracic spine often scan cadaveric segments by dual energy X-ray absorptiometry (DXA) to obtain measures of bone mass. Only one study has reported the accuracy of lateral scans of thoracic vertebral bodies. The accuracy of DXA scans of thoracic spine segments and of anterior-posterior (AP) thoracic scans has not been investigated. We have examined the accuracy of AP and lateral thoracic DXA scans by comparison with ash weight, the gold-standard for measuring bone mineral content (BMC). We have also compared three methods of estimating volumetric bone mineral density (vBMD) with a novel standard-ash weight (g)/bone volume (cm3) as measured by computed tomography (CT). Twelve T5-T8 spine segments were scanned with DXA (AP and lateral) and CT. The T6 vertebrae were excised, the posterior elements removed and then the vertebral bodies were ashed in a muffle furnace. We proposed a new method of estimating vBMD and compared it with two previously published methods. BMC values from lateral DXA scans displayed the strongest correlation with ash weight (r=0.99) and were on average 12.8% higher (p<0.001). As expected, BMC (AP or lateral) was more strongly correlated with ash weight than areal bone mineral density (aBMD; AP: r=0.54, or lateral: r=0.71) or estimated vBMD. Estimates of vBMD with either of the three methods were strongly and similarly correlated with volumetric BMD calculated by dividing ash weight by CT-derived volume. These data suggest that readily available DXA scanning is an appropriate surrogate measure for thoracic spine bone mineral and that the lateral scan might be the scan method of choice.

Pitch ranking ability of cochlear implant recipients: a comparison of sound-processing strategies.

Pitch ranking of sung vowel stimuli, separated in fundamental frequency (F0) by half an octave, was measured with a group of eleven Nucleus 24 cochlear implant recipients using different sound coding strategies. In three consecutive studies, either two or three different sound coding strategies were compared to the Advanced Combinational Encoder (ACE) strategy. These strategies included Continuous Interleaved Sampling (CIS), Peak Derived Timing (PDT), Modulation Depth Enhancement (MDE), F0 Synchronized ACE (FOSync), and Multi-channel Envelope Modulation (MEM), the last four being experimental strategies. While pitch ranking results on average were poor compared to those expected for most normal hearing listeners, significantly higher scores were obtained using the MEM, MDE, and FOSync strategies compared to ACE. These strategies enhanced coding of temporal F0 cues by providing deeper modulation cues to F0 coincidentally in time across all activated electrodes. In the final study, speech recognition tests were also conducted using ACE, CIS, MDE, and MEM. Similar results among all strategies were obtained for word tests in quiet and between ACE and MEM for sentence tests in noise. These findings demonstrate that strategies such as MEM may aid perception of pitch and still adequately code segmental speech features as per existing coding strategies.