Eitan Prisman

Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of “fitness” for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (nu200a=u200a10), without CMS (nu200a=u200a10) and sea-level controls from Lima (nu200a=u200a20) with those obtained from CMS (nu200a=u200a8) and controls (nu200a=u200a5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (nu200a=u200a8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (nu200a=u200a8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.

Traumatic perilymphatic fistula with pneumolabyrinth: diagnosis and management.

A perilymphatic fistula (PLF) is an abnormal communication between the inner and middle ear resulting in vestibular or cochlear symptoms. We review three pediatric traumatic temporal bone fractures with pneumolabyrinth, confirmed radiologically by the presence of air within the cochlea (pneumocochlea) or vestibule (pneumovestibule). Patients were treated conservatively with complete resolution of vestibulopathy. Hearing outcome was variable and worse in two patients with pneumocochlea. A pneumolabyrinth on radiologic imaging confirms a PLF and obviates the need for exploration to reach a diagnosis. We suggest exploration be reserved for patients with persisting cerebrospinal fluid leakage, progressive sensorineural hearing loss, or vestibular symptomatology. Laryngoscope, 2011

3D Rapid Prototyping for Otolaryngology-Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling.

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques across a variety of otolaryngological sub-specialties suggests an emerging role for rapid prototyping technology in surgical education, procedure simulation, and clinical practice.

Fusion of intraoperative cone-beam CT and endoscopic video for image-guided procedures

Methods for accurate registration and fusion of intraoperative cone-beam CT (CBCT) with endoscopic video have been developed and integrated into a system for surgical guidance that accounts for intraoperative anatomical deformation and tissue excision. The system is based on a prototype mobile C-Arm for intraoperative CBCT that provides low-dose 3D image updates on demand with sub-mm spatial resolution and soft-tissue visibility, and also incorporates subsystems for real-time tracking and navigation, video endoscopy, deformable image registration of preoperative images and surgical plans, and 3D visualization software. The position and pose of the endoscope are geometrically registered to 3D CBCT images by way of real-time optical tracking (NDI Polaris) for rigid endoscopes (e.g., head and neck surgery), and electromagnetic tracking (NDI Aurora) for flexible endoscopes (e.g., bronchoscopes, colonoscopes). The intrinsic (focal length, principal point, non-linear distortion) and extrinsic (translation, rotation) parameters of the endoscopic camera are calibrated from images of a planar calibration checkerboard (2.5×2.5 mm2 squares) obtained at different perspectives. Video-CBCT registration enables a variety of 3D visualization options (e.g., oblique CBCT slices at the endoscope tip, augmentation of video with CBCT images and planning data, virtual reality representations of CBCT [surface renderings]), which can reveal anatomical structures not directly visible in the endoscopic view - e.g., critical structures obscured by blood or behind the visible anatomical surface. Video-CBCT fusion is evaluated in pre-clinical sinus and skull base surgical experiments, and is currently being incorporated into an ongoing prospective clinical trial in CBCT-guided head and neck surgery.

Modified oxygen mask to induce target levels of hyperoxia and hypercarbia during radiotherapy: a more effective alternative to carbogen.

Purpose: Carbogen has long been under investigation as an adjuvant to radiotherapy of tumors. A major factor confounding its evaluation is its inconsistency in raising blood partial pressure of CO2 (pCO2). We investigated whether a new partial rebreathing method would provide better control of pCO2 than carbogen. Methods and materials: We compared the efficacy of each method in 10 healthy volunteers. Volunteers breathed 1.5, 3 and 5% carbogen in 5-min stages via the usual non-rebreathing circuit. All the volunteers then breathed 100% O2 through a commercial sequential gas delivery (SGD) circuit modified by attaching a reservoir to its exhalation port. Hypercarbia was induced by step reductions in oxygen flow to the SGD circuit. We monitored minute ventilation and end-tidal pCO2 (ETpCO2) as a surrogate for its arterial value. Results: Inhalation of 1.5 and 3% carbogen did not increase ETpCO2 from baseline (40 ± 1.5 mmHg); 5% carbogen increased ETpCO2 to 45 ± 1.6 mmHg (p < 0.001). With the SGD circuit, reducing O2 flow to 4.3 ± 0.7 l/min increased ETpCO2 in all subjects from 41 ± 2.0 mmHg (baseline) to 46 ± 2.1 mmHg (p < 0.001). Voluntary hyperventilation reduced ETpCO2 with 5% carbogen but not with SGD (p = 0.379). Conclusions: We confirm previous observations that carbogen inhalation does not result in a predictable rise in ETpCO2 and suggest that a precise and stable target ETpCO2 can instead be induced by simply controlling O2 flow into a modified SGD circuit. We hoped that the reliable control of pCO2 will enable studies that address first, the efficacy of raising ETpCO2 on specific tumor blood flow, and eventually, its benefit as an adjuvant to radiotherapy.

Real-time tracking and virtual endoscopy in cone-beam CT-guided surgery of the sinuses and skull base in a cadaver model

Custom software was developed to integrate intraoperative cone‐beam computed tomography (CBCT) images with endoscopic video for surgical navigation and guidance. A cadaveric head was used to assess the accuracy and potential clinical utility of the following functionality: (1) real‐time tracking of the endoscope in intraoperative 3‐dimensional (3D) CBCT; (2) projecting an orthogonal reconstructed CBCT image, at or beyond the endoscope, which is parallel to the tip of the endoscope corresponding to the surgical plane; (3) virtual reality fusion of endoscopic video and 3D CBCT surface rendering; and (4) overlay of preoperatively defined contours of anatomical structures of interest.

Transoral robotic excision of ectopic lingual thyroid: Case series and literature review.

Surgical excision of an ectopic lingual thyroid has traditionally been associated with significant morbidity and has therefore been reserved for patients with severe obstructive symptoms or suspected malignancy. Transoral robotic surgery (TORS) has provided a minimally invasive approach to completely and safely excise ectopic lingual thyroid.

Value of preoperative mandibular plating in reconstruction of the mandible

The purpose of this study was to evaluate the efficacy of preoperative versus intraoperative mandibular contouring using rapid prototyping technology.

Nodal Disease Burden for Early-Stage Oral Cancer.

ImportancenNodal disease has a significant effect on survival of patients with oral squamous cell carcinoma (OSCC). The decision for elective neck dissection for clinically node-negative (cN0) disease remains elusive.nnnObjectivesnTo determine the efficacy of prophylactic neck treatment and to assess the value of commonly used clinicopathologic factors associated with nodal disease for early-stage OSCC.nnnDesign, Setting, and ParticipantsnThis retrospective study from a population-based cancer registry included patients diagnosed as having OSCC from January 11, 2001, to December 24, 2007, who were identified from the British Columbia Cancer Agency Registry. Comprehensive clinicopathologic data, treatment information, and time to outcome were collected. Five-year overall survival, disease-specific survival, and cumulative incidence of regional failure (RF) were analyzed. Receiver operating characteristic curve analysis with sensitivity and specificity was used to determine the association of these covariates with RF during follow-up. Data were analyzed from January 16 to June 30, 2015.nnnInterventionsnFollow-up of patients with cN0 OSCC with or without prophylactic neck treatment (elective neck dissection [END] and or radiotherapy).nnnMain Outcomes and MeasuresnPatient demographic characteristics, clinicopathologic data, treatment data, and time from the initial surgery to last follow-up, the development of RF, or death due to oral cancer or other causes.nnnResultsnOf the 469 patients with cN0 primary OSCC who underwent intent-to-cure surgery for the intraoral lesion, 447 received local excision (LE) for the primary tumor (256 men [57.3%] and 191 women [42.7%]; mean [SD] age, 63.3 [14.7] years). Patients who received prophylactic treatment of the neck (nu2009=u2009125) compared with LE only (nu2009=u2009322) had no survival advantage. The estimated 5-year overall and disease-specific survival rates were 61.9% (95% CI, 56.5%-67.8%) and 80.8% (95% CI, 76.1%-85.6%), respectively, for the LE-only group; 54.4% (95% CI, 45.9%-64.5%) and 73.1% (95% CI, 65%-82.3%), respectively, for the LE + END ± radiotherapy group; and 61.7% (95% CI, 52.3%-72.8%) and 80.3% (95% CI, 72%-89.4%), respectively, for the LE + END group. Among the patients with cN0 disease receiving LE only, 89 (27.6%; 95% CI, 23%-33%) developed RF at a median time of 10.8 months, and 71 of the RFs (79.8%) developed within 30 months. Tumor depth of invasion of at least 4 mm and tumor grade of 2 or 3 showed an association with RF but had poor sensitivity and specificity.nnnConclusions and RelevancenCommonly used pathologic factors to decide neck dissection for cN0 OSCC are not effective and can cause overtreatment or undertreatment. The need for identification of new objective approaches for risk assessment of RF is urgent.

Hurthle Cell Lesions- A Retrospective Review of Final Surgical Pathology

Introduction: The thyroid is a very rare site of presentation of primary tuberculosis or associated with miliary tuberculosis, mistaken in most of the cases with other pathologies such as thyroid cancer. Case Report: Here is described a case of primary thyroid tuberculosis with skin fistula and formation of a prevertebral abscess, in a male patient with malnutrition and alcoholism, whose diagnosis was established during the intraoperative frozen section study of hemi-thyroidectomy. Conclusion: Clinical suspicion and following a protocol including fine needle biopsy and intraoperative frozen section study is essential for the diagnosis of thyroid tuberculosis.