Browsing by Author "Davidson, Darrell D."
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Item Baseline Biomechanical Properties of Epithelia prior to Tissue Expansion in Dogs(Lippincott, Williams & Wilkins, 2018-05-14) Bowling, Jay; Davidson, Darrell D.; Tholpady, Sunil S.; Park, Kinam; Eckert, George J.; Katona, Terrence; Chu, Tien-Min G.; Barco, Clark T.; Periodontology, School of DentistryBackground: Soft-tissue deficiencies pose a challenge in a variety of disease processes when the end result is exposure of underlying tissue. Although multiple surgical techniques exist, the transposition of tissue from one location to another can cause donor-site morbidity, long incisions prone to dehiscence, and poor patient outcomes as a result. Use of tissue expansion prior to grafting procedures has been shown to have success in increasing available soft tissue to aid in repairing wounds. However, the current tissue expanders have biomechanical limits to the extent and rate of expansion that usually exceeds the tissue capacity, leading to incisional dehiscence or expander extrusion. Understanding the baseline biomechanical properties of the tissue to be expanded would provide useful information regarding surgical protocol employed for a given anatomical location. Therefore, the aim of this study was to test and compare the baseline (preexpansion) biomechanical properties of different common expansion sites in dogs. Methods: Four samples measuring approximately 20 × 15 × 1 mm were harvested from 8 dogs. The samples were collected from the hard palate, alveolar mucosa, scalp, and chest of the animal and analyzed for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength using a Texture Technologies TA.XT texture analyzer with corresponding biomechanical measurement software. Samples were compared as to their baseline biomechanical properties prior to any soft-tissue expansion. Histological sections of the samples were analyzed using hematoxylin eosin in an attempt to correlate the histological description to the biomechanical properties seen during testing. Summary statistics (mean, standard deviation, standard error, range) are reported for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength and for the histological parameters by intraoral site. Analysis of variance was used to compare the biomechanical and histological parameters among the 4 locations while accounting for multiple measurements from each dog. Results: The scalp had significantly higher maximum stress (σmax) than chest, mucosa, and palate (P < 0.0001), with no differences among the other 3 locations (P > 0.63). Scalp site also had significantly higher maximum tangential modulus (ε) than chest, mucosa, and palate (P < 0.006), with no differences among the other 3 locations (P > 0.17). The locations did not have significantly different maximum tangential stiffness (k; P = 0.72). Histologically, 2 separate patterns of collagen disruption were evident. Conclusion: Although different results were obtained than theorized, this study showed that the scalp had the greatest resiliency to expand prior to tearing, and the highest tangential modulus, with all sites having statistically similar modulus of elasticity. Based on this study, the scalp could be expanded more aggressively compared with the other sites.Item Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers(Impact Journals, 2016-08-30) Radovich, Milan; Kiel, Patrick J.; Nance, Stacy M.; Niland, Erin E.; Parsley, Megan E.; Ferguson, Meagan E.; Jiang, Guanglong; Ammakkanavar, Natraj R.; Einhorn, Lawrence H.; Cheng, Liang; Nassiri, Mehdi; Davidson, Darrell D.; Rushing, Daniel A.; Loehrer, Patrick J.; Pili, Roberto; Hanna, Nasser; Callaghan, J. Thomas; Skaar, Todd C.; Helft, Paul R.; Shahda, Safi; O’Neil, Bert H.; Schneider, Bryan P.; Medicine, School of MedicinePatients and methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014-October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs. 3 of 57 (5.3%) treated with non-genomically guided therapy (p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy (p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.Item Fluorescence in situ Hybridization in Surgical Pathology: Principles and Applications(Wiley, 2017) Cheng, Liang; Zhang, Shaobo; Wang, Lisha; MacLennan, Gregory T.; Davidson, Darrell D.; Department of Pathology and Laboratory Medicine, IU School of MedicineIdentification of recurrent tumour-specific chromosomal translocations and novel fusion oncogenes has important diagnostic, therapeutic and prognostic implications. Over the past decade, fluorescence in situ hybridization (FISH) analysis of tumour samples has been one of the most rapidly growing areas in genomic medicine and surgical pathology practice. Unlike traditional cytogenetics, FISH affords a rapid analysis of formalin-fixed, paraffin-embedded cells within a routine pathology practice workflow. As more diagnostic and treatment decisions are based on results of FISH, demand for the technology will become more widespread. Common FISH-detected alterations are chromosome deletions, gains, translocations, amplifications and polysomy. These chromosome alterations may have diagnostic and therapeutic implications for many tumour types. Integrating genomic testing into cancer treatment decisions poses many technical challenges, but rapid progress is being made to overcome these challenges in precision medicine. FISH assessment of chromosomal changes relevant to differential diagnosis and cancer treatment decisions has become an important tool for the surgical pathologist. The aim of this review is to provide a theoretical and practical survey of FISH detected translocations with a focus on strategies for clinical application in surgical pathology practice.Item Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction(Wolters Kluwer, 2017-08-28) Barwinska, Daria; Garner, John; Davidson, Darrell D.; Cook, Todd G.; Eckert, George J.; Tholpady, Sunil S.; March, Keith L.; Park, Kinam; Barco, Clark T.; Cellular and Integrative Physiology, School of MedicineBackground: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries.Item Predicting progression of in situ carcinoma in the era of precision genomics(AME Publishing Company, 2019-06) Cheng, Monica; Hanna, Nasser H.; Davidson, Darrell D.; Gunderman, Richard B.; Radiology and Imaging Sciences, School of MedicineItem Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer(Elsevier, 2017) Wang, Lisha; Liu, Zebing; Fisher, Kurt W.; Ren, Fei; Lv, Jiaojie; Davidson, Darrell D.; Baldridge, Lee A.; Du, Xiang; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of MedicineCurrent prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P = .001) and higher Ki-67 labeling index (LI) (P = .031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P = .031), positive p53 expression (P = .031), and negative PD-L1 expression (P = .003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P < .001). In univariate analysis, negative p53 (P = .001), low Ki-67 LI (P = .006), low PD-L1 expression (P = .044), low TNM stage (P < .001), recto-sigmoid location (P = .026), and small size (P = .013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P = .004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P = .027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P < .001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score ≥ 35 and Ki-67 LI ≥ 20% identifies patients with poor clinical outcome.Item Reshapeable hydrogel tissue expander for ridge augmentation: Results of a series of successive insertions at the same intraoral site(Wiley, 2019) Garner, John; Davidson, Darrell D.; Barwinska, Daria; Eckert, George J.; Tholpady, Sunil S.; Park, Kinam; Barco, Clark T.; Pathology and Laboratory Medicine, School of MedicineBackground Tissue expansion of oral mucosa prior to ridge augmentation promises to reduce the soft tissue exposure and improve the final intraoral bone graft density and volume. This study explored a novel, shapeable hydrogel tissue expander (HTE) in intraoral sites that had undergone previous expansion and surgery. Methods Nine beagle dogs had all premolar teeth extracted with alveolar bone reduction. At least 3 months healing followed before placing the hydrogels at 4 sites for each dog: maxilla and mandible, right and left. After 6 weeks of expansion, the expanded hydrogels were removed and measured for volume expansion and hydrogel condition. Punch biopsies were taken of the expanded oral mucosa. After healing of 3 months a second insertion of hydrogels was done at the same sites. Again, volume and hydrogel condition were recorded. Three dogs received ultrasound imaging of the expanding hydrogels upon the second insertion. Necropsy specimens were taken of both expanded and non‐expanded oral mucosa. Results Blood flow returned to that observed before insertion within two weeks after HTE insertion in both first and second insertions. First insertion resulted in linear gain of 8.13 mm, and second insertion showed a linear gain of 6.44 mm of oral mucosa. First and second insertion erupted at approximately 3% and 4% of the sites, respectively. There was no directional migration of the expanding hydrogels. Histology indicated little inflammatory reaction to any hydrogel implant. Conclusion Oral mucosa can be consistently and successfully expanded prior to bone graft for ridge augmentation even at sites with a history of prior surgeries.Item Safety and feasibility of carotid revascularization in patients with cerebral embolic strokes associated with carotid webs and histopathology revisited(Sage, 2021) Mathew, S.; Davidson, Darrell D.; Tejada, J.; Martinez, M.; Kovoor, J.; Ophthalmology, School of MedicineIntroduction: Carotid web is increasingly recognized as the cause of ischemic embolic strokes in younger patients. The best way to treat carotid web is debatable and carotid artery stenting (CAS) has been reported as a treatment for the carotid web in only a few case series. In this study we evaluate the safety and feasibility of CAS in symptomatic carotid webs and examined the histopathology of a carotid web. Materials and methods: At our institution between 2017 and 2019, 10 consecutive patients with symptomatic carotid webs were treated. We retrospectively analyzed the data for patient demographics, clinical presentation, imaging, treatment methodology and follow up. Results: All the patients had presented with ipsilateral embolic stroke. The mean age at presentation was 50 years (range 37-71) with seven female and three male patients. All patients underwent CAS except one patient who underwent carotid endarterectomy (CEA). In one stented patient, there was significant hypotension in the post-procedural period lasting a week. The patients were followed for a mean of 5.5 months (range one day-12 months). No recurrent stroke or transient ischemic attack (TIA) occurred. Surgical pathological studies confirmed fibromuscular dysplasia in one specimen. Conclusion: In our experience CAS for carotid web is feasible and safe in patients presenting with ischemic embolic strokes.