'Cytology-on-a-chip' based sensors for monitoring of potentially malignant oral lesions.

UNLABELLED: Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials.

OBJECTIVE: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. STUDY DESIGN: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. RESULTS: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. CONCLUSIONS: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis.

Pitfalls in determining head and neck surgical margins.

Accurate assessment of surgical margins in the head and neck is a challenge. Multiple factors may lead to inaccurate margin assessment such as tissue shrinkage, nonstandardized nomenclature, anatomic constraints, and complex three dimensional specimen orientation. Excision method and standard histologic processing techniques may obscure distance measurements from the tumor front to the normal tissue edge. Arbitrary definitions of what constitutes a "close" margin do not consider the prognostic significance of resection dimensions. In this article we review some common pitfalls in determining margin status in head and neck resection specimens as well as highlight newer techniques of molecular margin assessment.

Topical silver nanoparticles result in improved bleb function by increasing filtration and reducing fibrosis in a rabbit model of filtration surgery.

PURPOSE: To compare the effects of silver nanoparticles (AgNPs) and mitomycin C (MMC) on intraocular pressure (IOP) and external, histologic, and immunohistochemical bleb characteristics in a rabbit model of filtration surgery. METHODS: Filtration surgery with concurrent topical application of either AgNPs or MMC was performed on 14 pigmented Dutch Belted rabbits. IOP and bleb characteristics were compared on postoperative day 1 and at weeks 1 through 6. Hematoxylin and eosin staining and smooth muscle actin (SMA) immunohistochemistry were performed at postoperative week 6. RESULTS: Average IOP across all time points was reduced 5.8 and 3.8 mm Hg in AgNP- and MMC-treated eyes, respectively. At week 6, IOP was reduced 4.1 and 0.2 mm Hg in AgNP- and MMC-treated eyes, respectively. Blebs were smaller, thicker, and less ischemic in AgNP-treated eyes. AgNP-treated eyes showed less fibrosis and more stromal edema, suggesting increased filtration, and also had fewer SMA-positive myofibroblasts, suggesting reduced bleb contraction. AgNP-treated eyes showed more lymphocytes than MMC-treated eyes. There were few complications in both groups. CONCLUSIONS: In a rabbit model of filtration surgery, AgNPs are a reasonable alternative to MMC as adjunctive therapy. Compared to MMC, AgNPs result in an improved and sustained reduction of IOP and promote blebs with decreased fibrosis and ischemia as well as increased filtration despite a smaller overall size. This combination may offer an opportunity to promote long-term surgical IOP reduction with an improved complication profile.

Reconstruction of extensive head and neck defects with multiple simultaneous free flaps.

BACKGROUND: Extensive head and neck defects may not be amenable to reconstruction with a single flap. The authors' evaluated the feasibility and functional outcomes of reconstructive surgery involving multiple simultaneous free flaps. METHODS: Cases involving multiple simultaneous free flaps for head and neck reconstruction between 2001 and 2007 at the University of Texas M. D. Anderson Cancer Center were reviewed. RESULTS: Seventy-nine free flaps were performed in 39 patients. Thirty-four patients (87 percent) underwent mandibular reconstruction for 14 bone and full-thickness cheek defects (36 percent), nine bone and hemiglossectomy defects (23 percent), and 11 bone and near total or total glossectomy defects (28 percent). Five patients (13 percent) had extensive palatomaxillary defects. The mean operation time, including the time for extirpative surgery, was 13.8 hours. The mean intensive care unit stay was 4.3 days, and the mean hospital stay was 11.5 days. Two patients had laryngectomies and the remainder received tracheostomies. Of the tracheostomy group, 33 patients (89 percent) were decannulated. In this same group, 30 patients (81 percent) demonstrated speech with greater than 80 percent of words intelligible. Twenty-three of 29 patients (79 percent) who were feeding tube-independent preoperatively received all of their nutrition orally postoperatively. Patients who were partially or totally feeding tube-dependent postoperatively underwent either a hemiglossectomy or near total or total glossectomy, with mandibulectomy. CONCLUSIONS: Multiple simultaneous free flaps can be performed safely in patients, with acceptable recovery times and functional outcomes. In select cases, the authors advocate multiple free flap reconstruction to maximize quality of life even in patients with advanced cancers.

Predictors of level V metastasis in well-differentiated thyroid cancer.

BACKGROUND: Cervical lymphadenectomy is frequently performed in patients with lateral cervical lymph node metastases to improve regional control of disease. However, there is no consensus regarding the appropriate levels of the neck that need to be dissected. Treatment options that have been advocated include the modified radical neck dissection, limited neck dissections, and selective nodal excisions. In particular, the routine dissection of level V remains controversial due to the attendant morbidity to the spinal accessory nerve. To identify clinical and pathological predictors of cervical node metastases to level V in differentiated thyroid carcinoma, we reviewed our experience at The University of Texas M. D. Anderson Cancer Center for the management of metastatic well-differentiated thyroid cancer. METHODS: We retrospectively analyzed 70 patients who underwent thyroidectomy and neck dissection for well-differentiated thyroid cancer at M. D. Anderson Cancer Center. RESULTS: In our series, 53% of neck specimens harbored metastatic thyroid carcinoma at level V. Additionally, 13 level V contralateral neck dissections were performed, and 57% were found positive for metastases. The presence of ipsilateral level V metastases was significantly associated with multifocal disease (p <.05), ipsilateral level II (p <.05), III (p <.05), or IV (p <.01) metastases. Furthermore, ipsilateral involvement of level V was associated with contralateral lymph node metastases (p <.05). Age, sex, and size of primary tumor were not found to be associated with level V metastases. Additionally, preoperative imaging was not sensitive for detecting the presence of level V metastases. CONCLUSION: In our series, cervical metastases from differentiated thyroid carcinoma were commonly present at level V. Patients with multifocal cancer within the thyroid gland, and cervical metastases in the ipsilateral jugular nodes have a higher risk of harboring metastatic disease at level V. We believe that routine dissection of the level V lymph nodes should be performed in the setting of a comprehensive neck dissection for patients with lateral neck metastasis from well-differentiated thyroid cancer.