Anthony Sparano

Multivariate Predictors of Occult Neck Metastasis in Early Oral Tongue Cancer

OBJECTIVES: The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multi-variate analysis to correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue. STUDY DESIGN AND METHODS: The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness. RESULTS: Independent correlates of positive occult neck metastasis included greater tumor thickness (P = 0.01), greater depth of muscle invasion (P = 0.01), T2 stage (P = 0.01), poorly differentiated tumors (P = 0.007), infiltrating-type invasion front (P = 0.03), presence of perineural invasion (P = 0.001), and presence of angiolymphatic invasion (P = 0.005). The final multivariate model for estimation of an increased probability of occult neck disease included greater tumor thickness, presence of perineural invasion, infiltrating-type invasion front, poorly differentiated tumors, and T2 stage. CONCLUSIONS: The clinical and histopathologic factors studied herein permit greater selectivity and more informed decision-making than does presurgical evaluation, when addressing elective neck treatment for early N0 oral tongue cancer. The multivariate model derived from this study appears to be a more reliable method for determining the patients most likely to benefit from elective neck dissection.

Genome-Wide Profiling of Oral Squamous Cell Carcinoma by Array-Based Comparative Genomic Hybridization†

Objectives: Array‐based comparative genomic hybridization (aCGH) was used to develop a genome‐wide molecular profile of oral squamous cell carcinoma (OSCC). Copy number alterations (CNAs) were identified by chromosomal region, mapped to specific genes, and compared with several previously documented CNAs associated with head and neck squamous cell carcinoma (HNSCC). The status of 512 commonly altered cancer genes was assessed and evaluated as potential correlates of tumor behavior.

Angiographic methods to assess human coronary angiogenesis

It is unclear how agents designed to promote angiogenesis in the human heart affect the arteriographic appearance of the collateral circulation. Possible changes in collateral vessels include new collateral vessels arising from epicardial arteries, new branches emanating from existing collateral vessels, wider or longer collateral vessels, and higher dye transit rates that result in improved recipient vessel filling. Given the multiple mechanisms by which these new agents may improve myocardial perfusion, a rigorous, systematic, and comprehensive analysis of coronary arteriograms is required to discern the true mechanism of benefit. The method of analysis must account for potential changes in collateral blood flow, number, branching pattern, and length as well as changes in recipient vessel filling. The ability to detect differences between intricate networks of vessels in an angiographic study is dependent on maintaining consistency in cinefilming as well as the core laboratory methods between time points. In this report, we describe the methodology our angiographic core laboratory has found to be most effective to evaluate these very complex angiograms and attempt to capture all the possible modalities of angiogenesis.

Mechanical debulking versus balloon angioplasty for the treatment of true bifurcation lesions

OBJECTIVES The purpose of this study was to compare the immediate angiographic and long-term results of debulking versus balloon angioplasty for treatment of true bifurcation lesions. BACKGROUND Previous studies have shown true bifurcation lesions to be a high risk morphological subset for percutaneous transluminal coronary angioplasty (PTCA). Although atherectomy devices have been used to treat bifurcation lesions, no studies have compared the outcomes of these alternative treatment modalities. METHODS Between January 1992 and May 1997, we treated 70 consecutive patients with true bifurcation lesions (defined as a greater than 50% stenosis in both the parent vessel and contiguous side branch) with conventional PTCA (n = 30) or debulking (with rotational or directional atherectomy) plus adjunctive PTCA (n = 40). Paired angiograms were analyzed by quantitative angiography, and clinical follow-up was obtained in all patients. RESULTS Acute procedural success was 73% in the PTCA group and 97% in the debulking group (p = 0.01). Major in-hospital complications occurred in two patients in the PTCA group and one in the debulking group. Treatment with atherectomy plus PTCA resulted in lower postprocedure residual stenoses than PTCA alone (16+/-15% vs. 33+/-17% in the parent vessel, and 6+/-15% vs. 39+/-22% in the side branch; p < 0.001 for both comparisons). At 1 year follow-up, the incidence of target vessel revascularization (TVR) was 53% in the PTCA group as compared with 28% in the debulking group (p = 0.05). Independent predictors of the need for repeat TVR were side branch diameter >2.3 mm, longer lesion lengths, and treatment with PTCA alone. CONCLUSIONS For the treatment of true bifurcation lesions, atherectomy with adjunctive PTCA is safe, improves acute angiographic results, and decreases target vessel revascularization compared to PTCA alone. The benefits of debulking for bifurcation lesions were especially seen in lesions involving large side branches.

Characterization CSMD1 in a large set of primary lung, head and neck, breast and skin cancer tissues

The Cub and Sushi Multiple Domains-1 (CSMD1) is a tumor suppressor gene on 8p23.2, where allelic loss is both frequent and associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). To understand the extent of CSMD1 aberrations in vivo, we characterized 184 primary tumors from the head and neck, lung, breast, and skin for gene copy number and analyzed expression in our HNSCCs and lung squamous cell carcinomas (SCCs). We detected loss of CSMD1 in a large proportion of HNSCCs (50%), lung (46%) and breast cancers (55%), and to a lesser extent in cutaneous SCCs (29%) and basal cell carcinomas (BCCs, 17%) using array-based comparative genomic hybridization (aCGH). Studying the region more closely with quantitative real-time PCR (qPCR), the loss of CSMD1 increased to 80% in HNSCCs and 93% in lung SCCs. CSMD1 expression was decreased in tumors compared to adjacent benign tissue (65%, 13/20) and was likely due to gene loss in 45% of cases (9/20). We also identified truncated transcripts lacking exons due to DNA copy number loss (30%, 5/17) or aberrant splicing (24%, 4/17). We show loss of CSMD1 in primary HNSCC tissues, and document for the first time that CSMD1 is lost in breast, lung and cutaneous SCCs. We also show that deletions of CSMD1 and aberrant splicing contribute to altered CSMD1 function in vivo.

Predictors of Thyroid Gland Invasion in Glottic Squamous Cell Carcinoma

Objective: This study examines preoperative clinical and intraoperative histopathologic characteristics that can be used to predict thyroid gland invasion in the setting of squamous cell carcinoma (SCC) of the glottis.

Extending the Inferior Limits of Supracricoid Partial Laryngectomy: A Clinicopathological Correlation

Objectives/Hypothesis: The study examined preoperative clinical characteristics that can be used to predict secure inferior margins of glottic squamous cell carcinoma extending toward the cricoid cartilage when performing organ preservation surgery of the larynx.

Laser-assisted cerebrospinal fluid leak repair: An animal model to test feasibility

Objectives To test the feasibility of laser tissue welding as a method of creating an endonasal tissue bond for the purpose of cerebrospinal fluid leak repair. Study Design and Setting An 808 nm diode laser was used with a 42% albumin solder to create laser welds in sheep nasal septal mucosa, periosteum, and in situ rabbit maxillary sinus mucosa. Each condition was tested five times. Groups were compared with Kruskal-Wallis nonparametric analysis of variance (ANOVA) and post-hoc multiple-comparisons testing with the Bonferroni test. Results The burst pressures of sheep septal mucosa (34.88 ± 3.49 mmHg) and periosteum (30.02 ± 2.23 mmHg) were significantly higher than suture repair. A burst pressure of 69.58 ± 2.85 mmHg was achieved in rabbit in situ maxillary sinus mucosa. Conclusion Laser welding is capable of producing tissue bonds whose burst strength exceeds that of human intracranial pressure. Significance This is the first study to examine the feasibility of laser tissue welding in endonasal tissues. The ability to produce instant transnasal tissue bonds with burst pressures that exceed human intracranial pressure make this technology ideal for cerebrospinal fluid leak repair.