Faculty Bibliography

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups. METHODS: A retrospective multicenter study was conducted on 322 patients from three Australian and three North American institutions. All had metastatic cutaneous SCC involving the parotid gland and/or neck and all were treated for cure with a minimum followup time of 2 years. These patients were restaged using a newly proposed system that separated parotid disease (P stage) from neck disease (N stage) and included subgroups of P and N stage. Metastases involved the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322 received radiotherapy. RESULTS: Neck nodes were pathologically involved in 32% of patients with parotid metastases. Disease recurred in 105 (33%) of the 322 patients, involving the parotid in 42, neck in 33, and distant sites in 30. Parotid recurrence did not vary significantly with P stage. Disease-specific survival was 74% at 5 years. Survival was significantly worse for patients with advanced P stage: 69% survival at 5 years compared with 82% for those with early P stage (P = 0.02) and for those with both parotid and neck node involvement pathologically: 61% survival compared with 79% for those with parotid disease alone (P = 0.027). Both univariate and multivariate analysis confirmed these findings. Clinical neck involvement among patients with parotid metastases did not significantly worsen survival (P = 0.1). CONCLUSIONS: This study, which included a mixed cohort of patients from six different institutions, provides further information about the clinical behavior of metastatic cutaneous SCC of the head and neck. The hypothesis that separation of parotid and neck disease in a new staging system is supported by the results. The benefit of having subgroups of P and N stage is uncertain, but it is likely to identify patients with unfavorable characteristics that may benefit from further research

We present an unusual case of empyema of the gallbladder associated with a pyogenic liver abscess in a patient with Crohn's disease on Infliximab. It manifested by weakness, weight loss, and vague abdominal pain, which eventually localized to the right upper quadrant 4 days prior to admission. Diagnostic evaluation, which included ultrasonography and computed tomography, revealed cholelithiasis, gallbladder wall thickening, and a low-attenuation, complex mass in the left hepatic lobe. Cholecystectomy and open drainage of the liver abscess were successfully performed. There are few reports of intrahepatic abscess associated with Crohn's disease. The relationship between acute cholecystitis and Crohn's disease has also been documented. However, this report documents the unusual complication of pyogenic liver abscess secondary to acute cholecystitis in the unique population of Crohn's disease patients on Infliximab

BACKGROUND: We recently identified MUC1 as a target driving selection for 1q21 amplification and validated it as an independent marker of aggressive behavior in thyroid cancer (TC). The aims of this study were to determine whether TC cell lines retain MUC1 expression patterns that are seen in primary tumors, assess the role of MUC1 in tumor maintenance, and develop a virally delivered anti-MUC1 RNA interference (RNAi) that is effective in decreasing MUC1 expression in vitro. METHODS: Fifteen TC cell lines were screened for MUC1 protein expression. Cell lines with varying MUC1 protein levels were treated with anti-MUC1 monoclonal antibody to assess cell viability. A recombinant retroviral short hairpin RNAi delivery system against MUC1 was developed. Efficacy and optimal dosing of short hairpin RNA against MUC1 was determined. RESULTS: MUC1 expression patterns in TC cell lines were found to be similar to that seen in primary tumors. Treatment with anti-MUC1 antibody resulted in a significant decrease in cell viability in MUC1 over-expressing cell lines. MUC1-779 RNAi construct showed excellent infection efficiency and reproducible silencing. CONCLUSION: These data offer functional evidence that implicates MUC1 over-expression as a key molecular event in the pathogenesis of aggressive TC. Retrovirally delivered anti-MUC1 RNAi is effective in silencing MUC1 and merits further investigation to establish therapeutic efficacy and safety in anticipation of potential clinical application

PURPOSE OF REVIEW: The purpose of this review is to summarize existing literature with respect to locally advanced thyroid cancer and define the intricacies of preoperative evaluation, surgical management of involved sites and postoperative treatment. RECENT FINDINGS: Locally invasive thyroid cancer is an uncommon disease process, which carries significant morbidity and mortality. Current treatment modalities include appropriate surgery, radioactive iodine treatment and external beam radiation therapy. Proper evaluation of the extent of disease, with complete gross tumor removal, is paramount in managing this difficult problem. Surgical treatment is still the mainstay for locally advanced thyroid cancer. SUMMARY: Little progress has been made in advancing the treatment of locally advanced thyroid cancer. Patient identification, evaluation and proper surgical management with adjuvant therapy, still remain the most effective course of treatment. Aggressive surgical treatment including removal of all gross tumor and still preserving vital structures along with adjuvant therapy is likely to offer the best results. There is a very high incidence of locoregional and distant failure in this group of patients. The understanding and recognition of histopathological variations, such as poorly differentiated thyroid cancer is also important. New molecular markers are needed to help identify and predict aggressive tumor behavior

Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0.03). Analysis of a validation series containing a matched group of aggressive and indolent cPTCs confirmed the association between MUC1 overexpression and survival (relative risk, 2.3; 95% confidence interval, 1.1-5.5; P = 0.03). Our data suggest that MUC1 dysregulation is associated with aggressive behavior of PTC and may serve as a prognostic marker and potential therapeutic target in this disease