Faculty Bibliography

BACKGROUND: Newcastle disease virus (NDV) is a paramyxovirus that is pathogenic in birds but causes only mild flulike symptoms in human beings. NDV(F3aa)-GFP is a genetically modified, fusogenic NDV. We assessed the utility of NDV(F3aa)-GFP in treating head and neck squamous cell carcinoma. METHODS AND RESULTS: At a multiplicity of infection (MOI) of 1, NDV(F3aa)-GFP infection of 3 cell lines supported strong GFP expression by 36 hours. Four cell lines were highly sensitivite to viral cytotoxicity, with >75% of cells lysed by day 6 at MOI 0.1, and 2 other cell lines were partially susceptible. Murine SCC25 flank tumors exhibited robust GFP expression after a single intratumoral viral injection and showed near-complete tumor regression over 34 days. There were no adverse effects attributable to therapy. CONCLUSIONS: We demonstrate that a fusogenic NDV exerts potent oncolytic effects against human head and neck cancer and support its continued investigation for clinical application.

BACKGROUND: There is a paucity of outcomes data for patients with lymph node metastasis from cutaneous squamous cell carcinoma of head and neck (SCCHN). METHODS: Patients from a tertiary care center with cutaneous SCCHN metastatic to parotid and or cervical lymph nodes were identified. Data were abstracted and analyzed using COX multivariate analysis. RESULTS: Fifty-one patients (47 men, and 4 women) with a median age of 73 years were identified. Eight patients (16%) had recurrent disease and 11 (22%) were immunosuppressed. Forty patients (71%) received adjuvant radiation therapy. Median overall survival was 23 months (range, 3-148 months). Recurrent disease was associated with higher risk of death (hazard ratio [HR], 2.7; 95% confidence interval [CI] 1.1-6.9) and radiation therapy with reduced risk (HR, 0.18; 95% CI, 0.06-0.54). CONCLUSION: Lymph node metastases from cutaneous SCCHN is associated with poor survival.

We report the pathology and outcome of secondary skull base tumors in patients previously treated with external beam radiation for retinoblastoma (Rb). Rb patients are at increased risk of second head and neck primary malignancies due to early radiation exposure during treatment and loss of RB1 protein in genetic carriers. An institutional database was reviewed for patients with retinoblastoma who had previously received radiation therapy and subsequently developed skull base tumors. Seventeen patients met the selection criteria. The median age of Rb diagnosis was 12 months. Thirteen cases underwent enucleation in addition to radiation therapy as part of initial Rb treatment. A median of 19 years elapsed between the diagnosis of Rb and diagnosis of skull base malignancy. The most common tumors were osteogenic sarcoma (39%) and leiomyosarcoma (22%). Eleven (71%) patients received postoperative chemotherapy, and 7 (41%) received postoperative radiotherapy. Three (24%) patients underwent salvage surgery for recurrent disease. Five-year survival was 68%, and 10-year survival was 51% by Kaplan-Meier analysis. Secondary malignancy in Rb patients is a well-defined event. The use of surgery with appropriate adjuvant therapy was associated with a 51% 10-year survival in this study population.

Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. The cause is unknown, but clinical correlations with different genetic syndromes exist. Mutations in the HPRT2 gene seem to play a significant role in the pathogenesis of this disease. Men and women are equally affected, usually in the fourth or fifth decade of life. Most patients will present with signs and symptoms of hypercalcaemia. Cases of non-functioning carcinoma are exceedingly rare. Surgical resection is the most effective method of treatment and palliation. A significant proportion of patients will experience recurrence, and will need further surgical and, eventually, medical management of hypercalcaemia. The disease is progressive but slow growing. Most patients will require multiple operations to resect recurrent disease. The main cause of morbidity and mortality is the sequela of uncontrolled chronic hypercalcaemia rather than tumour burden. The current paper will review the epidemiology, pathogenesis, clinical presentation and diagnostic work-up of this disease. Surgical management in different scenarios is reviewed in detail, followed by other types of treatment and management of incurable disease.

BACKGROUND: Hepatic metastases from neuroendocrine cancer dramatically reduce survival, introducing an important opportunity for intervention. Several treatment modalities have been examined, but an optimal treatment approach has been difficult to define. We evaluated a regimen combining hepatic artery chemoinfusion with chemoembolization. METHODS: Patients with neuroendocrine cancer and diffuse hepatic metastases were treated with hepatic artery chemoinfusion and chemoembolization when they demonstrated disease progression despite octreotide therapy. Four monthly cycles of 5-fluorouracil were administered via hepatic artery infusion with chemoembolization after the final 2 cycles. Response was defined by radiologic response or symptomatic improvement. RESULTS: Seventy-seven patients were treated; 18 received chemoinfusion only. The treatment-related mortality rate was 7%. The overall response rate was 80% for patients with carcinoid or islet cell neoplasms. Median progression-free survival was 19 months. Median disease-specific survival was 39 months from the first treatment; 1- and 5-year survival rates were 78% and 27%, respectively. CONCLUSION: Survival after initiating this regimen was over 3 years for the majority of patients exhibiting progression of extensive, unresectable hepatic disease despite octreotide therapy. The addition of hepatic artery chemoinfusion to chemoembolization offers a high probability of clinical benefit to patients who, otherwise, have severely limited therapeutic options and a dismal survival.

Neck dissection is one the most commonly performed operations in head and neck surgery. Better understanding of the structure and patterns of lymphatic flow in the neck has transformed this operation into a more selective and less morbid treatment. Rationale for this operation and modifications of it in different clinical scenarios such as node negative, node positive and radiated neck are detailed in this article. Recommendations are made based on the available evidence.

CONTEXT: Although commonly performed, data are lacking regarding efficacy and safety of lymph node dissection (LND) for recurrent/persistent papillary thyroid cancer (PTC). OBJECTIVE: Evaluate the efficacy and morbidity of LND in recurrent/persistent PTC. DESIGN: Retrospective review of central or lateral LND performed for persistent/recurrent PTC between January 2004 and March 2006. SETTING: Multidisciplinary thyroid cancer clinic with a single surgeon at an academic medical center. PARTICIPANTS: Seventy-five patients who underwent 79 LND for persistent/residual PTC. Safety analysis included all 79 resections. Exclusion criteria for the efficacy analysis were factors prohibiting evaluation of thyroglobulin (Tg) response. Forty-one resections were included in the efficacy analysis. INTERVENTION: Selective LND per standard of care. MAIN OUTCOME MEASURE: Primary outcome was the Tg response to LND. Secondary outcomes were surgical complications. RESULTS: Thirty-nine of the 41 evaluable resections also had Tg data allowing classification of Tg response. Of 39 classifiable resections, 16 (41%) resulted in undetectable postoperative stimulated Tg levels. An additional 12 resections resulted in significant (> or =50%) reductions in suppressed or stimulated Tg levels for an overall improvement rate of 72%. Of all 79 resections, 25 (32%) resulted in minor and 7 (9%) resulted in major complications. CONCLUSIONS: LND for persistent/recurrent PTC is a relatively safe procedure in experienced hands. It can lead to an undetectable Tg in 41% of cases and produce a major Tg reduction in an additional 31%. Its efficacy in short-term follow-up is comparable with that reported for I-131, and it should be considered in the management of persistent/recurrent PTC.

BACKGROUND: It is unclear whether there is a benefit to resection of primary gastrointestinal carcinoid neoplasm with hepatic metastases. We investigated whether primary tumor resection in this setting led to a significant difference in outcomes. METHODS: A retrospective review of patients with abdominal carcinoid neoplasms between 1995 and 2006 was performed. Data collected on patients with proven carcinoid liver metastases at initial diagnosis included whether the primary neoplasm was resected, time to progression of liver metastases, and status at last follow-up. Progression-free survival and survival were calculated by the method of Kaplan-Meier and compared by the log-rank test. RESULTS: There were 84 patients, 60 of whom had their primary neoplasm resected. The resected group had a greater median progression-free survival of 56 months, compared with 25 months for the primary nonresected group (P < .001). Median survival time for the resected group was longer at 159 months, compared with 47 months for the nonresected group (P < .001). CONCLUSIONS: Resection of the primary neoplasm is associated with better progression-free survival and overall survival in patients with abdominal carcinoid neoplasms. Therefore, localization and resection of the primary neoplasm should be considered, even among patients in whom the primary neoplasm is asymptomatic.