Isolated cervical recurrence of squamous cell carcinoma in the previously treated neck.

PURPOSE: Our study goal was to identify clinical factors associated with, and that might predict, treatment outcome for patients with an isolated cervical recurrence of squamous cell carcinoma in the previously treated neck (ICR-PTN). MATERIALS AND METHODS: We reviewed all patients with noncutaneous head and neck squamous cell carcinoma treated at our tertiary care center between 1987 and 1997, and identified 17 patients (2%) who later developed an isolated recurrence in a previously treated neck. These patients made up our study group, and their charts were thoroughly reviewed. Outcome of salvage therapy (surgery, radiation, or combined therapy) for these patients was compared with pooled clinicopathologic data using the Fisher exact test (one tail). RESULTS: Fifteen such ICR-PTN patients consented to salvage therapy. Six patients were without disease at last follow-up, and 3 were successfully palliated. A statistically significant association between the side of ICR-PTN relative to the primary tumor and outcome of salvage therapy (P =.026) was noted, with ipsilateral neck recurrence being a favorable prognostic factor. Trends that did not meet the standard for statistical significance were observed between a better outcome of salvage therapy and the following parameters: age of less than 60, nonsurgical initial treatment of the neck, and lack of a history of a recurrence before they developed the ICR-PTN. CONCLUSIONS: The current study showed that only the side of the ICR-PTN relative to the primary site is associated with outcome of salvage therapy. Based on our findings and a review of the literature, we have developed a summary of factors that might predict which patients with an ICR-PTN are most likely to benefit from aggressive salvage therapy.

Factors related to outcome of salvage therapy for isolated cervical recurrence of squamous cell carcinoma in the previously treated neck: a multi-institutional study.

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

The expression of a functional, secreted human lysyl hydroxylase in a baculovirus system.

This study reports the expression of functional human lysyl hydroxylase (LH), a post-translational modifying enzyme that catalyzes the hydroxylation of the lysine residues essential for cross-linking in collagen biosynthesis. We have developed a novel baculovirus system for the expression of LH, a protein that exists normally within the lumen of the endoplasmic reticulum, using a powerful baculovirus signal sequence for secretion. The supernatant from Sf9 cells infected with the viral recombinant showed significant LH activity that increased linearly with supernatant concentration, whereas there was no detectable LH activity in the cell pellet. Silver staining of the fractions purified from the active supernatant by concanavalin A Sepharose chromatography and separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis demonstrated an 85-kDa protein (the expected size of the LH subunit) that was most prominent in those fractions with the highest LH activity. N-terminal amino acid sequencing verified that the N-terminal primary structure of this 85-kDa protein was identical to human LH. Moreover, the activity of the expressed protein was shown to be dependent on the presence of Fe++, ascorbate, and alpha-ketoglutarate, three essential cofactors for LH activity. We have therefore successfully developed a novel expression system that produces functional human LH and enables this normally nonsecretory enzyme to be secreted, facilitating its separation from the intracellular proteins of insect cells. Future applications should allow characterization of the LH active site by crystallographic studies and site-directed mutagenesis for structure-function comparison.