Brian D. Kulbersh

Pretreatment, Preoperative Swallowing Exercises May Improve Dysphagia Quality of Life

Objectives: Dysphagia is commonly associated with head and neck cancer treatment. Traditional dysphagia management strategies focus on post‐treatment therapy. This study evaluated the utility of pretreatment swallowing exercises in improving post‐treatment swallowing quality of life (QOL).

Use of fluorescent labeled anti–epidermal growth factor receptor antibody to image head and neck squamous cell carcinoma xenografts

Physicians and surgeons rely on subtle tissue changes to detect the extent of tumors and the presence of residual disease in the clinical setting. The development of a cancer-specific fluorescent contrast agent has the potential to provide real-time tumor imaging in the clinic or operating room. Because epidermal growth factor receptor (EGFR) is highly overexpressed on the surface of head and neck squamous cell carcinoma (HNSCC), we sought to determine if fluorescently labeled anti-EGFR antibody could be used to image HNSCC xenografts in vivo. Cetuximab or control isotype-matched IgG1 was conjugated with the Cy5.5 fluorochrome and systemically injected into mice bearing human split thickness skin grafts, tumor cell line xenografts, transplanted human tumor xenografts, or mouse mesothelioma tumors. Xenografts were imaged by time-domain fluorescence imaging or fluorescence stereomicroscopy. Both imaging modalities detected specific uptake of cetuximab-Cy5.5 in HNSCC xenografts with significantly higher fluorescence levels relative to control IgG1-Cy5.5. Tumor xenograft fluorescence was higher compared with background (before injection), human split thickness skin grafts, or mouse mesothelioma tumors at 24, 48, and 72 h. Fluorescence was detected in multiple HNSCC tumor cell lines with variable EGFR expression levels. Mock resections of flank tumors using fluorescence stereomicroscopy showed that small (2 mm) specimens could be detected in the surgical wound bed. These results show the feasibility of using fluorescently labeled anti-EGFR antibody to detect human tumors in the surgical setting. [Mol Cancer Ther 2007;6(4):1230–8]

In vivo detection of head and neck cancer orthotopic xenografts by immunofluorescence.

Purpose: To determine whether Cy5.5‐labeled antiepidermal growth factor (EGFR) antibody could be used to detect head and neck squamous cell carcinoma (HNSCC) xenografts in vivo.

Minimally invasive parathyroidectomy: use of intraoperative parathyroid hormone assays after 2 preoperative localization studies.

OBJECTIVES To review minimally invasive parathyroidectomy (MIP) in patients undergoing initial surgical management of primary hyperparathyroidism (HPT) with preoperative, localizing sestamibi scanning (MIBI), and concordant ultrasonography (US) to determine if intraoperative parathyroid hormone (iPTH) is necessary in these cases. Minimally invasive parathyroidectomy has become an acceptable therapeutic option in treating primary HPT. Preoperative MIBI scanning, high-resolution US with color Doppler flow, and iPTH monitoring have refined this technique. DESIGN Retrospective review. PATIENTS The medical records of 738 consecutive patients who had undergone surgery for HPT. After excluding revision surgical procedures, secondary and tertiary HPT, unavailable intraoperative parathyroid (PTH) data, concomitant thyroid disease requiring thyroidectomy, and patients without preoperative MIBI or US, 428 patients (58%) were included in the study. RESULTS The mean decrease in PTH level was 85%. Of the 428 patients with primary HPT included in the study, 209 patients (49%) had localizing, concordant preoperative MIBI and US. A decline of more than 50% in iPTH levels was observed in 202 patients (97%) after removal of parathyroid tissue localized by MIBI and US. The procedures for 4 patients were converted to bilateral neck explorations after the postexcision PTH level failed to drop less than 50%. CONCLUSIONS Our results show that iPTH monitoring may be eliminated in MIP surgery in a carefully selected group of patients who have preoperative, localizing MIBI with concordant US. This potentially allows an increase in operating room efficiency and a decrease in costs while performing MIP.

Role of microvascular density in nonlocalizing parathyroid sestamibi scans.

Objectives: Sestamibi scans for localization of abnormal parathyroid glands in patients with hyperparathyroidism are widely used at many institutions. Minimally invasive parathyroid surgery demands accurate preoperative localization imaging; however, nonlocalizing sestamibi scans occur in 15% of patients with primary hyperparathyroidism. It remains unknown why some sestamibi scans fail to localize. We hypothesize that an increase in microvascular density (MVD) within an adenoma will result in rapid tracer washout and a subsequent nonlocalizing scan. This study investigates the role of MVD in sestamibi localization.

S112 Assessment of Fluorescent Immunoguided Neoplasm Detection to Identify Microscopic Disease In Vivo

Background: During ablative head and neck cancer procedures, a surgeon’s assessment of tumor extent is dependent on subtle tissue changes and palpation. Accurate assessment of tumor extent by fluorescent optical imaging has the potential to provide surgeons real-time, intraoperative information about the local extent of tumor and the presence of residual disease. Design: Orthotopically inoculated head and neck squamous cell carcinoma cells UM-SCC-1 (n=6), CAL 27 (n=6), or saline-injected controls were monitored for 14 days and then underwent mock surgical resections. Antiepidermal growth factor receptor antibody (cetuximab) was labeled with a near-infrared fluorochrome, Cy5.5. The cetuximab-Cy5.5 conjugate was systemically administered by tail vein injection 3 days prior to the resection. Near-infrared fluorescent monitoring was performed before resection and after partial and complete surgical excision of the tumors. After resection, the mandible and attached soft tissues were resected, paraffin embedded, and serial sectioned. Results: After transcervical serial tumor resections, near-infrared stereomicroscopy was used to detect residual disease attached to the soft tissues or mandible in both cell lines. Histological analysis of serial sections of the mandible and floor of mouth after resection demonstrated that in every case negative fluorescence corresponded to the absence of residual tumor. The smallest residual disease that could be detected (SCC-1 cell line) was 0.7 mm. The location of residual disease visualized by fluorescence stereomicroscopy was confirmed on histological sections. Conclusion: Near-infrared stereomicroscopy after systemic administration of cetuximab labeled with Cy5.5 may enable surgeons to visualize residual disease intraoperatively. S115 The Receptor Tyrosine Kinase c-MET Is Mutated in Head and Neck Cancer and Is a Promising Novel Target