Intra-operative use of PET probe for localization of FDG avid lesions.

Localizing positron emission tomography (PET)/computed tomography (CT) findings in heavily scarred surgical fields can be challenging. A high energy gamma probe (PET probe) can be used to guide surgery in those difficult areas. We describe our experience localizing and removing fluorodeoxyglucose (FDG) avid lesions in different body areas. Between 2004 and 2007, we used the PET probe to localize and remove 12 lesions from 9 patients. The lesions were removed confirming ex vivo and tumor bed FDG activity. Five patients had lesions in previously operated and sometimes radiated fields. One patient had FDG avid spots in the retroperitoneum. Two lymphoma patients had been previously treated and had new FDG avid spots in a background of scarred nodes. The last patient had a core biopsy suspicious for lymphoma but a repeat CT was non-specific. One patient with gastric cancer patient, two patients with melanoma patients and two patients with breast cancer had 10 metastatic lesions easily identified and removed. After a median follow-up of 14 months all five patients are alive. The two patients with lymphoma had their FDG avid lymph nodes easily identified and biopsied. In one patient with melanoma and one patient with suspected lymphoma, the preoperative scan revealed no FDG avid lesions. The PET probe confirmed this finding in the operating room. Clinical applications of PET probe guided surgery include restaging for previously treated lymphoma patients, localization and resection of metastatic FDG avid nodules especially in previously operated or radiated fields and biopsy of PET findings difficult to localize.

Distant metastases from oropharyngeal cancer.

Distant metastasis is a significant problem in patients with carcinoma of the oropharynx, occurring in approximately 15-20% off all patients over the course of the disease. It is, however, a relatively uncommon first site of failure, as compared to local and regional recurrence. Distant spread occurs most commonly to the lungs, in patients who present with advanced disease, and especially in those with pathologically proven lymph nodes at multiple levels of the neck or in the lower neck. Metastasis to distant sites also occurs more often in patients who recur locally or in the neck.

A novel CD44 v3 isoform is involved in head and neck squamous cell carcinoma progression.

OBJECTIVES: CD44 comprises a family of isoforms involved in tumorigenesis. Here we investigate the role of CD44 isoforms in head and neck squamous cell carcinoma (HNSCC) progression. MATERIALS AND METHODS: HNSCC specimens underwent reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. After surface biotinylation, FaDu (hypopharyngeal HNSCC) and CD44v3-transfected COS-7 cells were CD44 antibody-precipitated and compared by Western blot analysis. FaDu cells underwent double immunofluorescence staining and growth assays. RESULTS: Southern blot analysis suggested differential CD44v3 isoform expression in tumor and normal tissue. Cloning and sequencing revealed 2 novel CD44v isoforms. Western blot analysis suggested CD44v3 expression in COS-7 transfectants and FaDu. Double immunofluorescence staining revealed co-localization of CD44v3 and actin in FaDu projections. Anti-CD44v3 antibody decreased FaDu growth. CONCLUSION: HNSCC tissue and FaDu appear to express CD44v3 isoforms. These isoforms may promote tumorigenesis. CLINICAL SIGNIFICANCE: CD44v3 isoforms may be effective tumor markers and targets for HNSCC therapy.

Randomized trial of supplemental beta-carotene to prevent second head and neck cancer.

Beta-carotene has established efficacy in animal models of oral carcinogenesis and has been shown to regress oral precancerous lesions in humans. The purpose of this study was to see whether these effects extended to the prevention of oral/pharyngeal/laryngeal (head and neck) cancer in humans. The subject population for this randomized, placebo-controlled, double-blinded clinical trial included 264 patients who had been curatively treated for a recent early-stage squamous cell carcinoma of the oral cavity, pharynx, or larynx. Patients were assigned randomly to receive 50 mg of beta-carotene per day or placebo and were followed for up to 90 months for the development of second primary tumors and local recurrences. After a median follow-up of 51 months, there was no difference between the two groups in the time to failure [second primary tumors plus local recurrences: relative risk (RR), 0.90; 95% confidence interval (CI), 0.56-1.45]. In site-specific analyses, supplemental beta-carotene had no significant effect on second head and neck cancer (RR, 0.69; 95% CI, 0.39-1.25) or lung cancer (RR, 1.44; 95% CI, 0.62-3.39). Total mortality was not significantly affected by this intervention (RR, 0.86; 95% CI, 0.52-1.42). Whereas none of the effects were statistically significant, the point estimates suggested a possible decrease in second head and neck cancer risk but a possible increase in lung cancer risk. These effects are consistent with the effects observed in trials using intermediate end point biological markers in humans, in which beta-carotene has established efficacy in oral precancerous lesions but has no effect or slightly worsens sputum cytology, and in animal carcinogenicity studies, in which beta-carotene has established efficacy in buccal pouch carcinogenesis in hamsters but not in animal models of respiratory tract/lung carcinogenesis, with some suggestions of tumor-promoting effects in respiratory tract/lung. If our results are replicated by other ongoing/completed trials, this suggests a critical need for mechanistic studies addressing differential responses in one epithelial site (head and neck) versus another (lung).

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract.

OBJECTIVES: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. STUDY DESIGN: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. RESULTS: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. SIGNIFICANCE: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors.

Sensory recovery in melolabial flaps used for oral cavity reconstruction.

Current literature advocates the use of complex reinnervated free flaps to re-establish oral sensation after resection of oral cavity cancers. It has been demonstrated that noninnervated flaps can also re-establish sensation. We assessed the return of sensation in local melolabial flaps used in oral reconstruction. Seven patients underwent sensory testing at intervals from 12 to 18 months after surgery. The ability to distinguish differences in temperature was present in all patients. Spontaneous return of sensitivity to touch was documented by clinical testing in 71% of the patients. Less return of sensation was seen in flaps used for defects of the buccal mucosa relative to the floor of mouth. We conclude that spontaneous return of flap sensation does occur with local melolabial flaps. Given the simplicity of these procedures, melolabial flaps represent a reasonable alternative in floor-of-mouth reconstruction for selected patients.

Salvage surgery for patients with recurrent squamous cell carcinoma of the upper aerodigestive tract: when do the ends justify the means?

OBJECTIVES/HYPOTHESES: Salvage surgery is widely viewed as a "double-edged sword." It is the best option for many patients with recurrent cancer of the upper aerodigestive tract, especially when original therapy included irradiation, yet it may provide only modest benefit at high personal cost to the patient. The stakes are high because alternatives are of limited value. The primary objective of this study was to fully assess the value of salvage surgical procedures in the treatment of local and regional recurrence. The following hypotheses were developed to focus the study design and data analysis. 1) The efficacy of salvage surgery correlates recurrent stage, recurrent site, and time to presalvage recurrence. 2) The economic and noneconomic costs of salvage surgery increase with higher recurrent stage. 3) Information relating the value of salvage surgery to recurrent stage and recurrent site will be useful to these patients and the physicians who treat them. STUDY DESIGN: Two complimentary methods of investigation were used: a meta-analysis of the published literature and a prospective observational study of patients undergoing salvage surgery for recurrent cancer of the upper aerodigestive tract. METHODS: The meta-analysis combined 32 published reports to obtain an estimate of average treatment effect for salvage surgery with regard to survival, disease-free survival, surgical complications, and operative mortality. The prospective observational study included detailed data in 109 patients who underwent salvage surgery. In addition to parameters studied in the meta-analysis, we obtained baseline and interval quality of life data (Functional Living Index for Cancer [FLIC] scores), baseline and interval performance status evaluations (Performance Status Scale for Head and Neck Cancer Patients [PSS head and neck scores]), length of hospital stay, and hospital and physician charges, and related this data primarily to recurrent stage, recurrent site, and time to presalvage recurrence. RESULTS: The weighted average of 5-year survival in the meta-analysis was 39% in 1,080 patients from 28 different institutions. In the prospective study, median disease-free survival was 17.9 months in 109 patients, and this correlated strongly with recurrent stage, weakly with recurrent site, and not at all with time to presalvage recurrence. Noneconomic costs for patients and economic costs correlated with recurrent stage, but not with site. Baseline FLIC and PSS head and neck scores correlated with recurrent stage, but not with site. After salvage surgery the percentage of patients reaching or exceeding baseline was 51% for FLIC scores, and this differed significantly with recurrent stage. Postoperative interval "success" in PSS head and neck subscale scores for diet and eating in public also correlated with recurrent stage. CONCLUSIONS: Overall, the expected efficacy for salvage surgery in patients with recurrent head and neck cancer was surprisingly good, but success was limited and costs were great in stage III and, especially, in stage IV recurrences. A strong correlation of efficacy and noneconomic costs with recurrent stage allowed the creation of expectation profiles that may be useful to patients. Additional systematic clinical research is needed to improve results. In the end, the decision to undergo salvage surgery should be a personal choice made by the patient after honest and compassionate discussion with his or her surgeon.

Plasma lycopene concentrations in humans are determined by lycopene intake, plasma cholesterol concentrations and selected demographic factors.

Higher plasma lycopene concentrations have been associated with a reduced risk of several chronic diseases. Determinants of lycopene concentrations in humans have received limited attention. We had blood lycopene concentrations and lycopene consumption data available from 111 participants in a two-center cancer prevention trial involving beta-carotene and examined determinants of plasma lycopene levels cross-sectionally. The median plasma lycopene level was 0.59 micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were associated with the following variables in univariate analyses: study site (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels did not differ in smokers and nonsmokers. In stepwise regression analyses, the determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and marital status; these three variables explained 26% of the variance in plasma lycopene. Relatively few lifestyle and demographic factors were important determinants of plasma lycopene levels, with plasma cholesterol, marital status, and lycopene intake being of greatest importance.

Giant lipoma of the larynx: a case report and literature review.

Fewer than 15% of lipomas occur in the head and neck. To date, fewer than 100 cases of laryngeal lipoma have been reported in the literature. Typical clinical manifestations include dysphagia, dyspnea and hoarseness, as well as the presence of a smooth or pedunculated mass seen endoscopically and a low attenuation mass on computed tomography scan. Pathologic sections commonly reveal a tumor consisting of mature adipocytes, which is often encapsulated. Treatment of laryngeal lipoma varies from conservative total endoscopic removal to external surgical approaches. The following is a report of a single case of laryngeal lipoma, including pathologic and radiologic findings, as well as a review of the literature.

Effect of supplemental beta-carotene on plasma concentrations of carotenoids, retinol, and alpha-tocopherol in humans.

High doses of beta-carotene, a lipid-soluble nutrient, may affect the plasma concentrations of other lipid-soluble nutrients. The purpose of this study was to assess the effects of long-term daily supplementation with beta-carotene (50 mg/d) on circulating concentrations of other carotenoids, retinol, and alpha-tocopherol over time. Data were available from 259 men and women participating in the Carotene Prevention Trial, a 2-center chemoprevention trial designed to determine whether supplemental beta-carotene can prevent second malignant tumors in patients cured of an early stage cancer of the oral cavity, pharynx, or larynx. Up to 2 blood samples were obtained before the intervention (before and after a 1-mo placebo run-in), with postrandomization samples obtained at 3, 12, 24, 36, 48, and 60 mo. Supplementation with beta-carotene produced a persistent 9- to 10-fold increase in median plasma beta-carotene concentrations (225 nmol/L at baseline to 2255 nmol/L at 3 mo) and a persistent 2-fold increase in median plasma alpha-carotene concentrations (45 nmol/L at baseline to 95 nmol/L at 3 mo). Concentrations of retinol, alpha-tocopherol, lycopene, and lutein/zeaxanthin were not affected by supplemental beta-carotene. Up to 5 y of daily supplementation with beta-carotene increased circulating concentrations of alpha- and beta-carotene, but did not alter concentrations of lycopene, lutein/zeaxanthin, retinol, or alpha-tocopherol.

Somatostatin receptor expression in Hürthle cell cancer of the thyroid.

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.

Giant cell reparative granuloma of the maxilla.

Giant cell reparative granuloma (GCRG) is a rare nonneoplastic proliferative lesion of unknown etiology. It most commonly occurs in the mandible, but also occurs in other bones of the facial skeleton and cranial vault. Two cases of GCRG arising from the maxilla are presented. Histological and radiological features, and the pertinent literature on the subject are reviewed.

Use of galeal or pericranial flaps for reconstruction or orbital and eyelid defects.

The use of galeal or pericranial flaps for craniofacial reconstruction is well recognized. The excellent blood supply of the flap permits vascularized support for skin, bone, or cartilage grafts in otherwise unsatisfactory recipient sites. The pericranial flap was used in 1 patient with a large orbital bony defect and the galeopericranial flap was used in 3 patients with various periocular defects produced by trauma or following tumor extirpation. In the case of an orbital defect induced by chronic cocaine abuse, the pericranial flap successfully sequestered the orbit from the nasal cavity while providing support for the globe. In 3 of the 4 cases involving eyelid reconstruction, the galeopericranial flap served a dual function in providing vascular supply to the underlying free tarsal graft and to the overlying free skin graft. This tissue flap is analogous to a median forehead flap, except skin is not transposed and a second-stage inset revision is not required.

Hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and mitomycin-C (+/- granulocyte-colony stimulating factor) in the treatment of patients with locally advanced head and neck carcinoma.

BACKGROUND: The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte-colony stimulating factor (G-CSF) was added during the second phase of this study. METHODS: Seventy patients (53 with Stage IV and 17 with Stage III disease) were entered between May 1988 and June 1995 into a Phase I/II trial of concurrent radiation therapy (74.4 gray (Gy) total dose; 1.20 Gy twice daily), 5-fluorouracil (1000 mg/m2/24 hours for 72 hours), and cisplatin (50 mg/m2) for 3 cycles with the addition of mitomycin C (8 mg/m2) in Cycle 2. G-CSF was added after the initial entry of 34 patients. RESULTS: At a median follow-up of 41 months (range, 12-80 months), 44 patients were alive with a projected median overall survival of 54 months. Grade 3/4 mucositis, observed in 65% of patients, was equally prevalent and prolonged in both G-CSF-treated (+) and G-CSF-naive (-) patients. Grade 3/4 leukopenia was present in 45% and 36% of G-CSF- and G-CSF+ patients, respectively. The 3-year locoregional control and cause specific survival rates were 68% and 75%, respectively. CONCLUSIONS: This regimen was feasible and effective but caused severe mucositis. No benefit was derived from the addition of G-CSF. This regimen deserves further modification to reduce acute mucositis toxicity yet maintain the high locoregional control rate.

Use of the melolabial flap in intraoral reconstruction.

Functional reconstruction of the oral cavity after tumor ablation is challenging. A variety of methods are available for reconstruction including primary closure, skin grafts, local cutaneous flaps, musculocutaneous flaps, and free flaps. Appropriate reconstruction addresses the size, location, and tissue needs of the defect. The melolabial flap allows for reliable and effective intraoral reconstruction with minimal donor morbidity, making it ideal for select defects. From 1989 to 1993 16 patients aged 51 to 81 years underwent reconstruction of intraoral defects with 24 melolabial flaps. Twenty-two flaps survived without complication and two flaps failed, for success rate of 91.7%. The two failed flaps occurred in the same patient. Of the remaining patients 8 had prior radiation therapy and 11 had prior or concomitant neck dissections. The flaps were used to reconstruct 13 floor-of-mouth, 1 buccal mucosa, 1 retromolar trigone, and 1 gingival defect. We conclude that the melolabial flap is ideal for select intraoral defects.

Imaging of the postoperative neck with emphasis on surgical flaps and their complications.

Radiologists are playing an increasingly important role in the management of patients with head and neck cancer. Imaging is often essential in preoperative planning. It is therefore imperative for the radiologist to be familiar with the wide variety of surgical procedures used as well as the normal CT and MR imaging appearance after such procedures. In addition, familiarity with the appearance of tumor recurrence and postoperative complications is essential. This pictorial essay illustrates the appearance of the normal and abnormal postoperative neck on CT scans and MR images, with an emphasis on reconstructive flaps. Postoperative complications evident on imaging studies are depicted, as is the appearance of tumor recurrence. One lymph node classification system is briefly reviewed as a basis for discussion of neck dissection and other surgical procedures.

Nutritional management of the head and neck cancer patient.

Approximately one third of patients with advanced cancer of the head and neck are severely malnourished. Another one third of patients suffer from mild malnutrition. Adequate nutritional support given before cancer therapy will reduce therapy-related complications in severely malnourished patients. Patients who are less severely malnourished should receive definitive cancer therapy promptly with concurrent concern for nutritional support. Advantages of nutritional support are that patients feel better, have a higher tolerance to therapy with fewer complications, and achieve a higher response rate to therapy. The disadvantages to such a program are modest but real. This therapy is expensive and it is hard to prove its long-term benefit. Attempting treatment may be frustrating in poorly motivated patients. Appropriate delivery of nutritional support in selected patients has been determined as highly rewarding to the physician.