John M. Truelson

Predictive markers for response to chemotherapy, organ preservation, and survival in patients with advanced laryngeal carcinoma.

OBJECTIVE: A systematic retrospective study of the largest randomized trial of induction chemotherapy and radiation for advanced laryngeal cancer was undertaken to determine whether specific tumor or biologic factors were predictive of chemotherapy response, organ preservation, or survival. METHODS: The variables analyzed included clinical and histologic factors, immunohistochemical expression of proliferating cell nuclear antigen and p53, and adjusted DNA index measurements. Variables were evaluated for correlation with outcomes of tumor response, organ preservation, and survival. RESULTS: Multivariate analysis revealed that the best predictor of complete response to induction chemotherapy was low T class. The full multivariate model for predicting larynx preservation in patients treated with induction chemotherapy plus radiation shows that T class, p53 overexpression, and elevated proliferating cell nuclear antigen index were independent predictors of successful organ preservation. CONCLUSIONS: These predictive markers should be included in future clinical trials of advanced laryngeal cancer to determine their usefulness prospectively.

DNA Content and histologic growth pattern correlate with prognosis in patients with advanced squamous cell carcinoma of the larynx

Background. Alterations in DNA content, nuclear morphologic characteristics, and histologic grading have been associated with prognosis in several types of solid malignant neoplasms.

Genetic alterations of chromosome band 9p21-22 in head and neck cancer are not restricted to p16INK4a

Although genetic alterations of chromosome band 9p21 – 22 occur frequently in head and neck squamous cell carcinoma (HNSCC) cell lines, alterations of the cyclin-dependent kinase inhibitor p16INK4a located in this region are less common in corresponding primary tumors. To further investigate genetic alterations at 9p21 – 22 and p16INK4a in primary HNSCC, a paired set of 21 tumors and blood specimens that were shown previously to exhibit allelic loss at 3p and elsewhere, were tested for LOH at 9p21 – 22 using eight different highly polymorphic marker. Sixteen of the samples (81%) exhibited LOH for at least one marker. Frequent LOH was found surrounding p16INK4a and at three additional non-contiguous regions of 9p21 – 22. No homozygous deletions were identified. SSCP screening and direct sequence analysis led to the identification of mutations the p16INK4a gene in two tumors. p16INK4a was not hypermethylated in any of the samples studied. Furthermore, there was no correlation between LOH at 9p21 – 22 and the RB1 tumor suppressor gene. These findings indicate that in the set of tumors that we tested, LOH at 9p21 – 22 is common in primary HNSCC but that genetic alterations of p16INK4a located in this region are unusual. Additional tumor suppressor genes at 9p21 – 22 may therefore be involved in the pathogenesis of this tumor.

DNA content and regional metastases in patients with advanced laryngeal squamous carcinoma

Abnormal DNA content of cancer cells in a primary tumor is thought to reflect the altered proliferative capacity of that cancer and overall patient prognosis. Recently, increased DNA content has been associated with early tumor recurrence in patients with advanced laryngeal cancer. To determine if DNA content correlates with a tumors metastatic behavior, 94 previously untreated patients with stage III (n = 54) or stage IV (n = 40) squamous carcinoma of the larynx were prospectively studied. The adjusted DNA index (aDI) of the primary tumor was measured by computerized cytomorphometry, and correlations with regional metastases, number of positive nodes, extracapsular spread, and pattern of relapse were determined. Median follow‐up was 35 months. Of 94 patients, 73 underwent neck dissection. Positive nodes were found in 51 patients (70%) and three or more positive nodes were found in 31 patients (42%). High aDI (>.024) was significantly associated with the presence and number of histologically positive nodes (P = .016). Among patients with high aDI, 19 (50%) of 38 had three or more nodes positive compared to 12 (21%) of 56 of those with low aDI. Median aDI levels in patients with three or more nodes were significantly higher than in patients with 1 or 2 nodes (P = .003). Time to recurrence was shorter in patients with high aDI (P = .0078). These findings provide further evidence that increased DNA content is associated with more aggressive laryngeal cancers having high rates of multiple lymph node metastases and worse overall prognosis.

Correlation Between Intraoperative Hypothermia and Perioperative Morbidity in Patients With Head and Neck Cancer

OBJECTIVE To determine if intraoperative hypothermia correlates with perioperative complications in patients undergoing head and neck surgery with regional or free flap reconstructions. DESIGN Retrospective medical chart review. SETTING Academic tertiary care hospital. PATIENTS A sample of 136 patients who underwent ablative surgery for head and neck cancer and subsequently required reconstruction with free tissue or a regional flap in the last 10 years. MAIN OUTCOME MEASURES Rate of early (within 3 weeks of surgery) perioperative complications and its correlation with patient hypothermia (core body temperature, <35 degrees C). RESULTS There were 43 patients with complications. Two patients died. Complications included 10 partial or total flap losses, 9 hematomas, 8 episodes of pneumonia, 7 fistulas, 7 wound infections, 5 wound breakdowns, and 2 cerebrospinal fluid leaks. Factors that did not correlate with complications included having received prior chemotherapy (P = .84), having stage IV cancer (P = .16), sex (P = .43), tobacco use (P = .58), prior radiotherapy (P = .30), the presence of comorbidities (P = .43), age (P = .27), length of surgery (P = .63), and the use of blood products perioperatively (P = .73). Patients who were hypothermic had a significantly higher rate of complications that normothermic patients (P = .002). Stepwise logistic regression analysis identified intraoperative hypothermia as a significant independent predictor for the development of early perioperative complications (odds ratio, 5.122; 95% confidence interval, 1.317-19.917). CONCLUSIONS Intraoperative hypothermia in head and neck surgery is correlated with perioperative complications. Maintaining normothermia through aggressive warming may decrease the incidence of perioperative morbidity for these patients.

Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum.

Objectives: This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum.

Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma

Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10 157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of different origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidentified tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.

Predictive value of objective esophageal insufflation testing for acquisition of tracheoesophageal speech

This prospective study was undertaken to assess the predictive value of esophageal insufflation on the acquisition of tracheoesophageal (TE) speech. Fourteen total laryngectomy patients were evaluated prior to tracheoesophageal puncture (TEP) using objective esophageal pressure measurements. These patients then were followed prospectively for 6 to 13 months. Speech was assessed at the time of prosthesis fitting, at 1 month, at less than 6 months, and at greater than 6 months post‐TEP. No patient underwent pharyngeal myotomy. Pre‐TEP esophageal insufflation pressure was associated (P = .065) with successful TE speech at the time of prosthesis fitting, but was not associated with successful TE speech acquisition after 6 months. This studys results suggest that patients with poor pre‐TEP esophageal insufflation test results will usually obtain successful TE speech given adequate time and training, even without pharyngeal myotomy.

Management of middle meningeal and superficial temporal artery hemorrhage from total temporomandibular joint replacement surgery with a gelatin-based hemostatic agent

Complications associated with temporomandibular joint (TMJ) replacement surgery may include injury to nerves, blood vessels, and otologic structures. Vascular injuries can be associated with trauma to the carotid artery and its terminal branches, the superficial temporal artery, and the internal maxillary artery. Suggested management to control hemorrhage has included uniand bipolar electrocautery, laser ablation, local anesthetics with vasoconstrictors, direct pressure, embolization, and ligation. In this case report, the iatrogenic injury to both the middle meningeal and superficial temporal arteries during total TMJ replacement surgery controlled by using a gelatin-based hemostatic agent is discussed.

Patterns of regional metastasis in advanced stage cutaneous squamous cell carcinoma of the auricle

Objective. To determine patterns of regional metastasis in patients with advanced stage cutaneous squamous cell carcinoma of the auricle. Study Design. Case series with chart review. Setting. University-based tertiary care hospitals. Subjects and Methods. We analyzed 41 patients with stage III and IV squamous cell carcinoma of the auricle. Results. The mean age was 74.2 years (range, 20.6-91.7 years). Thirty-five patients (85.4%) were stage IV. Twenty-nine patients (70.7%) had a prior history of nonauricular, nonmelanotic skin carcinoma. Twenty-four patients (58.5%) had regional metastasis to either the cervical or parotid nodal basin. In patients with cervical metastasis, the involvement by level was 6.7% (n = 1), 80.0% (n = 12), 46.6% (n = 7), 13.3% (n = 2), and 40.0% (n = 6), respectively. Of the 6 patients with a level 5 metastasis, 3 had primaries in the preauricular region, 2 had primaries of the auricle, and 1 had a primary of the postauricular region. Occult disease was present in 2 patients (9.1%) with cervical metastasis and in 4 patients (18.2%) with periparotid lymph node metastasis. Perineural invasion was seen in 84.4% of the study population. The recurrence rate was 46.3% (n = 19). The median time to recurrence was 28.3 months. Conclusion. Patients with advanced stage auricular cutaneous squamous cell carcinoma have a high rate of regional metastasis and recurrence. When planning neck dissections for these patients, level 5 should be included in the resection. Patients demonstrating locally advanced disease without clinical or radiographic evidence of metastasis to the parotid or cervical drainage basin should undergo a parotidectomy and comprehensive neck dissection.