David I. Kutler

Re: Human Papillomavirus DNA and p53 Polymorphisms in Squamous Cell Carcinomas From Fanconi Anemia Patients

Fanconi anemia is an autosomal recessive disorder characterized by congenital malformations, bone marrow failure, and the development of squamous cell carcinomas (SCCs) and other cancers. Recent clinicopathologic evidence has raised the possibility that an environmental factor such as human papillomavirus (HPV) may be involved in the pathogenesis of SCCs in Fanconi anemia patients. Given the high prevalence of p53 mutations in SCCs among the general population and the lack of p53 mutations in HPV-related carcinogenesis, we evaluated the role of HPV and p53 mutations and polymorphisms in SCC from Fanconi anemia patients. We used polymerase chain reaction (PCR) screening and real-time PCR to detect and quantify HPV DNA in DNA extracted from microdissected SCCs obtained from 24 Fanconi anemia patients (n = 25 SCCs; case subjects) and 50 age-, sex-, and tumor site-matched SCC patients without Fanconi anemia (n = 50 SCCs; control subjects). We PCR-amplified and sequenced exons 4-9 of the p53 gene from SCC DNA. We detected HPV DNA in 84% of the SCC specimens from the case subjects and in 36% of the SCC specimens from the control subjects (P<.001). The prevalence of p53 mutations in SCCs from the case subjects (0%, 0/25) was statistically significantly lower than that of SCCs from the control subjects (36%, 12/33; P<.001). A greater proportion of patients with Fanconi anemia and SCC were homozygous for Arg72, a p53 polymorphism that may be associated with increased risk for HPV-associated human malignancies, than an ethnically-matched cohort of Fanconi anemia patients without SCC (75% versus 51%; P =.05). These data suggest that Fanconi anemia is associated with increased susceptibility to HPV-induced carcinogenesis.

Parathyroid localization with modified 4D-computed tomography and ultrasonography for patients with primary hyperparathyroidism†

In this article, we report our decade‐long experience in using modified 4D‐computed tomography in combination with ultrasonography (Mod 4D‐CT/US) to localize abnormal parathyroid glands in patients with primary hyperparathyroidism.

Sialoendoscopy in the diagnosis and management of obstructive sialadenitis

Sialoendoscopy is a new technology being used at a limited number of institutions for the diagnosis and management of obstructive sialadenitis. This technique is promising for its superior diagnostic potential as well as its decreased morbidity compared to traditional more invasive techniques for managing obstruction. Our objective is to review the sialoendoscopy experience at our institution to identify successes, areas of improvement, and to provide guidance to other programs that may be interested in sialoendoscopy.

Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma.

OBJECTIVE To describe the complications and adverse effects of postoperative radiotherapy in patients with Fanconi anemia (FA). DESIGN Cohort study. SETTING Patients with FA treated at community and tertiary care hospitals throughout the United States. PATIENTS The study included patients with FA who were enrolled in the International FA Registry (IFAR) and who developed head and neck squamous cell carcinoma and received postoperative radiotherapy. MAIN OUTCOME MEASURES Demographics of patients with FA and adverse effects and dosages of radiotherapy. RESULTS Twelve patients with FA (7 men and 5 women) were identified. They developed cancers at a mean age of 35.5 years (age range, 20-48 years). The sites of primary cancer were the oral cavity (n = 8), larynx (n = 2), pharynx (n = 1), and unknown (n = 1). The median radiation dose was 5590 cGy (range, 2500-7020 cGy). The most common adverse effects were mucositis (n = 9), dysphagia (n = 8), and pancytopenia (n = 6). Other complications included esophageal stenosis, laryngeal edema, and wound breakdown. Radiotherapy could not be completed in 5 cases. Overall, 8 patients died, 4 during the course of radiotherapy. The postoperative disease-free survival time ranged from 0 to 55 months. CONCLUSIONS Patients with FA have a high rate of complications from radiotherapy. Common adverse effects, particularly mucositis, are especially prevalent and difficult to manage in this population. Pancytopenia is common and may lead to further complications, particularly bleeding and infection. Overall survival is poor. Further study of the response to radiotherapy in patients with FA should be attempted to establish appropriate dosages to balance treating disease while limiting adverse effects.

Routine central compartment lymph node dissection for patients with papillary thyroid carcinoma

The role of routine central compartment neck dissection in papillary thyroid cancer is controversial.

Localization of Small Parathyroid Adenomas Using Modified 4-Dimensional Computed Tomography/Ultrasound

Objective. To investigate whether parathyroid gland weight has an impact on the accuracy of preoperative localization of parathyroid adenomas with modified 4 dimensional computed tomography/ultrasound. And to determine if the weight of parathyroid adenomas can be calculated accurately based on the dimensions of the gland on the CT images. Study Design. Case series with chart review. Setting. Tertiary care hospital. Subjects and Methods. One hundred forty-two patients who had a preoperative modified 4-dimensional computed tomography/ultrasound and underwent parathyroidectomy for hyperparathyroidism due to a parathyroid adenoma between 1998 and 2009. Charts were reviewed to identify (1) the sensitivity and specificity for localization of parathyroid adenomas according to gland weight and (2) correlation between preoperative estimate of parathyroid weight and the surgical weight of the parathyroid gland. Results. Modified 4-dimensional computed tomography/ultrasound displayed 92% sensitivity for localizing adenomas weighing <150 mg to the correct side of the neck (95% confidence interval [CI], 65%-99%), 100% sensitivity for glands weighing 150 to 500 mg (95%-100%), and 98% sensitivity for glands weighing >500 mg (92%-100%). For localization to the correct quadrant of the neck, sensitivity was 75% (95% CI, 47%-91%) for glands weighing <150 mg, 89% (79%-95%) for those weighing 150 to 500 mg, and 94% (85%-97%) for glands weighing >500 mg. A positive correlation was seen between the preoperative weight estimate based on imaging and the operative weight of the gland, with a Pearson correlation coefficient of 0.96. Conclusion. Modified 4-dimensional computed tomography/ultrasound can closely predict the weight of parathyroid glands preoperatively and has good sensitivity for localization of adenomas, even in glands weighing less than 150 mg.

Natural history and management of Fanconi anemia patients with head and neck cancer: A 10 year follow‐up

To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma.

Cesium-131 permanent seed brachytherapy: Dosimetric evaluation and radiation exposure to surgeons, radiation oncologists, and staff

PURPOSE Cesium-131 ((131)Cs) radioactive seed is Food and Drug Administration approved for permanent seed implant for all cancers, including lung and head and neck (HN) cancers. We describe the first clinical report of (131)Cs dosimetry and exposure rates to treating physicians and staff. METHODS AND MATERIALS Twenty-eight patients received (131)Cs implant for early stage lung and recurrent HN cancers. A nomogram was developed to calculate the number of seeds needed to cover the wedge line with the prescription dose (80 Gy). Final dosimetry was obtained after CT planning a few days following the surgical procedure. Radiation exposure to the treating physicians and staff was measured at the completion of the procedure. RESULTS A nomogram was developed using the variseed software with source data from American Association of Physicists in Medicine TG-43 report. The total volume covered by the prescription isodose line of (131)Cs was measured and compared with (125)I. The prescription volume was smaller for (131)Cs. In addition, the exposure rate with (131)Cs was found to be acceptable. CONCLUSION Our preliminary experience with (131)Cs lung and HN brachytherapy has been very encouraging with excellent dosimetric coverage and acceptable exposure to the treating physicians and staff.

Factors Predictive of Voice and Swallowing Outcomes after Anterior Approaches to the Cervical Spine

Objective To quantify the incidence of postoperative voice, swallowing, and other problems, including time to resolution following anterior transcervical approaches to the cervical spine, and to assess surgical factors associated with outcomes. Study Design Historical cohort study. Setting Academic medical center. Subjects and Methods One hundred eighty-eight consecutive patients with cervical spine disease who underwent an anterior transcervical approach to the spine by a single head and neck surgeon over a 4-year time period. Rather than primary, single-level approaches, all patients in this study had multilevel, high-cervical (above C4), low-cervical (below C6), and/or revision approaches. Postoperative voice, swallowing, and other complaints were measured as well as time to resolution using Kaplan-Meier method. Surgical factors related to outcomes were analyzed using regression analysis. Results Follow-up was available for 129 patients, with average and median time of 35 months. Seventy-seven patients (60%) had a postoperative issue, including 35 patients (27%) with postoperative voice complaint, 62 patients (48%) with postoperative swallowing complaint, and 16 patients (12%) with other problems. Swallowing and voice complaints persisted beyond 1 year in 28% and 9% of patients, respectively. Approaching spinal levels above C4 and exposing more than 3 spinal levels were 2 factors significantly related to voice and swallowing problems. Conclusion There is a high incidence of subjective voice and swallowing complaints following transcervical anterior approaches to the spine, and such complaints can persist beyond 1 year in many patients. Exposure of more than 3 spinal levels or above level C4 are 2 factors significantly associated with outcome.

Adoption of transoral robotic surgery compared with other surgical modalities for treatment of oropharyngeal squamous cell carcinoma.

Transoral robotic surgery (TORS) has increased for treatment of oropharyngeal squamous cell carcinoma (OPSCC). To define the adoption of TORS, we analyzed patterns of surgical treatment for OPSCC in the US.