Vishad Nabili

SALIVARY DUCT CARCINOMA: A CLINICAL AND HISTOLOGIC REVIEW WITH IMPLICATIONS FOR TRASTUZUMAB THERAPY

Salivary duct carcinoma (SDC) is an aggressive tumor of the head and neck with a poor prognosis. The objective was to study SDC and recommend the use of trastuzumab as adjuvant therapy.

Prevalidation of Salivary Biomarkers for Oral Cancer Detection

Background: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL). Methods: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL. Results: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts. Conclusions: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. Impact: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. Cancer Epidemiol Biomarkers Prev; 21(4); 664–72. ©2012 AACR.

Comparison of Dental Health of Patients with Head and Neck Cancer Receiving IMRT vs Conventional Radiation

Objective To analyze the dental health of patients with head and neck cancer who received comprehensive dental care after intensity-modulated radiation therapy (IMRT) compared with radiation therapy (RT). Study Design Historical cohort study. Setting Veteran Affairs (VA) hospital. Subjects and Methods In total, 158 patients at a single VA hospital who were treated with RT or IMRT between 2003 and 2011 were identified. A complete dental evaluation was performed prior to radiation treatment, including periodontal probing, tooth profile, cavity check, and mobility. The dental treatment plan was formulated to eliminate current and potential dental disease. The rates of dental extractions, infections, caries, mucositis, xerostomia, and osteoradionecrosis (ORN) were analyzed, and a comparison was made between patients treated with IMRT and those treated with RT. Results Of the 158 patients, 99 were treated with RT and 59 were treated with IMRT. Compared with those treated with IMRT, significantly more patients treated with RT exhibited xerostomia (46.5% vs 16.9%; P < .001; odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.52), mucositis (46.5% vs 16.9%; P < .001; OR, 0.24; 95% CI, 0.11-0.52), and ORN (10.1% vs 0%; P = .014; OR, 0.07; 95% CI, 0.00-1.21). However, significantly more patients treated with IMRT were edentulous by the conclusion of radiation treatment (32.2% vs 11.1%; P = .002; OR, 3.8; 95% CI, 1.65-8.73). Conclusion Patients who were treated with IMRT had fewer instances of dental disease, more salivary flow, and fewer requisite posttreatment extractions compared with those treated with RT. The number of posttreatment extractions has been reduced with the advent of IMRT and more so with a complete dental evaluation prior to treatment.

Disease relapse after segmental resection and free flap reconstruction for mandibular osteoradionecrosis

Objective: The objective of this study was to assess the outcomes, complications, and incidence of disease recurrence of mandibular osteoradionecrosis (ORN) after resection and microvascular free flap reconstruction. Study Design: Case series with chart review. Setting: Academic medical center. Subjects And Methods: Retrospective patient data review of 40 patients with mandibular ORN who were treated by segmental mandibulectomy and microvascular reconstruction between 1995 and 2009. All patients received radiation therapy for previous head and neck cancer, and 12 of 40 patients received concurrent chemotherapy. All patients failed to respond to conservative management. There were 26 males and 14 females, with a median age of 62 years. Median follow-up was 17.4 months. Results: There were no free flap failures. The incidence of wound-related complications was 55 percent. Median time to complication was 10.6 months. Ten (25%) patients developed symptoms of residual or recurrent ORN, with 70 percent of the recurrences arising in unresected condyles that were adjacent to the segmental mandibulectomy. Statistical analysis revealed that current smokers were at reduced risk to develop residual or recurrent ORN. Conclusion: This present study confirms that microvascular free flaps are reliable for treatment of advanced mandibular ORN. Nevertheless, there remains a 55 percent incidence of wound-healing complications. The lack of objective clinical criteria to judge the appropriate amount of mandible resection in patients with ORN remains an unresolved issue that resulted in the development of recurrent ORN in 25 percent of patients. Further investigations are needed to better understand the pathophysiology of ORN to prevent postoperative wound complications and disease recurrence.

Animal model of radiogenic bone damage to study mandibular osteoradionecrosis.

OBJECTIVE The objective of the study was to create an animal model to study mandibular osteoradionecrosis (ORN) using high-dose rate (HDR) brachytherapy. METHODS Ten Sprague-Dawley male rats were used in this study. Six rats received a single dose of 30 Gy using an HDR remote afterloading machine via a brachytherapy catheter placed along the left hemimandible. The remaining 4 rats served as controls with catheter placement without radiation (sham). On the day following irradiation or sham, all 3 left mandibular molars were atraumatically extracted. Twenty-eight days after irradiation, mandibles were examined using nondecalcified histology with sequential fluorochrome labeling, decalcified histology, and micro-computed tomography scanning. RESULTS Irradiated rats demonstrated exposed bone at the extraction sockets, whereas the control animals had complete mucosalization. Alopecia was also seen in the irradiated group. Both histologic and radiologic analyses of the mandible specimens demonstrated a reduction in bone formation in the radiated mandibles as compared with controls. CONCLUSIONS Our HDR brachytherapy model incorporating postradiation dental extractions has successfully demonstrated reproducible radiogenic mandibular bone damage analogous to the clinical ORN. Although clinical criteria continue to be used today in describing ORN, this model can serve as a platform for future studies to define ORN and delineate its pathogenesis.

Perineural invasion detected by high-field 3.0-T magnetic resonance imaging

The presence of perineural invasion (PNI) with cutaneous squamous cell carcinoma portends a poor prognosis. PNI may be detected radiographically or clinically, with motor or sensory deficits, and is confirmed by histologic evaluation. Recent interest has grown regarding the role of imaging in determining the presence of PNI and its preoperative implications. We report on a patient with cutaneous squamous cell carcinoma invading the parotid gland with clinical evidence of facial nerve weakness. On standard 1.5 Tesla (T) magnetic resonance imaging (MRI), bilateral parotid glands were symmetric; however, a second high-field 3-T MRI revealed asymmetric enhancement of the left facial nerve at the stylomastoid foramen and extending throughout the left parotid gland. PNI was later confirmed on histopathology. The presurgical determination of PNI was essential in our mapping the exact tumor location and in our surgical planning.

Reirradiation after salvage surgery and microvascular free flap reconstruction for recurrent head and neck carcinoma

Objective To evaluate the outcome and complications of reirradiation of recurrent head and neck cancer after salvage surgery and microvascular reconstruction. Study Design Retrospective. Subjects and Methods Twelve patients underwent salvage surgery with microvascular reconstruction for recurrent or second primary head and neck cancer in a previously irradiated field. Median prior radiation therapy dose was 63.0 Gy. Patients then underwent postoperative reirradiation, and received a median total cumulative radiation dose of 115.0 Gy. Results Three (25%) patients experienced acute complications (<3 months) during reirradiation. Four (33%) patients developed grade 3 or 4 late reirradiation complications (>3 months). There were no incidences of free flap failure, brain necrosis, spinal cord injury, or carotid rupture. The incidence of soft tissue necrosis and osteoradionecrosis was 8%. Six (50%) patients are alive without evidence of recurrent disease a median of 40 months after reirradiation. Conclusion Microvascular free flaps allow for maximal resection and reliable reconstruction of previously irradiated cancers before high dose reirradiation and may reduce the incidence of severe late complications and treatment related mortality.

Standardized Analysis of Mandibular Osteoradionecrosis in a Rat Model

Objective. To develop a rat model of mandibular osteoradionecrosis (ORN) that uses novel micro-computed tomography bone volume analysis and detailed histology to provide a more effective, quantifiable, and standardized way to study ORN in vivo. Study Design. Animal model. Setting. Academic medical center. Subjects and Methods. Modifications to our previously published rat model of mandibular ORN were done to develop an ideal protocol consisting of 10 rats (6 experimental and 4 controls) with their left middle mandibular molar removed 7 days after either 20 Gy high dose rate brachytherapy or sham irradiation. Rats were sacrificed 21 days after extraction for landmark defined bone volume and histologic analysis. Results. A standardized method of quantification was achieved in all samples. The radiated group (XRT) had a mean bone volume/total volume (BV/TV) of 13.8% compared to 65.9% for controls (P < .001). There were increases in osteoclasts and fibrosis, decreases in osteoblasts, and less bone in radiated samples with a mean (SD) of 5.91 (3.77) osteoclasts/high-powered field (HPF) and 4.00 (1.83) osteoblasts/HPF in XRT samples compared to 1.08 (1.08) osteoclasts/HPF and 22.49 (6.00) osteoblasts/HPF for controls (P < .001). Conclusion. Our updated model continues to be clinically analogous to human mandibular ORN and improves the radiologic and histologic analysis of bony defects, providing a method for quantification of bone loss. Further cell-specific staining, including immunohistochemistry, can be used with this model to study potential cellular mechanisms of mandibular ORN and test any future therapeutic options.

Resolution of pain and complete healing of mandibular osteoradionecrosis using pentoxifylline and tocopherol: a case report

The radiation-induced fibroatrophic process (RIF) is a time-dependent adverse sequela to high-dose radiotherapy that can result in irreversible tissue death and bone exposure in the irradiated tissue. Osteoradionecrosis (ORN) is a late effect of RIF, described as bony exposure present for more than 3 months that can occur in 20% of patients irradiated for head and neck cancer. The intractable characteristics of ORN make both management and resolution of the disease process challenging, with 25% of cases recurring despite aggressive treatment with resection and reconstruction of the necrotic bone. In this article, we present a case of a 66-year-old man with unevoked ORN of the left posterior lingual mandibular cortex that was successfully treated and resolved with 6 months of pentoxifylline 400 mg twice a day and tocopherol 1000 IU every day.

Transnasal, transfacial, anterior skull base resection of olfactory neuroblastoma.

PURPOSE Using a transnasal, transfacial, anterior skull base approach, we have removed olfactory neuroblastomas (OFN) obviating the need for a frontal craniotomy. The objectives were to present our surgical approach in achieving clear margins, to assess patient survival, and to recommend eligibility criteria. MATERIALS AND METHODS A retrospective chart review was done to identify patients diagnosed with OFN who underwent this surgical approach. Thirteen patients were identified who underwent our pictorially described approach. Postoperative assessment of pathologic margins, patient survival, and limitations of surgical approach was determined. RESULTS Of the 13 patients, 12 (92%) had clear postsurgical margins. One patient had residual intracranial disease due to coagulopathy preventing further resection. Twelve patients remain alive with 10 patients remaining disease-free (follow-up ranging from 11 to 64 months). Three patients presented with recurrent disease initially, with 2 having had subsequent repeat local and regional recurrences, respectively; one of whom died recently of the re-recurrent disease. One patient had a postoperative cerebrospinal fluid leak repaired via the original surgical approach. CONCLUSIONS Although craniofacial resection remains an accepted approach for surgical treatment of OFN, we have adopted a transnasal, transfacial approach eliminating the need for a frontal craniotomy. This approach allows for adequate exposure of the cribriform plate, dura, and anterior skull base. Our technique minimizes dural defects and prevents many craniotomy-associated complications, including frontal lobe retraction. Long-term follow-up is needed to compare survival using this approach; however, our results to date are quite promising.