Mark L. Urken

Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival.

To analyze the impact of resection margin status and histologic prognosticators on local recurrence (LR) and overall survival (OS) for patients with oral squamous cell carcinoma (OSCC). This study was both retrospective and prospective in design. Cohort 1 refers to the entire group of 292 patients with OSCC. The slides from the earliest resection specimens from Cohort 1 were examined in an exploratory manner for multiple parameters. Cohort 2 refers to a subset of 203 patients, who did not receive any neoadjuvant therapy and had outcome data. Cohort 3 represents a subset of Cohort 2 (n = 168) wherein the histologic resection margin status could be reconfirmed. Cohort 4 refers a subset of 85 patients with tongue/floor of mouth tumors. Margin status was designated as follows: group 1, clearance of ≥5 mm with intraoperative analysis, no need for supplemental margins (n = 46); group 2, initial margins were measured as <5 mm during intraoperative frozen section; supplemental resection margins were negative on final pathology (n = 73); group 3, the final pathology revealed resection margins <5 mm (n = 30); group 4, the final pathology revealed frankly positive resection margins (n = 19). The endpoints of LR and OS were queried with respect to T stage, tumor site, margin status, and numerous histologic variables, by Cox regression and Kaplan-Meier survival analyses. Tumor stage (T) was significantly associated with LR (P = 0.028). Kaplan-Meier analysis for stage and for intraoral site was significantly associated with LR for T4 tumors. The increased likelihood of LR was higher for T4 OSCC of the buccal mucosa (75%), sinopalate (50%), and gingiva (100%) compared with mobile tongue (27%), and oropharynx (13%) (P = 0.013). Margin status was not associated with LR or OS (Cohort 3). This was so when all tumors were grouped together and when separate analyses were performed by tumor stage and oral subsite. No significance was demonstrated when margin status was examined for patients with similar treatment (surgery alone or surgery with adjuvant RT). However, the administration of adjuvant RT did significantly increase local disease-free survival (P = 0.0027 and P = 0.001 for T1 and T2 SCC, respectively). On exploratory analyses of histologic parameters, worst pattern of invasion was significantly associated with LR (P = 0.015) and OS (P < 0.001). Perineural invasion involving large nerves (>1 mm) was associated with LR (P = 0.005) and OS (P = 0.039). Limited lymphocytic response was also significantly associated with LR (P = 0.005) and OS (P = 0.001). When used as covariates in a multivariate Cox regression model, worst pattern of invasion, perineural invasion, and lymphocytic response were significant and independent predictors of both LR and OS, even when adjusting for margin status. Thus, these factors were used to generate our risk assessment. Our risk assessment classified patients into low-, intermediate-, or high-risk groups, with respect to LR (P = 0.0004) and OS (P < 0.0001). This classification retained significance when examining patients with uniform treatment. In separate analyses for each risk group, we found that administration of adjuvant radiation therapy is associated with increased local disease-free survival for high-risk patients only (P = 0.0296) but not low-risk or intermediate-risk patients. Resection margin status alone is not an independent predictor of LR and cannot be the sole variable in the decision-making process regarding adjuvant radiation therapy. We suggest that the recommendation for adjuvant radiation therapy be based on, not only traditional factors (inadequate margin, perineural invasion, bone invasion) but also histologic risk assessment. If clinicians want to avoid the debilitation of adjuvant radiation therapy, then a 5-mm margin standard may not be effective in the presence of high-risk score.

Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to ones “own” criteria, and then according to the AFIP criteria proposed by Goode et al. 10 Weighted kappa (&kgr;) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15–86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their “own” grading, as expressed by the &kgr; value, ranged from good agreement (&kgr; = 0.79) to poor (&kgr; = 0.27) (average &kgr; = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average &kgr; = 0.61, range 0.38–0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using ones own grading systems (p = 0.0001) but not in applying the AFIP “standardized” grading (p = 0.33). When ones own grading was compared with the AFIP grading, there were 100 pairs of grading “events,” with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading “downgraded” tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: A comparative study of reconstructed and nonreconstructed patients

Over the past decade, the use of free flap transfers in head and neck surgery has led to remarkable advances in the reliability and the ultimate results of oromandibular reconstruction. Stable and retentive dental restorations have been achieved using enosseous implants placed directly into the vascularized bone flaps. However, the functional assessment of patients who underwent primary mandibular reconstruction with these techniques has not been previously reported. A group of 10 reconstructed and 10 nonreconstructed segmental hemimandibulectomy patients were compared using a battery of tests to assess their overall well‐being, cosmesis, deglutition, oral competence, speech, length of hospitalization, and dental rehabilitation. In addition, objective measures of the masticatory apparatus (interincisal opening, bite force, chewing performance, and chewing stroke) were used to compare these two groups as well as normal healthy subjects and edentulous patients restored with conventional and implant‐borne dentures. The results show a clear advantage for the reconstructed patients in almost all categories. Persistent problems and future directions in oromandibular reconstruction are discussed.

The neurofasciocutaneous radial forearm flap in head and neck reconstruction: A preliminary report

The radial forearm free flap has achieved considerable popularity as a reconstructive technique due to its thin, pliable tissue and long vascular pedicle. The successful use of this flap as a carrier of a vascularized nerve to bridge motor nerve gaps and as a sensate flap has not been previously reported in head and neck reconstruction. The superficial branch of the radial nerve was used as a vascularized nerve graft to bridge a facial nerve defect following radical parotidectomy. The medial and lateral antebrachial cutaneous nerves were used to re‐establish sensation in a reconstructed pharyngeal mucosal defect. The published clinical and experimental studies on vascularized nerves and sen‐sate flaps are reviewed in detail.

Atlas of regional and free flaps for head and neck reconstruction

Documenting in unprecedented detail the surgical procedures, techniques, and approaches used by the experts, this new atlas/text is the definitive full-color pictorial reference on major flap transfers for reconstructive head-and-neck surgery. The book chronicles three decades of innovations and progress in the field, and presents detailed descriptions of anatomy and anatomical variations, step-by-step guidance on identifying and preparing appropriate donor and recipient sites, and techniques for successfully grafting selected tissue. This one-of-a-kind atlas covers the spectrum of donor sites most frequently used in head-and-neck surgery, and through more than 300 color illustrations and a concise narrative text, the authors provide step-by-step guidance and invaluable technical advice. Each chapter includes the details of normal donor site anatomy as well as anatomic variations, and every section of the book presents the most important options in flap design and the most optimal and desirable application. The text also addresses important topics such as pre- and postoperative care and potential pitfalls and complications

Primary Placement of Osseointegrated Implants in Microvascular Mandibular Reconstruction

The goal of mandibular reconstruction is to rehabilitate the patient by restoring occlusal relationships, lower facial contour, oral continence, and a denture-bearing surface. One of the major advantages of the use of vascularized bone over all other methods of mandibular reconstruction is its ability to achieve dental rehabilitation rapidly. The use of osseointegrated dental implants is a valuable adjunct in oral rehabilitation. It provides the most rigid form of stabilization to withstand the forces of mastication. In situations In which soft tissue reconstruction or the height of the alveolar ridge is not sufficient for a tissue-borne denture, implants offer the most suitable alternative. Mandibular reconstruction with free tissue transfer techniques is Ideally suited for the placement of implants. These can be inserted at the time of mandibular reconstruction. Four months after surgery, when the integration process has occurred, the implants are unroofed, loaded, and ready for prosthetic placement. We will present several representative patients who underwent mandibular reconstruction with microvascular free bone transfer who have been successfully rehabilitated by osseointegrated implants. The process of osseointegration, different types of dental implants, and issues regarding radiation and Implants are discussed. This is the first report of dental rehabilitation by primary placement of dental implants in patients undergoing microvascular mandibular reconstruction.

American Thyroid Association statement on outpatient thyroidectomy.

BACKGROUND The primary goals of this interdisciplinary consensus statement are to define the eligibility criteria for outpatient thyroidectomy and to explore preoperative, intraoperative, and postoperative factors that should be considered in order to optimize the safe and efficient performance of ambulatory surgery. SUMMARY A series of criteria was developed that may represent relative contraindications to outpatient thyroidectomy, and these fell into the following broad categories: clinical, social, and procedural issues. Intraoperative factors that bear consideration are enumerated, and include choice of anesthesia, use of nerve monitoring, hemostasis, management of the parathyroid glands, wound closure, and extubation. Importantly, postoperative factors are described at length, including suggested discharge criteria and recognition of complications, especially bleeding, airway distress, and hypocalcemia. CONCLUSIONS Outpatient thyroidectomy may be undertaken safely in a carefully selected patient population provided that certain precautionary measures are taken to maximize communication and minimize the likelihood of complications.

The combined sensate radial forearm and iliac crest free flaps for reconstruction of significant glossectomy‐mandibulectomy defects

The loss of motor and sensory function of the tongue following ablative surgery has a devastating effect on oral function. At the present time, there is no way to restore lost tongue musculature following partial glossectomy. The use of sensate cutaneous flaps has been shown to restore sensory feedback to reconstructed areas of the oral cavity. No single composite flap supplies a sensate soft‐tissue component together with an osseous component of sufficient bone stock for functional mastication. In this article, the combination of the radial forearm free flap with the iliac crest osteocutaneous or osteomyocutaneous free flap is reported. The radial forearm free flap was used to resurface the resected portion of the tongue to provide maximum mobility and sensation. The lingual nerve was the recipient nerve for anastomosis to the antebrachial cutaneous nerves in all but one case. The iliac bone was used to reconstruct the mandible, with the iliac skin paddle or the internal oblique muscle used to reconstruct the neoridge. This combination of flaps was used in 10 patients. There was one flap failure due to vascular kinking from“piggybacking” the iliac crest to the distal end of the radial forearm flap. As a result, the use of two separate sets of recipient vessels is now advocated.

Low-grade salivary duct carcinoma: description of 16 cases.

Low-grade salivary duct carcinoma is a rare neoplasm. We report on 16 patients, with a median age of 64 years. All but one tumor arose from the parotid gland, including one tumor that arose in an intraparotid lymph node; one arose in the submandibular gland. Tumors consist of single to multiple dominant cysts, accompanied by adjacent intraductal proliferation. Cysts are lined by small, multilayered, proliferating, bland ductal cells with finely dispersed chromatin and small nucleoli. Separate, smaller ductal structures are variably filled by proliferating ductal epithelium with cribriform, micropapillary, and solid areas. The overall appearance is very similar to breast atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Foci of definitive stromal invasion were seen in four tumors. Two tumors demonstrated transition from low- to intermediate- or high-grade cytology, with scattered mitotic figures and focal necrosis. S-100 revealed diffuse strong expression in all 9 cases studied. Myoepithelial markers (calponin) highlighted supportive myoepithelial cells rimming the cystic spaces, confirming the intraductal nature of most, or all, of six tumors studied. Nine tumors studied for Her2-neu antigen were uniformly negative. Follow-up was obtained on 13 of our 16 patients. All patients were disease-free after surgery 6 to 132 months (median 30 months). Low-grade salivary duct carcinoma is a low-grade neoplasm with an excellent prognosis; it may be treated by conservative but complete resection. Its resemblance to atypical breast ductal hyperplasia, or micropapillary/cribriform intraductal carcinoma, distinguishes it from high-grade salivary duct carcinoma, papillocystic acinic cell carcinoma, and cystadenocarcinoma.

Mobilization regimens for the prevention of jaw hypomobility in the radiated patient: A comparison of three techniques

This study evaluated and compared the Therabite Jaw Motion Rehabilitation System (Therabite Corporation, Bryn Mawr, PA) to tongue blades as a technique for maintaining and/or improving mandibular range of motion in post-irradiated patients. Three groups of patients were evaluated and compared: 1) unassisted exercise, 2) mechanically assisted mandibular mobilization with stacked tongue depressors combined with unassisted exercise, and 3) the Therabite System combined with unassisted exercise. The initial average maximum incisal opening (MIO) for the study population was 21.6 mm, and did not vary significantly among the groups. Measurements were recorded at 2-week intervals for 10 weeks. At week 6 and thereafter, the net increase in MIO of group 3 (13.6 mm [+/- 1.6 mm]) was significantly greater than group 1 (6.0 mm [+/- 1.8 mm]) and group 2 (4.4 mm [+/- 2.1 mm]) (P < .05). The rate of improvement leveled after 4 week in group 1 and group 2. However, the rate of gain in MIO in the Therabite group (group 3) remained constant at 10 weeks. There was no statistical difference between groups 1 and 2.