Anthony P. Tufaro

BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Biopsy Specimens for Preoperative Risk Stratification in Papillary Thyroid Cancer

PURPOSE This study investigated the utility of BRAF mutation testing of thyroid fine-needle aspiration biopsy (FNAB) specimens for preoperative risk stratification in papillary thyroid cancer (PTC). PATIENTS AND METHODS We assessed the T1799A BRAF mutation status in thyroid FNAB specimens obtained from 190 patients before thyroidectomy for PTC and its association with clinicopathologic characteristics of the tumor revealed postoperatively. RESULTS We observed a significant association of BRAF mutation in preoperative FNAB specimens with poorer clinicopathologic outcomes of PTC. In comparison with the wild-type allele, BRAF mutation strongly predicted extrathyroidal extension (23% v 11%; P = .039), thyroid capsular invasion (29% v 16%; P = .045), and lymph node metastasis (38% v 18%; P = .002). During a median follow-up of 3 years (range, 0.6 to 10 years), PTC persistence/recurrence was seen in 36% of BRAF mutation-positive patients versus 12% of BRAF mutation-negative patients, with an odds ratio of 4.16 (95% CI, 1.70 to 10.17; P = .002). The positive and negative predictive values for preoperative FNAB-detected BRAF mutation to predict PTC persistence/recurrence were 36% and 88% for overall PTC and 34% and 92% for conventional PTC, respectively. CONCLUSION Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence. BRAF mutation, as a powerful risk prognostic marker, may therefore be useful in appropriately tailoring the initial surgical extent for patients with PTC.

Craniofacial distraction osteogenesis: A review of 3278 cases

&NA; The nascent field of craniofacial distraction osteogenesis has not yet been subjected to a rigorous evaluation of techniques and outcomes. Consequently, many of the standard approaches to distraction have been borrowed from the experience with long bones in orthopedic surgery. The ideal “latency period” of neutral fixation, rate and rhythm of distraction, and consolidation period have not yet been determined for the human facial skeleton. In addition, because the individual craniofacial surgeons experience with distraction has generally been small, outcomes and meaningful complication rates have not yet been published. In this study, a four‐page questionnaire was sent to 2476 craniofacial and oral/maxillofacial surgeons throughout the world, asking about their experiences with distraction osteogenesis. Information about the types of cases, indications for surgery, surgical techniques, postoperative management, outcomes, and complications were tabulated. Of 274 respondents (response rate, 11.4 percent), 148 indicated that they used distraction in their surgical practice. One hundred forty‐five completed surveys were entered into a database that provided information about 3278 craniofacial distraction cases. Statistical analyses were performed comparing the rates of premature consolidation, fibrous nonunion, and nerve injury, on the basis of the use of a latency period and different rates and rhythms of distraction. In addition, the rates of all complications were determined and compared on the basis of the number of distraction cases performed per surgeon. The results of the study clearly show a wide variation in the surgical practice of craniofacial distraction osteogenesis. Although the cumulative complication rate was found to be 35.6 percent, there is a pronounced learning curve, with far fewer complications occurring among more experienced surgeons (p < 0.001). The presence of inferior alveolar nerve injury as a result of mandibular distraction was much lower for respondents whose distraction regimens consisted of no more than 1 mm of distraction per day (19.5 percent versus 2.4 percent; p < 0.001). No evidence was found to support the use of a latency period or to divide the daily distraction regimen into more than one session per day. Conclusions could not be drawn from this study regarding the length of the consolidation period. Overall, the surgeon‐reported outcomes are comparable with those published for other craniofacial procedures, despite the higher incidence of complications. Although conclusions made on the basis of a subjective questionnaire need to be interpreted cautiously, this study has strength in the large numbers of cases reviewed. Because of the anonymity of responses, it has been assumed that surgeons who responded to the survey reported accurate numbers of complications and successful outcomes. Finally, additional clinical and animal studies that will be of benefit in advancing the field of craniofacial distraction osteogenesis are outlined. (Plast. Reconstr. Surg. 108: 1103, 2001.)

A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: Creation and rationale for inclusion of tumor (T) characteristics

BACKGROUND The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. Although most patients achieve complete remission with surgical treatment, those with advanced disease have a poor prognosis. The American Joint Committee on Cancer (AJCC) is responsible for the staging criteria for all cancers. For the past 20 years, the AJCC cancer staging manual has grouped all nonmelanoma skin cancers, including cSCC, together for the purposes of staging. However, based on new evidence, the AJCC has determined that cSCC should have a separate staging system in the 7th edition AJCC staging manual. OBJECTIVE We sought to present the rationale for and characteristics of the new AJCC staging system specific to cSCC tumor characteristics (T). METHODS The Nonmelanoma Skin Cancer Task Force of AJCC reviewed relevant data and reached expert consensus in creating the 7th edition AJCC staging system for cSCC. Emphasis was placed on prospectively accumulated data and multivariate analyses. Concordance with head and neck cancer staging system was also achieved. RESULTS A new AJCC cSCC T classification is presented. The T classification is determined by tumor diameter, invasion into cranial bone, and high-risk features, including anatomic location, tumor thickness and level, differentiation, and perineural invasion. LIMITATIONS The data available for analysis are still suboptimal, with limited prospective outcomes trials and few multivariate analyses. CONCLUSIONS The new AJCC staging system for cSCC incorporates tumor-specific (T) staging features and will encourage coordinated, consistent collection of data that will be the basis of improved prognostic systems in the future.

Recipient Vessel Analysis for Microvascular Reconstruction of the Head and Neck

The selection of recipient vessels that are suitable for microvascular anastomosis in the head and neck region is one of many components that is essential for successful free tissue transfer. The purpose of this study was to evaluate a set of factors that are related to the recipient artery and vein and to determine how these factors influence flap survival. A retrospective review of 102 patients over a 5-year consecutive period was completed. Indications for microvascular reconstruction included tumor ablation (n = 76), trauma (n = 13), and chronic wounds or facial paralysis (n = 13). The most frequently used recipient artery and vein included the facial, superficial temporal, superior thyroid, carotid, and jugular. Various factors that were related to the recipient vessels were analyzed and included patient age, recipient artery and vein, diabetes mellitus, tobacco use, the timing of reconstruction, the method of anastomosis, previous radiation therapy, creation of an arteriovenous loop, and use of an interposition vein graft. Successful free tissue transfer was obtained in 97 of 102 flaps (95%). Flap failure was the result of venous thrombosis in 4 and arterial thrombosis in 1. Statistical analysis demonstrated that anastomotic failure was associated with an arteriovenous loop (2 of 5, P = 0.03) and tobacco use (3 of 5, P = 0.03). Flap failure was not related to patient age, choice of recipient vessel, diabetes mellitus, previous irradiation, the method of arterial or venous anastomosis, use of an interposition vein graft, or the timing of reconstruction.

Recalcitrant abdominal wall hernias: long-term superiority of autologous tissue repair.

Secondary repair of recurrent ventral hernia is difficult, and success depends on re-establishing the functional integrity of the abdominal wall. Current techniques used for closure of these defects have documented recurrence rates as high as 54 percent. The authors’ 8-year experience utilizing variations of the components separation technique for autologous tissue repair of recalcitrant hernias emphasizes that recurrent or recalcitrant hernias benefit from the creation of a dynamic abdominal wall. A total of 389 patients were retrospectively identified as having abdominal wall defects, and 284 of these patients met the selection criteria. Study patients were grouped according to the type of surgical repair used. The recurrence rate was 20.7 percent over all study groups and was directly related to the extent of repair required. Group 1 patients (wide tissue undermining) had a recurrence rate of only 15 percent, while in group 2 (complete components separation), the recurrence rate was 22 percent. Group 3 patients (interpositional fascia lata graft) had a 29 percent recurrence rate. Time to recurrence was also significantly different across treatment groups, with study group 3 experiencing earlier hernia recurrence. The most frequent postoperative complication was wound infection, which was directly related to the repair performed. The relative odds of recurrence versus the risk factors of age, sex, perioperative steroid use, wound infection, defect size, and the presence of enterocutaneous fistula were studied with a logistic regression analysis. These factors did not possess statistical significance for predicting hernia recurrence. The preoperative presence of mesh was independently significant for hernia recurrence, increasing the relative odds 2.2 times (p = 0.01). Similarly, when other risk factors were controlled for, increasing the complexity of the treatment group, from study group 1 (wide tissue undermining) to study group 3 (interpositional fascia lata graft), also increased the odds of hernia recurrence 1.5-fold per group (p = 0.04). Average inpatient cost was

The use of artificial dermis in the reconstruction of oncologic surgical defects.

24,488. The length of inpatient stay ranged from 2 to 172 days (average, 12.8 days). The length of inpatient stay and costs were directly related to the extent of repair required. Using the analysis of variance test for multiple factors, the presence of an enterocutaneous fistula (p = 0.0014) or a postoperative wound infection (p = 0.008) independently increased the length of inpatient stay and hospital costs. A total of 108 successfully repaired patients were contacted by telephone and agreed to participate in a self-reported satisfaction survey. The patients noticed improvements in the appearance of their abdomen, in their postoperative emotional state, and in their ability to lift objects, arise from a chair or a bed, and exercise. These results suggest that recalcitrant hernia defects should be solved, when possible, by reconstructing a dynamic abdominal wall.

Correlation of plasma 25-hydroxyvitamin D levels with severity of primary hyperparathyroidism and likelihood of parathyroid adenoma localization on sestamibi scan.

Background: Integra dermal substitute has been used in burn reconstruction with great success. Its use in general reconstruction is currently being reported. The authors set out to evaluate the utility of Integra in the reconstruction and resurfacing of defects created by tumor excision. Methods: Since 2003, 17 patients with soft-tissue tumors involving the head and neck, lower extremity, and anterior chest wall underwent tumor resection and reconstruction with Integra dermal substitute. These patients were followed and clinical outcomes were assessed. Results: Seventeen patients with a mean age of 54 ± 21 years underwent tumor resection and reconstruction with Integra dermal substitute. Twelve patients (71 percent) were male and five (29 percent) were female. Twelve cases (71 percent) involved recurrent tumor resection. The 17 cases involved 10 different tumor types at six different anatomical locations. The mean defect size was 172 ± 260 cm2 (range, 20 to 1080 cm2). The second stage of the reconstruction occurred on postoperative day 23 ± 6. The mean follow-up was 12.3 ± 7.2 months (range, 3 to 26 months). Clinically, 16 patients had 100 percent take of skin grafts and one patient had approximately 97 percent take of his graft. All patients experienced excellent defect contouring and cosmesis. Conclusions: Artificial bilaminate acellular dermis is an excellent option for reconstructing defects created by tumor resection and can be used in a wide variety of locations. It is especially useful in large defects that usually require flaps for coverage. Patients experience minimal donor-site morbidity and have outstanding cosmetic and functional results.

Sentinel lymph node biopsy for the T1 (thin) melanoma: Is it necessary?

OBJECTIVES To determine the relationship between preoperative plasma 25-hydroxyvitamin D (25[OH]D) levels and severity of primary hyperparathyroidism (PHPT) and to explore whether presurgical 25(OH)D levels could predict the likelihood of positive results on technetium Tc 99m sestamibi scintigraphy. DESIGN Retrospective analysis. SETTING Tertiary university referral center. PATIENTS A total of 421 consecutive patients underwent preoperative sestamibi scintigraphy and parathyroid exploration. Patients with cholecalciferol (vitamin D) deficiency, defined as plasma levels lower than 25 ng/mL, were compared with patients having no vitamin D deficiency. We explored the relationship between 25 (OH)D levels and intact parathyroid hormone (iPTH) levels, alkaline phosphatase (ALKP) levels, adenoma weight, binary sestamibi scan results, and postoperative serum calcium levels (at 1 week and 6 months). MAIN OUTCOME MEASURES We hypothesized that severity of hypovitaminosis D would correlate with severity of PHPT and predict the likelihood of a positive finding on sestamibi scan. RESULTS Concentrations of iPTH and ALKP and parathyroid adenoma weight were significantly higher in patients with lower 25(OH)D levels (P < .01 for all). Patients with hypovitaminosis D had a greater percentage decrease in serum calcium levels 1 week and 6 months postoperatively (P < .05). Median 25(OH)D levels were lower in patients with positive sestamibi scan results (P < .001). CONCLUSIONS Patients with hypovitaminosis D present with more advanced indices of PHPT. Parathyroid sestamibi scanning is more likely to show positive results for this subset of patients who may then benefit from sestamibi scan-directed surgical intervention.

Clinical implications of the innervation of the temporomandibular joint

The use of sentinel lymph node biopsy for the T1 melanoma is controversial. Recent reports have demonstrated that certain T1 melanomas are at increased risk for early regional metastases and late recurrence when compared with all thin melanomas. The purpose of this study was to review the authors’ experience with wide excision and sentinel lymph node biopsy for certain patients with T1 melanoma. A retrospective analysis of 34 patients with T1 melanoma was completed over a 3-year period. Indications for sentinel lymph node biopsy included a Breslow thickness of less than or equal to 1 mm a Clark level of III or IV tumor ulceration, or tumor regression. Twenty-four patients met these criteria (13 men and 11 women). Mean age was 47.6 years (range, 23–88 years). Mean tumor thickness for all patients was 0.69 mm (range, 0.3–1.0 mm), 0.61 mm for the Clark level III patients (N = 15), and 0.72 mm for the Clark level IV patients (N = 9). Tumor ulceration was present in 1 patient and histological regression was present in 2 patients. Regional lymph node metastases were confirmed histologically in 2 of 24 patients (8.3%) in whom the thickness of the melanoma was 0.9 mm and 1 mm. Both patients have died of metastatic melanoma. No recurrence has been demonstrated in the remaining 22 patients at the 2 to 5-year follow-up. Current indications for sentinel lymph node biopsy for patients with T1 melanoma include tumors associated with Clark level IV or V invasion, ulceration, regression, a positive deep margin on initial biopsy, or previous melanoma. Acral lentiginous melanoma associated with at least a Clark level III invasion warrant sentinel lymph node biopsy. Superficial spreading or nodular melanoma larger than 0.9 mm should include sentinel lymph node biopsy regardless of other associated histological factors.

Financial Conflicts of Interest: An Association between Funding and Findings in Plastic Surgery.

The successful management of temporomandibular joint (TMJ) pain remains elusive. Often, the initial relief of pain is complicated by recurrence of the symptoms. This time frame suggests that the pain may be related to neuromas of the nerves that innervate the TMJ. The current study attempted to define the innervation pattern of the TMJ as identified in 16 embalmed and 8 fresh-frozen specimens. In each specimen, the auriculotemporal nerve, a branch of the mandibular portion (V3) of the trigeminal nerve, was found to innervate the lateral capsule of the TMJ. In 75% of the specimens, the masseteric nerve, a branch of the maxillary portion (V2) of the trigeminal nerve, was found to innervate the anteromedial capsule of the TMJ. In 33% of the specimens, there was a branch coming through the mandibular notch to innervate the anteromedial capsule that was not from the masseteric nerve; this nerve is believed to have passed through the lateral pterygoid muscle after leaving V2. These consistent patterns of innervation of the TMJ suggest that diagnostic nerve blocks can be done to determine the pain pathway in these patients. It is suggested that if the nerve blocks are successful, TMJ denervation may be a future method of pain relief in patients with recalcitrant or recurrent TMJ pain.