David Hiltzik

BACKGROUND: Poorly differentiated thyroid carcinomas (PDTC) occupy an intermediate position at the prognostic level on the spectrum of thyroid carcinoma progression. However, their histologic definition is controversial. The objective of the current study was to assess the prognostic significance of PDTC defined on the basis of mitosis and necrosis and search for prognostic markers within this group of tumors that are predictive of overall survival (OS) and progression-free survival (PFS). METHODS: PDTC was defined as thyroid carcinoma with follicular cell differentiation at the histologic and/or immunohistochemical levels and displaying tumor necrosis and/or > or = 5 mitoses per 10 high-power fields (x400). Retrospective chart review and microscopic examination identified 58 patients with primary tumors meeting the above criteria and seen at the Memorial Sloan-Kettering Cancer Center between 1992 and 2004. These 58 patients were analyzed for various histologic, clinical, and imaging parameters. Each parameter was correlated with OS and PFS. RESULTS: Of the 58 patients studied, 22 (38%) patients died of disease with a 5-year OS rate of 60%. Forty-three of the 58 patients (74%) developed disease recurrence or disease progression, with a 5-year PFS rate of 25%. The median follow-up for the entire patient population was 42.6 months (range, 4-205 mos). A tumor size > 4 cm was found to be correlated with a decreased PFS time (P < 0.001). Those tumors with a capsule demonstrated a significantly improved OS compared with unencapsulated tumors (P = 0.001). The extent of capsular invasion was found to be a significant adverse factor for PFS (P = 0.05). The presence of extrathyroid extension into perithyroid soft tissue was found to be correlated with a decreased OS (P = 0.001) and PFS (P = 0.004). Of 27 patients with distant metastasis, 19 (70%) had concentrated radioactive iodine (RAI) at their metastatic sites. On multivariate analysis, extrathyroid extension and tumor size emerged as the only significant variables in predicting PFS (P = 0.04 and P = 0.01, respectively) whereas extrathyroid extension was found to be the sole independent prognostic factor for OS (P = 0.01). Growth pattern and cell type did not appear to influence outcome. CONCLUSIONS: PDTC defined on the basis of mitosis and necrosis constitutes a group of tumors that is more aggressive and homogeneous than PDTC defined by growth pattern. Within this group of patients, microstaging (tumor size, the extent of capsular invasion, and, especially, extrathyroid extension), and not growth pattern or cell type, is able to stratify patients into different prognostic categories. RAI uptake occurs in a significant number of patients with PDTC.

OBJECTIVE: Intraoperative identification of cerebrospinal fluid (CSF) leakage is critical in successful closure after endoscopic cranial base surgery. Intrathecal injection of fluorescein is quite useful in identifying CSF leaks. However, complications have been reported with various doses and the technique has fallen out of favor. We explored the safety of low-dose intrathecal fluorescein administered to patients undergoing endoscopic cranial base surgery. METHODS: A retrospective chart review and postoperative patient survey were performed. The nature and incidence of complications and subjective complaints were recorded in 54 patients who underwent endoscopic, endonasal approaches to the anterior cranial base and received intrathecal fluorescein after premedication with dexamethasone and diphenhydramine. RESULTS: Intraoperative CSF leak was identified with fluorescein in 46.3% of the patients and helped determine the reconstruction technique. Postoperative CSF leak occurred in 9.3% of the patients and resolved with lumbar drainage. There were no seizures. Most side effects were nonspecific, transient, and likely not caused by fluorescein including malaise (57.4%), headache (51.9%), dizziness (31.5%), or nausea/vomiting (24.1%). Three patients (5.6%) experienced persistent subjective lower extremity weakness (n = 2) and numbness (n = 2) postoperatively; however, two of them had undergone lumbar drainage. CONCLUSION: Low-dose injection of intrathecal fluorescein after premedication with steroid and antihistamine agents is generally safe. Most symptoms are nonspecific and transient, likely caused by the surgery or lumbar drainage. However, fluorescein should be administered with some caution because it may be responsible for occasional lower extremity weakness and numbness.

With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.