Faculty Bibliography

Organelle transport by myosin-V is down-regulated during mitosis, presumably by myosin-V phosphorylation. We used mass spectrometry phosphopeptide mapping to show that the tail of myosin-V was phosphorylated in mitotic Xenopus egg extract on a single serine residue localized in the carboxyl-terminal organelle-binding domain. Phosphorylation resulted in the release of the motor from the organelle. The phosphorylation site matched the consensus sequence of calcium/calmodulin-dependent protein kinase II (CaMKII), and inhibitors of CaMKII prevented myosin-V release. The modulation of cargo binding by phosphorylation is likely to represent a general mechanism regulating organelle transport by myosin-V

A number of controversies exist in the treatment of differentiated thyroid carcinoma with respect to the extent of surgery, use of radioactive iodine and post-operative thyroxine suppression. Recent recognition of prognostic factors has helped to assign patients, based on their risk profile, as being at high risk of developing recurrence. This has facilitated the development of a selective approach to therapy, thus, avoiding unnecessary treatment and reducing morbidity without compromising treatment outcome. This review attempts to evaluate the current concepts of management of differentiated thyroid carcinoma in the light of these new developments

OBJECTIVES/HYPOTHESIS: Unilateral vocal fold paralysis resulting in glottal incompetence can cause significant morbidity attributable to impaired speech, swallowing, and ability to protect the airway. Type I thyroplasty in combination with arytenoid adduction is a proven technique for medialization of the paralyzed vocal fold but must be evaluated in light of potential complications following laryngeal framework surgery. STUDY DESIGN AND METHODS: The charts of 237 patients who underwent unilateral vocal fold medialization surgery between July 1, 1991, and August 30, 1999, at a tertiary care cancer referral center were retrospectively reviewed. RESULTS: There were 98 cases of type I thyroplasty alone and 96 cases of type I thyroplasty with arytenoid adduction. The two groups had similar patient characteristics. Mean time of surgery (45 vs. 73 min, P <.0001) and length of hospital stay (1.1 vs. 1.8 d, P <.0001) were increased when arytenoid adduction was performed. Overall improvement of symptoms was similar in both groups (93%-94%), but posterior glottic closure appeared subjectively improved when arytenoid adduction was used (P =.0054). Overall complication rates were slightly higher in the arytenoid adduction group (14% vs. 19%), primarily because of transient vocal fold edema and wound complications (9 vs. 19 cases), but the increase was not statistically significant (P =.1401). Complications warranting medical or surgical intervention occurred in 8% of cases. Two patients who underwent type I thyroplasty with arytenoid adduction required tracheotomy as a consequence of postoperative complications. The three patients who had extrusion of the implant underwent type I thyroplasty alone. CONCLUSION: Using the appropriate technique, the potential benefits of improved glottic function following type I thyroplasty with arytenoid adduction outweigh the small risk of significant complications observed

We retrospectively evaluated the cases of 55 patients who had undergone surgery for primary hyperparathyroidism at our institution to determine whether their parathyroid glands were abnormal on both sides. Thirty-six of these patients had undergone a bilateral neck exploration, and 19 had had a unilateral investigation. Of the 36 bilaterally explored patients, 30 had a solitary adenoma and no parathyroid pathology on the opposite side, five patients had hyperplastic glands with more than one gland involved, and one patient had two adenomas. In the unilaterally explored group, all 19 patients had a solitary adenoma. There were no failures in the way of persistent hypercalcemia in either group. Based on our findings, we conclude that a unilateral neck exploration should be performed during surgery for primary hyperparathyroidism whenever a large parathyroid adenoma and a normal parathyroid gland are found on the same side. Bilateral exploration should be reserved for patients in whom pathology cannot be found on the initially explored side during surgery and for patients who have obvious parathyroid hyperplasia

We describe the case of a 59-year-old man who came to us with a right neck mass of 4 to 5 months' duration. A histologic diagnosis of malignant fibrous histiocytoma was made, and the patient underwent wide local excision and neck dissection followed by postoperative radiation therapy. We briefly discuss the characteristics and treatment of this rare entity

BACKGROUND: Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS: We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS: Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS: The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

OBJECTIVE: To determine the relationship between coin size, coin location, patient age, and patient weight and likelihood of coin passage through the esophagus following pediatric coin ingestion. A secondary objective is to test the hypothesis that coin denomination can be determined based on radiographic appearance. METHODS: A retrospective review was performed of all children seen and evaluated for coin ingestion at a single institution over a 25-month period. Outcome measures included the number of coins that were retained in the esophagus, and the number that passed. Various factors were assessed for their predictive value in judging outcome in coin ingestion cases. RESULTS: Nineteen percent of patients (15/79) in the study passed their ingested coins. Coin denomination could be accurately determined on every patient that had a standard AP or lateral X-ray film. These findings were marked when compared with the lack of reliability of history in determining coin denomination. Patients who passed coins were as a group older (4.6 vs. 3.2 year, P=0.04), but did not differ significantly by weight (19.5 vs. 15.4 kg, P=0.07) from those that retained the coins. Coins located at the gastroesophageal junction had a significantly higher passage rate than coins located elsewhere in the esophagus (89 vs. 8.2%, P<0.01). Coin size was not predictive of coin passage (P=0.7 by chi(2)). CONCLUSIONS: Radiographic assessment of coin denomination is reliable, but in this study could not be used to predict coin passage. Patient age and coin location at the gastroesophageal junction, however, do correlate with this event

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 one's 'own' criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) 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 kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 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 one's own grading systems (p = 0.0001) but not in applying the AFIP 'standardized' grading (p = 0.33). When one's 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