Faculty Bibliography

OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy with optimal management remains unclear. We performed a review of the impact of trimodality approach on SNUC outcome. METHODS: This is a single-institution retrospective study of 18 patients, who were managed between 1997 and 2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%) were female. Three patients had stage II disease and underwent surgery alone, 12 had stages III and IVa and underwent surgery combined with chemoradiation, and 3 had stage IVb and underwent definitive chemoradiation. Patients who underwent preoperative, postoperative, and definitive chemoradiation received 60, 66, and 70 Gy of radiation, respectively. In all patients receiving concurrent chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3 cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5-fluorouracil (TPF) every 3 weeks for 2 to 3 cycles. RESULTS: After a median follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%; 75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach provided 83% LC and 92% DM-free survival, whereas other modalities provided 50% LC and 33% DM-free survival. The causes of death for the entire cohort were DM and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2 dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and 6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11% retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3 peripheral neuropathy. CONCLUSIONS: SNUC is an aggressive neoplasm that frequently presents at an advanced stage. Our data show that trimodality approach in the form of surgery combined with chemoradiation seems to offer better LC and lower DM compared with other modalities.

Background/Purpose: Rheumatoid arthritis (RA) patients are at increased risk of infection due to both RA itself and immunomodulating treatments. Infection rates are often difficult to compare across studies, since the rates may vary across the world, and due to methodological and demographic differences between studied populations or cohorts. We investigated rates of hospitalized infection in 5 RA registries from 4 continents, employing a standard set of analyses and standardizing rates to a common population. Methods: Participating registries were CORRONA (USA), SRR (Sweden), NOAR (UK), CORRONA International (East Europe, Latin America, India) and IORRA (Japan). The definition of hospitalized infections was harmonized as much as possible across registries. Within each registry, we analyzed a primary cohort of all RA patients from January 2000 to last available data of each registry (2010-2013), and several subcohorts for sensitivity analyses, defined by disease activity, treatment status, calendar time, duration of follow-up and prior comorbidity. Rates were standardized for age, sex and, in 1 sensitivity analysis, also for HAQ, using the distributions from a typical RA trial program population. Results: There was relatively high consistency in rates across registries, and sex/age standardization increased consistency further (Table 1). Generally, the primary cohorts provided the lowest or close to lowest rate (Table 2). In most registries, the highest rates were seen in subcohorts (either biologic naive or with prior biologic treatment) with only 18 months follow-up after treatment change (Table 2). Additional standardization for HAQ score according to a trial patient distribution led to increased rates in all registries (Table 2). Conclusion: This study constitutes the first attempt to compare the incidence of hospitalized infections internationally using existing RA cohorts. Consistent methodology, outcome definitions and analysis with standardization of rates facilitated comparison across !

OBJECTIVES/HYPOTHESIS: To report tolerance and toxicity of radiotherapy (RT) with or without chemotherapy in HIV seropositive patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: This is a single institution retrospective study of 73 HIV seropositive patients with SCCHN treated from January 1997 through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively. The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51 (32-72), 34 (25-50), and 11 (6-20) years, respectively. Patients were treated definitively with RT alone (35%) or concurrent chemo-RT (65%). Median dose of 70 Gy (66-70) was delivered to the gross disease. Median duration of treatment was 52 (49-64) days. Fifty patients (70%) were on HAART. RESULTS: RT+/- chemotherapy induced acute toxicity was: median weight loss 20 pounds (6-40), 100% developed dysgeusia and xerostomia (grades 1-3). Acute mucositis and dysphagia/odynophagia grades 2 were 26% and 23% of patients, respectively. CONCLUSION: Our data show that primary RT +/-chemotherapy for HIV seropositive SCCHN is less tolerated compared to the historical data for SCCHN without HIV. LEVEL OF EVIDENCE: 2b.

BACKGROUND: The purpose of this article was to present the Beth Israel Medical Center experience using high-dose-rate intraoperative radiotherapy (HDR-IORT) in the management of recurrent head and neck cancer. METHODS: We conducted a retrospective review of all patients with locally or regionally recurrent head and neck cancer who underwent HDR-IORT at our institution between 2001 and 2010. RESULTS: Seventy-six patients were identified who underwent treatment to a total of 87 sites after gross-total resection. The 2-year estimate of in-field tumor control was found to be 62%. Median overall survival was 19 months with 42% of the patients surviving at least 2 years. Significantly longer survival was found for patients achieving in-field control versus infield progression (33 months vs 17 months, respectively; p = .01). CONCLUSION: HDR-IORT is well tolerated and associated with encouraging in-field disease control. In-field control is associated with improved survival. Further study is warranted to more fully investigate HDR-IORT in the salvage setting.

PURPOSE OF REVIEW: To weigh the clinical impact of new technological insights into heritable thyroid malignancies. RECENT FINDINGS: Medullary thyroid carcinoma and familial nonmedullary thyroid cancers represent the small minority of thyroid cancers that are inherited. New insights into the genetic alterations and molecular mechanisms implicated in these tumors are serving to refine the clinical tools available for their initial diagnosis as well as subsequent follow-up. In addition to an analysis of rearranged during transfection mutations and calcitonin profiles in medullary thyroid carcinoma, this review includes emphasis on familial nonmedullary thyroid cancer syndromes, including genetic findings in familial papillary thyroid cancer, familial adenomatous polyposis, Cowden syndrome, Carney complex, and Werner syndrome. SUMMARY: Genetic mutational information is increasingly available on medullary and familial nonmedullary thyroid cancer and their associated syndromes. The clinical significance of this information for affected patients and their families continues to undergo evaluation

BACKGROUND: Minimally invasive esophagectomy (MIE) via thoracoscopy and laparoscopy have reduced the morbidity and mortality of total esophagectomy at experienced centers. MIE has not been evaluated in combination with major head and neck surgery, or in the otolaryngology literature. METHODS: Case series of 11 consecutive patients undergoing either open or MIE with an ablative neck procedure. RESULTS: Comparing 4 MIEs and 7 open operations, similar operative time, blood loss, and ICU and hospital length of stay were observed. There was one mortality in the open group. A 100% rate of major complications was observed in the MIE group. CONCLUSION: Our multidisciplinary team was unable to achieve improved outcomes in a series of head and neck surgical patients undergoing MIE. This result may represent an early stage of the learning curve for MIE, but may also be attributed to the escalated surgical requirements of head and neck patients

The possibility that serum ferritin is a secreted protein and an acute phase reactant regulated by inflammatory hormones and iron was examined in a hepatic cell line that secretes plasma proteins. Differentiated rat hepatoma cells released albumin and ferritin into the medium, as determined by rocket immunoelectrophoresis and isolation of ferritin by standard procedures plus immunoaffinity chromatography, following labeling with radioactive amino acid. Administration of interleukin-1-beta (IL-1) or tumor necrosis factor-alpha (TNF) doubled the amounts of ferritin released into the medium over 24 and 48 hours. Together, the cytokines had more than an additive effect. Albumin secretion was diminished by IL-1, but not TNF. Iron, administered as an iron dextran complex or as a 1:1 chelate with nitrilotriacetate (Fe-NTA), also enhanced ferritin release, but had no effect on albumin. Intracellular ferritin concentrations did not change significantly with cytokine treatment, but increased in response to iron. With or without treatments, release of ferritin and albumin from cells into the medium was inhibited by brefeldin A, an inhibitor of Golgi function. The effect of each of the cytokines and of iron on ferritin and albumin was also blocked by dichlorofuranosylbenzimidazole (DRB), an inhibitor of transcription. The stimulatory effect of Fe-NTA on ferritin secretion was diminished by TNF, and this was partially counteracted by IL-1, indicating additional regulatory complexity. These results show for the first time that hepatic cells secrete ferritin, that this ferritin secretion is regulated by iron and inflammatory cytokines, and that the mechanisms of regulation differ from those for intracellular ferritin. The results would explain why serum ferritin increases in inflammation or when iron flux is enhanced.