Faculty Bibliography

Understanding the biology of Waldenström macroglobulinemia is hindered by a lack of preclinical models. We report a novel cell line, RPCI-WM1, from a patient treated for WM. The cell line secretes human immunoglobulin M (h-IgM) with κ-light chain restriction identical to the primary tumor. The cell line has a modal chromosomal number of 46 and harbors chromosomal changes such as deletion of 6q21, monoallelic deletion of 9p21 (CDKN2A), 13q14 (RB1) and 18q21 (BCL-2), with a consistent amplification of 14q32 (immunoglobulin heavy chain; IgH) identical to its founding tumor sample. The clonal relationship is confirmed by identical CDR3 length and single nucleotide polymorphisms as well as a matching IgH sequence of the cell line and founding tumor. Both also harbor a heterozygous, non-synonymous mutation at amino acid 265 in the MYD88 gene (L265P). The cell line expresses most of the cell surface markers present on the parent cells. Overall, RPCI-WM1 represents a valuable model to study Waldenström macroglobulinemia.

BACKGROUND: Ceruminous mucoepidermoid carcinoma of the external auditory canal is extremely rare. This paper highlights the impact of concurrent chemoradiotherapy on the outcomes of this disease. CASE REPORT: A 47-year-old female presented with a 2-month history of otalgia and a mass in her right ear. Biopsy revealed high grade ceruminous mucoepidermoid carcinoma. She underwent surgical excision of the right external auditory canal and right upper neck dissection. Pathological analysis of tumour-node-metastasis staging revealed a T2 N0 (stage II) tumour. One year later, computed tomography scanning of the temporal bone showed tumour recurrence. Biopsy revealed recurrent ceruminous mucoepidermoid carcinoma. The patient underwent salvage resection. Pathology revealed that the tumour was diffusely invading nearby structures, with perineural invasion, lymphatic spread and extracapsular extension. Pathological analysis of tumour-node-metastasis staging revealed a T3 N1 M0 (recurrent stage IV) tumour. RESULTS: The patient subsequently received concurrent chemoradiotherapy. There was no evidence of disease at 37 months' follow up. CONCLUSION: The trimodality approach, using surgery plus concurrent chemoradiotherapy, provided reasonable loco-regional control with tolerable toxicity. Further detailed case reports are warranted to optimise the management of this rare malignancy.

OBJECTIVE: To examine whether there are gender disparities in scholarly productivity within academic otolaryngology departments, as measured by academic rank and the h-index, a published, objective measure of research contributions that quantifies the number and significance of papers published by a given author. STUDY DESIGN AND SETTING: Analysis of bibliometric data of academic otolaryngologists. METHODS: Faculty listings from academic otolaryngology departments were used to determine academic rank and gender. The Scopus database was used to determine h-index and publication range (in years) of these faculty members. In addition, 20 randomly chosen institutions were used to compare academic otolaryngologists to faculty members in other surgical specialties. RESULTS: Mean h-indices increased through the rank of professor. Among academic otolaryngologists, men had significantly higher h-indices than women, a finding also noted on examination of faculty members from other specialties. Men had higher research productivity rates at earlier points in their career than women did. The productivity rates of women increased and equaled or surpassed those of men later in their careers. Men had higher absolute h-index values at junior academic ranks. Women academic otolaryngologists of senior rank had higher absolute h-indices than their male counterparts. CONCLUSIONS: The h-index measures research significance in an objective manner and indicates that although men have higher overall research productivity in academic otolaryngology, women demonstrate a different productivity curve. Women produce less research output earlier in their careers than men do, but at senior levels, they equal or exceed the research productivity of men.

OBJECTIVE:To examine the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) against a panel of 5 human salivary gland carcinoma cell lines. DESIGN/METHODS:The susceptibility of 5 salivary gland carcinoma cell lines to infection and oncolysis by GLV-1h68 was assessed in vitro and in vivo. RESULTS:All 5 cell lines were susceptible to viral infection, transgene expression, and cytotoxic reactions. Three cell lines were exquisitely sensitive to infection by very low doses of GLV-1h68. Orthotopic parotid tumors exhibited more aggressive behavior compared with flank tumors. A single intratumoral injection of GLV-1h68 induced significant tumor regression without observed toxic effects in flank and parotid tumor models; controls demonstrated rapid tumor progression. CONCLUSION/CONCLUSIONS:These promising results demonstrate significant oncolytic activity by an attenuated vaccinia virus for infecting and lysing salivary gland carcinomas, supporting future clinical trials.

Killian-Jamieson diverticulum (KJD) is rare hypopharyngeal defect. As in other forms of esophageal diverticuli (i.e., Zenker's), recent literature has described minimally invasive endoscopic approaches to its management.1, 2 We present a case of a 62-year-old female with symptoms consistent with an esophageal diverticulum. A barium swallow study was consistent with a KJD. The patient was brought to the operating room and endoscopically examined to confirm the presence of this entity. A open transcervical approach was performed to remove the diverticulum without complication. During our dissection, the recurrent laryngeal nerve (RLN) was noted to be adherent to the base of the diverticulum and needed to be freed prior to performing the diverticulectomy. We provide a review of recent literature and medical illustrations to highlight the importance of the open transcervical approach in the management of KJD to avoid inadvertent transection of the RLN.

OBJECT/OBJECTIVE:This study was designed to determine if the "keyhole concept," proposed by Perneczky's group, can be verified quantitatively. METHODS:Fourteen (3 bilateral and 8 unilateral) sides of embalmed latex-injected cadaveric heads were dissected via 3 sequential craniotomy approaches: supraorbital keyhole, frontotemporal pterional, and supraorbital. Three-dimensional cartesian coordinates were recorded using a stereotactic localizer. The orthocenter of the ipsilateral anterior clinoid process, the posterior clinoid process, and the contralateral anterior clinoid process are expressed as a center point (the apex). Seven vectors project from the apex to their corresponding target points in a radiating manner on the parasellar skull base. Each 2 neighboring vectors border what could be considered a triangle, and the total area of the 7 triangles sharing the same apex was geometrically expressed as the area of exposure in the parasellar region. RESULTS:Values are expressed as the mean ± SD (mm(2)). The total area of exposure was as follows: supraorbital keyhole 1733.1 ± 336.0, pterional 1699.3 ± 361.9, and supraorbital 1691.4 ± 342.4. The area of exposure on the contralateral side was as follows: supraorbital keyhole 602.2 ± 194.7, pterional 595.2 ± 228.0, and supraorbital 553.3 ± 227.2. The supraorbital keyhole skull flap was 2.0 cm(2), and the skull flap size ratio was 1:5:6.5 (supraorbital keyhole/pterional/supraorbital). CONCLUSIONS:The area of exposure of the parasellar region through the smaller supraorbital keyhole approach is as adequate as the larger pterional and supraorbital approaches. The keyhole concept can be verified quantitatively as follows: 1) a wide area of exposure on the skull base can be obtained through a small keyhole skull opening, and 2) the side opposite the opening can also be visualized.

IMPORTANCE: Limited donor and recipient site complications support the osteocutaneous radial forearm free flap (OCRFFF) for mandibular reconstruction as a useful option for single-stage mandibular reconstruction. OBJECTIVE: To examine and report long-term outcomes and complications at the donor and recipient sites for patients undergoing the OCRFFF for mandibular reconstruction. DESIGN: Retrospective review. SETTING: Academic, tertiary care medical center. PATIENTS: The study population comprised 167 consecutive patients who underwent single-staged mandibular reconstruction with an OCRFFF. MEAN OUTCOME MEASURES: Rates of complications at the donor and recipient sites. RESULTS: The mean patient age was 61 years (range, 20-93 years). Men compromised 68% of the population. Follow-up interval ranged from 2 to 99 months (mean, 25.9 months). The median length of bone harvested was 7 cm (range, 2.5-12.0 cm). Prophylactic plating was completed for each of the radii at the time of harvest. Donor site complications included radial fracture (1 patient [0.5%]), tendon exposure (47 patients [28%]), and donor hand weakness or numbness (13 patients [9%]). Recipient site complications included mandible hardware exposure (29 patients [17%]), mandible nonunion or malunion (4 patients [2%]), and mandible bone or hardware fracture (4 patients [2%]). Using regression analysis, we found that patients were 1.3 times more likely to have plate exposure for every increase of 1 cm of bone harvest length; this was statistically significant (P = .04). CONCLUSIONS AND RELEVANCE: This is the largest single study reporting outcomes and complications for patients undergoing OCRFFF for mandibular reconstruction. Prophylactic plating of the donor radius has nearly eliminated the risk of pathologic radial bone fractures. Limited long-term donor and recipient site complications support the use of this flap for single-stage mandibular reconstruction.

Kikuchi-Fujimoto lymphadenitis is a self-limited disorder that typically presents in young females as painless cervical lymphadenopathy with fever, anemia, and leukopenia. The clinical manifestations and pathologic findings suggest a viral etiology, yet specific etiologic agents remain unknown. Although there are studies reporting positive associations between Kikuchi-Fujimoto lymphadenitis and parvovirus B19 and herpesviruses, other studies have failed to find an association with these viruses. To our knowledge, this current study is the largest study of Kikuchi-Fujimoto lymphadenitis in Western patients that used polymerase chain reaction testing for 4 different common viral pathogens often implicated as etiologic agents in Kikuchi-Fujimoto lymphadenitis. Archival material from 3 institutions was included, following confirmation of the diagnosis of Kikuchi-Fujimoto lymphadenitis by 2 independent pathologists. Polymerase chain reaction from the paraffin-embedded tissue sections for parvovirus B19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 was performed. Eighteen cases of Kikuchi-Fujimoto lymphadenitis were analyzed, 12 of which (60%) were cervical lymph nodes. All the cases showed typical geographic necrosis with abundant apoptotic debris, although the degree of necrosis was variable. Polymerase chain reaction revealed a high prevalence of parvovirus B19 in the controls (44%); there were fewer positive cases seen in the Kikuchi-Fujimoto lymphadenitis cases (11%), but this did not reach statistical significance (P = .25).There were no significant differences between cases and controls in the prevalence of Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 (P = .50 for all 3). Polymerase chain reaction failed to reveal a positive association between Kikuchi-Fujimoto lymphadenitis and 4 common suspected viral agents. These findings do not support a role for Epstein-Barr virus, human herpesvirus 6, human herpesvirus 8, or parvovirus B19 in the pathogenesis of Kikuchi-Fujimoto lymphadenitis.