Faculty Bibliography

BACKGROUND:This study reports the combined experience of the University of Miami and University of Pittsburgh with endoscopic endonasal resection of esthesioneuroblastoma (ENB). A retrospective case series review was performed in a tertiary care university hospital. METHODS:Twenty-three patients, 16 men and 7 women, were reviewed. Mean age was 56.6 years (15-79 years). Nineteen patients received primary endoscopic endonasal anterior skull base resection. Of these, the modified Kadish stage at presentation was A in 2 patients, B in 11 patients, C in 5 patients, and D in 1 patient. Three patients had revision surgeries for recurrent tumors. The main outcome measures were complete resection and margin assessment, short-term and long-term complications, and recurrence rate. RESULTS:Complete resection and negative intraoperative resection margins were achieved endoscopically in 17 of the primarily treated cases. The two other cases had one patient that required an additional craniotomy approach to complete the resection of a positive lateral dual margin, another patient had positive margins at the orbital apex. All patients tolerated the endoscopic procedure very well with no meningitis. There were four cerebral spinal fluid leaks. Mean follow-up period for the primarily treated cases was 45.2 months (11-152 months), all were disease free at the most recent available follow-up. CONCLUSION/CONCLUSIONS:In experienced hands and carefully selected patients, endoscopic resection of ENB respects the principles of oncologic surgery, providing an adequate exposure for margin assessment as well as reliable reconstruction of the anterior skull defect with a relatively low morbidity.

Leprosy is a chronic granulomatous infection of the skin and peripheral nerves that often leads to gross deformation of the nasal skeleton and subsequent formation of a saddle-nose deformity. Reconstruction of the nose following Mycobacterium leprae infection has challenged surgeons for centuries. As a result, a number of different techniques have been attempted with varying outcomes. This article describes the case and surgical treatment of a 37-year old female who presented with a subtotal nasoseptal perforation and saddle-nose deformity secondary to previous infection with leprosy. Reconstruction was achieved via an open septorhinoplasty approach using autologous costal cartilage grafts, yielding a successful postoperative result.

Apoptosis is frequently regulated by different protein kinases including protein kinase C family enzymes. Both inhibitory and stimulatory effects were demonstrated for several of the different PKC isoforms. Here we show that the novel PKC isoform, PKCeta, confers protection against apoptosis induced by the DNA damaging agents, UVC irradiation and the anti-cancer drug--Camptothecin, of the breast epithelial adenocarcinoma MCF-7 cells. The induced expression of PKCeta in MCF-7 cells, under the control of the tetracycline-responsive promoter, resulted in increased cell survival and inhibition of cleavage of the apoptotic marker PARP-1. Activation of caspase-7 and 9 and the release of cytochrome c were also inhibited by the inducible expression of PKCeta. Furthermore, JNK activity, required for apoptosis in MCF-7, as indicated by the inhibition of both caspase-7 cleavage and cytochrome c release from the mitochondria in the presence of the JNK inhibitor SP600125, was also suppressed by PKCeta expression. Hence, in contrast to most PKC isoforms enhancing JNK activation, our studies show that PKCeta is an anti-apoptotic protein, acting as a negative regulator of JNK activity. Thus, PKCeta could represent a target for intervention aimed to reduce resistance to anti-cancer treatments.

OBJECTIVE:To assess the utility of the pectoralis major muscle flap (PMMF) in patients undergoing salvage total laryngectomy. DESIGN/METHODS:Retrospective cohort analysis. SETTING/METHODS:Tertiary care cancer center. PATIENTS/METHODS:The study included 461 patients who underwent laryngectomy. Eighty of them underwent salvage surgery with primary pharyngeal closure. INTERVENTIONS/METHODS:Of the 80 patients, 69 (86%) underwent primary pharyngeal closure alone and 11 (14%) underwent a PMMF, which was used to buttress the pharyngeal suture line. MAIN OUTCOME MEASURE/METHODS:Two hundred thirty-six variables were recorded for each patient. Complications related to pharyngeal closure were measured. RESULTS:Sixty-four percent of the patients who underwent PMMF also underwent chemoradiation therapy as the initial definitive treatment compared with 25% in the non-PMMF group (P = .03). On multivariate analysis, chemoradiation therapy was the only independent predictor of pharyngocutaneous fistula formation (relative risk, 1.82; P = .02). Nevertheless, the pharyngocutaneous fistula rate was similar in the PMMF (27%) and the non-PMMF (24%) groups. Furthermore, similar durations of tube feeding, days to oral feeding, and hospitalization period were recorded in both groups. CONCLUSION/CONCLUSIONS:The PMMF should be used judiciously as a surgical adjunct in high-risk patients, with the goal of minimizing the risk for the development of a pharyngocutaneous fistula.

OBJECTIVE:To characterize the incidence and pattern of neural invasion (NI) in patients with cancers of the paranasal sinuses and anterior skull base. DESIGN/METHODS:Retrospective study. SETTING/METHODS:A tertiary referral cancer center. PATIENTS/METHODS:The study included 208 patients with cancer of the paranasal sinuses. Patients with brain invasion or neurogenic tumors were excluded. MAIN OUTCOME MEASURE/METHODS:Analysis of clinical and pathologic data on patients with cancer of the paranasal sinuses. RESULTS:Forty-one specimens (20%) had evidence of NI. Sinonasal undifferentiated, adenoid cystic, and squamous cell carcinoma had a high propensity for NI, whereas melanoma and sarcoma rarely invaded nerves. Intraneural invasion was found in 32% of these cases, and 34% invaded more than 1 cm distal to the tumor. Neural invasion was associated with a high rate of positive margins, maxillary origin, and previous surgical treatment (P < .04) but not with stage, orbital invasion, or dural invasion. Patients with NI were more likely to undergo adjuvant radiotherapy (P = .003), which significantly improved survival in patients with minor salivary gland carcinomas (P = .04). Multivariate analysis showed that pathologic evidence of NI was not an independent predictor of outcome. CONCLUSIONS:Paranasal carcinomas have high propensity for NI, whereas melanoma and sarcoma rarely invade nerves. Patterns of NI include both perineural and intraneural invasion. Neural invasion is associated with positive margins, maxillary origin, and previous surgery.

We have previously described a novel conjugal DNA transfer process that occurs in Mycobacterium smegmatis. To identify donor genes required for transfer, we have performed a transposon mutagenesis screen; we report here that LpqM, a putative lipoprotein-metalloproteinase, is essential for efficient DNA transfer. Bioinformatic analyses predict that LpqM contains a signal peptide necessary for the protein's targeting to the cell envelope and a metal ion binding motif, the likely catalytic site for protease activity. Using targeted mutagenesis, we demonstrate that each of these motifs is necessary for DNA transfer and that LpqM is located in the cell envelope. The requirement for transfer is specific to the donor strain; an lpqM knockout mutant in the recipient is still proficient in transfer assays. The activity of LpqM is conserved among mycobacteria; homologues from both Mycobacterium tuberculosis and Mycobacterium avium can complement lpqM donor mutants, suggesting that the homologues recognize and process similar proteins. Lipoproteins constitute a significant proportion of the mycobacterial cell wall, but despite their abundance, very few have been assigned an activity. We discuss the potential role of LpqM in DNA transfer and the implications of the conservation of LpqM activity in M. tuberculosis.