Ehab Y. Hanna

Endoscopic Resection of Sinonasal Cancers With and Without Craniotomy: Oncologic Results

OBJECTIVE To evaluate the oncologic outcomes of patients with sinonasal cancer treated with endoscopic resection. DESIGN Retrospective review. SETTING Tertiary care academic cancer center. PATIENTS All patients with biopsy-proved malignant neoplasm of the sinonasal region who were treated with endoscopic resection between 1992 and 2007 were included in the study, and their charts were reviewed for demographics, histopathologic findings, treatment details, and outcome. MAIN OUTCOME MEASURES Oncologic outcomes, including disease recurrence and survival. RESULTS Of a total of 120 patients, 93 (77.5%) underwent an exclusively endoscopic approach (EEA) and 27 (22.5%) underwent a cranioendoscopic approach (CEA) in which the surgical resection involved the addition of a frontal or subfrontal craniotomy to the transnasal endoscopic approach. Of the 120 patients, 41% presented with previously untreated disease, 46% presented with persistent disease that had been partially resected, and 13% presented with recurrent disease after prior treatment. The most common site of tumor origin was the nasal cavity (52%), followed by the ethmoid sinuses (28%). Approximately 10% of the tumors had an intracranial epicenter, most commonly around the olfactory groove. Tumors extended to or invaded the skull base in 20% and 11% of the patients, respectively. An intracranial epicenter (P < .001) and extension to (P = .001) or invasion of (P < .001) the skull base were significantly more common in patients treated with CEA than in those treated with EEA. The primary T stage was evenly distributed across all patients as follows: T1, 25%; T2, 25%; T3, 22%; and T4, 28%. However, the T-stage distribution was significantly different between the EEA group and the CEA group. Approximately two-thirds (63%) of the patients treated with EEA had a lower (T1-2) disease stage, while 95% of patients treated with CEA had a higher (T3-4) disease stage (P < .001). The most common tumor types were esthesioneuroblastoma (17%), sarcoma (15%), adenocarcinoma (14%), melanoma (14%), and squamous cell carcinoma (13%). Other, less common tumors included adenoid cystic carcinoma (7%), neuroendocrine carcinoma (4%), and sinonasal undifferentiated carcinoma (2%). Microscopically positive margins were reported in 15% of patients. Of the 120 patients, 50% were treated with surgery alone, 37% received postoperative radiation therapy, and 13% were treated with surgery, radiation therapy, and chemotherapy. The overall surgical complication rate was 11% for the whole group. Postoperative cerebrospinal fluid leakage occurred in 4 of 120 patients (3%) and was not significantly different between the CEA group (1 of 27 patients) and the EEA group (3 of 93 patients) (P > .99). The cerebrospinal fluid leak resolved spontaneously in 3 patients, and the fourth patient underwent successful endoscopic repair. With a mean follow-up of 37 months, 18 patients (15%) experienced local recurrence, with a local disease control of 85%. Regional and distant failure occurred as the first sign of disease recurrence in 6% and 5% of patients, respectively. The 5- and 10-year disease-specific survival rates were 87% and 80%, respectively. Disease recurrence and survival did not differ significantly between the EEA group and the CEA group. CONCLUSIONS To the best of our knowledge, this is the largest US series to date of patients with malignant tumors of the sinonasal tract treated with endoscopic resection. Our results suggest that, in well-selected patients and with appropriate use of adjuvant therapy, endoscopic resection of sinonasal cancer results in acceptable oncologic outcomes.

Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson cancer center

Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities.

CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: Implications for histogenesis and biologic behavior

We analyzed 55 primary salivary gland tumors including 22 mucoepidermoid carcinomas (MECs) to determine the association of MECT1/TORC1/CRTC1‐MAML2 fusion transcript to tumor types, level of MEC differentiation and clinicopathologic parameters. Our primary salivary gland tumors were composed of 22 MECs, 11 Warthins tumors, 10 adenoid cystic carcinomas, two basaloid carcinomas, five salivary duct carcinomas, and five adenocarcinomas, not otherwise specified. We also included, for the first time, three primary MECs of the thyroid gland. We used nested RT‐PCR and subsequent sequencing techniques for detection and verification of the fusion transcript in fresh and archival specimens. Eighteen (81%) of the 22 primary salivary and one of the three thyroid glands with MEC were positive for the fusion transcript. The transcript was detected equally in low, intermediate and high grade as well as low and high stage MECs. Significant correlation between fusion negative tumors and distant metastasis was noted (P = 0.005). Four (36%) of the 11 Warthins tumors were also positive for the transcript. None of the 22 primary non‐MEC gland salivary carcinomas were positive for the transcript. We conclude that the CRTC1/MAML2 transcript may be detected in both low and high grade MEC, that fusion negative tumors may define a subset of biologically aggressive MECs tumors, that the fusion is present in primary MECs of the thyroid gland and is also detectable in Warthins tumor, and that a subset of MECs can be targeted for therapeutic intervention.

Tunable plasmonic nanobubbles for cell theranostics

Combining diagnostic and therapeutic processes into one (theranostics) and improving their selectivity to the cellular level may offer significant benefits in various research and disease systems and currently is not supported with efficient methods and agents. We have developed a novel method based on the gold nanoparticle-generated transient photothermal vapor nanobubbles, that we refer to as plasmonic nanobubbles (PNB). After delivery and clusterization of the gold nanoparticles (NP) to the target cells the intracellular PNBs were optically generated and controlled through the laser fluence. The PNB action was tuned in individual living cells from non-invasive high-sensitive imaging at lower fluence to disruption of the cellular membrane at higher fluence. We have achieved non-invasive 50-fold amplification of the optical scattering amplitude with the PNBs (relative to that of NPs), selective mechanical and fast damage to specific cells with bigger PNBs, and optical guidance of the damage through the damage-specific signals of the bubbles. Thus the PNBs acted as tunable theranostic agents at the cellular level and in one process that have supported diagnosis, therapy and guidance of the therapy.

Sinonasal adenoid cystic carcinoma: the M. D. Anderson Cancer Center experience.

Adenoid cystic carcinoma of the sinonasal tract is a rare cancer that accounts for 10% of all malignancies at this site. The objective of the current study was to evaluate prognostic factors, treatment outcomes, recurrence patterns, and survival rates for sinonasal adenoid cystic carcinoma.

Ataxia-telangiectasia-mutated (ATM) gene in head and neck squamous cell carcinoma: promoter hypermethylation with clinical correlation in 100 cases.

The Ataxia-telangiectasia-mutated (ATM) gene product is a well-characterized tumor suppressor that plays a key role in maintenance of genomic stability. We have recently documented that the ATM promoter is a target for epigenetic silencing in cultured tumor cells. Here we show that aberrant methylation of the ATM promoter occurs in a significant percentage (25%) of head and neck squamous cell carcinomas. The presence of methylated ATM promoter shows a statistically significant correlation with an earlier age of initial diagnosis and decreased overall survival, particularly in early-stage tumors. These findings indicate that ATM promoter hypermethylation occurs in head and neck squamous cell carcinoma, and this feature is a potentially useful prognostic marker in this tumor type.

Risk factors for local recurrence of adenoid cystic carcinoma: The role of postoperative radiation therapy

PURPOSE Postoperative radiation therapy is often advocated in the treatment of patients with adenoid cystic carcinoma (ACC) of the head and neck. A retrospective analysis was performed to determine prognostic factors for local recurrence after surgery and to examine the role of postoperative radiation therapy. MATERIALS AND METHODS A retrospective analysis of 58 patients undergoing surgery for ACC of the head and neck at the University of Pittsburgh Medical Center from 1974 to 1994 was performed. Patients were followed up for a minimum of 24 months for the development of recurrent disease. The association of recurrence was correlated with clinical factors (age, sex, site, and stage); postoperative treatment (radiation therapy v no radiation); and pathologic variables (grade, margins of resection, and perineural invasion), and appropriate statistical analysis was performed. RESULTS Recurrent disease developed in 59% of patients, despite the addition of postoperative radiation therapy in 83% of patients. Tumor site was the single most important factor for the development of locally recurrent disease and was correlated with primary tumor stage and resection margins. Local recurrence rates were decreased (P = .07) in patients with negative surgical margins who were irradiated. CONCLUSIONS Larger perspective randomized trials are necessary to evaluate the efficacy of postoperative radiation, and new treatments need to be investigated to improve local control rates for ACC of the head and neck.

LANTCET: elimination of solid tumor cells with photothermal bubbles generated around clusters of gold nanoparticles

BACKGROUND We have developed a method, termed laser-activated nano-thermolysis as a cell elimination technology (LANTCET), for the selective detection and destruction of individual tumor cells by the generation of intracellular photothermal bubbles around clusters of gold nanoparticles. METHOD Bare nanoparticles and their conjugates to C225 tumor-specific monoclonal antibodies were applied in vitro to C225-positive squamous carcinoma cells and in vivo to an experimental tumor in a rat in order to form intracellular clusters of nanoparticles. RESULTS Single 10 ns laser pulses generated intracellular photothermal microbubbles at a near-infrared and visible wavelengths. The cells with the clusters yielded an almost 100-fold decrease in the laser fluence threshold for bubble generation and cell damage relative to that for the cells without clusters. Cell damage had a mechanical origin and single cell selectivity. Three LANTCET processes (cell detection, damage and optical guidance) were realized as a microsecond sequence and with the one device.

Prognostic factors in mucoepidermoid carcinoma of the salivary glands

Mucoepidermoid carcinoma (MEC) is the most common malignancy of the major salivary glands. Prior reports noted histological grade and tumor stage as consistently important prognostic factors. This study reviewed the experience of patients with MEC at the University of Texas MD Anderson Cancer Center to determine the impact of clinical and pathologic findings on disease outcomes.

Prognosis and risk factors for early-stage adenoid cystic carcinoma of the major salivary glands

Adenoid cystic carcinoma (ACC) is characterized by slow growth, frequent local recurrences, and distant metastasis (DM). However, these findings frequently are reported in patients with advanced‐stage tumors, but the outcomes of early‐stage tumors are poorly defined. We sought to evaluate the risk factors for the development of DM in early‐stage ACC.