Ashutosh Kacker

Endoscopic pituitary surgery: a systematic review and meta-analysis

OBJECT Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes. METHODS The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes. RESULTS Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67-89%). Hormone resolution was achieved in 81% (95% CI 71-91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76-92%) of growth hormone secreting tumors, and 82% (95% CI 70-94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0-4%) for CSF leak and 1% (95% CI 0-2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%. CONCLUSIONS The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

Endoscopic cranial base surgery: classification of operative approaches.

OBJECTIVE Endoscopic cranial base surgery is a minimal access, maximally aggressive alternative to traditional transfacial, transcranial, or combined open cranial base approaches. Previous descriptions of endoscopic approaches have used varying terminology, which can be confusing to the new practitioner. Indications for surgery are not well defined. Our objective was to create a comprehensive classification system of the various approaches and describe their indications with case examples. METHODS We prospectively compiled a comprehensive database of our endonasal endoscopic operations, detailing the nasal sinus transgressed, the cranial base approach, and the intracranial target for the first 150 consecutive cases performed at our institution. All cases were performed collaboratively by a neurosurgeon and an otolaryngologist. RESULTS We categorized the endonasal endoscopic cranial base operations into four nasal corridors, nine cranial base approaches, and 13 intracranial targets. Each of the various approaches is described in detail and illustrated with case examples. Pathology encountered included pituitary tumor (50%), meningocele/encephalocele (14%), craniopharyngioma and Rathke cleft cyst (10%), meningioma (8%), chordoma (5%), esthesioneuroblastoma (2%), and other (11%). CONCLUSION Endonasal endoscopic cranial base surgery is a minimal access, maximally invasive alternative to open transcranial cranial base approaches for specific indications. A clear understanding of the possible approaches is facilitated by an awareness of the nasal corridors and intracranial targets.

Effects of Cigarette Smoke on the Human Oral Mucosal Transcriptome

Use of tobacco is responsible for ∼30% of all cancer-related deaths in the United States, including cancers of the upper aerodigestive tract. In the current study, 40 current and 40 age- and gender-matched never smokers underwent buccal biopsies to evaluate the effects of smoking on the transcriptome. Microarray analyses were carried out using Affymetrix HGU133 Plus 2 arrays. Smoking altered the expression of numerous genes: 32 genes showed increased expression and 9 genes showed reduced expression in the oral mucosa of smokers versus never smokers. Increases were found in genes involved in xenobiotic metabolism, oxidant stress, eicosanoid synthesis, nicotine signaling, and cell adhesion. Increased numbers of Langerhans cells were found in the oral mucosa of smokers. Interestingly, smoking caused greater induction of aldo-keto reductases, enzymes linked to polycyclic aromatic hydrocarbon–induced genotoxicity, in the oral mucosa of women than men. Striking similarities in expression changes were found in oral compared with the bronchial mucosa. The observed changes in gene expression were compared with known chemical signatures using the Connectivity Map database and suggested that geldanamycin, a heat shock protein 90 inhibitor, might be an antimimetic of tobacco smoke. Consistent with this prediction, geldanamycin caused dose-dependent suppression of tobacco smoke extract–mediated induction of CYP1A1 and CYP1B1 in vitro. Collectively, these results provide new insights into the carcinogenic effects of tobacco smoke, support the potential use of oral epithelium as a surrogate tissue in future lung cancer chemoprevention trials, and illustrate the potential of computational biology to identify chemopreventive agents. Cancer Prev Res; 3(3); 266–78

The relationship between oral malodor and volatile sulfur compound-producing bacteria

Halitosis can be a crippling social problem, and standard dental treatments and mouthwashes often provide only temporary relief. The mouth is home to hundreds of bacterial species that produce several fetid substances as a result of protein degradation. Volatile sulfur compound (VSC)-producing bacteria colonizing the lingual dorsum have recently been implicated in the generation of halitosis. Detection of VSCs, such as methylmercaptan and hydrogen sulfite, via organoleptic and objective methods, can aid in the identification of their source. Following comprehensive evaluation for possible causes, most halitosis in patients seen in an ENT practice can be localized to the tongue. We review methods of diagnosis and treatment of oral malodor from the overgrowth of proteolytic, anaerobic, gram-negative bacteria on the crevices of the lingual dorsum. Bacteriologic analysis of biofilm and scraped specimens obtained from the lingual dorsum and other oral sites, primarily gingival pockets and tonsillar crypts, can identify VSC-producing bacteria. Porphyromonas, Prevotella, Actinobacillus, and Fusobacterium species are the most common organisms identified. Halitosis is an oral phenomenon, with almost no cases originating distal to the tonsils. Halitosis arising from the lingual dorsum secondary to overpopulated VSC-producing bacteria can be successfully managed with a combination of mechanical cleansing using tongue brushes or scrapes and chemical solutions containing essential oils, zinc chloride, and cetylpyridinium chloride.

Quantitative Videostroboscopic Measurement of Glottal Gap and Vocal Function: An Analysis of Thyroplasty Type I:

The goal of surgical medialization of the vocal fold is to attain complete glottic closure. The purpose of this study is to quantify the glottal gap and to examine the relationship between glottal gap and vocal function perioperatively in thyroplasty type I. Glottal gap area was measured in 20 patients at the point of maximum closure of vocal fold vibration in digitized laryngeal stroboscopic images and was normalized by the square of vocal fold length. Glottal gap area thus measured was correlated with results obtained from well-accepted acoustic, aerodynamic, and perceptual measures of vocal function. The glottal gap was significantly reduced after thyroplasty type I. In patients with small preoperative glottal gaps, the amplitude of vocal fold vibration was significantly improved. This study verifies that quantitative videostroboscopic measurement of the glottal gap is a useful means of objective evaluation of glottic incompetence and of the results of thyroplasty type I.

Endoscopic endonasal transethmoidal transcribriform transfovea ethmoidalis approach to the anterior cranial fossa and skull base.

OBJECTIVEThe anterior skull base, in front of the sphenoid sinus, can be approached using a variety of techniques including extended subfrontal, transfacial, and craniofacial approaches. These methods include risks of brain retraction, contusion, cerebrospinal fluid leak, meningitis, and cosmetic deformity. An alternate and more direct approach is the endonasal, transethmoidal, transcribriform, transfovea ethmoidalis approach. METHODSAn endoscopic, endonasal approach was used to treat a variety of conditions of the anterior skull base arising in front of the sphenoid sinus and between the orbits in a series of 44 patients. A prospective database was used to detail the corridor of approach, closure technique, use of intraoperative lumbar drainage, operative time, and postoperative complications. Extent of resection was determined by a radiologist using volumetric analysis. RESULTSPathology included meningo/encephaloceles (19), benign tumors (14), malignant tumors (9), and infectious lesions (2). Lumbar drains were placed intraoperatively in 20 patients. The CSF leak rate was 6.8% for the whole series and 9% for intradural cases. Leaks were effectively managed with lumbar drainage. Early reoperation for cerebrospinal fluid (CSF) leak occurred in 1 patient (2.2%). There were no intracranial infections. Greater than 98% resection was achieved in 12 of 14 benign and 5 of 9 malignant tumors. CONCLUSIONThe endoscopic, endonasal, transethmoidal, transcribriform, transfovea ethmoidalis approach is versatile and suitable for managing a variety of pathological entities. This minimal access surgery is a feasible alternative to transcranial, transfacial, or combined craniofacial approaches to the anterior skull base and anterior cranial fossa in front of the sphenoid sinus. The risk of CSF leak and infection are reasonably low and decrease with experience. Longer follow-up and larger series of patients will be required to validate the long-term efficacy of this minimally invasive approach.

Choanal Atresia, CHARGE Association, and Congenital Nasal Stenosis

Congenital bilateral narrowing or obstruction of the nasal airway can result in significant respiratory distress in the neonate, requiring emergency intervention. Some of these children have associated congenital malformations that may also impact on the management of the nasal anomaly. The embryology, presentation, and management of this spectrum of disorders are discussed, and the major surgical controversies are reviewed.

Use of potassium titanyl phosphate (KTP) laser in management of subglottic hemangiomas.

OBJECTIVE to study the role of KTP laser in management of subglottic hemangioma. DESIGN retrospective analysis of patients with subglottic hemangioma treated by the senior authors. SETTING tertiary care teaching hospital. PATIENTS twelve patients with subglottic hemangiomas. INTERVENTION patients were treated with KTP laser (eight cases), CO(2) laser (two cases) or observation (two cases). MAIN OUTCOME MEASURE resolution of symptoms, decrease in size of subglottic hemangioma or tracheotomy decannulation. RESULTS All patients treated with KTP laser or CO(2) laser had resolution of symptoms and five tracheotomy-dependent children were decannulated. CONCLUSION subglottic hemangioma is a potentially life-threatening disease seen in young children. Most authors recommend use of either CO(2) or open surgical excision. There is very little data available on the use of KTP lasers in the management of subglottic hemangiomas. The KTP laser beam is preferentially absorbed by hemoglobin making this laser system more applicable to the treatment of vascular tumors such as the hemangioma. KTP laser is a good tool for management of subglottic hemangioma with a low incidence of complications.

Endoscopic transphenoidal pituitary surgery with real-time intraoperative magnetic resonance imaging.

Background The aim of this study was to report and show the technique, results, and complications of combined endoscopic and intraoperative magnetic resonance imaging (IMRI) surgical treatment of pituitary disease from both a technical and a surgical perspective. Methods We performed a retrospective chart review of 10 endoscopic, endonasal resections of 10 pituitary macroadenomas using the Polestar N-10 IMRI system in a tertiary health care facility. The patient demographics, tumor measurements, and postoperative symptoms and complications were assessed. The effect of the magnetic field on the video screen, the image quality of the IMRI images, and IMRI detection of residual tumor were evaluated also. Results IMRI images were obtained in all cases and were of sufficiently high quality to indicate adequate decompression of the optic chiasm and the removal of all suprasellar tumor. However, there was significant distortion of the video monitor regardless of the viewing angle. This was overcome with a wall-mounted plasma screen. Residual tumor was found with IMRI and resected endoscopically in three cases. In two other cases, suspected residual tumor on IMRI was examined endoscopically and found to be a normal postoperative change. In two cases no tumor was seen on the IMRI. Five patients who had preoperative progressive visual loss preoperatively improved postresection and two patients who had increased insulin growth factor 1 preoperatively normalized postoperatively. No delayed cerebrospinal fluid leaks or any other complications occurred. Conclusion Combining intraoperative endoscopy and IMRI is an effective surgical modality for pituitary surgery. Each technology provides complimentary information, which can assist the surgeon in safely maximizing the extent of resection.

Effects of Tobacco Smoke on Gene Expression and Cellular Pathways in a Cellular Model of Oral Leukoplakia

Abstract In addition to being causally linked to the formation of multiple tumor types, tobacco use has been associated with decreased efficacy of anticancer treatment and reduced survival time. A detailed understanding of the cellular mechanisms that are affected by tobacco smoke (TS) should facilitate the development of improved preventive and therapeutic strategies. We have investigated the effects of a TS extract on the transcriptome of MSK-Leuk1 cells, a cellular model of oral leukoplakia. Using Affymetrix HGU133 Plus 2 arrays, 411 differentially expressed probe sets were identified. The observed transcriptome changes were grouped according to functional information and translated into molecular interaction network maps and signaling pathways. Pathways related to cellular proliferation, inflammation, apoptosis, and tissue injury seemed to be perturbed. Analysis of networks connecting the affected genes identified specific modulated molecular interactions, hubs, and key transcription regulators. Thus, TS was found to induce several epidermal growth factor receptor (EGFR) ligands forming an EGFR-centered molecular interaction network, as well as several aryl hydrocarbon receptor–dependent genes, including the xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Notably, the latter findings in vitro are consistent with our parallel finding that CYP1A1 and CYP1B1 levels were increased in oral mucosa of smokers. Collectively, these results offer insights into the mechanisms underlying the procarcinogenic effects of TS and raise the possibility that inhibitors of EGFR or aryl hydrocarbon receptor signaling will prevent or delay the development of TS-related tumors. Moreover, the inductive effects of TS on xenobiotic metabolizing enzymes may help explain the reduced efficacy of chemotherapy, and suggest targets for chemopreventive agents in smokers.