Optical coherence tomography allows for the reliable identification of laryngeal epithelial dysplasia and for precise biopsy: a clinicopathological study of 61 patients undergoing microlaryngoscopy.

OBJECTIVES/HYPOTHESIS: A newly developed microscope-based spectral-domain optical coherence tomography (SD-OCT) device and an endoscope-based time-domain OCT (TD-OCT) were used to assess the inter-rater reliability, sensitivity, specificity, and accuracy of benign and dysplastic laryngeal epithelial lesions. STUDY DESIGN: Prospective study. METHODS: OCT during microlaryngoscopy was done on 35 patients with an endoscope-based TD-OCT, and on 26 patients by an SD-OCT system integrated into an operating microscope. Biopsies were taken from microscopically suspicious lesions allowing comparative study of OCT images and histology. RESULTS: Thickness of the epithelium was seen to be the main criterion for degree of dysplasia. The inter-rater reliability for two observers was found to be kappa = 0.74 (P <.001) for OCT. OCT provided test outcomes for differentiation between benign laryngeal lesions and dysplasia/CIS with sensitivity of 88%, specificity of 89%, PPV of 85%, NPV of 91%, and predictive accuracy of 88%. However, because of the limited penetration depth of the laser light primarily in hyperkeratotic lesions (thickness above 1.5 mm), the basal cell layer was no longer visible, precluding reliable assessment of such lesions. CONCLUSIONS: OCT allows for a fairly accurate assessment of benign and dysplastic laryngeal epithelial lesion and greatly facilitates the taking of precise biopsies. Laryngoscope, 2010.

Studies on Paraherquamide Biosynthesis: Synthesis of Deuterium-Labeled 7-Hydroxy-Pre-Paraherquamide, a Putative Precursor of Paraherquamides A, E & F.

The stereocontrolled, asymmetric synthesis of triply deuterium-labeled 7-hydroxy-pre-paraherquamide (27) was accomplished, employing a diastereoselective intramolecular S(N)2' cyclization strategy. The deuterium-labeled substrate was interrogated in a precursor incorporation experiment in the paraherquamide-producing organism Penicillium fellutanum. The isolated sample of paraherquamide A revealed incorporation of one of the two geminal deuterons of the CD(2)-group at C-12 exclusively. The lack of signals for the second deuteron of the CD(2)-group at C-12 and for the CH(2)D-group (C-22/C-23) suggests that this substrate suffered an unexpectedly selective catabolic degradation and metabolic re-incorporation of deuterium thus casting doubt on the proposed biosynthetic intermediacy of 27. Consideration of alternative biosynthetic pathways, including oxidation of the indole C-6 position prior to hydroxylation at C-7 or oxidative spiro-contraction of pre-paraherquamide prior to construction of the dioxepin is discussed. The synthesis of 27 also provides for a concise, asymmetric stereocontrolled synthesis of an advanced intermediate that will be potentially useful in the synthesis of paraherquamide E & F.

Studies Towards Paraherquamides E & F and Related C-labeled Putative Biosynthetic Intermediates: Stereocontrolled Synthesis of the α-Alkyl-ß-Methylproline Ring System.

A substituted 2R-allyl-3S-methylproline ethyl ester suitable for elaboration to paraherquamides E, F and related (13)C-labelled putative biosynthesis intermediates have been prepared efficiently in six steps and 24% overall yield. The key steps are a 5-exo-trig cyclization of a zinc enolate on an unactivated alkene and a stereocontrolled alkylation of the enolate formed from 3S-methyl-pyrrolidine-1,2R-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester.

Classification and management of tracheoesophageal and tracheopharyngeal fistulas after laryngectomy.

OBJECTIVES: Tracheoesophageal fistulas (TEF) and tracheopharyngeal fistulas (TPF) are intentionally created for prosthetic or surgical voice restoration after laryngectomy or can develop after radiotherapy or surgical interventions. If the fistula does not shrink or close spontaneously or does not respond to conservative measures, surgical closure of the fistula is indicated. STUDY DESIGN: Retrospective study of 177 patients. METHODS: Data of 168 laryngectomy patients who needed a voice prosthesis (VP) replacement were obtained. Our experiences with nine severe TEF/TPF were analyzed, and a classification of these fistulas depending on the anatomic and clinical appearance was developed. RESULTS: TEF/TPF can be divided into five types: high TEF with leakage through the VP (type Ia), high TEF with leakage around the VP (type Ib), enlarged high TEF (type II), deep TEF (type III), TPF (type IV), and TPF associated with pharynx stenosis (type V). Persisting TEF/TPF after unsuccessful attempts at surgical closure in four patients and the surgical solutions and procedures in these rare cases are discussed in detail. CONCLUSIONS: Leakage of TEF in prosthetic voice restoration usually responds well to conservative measures. If these measures fail, and in all cases of TPF, surgical intervention is necessary for transtracheostomal or transcervical closure with multilayer sutures of the esophagus and trachea. Persisting TEF/TPF after unsuccessful surgical attempts at revision surgery remain challenging. Our experiences show that tracheostoma transposition for dissociation of the cranial end of the trachea and the hypopharynx and esophagus is essential for effective closure. In rare cases of TPF combined with pharyngoesophageal stricture formation, a resection and immediate reconstruction of the stenotic pharyngoesophageal segment with a tube-shaped fasciocutaneous radial forearm flap must be considered.

Enantioselective palladium-catalyzed total synthesis of vitamin e by employing a domino Wacker-Heck reaction.

An enantioselective total synthesis of vitamin E in which a novel palladium-catalyzed domino reaction was employed as the key step is described. This reaction allows the formation of the chiral chroman framework and the concurrent introduction of part of the side chain of vitamin E. The sequence comprises an enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly, reaction of alkenylphenol 12 with methyl vinyl ketone (13) in the presence of catalytic amounts of Pd(OTFA)(2) (TFA = trifluoroacetate), the enantiopure ligand (S,S)-Bn-BOXAX (8 b; Bn = benzyl, BOXAX = 2,2'-bis(oxazolyl)-1,1'-binaphthyl, and p-benzoquinone (9) as an oxidant gives access to chiral chroman 10 with an enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24 by an aldol condensation reaction with (3R)-3,7-dimethyloctanal (11). Subsequent 1,2-addition of methyllithium, elimination of water, and hydrogenation yields vitamin E.

Leiomyosarcoma of the parotid gland: a case report.

Primary leiomyosarcoma of the parotid gland is an extremely rare neoplasm. We here describe the case of a 78-year-old male patient presenting with such a tumor. Five years after surgical treatment, the patient is alive and recurrence-free. To our knowledge, our case represents just the sixth case of primary leiomyosarcoma of the parotid gland reported in the English literature. The clinical features of these cases are summarized.

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?

PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. PATIENTS AND METHODS: 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. RESULTS: 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. CONCLUSIONS: According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.

Intraoperative assessment of perilymphatic fistulas with intrathecal administration of fluorescein.

OBJECTIVES: Assessment of perilymphatic fistulas remains a diagnostic problem. Because of a lack of reliable clinical tests, exploratory tympanotomy is necessary to detect membrane leaks in the middle ear. To improve objectivity in the intraoperative visualization of perilymphatic fistulas, we used intrathecal fluorescein for perilymph staining to increase the sensitivity and specificity of diagnosis of perilymphatic fistulas. STUDY DESIGN: Prospective study in the setting of a tertiary, referral, and academic center. METHODS: Twenty-eight patients with suspected traumatic, idiopathic, iatrogenic, or inflammatory perilymphatic fistulas were admitted for exploratory tympanoendoscopy for perilymphatic fistula detection. Twenty-five to 100 mg sodium fluorescein 10%, diluted with cerebrospinal fluid, was administered by lumbar puncture 2.5 to 23.5 hours before tympanoendoscopy. The oval and round window niches were microscopically and endoscopically observed with white and blue light, using specific filters. RESULTS: In two patients (7%), obvious fluorescence was detected behind the round window membrane with blue light. Direct observation of perilymph in stapedectomy and in semicircular canal fistula revealed no staining. Neurological complications of intrathecal fluorescein, as reported by other authors, were not observed. CONCLUSIONS: Probably because of a different patency of the cochlear aqueduct, intrathecal fluorescein for intraoperative detection of perilymphatic fistula resulted in a significant perilymph staining in only a few patients. Considering the possible complications of this method, we would not recommend it for routine evaluation of perilymphatic fistula.