Lugol chromoendoscopy combined with brush cytology in patients at risk for esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Patients with achalasia or malignancies of the head and neck are at increased risk for esophageal squamous cell carcinoma. The discussion of a screening and surveillance program is controversial. The aim of the present study was to determine the diagnostic potential of Lugol chromoendoscopy combined with brush cytology to diagnose esophageal squamous cell carcinoma and high-grade dysplasia. Secondly, the benefit of additional biomarkers was investigated. PATIENTS AND METHODS: A total of 61 patients (21 patients with achalasia and 40 patients with malignancies of the head and neck) were included. Chromoendoscopy with 1.2% Lugol iodine solution with targeted biopsies and brush cytology processed by digital image cytometry (DICM) and fluorescence in situ hybridization (FISH) from unstained lesions (USLs) and stained mucosa were performed. RESULTS: Six of the 61 patients had USLs ≥2 cm. Four patients had high-grade dysplasia (HGD) or carcinoma in situ (CIS). One patient with HGD and one patient with CIS were detected only after Lugol chromoendoscopy. The sensitivity and specificity for detected HGD or CIS in USLs ≥2 cm were 100% and 96.5%. No dysplasia was found in USLs <2 cm. DNA ploidy by DNA cytometry and p53 loss of heterozygosity (LOH) by fluorescence in situ hybridization showed no additional impact on diagnostic accuracy. CONCLUSIONS: Lugol chromoendoscopy enhances the detection rate of high-risk lesions with dysplasia or carcinoma in situ in large unstained lesions. Biomarkers such as aneuploidy and p53 LOH from brush cytology were not of additional benefit in this setting.

[Blindness following reduction of a malar fracture]. / Erblindung nach Reposition einer Jochbeinfraktur.

Blindness is the most serious injury to the eye following a midfacial fracture. The onset of blindness complicating the midfacial fracture may be immediate (with the trauma), delayed (hours to days), or postoperative. The incidence of postoperative blindness lies between 0.3 and 8.3%. There are multiple mechanisms responsible for blindness but the most common reason with about 66% is probably increased intraorbital pressure attributable to intraorbital hemorrhage. The management of surgical decompression of the orbit for acute blindness is essential when treatment of a midfacial fracture is intended. Acute orbital compartment syndrome can effectively be relieved by lateral canthotomy and cantholysis and administration of high doses of corticosteroids. Further possibilities of surgical decompression of the orbit are discussed in this case report with postoperative irreversible blindness after reduction of a malar fracture and rapidly performed surgical decompression.

[Botulinum toxin A as a treatment of traumatic salivary gland fistulas]. / Botulinumtoxin A zur Therapie traumatischer Speichelfisteln.

Injury of salivary gland tissue in the head and neck, as the result of extensive trauma, can often be overlooked on initial examination. In two case reports, the primary treatment and further follow-up of injuries of the head resulting in a parotid-maxillary sinus fistula as well as a fistula between the skin and sublingual gland are illustrated. The successful use of botulinum toxin in the treatment of traumatic salivary gland fistulas is documented in both cases. Alternative diagnostic and treatment measures of salivary gland fistulas are discussed. Surgical repair of salivary fistulas as primary treatment should be carefully considered. Treatment of a salivary fistula with the injection of botulinum toxin is possibly advantageous compared to spontaneous fistula closure. The injection of botulinum toxin shortens fistula closure time, is minimally invasive, effective and tolerable for the patient.

Fiberoptically-guided insertion of transtracheal catheters.

IMPLICATIONS: Regular use of the transtracheal catheter (TTC) both offers an opportunity for training for the difficult airway and facilitates elective endoscopic surgery. Fiberoptic guidance and exploratory puncture improve the insertion of the TTC.

Proteasome- and p38-dependent regulation of ERK3 expression.

Proteasome inhibition leads to accumulation of transcription factors, heat shock proteins, cyclins, and other proteasome substrate proteins by blocking their proteolytic degradation. An increase in gene transcription upon proteasome inhibition was found for a group of proteins, including p21(WAF1/CIP1), ubiquitin, and transcription factors. In this study, we have demonstrated selective up-regulation of extracellular signal-regulated kinase 3 (ERK3) mRNA and protein expression upon treatment with peptide-based proteasome inhibitors or lactacystin. ERK3 is a family member of the mitogen-activated protein kinases (also called ERK) that are key mediators of signal transduction from the cell surface to the nucleus. ERK3 up-regulation is independent of the p53, Bcl2, and caspase 3 status of cells. p38 pathway kinase inhibitors prevent proteasome-dependent ERK3 induction and enhance the antiproliferative effect of proteasome inhibitors. MCF-7 cells expressing ERK3 ectopically show increased resistance toward proteasome inhibition. The results indicate that ERK3 expression is a consequence of p38 pathway activation and most probably represents an intracellular defense or rescue mechanism against cell stress and damage induced by proteasome inhibition.

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1.

The ubiquitin/proteasome pathway has been implicated in a wide variety of cellular processes and the number of substrates degraded by the proteasome is impressive. Most prominently, the stability of a large number of transcription factors is regulated by ubiquitination. To elucidate pathways regulated by the proteasome, gene expression profiles were generated, comparing changes of mRNA expression of 7900 genes from the UniGene collection upon exposure of cells to the proteasome inhibitors Lactacystin, Lactacystin-beta-lactone or MG132 by means of microarray based cDNA hybridization. The three profiles were very similar, but differed significantly from a gene expression profile generated with the histone deacetylase inhibitor Trapoxin A, indicating that the observed alterations were indeed due to proteasome inhibition. Two of the most prominently induced genes encoded the growth arrest and DNA damage inducible protein Gadd153 and the activating transcription factor ATF3, both transcription factors of the CCAAT/enhancer binding protein (C/EBP) family. A third gene encoded for the transcriptional repressor and c-Myc antagonist Mad1. Our results suggest that proteasome inhibition leads to upregulation of specific members of transcription factor families controlling cellular stress response and proliferation. Oncogene (2000).

[Thyroid surgery: traps and preventing complications]. / Schilddrüsenchirurgie: Fallen und Auswege.

A retrospective analysis was conducted of all thyroid operations performed at the ENT department in St. Gallen, Switzerland, between 1995 and 1997. The complications and technique of this surgery are outlined. In 79 patients 111 thyroid lobe resections were performed. No injury occurred to the superior laryngeal nerve. One recurrent laryngeal nerve injury and one permanent hypocalcaemia were observed. No revision operations were required for haematoma or infection. The different steps in the operative procedure, such as skin incision, handling of the strap muscles and identification of the parathyroid gland and superior laryngeal nerve, as well as the monitoring of the recurrent laryngeal nerve, are discussed.

[Cervical tuberculous lymphadenitis--an up-to-date guideline for management]. / Halslymphknotentuberkulose: aktuelles Abklärungs- und Behandlungskonzept.

For the past two decades the incidence of tuberculosis has been increasing, especially in developed countries. This is due to immigration from endemic countries, newly developed drug resistance, poor hygienic conditions for citizens of low socioeconomic status, and the spread of HIV-related immunodeficiency. Cervical tuberculous lymphadenitis is the most common form of extrapulmonary tuberculosis. In relation to the patients' age and immunocompetence, it is caused by typical or atypical mycobacteria. Within a period of 2 1/2 years we have treated 6 patients for mycobacterial infections in our department. We present an up-to-date guideline for management based on this experience. It combines well established diagnostic management with new criteria of ultrasonography, fine needle aspiration and mycobacterial cultures.

[Dislocation of the cricoarytenoid joint: diagnosis and therapy]. / Die Luxation des Krikoarytänoidgelenks: Diagnostik und Therapie.

BACKGROUND: Laryngeal joint injury or cricoarytenoid dislocation is a relatively rare laryngologic finding, according to the international medical literature. It may occur as a result of external neck trauma or more frequently as a result of intubation. Chief symptoms are hoarseness, vocal fatigue, and loss of voice control. PATIENTS: Between 1993 and 1997 we diagnosed an arytenoid dislocation in 2 female and 5 male patients, in every case the etiology was an intubation trauma. Videolaryngoscopic recording was the most useful aid in diagnosis. RESULTS: Six patients were treated with closed reduction surgery between 8 and 49 days after dislocations. Normal voice was restored in four patients, and in one patient as late as 49 days after the dislocation. One patient had an additional recurrent nerve paralysis. CONCLUSIONS: Our results suggest that a closed reduction of the arytenoid luxation can be successful even several weeks after the injury.

Position-independent expression of a human nerve growth factor-luciferase reporter gene cloned on a yeast artificial chromosome vector.

Two yeast artificial chromosomes containing the entire human nerve growth factor gene were isolated and mapped. By homologous recombination a luciferase gene was precisely engineered into the coding portion of the NGF gene and a neomycin selection marker was placed adjacent to one of the YAC telomeres. Expression of the YAC-based NGF reporter gene and a plasmid-based NGF reporter gene were compared with the regulation of endogenous mouse NGF protein in mouse L929 fibroblasts. In contrast to the plasmid-based reporter gene, expression and regulation of the YAC-based reporter gene was independent of the site of integration of the transgene. Basic fibroblast growth factor and okadaic acid stimulated expression of the YAC transgene, whereas transforming growth factor-beta and dexamethasone inhibited it. Although cyclic AMP strongly stimulated production of the endogenous mouse NGF, no effect was seen on the human NGF reporter genes. Downregulation of the secretion of endogenous mouse NGF already occurred at an EC50 of 1-2 nM dexamethasone, but downregulation of the expression of NGF reporter genes occurred only at EC50 of 10 nM. This higher concentration was also required for upregulation of luciferase genes driven by the dexamethasone-inducible promoter of the mouse mammary tumor virus in L929 fibroblasts.

[Inverted papilloma of the nose and paranasal sinuses]. / Invertierte Papillome der Nase und deren Nebenhöhlen.

BACKGROUND: Inverted papilloma is a rare benign tumor of the nose and the paranasal sinuses. There is a controversial discussion concerning the operative approach. The epidemiology, postoperative results, and recurrence rates of endonasally and extranasally operated patients are analysed. PATIENTS: Between 1984 and 1995, 25 patients with inverted papilloma were operated upon at the ENT Department St. Gallen, 18 patients by an endonasal microscopic approach, two by midfacial degloving and five through a lateral rhinotomy. RESULTS: After a minimal follow-up of 12 months (mean follow-up 52 months), a recurrence rate of 29% for the external approach and 31% for the endonasal approach was observed. CONCLUSIONS: In most cases it is possible to achieve a good result through an endonasal approach. External approaches are recommended in T4-tumors or carcinomas. A longtime follow-up is recommended for each case.

Temperature and pressure effects during erbium laser stapedotomy.

BACKGROUND AND OBJECTIVES: Laser-assisted stapedotomy has become a well-established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment. STUDY DESIGN/MATERIALS AND METHODS: On an inner ear model, time-resolved pressure measurements and Schlieren optical flash photography were performed during the perforation of the stapes foot plate using an erbium laser at 2.79 microns. The laser radiation was transmitted via an optical zirconium fluoride fiber. The laser-treated foot plates were investigated by light microscopy and scanning electron microscopy to visualise the laser-induced tissue effects. RESULTS: Perforation of the stapes foot plate can be performed with a few erbium laser pulses with high precision and a thermal damage zone of < 10 microns. Strong pressure transients were found to be generated by the bone ablation process and the collapse of a vapor channel created in the perilymph after fenestration. CONCLUSION: From the comparison of the laser-induced pressure with the limit graph to avoid hearing defects published by Pfander, an unobjectionable use of the erbium laser is deduced for fluences < 10 J/cm2. The erbium laser seems to represent an ideal instrument for middle ear surgery with all the advantages (precision, fiber optic transportable, high ablation efficiency, safety) desired for clinical application.

[Significance of Staphylococcus aureus in nose operations. Risk of toxic shock syndrome?]. / Bedeutung von Staphylococcus aureus bei Nasenoperationen. Gefahr des Toxic-shock-Syndroms?

In a prospective clinical trial the pre- and postoperative presence of S. aureus was examined in 130 patients undergoing nasal septal surgery. The patients were randomized into three groups. The first group received no perioperative antibiotics, the second group was given oral amoxicillin plus clavulanic acid, while the third group was treated with oral sulfamethoxazol and trimethoprim. A significant decrease in the incidence of S. aureus was observed in post-operative cultures, but the difference was not attributable to the antibiotic use. Overall, 18.9% of the S. aureus carriers harbored toxic shock syndrome toxin-1 positive strains. However, the decrease in the presence of S. aureus and the risk for toxic shock syndrome was not influenced by the antibiotics administered. These findings show that the routine use of oral prophylactic antibiotics for patients undergoing nasal surgery seems not indicated.

[Stapes revisions: clinical findings and results]. / Stapesrevisionen: Befunde und Resultate.

By correlating the intraoperative findings and the postoperative hearing gain it was attempted to determine the recommendable intraoperative management in stapesrevisions in order to obtain the best postoperative hearing. In a retrospective study the findings of 39 stapes revision operations were analyzed. In most of the cases hearing one year postoperatively was compared with preoperative hearing. The prognosis for good hearing was best following replacement of the prosthesis where the prosthesis was too short or dislocated, or in the presence of a loosened wire. Where treatment only entailed retightening the loosened wire at the long process of the incus, postoperative hearing did not improve. Patients with an obliterative otosclerosis or an additional fixed incus had a less favorable prognosis. Overall a postoperative air bone gap of 10 dB or below was obtained in 44% of the patients and a postoperative air bone gap of 20 dB or below in 77% of the patients. Twenty-one percent of the patients remained unchanged, and in one patient postoperative deterioration of the hearing was detected.

[Thyroidectomy and the recurrent laryngeal nerve]. / Thyreoidektomie und Nervus recurrens.

Iatrogenic injury of the recurrent laryngeal nerve is doubtless one of the main problems in thyroid surgery. 56 consecutive patients, which have undergone surgical treatment for thyroid disease over the past two years are analysed. The recurrent laryngeal nerve is routinely exposed during thyroid surgery in order to decrease the incidence of recurrent nerve lesions. Four patients had an unilateral paralysis prior to the operation. Six patients showed a paralysis after the surgical intervention, two of whom had a carcinoma, where the nerve had to be resected. The residual four cases had only a transitory functional loss of one vocal cord which recovered within two weeks. We are convinced that the incidence of permanent nerve injury can be greatly decreased by exposure of th recurrent laryngeal nerve during thyroid surgery.

[Results of a prospective open study of therapy of sudden deafness with flunarizine]. / Ergebnisse einer prospektiven offenen Studie zur Therapie des Hörsturzes mit Flunarizine.

The treatment effect of the lipophilic calcium antagonist flunarizine on the recovery of sudden hearing loss was evaluated in a prospective phase-II study. Thirty-seven patients presenting with recent and sudden onset of unilateral sensorineural hearing loss were treated with 50 mg flunarizine intravenously for the first two days followed by 10 mg flunarizine orally for four weeks. Pure-tone audiometry was done before the beginning of the treatment and after one and four weeks. The absolute and relative hearing gains after one and four weeks were compared to those of 67 similar patients previously treated with saline infusions and placebo tablets in the same institutions during a double blind study (Probst et al. Acta Otolaryngol. 112 (1992) 435-443). The mean absolute hearing gains of the flunarizine group was 17 dB and 21 dB, after one and four weeks respectively (placebo group: 16 dB and 24 dB). The corresponding relative hearing gains (defined as absolute gain divided by initial hearing loss) were 35% and 43% for the flunarizine group and 33% and 42% for the placebo group. We conclude that flunarizine treatment does not improve the recovery of sudden hearing loss.