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A J Nemechek

Publications and source records attributed to A J Nemechek.

8 recordsLinked to original sources
PubMed2001

Carcinomas of unknown primary in the head and neck.

In approximately 3% to 5.5% of patients presenting with squamous cell carcinoma metastasis to the cervical lymph nodes, the primary source remains elusive despite extensive evaluation and biopsy. The presenting symptom of a unilateral neck mass is initially evaluated with a complete history and physical. This is followed by flexible endoscopy, fine needle aspiration, laboratory and imaging studies and directed biopsies of the upper aerodigestive tract. While the initial attempt fails to locate the primary site, it will eventually become manifest in 20% to 40% of patients. Early identification decreases overall morbidity and mortality. This article summarizes contemporary diagnostic approaches, current imaging techniques, the role of tonsillectomy, and the management and outcomes of carcinoma of unknown primary.

Carcinoma, Squamous Cell↗
PubMed1999

PD 098059, an inhibitor of ERK1 activation, attenuates the in vivo invasiveness of head and neck squamous cell carcinoma.

Increased mortality of patients with oral cancer largely reflects the local and regional spread of the disease. The invasiveness of these tumours requires hydrolases which are regulated through AP-1-dependent transcriptional mechanisms. Since the amount/activity of transcription factors bound to the AP-1 motif are regulated partly through the extracellular signal-regulated kinases (ERK1/ERK2), we determined the effect of PD 098059, an inhibitor of ERK1/ERK2 activation, on the in vivo invasiveness of a human squamous cell carcinoma cell line (UM-SCC-1) derived from the oral cavity. We utilized the floor of mouth musculature consisting of the mylohyoid, geniohyoid and genioglossus muscle (which are sequentially arranged), as a natural barrier to assess tumour spread in vivo in the nude mouse. Mice were inoculated with tumour cells superficial to the mylohyoid muscle. After 18 days, tumours were injected with either empty liposomes (control) or liposomes containing 5 microM PD 098059 and, after an additional 22 days, the jaws of mice examined histologically. Highly infiltrative tumours, which had penetrated the genioglossus muscle, were evident in 10/12 control mice. In contrast, in 9/12 mice in which the tumours were injected with PD 098059, tumours did not extend beyond the mylohyoid or geniohyoid muscles. Tumours penetrated bone nutrient canals in 7/12 control mice but in only 3/12 PD 098059-treated mice. Neurotropism, characteristic of aggressive oral squamous cell carcinoma, was evident in 6/12 control mice but was completely abolished (0/12 mice) in the PD 098059-treated mice. Using a staging system based on the muscle layer involved, neurotropism, as well as bone involvement, we found the inhibition of invasion to be statistically significant (P < 0.01). The reduced invasiveness of the PD 098059-liposome-treated oral cancers was associated with diminished 92-kDa type IV collagenase and ERK1/ERK2 activities but was not a consequence of a slower tumour growth rate. This is the first study to demonstrate reduced in vivo invasiveness of a malignancy brought about by an inhibitor of ERK1/ERK2 activation. These results raise the exciting possibility that second generation PD 098059 congeners may reduce the spread of the disease in patients afflicted with oral cancers.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

An orthotopic floor-of-mouth cancer model allows quantification of tumor invasion.

OBJECTIVES: To establish an orthotopic murine floor-of-mouth cancer model for the analysis of the role of proteases such as urokinase-type plasminogen activator (u-PA) and the matrix metalloprotease MMP-9 (MMP-9) in in vivo invasion. STUDY DESIGN: Randomized, prospective animal study. METHODS: Two human squamous cell carcinoma cell lines, UM-SCC-1 and 022, were assayed via zymography for their in vitro secretion levels of u-PA and MMP-9. Both cell lines (5 x 10(6) cells) were injected into the cervical subcutaneous tissues of female athymic nude (nu/nu) mice superficial to the mylohyoid muscle. Mice were sacrificed after 30 days, and tumor invasion characteristics were histologically compared. Additional mice were then inoculated with invasive UM-SCC-1 cells and sacrificed 10, 30, and 40 days after inoculation to identify distinct stages of invasion. RESULTS: In vitro secretion levels of MMP-9 and activity of u-PA were higher in UM-SCC-1 cells than in 022 cells. In the in vivo studies, tumors formed from 022 cells were found to be noninvasive, whereas tumors derived from UM-SCC-1 cells progressed through distinct and readily identifiable histologic stages of invasion. These stages included invasion of adjacent muscle layers (mylohyoid, geniohyoid, and genioglossus muscles) and of associated structures (blood vessels, bone, nerve, and regional lymph nodes). A staging system was devised accordingly. CONCLUSION: We developed an in vivo quantitative cancer invasion model that allows determination of the effect of the expression and activity levels of the proteases MMP-9 and u-PA. Tumor invasion occurred in an orderly and stepwise fashion involving muscles and related vascular, nervous, and bony structures of the floor of the mouth and tongue. This orderly invasion allowed the development of a staging system. We anticipate that this model will have wide applicability in the study of in vivo tumor response to a variety of novel therapeutic approaches.

Animals↗
PubMed1997

Nebulized surfactant for experimentally induced otitis media with effusion.

Eustachian tube dysfunction frequently results in clinical evidence of otitis media with effusion (OME). Surface active substances, surfactants, are hypothesized to play a role in normal eustachian tube function. Recent work in a rodent model has demonstrated improved eustachian tube function with topical application of surfactants to the middle ear. A novel, noninvasive, and clinically practical method of delivering surfactant to the eustachian tube was studied in a gerbil model of OME. Otitis media with effusion was experimentally induced in 20 gerbils by transtympanic inoculation of heat-killed Streptococcus pneumoniae. This represents a well established model for creating a serous effusion in the gerbil that significantly increases eustachian tube opening pressure. Effusion developed in 27 of 40 ears (67.5%) after inoculation. An inhaled nebulized surfactant was used to treat the animals with microscopically confirmed OME in one or both ears. The treatment period was 5 days. Eustachian tube opening studies were performed on both affected and nonaffected animals. Successful eustachian tube opening pressures were obtained in 30 of 36 ears (83.3%). The mean opening pressure for ears without effusion (healthy ears) was 42.8 mmHg. The mean opening pressure for ears with effusion in animals treated with nebulized surfactant was 41.4 mmHg. The difference between these mean values was not statistically significant (t = 0.32; p > 0.50). This pilot study suggests that inhaled nebulized surfactant may be efficacious in treating eustachian tube dysfunction when manifested in disorders such as OME.

Administration, Inhalation↗
PubMed1996

Zenker's diverticula.

Zenker's diverticula, or hypopharyngeal diverticula, have a multifactorial etiology including both mechanical and structural factors. The diagnosis of the diverticula is based on an accurate history and physical examination and is confirmed with contrast radiography. Historically, the management of Zenker's diverticula has been controversial. Nonetheless, if the patient is symptomatic, surgical management is indicated. Surgical procedures include cricopharyngeal myotomy, diverticulopexy, diverticulum resection, and endoscopic diathermy (the Dohlman procedure). Each has its proponents and each has its disadvantages and complication rates. The decision as to which procedure to use hinges on clinical factors such as the patient's age, general state of health, and whether or not the lesion is recurrent. The pathophysiology of Zenker's diverticula is discussed with special reference to the anatomy of the hypopharynx. The evaluation of these patients is reviewed, as are some of the current surgical approaches employed when treating Zenker's diverticula.

Humans↗
PubMed1995

Tumors of the external ear.

A variety of medical specialists are exposed to patients who seek treatment of external ear neoplasms. They are uncommon occurrences, and malignancies of the external ear are even rarer. Only 1 patient in 10,000 with an ear complaint will have a pathologically proven malignancy of the external ear. Tumors of the external ear, both malignant and benign, commonly resemble one another. A timely and correct diagnosis is necessary to avoid affecting the external ear's ability to collect sound, but also to avoid the more morbid and mortal complications of an external ear malignancy. This paper briefly outlines the epidemiology of external ear tumors, their etiology, related histopathology, and treatment, which encompasses a myriad of modalities and specialties.

Ear Diseases↗
PubMed1994

Choanal atresia.

The epidemiology of choanal atresia is not always clear. it is a rare phenomenon having an incidence of between 1 in 6,000 to 1 in 8,000 live births. It exhibits a slightly female-to male preponderance, 51% to 53% versus 49% to 47%, in some studies. The unilateral form of choanal atresia is more common than bilateral, 60% to 64% versus 40% to 36%. The right nasal passage is affected more often than the left in unilateral lesions, and in 90% and more of lesions the atretic portion is bony rather than membranous.

Choanal Atresia↗