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Biomedical subjects

K D McClatchey

Publications and source records attributed to K D McClatchey.

At least 19 recordsLinked to original sources

Evidence that loss of chromosome 18q is associated with tumor progression.

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of 18q. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.

Carcinoma, Squamous Cell

Overexpression of p53 predicts organ preservation using induction chemotherapy and radiation in patients with advanced laryngeal cancer. Department of Veterans Affairs Laryngeal Cancer Study Group.

A critical research frontier in head and neck oncology involves defining the use of induction chemotherapy regimens to allow organ preservation and to avoid functionally debilitating surgical resections. Completed clinical trials in laryngeal cancer indicate that such an approach is feasible, but progress thus far has been limited by our inability to predict which patients are likely to respond to chemotherapy and preserve their larynx. Mutation of the p53 tumor-suppressor gene is the most common genetic alteration identified thus far in human cancers, and it may be important in regulation of cell proliferation and chemosensitivity. To determine whether p53 overexpression predicts chemotherapy response, organ preservation, and survival in patients with advanced laryngeal cancer, we analyzed immunohistologic expression of p53 in tissue sections from 178 patients with advanced laryngeal cancer who were entered in the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multiinstitutional clinical trial comparing induction chemotherapy (cis-platinum and 5-fluorouracil) plus radiation therapy (94 patients) to surgery plus postoperative radiation therapy (84 patients). Larynx preservation was significantly higher in the group of patients whose tumors overexpressed p53 (74% vs. 52.5%; p = 0.03). The presence of p53 overexpression did not predict survival in either the surgery or the chemotherapy groups (p = 0.82 and p = 0.53).

Antimetabolites, Antineoplastic

Presence of human papillomavirus predicts recurrence of inverted papilloma.

Recent evidence suggests that human papillomavirus may play a role in the pathogenesis of inverted papilloma, a benign but locally aggressive neoplasm with a high recurrence rate and an association with squamous cell carcinoma. Histologic features of inverted papilloma have not been useful in discriminating lesions at high risk for recurrence. We studied archival pathology specimens from 32 patients with inverted papilloma treated at the University of Michigan between 1980 and 1994 with polymerase chain reaction techniques and human papillomavirus E6 and L1 consensus primers. Twenty (63%) specimens tested positive for human papillomavirus. The clinical status of the remaining 25 patients was reviewed after seven patients with recent diagnosis or who were lost to follow-up were excluded. A significant association was identified between the presence of human papillomavirus DNA in inverted papilloma and recurrence after surgical excision. Thirteen of 15 patients whose tumors tested positive for HPV recurred, whereas none of the 10 patients whose tumors were human papillomavirus negative recurred (p < 0.00002). This strongly suggests that the presence of human papillomavirus predicts recurrence of inverted papilloma.

Adult

Perilesional interleukin-2 in the VX-2 carcinoma in rabbits: a preliminary investigation.

Immune system amplification by perilesional injection of interleukin-2 is a promising adjuvant approach for treating squamous cell carcinoma of the head and neck. A pilot study was designed to develop an animal model bearing squamous cell carcinoma in which to test the efficacy of perilesional interleukin-2. Rabbits were inoculated intramuscularly with the papilloma virus-induced squamous carcinoma VX-2 cell line. Tumor regression and host lymphatic response after perilesional interleukin-2 were measured. Variable responses were found. Growth of tumor cells implanted from cell culture was rapid in most animals. Tumor growth was prevented in animals receiving 10,000 units of interleukin-2 per injection initiated 9 days after tumor inoculation. This inhibition approached statistical significance when compared with growth of saline controls. Histologic responses consisted primarily of plasma cell and eosinophil infiltration. The intensity of the inflammatory response did not correlate with interleukin-2 dose. A trend toward enhanced tumor growth was seen with lower doses of interleukin-2 and when interleukin-2 therapy was initiated simultaneously with tumor inoculation. These findings suggest that high-dose recombinant interleukin-2 can prevent tumor growth if initiated after tumor inoculation. Whether this effect was caused by direct tumor cytotoxicity or mediated by the immune system is unclear. These preliminary results underscore the importance of understanding the effects of dose and schedule in the design of immunotherapy models before clinical use.

Animals

Human papillomavirus types important in progression of inverted papilloma.

Recent evidence suggests that human papillomavirus may play a role in the pathogenesis of inverted papilloma, a benign but locally aggressive neoplasm with a high recurrence rate and an association with squamous cell carcinoma. Histologic features of inverted papilloma have not been useful in discriminating lesions at high risk for malignant transformation. We studied archival pathology specimens from 39 patients with inverted papilloma treated at the University of Michigan between 1980 and 1994 using polymerase chain reaction techniques and human papillomavirus L1 and E6 consensus primers. Previously we reported that 63% of these specimens tested positive for human papillomavirus sequences and that presence of human papillomavirus predicted recurrence of inverted papilloma. We used type-specific primer pairs and polymerase chain reaction techniques as well as hybridization with type-specific oligonucleotide probes to determine human papillomavirus type. A significant correlation was observed between the severity of the lesion (dysplasia or carcinoma) and high risk human papillomavirus type (p < 0.01). All 12 benign inverted papilloma specimens that contained human papillomavirus tested positive for human papillomavirus 6 or 11. Of seven inverted papilloma specimens that exhibited dysplasia, five were human papillomavirus positive, three contained human papillomavirus 6, one contained human papillomavirus 11, and one contained human papillomavirus 18. In each of the three specimens that contained inverted papilloma in association with squamous cell carcinoma, the inverted papilloma portion of the specimen tested positive for a single human papillomavirus type: human papillomavirus 6, 11, or 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Eosinophilic infiltration in advanced laryngeal squamous cell carcinoma. Veterans Administration Laryngeal Cooperative Study Group.

Tumor-associated tissue eosinophilia (TATE) has been related to prognosis in epithelial cancers, including cancers at several head and neck sites. This study prospectively examined 248 patients with stage III and IV laryngeal squamous cell carcinoma to determine prevalence and potential prognostic significance of TATE. Pretreatment tumor specimens were histopathologically evaluated. Presence and degree of TATE were analyzed with regard to other tumor characteristics, patient characteristics, and outcome criteria. Median follow-up was 48 months. Eosinophilia was found in 22.5% of specimens and was not related to tumor site, stage, patient age or sex, or treatment modality. Overall and disease-free survival rates and response to induction chemotherapy did not differ significantly with respect to TATE. This study represents the first long-term, prospective evaluation of TATE and its prognostic significance in a single head and neck site. Contrary to the findings of earlier preliminary reports, our results suggest that TATE is not a clinical useful prognostic parameter in advanced laryngeal squamous cell carcinoma.

Age Factors

Laryngeal liposarcoma.

Laryngeal liposarcomas are rare, with only 13 previously well-documented cases (to our knowledge). We report an additional case, which documents the use of computed tomography for treatment planning. Laryngeal liposarcomas appear to have a better prognosis than nonlaryngeal liposarcomas; therefore, a critical analysis of reported cases enabled us to identify clinical characteristics that contribute to the favorable prognosis. We also propose a rational therapeutic approach.

Adult

Branchiogenic carcinoma.

The validity of the diagnosis 'branchiogenic carcinoma' has been debated for many years. Recently, Micheau, et al recorded 21 cases of metastatic squamous carcinoma that presented with cystic masses in the neck and concluded that most, if not all of the reported cases of branchiogenic carcinoma, were in fact of similar origin. This report contains histological evidence of the origin of squamous cell carcinoma from a branchiogenic cyst in an otherwise healthy young man. Five similarly convincing reports from the literature are also reviewed.

Adult

DNA content and histologic growth pattern correlate with prognosis in patients with advanced squamous cell carcinoma of the larynx. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group.

BACKGROUND: Alterations in DNA content, nuclear morphologic characteristics, and histologic grading have been associated with prognosis in several types of solid malignant neoplasms. METHODS: To determine the potential usefulness of these factors in predicting tumor behavior in patients with laryngeal squamous cell carcinoma, tumor specimens from 88 previously untreated patients with Stage III or IV cancers were studied. The DNA content and nuclear area (NA) were measured for individual nuclei of each tumor with the use of Azure A-stained frozen sections. An adjusted DNA index (aDI) for each patient was calculated from the slope of the linear regression analysis of nuclear DNA index on NA. Hematoxylin and eosinstained sections were examined and graded systematically for histologic growth pattern. All patients were enrolled in a prospective clinical trial and had laryngectomy and postoperative radiation therapy. RESULTS: The disease-free survival length was longer and the relapse rates were lower in patients with a low aDI (P less than 0.005) and with tumors exhibiting low-grade growth patterns (P less than 0.001). CONCLUSIONS: These parameters were independent of staging variables and were better predictors of tumor relapse than traditional clinical staging classifications.

Adult

Signet-ring cell adenocarcinoma metastatic to the maxillary sinus.

Signet-ring cell variant is a rare type of adenocarcinoma that has been reported in the paranasal sinuses and in other areas, most commonly the gastrointestinal tract. We describe a patient with signet-ring cell adenocarcinoma of the maxillary sinus who had dental and facial pain. Further evaluation revealed that the lesion was metastatic from an esophageal primary lesion. The unusual nature of this cell type and the importance of careful evaluation to exclude the possibility of these lesions representing metastatic lesions is discussed.

Adenocarcinoma, Mucinous

Mucoepidermoid carcinoma associated with acute lymphoblastic leukemia.

As treatment and survival of acute leukemia as well as other types of pediatric cancer improve, the number of second malignancies in these treated patients will increase. Occurrence of these second malignancies in the head and neck is not frequently reported although it is known that radiation treatment, chemotherapy and sometimes the primary lesion itself are risk factors for neoplasia. Malignancies of the parotid gland in the pediatric population are known to be unusual. We discuss a mucoepidermoid carcinoma in a 10-year-old female who 7 years earlier had undergone successful treatment of acute lymphoblastic leukemia.

Carcinoma

Integrating total quality management and quality assurance at the University of Michigan Medical Center.

Staff members from the University of Michigan Medical Center (UMMC), 1990 winner of the Commitment to Quality Award, describe how they integrated its quality assurance (QA) program into its total quality management (TQM) strategy. The QA program has changed in recent years to establish quality as a central priority, to educate staff in the importance of quality, and to disseminate information more effectively. While these initiatives were underway, UMMC began to embrace TQM as an operating philosophy. Recognizing both the strengths and weaknesses of QA, staff members have worked to apply TQM principles (eg, focus on processes) to QA while using the ongoing monitoring of QA to identify opportunities for improvement within the organization's TQM management system.

Forms and Records Control

Olfactory neuroblastoma associated with Kallman's syndrome.

Kallman's syndrome is an unusual clinical entity that includes anosmia and hypogonadotropic hypogonadism. We present a patient in whom an olfactory neuroblastoma was discovered during evaluation of his Kallman's syndrome. While other craniofacial abnormalities have been associated with this condition, to our knowledge this is the first report of its association with olfactory neuroblastoma.

Adolescent

In vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck.

Twenty-five squamous cell carcinoma (SCC) cell lines from 20 patients with head and neck cancer were assessed for radiosensitivity in vitro using a 96-well plate assay. Four non-SCC lines were also tested. Radiation sensitivity of individual cell lines was compared using the area under the survival curve (AUC) as a measure of the mean inactivation dose. Tumor lines were tested with either a cobalt-60 (60Co) gamma-irradiator having a dose rate of 100 cGy/minute or with a 4-meV photon beam having a dose rate of 200 cGy/minute. The mean AUC of the 25 SCC cell lines was 188 +/- 7 (SEM) cGy (range, 100 to 250 cGy) whereas the four non-SCC lines had a mean AUC of 225 +/- 9 cGy. The SCC cell lines with mean inactivation dose values greater than 188 cGy were classified as relatively radioresistant whereas those with values less than 188 cGy were considered relatively radiosensitive. In seven cases SCC cell lines were derived from patients who had already received radiation therapy. In four of these cases the tumor cell lines were radioresistant (AUC, 210 to 250) but in the other three cases the tumor lines were radiosensitive (AUC, 160 to 180). Thus, failure of a tumor to respond to radiation did not always select for radioresistant cells. The mean of the AUC for cell lines from previously irradiated patients (197 +/- 11 cGy) did not differ significantly from that of the cell lines from patients who received no prior radiation therapy (182 +/- 9 cGy). However, among radiation-resistant lines those from the four previously irradiated patients were significantly more resistant (mean AUC = 235 +/- 9) than seven other radioresistant lines from nonirradiated patients (mean AUC, 208 +/- 4) (P = 0.0194). In four cases more than one cell line was derived from different tumor specimens in the same patient. In each of these cases the lines from the same patients were similar to one another in their degree of radioresistance. Based on these observations the authors conclude that the degree of in vitro radiation resistance is an inherent property of some squamous cell tumors.

Adult

Primary adenocarcinoma of the temporal bone. A case with 40-year follow-up.

Adenomatous tumors of the temporal bone are rare neoplasms. This article records the 40-year course of a patient with adenocarcinoma of the temporal bone and reviews the literature pertinent to the biologic behavior, histologic appearance, prognosis, and treatment of this group of tumors.

Adenocarcinoma

An uncommon case of parotid sialolithiasis.

A vivid example of parotid sialolithiasis diagnosed with an anterior-posterior radiograph and subsequently followed with a superficial parotidectomy is presented. The case presentation is preceded and followed by a discussion of the pathogenesis and treatment of such an abnormality.

Fibrosis

Unilateral multicentric Warthin's tumors.

Papillary cystadenoma lymphomatosum, or Warthin's tumor, is known to have a high rate of multicentricity. An incidence of 5-14% is suggested by the literature. We present a female patient with three discrete masses noted in the superficial lobe of the parotid gland at the time of surgical resection. The epidemiology, histology and pathophysiology of Warthin's tumor is discussed and the need for adequate surgical resection is emphasized.

Adenolymphoma