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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
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

ABO Blood-Group System↗
PubMed1990

Phenotypic characterization, karyotype analysis and in vitro tamoxifen sensitivity of new ER-negative vulvar carcinoma cell lines, UM-SCV-1A and UM-SCV-1B.

Two cell lines (University of Michigan squamous carcinoma of the vulva UM-SCV-1A and UM-SCV-1B) were established from the primary tumor and a malignant pleural effusion of a 62-year-old woman. Both tumor specimens grew vigorously in vitro and could be passaged after only 14 and 10 days in culture, respectively. Both cell lines undergo 3 population doublings in 4 days, reaching saturation densities of 5 x 10(5) cells/cm2, and have been carried through more than 30 in vitro passages. In nude mice the cultured cells initially formed tumors but these regressed 2-3 weeks after inoculation. The regressing mouse tumors consisted of poorly differentiated squamous carcinoma surrounded by an inflammatory lymphoid infiltrate. The UM-SCV-1 cell lines express membrane antigens typically displayed by squamous-cell carcinomas. These include the HLA class-1 light chain beta 2-microglobulin, pemphigus, pemphigoid, and the alpha 6 beta 4 integrin defined by the UM-A9 monoclonal antibody (MAb). In contrast to the A431 vulvar carcinoma, these tumor lines do not have amplified expression of the epidermal growth factor (EGF) receptor. Although tissue from the primary tumor contained low levels of estrogen receptor activity, no receptor activity was detected in the cell lines. Nevertheless, both lines were sensitive to growth inhibition by tamoxifen. This effect was not reversible by estradiol, indicating an estrogen-receptor-independent mechanism. The tumors were both hypotetraploid, contained the same chromosome rearrangements and had stable karyotypes in vitro. Each contained inv(1)(p36.3q32.1), del(4)(q12), dic(4;11)(q12;p11.2), i(5p), der(6)t(3;6)(q25.1;p21.1), several rearrangements involving chromosomes 8 and 14, + i(13), i(18p), a dicentric t(11;19), and 2 or 3 unidentified markers. Since the karyotypes of both tumors were the same, no major karyotypic change was associated with metastatic spread. These paired primary and metastatic SCC lines from an unusually aggressive vulvar carcinoma provide an in vitro model for analysis of the biological basis of this tumor's behavior.

Animals↗
PubMed1990

Establishment and characterization of UM-EC-2, a tamoxifen-sensitive, estrogen receptor-negative human endometrial carcinoma cell line.

UM-EC-2 was established from a patient with poorly differentiated stage IB endometrial carcinoma. This cell line produces tumors in nude mice that have the same histological features as the patient's tumor. UM-EC-2 cells express b2-microglobulin, the epidermal growth factor receptor (EGF), and the H blood group antigen. This membrane antigen phenotype is consistent with cells of human endometrial origin. The karyotype of UM-EC-2 is fairly complex, with rearrangements affecting all chromosomes except 3, 10, 14, 19, and 20. There were two populations of cells, a hyperdiploid population with a modal number of 53-55 and a hypertetraploid population with a modal number of 109. A postulated sequence of events before and after tetraploidization is suggested based on the number of copies of individual chromosomes and rearrangements. Comparison of the UM-EC-2 karyotype to that of UM-EC-1 (a previously described line from a different patient with endometrial carcinoma) revealed that the two lines share eight very similar chromosome changes, which include loss of most of chromosome 4, breakpoints affecting proximal bands on 8p, loss of most of 9q, a breakpoint at 12q22, loss of 13q, breakpoints in proximal bands on 18q, and a breakpoint at 22p11. These changes may represent nonrandom chromosome abnormalities in poorly differentiated endometrial cancer. Estrogen (ER) and progesterone (PgR) receptors were not detected in either the primary tumor or the cell line. Nevertheless, UM-EC-2 cells were very sensitive to growth inhibition by tamoxifen (TAM) in vitro. One micromolar TAM caused 50% inhibition of cell growth, 2.5 microM caused cytostasis, and 5 microM TAM was cytotoxic, killing all cells after 5-7 days of exposure to the drug. Paradoxically, 100 nM estradiol (E2) caused a moderate increase in the growth of the cells but it did not prevent or reverse growth inhibitory effects of TAM. These findings support the concept that in some tumors TAM causes growth inhibition by an ER-independent mechanism. UM-EC-2 cells were also sensitive to growth regulation by EGF. Thus, these cells provide a new in vitro model of human endometrial cancer in which the roles of both TAM and EGF as growth regulatory substances can be investigated.

Antigens, Neoplasm↗
PubMed1990

Facial nerve paresis as the presenting symptom of leukemia.

Leukemic involvement of the temporal bone is not uncommon and may present in a variety of ways including auricular or external canal skin lesions, red or thick tympanic membrane, middle ear effusions, otitis media, hearing loss or mastoiditis. Symptomatic facial nerve involvement, on the other hand, is extremely unusual. We discuss a pediatric patient whose sudden onset facial nerve paresis was the presenting symptom that led to her diagnosis of leukemia. At the time of mastoidectomy, a granulocytic sarcoma or chloroma was noted to be overlying the VIIth nerve.

Child↗
PubMed1990

Squamous carcinoma of the head and neck in organ transplant recipients: possible role of oncogenic viruses.

A consistently increased incidence of malignancies in renal transplant recipients has been attributed to the effect of chronic immunosuppression required to prevent transplant rejection. Tumors arising in such patients offer a unique opportunity to study the interactions of the immune system and tumor development. A series of three cases of head and neck squamous cell carcinoma arising in patients after renal, cardiac, or bone marrow transplantation are reported. Patient ages at tumor diagnosis were 18, 29, and 53 years, respectively. Time from transplant to diagnosis of tumor ranged from 7 months to 12 years. Only the youngest patient lacked a history of exposure to the traditional pre-disposing factors of tobacco and alcohol use. Histopathologic examination in all three tumors showed features of koilocytosis with hyperkeratosis and parakeratosis suggestive of papillomavirus infection. Squamous carcinoma cells from one of these patients have been successfully established in cell culture. Immune system impairments secondary to the use of antirejection drugs could allow the expression of oncogenic viruses. A recent report of human papillomavirus (HPV) DNA in a primary and metastatic perianal squamous cell carcinoma from a renal transplant recipient, as well as the reported presence of HPV in benign and malignant neoplasms of the upper aerodigestive tract suggests that HPV infection could play a role in the development of squamous carcinomas in transplant recipients. Further studies of HPV infection in cultured cell lines derived from head and neck tumors occurring in immunosuppressed patients are needed to define this relationship.

Adolescent↗