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T M Ulbright

Publications and source records attributed to T M Ulbright.

At least 55 records · Page 3Linked to original sources
PubMed1995

[New parameters for prediction of pathological stage in clinical stage I non-seminomatous testicular tumors].

Traditional histopathological risk factors have failed to predict pathological stage accurately in clinical stage I nonseminomatous testicular germ cell tumours. Histopathology, flow cytometry, cytophotometry, and immunohistochemical staining techniques were used in an effort to define high- and low-risk groups for occult metastasis in a consecutive series of 105 patients who underwent retroperitoneal lymph node dissection. After multiple logistic regression analysis, the proliferative S + G2M cell cycle fraction of the aneuploid tumour stemline was the most highly predictive parameter of pathological stage (P = 0.0004). Using a cut-off of 41%, pathological stage II patients were predicted with a sensitivity of 71%. There were 61 patients with S + G2M values below 41%, and 43 of them had pathological stage I disease (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in low-risk patients, and MIB-1 immunohistochemical staining identified a subgroup of 23% of patients with pathological stage I disease and at extremely low risk of metastatic disease. Assessment of tumour cell proliferation does not allow accurate classification of high-risk patients at a level that is adequate for clinical application. Patients who are at low risk of metastasis, however, can be identified by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma with 90% certainty. These parameters deserve further study, since identification of a subgroup of patients at extremely low risk of metastasis could potentially reduce the overall morbidity in the management of clinical stage I nonseminomatous testis cancer.

Animals↗
PubMed1994

Predictive parameters of biologic behavior of early stage nonseminomatous testicular germ cell tumors.

BACKGROUND: Thirty percent of patients presenting with clinical stage A nonseminomatous testicular germ cell tumors in fact have pathologic stage B disease. This pilot study was performed to determine whether DNA content and cell cycle analysis by flow cytometry and single-cell cytophotometry can improve clinical staging in these patients. METHODS: The orchiectomy specimens of 102 patients with clinical stage A disease were analyzed retrospectively using histopathologic classification, flow cytometry, and single-cell cytophotometry. All patients had undergone retroperitoneal lymph node dissection. RESULTS: The multivariate analysis in this group of patients resulted in the following model: If the primary tumor consisted of 100% embryonal carcinoma, the patient was classified as high risk for retroperitoneal metastasis. If the patient was found to have less than 100% embryonal carcinoma in the primary tumor, the percent of aneuploid tumor cells in S-phase as identified by flow cytometry was most predictive for pathologic stage. Using this approach, 91% of all patients with pathologic stage B, and 77% of the patients with pathologic stage A were correctly classified; test efficiency was 82%. CONCLUSIONS: These results demonstrate an improvement in clinical staging in this group of patients. This paradigm, developed from retrospective analysis, will be tested prospectively in consecutive patients to determine if it is clinically useful.

Aneuploidy↗
PubMed1994

Flow-cytometric and quantitative histologic parameters as prognostic indicators for occult retroperitoneal disease in clinical-stage-I non-seminomatous testicular germ-cell tumors.

Our study was performed to clarify whether the combination of DNA flow-cytometric and quantitative histopathological parameters improves the prediction of occult metastatic disease in clinical stage-I non-seminomatous testicular germ-cell tumors (NSGCT). We used archival paraffin primary-tumor tissue of 67 clinical stage-I NSGCT patients who had undergone retroperitoneal lymph-node dissection (RPLND). According to the RPLND specimens, 24 patients were at pathological stage I and 43 at pathological stage II. Archival blocks were redissected for histological re-evaluation. In addition, 50 microns sections were prepared according to the Hedley technique in order to obtain nuclear suspensions which were processed for flow cytometry (FC). In univariate analysis, the percentage of embryonal carcinoma, the percentage of immature teratoma and vascular invasion were the most accurate predictive histopathological parameters. The percentage of aneuploid cells in S-phase was the best predictive FC parameter. In multivariate analysis, the percentage of embryonal carcinoma and the S-phase fraction of aneuploid cells were the only independent markers for occult metastatic disease. According to this statistical approach, 91.0% of pathological stage-I and stage-II cases were correctly classified. Sensitivity was 95.3% and specificity was 83.3%. Using histopathological criteria alone, only 56.7% NSGCT patients were correctly classified.

Aneuploidy↗
PubMed1994

Persistent cancer in postchemotherapy retroperitoneal lymph-node dissection: outcome analysis.

Surgery following chemotherapy for treatment of metastatic testis cancer is reserved for partial remissions with localized tumors considered resectable. After primary chemotherapy, about 90% will have teratoma or necrosis and only 10% will have cancer. The concept of two cycles of post operative chemotherapy in this small group with cancer is supported by a 70% long term cure rate. A more difficult group of patients are those who have had not only primary but also salvage chemotherapy for refractory tumor. About 55% of these patients undergoing post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected specimen. There is no data to support the routine use of repeat salvage chemotherapy post operatively. Of 91 patients presenting for surgery post salvage chemotherapy, 53 were considered completely resected and 36 incompletely resected. Of the 53 realistic candidates for cure with complete resections, 25 were given post operative repeat salvage chemotherapy and 28 received none. 9 (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none remained NED. 12 in each group died of disease. Therefore, there is no data to support routine repeat salvage chemotherapy in patients considered completely resected who had already received salvage chemotherapy pre-operatively. Rather the outcome in this cohort depends more on the completeness of its resectability.

Antineoplastic Agents↗
PubMed1994

Unusual neoplasms detected in testicular cancer patients undergoing postchemotherapy retroperitoneal lymphadenectomy.

Approximately 30% of patients with disseminated testicular cancer who receive platinum-based chemotherapy will experience normalization of tumor markers but have persistent, radiographically evident disease in the retroperitoneum. These patients are usually subjected to retroperitoneal lymph-node dissection (RPLND). In all, 45 of 557 patients (8.1%) undergoing postchemotherapy RPLND at Indiana University Medical Center (IUMC) were found to have neoplastic elements distinct from the classic germ-cell tumor types within their resected specimens. Examples included various sarcomas in 14 patients (3.7%), other nonsarcomatous non-germ-cell cancers in 18 patients (3.2%), and cystic atypical choriocarcinoma in 8 patients (1.4%). No distinct patient characteristic or histologic pattern in the primary tumor was predictive of these unusual findings in the RPLND specimen, although sampling error in the orchiectomy specimen could be the reason for this lack of correlation. Surgical resection of these chemoresistant tumors is potentially curative, with disease-free survival being obtained in 13 of 19 patients (68.4%) with sarcoma, 10 of 18 patients (55.6%) with nonsarcomatous cancers, and 7 of 8 patients (87.5%) with cystic atypical choriocarcinoma at mean follow-up intervals of 30.6, 42.5, and 24.7 months, respectively.

Adult↗
PubMed1994

Predictive parameters in biologic assessment of low-stage retroperitoneal lymph-node dissection.

In all, 30% of patients felt to have clinical stage A nonseminomatous testis cancer in fact have pathologic stage B disease. Although patients with clinical stage A nonseminoma currently enjoy a very high change for cure, a better assignment of therapy at diagnosis could lead to an overall decrease in the morbidity of treatment. This study analyzed orchiectomy specimens from 102 patients with clinical stage A nonseminomatous testis cancer, all of whom underwent pathologic staging via retroperitoneal lymph-node dissection (RPLND). Various parameters of the orchiectomy specimen were analyzed to determine whether or not clinical staging could be improved on the basis of these factors. Statistical analysis resulted in the following model. If the orchiectomy specimen consisted of 100% embryonal carcinoma the patient was classified as being at high risk for retroperitoneal metastasis. In the absence of this finding the aneuploid cell line as determined by flow cytometry was considered. If the percentage of aneuploid cells in the S phase was less than 29% the patient was felt to be at low risk for retroperitoneal metastasis. If this percentage was greater than 29% the patient was classified as being at high risk. Using this paradigm, 77% of pathologic stage A patients and 91% of pathologic stage B patients were correctly classified. The test efficiency was 82%. This pilot study resulted in an interesting model that should be tested prospectively in consecutive patients to determine whether it is clinically useful.

Aneuploidy↗
PubMed1994

Quantitative DNA measurement by flow cytometry and image analysis of human nonseminomatous germ cell testicular tumors.

Current clinical staging, which includes the use of serum tumor markers and imaging techniques, fails to identify the 30-40% of clinical stage I (CS I) nonseminomatous germ cell testicular tumor (NSGCT) patients who have occult metastatic disease. Therefore, there is a real clinical need to evaluate new biological parameters of the primary tumor that might be useful as predictors of occult metastatic disease. This study was undertaken to compare quantitative DNA measurements by flow cytometry and image analysis in CS I NSGCT, and to analyze the relevance of these parameters for predicting occult lymph node involvement. Different blocks of formalin-fixed, paraffin-embedded NSGCTs of 62 CS I patients who underwent retroperitoneal lymph node dissection between 1985 and 1989 were prepared according to the Hedley technique, and analyzed by quantitative cytometry. Thirty-six (58.1%) patients had histologically proven lymph node involvement (pathological stage II), whereas 26 (41.9%) patients (pathological stage I) had neither lymph node metastases according to retroperitoneal lymph node dissection (RPLND) specimens nor tumor recurrence during follow-up. Concordant results were found in 76.5% of the samples by both cytometric techniques. For flow cytometry, the percentages of aneuploid cells in the S- and the G2M + S-phase were the most robust predictive parameters for lymph node involvement, whereas for image analysis the 5c exceeding rate (5cER) had the most predictive significance. Based on the experience obtained in this study, both cytometric techniques provide additional information on tumor aggressiveness that might be useful in therapeutic selection of early stage NSGCT patients for either RPLND or surveillance only.

DNA, Neoplasm↗
PubMed1994

The yield of a second screening flexible sigmoidoscopy in average-risk persons after one negative examination.

BACKGROUND/AIMS: The American Cancer Society recommends that asymptomatic persons aged > or = 50 years undergo sigmoidoscopy every 3-5 years. However, the yield of a second examination 3 years later in persons who are initially negative is unknown. The aim of this study was to determine the yield of a second flexible sigmoidoscopy in average-risk persons aged > or = 50 years after an initial negative examination. METHODS: Two hundred fifty-nine asymptomatic, average-risk persons who had undergone a negative screening flexible sigmoidoscopy examination at age > or = 50 years underwent a second examination at least 2 years later (mean, 3.4 years). RESULTS: The second examination found adenomas in 15 (6%) screenees, but no cancers or large (> 1 cm) or severely dysplastic adenomas were detected. Persons aged > or = 60 years at the time of the second examination were more likely (10%) to have adenomas than those < 60 years (3%) (odds ratio, 3.76; 95% confidence interval, 1.17-12.2), but no advanced lesions were found in persons aged > or = 60 years. CONCLUSIONS: These data suggest that the American Cancer Society should consider changing its recommendation for screening flexible sigmoidoscopy in asymptomatic, average-risk persons to 5-year intervals after a negative examination.

Adenoma↗
PubMed1994

Spermatocytic seminoma: an immunohistochemical study.

Spermatocytic seminoma (SS) is an unusual germ cell tumor that behaves in an indolent fashion. Because orchiectomy alone in adequate treatment, it is important to distinguish SS from classic seminoma and other germ cell tumors. Light microscopic distinction usually is possible; however, occasional cases of SS exhibit atypical features, including the presence of a lymphoid infiltrate or microcystic change, which simulate classic seminoma and yolk sac tumor, respectively. Immunohistochemistry might aid in this differential diagnosis, but the immunohistochemical profile of SS is not well reported in the literature. We examined seven SS cases (six men and one non-human primate) with a panel of 14 antibodies directed against placental-like alkaline phosphatase (PLAP), keratins (CAM 5.2, AE1/AE3), vimentin, human chorionic gonadotropin, alpha-fetoprotein, muscle-specific actin, carcinoembryonic antigen, S-100 protein, epithelial membrane antigen, desmin, leukocyte-common antigen, neuron-specific enolase, and human placental lactogen. A previously unreported finding was the presence of focal cytoplasmic staining for low molecular weight cytokeratin (CAM 5.2) in three cases. All other antibodies produced essentially negative results, including anti-PLAP. The PLAP and neuron-specific enolase negativity of SS are in contrast to the positivity of classic seminoma for these markers. A simplified panel of antibodies is recommended to assist in the differentiation of SS from other forms of germ cell neoplasia.

Adult↗
PubMed1994

Unusual neoplasms detected in testis cancer patients undergoing post-chemotherapy retroperitoneal lymphadenectomy.

Approximately 30% of patients with disseminated testis cancer who receive platinum-based chemotherapy will experience normalization of tumor markers but have persistent, radiographically evident disease in the retroperitoneum. These patients usually undergo retroperitoneal lymph node dissection. Of 557 patients undergoing post-chemotherapy retroperitoneal lymph node dissection at our university medical center 45 (8.1%) had neoplastic elements distinct from the classical germ cell tumor types within the resected specimens. Examples include various sarcomas in 19 patients (3.7%), other nonsarcomatous nongerm cell cancers in 18 (3.2%) and cystic atypical choriocarcinoma in 8 (1.4%). No distinct patient characteristics or histological patterns in the primary tumor are predictive of these unusual findings in the retroperitoneal lymph node dissection specimen, although sampling error in the orchiectomy specimen could be the reason for this lack of correlation. Surgical resection of these chemoresistant tumors is potentially curative, with disease-free survival in 13 of 19 patients (68.4%) with sarcoma, 10 of 18 (55.6%) with nonsarcomatous cancer and 7 of 8 (87.5%) with cystic atypical choriocarcinoma at a mean followup of 30.6, 42.5 and 24.7 months, respectively.

Combined Modality Therapy↗
PubMed1994

The correlation of P53 protein expression with proliferative activity and occult metastases in clinical stage I non-seminomatous germ cell tumors of the testis.

Sixty-nine cases of clinical Stage I non-seminomatous germ cell tumors (NSGCT) of the testis were immunostained for the protein product of the p53 tumor suppressor gene using a microwave-based antigen retrieval method. It was assumed that the immunohistochemical detection of the p53 protein corresponded to a point mutation in the p53 gene, the wild-type p53 protein turning over too rapidly to be detected by routine immunohistochemical techniques. The results of p53 staining were then compared with the results, on the same paraffin tissue blocks, of S-phase analysis, as determined by flow cytometry, and the percentage of neoplastic cells exhibiting immunohistochemical positivity for proliferating cell nuclear antigen (PCNA). Thirty-four of 69 (49%) of the clinical Stage I NSGCT exhibited p53-positivity as strong, but focal, intranuclear positivity. Both the mean total S-phase and the mean percentage of PCNA-positive neoplastic cells were significantly higher in the p53-positive cases (27.8% and 89.6%, respectively) compared with the p53-negative cases (17.6% and 66.1%, respectively). Stratification of cases into high (> or = 76%) and low categories for PCNA values correlated significantly (P < 0.0005) with p53-positivity and negativity, respectively, by chi 2 analysis. The positive association of p53 protein expression with higher proliferative indices in NSGCT of the testis is consistent with the observation of p53 mutations correlating with markers of increased tumor aggressiveness in other types of neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA, Neoplasm↗
PubMed1993

Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors.

BACKGROUND: Patients with mediastinal germ cell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy. It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing non-germ cell (hematopoietic) differentiation. METHODS: To assess this hypothesis, histologic material from six patients with MGCTs associated with leukemia was examined using monoclonal and polyclonal antibodies capable of labeling cells of the different marrow cell lineages. RESULTS: Morphologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients. In three of the four cases, the cells consisted of poorly differentiated blast cells, whereas in the fourth, clusters of erythroblasts were identified. The leukemic cells within the MGCT and in the bone marrow had similar morphology, constant expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers. Three cases expressed p53, a nuclear protein associated with neoplastic transformation in a wide range of malignancies, including testicular cancers, but which rarely is reported in leukemias. Karyotype of the leukemia was assessed in five cases: two showed an i(12p), a cytogenetic marker of GCT not identified in the usual cases of leukemia. CONCLUSIONS: The results support the hypothesis that these leukemic conditions originate in the MGCT through a mechanism of differentiation from a yolk sac tumor-derived progenitor cell, with subsequent homing to the marrow.

Adolescent↗
PubMed1993

Thymic carcinoma. A distinct clinical entity responsive to chemotherapy.

BACKGROUND: Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. METHODS: Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. RESULTS: Three patients responded (two completely) to cisplatin-based chemotherapy. CONCLUSIONS: This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors.

Adult↗
PubMed1993

Germ cell neoplasms of the testis.

Testicular germ cell neoplasia, a disease predominantly of young men, is, for unknown reasons, increasing in incidence. Cryptorchidism, a prior testicular germ cell tumor, a family history of testicular germ cell tumors, and somatosexual ambiguity syndromes remain well-established risk factors. Intratubular germ cell neoplasia of the unclassified type represents the common precursor to the great majority of testicular germ cell tumors, and its identification in testicular biopsies reliably identifies those patients who will often progress to an invasive lesion. Seminoma appears to represent the invasive derivative of intra-tubular germ cell of neoplasia of the unclassified type; problematic variants include seminomas with tubular, granulomatous, and edematous patterns. Spermatocytic seminoma is an essentially nonmetastasizing neoplasm unless complicated by the rare development of a sarcomatous component. Embryonal carcinomas usually occur admixed with other germ cell tumor types. The combination of positivity for placental alkaline phosphatase and negativity for epithelial membrane antigen can assist in the distinction of embryonal carcinomas from somatic carcinomas. The treatment of clinical stage I patients with nonseminomatous germ cell tumor with "surveillance only" may be contraindicated depending on features that include the proportion of embryonal carcinoma and the presence of lymphovascular invasion in the orchiectomy specimen. It is important to be aware that pure, mature teratomas in postpubertal patients may be associated with metastases of teratomatous or nonteratomatous type Yolk sac tumor is characterized by numerous patterns including glandular, myxomatous, sarcomatoid, hepatoid, and parietal variants. Choriocarcinomas classically have a biphasic pattern of syncytiotrophoblast and cytotrophoblast; trophoblastic proliferations lacking a biphasic pattern also occur but are difficult to classify unless this category is broadened. Mixed germ cell tumors, consisting of two or more different elements, are quite common. The polyembryoma is a distinctive, well-organized form of mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor.

Choriocarcinoma↗
PubMed1993

Ovarian Brenner tumors and transitional cell carcinoma: recent developments.

Brenner tumor variants--such as metaplastic, proliferating, and low-malignant-potential (three categories recently designated as intermediate Brenner tumors)--and malignant Brenner tumors are unusual tumors presenting problems in classification. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low-malignant-potential Brenner tumors. The category of "transitional cell carcinoma of the ovary" has been proposed for those primary ovarian carcinomas in which definite urothelial features are present, but no benign, metaplastic, and/or proliferating Brenner tumor is identified. Two subtypes have been described, the papillary and the malignant Brenner-like types. These tumors are more aggressive than malignant Brenner tumors, but they appear to respond better to chemotherapy than other types of ovarian epithelial cancer.

Brenner Tumor↗
PubMed1993

Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections.

PURPOSE: We review the long-term outcome of patients with viable nonteratomatous germ cell tumor (NTGCT) in retroperitoneal lymph node dissection (RPLND) specimens after primary or salvage chemotherapy, and the impact of postoperative therapy with two courses of standard-dose cisplatin-based induction chemotherapy. PATIENTS AND METHODS: All patients with viable NTGCT in postchemotherapy RPLND specimens from surgeries performed at Indiana University between July 1975 and March 1991 were retrospectively reviewed. RESULTS: Of 580 postchemotherapy RPLNDs performed, 133 had viable NTGCT in their pathology specimens. Of these 580 postchemotherapy RPLNDs, 417 were performed after primary chemotherapy, and 43 (10%) had viable NTGCT in their pathology specimens. There were 163 RPLNDs performed after salvage chemotherapy and 90 (55%) had viable NTGCT in their pathology specimens. After primary chemotherapy, 34 of 43 had complete resections, and 27 of the 34 received postoperative cisplatin-based chemotherapy. Nineteen of 27 (70%) are continuously disease-free (c-NED). All seven who received no postoperative chemotherapy have relapsed. After salvage chemotherapy, 53 of 90 had complete resections. Of those 53, 25 received postoperative chemotherapy, and nine (36%) are c-NED. Twenty-eight received no postoperative chemotherapy, and 12 (43%) are c-NED. Overall, 43 of 133 patients had incomplete resections, and only four are currently disease-free. There were four postoperative deaths (PODs). CONCLUSION: (1) Incomplete resection of viable NTGCT after primary or salvage chemotherapy portends a very poor prognosis. (2) For patients with complete resection of viable NTGCT following primary chemotherapy, two additional courses of cisplatin-based chemotherapy appear to be safe and effective therapy for reducing the risk of relapse. (3) Additional standard-dose chemotherapy appears to offer no benefit to patients with viable NTGCT in the resected specimen after salvage chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗