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Biomedical subjects

J Crissman

Publications and source records attributed to J Crissman.

At least 19 recordsLinked to original sources

Immunohistologic analysis of invasive phenotype in breast carcinoma. A clinicopathologic study.

Acetone-fixed, cryostat sections of 81 snap-frozen invasive breast carcinomas were immunostained with monoclonal antibodies to Cathepsin D (CD), a protease believed to mediate extracellular matrix dissolution, and Type IV collagen, a constituent of basal lamina (BL). Most cases (48/81, 53%) exhibited focal, patchy BL distribution (1+) around tumor cell nests, although subsets with diffuse continuous (2+) peritumoral sheets (15/81, 19%) or near complete absence (0+, 23/81, 28%) were also observed. Elaboration of BL was correlated with favorable morphologic differentiation (0+ BL-57% poorly differentiated vs. 2+ BL-13% poorly differentiated, p = .01), absence of nodal or systemic metastases (0+ BL-78% metastatic vs. 2+ BL-40% metastatic, p = .02), and improved disease-free survival (0+ BL-63% recurred vs. 2+ BL-20% recurred, p = .05). In addition, neoplastic cells expressed CD more frequently in tumors which lacked detectable BL synthesis (0+ BL-91% CD+ vs. 2+ BL-57% CD+, p = .03). The observed relationships between morphologic growth pattern, BL synthesis and CD expression imply conventional grading in large parts reflects activity or extent of host tissue invasion by a given neoplasm. Widespread but heterogeneous distribution of BL in breast tumors also suggests partial equilibrium between neoplastic and host tissues in most cases.

Antibodies, Monoclonal

Clinicopathologic significance of p53 immunostaining in adenocarcinoma of the breast.

Methanol/acetone-fixed frozen sections of 87 breast carcinomas were studied with a panel of three anti-p53 monoclonal antibodies that had specificities for wild-type, mutant, or combined wild-type plus mutant epitopes by using the avidin-biotin method. Nuclear staining was present in 13 (15%) of 87 cases with the mutant-specific antibody. The combined-specificity antibody stained 28 (32%) of 87 cases, including all but one of the tumors that was positive with the mutant-specific antibody. None of the cases reacted with the wild-type-specific antibody. Immunostaining for mutant form p53 was strongly correlated with adverse clinicopathologic factors, including poor differentiation, absence of estrogen receptor protein, nodal metastases, and large tumor size. In groups that were stratified by axillary node status, disease-free survival (52-month mean follow-up) was worse among cases with positive staining for either antibody. This difference was statistically significant in node-positive patients with the combined-specificity antibody (disease free, 22% [p53+] vs recurred, 57% [p53+]). We concluded that (1) immunostaining for mutant forms of p53 characterizes a clinically aggressive subset of breast tumors and may have prognostic utility in some patient populations, and (2) antibody-dependent-staining patterns for p53 may reflect epitope specificities of various mutant forms.

Adenocarcinoma

Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17.

One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life-threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck.

Carcinoma, Squamous Cell

Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma.

Twenty-four patients with recurrent and/or locally advanced nasopharyngeal carcinoma who received cis-platinum-based chemotherapy are reported. Twelve patients with recurrent disease previously treated with radiotherapy received cis-platinum-based chemotherapy. An overall response rate of 67% (8/12) and a complete response (CR) of 25% (3/12) were achieved. All the CR patients were treated with cis-platinum and 5-fluorouracil (5-FU) infusion. Twelve patients with locally advanced (stage IV) previously untreated nasopharyngeal carcinoma received cis-platinum-based chemotherapy. Eight of those patients received cis-platinum and 5-FU combination chemotherapy followed by radiation therapy. An overall response of 75% (6/8) and a complete response of 50% (4/8) were achieved by induction chemotherapy. Subsequent radiation therapy to the 6 responding patients (CR 4, PR 2) to chemotherapy increased the complete response to 100% (6/6). The other two stable patients refused further therapy and died in less than 1 year from locoregional disease. Four patients were treated with concurrent cis-platinum and radiation therapy. A complete response of 100% (4/4) was achieved.

Adolescent

Influence of nonbiologic implants on laminectomy membrane formation in dogs.

The effects of various surgical implants, spinal cord hypothermia, and glucocorticoid administration on formation of the laminectomy membrane were evaluated in 32 preconditioned chondrodystrophoid dogs. Modified dorsal laminectomies and full-length durotomies, from T12 to L1, were performed on all dogs. Dogs were allotted to 2 groups. Group-1 dogs (n = 20) were further allocated to 4 subgroups (a, b, c, and d) consisting of 5 dogs each. Group-1a dogs received no implant, group-1b dogs had absorbable gelatin sponges implanted, group-1c dogs had absorbable gelatin films implanted, and group-1d dogs had absorbable gelatin sponges and absorbable gelatin films implanted. Daily neurologic examinations permitted correlation of neurologic dysfunction with secondary spinal cord compression in those dogs in which it developed. The influence of these implants on laminectomy membrane formation and dural healing was assessed by gross and microscopic evaluation of transverse sections of the vertebrae and spinal cord after euthanasia of one member of each subgroup at 1, 2, 4, 8, and 16 weeks after surgery. Group-2 dogs (n = 12) were further allotted to 3 subgroups (a, b, and c) consisting of 4 dogs each. One dog in each group-2 subgroup underwent the same surgical procedures described for the group-1 subgroups (ie, 4 procedures/group-2 subgroup). The additional effects of 3 conventional supportive techniques (selective regional spinal cord hypothermia, glucocorticoid administration, or spinal cord hypothermia and glucocorticoid administration) on laminectomy membrane formation and on immediate postoperative recovery were examined in groups 2a, 2b, and 2c, respectively. Neurologic examinations were performed daily until this time. All dogs in group 2 were euthanatized 1 week after surgery for gross and microscopic examination of transverse sections of the vertebrae and spinal cord. Qualitative histopathologic effects of the different implants and supportive techniques on formation of the laminectomy membrane were determined. Statistical analysis of the degrees of secondary spinal cord compression was performed in group-1 dogs by measuring and comparing ratios of the vertical to the horizontal diameters of the transverse spinal cord sections from locations within (T12 to L1) and out of (T11, T11-12, L1-2, and L2) the region of surgical intervention. The vertical/horizontal diameter ratios measured from transverse sections from T11 to L2 in size-matched, untreated control dogs formed the standards for a mean roundness index of the spinal cord in the various anatomic locations of the vertebral column.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5-fluorouracil (5-FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty-two of the chemotherapy-induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5-FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow-up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response.

Adult

Solid tumor preparation for flow cytometry using a standard murine model.

The application of flow cytometry (FCM) to solid human tumors has been hindered by the difficulty in producing high yield, viable, unaltered single cell suspensions. Carcinomas containing a high desmosomal content, such as well-differentiated squamous cell (SCC) cancers of the head and neck (H&N) region, are particularly difficult to prepare. The desire to employ FCM to study cellular DNA parameters of these tumors led to the use of a 3-methylcholanthrene induced murine SCC for the comparative testing of preparative techniques. Dissociation techniques, including mechanical, enucleation, chemical, single and combination enzymes methods, were comparatively tested. Of these, the combination enzyme treatment employing trypsin and collagenase produced the highest cell yields in the shortest time with the highest dye exclusion viability and the least expense. Several fixation systems including glutaraldehyde, paraformaldehyde, acetic acid, and ethanol were comparatively tested using percent of cell loss and quality of the DNA histograms produced as end points. Ethanol-water systems with added fetal calf serum provided minimal cell loss and high quality histograms which were stable for extended periods of time. A murine tumor, closely mimicking the histology of the human tumor of interest, may be used as a model for the determination of optimum techniques of solid tumor preparation for flow cytometric analysis.

Animals

Solid tumor preparation for clinical application of flow cytometry.

Intense interest in advanced squamous cell cancers of the head and neck (SCC of H&N) has resulted from the recent progress made in tumor responses with chemotherapy and radiotherapy. Unfortunately, the response patterns and clinical outcome of such patients are not adequately predicted on an individual patient basis using clinical parameters or conventional morphology. The study of flow cytometrically determined cellular parameters in such tumors is therefore of interest, but is hindered by inadequate tumor preparative technology. The previous article (10) in this journal describes the use of a murine SCC tumor, LC12, which was employed for comparative testing and determination of optimum techniques of preparation for this tumor. This report describes the application of these techniques to 144 specimens of human SCC of H&N. The mean total yield for these specimens is 7.4 X 10(7) cells/g of tissue. The mean viable enzymatic yield (3.3 X 10(7) cells/g) was higher than the mean viable mechanical yield (2.0 X 10(7) cells/g) except when lymph nodes were the source of the specimen (5.4 X 10(7) cells/g). The mean dye exclusion viability from enzymatically dissociated specimens were above 90%. Significant aneuploidal subpopulation losses were evident in mechanically dissociated and enucleated specimens. 65% of the enzymatically dissociated specimens were successfully cultured with a mean cloning efficiency of 2.1 X 10(-3). Preparative techniques derived from comparative testing with a murine standard tumor have been successfully applied to 144 specimens of SCC of H&N with resultant high yields and excellent viability. Technical problems detected during the preliminary testing with LC12 were confirmed in the human tumors.

Adult

The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy.

The response to initial treatment with cisplatin-containing combination chemotherapy as well as survival, were correlated with tumor differentiation (well, moderate or poorly differentiated) in 164 patients with advanced, untreated squamous cell carcinoma of the head and neck. Thirty-three percent of the tumors were graded as poorly differentiated, 59% moderately differentiated, and 8% were well differentiated. The overall clinical response rates were nearly equal for the three grades of differentiation: 79% for well differentiated, 86% for moderately differentiated, and 89% for poorly differentiated. The complete response rate was somewhat higher for poorly differentiated tumors: 46% as compared to 32% and 29% for moderately and well differentiated respectively, but the differences were not statistically significant. The median survival for each morphologic group was 22, 16, and 12 months for well differentiated, moderately differentiated and poorly differentiated tumor, respectively (P = 0.097). For patients achieving a complete clinical response to chemotherapy, there was a difference in survival when stratified according to degree of histologic differentiation. Patients who were complete responders and had well or moderately differentiated tumors attained 75% and 38% survival at 36 months, respectively, versus 19% for patients with complete response and poorly differentiated tumors (P = 0.064). The degree of differentiation of previously untreated squamous cell cancers of the head and neck does not conclusively predict tumor response to combination chemotherapy, but may reflect differences in natural history. Survival is improved in patients with differentiated tumors as compared to those with poorly differentiated tumors. Morphologic grading in patients achieving a complete response reveals a decrease in survival for patients with poorly differentiated tumors.

Adult

Malignant fibrous histiocytoma of the larynx.

Malignant fibrous histiocytomas of the upper respiratory tract are rare, aggressive, mesenchymal neoplasms. There have been sporadic cases reported in the English language literature. This paper reports the case of a subglottic malignant fibrous histiocytoma in a 26-year-old female. A review of the important clinical-pathological features of this type of tumor is presented. The treatment of choice appears to be wide surgical resection of the tumor. Although the published experience is small, it appears that tumors of the subglottic space are characterized by a younger patient population and a better prognosis than those of the larynx.

Adult

Combined modality therapy utilizing a cisplatin combination for effective chemotherapy in patients with previously untreated head and neck cancer.

In patients with locally advanced head and neck cancer, the results of standard definitive treatments of surgery, radiotherapy, or both were disappointing. The local and regional recurrence rates were high, despite adequate surgical resection with negative margins and postoperative radiotherapy to all known or possible disease areas. Combination cisplatin chemotherapy given initially before definitive treatments produced a high overall antitumor response and up to 50 percent clinical complete response. Before answering the question of value of chemotherapy as part of the multimodality treatment, it is important to identify the safest and most form of chemotherapy. The degre of chemotherapy effectiveness is defined by the incidence of clinical and, most important, histologic complete response. To assess this effectiveness, chemotherapy was given before definitive treatments to patients with measurable disease. From our 10 year experience we have concluded that continuing the development of induction chemotherapy, including investigating the timing of such effective treatment and assessing the value of such therapy, is of the utmost importance.

Antineoplastic Combined Chemotherapy Protocols

The value of blood group-specific lectin and endothelial associated antibodies in the diagnosis of vascular proliferations.

Blood vascular and lymphatic tumors were evaluated immunohistochemically by studying a spectrum of endothelial associated antigens. UEA-1 lectin reacted with the tumor cells of one patient with malignant angioendothelioma in the non-metastatic stage. However, when metastasis occurred, the binding sites of this lectin completely disappeared from the surface of the tumor cells in both original and metastatic lesions, suggesting the loss of blood group H antigen from the tumor cells could be used as an indicator of metastasis in this tumor. Reaction with anti-HLA-A, B, C, intense in normal blood vessels, remained intensely positive in pyogenic granuloma and Kaposi's sarcoma, whereas it did not react with normal lymphatics and lymphangioma. This indicates that anti-HLA-A, B, C is useful in differentiating blood vascular structures from lymphatic structures in both normal and pathological conditions. OKM5 reacted intensely with benign hyperplasias in pyogenic granuloma, while barely reacting with proliferating parts in Kaposi's sarcoma, suggesting the difference in staining patterns can be used to distinguish vascular proliferation or malignancy. Reaction with anti-Type IV collagen and anti-laminin was intense in normal blood vessels, pyogenic granuloma and Kaposi's sarcoma, whereas reaction with these antibodies in normal lymphatics was patchy and irregular in its thickness.

Antibodies, Neoplasm

Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin.

In a series of three consecutive pilot studies carried out between 1977 and 1981 at Wayne State University, Detroit, Michigan, designed to test the feasibility of multimodality therapy in patients with previously untreated advanced squamous cell carcinoma of the head and neck, patients received three different induction chemotherapy regimens: cisplatin + Oncovin (vincristine) + bleomycin (COB) for two courses; 96-hour 5-fluorouracil (5-FU) infusion and cisplatin for two courses, or 120-hour 5-FU infusion + cisplatin for three courses. Over-all response rates (complete response + partial response) to each of the three induction chemotherapy regimens were high: 80%, 88%, and 93%, respectively. Superior complete response rate in the group receiving three courses of 120-hour 5-FU infusion + cisplatin was 54% versus 29% for COB and 19% for two-course 96-hour 5-FU infusion + cisplatin (P = 0.04). Significant survival advantage at 18 months minimum follow-up for the group receiving three courses of 120-hour 5-FU + cisplatin induction therapy was found. Actual T and N stage may influence the clinical complete response rate. Responders to initial chemotherapy have significantly better survival as compared to nonresponders regardless of subsequent surgery and/or radiotherapy. These studies show that a multimodality approach to management of advanced head and neck cancer is feasible. Superior complete response rate and survival in one of the treatment groups suggest that choice of induction chemotherapy regimens and/or number of courses is of prime importance in such multimodality treatment programs.

Adolescent

Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck.

Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty-one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.

Antineoplastic Combined Chemotherapy Protocols

Superior clinical response and survival rates with initial bolus of cisplatin and 120 hour infusion of 5-fluorouracil before definitive therapy for locally advanced head and neck cancer.

One hundred ninety-one patients were treated by one of three cisplatin-containing multidrug protocols. The initial 77 patients received two courses of cisplatin and vincristine plus bleomycin. The next 26 patients received two courses of 5-fluorouracil and cisplatin, and the final 88 patients were placed on a three course 5-fluorouracil and cisplatin protocol. Overall response rates were similar for each of the three protocols. The complete response rate, however, was much better (54 percent) for three course 5-fluorouracil and cisplatin versus cisplatin vincristine, and bleomycin (29 percent) and two course 5-fluorouracil and cisplatin (19 percent). Survival curves were also better for the three course 5-fluorouracil and cisplatin segment of this nonrandomized pilot study.

Adolescent

Chemotherapy for nasopharyngeal carcinoma. A ten-year experience.

Seventeen patients, 14 after radiation therapy relapse, with measurable nasopharyngeal carcinoma were treated with chemotherapy. Remissions were observed in 9 of 17 (53%) with 3 complete (CR) and 6 partial responses (PR). Five (2 CR + 3 PR) of seven patients with lymphoepithelioma achieved remission, 4 (1 CR + 3 PR) of 8 with keratinizing squamous cell carcinoma, and 2 progressions with transitional cell carcinoma. Complete remissions were only achieved with CDDP-based combinations, with 2 of the 3 CR rendered histologically free of disease at the time of repeat biopsy of the tumor bed. Nasopharyngeal carcinoma is responsive to chemotherapy, even after radiation therapy relapse. The most effective chemotherapy combinations contain CDDP. Histologic differentiation did not appear to influence the frequency of remissions.

Adolescent

Cis-platinum and 5-fluorouracil as induction therapy for advanced head and neck cancer.

Sixty-one patients were treated with a three course induction regimen of 5-fluorouracil and cis-platinum for advanced squamous cell carcinoma of the head and neck area. Thirty-three patients (54 percent) had complete clinical remission with the administration of these drugs. Twenty-four patients (39 percent) showed a 50 percent or greater reduction in tumor size, for a significant response rate of 93 percent. The toxicities were within acceptable limits, and only three patients did not complete all three courses. Surgery and radiation therapy were supposed to follow the chemotherapy but several patients refused surgery after the disappearance of their lesion. This has created a problem in patient management.

Carcinoma, Squamous Cell