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J Crissman

Publications and source records attributed to J Crissman.

At least 19 recordsLinked to original sources

Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant.

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.

Adult↗

Screening methods for thyroid hormone disruptors.

The U.S. Congress has passed legislation requiring the EPA to implement screening tests for identifying endocrine-disrupting chemicals. A series of workshops was sponsored by the EPA, the Chemical Manufacturers Association, and the World Wildlife Fund; one workshop focused on screens for chemicals that alter thyroid hormone function and homeostasis. Participants at this meeting identified and examined methods to detect alterations in thyroid hormone synthesis, transport, and catabolism. In addition, some methods to detect chemicals that bind to the thyroid hormone receptors acting as either agonists or antagonists were also identified. Screening methods used in mammals as well as other vertebrate classes were examined. There was a general consensus that all known chemicals which interfere with thyroid hormone function and homeostasis act by either inhibiting synthesis, altering serum transport proteins, or by increasing catabolism of thyroid hormones. There are no direct data to support the assertion that certain environmental chemicals bind and activate the thyroid hormone receptors; further research is indicated. In light of this, screening methods should reflect known mechanisms of action. Most methods examined, albeit useful for mechanistic studies, were thought to be too specific and therefore would not be applicable for broad-based screening. Determination of serum thyroid hormone concentrations following chemical exposure in rodents was thought to be a reasonable initial screen. Concurrent histologic evaluation of the thyroid would strengthen this screen. Similar methods in teleosts may be useful as screens, but would require indicators of tissue production of thyroid hormones. The use of tadpole metamorphosis as a screen may also be useful; however, this method requires validation and standardization prior to use as a broad-based screen.

Animals↗

"Histiocytic markers" in melanoma.

BACKGROUND: Tumor cells of malignant melanoma, the "great imitator," may morphologically mimic almost any cell, including histiocytes. Immunohistochemical stains for histiocytes are often used to distinguish histiocytic lesions that resemble melanomas, but we have noted and others have reported that these markers may be immunoreactive in melanomas. METHODS: We evaluated 43 primary and metastatic melanomas with traditional markers for melanomas (S100, HMB45, and NKI-C3) and common markers used for histiocytes (alpha-1-antitrypsin or AAT, CD68/KP1, HAM56, Mac387, and Muramidase). The extent (<5%, 5 to 30%, 30 to 60%, 60 to 90%, >90%) and intensity (1+ to 4+) of staining were recorded semi-quantitatively. RESULTS: Melanoma immunoreactivity (>5% of tumor cells) was as follows: S100, 100%; HMB45, 91%; NKI, 91%; AAT, 95%; CD68, 86%; HAM56, 26%; Mac387, 7%; and Muramidase, 30%. Among the histiocytic markers, staining by AAT and CD68 was typically diffuse but weak. Staining by HAM56, Mac387, and Muramidase was usually focal. In contrast, the traditional melanoma markers showed diffuse and strong staining. Interpretation of the histiocytic markers was complicated by scattered atypical histiocytes and pigmented tumor cells. CONCLUSION: Melanomas are commonly immunoreactive for histiocytic markers. AAT and CD68 immunostains are diffusely positive almost as frequently as traditional melanoma markers, although with weaker intensity. HAM56, Mac387, and Muramidase are less commonly positive and exhibit focal staining. Therefore, depending on the context, histiocytic markers may not be helpful in differentiating histiocytes and histiocytic tumors from melanomas.

Adult↗

Evaluation of epidermal growth factor receptor, transforming growth factor alpha, epidermal growth factor and c-erbB2 in the progression of invasive bladder cancer.

INTRODUCTION: Determination of the risk of invasive bladder tumors progressing is still imprecise due to the heterogeneous biological behavior of this neoplasm. The goals of this study were to evaluate the patterns of expression of the epidermal growth factor (EGF) system in invasive bladder cancer and to assess its prognostic value. METHODS: This immunohistochemical study was performed using fresh frozen tumor samples and a panel of monoclonal antibodies on a series of 43 invasive bladder cancers treated by cystectomy. RESULTS: EGF was detected in 45% of the tumors and did not correlate with survival from bladder cancer. Transforming growth factor alpha (TGF alpha) was expressed by 60% of the tumors and correlated strongly with death from bladder cancer. Epidermal growth factor receptor (EGF-R) expression was seen in 86% of cases and had no prognostic significance. c-erbB2 was expressed in 50% of cases and was inversely related to a poor prognosis. When EGF and TGF alpha were both expressed, there was little or no expression of c-erbB2. CONCLUSION: The accumulation of several growth factors and the relevant receptor are necessary for the progression of invasive bladder cancers. They could be used as indicators of tumor aggressiveness.

Adult↗

Clinicopathologic analysis of bcl-2 immunostaining in breast carcinoma.

Tissue sections of 81 breast carcinomas and 19 benign breast tissues were immunostained with a monoclonal antibody to the bcl-2 gene product, a cytoplasmic protein that regulates apoptosis. The degree of immunoreactivity was then compared with clinicopathologic parameters and to immunostaining for mutated p53 gene product. Immunoreactivity for bcl-2 was present consistently in lymphocyte populations and in residual benign lobules. Apocrine metaplasia (n = 6) and lactating breast (n = 1) exhibited minimal bcl-2 expression, whereas duct hyperplasia (n = 10) showed staining of cells primarily at the periphery of the involved structure and adenosis (n = 7) displayed staining in a majority of cells. Neoplastic epithelial bcl-2 immunoreactivity was negative or minimally positive (staining in 1-5% of cells) in 42% of cases, heterogeneous (staining in 6-30% of cells) in 27% of cases, and diffuse (> 30% of cells) in 31% of cases. Immunostaining for bcl-2 correlated with the presence of estrogen receptor (bcl-2 negative, 16% estrogen receptor positive versus bcl-2 positive, 88% estrogen receptor-positive; P < 0.001), with differentiation (bcl-2 negative, 62% poorly differentiated versus bcl-2 positive, 8% poorly differentiated; P < 0.001) and with better disease-free survival (bcl-2 negative, 82% recurrence versus bcl-2 positive, 28% recurrence; P = 0.0001; 52-mo mean follow-up). Immunostaining for p53 in greater than 5% of tumor cells was observed in 39% of cases and was more frequent in bcl-2-negative tumors (18/35, 51%) as opposed to bcl-2-positive tumors (14/46, 30%); P = NS. Disease recurrence correlated with p53 staining, which was observed in 51% of tumors that relapsed versus only 22% of tumors that did not recur. We conclude that bcl-2 is expressed in benign breast tissues that retain proliferative capacity and partial differentiation. Moreover, in neoplastic breast tissue, it is better correlated with a differentiated, "hormonally responsive," prognostically favorable phenotype than with disabled p53 gene function.

Breast Diseases↗

Geographic distribution of co-dominant DNA stemlines in breast carcinoma.

Breast carcinomas often contain multiple DNA stemlines in flow cytometric DNA histograms. However, due to mixing during tissue disaggregation the microanatomical relationship between the cells which comprise distinct stemlines is unclear. We performed image cytophotometric DNA analysis (IA) on two separate areas of intact tissue sections of 19 breast carcinomas which were selected on the basis of flow cytometric (FCM) DNA content heterogeneity (i.e., multiple stemlines). For comparison, similar analyses were performed on seven tumors with unimodal FCM DNA histograms. Six of the 7 tumors (86%) with unimodal FCM histograms were also unimodal in both IA DNA histograms. Among tumors with heterogeneous FCM DNA histograms, the presence of multiple stemlines was confirmed in IA DNA histograms in 16/19. In nine of these 16 cases, multiple DNA stemlines having similar DNA indices were present in both areas of neoplasm examined with IA. The remaining seven cases displayed unimodal IA histograms in both areas, however DNA indices differed between the two histograms. These findings imply that cell populations corresponding to flow cytometrically detected DNA stemlines are often intimately admixed, even within geographically separated portions of breast tumors. This pattern suggests that productive interactions between genetically distinct tumor populations may lead to stable co-dominance of ancestral clones during progression of some breast carcinomas.

Breast Neoplasms↗

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↗