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Background and Aims: The diagnosis of early and pre-malignant lesions of oral squamous cell carcinoma is of paramount importance given the mortality rate of late stage disease. Although studies have been undertaken examining how dentists manage and refer potentially malignant lesions, the majority of the research has used questionnaires, with the inherent bias this introduces. The aim of this study was to use qualitative methods to understand in more detail how practitioners manage potentially malignant lesions once they have been discovered., Methods: Semi-structured interviews were undertaken with eighteen dentists in Sheffield, transcribed and analysed using thematic analysis., Results: Five codes were identified relating to the mechanics of the referral, the management of the lesion and the patient's risk factors. Health promotional activities were not being undertaken by all the participants and for some, explaining positive results and giving advice about alcohol was perceived as particularly difficult., Conclusion: Overall, the present research suggests that further training is required to help dentists broach difficult issues with their patients.

Background and Aims: Many oral squamous cell carcinomas present as late stage disease and so the detection of early and pre-malignancy is considered to be of paramount importance. The majority of research examining primary care dentists' experience of the detection and management of early disease has been undertaken using questionnaires, with the inherent bias this introduces. The aim of this study was to use qualitative methods to develop a richer account of practitioners' views about screening and what factors influence the decision to refer a patient., Methods: Semi-structured interviews were undertaken with eighteen dentists in Sheffield, transcribed and analysed using thematic analysis. Ten codes were identified according to the aims of the study and organized into four overarching themes., Results: Although many dentists were screening regularly, some did not appear to be adopting a rigorous and systematic approach. A number of participants also placed more reliance on 'classical' presentations rather than the more varied presentation of potentially malignant lesions and were more influenced by the clinical history of the lesion rather than risk factors., Conclusion: Overall, the present research suggests that for some dentists, more rigour is required when examining for early disease.

Context: Reconstruction of extensive nasal defects often represents a significant challenge owing to several unique qualities of the nose, such as complex topography, mobile free margins, and multiple nasal subunits. Furthermore, loss of internal nasal lining and/or structural skeletal support may be present following removal of extensive skin cancers., Objective: To describe our experience with the use of forehead flap reconstruction for extensive nasal defects., Design: Retrospective case series., Setting: Academic health care hospital system., Patients/intervention: One hundred forty-seven patients with extensive nasal defects repaired with a forehead flap., Main Outcome Measures: The functional and aesthetic results were assessed. The characteristics of defects repaired with the forehead flap and the need for lining and/or cartilage were examined., Results: The forehead flap was used to repair 147 nasal defects after Mohs excision of nonmelanoma skin cancer. Full-thickness skin was lost in all cases, structural skeletal support in 68 cases (46%), and internal mucosal lining in 45 cases (31%). Our experience and surgical technique using the forehead flap are described., Conclusions: The forehead flap represents one of the best methods for repair of extensive nasal defects. Near-normal functional and cosmetic results can be achieved.

We characterized the breakpoints, gains, and losses of chromosome material in squamous cell carcinomas of the head and neck region from 29 patients. Cell lines were karyotyped in 1/3 of cases, direct preparations or early in vitro harvests in 1/3, and both in 1/3 of cases. GTG-banding was employed in all cases, as were C-banding and RBG- and AgNOR-staining in most. Some tumors were near-diploid and others near-tetraploid, but many had mixed populations, with diploid, tetraploid, and octoploid subclones representing essentially the same karyotypic pattern. The most frequent changes were deletions. Losses affecting 3p13-p24, 5q12-q23, 8p22-p23, 9p21-p24, and 18q22-q23 ranged in frequency from 40% to 60% of tumors. Loss of the short arm of the inactive X occurred in 70% of tumors from female patients, and loss or rearrangement of the Y occurred in 74% of tumors from male patients. Loss of 18q appeared to be associated with short survival, as did the presence of multiple deletions. There was gain (2-5 extra copies) of 3q21-qter, 5p, 7p, 8q, and 11q13-q23 in 28-38% of tumors. Three tumors had an hsr involving 11q13-q21. Gain of material at 11q13 is postulated to be associated with amplification of the PRADI/CCND gene at that locus. A translocation between proximal 1p and either an acrocentric short arm or proximal 8p or 9p was observed in squamous cell carcinomas of the head and neck region but not in female genital tract tumors. No other abnormalities appeared to be site specific, suggesting a pattern of genetic evolution in squamous cell carcinoma that is independent of anatomic site.

In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.

To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed.

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.

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.

The squamous cell carcinoma (SCC) cell lines UM-SCC-17A and -17B were derived, respectively, from the primary laryngeal cancer and a metastatic neck tumor of a patient who failed to respond to radiation therapy but achieved long-term remission after surgery. The karyotypes of both cell lines and a subline of 17A were pseudodiploid and stable in multiple in vitro passages. Several karyotypic abnormalities were common to all three cell lines and therefore represent mutations present in the tumor before the divergence of the metastatic and subline populations whereas those rearrangements observed only in one cell are more likely to be secondary. The shared mutations include: duplication of the short and proximal long arm of chromosome 2, isochromosome 3q, duplication 7, inversion 8, duplication of the distal long arm of 18, and monosomy 21 or ring 21. Each line had different rearrangements involving chromosome 7 that resulted in three copies of most of the short arm being present in both cell lines, except for high passages of 17B, in which one structurally normal 7 was replaced by a dicentric isochromosome, dic(7)(q11.22), resulting in four copies of 7p. The dic(7) may represent an in vitro mutation. An isochromosome 13q was noted in both the stemline and subline of UM-SCC-17A but not in UM-SCC-17B. A del(11p) and an iso(21q) were present only in the 17A subline. The cell lines expressed the membrane antigen phenotype characteristic of squamous cancers although the UM-SCC-17A subline differed with respect to three markers. Of these, the A9 and blood group antigen changes are thought to be associated with progression. The subline, which carried the del(11)(p13-p15.1), also failed to express the E7 antigen mapped to the band 11p13. It is possible that the two apparently normal 11s in this subline carry a point mutation or microscopically undetected deletion involving the E7 antigen locus.

Forty-two patients with metastatic squamous cell carcinoma were treated with bleomycin, vincristine, and mitomycin C with or without methotrexate (BOM +/- M). The overall response rate of 64% (complete response [CR] rate, 19%) included 19 responses among 26 patients (seven CRs) with head and neck cancer, three responses among eight patients with cervical cancer, and three responses among five patients (one CR) with lung cancer. Six of 12 patients (two CRs) responded to BOM and 21 of 30 patients (six CRs) responded to BOMM. The median duration of response was 16 weeks. Toxic effects included nausea or vomiting in 33% of the patients, fever of > 101 degrees C in 26%, stomatitis in 29% and pulmonary toxicity in 19%. Four of eight cases of pulmonary toxicity were fatal and the incidence was related to the amount of both bleomycin and mitomycin C administered. The occurrence of pulmonary toxicity could not be predicted by serial determination of pulmonary function or blood gases. A wbc count nadir of < 2500/mm3 occurred in 15 of 42 patients. There were two episodes of sepsis with one death. A platelet count nadir of > 75,000/mm3 occurred in eight of 42 patients with no episodes of hemorrhage. BOMM produces a high objective response rate in patients with squamous cell cancer. However, the duration of remission is brief, and use of the regimen carries an increased risk of fatal pulmonary toxicity.

The high tumor response rates associated with intensive chemotherapy in previously untreated patients with advanced head and neck squamous cell carcinoma (HNSCC) led to the initiation of a multi-institutional National Cancer Institute trial. This trial used preoperative chemotherapy in patients with resectable Stage III and IV squamous cell carcinoma of the oral cavity or larynx/hypopharynx. Response rates, toxicity, and a variety of patient and tumor characteristics were analyzed to determine which factors might be useful in predicting tumor response to preoperative chemotherapy. Two hundred eighty-two patients received one course of preoperative cisplatin and bleomycin chemotherapy and were evaluable. There were 22 complete responses (CR) and 114 partial responses (PR) at the primary site (48% response rate). Of 197 patients with clinically positive regional adenopathy, 29 CRs and 73 PRs were observed (52%). Toxicity associated with the chemotherapy regimen was minimal. Primary tumor and regional node responses to chemotherapy were strongly correlated. No significant differences were found in primary or nodal response rates with respect to differing tumor site, stage, histologic differentiation, patient performance status, nutritional status, leukocyte count, hemoglobin level, age, sex, or alcohol use. Primary tumor response, however, was significantly related to T classification (P = 0.048). Nodal response was strongly associated with N classification and nodal size (P = 0.02 and P = 0.075, respectively). These findings suggest that, of the patient and tumor characteristics analyzed, none were more useful in predicting tumor response than clinical tumor staging parameters.

Twenty-six patients with advanced squamous cell cancer of the head and neck were treated with bleomycin, Oncovin, mitomycin C, and methotrexate (BOMM) for ten weeks. Partial and nonresponders then received adriamycin, cisplatin, and cyclophosphamide (APC) in a planned sequential program. The response rate to BOMM was 65% (19% complete remission, CR). The overall response rate to APC was 20%. Only three of eight nonresponders to BOMM could receive APC and non responded. Six of seven partial responders received APC and only one responded. One complete responder to BOMM received APC at relapse and attained a partial response. The major side effects of BOMM were mucositis and myelosuppression. Patients receiving methotrexate 60-72 hours following the bleomycin infusion had less myelosuppression than patients who were treated 36-42 hours after bleomycin. The toxicities with APC included nausea, vomiting, and myelosuppression. Including a prior series, a total of 45 patients have been treated with BOMM with a 71% response rate (69% in previously irradiated patients). Twenty-eight percent of previously treated patients achieved complete remission, and two of these patients are disease free at 31 and 37 months. Methotrexate dose-rate alteration to low dose twice weekly followed by a single dose of oral leucovorin did not improve the complete or partial response rate when compared to weekly methotrexate administration. The complete remission rate and response duration were also not improved by the planned sequential use of this cisplatin-containing regimen.

Prior studies of impaired cellular immune reactivity in patients with head and neck squamous carcinoma (HNSC) suggest that immune deficiency associated with tumor growth may be related, in part, to alterations in immunoregulatory functions. To determine if production of soluble mediators of the immune response (lymphokines) is impaired in patients with HNSC, leukocyte migration inhibition in response to phytohemagglutinin was assessed in 32 patients with HNSC and 29 normal subjects and was correlated with levels of specific peripheral blood lymphocyte subpopulations to determine if quantitative levels of immunoregulatory lymphocyte subpopulations were related to in vitro lymphokine production. In the patients with cancer, leukocyte inhibitory factor production was consistently and significantly impaired and was directly related to levels of T4-positive (helper/inducer) lymphocytes. Substantial differences in levels of individual subpopulations were not detected among normal subjects and patients with cancer; however, the mean T4/T8 ratio was substantially increased in the patients with cancer. The findings confirm and extend prior observations of impaired cellular immune mechanisms in patients with HNSC and suggest that impaired lymphokine production may be related to quantitative and qualitative alterations in lymphocyte subpopulations.

Carcinoma of the lip is a common variety of head and neck malignancy frequently seen in the elderly Caucasian male. Three hundred and fifty consecutive cases of invasive squamous cell carcinoma of the lip are anlayzed and the treatment methods and their results are presented. Surgical management is recommended for most patients because of the advantage of tumor margin assessment, avoidance of radiotherapy complications, and rapid rehabilitation.

A retrospective review was performed of 66 patients with squamous cell carcinoma of the maxillary sinus. The majority of patients presented with tumors classified as T3 (31.8%) and T4 (54.5%). Seven (10.6%) patients presented initially with neck metastases and 13 (19.7%) patients subsequently developed regional disease. For the 66 patients studied, the observed 5 and 10 year actuarial survival rate was 27.3% and 20.7% respectively. The presence of cervical metastases, particularly when they developed subsequent to initial therapy, was associated with a poorer survival rate. Five year survival rate for patients without cervical metastases was 32.6% in contrast to 28.6% for patients initially presenting with nodal disease and 7.7% for patients who subsequently developed regional metastases. Overall, 5-year survival rate for all patients with cervical metastases was 15.0%. A combined treatment regimen (surgery and radiation therapy) appeared to be superior to single modality therapy. A 58.0% observed 5-year actuarial survival rate was achieved with combined therapy. Surgery or radiation therapy when used alone as a single modality resulted in a 5-year survival rate of 20.0% and 15.7% respectively.

One hundred and twenty patients with malignancy of the nasopharynx were reviewed. The most common presenting symptoms of this disease were cervical mass and hearing loss. Neoplasm occurred three times more frequently in males than in females. Cranial nerve dysfunction was present in 17.5% of patients at the time of initial evaluation. The overall 3- and 5-year determinate survival for the entire series of nasopharyngeal malignancies was 38.9, and 27.0%, respectively. Nonsquamous cell and undifferentiated neoplasms (24%). The presence of cervical metastases offered a poorer prognosis. A 39.6% 5-year survival was recorded for patients without nodal disease. Massive lymphadenopathy or bilateral cervical metastases forecasted an ominous 5-year survival of 13.6%. Control rate was greatest among patients with tumors restricted to one area of the nasopharynx and without regional metastases. The 5-year survival of such patients was 71.4% compared to 13.3% for patients having tumor extension beyond the nasopharynx producing cranial nerve impairment or bone erosion.

Dichloromethotrexate, a dihalogenated analog of methotrexate, is excreted and metabolized by the liver; therefore, blood levels are not dependent on renal function. The possibility that dichloromethotrexate could be given at its maximally tolerated dose in combination with high-dose cisplatin has been evaluated in 30 patients with advanced squamous cell cancer of the head and neck. Overall, this regimen was well tolerated, and 13 of 24 evaluable patients had an objective response to therapy (25% complete response and 29% partial response). The maximum dose of dichloromethotrexate that could be delivered was related to the serum albumin. Patients with an albumin less than 3.8 g/100 mL rarely tolerated doses of 500 mg/m2 or greater. Cisplatin plus dichloromethotrexate is an active drug combination in squamous cell cancer of the head and neck, and deserves further evaluation in randomized studies and in an adjuvant setting.

We are studying membrane antigens of human squamous cell cancer with the use of naturally occurring autologous antibodies from patients' sera, along with a set of other serologic reagents and monoclonal antibodies raised against cultured squamous cell lines. Twenty-eight squamous cell carcinoma cell lines have been established in our laboratory from tissues obtained from 23 patients. Antibody reactivity has been found against the autologous tumor cell line in 13 of 23 patients. One of these is of sufficient titer for detailed analysis. Four cell lines are available from this patient. UM-SCC-17A is derived from the primary laryngeal carcinoma, and UM-SCC-17B is derived from a lymph node metastasis removed during the same surgical procedure. Fibroblasts have been cultured from normal mucosa, and a B-lymphoblastoid line has been developed by Epstein-Barr virus transformation of the patient's peripheral blood lymphocytes. Antibody from this patient reacts with the UM-SCC-17A and -17B tumor cell lines but does not react with the normal fibroblasts (UM-NF-17).

A phase II trial of ICRF-187 (1.0 g/m2/48 hours by continuous infusion every 3 weeks) was conducted in 25 patients with advanced squamous cell cancer of the head and neck. There were two partial responders for an overall response rate of 8%. Sixteen of the patients had not received prior chemotherapy and both responding patients were in this group. The major side effect of ICRF-187 was reversible leukopenia.

Certain risk factors appear to separate subjects with repeated primary carcinomas of the lip from the general population of patients with carcinoma of the lip. Factors that were found statistically significant in increasing the chance of recurrent carcinoma of the lip include outdoor occupations requiring prolonged exposure to sunlight or the use of tobacco on a regular basis. Significant risk factors of a clinical nature include a positive serologic reaction for syphilis; the presence of leukoplakia, hyperkeratosis, or actinic cheilitis; or the presence of a basal cell or squamous cell carcinoma of the facial skin.

A multi-institutional National Cancer Institute trial of preoperative cisplatin (100 mg/sq m, day 1) and intravenous bleomycin sulfate (15-mg/sq m bolus, day 3, followed by 15 mg/sq m/day, 24-hour infusion, days 3 to 7) was carried out in patients with previously untreated, resectable stage III and IV squamous cell carcinoma of the oral cavity or larynx and hypopharynx. Of the first 113 patients who received a single course of induction chemotherapy, eight complete responses and 47 partial responses at the primary site were observed (49%). Of 76 patients who had clinically positive regional adenopathy, 11 complete responses and 31 partial responses of neck nodes were observed (55%). The response rates of the primary tumor and the regional nodes to induction chemotherapy were assessed with respect to several pretreatment patient and tumor characteristics and to reported toxic effects after chemotherapy. Of the factors examined, no prognostic indicators were highly useful to predict the response of the primary tumor. However, the response of regional adenopathy was associated with the initial N class, the site of primary tumor, and the response of the primary tumor to induction chemotherapy.

Despite almost 3 decades of experience, the use of intraarterial (IA) chemotherapy for the treatment of head and neck cancer is not universally accepted. The overall reported response rates are not substantially different from the therapeutic results obtained with systemic therapy. The additional complications associated with establishing and maintaining arterial access have further dampened enthusiasm for this approach. It is clear that considerable improvement in the techniques and efficacy of IA chemotherapy is necessary. This second and last part of this article considers the past and present clinical experience with IA therapy in the treatment of head and neck cancer and explores future developments.

Serum antibody reactivity to squamous cell carcinoma of the head and neck (SCCHN) was evaluated in 41 autologous serum-tumor cell line combinations using the protein A hemadsorption assay. Autologous antibody reactivity (median titer of 1:4) was detected in sera from 24 of the patients tested. In 10 cases autologous antibody reactivity could be detected only in undiluted serum precluding further analysis. Analysis of higher titer sera from one patient revealed antibodies that define an antigen expressed on autologous tumor cells cultured from both the primary tumor (UM-SCC-17A) and from a metastasis (UM-SCC-17B). Absorption analysis showed that this antigen was also expressed on 6 of 10 allogeneic SCCHN cell lines but not on autologous fibroblasts or on allogeneic melanoma cell lines. Due to the low titer of autologous antibody reactivity in most sera, we sought to determine if dissociation of immune complexes through acidification and ultrafiltration of serum might enhance detectable antibody reactivity as has been done in previous studies in melanoma. Twelve serum samples from eight patients were subjected to acid dissociation and ultrafiltration (AD-U). Only six of the untreated sera had detectable antibody reactivity against the autologous SCCHN cell line whereas following AD-U all 12 sera had enhanced IgG reactivity against autologous SCCHN. Specificity analysis of one serum sample after dissociation revealed that the antibody detected an antigen common to SCCHN cell lines as well as melanoma, glioma, renal, and colon carcinoma cell lines. Circulating immune complexes may provide a reservoir of antibody with potential diagnostic and therapeutic applications.

In 22 patients with advanced squamous cell carcinoma of the head and neck we evaluated the efficacy and toxicity of 200 mg/m2 cisplatin administered in 3% NaCl with vigorous hydration. Six patients had previously untreated stage IV disease and 16 patients had recurrent disease, including eight with prior chemotherapy including low-dose cisplatin and carboplatin. Cisplatin was administered as a brief infusion, either 40 mg/m2/day X 5 or 50 mg/m2/day X4, every 28 days. Objective responses were observed in 16 of 22 (73%) patients, including 5 of 6 (83%) previously untreated patients and 11 of 16 (69%) patients with recurrent disease. This included two complete responses, one confirmed pathologically. Fifty-seven courses of drug were administered and toxicity was monitored with serial creatinine clearance determinations, audiograms, and sensorimotor exams. Neuropathy and ototoxicity were dose-limiting and led to the stopping of treatment in 12 of the 16 responders after one to four courses (median three courses). Only two responding patients continued treatment until disease progression occurred at 3 and 4 months after achieving maximum response. Acute, transient nephrotoxicity occurred in four patients; two were retreated. Moderate myelosuppression occurred in all patients but was not treatment-limiting. For most patients the maximally tolerated number of courses was three. The median survival time was 33.5 weeks for recurrent disease patients, 108 weeks for newly diagnosed patients. This regimen is not recommended for the palliation of recurrent disease. However, the very high response rate suggests that high-dose cisplatin may have a useful role in induction or adjuvant chemotherapy regimens.

In recent years, the successful grafting of human tumors into immune deprived animals has spurred the hopes of developing a reliable in vivo model for evaluation of human cancer. The nude mouse has created new perspectives in many different areas of cancer research, and has proved to be the most useful recipient of any animal system for tumor heterotransplantation. This study determined which of several squamous cell carcinoma (SCC) cell lines would reproducibly grow as heterotransplants in nude mice, and allowed an opportunity to determine whether characteristics of the tumor changed as a result of propagation in tissue culture. Sixteen (76%) of the 21 SCC lines heterotransplanted in nude mice remained as viable tumor nodules. Nine (43%) of these lines reproducibly produced progressively enlarging tumor masses. Five (24%) SCC lines failed to grow as heterotransplants. The average lag phase between implantation and the beginning of growth for all SCC lines tested was approximately 7 weeks and emphasizes the need for prolonged observation of nude mice following SCC heterotransplantation. The rate and pattern of growth of SCC in nude mice appears to be related specifically to the tumorigenic factors of a given cell line. The concurrent presence of other SCC or non-SCC tumors in a given mouse do not appear to influence the growth of a specific cell line. In addition, specific host factors that might vary from one mouse to another did not alter the growth patterns of SCC. Histological examination of the SCC lines successfully heterotransplanted in nude mice showed similar histological appearances to the original tumor in the human host.

Squamous cell carcinoma of the nasopharynx is an uncommon disease in childhood. Ten patients under the age of 18 years with nasopharyngeal carcinoma are reviewed. The average patient age was 13 years and the average duration of symptoms was 18 weeks. Cervical mass (8/10) and hearing loss (4/10) were the most frequently encountered complaints. Three- and five-year determinate survival was 50% and 44% respectively. Bilateral cervical metastases or cranial nerve impairment from neoplasm offered a poor prognosis.

Cancer of the ethmoid sinus is a rare tumor in the head and neck, accounting for less than 1 per cent of all such malignancies. This paper examines squamous cell carcinoma arising in the ethmoid sinus, the most common form of ethmoidal malignancy in a series reviewed at the University of Michigan. Sixteen cases diagnosed between 1964 and 1974 (inclusive) were included in this study. Peak incidence of the disease occurred in the seventh decade of life. All patients had a minimum follow-up of at least five years. The patients had relatively common nasal complaints that unfortunately represented an unusual and frequently fatal disease. The symptoms of ethmoid sinus cancer are reviewed, and the many modalities of treatment that can be used are discussed. The problems of staging ethmoid sinus cancer are elucidated, and difficulties with the suggested classification systems are discussed. Ultimately, only 29 per cent of the patients survived five years.