Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson''s disease

Although pulmonary metastases are typical of chondrosarcoma, only 2 patients with intermediate grade tumours have been reported with bone metastases and without pulmonary involvement. We report one patient with an intermediate grade chondrosarcoma which metastasised to the lumbar spine following surgical resection of a locally recurrent tumour. The local recurrence and the metastases were resected and she is alive and well after 20 months.     

Phorbol ester effects in atypical protein kinase C zeta overexpressing NIH3T3 cells: possible evidence for crosstalk between protein kinase C isoforms

Only 27 cases of Paget's disease of the groin have been reported to the present. Our aim was to describe the clinical behavior and treatment of this disease. A retrospective analysis of patients seen at the Mayo Clinic over a period of 25 years (January of 1970 to December of 1995) was undertaken. We included patients with lesions of the groin (isolated or associated with penile/scrotal locations) and with histologic confirmation of the diagnosis. We found seven patients, all male; three patients had isolated lesions. Their mean (SD) age was 73 (8.3) years. Special stains and immunohistochemistry confirmed the diagnosis in all patients. A wide local excision was performed in every patient. Three patients had recurrence; one of them died with multiple pulmonary metastases 4 years later. Two patients presented with history of associated malignancy (prostatic and renal cell carcinoma). Paget's disease of the groin is extremely infrequent. Its origin seems not to be a simple extension from the genital area. Most diagnoses can be made by light microscopy. Wide local excision with free margins is the treatment of choice. Local recurrence occurs in half of patients with tumor-free margins by frozen section; long-term follow-up is warranted. Distant metastases occur rarely, although they can be fatal.     

Mesenchymal chondrosarcoma of the jaw bones: clinicopathologic study of 19 cases

BACKGROUND: Patients with mesenchymal chondrosarcomas in general have a 5-year survival rate ranging from 42-54.6% and a 10-year survival rate of 28%. Nineteen cases of mesenchymal chondrosarcoma of the jaw bones were reviewed to study their clinicopathologic features and to compare their clinical behavior with that of mesenchymal chondrosarcomas of other locations. METHODS: The patients were 10 males and 9 females (age range, 2-51 years). Sixteen patients were age < 30 years, and the average age at presentation was 19 years. Eleven tumors involved the mandible and eight involved the maxilla. RESULTS: Histologically, the classic picture of a bimorphic tumor, composed of islands of well differentiated hyaline cartilage juxtaposed to a small cell undifferentiated malignancy, was present in every case. Resection, including hemimandibulectomy and hemimaxillectomy, was the main treatment in 16 patients. Seven patients had local recurrence, and five patients developed distant metastases. Six patients died of disease, and the 5-year and 10-year survival rates were 82% and 56%, respectively. CONCLUSIONS: Mesenchymal chondrosarcoma of the jaw bones appears to have a more indolent course than mesenchymal chondrosarcoma of other anatomic     

Osteosarcoma of the pelvis. Oncologic results of 40 patients

The cases of 40 patients with osteosarcoma of the pelvis treated between 1977 and 1994 were reviewed. The location of the tumor was ilium in 30 patients, ischium in four, pubis in one, and sacrum in five. Most (58%) of the tumors were of the chondroblastic subtype. Thirty patients had surgical excision of the tumors: 10 with hemipelvectomies and 20 with limb sparing procedures. A wide margin was achieved in 16 of 30 (53%) patients, including 12 of 14 who had no sacral tumor involvement. Positive margins occurred at the sacrum in 11 patients, lumbar vertebra in one, perirectal space in one, and contralateral pubic body in one. Macroscopic tumor emboli within the regional large vessels were found in seven patients. The incidence of local recurrence was 32%: 13% in wide excisions, 38% in marginal excisions, and 80% in intralesional excisions. The 1- and 5-year overall patient survivals were 73% and 34%, respectively. Patients who had a surgical excision of the primary tumor had a significantly better survival than did those treated without surgery (5-year survival; 41% and 10%, respectively). Tumor size, surgical excision of the primary tumor, surgical margin, and type of surgical procedure were the prognostic factors for patients with Stage IIB tumors.     

Conservative surgical therapy for penile and urethral carcinoma

OBJECTIVES: Invasive penile and urethral tumors are traditionally treated with aggressive excision that requires involved organ and adjacent organ sacrifice. An alternative approach seeks to completely excise the tumor with adequate margins while preserving form and function of the organ. We present 6 patients who underwent such organ-sparing surgery. METHODS: Six selected cases (4 penile and 2 urethral) are presented with operative photographs and pertinent data. RESULTS: Three distal tumors of the penis were treated with excision limited to the glans with histopathologic findings of verrucous carcinoma, melanoma, and angiosarcoma. One patient with squamous cell carcinoma of the distal shaft refused partial penectomy and underwent a local wedge resection. A patient with locally advanced bulbourethral transitional cell carcinoma (TCC) refused cystourethrectomy and underwent an anterior urethrectomy and perineal urethrostomy. A 48-year-old woman with an adenocarcinoma contained in a very distal urethral diverticulum underwent simple diverticulectomy and excision of distal urethra. Postoperative voiding and sexual function were well preserved. Follow-up was 12 to 48 months. The patient with angiosarcoma died of lung metastases at 48 months with no local disease, and the patient with bulbourethral TCC developed pelvic disease at 12 months with no local recurrence and died of metastases at 25 months. CONCLUSIONS: Organ-sparing surgery is appropriate in selected patients on the basis of stage and location, high risk of distant failure, and patient disposition. Close follow-up is necessary. Comanagement with reconstructive and oncologic specialists optimizes results and outcomes.     

Microsporidia of the genus Trachipleistophora--causative agents of human microsporidiosis: description of Trachipleistophora anthropophthera n. sp. (Protozoa: Microsporidia)

Only limited data are available on chromosomes specifically involved in prostatic tumour progression. This study has evaluated the cytogenetic status of primary prostatic carcinomas, local tumour recurrences, and distant metastases, representing different time points in prostatic tumour progression. Interphase in situ hybridization (ISH) was applied with a set of (peri) centromeric DNA probes, specific for chromosomes 1, 7, 8 and Y, to routinely processed tissue sections of 73 tumour specimens from 32 patients. Longitudinal evaluation was possible in 11 cases with local recurrence and nine cases with distant metastases. The remaining 12 patients showed no evidence of local recurrence or distant metastasis after radical prostatectomy on follow-up (mean 60.5 months) and served as a reference. Numerical aberrations of at least one chromosome were found in 27 per cent of the local recurrences and 56 per cent of the distant metastases. In decreasing order of frequency, +8, +7, and -Y were observed in the recurrences and +8, +7, -Y, and +1 in the distant metastases. Evaluation of the corresponding primary tumour tissue of the recurrence group showed numerical aberrations in 45 per cent of cases. The aberrations found were, in decreasing order of frequency, -Y, +7, and +8. In the concomitant primary tumour tissue of the distant metastasis group, numerical aberrations were detected in 67 per cent of cases. The aberrations most frequently encountered were +8, -Y, followed by +7. In four cases, a concordance was found between the primary tumour and its recurrence or distant metastasis. Discrepancies might have been caused by cytogenetic heterogeneity. Comparison of the primary tumour tissue of the reference, the recurrence, and the distant metastasis groups showed a significant increase for the percentage of cases with numerical aberrations (Ptrend = 0.02). Likewise, a trend was seen for gain of chromosome 7 and/or 8 (Ptrend < 0.05). The number of DNA aneuploid tumours also increased in these different groups (Ptrend = 0.03). These data suggest that cancers which recur in time display an intermediate position between tumours of disease-free patients and metastatic cancers.     

Occult tumor cells of malignant melanoma and consequences for surgical treatment

Immediate and complete surgical excision is the standard mode of treatment for primary malignant melanoma. There is still a controversy about the adequate resection margins. In this study we looked for microscopic satellites in order to estimate the extent of local therapy. METHOD: 19 patients with malignant melanoma of the trunk or extremities, treated by wide excision, were included. Clinical courses were documented. Postoperative follow-up was 1.4 years in the mean. In primary tumours and cutaneous excisions we looked for microscopic satellites with routine histology and immunohistochemistry (APAAP-technique, monoclonal antibody HMB-45). RESULTS: Using APAAP-technique in combination with routine histology, we could show that microscopic satellites only occurred in specimens of melanomas of more than 5 mm thickness. In the two cases where evident microscopic satellites were present a systemic dissemination obviously evolved already before the first surgical treatment. Therefore, in those cases wide resection margins do not provide an increasing chance of survival. CONCLUSION: The idea to remove microscopic satellites by wide surgical excisions and thus to reduce the risk for systemic dissemination and local recurrence cannot be supported.     

Viruses and atherosclerosis: do they play a pathogenic role?

PURPOSE: To evaluate the results of interstitial radiotherapy of anorectal tumors. PATIENTS AND METHODS: From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. RESULTS: Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. CONCLUSIONS: A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.     

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.     

Small-intestinal digestion of partially resistant cornstarch in healthy subjects

Primary adenocarcinoma of sweat glands is a rare tumor; approximately 220 cases have been reported in the last 30 years. We reviewed the charts of patients with primary diagnosis of this tumor treated at the Mayo Clinic between 1935 and 1995. We included only cases with initial histology slides available for re-examination. Tumors were classified into five recognizable histologic patterns (solid, ductal, mucinous, microcystic adnexal, and adenocystic carcinoma) and graded by the Broder system. Statistical analysis consisted of Kaplan-Meier product limit method and Cox multiple regression test. In total, 55 patients were identified, and age ranged from 13 to 85 years (mean 59 years). Thirty-six patients (65 percent) presented to the Mayo Clinic for initial treatment; all except one had disease limited to the primary site. Microcystic adnexal carcinoma was the most frequent type, and more than 50 percent were grade 2 tumors. Among these 36 patients, 4 had some type of recurrence. Patients who developed metastasis had a high-grade tumor in the initial biopsy. Nineteen patients were referred with recurrence; 13 had local recurrence, 4 had regional diseases, and 2 had distant metastases. The histologic distribution showed 47 percent solid tumors, and 37 percent of them were grade 3. Multiple regression analysis did not show a difference in recurrence or survival when gender, age, tumor location, or histologic pattern was evaluated. In addition, there was no difference in the outcome between wide surgical resection and micrographic surgery. The only predictive factor for distant metastases and/or death (p < 0.003) was histologic grade. Overall 10-year survival rate was 86 and 60 percent for primary and referred patients, respectively. We conclude that histologic diagnosis of sweat gland carcinoma must be complemented by clinical examination to evaluate metastases. Clinical behavior depends on the histologic type of tumor, degree of differentiation, and clinical stage. On recurrence, the likelihood of further recurrences and mortality increases dramatically. Aggressive initial local ablation with tumor-free margins is recommended. In high-grade tumors, prophylactic regional lymph node dissection may further characterize tumor aggressiveness and may justify adjuvant radiotherapy as part of the primary treatment.     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Variable management of soft tissue sarcoma: regional audit with implications for specialist care

BACKGROUND: The aim of this study was to determine how and by which specialties patients with soft tissue sarcoma are investigated and treated within a single large health region and with what outcomes and implications for resource uptake. METHODS: By retrieving the records of 377 patients with primary soft tissue sarcoma treated in the South-East Thames Region between 1986 and 1992, the presentation, investigation, treatment and outcome were compared with defined criteria for optimal management. Patient management was assessed and compared between specialties and districts on the basis of outpatient time, appropriate use of radiological investigations and preoperative biopsy, type of surgery, content of the pathology report and the incidence of local recurrence, metastasis and death over a mean follow-up period of 2.5 years. RESULTS: Most patients (53.6 per cent) were treated by general surgeons, irrespective of tumour location. Overall only 21.3 per cent of patients were investigated optimally with wide variation among specialties. Only 60.0 per cent were treated adequately (wide excision or surgery with radiotherapy). Uptake of adjunctive therapy and follow-up were variable. Outcome was poorer in patients having a marginal excision and recurrence. CONCLUSION: Investigation and management of many patients with soft tissue sarcoma was both variable and suboptimal. This has implications for patient care, resource uptake and costs. As has been amply demonstrated elsewhere, patients with sarcoma are more appropriately managed in specialist centres.     

Anorectal melanoma--an incurable disease?

PURPOSE: This study was designed to describe recurrence and survival rates after operative treatment for anorectal melanoma and to identify predictive factors for recurrence. METHODS: Records of 50 patients with anorectal melanoma from 1939 to 1993 were reviewed. RESULTS: Overall five-year survival and disease-free survival were 22 and 16 percent, respectively. At the time of diagnosis, 26 percent of patients had metastatic disease, and all died within 12 (mean, 6.3) months. Five-year survival and recurrence rates were identical after either abdominoperineal resection (APR) or wide local excision, both with curative intent. Gender, size of tumor, presence of melanin, positive perirectal lymph nodes, or treatment were not predictive of recurrence. Anorectal melanoma was found incidentally after hemorrhoidectomy or polypectomy in five patients. Three other patients underwent an excisional biopsy of a lesion measuring less than 2 cm. Of these eight patients, five underwent APR and three underwent wide local excision with no microscopic residual tumor at pathology. All developed regional or systemic recurrence at a mean of 21 (range, 4-88) months, and all died of their disease at a mean of 29 (range, 5-98) months. CONCLUSION: Prognosis for anorectal melanoma is poor, irrespective of surgical treatment performed. No predictive factors for recurrence were identified in this series. Wide local excision with a negative margin of a least 1 cm is suggested as the treatment of choice. APR should be reserved for tumor not amenable to local excision or for palliative treatment of large obstructive lesion until effective adjuvant therapies are available.     

Metastatic carcinoma to skeletal muscle. A report of 15 patients

The records of 15 patients with metastatic carcinoma to skeletal muscle treated between 1979 and the present were reviewed. Fourteen patients were referred with a diagnosis of soft tissue sarcoma and one with suspected infection. There was a previous diagnosis of carcinoma in eight patients but seven patients had no prior diagnosis of a known malignancy. Primary tumors were lung (eight), melanoma (two), gastrointestinal (one), kidney (one), and bladder (one). No primary tumor could be identified in two patients. Local control of metastatic lesions was achieved by radiotherapy in 11 patients as an initial measure. Two patients underwent wide excision and one declined treatment for local tumor control. Eight patients died within 12 months of presentation and survival analysis indicated a 25% overall survival at 60 months. Two patients remained free of disease at 132 months and 72 months. From this study and a review of 52 cases reported in the literature, the authors are unable to find any clinical or radiographic characteristics that distinguish metastatic carcinoma to muscle from soft tissue sarcomas. Surgical resection can be reserved for cases in which radiation does not provide local control.     

Mesenchymal chondrosarcoma of the orbit. Report of three new cases and review of the literature

BACKGROUND: Extraskeletal mesenchymal chondrosarcoma is a rare tumor characterized by undifferentiated mesenchymal cells with islands of mature hyaline cartilage. Considering all sites, long-term survival is approximately 30%. Only seven cases of orbital mesenchymal chondrosarcoma have been reported. METHODS: The records of three cases of orbital mesenchymal chondrosarcoma treated at the Columbia-Presbyterian Medical Center, and the seven previously reported cases of this tumor were reviewed to determine clinical characteristics and appropriate therapy. RESULTS: Nine of the 10 patients were female; age of onset ranged from 10 to 35 years. Of eight patients with at least 2 years of observation, five survived 5 or more years after resection, or after resection plus adjuvant therapy. Two patients died of metastatic disease 2 and 5 years, respectively, after the initial treatment, and one died of pneumonia 6 months after surgery. Review of the histology of the three cases treated at Columbia-Presbyterian Medical Center did not identify distinct histologic types that might guide therapy. Presenting symptoms were typical of symptoms of an orbital mass: proptosis, pain, diplopia, change in visual acuity, ptosis, and tearing. CONCLUSION: The small number of reported cases of mesenchymal chondrosarcoma of the orbit prevents definitive conclusions, but it appears that resection is adequate therapy in some cases. Extraskeletal mesenchymal chondrosarcoma of the orbit may have a better prognosis than tumors in other sites.     

Metastasis of chondrosarcoma

This study was undertaken to analyse metastases of patients with intermediate- or high-grade chondrosarcomas. Out of 24 intermediate-grade tumours, 5 (21%) developed metastases, as did 6 of 10 high-grade tumors (60%) (P = 0.04). Four patients developed pulmonary metastasis only, 5 developed both pulmonary metastasis and metastases of the other sites. Two patients showed a rare metastatic pattern: bone metastases only. The metastasis rate in the primary chondrosarcoma (42%) was higher than that in the secondary chondrosarcomas (0%) (P = 0.03). The metastasis rate was higher in patients with local recurrence (86%) than in those without local recurrence (19%) (P = 0.01). In 5 of 6 patients who had a local relapse and metastasis, the interval between the two relapses was a few months.     

Glycine agonists: what can they teach us about schizophrenia?

Plantar fibromatosis is a rare, benign lesion involving the plantar aponeurosis. Eleven patients (13 feet) underwent 24 operations, including local excision, wide excision, or complete plantar fasciectomy. Clinical results were evaluated retrospectively. There were no differences among the subgroups in postoperative complications. Two primary fasciectomies did not recur. Three of six revised fasciectomies, seven of nine wide excisions, and six of seven local excisions recurred. Our results indicate that recurrence of plantar fibromatosis after surgical resection can be reduced by aggressive initial surgical resection.     

Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities

We reviewed the cases of sixty-two patients who had had a subcutaneous sarcoma to determine the effect of tumor and treatment-related variables on the rates of survival and local recurrence. Fifty-nine (95 per cent) of the patients had had an operation at another hospital before being referred to us. Twenty-nine (47 per cent) of the sixty-two tumors were high-grade, forty-two (68 per cent) were small (five centimeters or less), and thirty (48 per cent) were malignant fibrous histiocytomas. We followed a treatment strategy that consisted of repeat excision with the goal of obtaining wide margins. Excluding thirteen patients who had had a palpable local recurrence at the time of presentation, twenty (49 per cent) of forty-one patients who had had a marginal excision at another hospital had microscopic residual tumor on repeat excision. At a median of fifty-six months after the repeat excision, fifty (81 per cent) of the sixty-two patients had been continuously disease-free, one had no evidence of disease, eight had died of the disease, and three had died of other causes. The five-year rate of disease-free survival was 85 per cent (fifty-three of sixty-two patients). There were three local recurrences, all in patients who had had a marginal resection. No recurrences were noted in patients who had had a wide local excision of the tumor or of the previous operative field. Multivariate analysis revealed that a large tumor (greater than five centimeters), a marginal excision, and adjuvant radiation therapy were associated with a worse prognosis. Excellent rates of survival for patients who have a subcutaneous sarcoma, including those who have a large or high-grade tumor and those who have residual tumor following a previous operation, can be obtained with carefully planned operative treatment alone. We recommend operative excision or repeat excision with wide margins because of the high prevalence of residual tumor. Size is the most important tumor-related factor, and the operative margin is the most important treatment-related factor. The additional value of adjuvant radiation therapy remains unproved.     

Surgical treatment of thymoma

This paper presented 6 cases of thymomas, surgically treated at the Newcastle Regional Cardiothoracic Surgical Service-England during the period 1970-1971. Excision of the tumour alone was carried-out in two patients. In the remaining four, a thymectomy and removal of the tumour was performed. In one case histological appearance suggested malignancy. The author insists upon an early excision, because the because the benign thymomas are potentially malignant tumours and the possibility of recurrence can be more effectively prevented by thymectomy at the same time. The coincidence of thyretoxicosis and thymoma, respectively aplastic anaemia and thymoma, were presented in 2 patients. To date, all patients have been well.     

Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors

PURPOSE: This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. METHODS AND MATERIALS: From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. RESULTS: Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient. CONCLUSIONS: Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.