Characterization of the translocation between chromosomes X and 18 in human synovial sarcomas.

Recent studies have identified a specific chromosomal translocation, t(X;18)(p11.2;q11.2), in a high proportion of human synovial sarcomas. As a first step towards characterizing the X;18 translocation we have established a synovial sarcoma cell line. Fusion of this cell line to mouse RAG cells gave rise to somatic cell hybrids that contain the derivative (X) marker chromosome in the absence of other genetic material from chromosomes 18 and X. Southern analysis of DNA from these somatic cell hybrids demonstrated that the human X chromosome markers DXS94, DXS14, DXZ1 and DXS62 were retained. In contrast DXS7, GAPDP1, ARAF1, DXS146 were not consistently present in the hybrids indicating that these markers were on the region of the X chromosome replaced by part of the long arm of chromosome 18 during the generation of the X;18 translocation. The predicted position of the translocation relative to X chromosome markers is DXS7-DXS146-X; 18-DXS14-DXZ1-DXS94.

Limb function following conservation treatment of adult soft tissue sarcoma.

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P less than 0.001), muscle power or range of movement (P less than 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P less than 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P less than 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.

Radiotherapy and conservative surgery in the management of musculo-aponeurotic fibromatosis.

Fifty-four patients with musculo-aponeurotic fibromatosis treated with surgery, surgery and planned post-operative radiotherapy, or radiotherapy alone between 1936 and 1982 have been retrospectively reviewed. Twenty-seven patients had a previous excision before definitive treatment. All patients in whom surgery was known to be incomplete and who had no further treatment relapsed. Nine patients had a complete surgical excision alone and 1 relapsed. Twenty-nine patients were treated with surgery and post-operative radiotherapy and 7 relapsed. Relapse was associated with small field size, orthovoltage irradiation, and doses less than 50 Gy. Radiotherapy was effective in preventing relapse in 6 of 8 cases incompletely excised and in all of these cases the total dose was more than 50 Gy. In 13 assessable patients with clinically evident disease, 14 fields were treated with radiotherapy. Complete response was achieved in 9 fields (although one subsequently relapsed and 2 had a marginal relapse), partial response in 4, and disease stasis in one. Complete resolution took up to 21 months and total doses ranged from 35.2 Gy to 64 Gy. Radiotherapy is indicated in cases of incomplete excision and inoperable disease. Doses should be radical and fields should be sufficiently generous to encompass the anatomical limits of the infiltrated tissues.

Treatment of extremity soft tissue sarcomas with surgery and radiotherapy.

The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy-nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre- and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival.

High dose hyperfractionated radiotherapy in the treatment of extremity soft tissue sarcomas.

A hyperfractionated radiotherapy schedule has been evaluated in the treatment of 29 adults with limb or limb girdle soft tissue sarcomas. The objective was to increase the total administered dose and possibly improve local control, without increasing late normal tissue damage. Twice daily 1.25 Gy fractions (with a minimum interval of 6 h) have been given over 5 to 6 weeks to 12 patients pre-operatively, 10 post-operatively and 7 palliatively. Five patients received 62.5 Gy in 5 weeks pre-operatively and 3 palliatively. Nineteen of the remaining 21 patients received 75 Gy in 6 weeks with a field size reduction after 5 weeks. Sixteen of 29 tumours were situated in the thigh and only 2 were in the upper limb. Twenty were of high grade. The mean tumour size of those treated radically was 13.1 cm (range 5 to 40 cm). Sixteen patients (76%) given 75 Gy developed moderate or severe skin erythema maximal at 5 weeks. Despite the large field sizes used (mean phase one of 34.5 cm, and phase two of 22.8 cm) only 2 patients failed to complete the planned treatment because of the severity of these reactions. Two other patients developed partial wound breakdowns after the end of treatment--both healing spontaneously. Fourteen patients developed an area of moist desquamation--11 mild, 2 moderate and one severe. There have been four late wound breakdowns requiring surgical intervention; all have since healed well. The median follow up is short at 556 days. Ten of 19 evaluable patients have developed moderate/severe induration, 5/19 mild and 4/19 none.(ABSTRACT TRUNCATED AT 250 WORDS)

Vindesine as a single agent in the treatment of advanced malignant melanoma.

The antitumour effect of vindesine (desacetyl vinvlastine amide sulfate) in disseminated malignant melanoma has been investigated in our oncology service in a phase-II study. Of 25 patients exposed to the drug, 23 were evaluable, and seven of these (30%) were considered objective responders. The observed response of malignant effusions is of particular interest. Side effects related to vindesine are similar to those of the other vinca alkaloids, although alopecia may be more pronounced with the doses used in this study.

Ifosfamide plus mesna with and without adriamycin in soft tissue sarcoma.

Early results with ifosfamide plus mesna in soft tissue sarcoma showed an initial response rate of 38% in 42 patients. All these patients treated at The Royal Marsden Hospital plus 30 more (total 67) have now been analysed. Single doses of 5 or 8 g/m2 ifosfamide were given over 24 h by infusion in dextrose saline together with 400 mg/m2 or 600 mg/m2, respectively, of mesnum every 4 h to give a total of 9 doses. A diuresis of 200 ml/hour was maintained during therapy. Treatment was repeated 3-weekly. CR was seen in 6 and PR in 10 patients. More recently doxorubicin was added to ifosfamide therapy in an attempt to improve on these results. At first only 20 mg/m2 doxorubicin was given but this was escalated to 40 mg/m2 and 60 mg/m2. Mesna has been given in higher dosage (5 g/m2 over 24 h), but otherwise the schedule is as above. In all 60 patients have been treated and most are now evaluable for response. Encephalopathy has been seen with both regimens. The incidence and patient characteristics are reported.

Anatomy of the accessory nerve and its cervical contributions in the neck.

Details of the course of the accessory nerve and the pattern of the cervical contributions to the nerve are essential for planning neck dissection. Based on a recent anatomic description, a technique was devised to preserve the distal accessory nerve; the theory advanced was that the trapezius was supplied by motor fibers from the cervical plexus, which join the accessory nerve in the posterior triangle. Dissections were performed on 23 cadavers to test such a theory. The course of the accessory nerve in the neck was mapped in each dissection, and landmarks for use during surgery determined. Cervical contributions to the nerve usually joined deep to the sternocleidomastoid, and not in the posterior triangle. Branches from the cervical plexus, independent of the accessory nerve, entered the trapezius in the posterior triangle. None of the bilateral dissections showed symmetry of the cervical contributions.

Chondrosarcoma of the pelvis: the role of palliative debulking surgery.

Curative resection of pelvic chondrosarcoma is sometimes technically impossible. In such cases, surgical debulking on one or more occasions may provide symptomatic relief. In a series of 12 patients with pelvic chondrosarcoma, three have undergone a single debulking procedure and three two or more such procedures. All six patients obtained symptomatic relief and five remain alive and well at a median of 12 months from surgery. Two patients have no clinical evidence of recurrent disease 21 and 25 months after the last debulking procedure.

Angiosarcoma arising in a patient with Maffucci syndrome.

Maffucci syndrome comprises multiple enchondromas together with cutaneous haemangiomas. Review of the literature shows a 15-20% incidence of sarcomatous change in one or more of the enchondromas. Malignancy arising from the vascular component, however, has only been reported in one case. We present a further case where a patient with Maffucci syndrome presented with multifocal angiosarcoma.

Combined craniofacial resection for malignant disease.

A combined craniofacial approach has been employed in nineteen patients with tumors involving the base of the skull. Monoblock resection of the temporal bone, anterior fossa, or anterior and middle fossa can be achieved with acceptable mortality, even in cases of advanced cancer that recurs after radiation. Immediate reconstruction with a full thickness flap was routinely employed to provide improved cosmesis and to minimize the risk of intracranial infection.

Focal myositis, a benign inflammatory pseudotumour: CT appearances.

Focal myositis is a rare benign pseudotumour of skeletal muscle, of unknown cause. Clinically it presents as an enlarging mass within muscle, usually of an extremity, and is often mistaken for a soft tissue neoplasm. The diagnosis is made by biopsy which reveals characteristic histological changes of inflammation, focal degeneration and regeneration, and some evidence of denervation. The CT findings include irregularity and enlargement of the muscles involved, with diffuse, poorly defined fatty infiltration of the muscle planes, but no evidence of an associated mass. We present two cases of focal myositis of the calf, both of which mimicked a soft tissue neoplasm, and in which CT was helpful in determining the nature and extent of the abnormality, for needle biopsy, and follow-up.

Surgery in the management of soft tissue sarcoma.

Surgery and radiotherapy are complementary methods of achieving control of primary soft tissue sarcoma. The extent of operation is influenced by adjuvant irradiation which is important in limb conservation surgery where satisfactory margins are not always possible. Modern reconstructive techniques have extended the possibilities of salvage especially in the irradiated limb. Trucut needle biopsy provides an accurate tissue diagnosis in a high proportion of cases.

Intra-arterial adriamycin, conventionally fractionated radiotherapy and conservative surgery for soft tissue sarcomas.

Thirteen patients with soft tissue sarcomas were treated with a combination of intra-arterial Adriamycin, conventionally fractionated radiotherapy (2 Gy per day), and conservative surgery (trimodal therapy). Severe acute complications occurred in 10 patients: 3 brachial artery thromboses, 6 delayed wound healing, 4 wound infections, and 3 cases of necrosis of the skin plus subcutaneous tissues. Three patients have developed local recurrence. Five patients are alive, 4 of whom are disease-free, and the median follow up time of surviving patients is 56 months. One has significant impairment of limb function due to joint ankylosis. An additional 2 patients were treated with intra-arterial Adriamycin and conservative surgery for local recurrence after previous surgery and radiotherapy; both died of subsequent metastatic disease, one having a further local recurrence. One patient with multifocal angiosarcoma was treated with intra-arterial Adriamycin and radiotherapy but no surgery, and is alive free of disease 49 months later. The combination of radiotherapy and intra-arterial Adriamycin with surgery resulted in significant acute toxicity. This small study has not demonstrated any improvement in local control compared with that expected with conservative surgery and radiotherapy alone.

Long-term venous access using a subcutaneous implantable drug delivery system.

To facilitate long-term venous access in patients receiving chemotherapy, a subcutaneous totally implantable system (Port-a-Cath, Phamacia) has been used in 14 patients. The method of implantation and the advantages over conventional central venous catheters are discussed. The expense of the system necessitates careful patient selection.