Glutathione S-transferase expression in the human testis and testicular germ cell neoplasia.

Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of neoplasms and the enzymes are implicated in metabolism of carcinogens and resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both orchidectomy and post-treatment residual surgical masses were studied. All four isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent from normal spermatogonia but strongly expressed by the neoplastic germ cells of ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma, irrespective of differentiation. There were no qualitative differences in expression between primary and post-chemotherapy metastases. GST Alpha expression in teratoma correlated with epithelial differentiation. GSTs may be important in normal spermatogenesis and protection of germ cells from teratogens and carcinogens. They may have a role in testicular tumour drug resistance but this role is not well defined. GST Pi is a new marker for ITGCN.

Radical radiotherapy with salvage surgery for invasive bladder cancer: results following a reduction in radiation dose.

The management of invasive bladder cancer in Edinburgh, as in many other centres in the UK, has been by radical radiotherapy, with cystectomy reserved for local treatment failure or relapse. A review of the results of this policy in 1987 highlighted what was felt to be an unacceptably severe morbidity rate of 15%. The dose of radiation was therefore reduced from 55 Gy in 20 daily fractions to 52.5 Gy. Forty of 80 patients (50%) treated in this way have achieved a complete response at 6 months which is a similar response rate to that in previous reports. In addition, ten of 23 frail or elderly patients (43%) achieved a complete response with a lower dose of 50 Gy given as a split course over 7 weeks. Eighteen patients have had a salvage cystectomy, and 12 of 18 (67%) are alive and disease-free. Although follow-up is short, to date toxicity has been reduced, and our results support our decision to reduce the radiation dose.

Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity.

A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy.

Surgery following chemotherapy for metastatic testicular teratoma.

Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease-free survival.

Low dose bleomycin with etoposide and cisplatin for metastatic testicular teratoma.

Thirty-nine men with metastatic testicular teratoma were treated with a combination of bleomycin, etoposide and cisplatin (BEP). Unlike the usual regimen of these 3 agents, bleomycin and cisplatin were given on day 1 only of the cycle, with etoposide for 3 days. Thirty patients (77%) are alive and disease-free after a median follow-up of 31 months--24/25 (96%) with disease confined to lymph nodes but only 6/14 (43%) patients with lung involvement. Modified BEP chemotherapy is a well tolerated alternative to standard BEP chemotherapy for small volume nodal disease; it minimises in-patient time, hospital visits and the risk of bleomycin lung toxicity. However, omission of the weekly doses of bleomycin and shortening of the administration schedule of cisplatin and etoposide may be detrimental in patients with more extensive disease, for whom more intensive therapy may be necessary.

Failure of salvage treatment in metastatic testicular teratoma.

From January 1978 to March 1989, 92 consecutive patients with metastatic testicular teratoma have been treated with cisplatin-based chemotherapy. Thirty seven failed to achieve a complete response, and another four subsequently relapsed. These 41 have required further treatment, consisting of surgery (16 patients), radiotherapy (n = 13) and chemotherapy (n = 12). Surgery was generally used for residual masses where tumour markers were normal, radiotherapy for masses where surgery was not possible or for palliation, and second line chemotherapy was used in patients with raised serum tumour markers or in the presence of multiple inoperable pulmonary metastases. Nine of 16 (56%) patients treated surgically are disease-free, including two who had malignant teratoma in the resection specimen. Three of 13 patients irradiated are disease-free, although two of these three had subsequent excision of residual masses. All 12 patients treated with second-line chemotherapy have died. Surgical excision of residual masses appears to be the most effective way of rendering patients disease-free, providing serum tumour markers are normal. Most of these residual masses will consist of differentiated teratoma or necrosis, but it may be possible to salvage patients with residual malignant disease, providing complete clearance can be achieved. Incompletely resected malignant disease carries a poor prognosis, and incompletely resected disease that is histologically benign will run the risk of subsequent relapse. Radiotherapy provides good palliation but is much less effective than surgery as treatment for residual masses, and should only be used if complete excision cannot be accomplished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma from an unknown primary presenting in women with an axillary mass.

Adenocarcinoma from an unknown primary is generally associated with a poor prognosis. This is not the case with women who present with disease confined to one axilla, when the primary, despite negative investigations, is often found to lie in the ipsilateral breast. Twenty such patients presented to our department between 1977 and 1989 and were generally treated by radical radiotherapy to the breast and peripheral lymphatics. Local control was achieved in the axilla in 17 of the 20 patients (85%). No primary has appeared in the breast, although one patient has died of a carcinoma of the colon. The 5-year actuarial survival of the group is 66%, similar to stage II breast carcinoma patients. The value of radiological and histopathological investigations is discussed. The cosmetic results are good and in view of the excellent local control achieved by irradiation we feel mastectomy is unnecessary in this rare presentation of breast cancer.