A national trainee advisory network: a proposal.

Trainees should have a well-defined and consistent communication conduit to the authorities involved with their training. It is important that trainees are involved in the evolution of structured training programmes and for training authorities to receive feedback from individuals in each specialty. This paper proposes a structure for trainee representation on regional and national training authorities to facilitate an advisory network.

Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature.

Selective induction of vascular damage within tumors represents an emerging approach to cancer treatment. Histological studies have shown that several tubulin-binding agents can induce vascular damage within tumors but only at doses approximating the maximum tolerated dose, which has limited their clinical applicability. In this study, we show that the combretastatin A-4 prodrug induces vascular shutdown within tumors at doses less than one-tenth of the maximum tolerated dose. In vitro studies indicate that a short drug exposure results in profound long-term antiproliferative/cytotoxic effects against proliferating endothelial cells but not cells that are quiescent prior to and during drug exposure. Vascular shutdown, within experimental and human breast cancer models in vivo following systemic drug administration, was demonstrated with a reduction in functional vascular volume of 93% at 6 h following drug administration and persisted over the next 12 h, with corresponding histology consistent with hemorrhagic necrosis resulting from vascular damage. These actions against tumor vasculature and the broad therapeutic window demonstrate the clinical potential of these drugs and warrant further study to elucidate the mechanisms responsible for the antivascular effects of combretastatin A-4.

Surveillance policy for stage I ovarian germ cell tumors.

PURPOSE: Surveillance for stage I male germ cell tumors (GCT) is well established as a standard practice; however, such a policy has not been evaluated for women with equivalent tumors. This study was designed to evaluate the management of grade II or higher stage Ia tumors by close surveillance to minimize treatment, while reserving chemotherapy for patients with residual or recurrent disease. PATIENTS AND METHODS: Between 1973 and 1995, 24 patients with malignant stage Ia ovarian GCT were enrolled onto a surveillance program. The group consisted of nine patients with dysgerminoma, nine with pure immature teratoma, and six with endodermal sinus tumor (with or without immature teratoma). Treatment consisted of surgical resection without adjuvant chemotherapy, followed by a surveillance program of clinical, serologic, and radiologic review, and included a second-look procedure for patients enrolled after 1982. RESULTS: All but one patient are alive and in remission after a median follow-up of 6.8 years. The 5-year overall survival is 95%, and the 5-year disease-free survival is 68%. Eight patients have required chemotherapy for recurrent disease or second primary ovarian GCT. This includes three patients with grade II immature teratoma and three patients with dysgerminoma, and a further two women with dysgerminoma who developed contralateral (presumed second primary) dysgerminoma 4.5 and 5.2 years after their first tumor. All but one, who died of a pulmonary embolus, have been successfully salvaged with chemotherapy. CONCLUSION: Our experience emphasizes that patients with true stage Ia ovarian GCT are adequately managed by surgical resection followed by careful clinical, radiologic, and serologic surveillance. These patients do not require adjuvant chemotherapy or radiotherapy, thus avoiding the potential complications of secondary leukemia and infertility.