A review of the close surveillance policy for stage I female germ cell tumors of the ovary and other sites.

Ovarian germ cell tumors are rare but very curable at all stages of disease. There is good evidence that surveillance for stage I dysgerminomas is a safe option although many centers worldwide still advocate adjuvant chemotherapy for stage IA nondysgerminomatous tumors, despite the significant risk of developing long-term treatment side effects. Here, we review the safety of our ongoing surveillance program of all stage IA female germ cell tumors. Thirty-seven patients (median age 26, range 14-48 years) with stage I disease were referred to Mount Vernon and Charing Cross Hospitals between 1981 and 2003. Patients underwent surgery and staging followed by intense surveillance, which included regular tumor markers and imaging. The median period of follow-up was 6 years. Relapse rates for stage IA nondysgerminomatous tumors and dysgerminomas were 8 of 22 (36%) and 2 of 9 (22%), respectively, plus one patient with mature teratoma and glial implants also relapsed; 10 of these 11 patients (91%) were successfully cured with platinum-based chemotherapy. Only one patient died from chemoresistant disease. All relapses occurred within 13 months of initial surgery. The overall disease-specific survival of malignant ovarian germ cell tumors was 94%. Over 50% of patients who underwent fertility-sparing surgery went on to have successful pregnancies. We have confirmed again that surveillance of all stage IA ovarian germ cell tumors is very safe and that the outcome is comparable with testicular tumors. We question the need for potentially toxic adjuvant chemotherapy in nondysgerminoma patients who have greater than 90% chance of being salvaged with chemotherapy if they relapse later.

Vascular damaging agents.

To provide a comprehensive overview on vascular targeting agents and the application of radiobiological principles in pre-clinical and clinical studies, we completed a comprehensive review of published medical studies on vascular targeting agents using Pub Med. Vascular targeting agents are now divided into vascular disrupting agents (VDAs), which target the pre-existing tumour vasculature, and angiogenesis inhibitors (AIs), which prevent the formation of new blood vessels. Modest success has been seen when VDAs and AIs are used as single agents and therefore combination therapies that can work in a complimentary and synergistic manner, targeting both the tumour cells and endothelial cells, are needed. Radiobiological principles have been used to increase our understanding of these agents, and can explain the increased efficacy of combination treatments. In particular, the alteration of the tumour microenvironment by AIs and VDAs can lead to enhanced efficacy when combined with chemotherapy or radiotherapy, with phase II/III trials showing encouraging results. The optimal use and scheduling of AIs and VDAs remains to be determined. Further understanding of the mechanisms of action of these potentially very exciting anti-neoplastic agents is urgently required.

The response of breeding doses to nematodiasis: segregation into "responders" and "non-responders".

Responder and non-responder does were identified from a flock of 95 Scottish cashmere 2-6 year-old does exposed to natural nematode infection over a 12-month period. Every 5 weeks, the does were faecal sampled for worm-egg counts prior to anthelmintic treatment. Responsive and non-responsive individuals were identified on the basis of their cumulative faecal egg count (FEC) rankings: the 8 lowest and 8 highest rankings were deemed to be responders and non-responders, respectively. Retrospective analysis showed that the mean egg count of the 8 responders was significantly lower than that of the 8 non-responders. The selected responders and non-responders were subsequently housed together with 8 randomly selected does from a control line, and given a mixed trickle challenge with Teladorsagia circumcincta and Trichostrongylus vitrinus larvae (L3). Mean responders FEC was significantly lower following artificial infection than that of non-responder and unselected does. Peripheral eosinophilia was significantly greater in responders in the first 3 weeks of this infection. On day 60, the infection was terminated with anthelmintic and 7 days later the goats were given a single challenge of 50,000 T. circumcincta L3. The mean responder worm burden was lower, and exhibited greater evidence of retardation of worm development, than those of non-responder and unselected does. Responders had significantly more mast cells and globule leukocytes post-challenge than did the other 2 groups. These results suggest that under the conditions encountered in this experiment, it is possible to segregate goats into responders and non-responders using simple parasitological criteria, as individual responsiveness is a relatively repeatable phenomenon.

Studies on caprine responsiveness to nematodiasis: segregation of male goats into responders and non-responders.

Eighty-three 2-4-year-old intact male goats exposed to a combination of artificial and natural challenge were segregated into responders and non-responders by ranking of weekly faecal egg counts (FECs). Retrospective analysis of samples over a 15-week-period showed responders had a statistically lower mean FEC than non-responders. Estimates of repeatability between consecutive egg counts were significant in both groups. The 6 top responders and bottom non-responders were subsequently given an artificial trickle challenge with Teladorsagia circumcincta and Trichostrongylus vitrinus. Mean faecal egg output was significantly lower in responders than non-responders. Peripheral eosinophil numbers following challenge were significantly greater in responder than non-responder goats. Abomasal and intestinal worm burdens were considerably lower in responders, with evidence of retardation of worm development compared to non-responders. Both abomasal and jejunal tissue eosinophil numbers were significantly higher in responders, although there was no difference in mucosal mast cell or globule leucocyte numbers. These results suggest that under temperate climatic conditions, it is possible to segregate male goats into responders and non-responders on the basis of simple parasitological criteria.