All right, good. You can record these, you can throw them around. Anybody can have them. And I'm just going to talk about the malignant tumors, the intermediate trophoblast, PSTT and ETT for short. I should be able to advance my slides, yes. So just in brief, the classification of gestational trophoblastic disease or GTD in general, benign GTD entities are complete and partial hidatidiform mole. We're not going to talk about them tonight. Malignant gestational trophoblastic neoplasia or GTN consists of post-molar GTN. And usually those are patients treated without regard for histology after evacuation of a mole. Gestational choriocarcinoma originates from the villous trophoblast. And there are neoplastic cytotrophoblast and syncytiotrophoblastic cells. The placental site trophoblastic tumor or PSTT originates from the extra villous trophoblast. And these are neoplastic intermediate trophoblast or IT cells as are the cells for epithelioid trophoblastic tumors or ETT. So just briefly, normal trophoblast cell function. The cytotrophoblast is a polygonal stem cell for other forms of trophoblast. The syncytiotrophoblast are multinucleic cells that interface between the mother maternal tissues and the fetal tissues, the placenta. And through these come the exchange of nutrients, oxygen and carbon dioxide exchange. They also are the cells that produce the majority of placental hormones and including elaboration of intact alpha beta HCG. The intermediate trophoblast where these tumors originate shares features of both and is really the cell that is responsible for invasion of the deciduo, the myometrium and the maternal spiral arteries. They can elaborate some HCG or other hormones but at a much lower rate than the syncytiotrophoblast cells. So clinical features of these tumors compared to choriocarcinoma. First, they are very rare and comprise less than 2% of all cases of GTN. Whereas choriocarcinomas histologically or clinically account for about 50% and post-molar GTN, the other 50%, give or take a few percentage points for each. Mixed lesions of placental site trophoblastic tumor or ETT combined with choriocarcinoma have been described. And sometimes patients will respond to treatment of the choriocarcinoma and have residual PSTT or ETT that doesn't respond as well to conventional chemotherapies. These tumors have a very slow growth rate compared to choriocarcinoma and often present years after the last pregnancy event as compared with the rapid doubling of gestational choriocarcinoma where doubling times can be a matter of weeks. And again, these tumors have a much slower growth rate. The majority are diagnosed, confined to the uterus and or the cervix. And the most common presenting features abnormal vaginal bleeding. They can have HCG values that are elevated but generally much lower levels compared to the tumor volume than gestational choriocarcinomas. There are a few studies that suggest that free beta HCG may be a marker for placental site trophoblastic tumor. Unfortunately, that's not uniformly available for assays. When we conventionally see patients with GTN, we stage them according to FIGO and assign a risk score but the risk score doesn't seem to correlate well with outcome in these tumors. The most important prognostic factors are the clinical stage, stages greater than stage two or patients who have a very prolonged time interval from the last pregnancy have a much poorer outcome than patients who are in stage one or two or have a low time interval between the last pregnancy and diagnosis. The radiologic evaluation prior to treatment should consist of a contrasted brain MRI or if not available CT and a contrasted CT of chest, abdomen and pelvis. Pelvic ultrasound and MRI scan may be helpful for planning surgery. These are extremely chemo-resistant tumors and do not respond to a single agent chemotherapy that's conventionally used for choreocarcinomas such as single agent methotrexate or actinomycin D. Just some histologic slides. This is a choreocarcinoma invading into the myometrium. You can see the multinucleated syncytiotrophoblastic cells and then these polygonal cytotrophoblast cells. This is a PSTT and you can have a few scattered multinucleated cells but much less than choreocarcinoma. In this lesion, it's invading along a uterine vein and these tend to invade into the myometrium in kind of a pushing pattern or with angiolymphatic direct extension. And ETT, again, these are large, obviously malignant cells and there's this highland background that sometimes can be mistaken for keratin pearls. And in fact, we've had patients who presented with a lesion involving the cervix and were treated initially for cervical cancer before the diagnosis was made. Just briefly to treat these lesions, patients with stage one and two disease, really the standard of care is to perform a hysterectomy. There's a question as to whether there's an increased incidence of lymphatic metastases but there's no evidence that performing a lymphadenectomy improves overall survival. And then many people will give chemotherapy based on risk factors, the most common being if there's been a duration of more than four years from the prior chemotherapy. And in patients who are thought to have low risk disease, the overall survival is better than 90% in patients treated with surgery alone. Patients who have high risk disease, especially prolonged duration of survival drops to about 70 to 75% in patients who are treated with surgery and usually receive chemotherapy. Is there a role for conservative surgical management of these patients if they desire preservation of fertility? And there are certainly scattered anecdotal cases of patients who are treated with a DNC or a section of a small myometrial lesion. I think most of us would treat these patients with chemotherapy after performing a conservative surgical procedure but there's really not a great body of information. For example, the largest series of patients with ETT is 54 patients in a registry and it's very difficult to make firm recommendations for conservative surgery on small numbers and the majority of those patients underwent a hysterectomy. For advanced stage disease or recurrent disease, combination chemotherapy is really the mainstay. Survival's 40 to 50% overall but many patients require surgery or localized radiation to achieve a long-term remission. I've got a patient who I've been treating over about 10 years. It's been five years since her second thoracotomy and resection of a pulmonary metastasis and every time I see her and re-scan her, I cross my fingers and hope we don't have to treat her again. What kind of chemotherapy do we recommend? MEP is usually the initial recommendation and it's detailed here. When you get the slides, you can review the doses. It's pretty standard but generally, it's a two-day atoposite dactinomycin rather than a single day and giving support after the day eight dose of atoposite cisplatin for marrow function because of the increased EMA. And then taxol platen, taxol atoposide, 28-day cycle chemotherapy is probably the second most widely recommended regimen. Currently, it's very difficult to come up with large series of patients treated with either of these regimens and other regimens that have been used are EMICO, BEP or EP, ICE, FAB, FAVE, chemotherapy and very similar results in the collected series of patients with PSTTs or ETTs. So this was a short presentation, hopefully some information that's useful and those of you who are rounding can go to rounds and the.

malignant tumors

gestational trophoblastic disease

trophoblast cells

chemotherapy regimens

prognosis