Selected issues in trophoblastic tumors

Since the vast majority of GTN patients do not survive histologic pathologic diagnosis, persistent elevated blood HCG levels after pregnancy and imaging or lesions without metastases are the most important basis for diagnosis. The International Federation of Gynecology and Obstetrics (FIGO) and the International Society of Gynecologic Oncology (ISCG) recognize the only type of gynecologic malignancy that can be clinically diagnosed without histopathologic evidence. Any persistent elevation or unsatisfactory decrease in blood HCG after miscarriage, postpartum and gravida should be considered as a possibility of GTN. FIGO anatomical staging criteria for gestational trophoblastic neoplasm in 2000 Stage Definition Ⅰ lesion limited to uterus Ⅱ lesion beyond uterus but limited to genital organs (parametrium, adnexa and vagina) Ⅲ lesion metastasized to lung with or without genital tract metastasis Ⅳ lesion metastasized to brain, liver, intestine, kidney and other organs FIGO indications for discontinuation of chemotherapy for low-risk GTN are: at least 1 course of consolidation chemotherapy after normal HCG For those with slow decreasing HCG or extensive lesions, 2-3 courses of consolidation chemotherapy can be given after normal HCG. EMA-CO is well tolerated, and the common side effects are bone marrow suppression, followed by hepatic and renal toxicity. Indications for discontinuation of chemotherapy in patients with high-risk GTN: disappearance of signs and symptoms and metastases, weekly HCG measurement, and consolidation for 2-3 courses after 3 consecutive negative results. FIGO recommended indications for discontinuation of chemotherapy: 3 courses of consolidation after HCG negativity in patients with primary treatment norms. The overall recurrence rate after GTN treatment is 3.4-8%. The recurrence rate correlates significantly with the clinical stage and prognostic high-risk factors of the patients. Staphylococci: Staphylococci are named after the proliferation of placental chorionic villi after pregnancy and the interstitial edema, resulting in the formation of blisters of varying sizes, which are connected to each other by tissues and resemble grapes. It is called “complete hydatidiform mole CHM” and “partial hydatidiform mole PHM”. PHM is often misdiagnosed as incomplete miscarriage or miscarriage and requires pathology to confirm the diagnosis. The diagnosis is confirmed by pathology. The diagnosis of PHM is often misdiagnosed as incomplete miscarriage or abortion and requires pathology. Genetically, most CHMs are of solitary male origin with vacuolar fertilization and have double chromosomes, the main karyotypes being 46XX and 46XY, and can be classified according to their genetic origin as complete staphylocytes of paternal origin (androgenetic CHM anCHM) and complete staphylocytes with two sets of chromosomes from both parents (bipartenal CHM biCHM); whereas PHM is a double sperm fertilization of normal oocytes with triplet chromosomes and major karyotypes 69XXY, 69XXX and 69XYY. The abnormal genes form the basis for the pathogenesis of AnCHM. Age is a high risk factor for CHM, mainly at both extremes, with the risk of staph under 16 years of age being 6 times higher than in women aged 16-40 years; over 40 years of age is 5-10 times higher than in younger women, and the incidence can be as high as 1/3 of pregnancies over 50 and 40 years of age.PHM, on the other hand, has little correlation with age. The malignancy rate is 15% for CHM and 0.5% for PHM. The rate of malignancy in CHM is 15% and that in PHM is 0.5%. Several important factors are related to the malignancy of staphyloma: ① Age factor: <35 malignancy rate 15% >35 malignancy rate 30% >40 malignancy rate 37% >50 malignancy rate 56% ② Rate of uterine enlargement: uterus greater than menopause month malignancy rate 20% uterus equal to menopause month malignancy rate 10.4% uterus less than menopause month malignancy rate 3.6% ③ HCG level: high titer HCG > 105U/ L malignancy rate 31% medium L malignancy rate 31% medium titer HCG<105 U/L malignancy rate 12% low titer HCG≤103 U/L malignancy rate 10.9% ④ ovarian flavinized cyst diameter>6cm ⑤ staphylococcal blister size large blister malignancy rate 0 small blister (d<1cm ) malignancy rate 22.9% ⑥ repeated staphylococytes, persistent staphylococytes local invasion and distant metastasis incidence best 3-4 times. It is recommended that prophylactic chemotherapy can be administered to those with one of the high-risk factors or CHM without conditional follow-up. The timing of prophylactic chemotherapy is usually 2-3 days before or at the same time as the removal of the gravida, and at the latest on the day after the curettage. The recommended drugs are MTX or actinomycin D. Special types of GTN: placental site trophoblastic tumor (PSTT) and epithelial trophoblastic tumor (ETT) are special types of trophoblastic tumors of intermediate trophoblast origin. PSTT is derived from intermediate trophoblastic cells at the implantation site and ETT is derived from villous-type intermediate trophoblastic cells. PSTT: The average age is 30 years, most of them are born at term, but can also be secondary to miscarriage or induction of labor, and 5-8% have a history of complete staphyloma. HCG is mildly elevated or not, and HPL is usually mildly elevated or negative. 10-15% of patients have already had ectopic metastases at the time of diagnosis, with up to 30% recently reported in the literature. The most common sites of metastasis are the lungs, pelvis and lymph nodes. Liver, kidney and central nervous system metastases are relatively rare. The survival rate for stage I patients is up to 100%, while the survival rate for metastatic patients is only 30%. 10% recur after treatment. ETT: It is mainly seen in women of childbearing age, with a mean age of 36 years, and most ETT is secondary to term delivery, miscarriage, gravida and choriocarcinoma. 67% are secondary to term delivery, 16% to spontaneous abortion and 16% to gravida. ETT is diagnosed 6.2 years after the previous pregnancy. The common clinical presentation is vaginal bleeding. In a few patients, metastatic symptoms are the first manifestation, and only metastatic lesions may be seen, while the primary uterine lesions have disappeared. The majority of ETT have mildly elevated HCG or no HCG, usually not higher than 2500 U/L. High risk factors affecting the prognosis of PSTT are: ① having an extra-uterine metastatic lesion. (ii) mitotic count >5 mitoses/10 HPF. (iii) >2 years from previous pregnancy. In addition, complications such as age ≥ 40 years, blood HCG > 1000 U/L, large tumor size, myelomeningocele invasion depth > 1/2, vascular involvement, tumor necrosis, presence of a large number of cytoplasmically clear tumor cells, hypertension, numerous erythrocytes, and splenomegaly suggest a poor prognosis. Treatment of PSTT and ETT: Surgery: total hysterectomy Chemotherapy:EMA-CO EP-EMA Trophoblastic tumors have two prominent features: short tumor cell multiplication time and the ability to produce HCG. The antimetabolites 5-Fu and MTX are the first-line chemotherapeutic agents for trophoblastic tumors, while etoposide (VP-16) and platinum regimens are often the second-line regimens. Used in the treatment of drug-resistant patients, 5-Fu can cause bacterial dysbiosis diarrhea and myocardial damage, MTX causes renal tubular damage and MTX pneumonia, and VP-16 can cause secondary tumors. The time interval of chemotherapy is the birth date of discontinuation of chemotherapy, not the time interval from the first day of this chemotherapy to the first day of the next chemotherapy. The normative use of granulocyte colony-stimulating factor (G-CSF) is at least 24 hours from chemotherapy and not at the same time as chemotherapy. Most scholars believe that after 1 course of chemotherapy, the HCG decline is not logarithmic, suggesting the possibility of drug resistance; after 2 courses of chemotherapy, the HCG decline still does not reach a logarithm, then it is drug resistance. Drug resistance, relapse: Drug-resistant GTN means that HCG does not drop significantly or plateau or even rise during chemotherapy, and other tests indicate that the tumor does not shrink or increase, or even new lesions appear. If HCG decreases <20% in 1 course of treatment, it is drug resistant. If HCG is negative for 3 consecutive weeks after some treatments and other examinations indicate that the lesions have disappeared for 3 months, but HCG rises or other examinations reveal new lesions, it indicates relapse; if the above situation occurs after 1 year, it is late relapse; if the above situation occurs within 3 months, it is persistent GTN. The causes of drug resistance and relapse are: ① Insufficient treatment course and prolonged interval. ②Insufficient dose. ③Irrational chemotherapy regimen. ④Not consolidating chemotherapy. ⑤ Failure to select sensitive drugs. (6) Extensive metastasis, especially liver-brain metastasis. (vii) Large persistent lesions. (8) Missed surgery and chemotherapy. ⑨Insensitive method of detecting HCG. ⑩The clinician has limited experience in dealing with GTN disease. ⑪The patient's economic situation is poor. The surgical scope of hysterectomy or hysterectomy for GTN is as follows: 1. For low-risk non-metastatic patients without fertility requirements, hysterectomy is performed after a short course of chemotherapy, one to shorten the treatment time and reduce the course of chemotherapy. 2.For drug-resistant lesions confined to the uterus, hysterectomy or hysterectomy with preservation of the uterus can be performed according to the requirement for fertility or not. 3.For GTN patients with perforated uterine lesions with intra-abdominal bleeding or uterine hemorrhage, hysterectomy is performed on an emergency basis. 4.PSTT and ETT surgery are the preferred treatment modalities. Indications for lobectomy for GTN: lobectomy is an important tool in the management of patients with pulmonary metastases and resistant to drugs. Those who have negative lung CT examination without symptoms are unlikely to have liver or brain metastases and can not do the related examination, but for patients with lung or vaginal metastases, cranial CT suffering from MRI should be performed. 1.Surgery can be tolerated. 2.The primary lesion has been controlled. 3.Lung metastasis is limited to one side. 4.No other metastatic lesions. 5.Blood HCG titer ∠1000U/L (105 trophoblast cells produce 1U/L HCG). GTN resistance basically belongs to non-cross-resistance, such as MTX resistance choose Act-D (actinomycin D); 5-Fu, FUDR (fluoroguanosine) resistance choose MTX. 5-Fu, FUDR, Act-D, MTX and VP-16 generally do not occur cross-resistance. EMA-CO: EMA-EP: TP/TE/FAEV: Myelosuppression after chemotherapy: Absolute neutrophil values below 1 x 109/L PLT below 50 x 109/L, which is the threshold for possible bleeding complications and requires intervention. For granulocytopenia with fever, antibiotics should be used; for fourth-degree myelosuppression, antibiotics must be used prophylactically, with or without fever. In general, platelet counts can be raised by 10×109/L - 20×109/L per unit of single platelet collection,and the life span of exogenous platelets is only maintained for about 72 hours.