The potential value of red blood cell distribution width in patients with invasive hydatidiform mole.

BACKGROUND: Red blood cell distribution width (RDW) has attracted increasing attention in cancer. The aim of this study was to assess the changes of RDW in patients with invasive hydatidiform mole and analyze the relationship between RDW and invasive hydatidiform mole. METHODS: A retrospective analysis was performed on 102 patients diagnosed as invasive hydatidiform mole in the First Affiliated Hospital of Guangxi Medical University from January 2009 to March 2018. A total of 120 healthy subjects were used as a control group. The Mann-Whitney U test was used for comparison between the invasive hydatidiform mole and control groups. Comparison of RDW with other blood parameters was performed using Spearman's. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were also determined. RESULTS: The RDW, platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and absolute lymphocyte count were significantly elevated in the invasive hydatidiform mole group compared with control group. The hemoglobin (Hb) concentration, mean red blood cell volume (MCV) and platelet count (PLT) were significantly lower in invasive hydatidiform mole group than control group. Grade III and above invasive hydatidiform mole patients had higher levels of RDW than grade I and II patients. Correlation analysis showed that RDW was negatively correlated with Hb, MCV, NLR, and neutrophil count, but positively correlated with PDW and different stages of invasive hydatidiform mole. The ROC curve showed that the AUC of the RDW was 0.660 (95% CI 0.581-0.740; P < 0.01). CONCLUSION: This study reveals the potential value of RDW in invasive hydatidiform mole.

Histopathological and clinical features of molar pregnancy.

OBJECTIVE: To analyse own set of molar pregnancies and to develop clinically relevant procedures. TYPE OF STUDY: Review article with analysis of own data. SETTINGS: Department of Pathology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague; Department of Obstetrics and Gynecology 3rd Faculty of Medicine, Charles University, Faculty Hospital Královské Vinohrady, Prague. INTRODUCTION: The study monitors the decrease of laboratory values of beta-subunit of hCG gonadotropin (beta-hCG) after evacuation of partial and complete hydatidiform moles in a set of 45 partial and 46 complete moles. Two case reports of invasive moles. RESULTS: In cases of partial hydatidiform moles there was complete regression of beta-hCG in all cases, 89% regressed in six weeks, none of the women showed no subsequent elevation after reaching negativity. In cases of complete hydatidiform moles the decrease was less gradual, the negativity after six weeks was confirmed in 78%, three complete moles became malignant. CONCLUSION: The decrease of beta-hCG after molar pregnancy termination is variable. Even if in cases of complete hydatidiform moles the risk of malignization after reaching negativity is low, beta-hCG checks are recommended at monthly intervals for 6 months. Correct diagnosis of complete mole and its differentiation from partial mole can be achieved using immunohistochemistry - p57 antibody.

Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors.

OBJECTIVE: To determine the ability of several radioimmunoassays and commercial two-site immunoassays to detect the first World Health Organization International Reference Reagents (IRRs) for 6 defined human chorionic gonadotropin (hCG) variants and to compare their performance in measuring hCG in sera from patients with gestational trophoblastic disease (GTD) and germ cell tumors (GCTs) of the testis or ovary. STUDY DESIGN: The reactivity of the different assays with the 6 IRRs together with the current fourth International Standard (IS, 75/589) was tested using 5 commercial two-site assays as well as 2 competitive polyclonal radioimmunoassays (RIAs) and a competitive monoclonal immunoassay. Individual samples from 41 patients (19 GCT and 22 GTD) with high circulating levels of hCG (range, 718-6,055,000 IU/L) were diluted and measured using the various immunoassays. RESULTS: The results of 4 GCT patient samples varied markedly among the assays, including 1 sample that was grossly underestimated by 3 of the commercial assays. CONCLUSION: Comparison of each assay's reactivity to the variant isoforms revealed that recognition of the isoforms was highly variable, particularly for hCGbeta and hCGbeta core fragment (hCGbetacf).

Japanese trial for classification of gestational trophoblastic disease.

OBJECTIVE: To evaluate the clinical usefulness of the Japanese Diagnostic Score to differentiate choriocarcinoma clinically without histologic findings from persistent gestational trophoblastic disease (GTD). STUDY DESIGN: We reviewed the clinical records and histologic reports on all 809 patients with persistent GTD treated with surgery and chemotherapy in Japan. There were 347 cases of choriocarcinoma and 462 cases of invasive mole with histologic confirmation. We retrospectively applied the Japanese Diagnostic Score to all patients for detection of choriocarcinoma in persistent trophoblastic disease. RESULTS: The sensitivity of the score for choriocarcinoma was 92.2%. The specificity was 93.5%. This retrospective study showed that the accuracy of this scoring system to differentiate true malignant choriocarcinoma clinically from both low risk and high risk gestational trophoblastic neoplasia without histologic findings was 92.9%. CONCLUSION: Our trial to differentiate choriocarcinoma clinically from persistent GTD without histologic findings using a unique scoring system was successful. Proper management in the early stages strongly influences the outcome of these diseases. This scoring system should be very useful in comparing the incidence and survival rate of choriocarcinoma between nations.

Invasive mole--case report of massive uterine destruction.

Patient with malignant Gestational Trophoblastic Neoplasm (GTN) was treated by mean of MTX-FA, MAC, EMA-CO and EMA-EP. Changes in serum human chorionic gonadotropine (beta hCG) levels and changes in ultrasonographic findings were checked weekly. Finally transabdominal hysterectomy with ovaries conservation was done and polychemotherapy administrated after the operation until three consecutive serum chorionic gonadotropine values were negative. This is a case report of Invasive mole in 32 years old patient without possibility to preserve reproductive health. GTN developed two months after spontaneous abortion in 13th week gestation. No changes in uterine structure were found during the first ultrasonographic examination. Three months after abortion and one month after GTN confirmed, massive destruction of lateral uterine wall was detected during transvaginal Doppler ultrasound examination. Resistance index of 0,366 was significantly lower than normal, with hypervascularisation in affected tissue. Serum beta hCG confirmed poor effect of polychemotherapy treatment and decision for operative treatment was made. Hystological findings after the operation confirmed malignant GTN- invasive mole. Specific changes in ultrasonographic picture could have an impact in therapy making decision and could not be refereed without the most relevant parameter such is serum human chorionic gonadotropine.

Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies.

AIM: The aim of this study was to discriminate mole pregnancies and invasive forms among cases with first trimester vaginal bleeding by the utilization of some complete blood count parameters conjunct to sonographic findings and beta human chorionic gonadotropin concentration. MATERIALS AND METHODS: Consecutive 257 cases with histopathologically confirmed mole pregnancies and 199 women without mole pregnancy presented with first trimester vaginal bleeding who admitted to Zeynep Kamil Women and Children's Health Training Hospital between January 2012 and January 2016 were included in this cross-sectional study. The serum beta HCG level at presentation, and beta hCG levels at 1st, 2nd and 3rd weeks of postevacuation with some parameters of complete blood count were utilized to discriminate cases with molar pregnancy and cases with invasive mole among first trimester pregnants presented with vaginal bleeding and abnormal sonographic findings. RESULTS: Levels of beta hCG at baseline (AUC = 0.700, p < 0.05) and 1st (AUC = 0.704, p < 0.05), 2nd (AUC = 0.870, p < 0.001) and 3rd (AUC = 0.916, p < 0.001) weeks of postevacuation period were significant predictors for the cases with persistent disease. While area under curve for mean platelet volume is 0.715, it means that mean platelet volume has 21.5% additional diagnostic value for predicting persistency in molar patients. For 8.55 cut-off point for mean platelet volume, sensitivity is 84.6% and specificity is 51.6%. Area under curve for platelet/lymphocyte ratio is 0.683 means that platelet/lymphocyte ratio has additional 18.3% diagnostic value. For 102.25 cut-off point sensitivity is 86.6% and specificity is 46.2. CONCLUSIONS: Simple, widely available complete blood count parameters may be used as an adjunct to other risk factors to diagnose molar pregnancies and predict postevacuation trophoblastic disease.

Partial hydatidiform mole.

A case of partial hydatidiform mole is presented, occurring in a young primiparous woman after natural conception. She presented with incomplete miscarriage. Histological diagnosis of partial mole was made. Failure of beta HCG to fall resulted in the start of chemotherapy. WHO scoring placed her in low risk group. In spite of the low risk, she required third line chemotherapy for complete eradication of disease.

Radioimmunoassay of the serum free beta-subunit of human chorionic gonadotropin in trophoblastic disease.

We developed a RIA specific for the free beta hCG employing anti-beta hCG monoclonal antibody 1D12. This RIA was highly sensitive to free beta hCG; the minimum detectable concentration was 0.4 ng/ml. alpha hCG, LH, beta LH, and FSH had little effect in the assay; the cross-reactivity of hCG was about 4%. Using this RIA, we measured serum free beta hCG concentrations in 38 normal pregnant women and 72 untreated patients with 3 types of trophoblastic disease: hydatidiform mole (n = 15), invasive mole (n = 29), and choriocarcinoma (n = 28). All of these samples were simultaneously assayed for hCG by RIA. In normal pregnant women, serum hCG changed as pregnancy progressed, but serum free beta hCG was not detected at any time. In contrast, serum free beta hCG was measurable in the majority of patients with trophoblastic disease. Strong correlations were found between the concentration of free beta hCG and that of hCG in each type of trophoblastic diseases. The mean free beta hCG to hCG ratio was lowest for hydatidiform mole and highest for choriocarcinoma, and the difference between the ratios in these 2 groups was statistically significant. Serial measurements in 7 patients with trophoblastic disease failed to reveal remarkable changes in the free beta hCG to hCG ratio throughout their clinical course. We conclude that the production of free beta hCG increases with the immaturity of the trophoblastic cell, and the degree of differentiation of trophoblastic cells may be reflected by the free beta hCG to hCG ratio.

Invasive mole.

A case of persistent trophoblastic disease with resistance to chemotherapy is presented. The value of continued and frequent serum hCG measurements in such cases is discussed as well as the indications for performing hysterectomy.

Serum SP1, hPL and beta-hCG levels in trophoblastic diseases.

Serum SP1 (pregnancy specific beta 1 glycoprotein), hPL (human placental lactogen) and beta-hCG (beta-human chorionic gonadotropin) in patients with choriocarcinoma, invasive mole, and hydati-diform mole were determined by radioimmunoassay (RIA), and compared with those in normal males, non-pregnant women and normal pregnant women in order to evaluate the clinical significance of SP1, hPL and beta-hCG determinations. Serum SP1 levels at the time of admission were highest in hydatidiform mole (5.1 +/- 0.6 micrograms/L) and lowest in choriocarcinoma (0.5 +/- 0.3 micrograms/L). Serum hPL levels were 68.2 +/- 9.7 ng/L in hydatidiform mole and 26.4 +/- 8.3 ng/L in choriocarcinoma. Serum SP1 and hPL levels in trophoblastic diseases were lower than in normal pregnancies (SP1 11.5 +/- 5.1 micrograms/L, hPL 216.8 +/- 48.1 ng/L). SP1/beta-hCG ratios were less than 1.5 in 4/43 (9.3%) cases of hydatidiform mole and 17/19 (89.5%) cases of invasive mole and choriocarcinoma. The beta-hCG/hPL ratios were below 15 in 35/43 (81.4%) cases of hydatidiform mole and 4/19 (21.1%) malignant trophoblastic diseases. The prognosis after operation and chemotherapy was favourable if patient's SP1 and beta-hCG levels gradually decreased.

Study and treatment of gestational trophoblastic diseases at the John I. Brewer Trophoblastic Disease Center, 1962-1990.

From 1962 through 1989, 5063 patients were referred to the John I. Brewer Trophoblastic Disease Center of the Northwestern University Medical School. Among these were 564 patients treated with chemotherapy for gestational trophoblastic tumors (choriocarcinoma and invasive mole). The overall cure rate was 94%, 100% for 323 patients without evidence of metastases and 85% for 241 patients with metastatic disease. Four factors were determined to significantly influence treatment response: (1) clinicopathologic diagnosis of choriocarcinoma, (2) metastases to sites other than the lung or vagina, (3) number of metastases, and (4) previous failed chemotherapy.

[Regression of hCG in various types of molar pregnancies--clinical course and prognosis]. / Regrese hCG u ruzných typu molárních tehotenství--klinický prubeh a prognóza.

OBJECTIVE: To evaluate spontaneous regression curves of hCG serum positivity in patients with surgically treated molar pregnancies. Comparison of complete, partial and invasive mole. The study should result in optimalisation of follow up criteria of molar pregnancies in respect to their potential malignant change. DESIGN: Retrospective comparative clinical study. SETTING: Obst. Gyn. Dpt., Oncogynecology div., 2nd Medical Faculty, FNM, Charles University Prague, Pathology Dpt., 2nd Medical Faculty, Institute of Biology and Medical Genetics. METHODS: Evaluation of spontaneous regression curves of serum hCG levels in 104 molar pregnancies. 46 patients with partial hydatiform mole, 48 patients with complete hydatiform mole, 10 patients with invasive mole. Serum hCG levels were detected by radioimunoassay (RIA) in the first period and imunochemoluminisent assay (LIA) in the second period. Regression curves of hCG positivity in particular moles were statistically evaluated by Fischer test and t-test. RESULTS: There is statistically significant difference in spontaneous regression of hCG positivity in different types of molar pregnancies. Recommended criteria for gestational trofoblastic disease (GTD) diagnosis and follow up are fully applicable in clinical practice. There is exception in partial hydatiform moles, where plateau in hCG regression does not necessarily implicate chemotherapy in patient with good compliance. CONCLUSION: Early diagnosis of GTD predominantly due to the widespread use of ultrasonography changes classical clinical features of molar pregnancies. Spontaneous regression in hCG positivity in serum is more rapid in patients with partial hydatiform mole, slower in complete hydatiform mole and invasive mole. There is no significant change in malignant potential regarding early detection and treatment.

[Chemotherapy in placental tumors]. / La chimiothérapie des tumeurs placentaires.

Chemotherapy is a useful element, but not the only element, for controlling placental tumours. In cases of simple mole routine chemotherapy does not seem to be justified and usually, in 9 cases out of 10, it is useless. It is certainly not always effective and sometimes it may even be dangerous because of the development of chemoresistance. Invasive mole and tumours where a histological diagnosis has not been made and where there is no particularly unfavourable prognosis, usually heal with twice weekly methotrexate carried on for two months after cure has been confirmed clinically, radiologically and biologically. Choriocarcinomata and cases where histology has not been carried out but which have poor prognosis (extra-pulmonary metastases, numerous or large pulmonary metastases, long delay in treatment and the excretion of high levels of HCG) justify chemotherapy in which vincristine is followed by methotrexate or vincristine is followed by actinomycine D. For cure in these bad cases secondary surgery to remove residual lesions, either in the uterus or the lungs, may be necessary.

PIP: The role of chemotherapy in the control of placental tumors is examined, both as a separate, single treatment, and as a conjuctive treatment. Its usefulness is most evident in the latter form of approach. In cases of the simple mole, its use is not really justified, and it does not appear to be effective in 9 out of 10 cases. In any therapeutic approach, it is not always effective and can be dangerous in the event of the development of chemoresistance. In cases of invasive mole and tumors where a histological diagnosis has not been made, and where a definite unfavorable prognosis is not evident, a twice weekly administration of methotrexate for a 2-month period after the cure has been clinically, radiologically, and biologically confirmed usually heals the formations. Choriocarcinomata and cases where a histology has not been carried out but where a negative prognosis is evident (extrapulmonary metastases, pulmonary metastases, delays in treatment, or the excretion of high levels of human chorionic gonadotropin), chemotherapy is considered justified with vincristine followed by methotrexate or actinomycin D. Surgical intervention to remove residual lesions may be necessary in these cases.

[Clinical evaluation of ultrasonography in diagnosis of the early invasive hydatidiform mole].

The consecutive uterine changes of the B ultrasonic scan were observed in 41 cases with invasive hydatidiform mole, which compared with the uterine changes in 10 controls who had induction of labor in second trimester. It was found that B ultrasonic scan was very useful technic in diagnosis of invasive mole. The time when the serum hCG titers fell to normal was earlier than the time of B scan reversed during treatment. Therefore, the B scan of uterus is of value in early diagnosis and therapeutic quide of invasive mole.

[Evaluation of serum ferritin in female genital neoplasms].

Serum ferritin concentrations of 50 normal women and 90 patients with neoplasms of female genital tract were determined by radioimmunoassay. The mean value of serum ferritin in 23 cases of ovarian carcinoma was 402.04 micrograms/L, significantly higher than that of normal subjects and patients with benign genital neoplasms. Serum ferritin levels in patients with endometrial carcinoma, endometrial stromal sarcoma, and benign genital neoplasms were significantly higher than that of the normal subjects. There was a positive correlation between the serum ferritin level and the clinical stage of ovarian carcinoma. The serum ferritin determination is useful in the diagnosis, differential diagnosis and prognosis of ovarian cancers.

[Molar pregnancy (primary or recurrent?)]. / Embarazo molar (ex novo aut resurrectio).

A peculiar case of gestational trophoblastic disease is described. A 24 year old female with former history of three molar pregnancies, spontaneous abortion and anembryoic pregnancy was admitted because of a newly diagnosed hydatiform mole (ex novo). After uterine curettage followed by a low oral dose of methotrexate (0.5 mg/kg/day) for five days. The HCG levels determined in plasma by beta-HCG- radioinmmunoassay, became negative until four months of follow3 up. An intrauterine device was installed. She resumed HCG positivity a year later and a histerectomy was performed. A post-surgical diagnosis of invasive mole was made. Since the possibility of intercurrent pregnancy was lowered by the presence of a intrauterine device, we assumed that trophoblastic transformation into an invasive mole adopted a sort of dormant period before its resurge (resurrection) independently either from curettage of chemotherapy.

Laparoscopically diagnosed invasive mole presenting as acute hemoperitoneum.

A young multipara presented with acute abdominal pain. She had history of dilatation and evacuation for a missed miscarriage 2 months back. The diagnosis of ectopic pregnancy was made on the basis of clinical presentation and laboratory investigations. Laparoscopy was performed which revealed features of invasive mole. The procedure was converted to laparotomy and hysterectomy was performed. Patient recovered well. Histopathology confirmed the diagnosis of invasive mole. Follow-up till 12 weeks reported return to normal ßhCG (beta subunit of human Chorionic Gonadotropin) levels.

Ovarian hyperstimulation syndrome in a spontaneous pregnancy with invasive mole: report of a case.

It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of severe OHSS in spontaneous pregnancy with invasive mole in a 34 years old woman. The clinical picture showed abdominal pain, massive ascites, nausea, dyspnea and amenorrhea. After imaging examinations and laboratory tests, the diagnosis was established. The patient was managed expectantly with no complications. Although spontaneous ovarian hyperstimulation is a rare entity, it is important that the physician recognizes this condition. Prompt diagnosis and successful management is likely to avoid serious complications, which may develop rapidly.