The role of surgery in gestational trophoblastic disease: an overview.

Gestational trophoblastic disease comprises a group of rare, and potentially malignant, conditions that arise from abnormal trophoblastic proliferation. When there is invasion and evidence of metastatic disease, gestational trophoblastic neoplasia is used. While chemotherapy is the mainstay of treatment for gestational trophoblastic neoplasia, the role of surgery has come full circle in recent years. Before the introduction of highly effective systemic treatment options, surgery was the default treatment. Surgery for gestational trophoblastic neoplasia often yielded unsatisfactory results and mortality remained high. In recent years, the role of adjuvant surgery in the management of gestational trophoblastic neoplasia has been examined with great interest. We aim to provide an overview of the various surgical approaches employed in managing gestational trophoblastic neoplasia, including their indications, techniques, and outcomes. Additionally, we discuss whether there is a role to do less in surgery for gestational trophoblastic neoplasia and describe our experience with a modified surgical technique for its treatment. By summarizing the current evidence, this article highlights the significant contributions of surgery to the holistic management of patients with gestational trophoblastic neoplasia and provides a framework on which to base management and treatment programs.

Chemotherapy is not needed when complete evacuation of gestational choriocarcinoma leads to hCG normalization.

BACKGROUND: The standard treatment for gestational choriocarcinoma is chemotherapy. OBJECTIVE: To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy. METHODS: A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization. RESULTS: Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases. CONCLUSIONS: This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients.

Second curettage versus conventional chemotherapy in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses for patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

BACKGROUND: Chemotherapy is the recommended treatment for gestational trophoblastic neoplasia (GTN). Second curettage had been advocated to avoid unnecessary chemotherapy and to reduce the courses of chemotherapy; however, consensus has not been reached as there are arguments claiming its inability of inducing complete regression. OBJECTIVES: The present study was performed to clarify the effectiveness of second curettage for avoiding unnecessary chemotherapy and lowering the number of chemotherapy courses in patients with post-molar GTN. SEARCH STRATEGY: Seven predominant electronic databases were searched, including four English databases and three Chinese databases, from the inception of each database until January 31, 2023. SELECTION CRITERIA: Studies were included if they were: (1) human, (2) explicitly indicated exposure to second curettage, (3) explicitly indicated control to conventional chemotherapy, (4) explicitly indicated the participants were patients with gestational trophoblastic neoplasia (GTN), and (5) compared the outcome of interest as the number of the course of chemotherapy. DATA COLLECTION AND ANALYSIS: Two authors extracted and analyzed the data independently. Disagreements were reconciled by reviewing the full text by a third author. The data of study location, data collection, study design, number of participants, intervention strategy, control strategy, the follow-up period, outcome, adverse events were analyzed. MAIN RESULTS: With regard to avoiding unnecessary chemotherapy, the overall pooled effect size of the second curettage group had a significant advantage over the conventional chemotherapy group with an OR of 0.02 (95% CI: 0.00-0.06). Meanwhile, for reducing the number of chemotherapy courses, the overall pooled effect size of the second curettage group had significant advantage over the conventional chemotherapy group with a mean difference of -2.11 (95% CI: -3.72 to -0.51). CONCLUSION: The second curettage group had a significant advantage over the conventional chemotherapy group in avoiding unnecessary chemotherapy and reducing the number of chemotherapy courses. Further larger multi-center randomized controlled trials should be conducted to confirm our results and to clarify the optimal patients' group for second curettage in patients with post-molar GTN.

Pulmonary resection of residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS: A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS: Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION: After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood ß human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.

High-intensity focused ultrasound as a pretreatment combined with hysteroscopic resection for gestational trophoblastic neoplasia with chemotherapy intolerance: a case report.

BACKGROUND: Due to resistance and intolerance to chemotherapy, localized lesion resection may be required in some patients with Gestational trophoblastic neoplasia (GTN), which may lead to massive bleeding. In this case report, we describe the successful use of high-intensity focused ultrasound (HIFU) as an effective pretreatment method for surgical procedure in a patient with GTN to reduce the perioperative risk and the impact on fertility. CASE PRESENTATION: A 26-year-old woman was diagnosed with high-risk GTN (FIGO Stage III: 12 prognostic scores) after a hydatidiform mole. The fifth chemotherapy cycle was interrupted due to severe chemotherapy toxicity. However, the uterine lesion was still present and the beta-human chorionic gonadotropin (ß-hCG) level was not restored to normal. Therefore, ultrasound-guided HIFU was performed as a pretreatment method to shrink the lesion and prevent massive bleeding during localized lesion resection. The effectiveness of ablation was evaluated immediately using contrast-enhanced ultrasound and Color Flow Doppler ultrasonography. One month after HIFU treatment, the uterine lesion was completely resected under hysteroscopic surgery. During the surgery, HIFU was found to have shrunk the lesion and there was minimal bleeding (5 mL). The uterine cavity morphology and menstruation returned to normal after surgery. The patient has showed no signs of recurrence as of one-year follow-up. CONCLUSION: Ultrasound-guided HIFU ablation may be a new choice for high-risk GTN patients with chemoresistance or chemo-intolerance. As a noninvasive pretreatment method, HIFU can shrink the uterine lesion, and reduce the risk of bleeding with no obvious effect on fertility.

Gestational trophoblastic neoplasia with primary lung cancer and mesenchymal tumor of sigmoid colon: a case report and literature review.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review. CASE PRESENTATION: The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors. CONCLUSIONS: GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.

Management of relapsed gestational trophoblastic neoplasia: What can help to reduce the re-recurrence rate?

AIM: To explore the risk factors for re-recurrence in relapsed gestational trophoblastic neoplasia (GTN) and therapeutic approaches to reduce the re-recurrence rate. METHODS: Data of relapsed GTN treated in the Obstetrics and Gynecology Hospital of Fudan University from January 1, 2015, to December 31, 2020, were reviewed retrospectively. Risk factors associated with re-recurrence were analyzed using Logistic regression analysis. RESULTS: A total of 39 relapsed GTN patients were included in our study. At the time of the first relapse, 14 patients received single-agent chemotherapy and 25 patients received multi-agent chemotherapy. Surgery was performed in 19 patients. Complete remission was achieved in all of the patients. Re-recurrence occurred in 21 patients. Univariate analysis suggested that unifocal recurrence was the only factor significantly associated with re-recurrence (OR = 0.25, p = 0.04). Recurrence pattern-based subgroup analysis showed that the proportion of re-recurrence was lower in patients who received both surgery and chemotherapy compared to those who received only chemotherapy in the unifocal recurrence group (3/11 vs. 2/4), but not in the non-unifocal recurrence group (7/8 vs. 9/16). The results of the multivariate analysis showed that there was no significant difference in re-recurrence rates between the surgical approaches and that the non-unifocal recurrence pattern was an independent risk factor for re-recurrence. CONCLUSIONS: For relapsed GTN with unifocal recurrence pattern, surgical removal of the lesion can effectively reduce the re-recurrence rate.

Effectiveness of craniotomy and long-term survival in 35 patients with gestational trophoblastic neoplasia with brain metastases: a clinical retrospective analysis.

OBJECTIVE: To investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy. METHODS: Thirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed. RESULTS: All 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55-85.15; p=0.017). CONCLUSION: Decompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.

Epithelioid Trophoblastic Tumour: A Case with Genetic Linkage to a Child Born over Seventeen Years Prior, Successfully Treated with Surgery and Pembrolizumab.

Epithelioid trophoblastic tumours are rare neoplasms showing differentiation towards the chorion leave-type intermediate cytotrophoblast, with only a handful of cases being reported in the literature. These tumours are slow-growing and are typically confined to the uterus for extended periods of time. While the pathogenesis is unclear, they are thought to arise from a remnant intermediate trophoblast originating from prior normal pregnancies or, less frequently, gestational trophoblastic tumours. A protracted time period between the gestational event and tumour development is typical. This case describes a 49-year-old previously healthy female who presented with a completely asymptomatic uterine mass, discovered incidentally during a routine gynaecological assessment. The pathological analysis of the hysterectomy specimen confirmed an epithelioid trophoblastic tumour, involving the uterus and cervix. This is a rare gynaecological tumour. A comparative short tandem repeat analysis revealed genetic similarities to a previous healthy gestation seventeen years prior. She was successful treated with adjuvant pembrolizumab, with no evidence of disease recurrence to date.

A novel approach with concomitant laparoscopic uterine artery ligation and D&C as initial treatment for complicated gestational trophoblast disease in cesarean scar and cervical ectopic pregnancies.

OBJECTIVE: Gestational trophoblast disease (GTD) in low-lying implantation ectopic pregnancy (LLIEP) is extremely rare. Surgical removal of GTD lesions which is the initial treatment of choice carries a high risk of intraoperative massive bleeding. Adequate management is challenging and inconclusive. CASE REPORT: We present two unusual cases with a diagnosis of GTD in advanced LLIEP. The first case had choriocarcinoma in cesarean scar and the second case had mole pregnancy in cervix. Both cases were managed with laparoscopy uterine artery ligations followed by transvaginal intrauterine curettage and vacuum aspiration with a small amount of surgical blood loss and then resumed regular menstruation. To understand the different surgical approaches and their potential advantages in managing such rare diseases, relevant cases in the literature were reviewed. CONCLUSION: Much attention should be paid to avoid massive bleeding at initial surgical intervention in patients with GTD in advanced LLIEP. This novel approach with combination of laparoscopic uterine artery ligations and evacuating curettage in selected patients is highly recommended to minimize surgical blood loss. The obvious advantages include technical feasibility, less surgery-related bleeding and potential fertility preservation.

High-intensity focused ultrasound ablation as an adjuvant surgical salvage procedure in gestational trophoblastic neoplasia chemotherapy with chemoresistance or recurrence: two case reports.

BACKGROUND: Chemotherapy is the main treatment strategy for gestational trophoblastic neoplasia (GTN). Surgical resection is crucial to deal with chemoresistance and recurrence following chemotherapy. The aim of this study was to explore if high-intensity focused ultrasound (HIFU) can be used as a complementary technique to surgical procedures in the management of GTN. CASE REPORT: This case report described two females who previously developed chemoresistance or recurrence during chemotherapy and then underwent HIFU as an adjuvant surgical salvage procedure. For high-risk GTN patients with chemoresistance, HIFU treatment decreased the risk of chemoresistance and shortened the course of chemotherapy. It also reduced the dosage of chemotherapeutic agents used for the patient who suffered a recurrence. CONCLUSION: For patients with GTN who desire to preserve their uterus, HIFU may be used as a complementary technique to surgical resection in the management of GTN.

Invasive mole with lung metastasis after an abdominal complete hydatidiform mole treatment.

A 27-year-old woman, gravida 1, para 0, was transferred to our hospital with acute abdominal pain. Her serum human chorionic gonadotropin level was 60 231 mIU/mL. Transabdominal ultrasound revealed an echo-free space, and emergency laparoscopy-assisted surgery was performed with a preoperative diagnosis of ruptured ectopic pregnancy. The pelvic cavity was filled with clots, and the peritoneal surface of the uterine fundus was swollen and showed continuous bleeding. The lesion was located on peritoneum and not connected with the uterine cavity. Histological examination of the conceptus showed features of a complete hydatidiform mole. After a mild decrease, hCG levels adversely increased 3 weeks later with multiple lung nodules. With a diagnosis of invasive moles, the patient was administered chemotherapy. This case demonstrates that it is important to recognize the potential of ectopic hydatidiform moles through abdominal pregnancy. This is the first report of an invasive abdominal hydatidiform mole, and hCG monitoring seemed to be essential for gestational trophoblastic neoplasia detection.

Surgery including fertility-sparing treatment of GTD.

Gestational trophoblastic disease (GTD) consists of a spectrum of diseases, including hydatidiform moles, invasive mole, metastatic mole, choriocarcinoma, placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). GTD is a relatively uncommon disease occurring in women of reproductive age, with high cure rates. Primary treatment of hydatidiform moles includes uterine evacuation, followed by close monitoring of serial hCG levels to detect for post-molar gestational trophoblastic neoplasia (GTN). In patients with GTN, the main therapy consists of chemotherapy, although some surgical procedures are important in selected patients to achieve curing. Hysterectomy is the mainstay treatment for PSTT or ETT and may be considered in selected patients for management of hydatidiform mole and malignant GTN especially in chemoresistant disease. Resection of metastatic lesions such as in the lung or brain can be considered in selected patients with isolated chemoresistant tumour. Surgical treatment of GTD will be discussed in this chapter.

Outcomes of minimally invasive versus open abdominal hysterectomy in patients with gestational trophoblastic disease.

OBJECTIVE: The aim of this study is to compare surgical and oncologic outcomes for women undergoing MIH or open abdominal hysterectomy (OAH) for management of gestational trophoblastic disease (GTD). METHODS: Patients who underwent hysterectomy for GTD between January 1, 2009 and December 31, 2018 were identified using an institutional database and tumor registry. Patients were stratified based on indication for and mode of hysterectomy. RESULTS: 39 patients underwent hysterectomy for GTD - 22 MIH and 17 OAH. 26 hysterectomies (66.7%) were performed for primary treatment of GTD, 7 (17.9%) for chemoresistance, 2 (5.1%) for uterine hemorrhage, and 4 (10.3%) for other indications. Mean tumor size (4.2 vs 4.6 cm; p = .81) and operative time (136 vs 163 mins; p = .42) were similar in both groups. MIH was associated with significantly less blood loss (71.5 vs 427.3 ml; p = .03) and shorter hospital stay (1.5 vs 3.9 days, p = .02) than OAH. Postoperative histology comprised 12 complete moles (6 invasive), 8 choriocarcinomas, 9 placental site trophoblastic tumors and 9 epithelioid trophoblastic tumors. Median follow-up was 67.2 months (50.2 MIH, 79.3 OAH; range 11.1-131.2) and there was no difference in remission (81.8% MIH vs 76.5% OAH; p = .68). There were 7 recurrences (4 MIH, 3 OAH) and 3 deaths (2 MIH, 1 OAH). Overall survival was 97.3% at 2 years and 88.5% at 5 years. There was no significant difference in 5-year survival by mode of surgery (MIH 90.9%, OAH 83.3%; p = .40). CONCLUSIONS: Patients undergoing MIH at our centers have similar oncologic outcomes, lower surgical blood loss and shorter hospital stay compared to those undergoing OAH. Overall survival is similar regardless of mode of surgery.

Hyperreactio Luteinalis (Multiple Luteinized Follicle Cysts): A Report of 10 Cases.

Hyperreactio luteinalis is a rare entity arising in pregnancy and in the setting of gestational trophoblastic diseases (ie choriocarcinoma, molar pregnancy) that presents with, typically, bilateral ovarian enlargement due to numerous follicle cysts. While the phenomenon is benign and spontaneously regresses following delivery or treatment, a specimen may be seen in pathology when oophorectomy or cystectomy is performed to exclude malignancy or to manage acute complications such as torsion. Such resections may exhibit overlapping microscopic features with cystic granulosa cell tumors. We thus reviewed 10 cases of hyperreactio luteinalis in the setting of pregnancy, the largest pathologic cohort to date, to highlight notable features of this disorder. Patients ranged from 22 to 30 yr old. Most patients (n=6) presented at time of cesarean section with incidentally discovered ovarian masses. Three patients presented in the postpartum period, and 1 underwent surgery at 28 wk gestation due to the finding of a unilateral ovarian mass. The ovaries ranged from 8.5 to 29 cm and were multicystic and bilateral in 8 of the cases. Histologic examination demonstrated multiple, variably sized cystic follicles lined by a granulosa cell layer of varying thickness and theca cells with marked eosinophilic cytoplasm. Stromal edema was often prominent, with theca cells occasionally noted in nests, cords, and as single cells in foci of edema. Mitoses were generally seen more often in the granulosa cell layer (mean=2.6 per high power fields) compared with the theca cell layer (mean=1 per 10 high power fields). This series documents the key features of hyperreactio luteinalis that differentiate it from the other benign mass forming lesions encountered in pregnancy, most notably large solitary follicle cyst of pregnancy and puerperium, as well as cystic granulosa cell tumors, especially the juvenile variant, which may also present during pregnancy. Of particular use in differentiating them from juvenile granulosa cell tumor is the absence of pale or vacuolated cytoplasm and solid growth of granulosa cells in cases of hyperreactio luteinalis.

Total laparoscopic hysterectomy in combination with dilation and evacuation of an 18-week-sized uterus with gestational trophoblastic neoplasia: a novel treatment approach.

Gestational trophoblastic disease is a spectrum that includes complete and partial hydatidiform moles, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. Although most cases of gestational trophoblastic neoplasia occur after a molar pregnancy, it can develop after any pregnancy. Suction curettage remains the standard first-line management in a molar pregnancy in patients desiring fertility. However, hysterectomy is a reasonable option in patients that do not desire to preserve fertility. Hysterectomy for gestational trophoblastic neoplasia can be difficult because of the enlarged uterus and prominent uterine vasculature. Traditionally, hysterectomy for gestational trophoblastic neoplasia is usually performed via laparotomy. In this article and accompanying video, we describe and illustrate a minimally invasive technique that demonstrates a safe and feasible laparoscopic removal of an enlarged uterus and illustrates alternative extraction techniques to avoid laparotomy in hysterectomy for gestational trophoblastic disease. In this case, a combination of laparoscopic transection of the vascular pedicles followed by dilation and evacuation was used before colpotomy. The addition of dilation and evacuation allowed us to reduce the overall size of the uterus and remove it intact through the vagina with minimal bleeding, avoiding unnecessary laparotomy. This allowed the patient to have an improved postsurgical recovery experience with minimal blood loss compared with standard laparotomy for gestational trophoblastic neoplasia.

Curative effect of second curettage for treatment of gestational trophoblastic disease - Results of the Belgian registry for gestational trophoblastic disease.

OBJECTIVE: We assessed the curative effect of a second curettage in patients with persistent hCG serum levels after first curettage for a gestational trophoblastic disease (GTD). STUDY DESIGN: This prospective observational study used the data of the Belgian register for GTD between July 2012 and January 2017. We analysed the data of patients who underwent a second curettage. We included 313 patients in the database. Primary endpoints were need for second curettage and chemotherapy. RESULTS: Thirty-seven patients of the study population (12 %) underwent a second curettage. 20 had persistent human chorionic gonadotropin hormone (hCG) elevation before second curettage. Of them, 9 patients (45 %) needed no further treatment afterwards. Eleven patients (55 %) needed further chemotherapy. Nine (82 %) were cured with single-agent chemotherapy and 2 patients (18 %) needed multi-agent chemotherapy. Of the 37 patients, patients with hCG levels below 5000 IU/L undergoing a second curettage were cured without chemotherapy in 65 % versus 45 % of patients with hCG level more than 5000 IU/L. Of the ten patients with a hCG level below 1000 IU/L, eight were cured without chemotherapy. CONCLUSIONS: Patients with post-mole gestational trophoblastic neoplasia can benefit from a second curettage to avoid chemotherapy, especially when the hCG level is lower than 5000 IU/L.