Urine and serum metabolomic analysis of endometrial cancer diagnosis and classification based on ultra-performance liquid chromatography mass spectrometry.

OBJECTIVE: This study aimed to reveal the urinary and serum metabolic pattern of endometrial cancer (EC) and establish diagnostic models to identify EC from controls, high-risk from low-risk EC, and type II from type I EC. METHOD: This study included 146 EC patients (comprising 79 low-risk and 67 high-risk patients, including 124 type I and 22 type II) and 59 controls. The serum and urine samples were analyzed using ultraperformance liquid chromatography mass spectrometry. Analysis was used to elucidate the distinct metabolites and altered metabolic pathways. Receiver operating characteristic (ROC) analyses were employed to discover and validate the potential biomarker models. RESULTS: Serum and urine metabolomes displayed significant differences between EC and controls, with metabolites related to amino acid and nicotinamide metabolisms. The serum and urine panels distinguished these two groups with Area Under the Curve (AUC) of 0.821 and 0.902, respectively. The panel consisting of serum and urine metabolites demonstrated the best predictive ability (AUC = 0.953 and 0.976 in discovering and validation group). In comparing high-risk and low risk EC, differential metabolites were enriched in purine and glutamine metabolism. The AUC values for serum and urine panels were 0.818, and 0.843, respectively. The combined panel exhibited better predictive accuracy (0.881 in discovering group and 0.936 in external validation). In the comparison between type I and type II group, altered folic acid metabolism was identified. The serum, urine and combined panels discriminated these two groups with the AUC of 0.829, 0.913 and 0.922, respectively. CONCLUSION: The combined urine and serum metabolome effectively revealed the metabolic patterns in EC patients, offering valuable diagnostic models for EC diagnosis and classification.

Efficacy and safety of an oral combination therapy of niraparib and etoposide in platinum resistant/refractory ovarian cancer: a single arm, prospective, phase II study.

OBJECTIVE: Non-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase II study aimed to evaluate the efficacy and safety of oral niraparib plus etoposide in platinum resistant/refractory ovarian cancer. METHODS: Platinum resistant/refractory ovarian cancer patients after ≤2 lines of platinum based chemotherapy, histologically confirmed as non-mucinous epithelial ovarian cancer, regardless of biomarker status, were eligible. Patients received niraparib with a starting dose of 200 mg/100 mg alternate once a day, and oral etoposide of 50 mg once a day, on days 1-20 of 30 days per cycle for a maximum of 6-8 cycles, followed by niraparib until disease progression or intolerable toxicity. The primary endpoint was investigator assessed progression free survival. RESULTS: 29 patients were enrolled from 22 May 2020 to 3 February 2023; 26 patients were included in the efficacy analysis set as per protocol. Median progression free survival was 4.2 months (95% confidence interval (CI) 3.9 to 4.4). Overall response rate was 26.9% (95% CI 8.7 to 45.2). Disease control rate was 57.7% (95% CI 37.3 to 78.0). Overall response rate in patients with a BRCA mutation and homologous recombination deficiency was 50% and 41.7%, respectively. Median progression free survival in patients with primary platinum resistance was 4.5 months (95% CI 3.6 to 5.3). 29 patients were included in the safety analysis set, and 8 (28%) patients experienced treatment related adverse events of grade ≥3. There was no treatment related discontinuation. CONCLUSIONS: Niraparib combined with etoposide showed evidence of antitumor activity in platinum resistant/refractory ovarian cancer after ≤2 lines of platinum based chemotherapy, particularly in patients with a BRCA mutation, homologous recombination deficiency, or primary platinum resistance. This once-a-day oral combination was a convenient option. TRIAL REGISTRATION NUMBER: NCT04217798.

Survival outcomes and the prognostic significance of clinicopathological features in patients with endometrial clear cell carcinoma: a 35-year single-center retrospective study.

BACKGROUND: To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes. METHODS: Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan-Meier method and Cox regression analysis were used. RESULTS: In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS. CONCLUSIONS: ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.

Oncological and reproductive outcomes for gonadotropin-releasing hormone agonist combined with aromatase inhibitors or levonorgestrel-releasing intra-uterine system in women with endometrial cancer or atypical endometrial hyperplasia.

OBJECTIVE: To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) or aromatase inhibitor (letrozole) in women with endometrial carcinoma or atypical endometrial hyperplasia who wished to preserve fertility. METHODS: Patients at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital between January 2013 and December 2020 were retrospectively reviewed. A total of 179 patients who were unsuitable to undergo treatment with high-dose oral progestin, including those with progestin allergies, body mass index ≥30 kg/m2, liver and/or renal dysfunction, hypercoagulable state, and thrombosis were included. Patient data were retrieved from medical records and a prospectively maintained database that represented the standard protocol was followed for all patients. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed. Logistic regression models were constructed to determine the associations between complete remission, recurrence, and fertility. RESULTS: Overall, 169 patients (94.4%) achieved complete remission; 58 (96.7%) had atypical endometrial hyperplasia and 111 (93.3%) had endometrial carcinoma. The complete remission rates for the GnRHa plus LNG-IUD and GnRHa plus letrozole groups were 93.5% and 95.8%, respectively. The median time to complete remission was 6 (range 3-18) months: 4 (range 3-10) months for atypical endometrial hyperplasia and 8 (range 3-18) months for endometrial carcinoma. After a median follow-up of 27.5 (range 3-92) months, 41 (24.3%) women developed recurrence, with a median recurrence time of 17 (range 6-77) months. Of the patients with complete remission, 134 patients desired to conceive and 42 (32.3%) became pregnant, 24 (17.9%) were successfully delivered, 5 (3.7%) were still pregnant, while 13 miscarried. CONCLUSION: GnRHa combined treatment provides favorable oncological and reproductive outcomes. Larger multi-institutional studies are required to confirm these preliminary findings.

Diagnosis and management of growing teratoma syndrome after ovarian immature teratoma: A single center experience.

OBJECTIVES: To evaluate the diagnostic, surgical, and oncological outcomes of patients with growing teratoma syndrome (GTS). METHODS: Patients diagnosed with ovarian immature teratoma (IMT) between 1980 and 2018 at Peking Union Medical College Hospital (PUMCH) were evaluated for the development of GTS. Their clinical characteristics, surgical and pathological data, and oncological outcomes were collected. RESULTS: Between 1980 and 2018, 175 cases of IMT were referred to PUMCH. Thirty-five patients subsequently developed GTS with a crude rate of approximately 20%. The median interval between the initial diagnosis of IMT and the first occurrence of GTS was 18.5 months (range, 6-78 months). Residual disease (P < 0.001) and gliomatosis peritonei (GP) at initial surgery (P = 0.023) were independent risk factors for GTS development. Fertility-sparing surgery for GTS was performed in 27 patients and four patients achieved five singleton pregnancies. The median follow-up time was 73 months (range, 11-401 months). Eleven patients developed at least one recurrence. Residual disease after GTS surgery was associated with GTS recurrence (P = 0.001). By the end of follow-up, 27 patients were alive without disease and the other eight patients were alive with disease. CONCLUSION: The presence of residual disease and GP at initial surgery are risk factors for GTS. Complete surgical resection is the cornerstone for treatment of GTS. The presence of residual disease after surgery for GTS is a risk factor for GTS recurrence. Fertility-sparing surgery should be performed because spontaneous pregnancy is possible. The overall prognosis of GTS is excellent.

Is Endothelial Neoplastic Implantation the Reason for the Intravenous Leiomyomatosis in the Heart without Direct Growth from Vena Cava? A Report of Six Cases.

Intravenous leiomyomatosis (IVL) with intracardiac involvement is a rare condition. Previous case reports have described direct tumor extension into the vena cava and cardiac chamber. Six patients with intracardiac lesion without direct growth from the IVC were admitted. Surgical resections were performed including total hysterectomy and bilateral salpingo-oophorectomy. Post-operative pathology revealed intravenous leiomyomatosis. The endothelial neoplastic implantation of IVL is a possible reason for the disseminated lesions of IVL within venous system. Awareness of this entity helps clinicians avoid misdiagnosis and take appropriate treatment.

Surgical Treatment Strategies of Intravenous Leiomyomatosis withRight Cardiac Cavities Extension.

Objective To investigate the diagnosis and surgical treatment strategies of intravenous leiomyomatosis(IVL)extending through inferior vena cava into the right cardiac cavities. Methods Thirty patients of IVL extending through inferior vena cava into the right cardiac cavities were treated in Peking Union Medical College Hospital from November 2002 to January 2015.The following variables were studied: age,cardiopulmonary bypass time,deep hypothermic circulatory arrest time,origins of IVL,blood loss,duration of post-operative hospital stay,hospitalization expenses,edema of lower extremity,blood transfusion,postoperative complication,residual IVL,and re-grow or recurrence. Results Thirteen of 30 patients reported double lower limb edema. The cardiopulmonary bypass was applied in 27 cases,and the average duration of cardiopulmonary bypass was(106.9±53.7)min. Then,21 patients were treated with the deep hypothermic circulatory arrest,and the mean time was(28.2±11.6) min. The tumors originated from the genital veins in 9 cases,the iliac vein in 13 cases,and both veins in 8 cases. The average intra-operative blood loss volume was (2060.5±2012.3)ml,and 21 patients received blood transfusion. The average hospitalization time was(18.9±8.3)days and the average hospitalization expenses was (80 840.4±28 264.2)RMB yuan. While 14 patients had postoperative complications,there was no serious postoperative complication or death.All patients have shown a favorable outcome.Conclusions Tumor embolus extending through inferior vena cava into the right cardiac cavities should be suspected in patients with multiple hysteromyoma. Successful therapy for IVL with right cardiac cavities extension is dependent on reasonable surgical treatment strategies. Surgical removal of the ovaries is vital to avoid IVL re-grow or recurrence.

[Pregnant rate and pregnancy-relating factors of patients with early endometrial carcinoma and severe atypical hyperplasia of endometrium after fertility-preserving treatment by progestin].

OBJECTIVE: To summarize the pregnant rate of patients with early endometrial carcinoma and severe atypical hyperplasia after fertility-preserving treatment and analyze their pregnancy-relating factors. METHODS: Endometrial curettage was used to evaluate the therapy response of endometrium after every 3 months of administration of high-dose progestin as fertility-sparing treatment for 51 patients with stage I endometrial carcinoma or severe endometrial atypical hyperplasia from Jun. 1996 to Jan. 2010. Individualized maintained treatment was given to patients after achieving complete remission of the endometrium. Pregnant results and pregnancy-relating factors were analyzed retrospectively. RESULTS: The median age of all the 51 patients was 29 years old. Forty-five (88%, 45/51) achieved complete response. Of the 34 cases who desired to conceive after complete response, 16 of them had 22 pregnancies, the pregnant rate was 47% (16/34); and 12 women obtained healthy live birth baby, the fertility rate was 35% (12/34). The pregnant rate of patients at age >35 or ≤ 35 was 0/2 and 50% (16/32) respectively (P > 0.05). The pregnant rate of patients with or without infertility was 40% (8/20) and 8/14, with endometrial cancer or severe atypical hyperplasia was 40% (10/25) and 6/9, respectively (all P > 0.05). The pregnant rate of patients who received in vitro fertilization-embryo transfer, ovulation promotion, or no treatment was 7/7, 6/16 and 3/11 respectively (P < 0.01). CONCLUSIONS: Fertility-preserving treatment for early endometrial cancer and severe atypical hyperplasia with high-dose progestin could achieve higher response rate. Assisted reproductive technologies could significantly increase the chance of conception.

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma.

Objective: Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM. Methods: 124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). Results: Clinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046). Conclusion: This study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.

[Management of invasive cervical cancer in pregnancy: clinical analysis of 13 cases].

OBJECTIVE: To analyze the clinical characteristics and assess the outcome of treatment for cervical cancer during pregnancy. METHODS: A cohort of 13 patients with cervical cancer diagnosed during pregnancy from January 2001 to September 2011 in Peking Union Medical College Hospital (PUMCH) was retrospectively studied. Clinical information, gestational age at diagnosis, treatment options and maternal and child outcomes were collected and analyzed. RESULTS: Thirteen patients out of 2030 cases of invasive cervical cancer were diagnosed during pregnancy with an incidence of 0.64% (13/2030). The Mean gestational age at diagnosis of 13 patients is 21(+6) weeks. Two cases were diagnosed during the first trimester, 8 cases at second trimester and 3 cases at third trimester respectively. Vaginal bleeding during the pregnancy was main clinical manifestation presented in 8 patients and all thirteen cases were diagnosed by biopsy with pathological types of squamous cell carcinoma in 10 cases. The International Federation of Gynecology and Obstetrics (FIGO) stage was I in eleven cases and stage II in two cases. Six patients of them received treatment promptly after diagnosis. The other 7 patients had delayed treatment with mean diagnosis-treatment interval time of 65 days due to fertility reasons, who ended pregnancy by cesarean section at mean gestational age of 34(+6) weeks, two of them received chemotherapy with cisplatin + fluorouracil (PF) or cisplatin respectively before the end of the pregnancy, while the one with PF chemotherapy experienced neonatal death. The rest 6 neonatal outcomes were good. As follow-up of 13 cases: 11 cases in stage I received surgical treatment, and two of which had recurrence respectively, 15 months and 7 months post surgery, and one case had died. One case of Stage II patients died and one had recurrence after 53 months after radiotherapy. The recurrence rate in 13 cases was 3/13 and the mortality rate was 2/13. CONCLUSIONS: Most cases of cervical cancer diagnosed during pregnancy were in early FIGO stage. For those patients diagnosed in late pregnancy with strong fertility demand, considering delayed treatment according to FIGO stage of the disease and fetus maturity is appropriate. Chemotherapy during pregnancy may cause neonatal complications.

Fertility-Sparing Treatment for Endometrial Cancer or Atypical Endometrial Hyperplasia Patients With Obesity.

OBJECTIVE: To evaluate the efficacy and prognosis of fertility-sparing treatment on endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with BMI ≥ 30 kg/m2. METHODS: A total of 102 EC or AEH patients with obesity who received fertility-preserving therapy in the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital were included in our study. All patients were followed up regularly. Clinical characteristics, treatment outcomes, adverse events, and reproductive outcomes were collected and analyzed. RESULTS: A total of 88 (86.3%) patients achieved complete response (CR), 92.5% in AEH and 82.3% in EC, with 6 months (3-12 months) median CR time. High remission rates were found in patients who received gonadotropin-releasing hormone agonist (GnRHa)-based regimen, were younger than 35 years old, and lost more than 10% of their weight. Fifteen (17.0%) women had developed recurrence with a median recurrence time of 26 (8-52) months. Patients who received GnRHa regimen, lost more than 10% weight, received maintenance therapy, or conceived during the follow-up period had a low probability of recurrence. Of the patients with CR, 57 women attempted to get pregnant and 16 (28.1%) patients became pregnant, 7 (12.3%) of them successfully delivered and 4 (7.0%) were in pregnancy, while 5 (8.8%) of them miscarried. CONCLUSION: For obese patients with EC and AEH, fertility-preserving treatment can still achieve a promising response. Weight loss of more than 10% has a positive influence on response, recurrence, as well as pregnancy rates. GnRHa could be an option for obese women due to less effect on weight gain compared to progestin therapy.

One-stage resection of intravascular leiomyomatosis involving the right heart chamber through a single laparotomy.

Objectives: This retrospective study aimed to summarize the feasibility and experience of utilizing a one-stage operation via single laparotomy to treat intracardiac leiomyomatosis (ICL). Materials and methods: A retrospective study of 13 patients with ICL who underwent one-stage resections was conducted at Peking Union Medical College Hospital from June 2015 to December 2021. All patients had their tumors removed by single laparotomy and were divided into a short venotomy group (6 cases) and an extensive venotomy group (7 cases). We reviewed the patient characteristics, surgical procedures, postoperative pathology, and perioperative and follow-up outcomes of all patients. Results: All patients underwent surgery for ICL resection using single laparotomy with a 100% success rate. Two patients had tumors distal to the right ventricle (RV), 2 patients had tumors that protruded into the RV in diastole and were confined to the right atrium (RA) in systole, and the other 9 patients had tumors confined to the RA that did not involve the tricuspid valve. The tumor was completely resected in 10 patients, yet 3 patients had a residual tumor. Six patients completed the surgery with short venotomy, 7 completed the surgery with extensive venotomy, and 9 underwent simultaneous total hysterectomy and bilateral adnexal resection. The mean operative time was 370.8 ± 111.0 min, and the mean blood loss was 992.3 ± 994.5 mL. Intraoperative blood loss was lower (483.3 ± 213.7 ml vs. 1429.2 ± 1208.0 ml; P = 0.020) and operative time was shorter (286.5 ± 71.9 min vs. 443.1 ± 84.4 min; P=0.004) in the short venotomy group than in the extensive venotomy group. At a mean follow-up of 26.3 ± 18.8 months, 1 patient had a local recurrence in the pelvis, and 1 patient died of pancreatic cancer, while the remaining patients had no recurrence during follow-up. Conclusion: One-stage resection of ICL patients by means of a single laparotomy is feasible and effective.

Non-open-heart surgery for intravascular leiomyomatosis extending from the inferior vena cava to the right heart chamber.

OBJECTIVE: In the present study, we analyzed the advantages and feasibility of non-open-heart surgery without cardiopulmonary bypass for intracardiac intravenous leiomyomatosis. METHODS: We retrospectively reviewed 23 cases of intracardiac intravenous leiomyomatosis and divided them into a noncardiopulmonary bypass (NCPB) group (9 cases) and a cardiopulmonary bypass (CPB) group (14 cases) according to the surgical treatment received. The clinical characteristics and anatomic features, including the diameter of the tumor, right atrium, and inferior vena cava, were recorded, and the perioperative data, including the operation time, blood loss, postoperative hemoglobin change, and follow-up results, were analyzed and compared between the two groups. RESULTS: The NCPB group had required a shorter operation time (321.9 ± 104.2 minutes vs 526.3 ± 95.6 minutes; P < .001) and had experienced less blood loss (456.3 ± 249.9 mL vs 815.4 ± 435.6 mL; P = .048) compared with the CPB group. The NCPB group had a small maximum cross-sectional area of the tumor inside the right atrium (475.5 ± 509.6 mm2), a low proportion of the maximum cross-sectional area of the entrance of the right atrium (average, 26.1%), no tricuspid valve or atrial wall involvement, and high mobility inside the inferior vena cava and heart chamber. All 23 patients had recovered well postoperatively, and no recurrence had developed during 24 months of follow-up. CONCLUSIONS: For intravenous leiomyomatosis with a smaller cross-sectional area in the right atrium that can be mobilized, surgery without CBP is feasible and should be considered.

Preservation of sexual and reproductive function in the treatment of extragonadal yolk sac tumors in the female genital tract.

Objective: This study aimed to summarize the clinical features, treatment modalities, therapeutic effects, menstruation and fertility outcomes, and prognosis of extragonadal yolk sac tumors (YSTs) of the female genital tract. Methods: We reviewed 32 cases of extragonadal YSTs in the genital tract treated between 1983 and 2021. The medical records, including clinical characteristics, histopathology, treatments, chemo-reduced adverse events, and outcomes on long-term follow-up, were collected. Results: Among the 32 cases, 30 were vaginal YSTs and two were uterine YSTs (endometrial and cervical). Thirty patients (30/32, 93.8%) were <4 years. Abnormal vaginal bleeding (n = 31) and elevated serum alpha-fetoprotein level (n = 32) were the most common presentations. Vaginohysteroscopy and/or pediatric rhinoscopy were used for diagnosis in 17 pediatric patients and evaluation of chemotherapeutic efficacy in 21 pediatric patients. All the patients received combination chemotherapy. Bleomycin/etoposide/cisplatin (BEP) was chosen with prior consideration in 28 cases; 21 patients were treated with BEP alone. Yellow or grayish-yellow tissue with irregular shape was found in 66.7% of the cases during repeat examinations. Five patients underwent surgeries during repeat examinations and follow-ups, and no evidence of malignancy was noted in them. Thirty-one patients achieved complete remission. During a median follow-up of 63 months (2.4-240.3 months), two patients experienced recurrence, three died, and 29 remained disease-free. One patient recovered menstruation and five had undergone menarche. Conclusion: BEP chemotherapy can serve as a preferred treatment modality for vaginal and uterine YSTs. Vaginohysteroscopy and pediatric rhinoscopy can be used for diagnosis and evaluation of chemotherapeutic efficacy in pediatric patients. YSTs possibly appear as yellow or grayish-yellow after chemotherapy.

[Clinicopathologic features and prognostic factors of endometrial stromal sarcoma: a study of 55 cases].

OBJECTIVE: To investigate the clinicopathologic features and the prognostic factors of endometrial stromal sarcoma (ESS). METHODS: 55 cases of endometrial stromal sarcoma were reviewed and categorized into 3 pathologic types based on the related literatures, i.e., low grade endometrial stromal sarcoma (LGESS), undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P). Meanwhile, the pathologic features were reviewed, including fibroid, myoid, mucoid, and epithelioid differentiation and mitotic index. Clinical and follow-up data were collected. RESULTS: In endometrial stromal sarcoma, two or three pathologic types co-existed in one case, including 12.8% (5/39) of LGESS, 5/9 of UES-U, and 5/7 of UES-P. Mitotic index varied in different regions of one tumor from rare to high. Multi-differentiation was also commonly seen in ESS. The numbers of cases in LGESS, UES-U and UES-P were 39, 9 and 7, with recurrence rate of 51.6% (16/31), 5/6 and 2/3, respectively. There was no death case in LGESS, and 2 cases were died in UES-U and UES-P, respectively. In the 2 death cases of UES-U, both had focus of UES-P. There was a significant difference in the recurrence rate between cases with different mitotic index (≥ 10/10 HPF and < 10/10 HPF, P = 0.009), especially in LGESS group. All death cases had high mitotic index (> 30/10 HPF). CONCLUSIONS: It is a common phenomenon in ESS that two or three pathologic types may exist in one case, especially in UES-U and UES-P. And multi-differentiation is also commonly seen in ESS. So adequate pathologic sampling is important for pathologists to make a correct diagnosis of ESS in daily work. The recurrence rates are significantly higher in cases with high mitotic index, especially in LGESS. In addition, the presence of UES-P and high mitotic index may increase the risk of death in the patients.

Management of Recurrent Endometrial Cancer or Atypical Endometrial Hyperplasia Patients After Primary Fertility-Sparing Therapy.

OBJECTIVE: To evaluate the efficacy and prognosis of fertility-sparing re-treatment on patients with recurrent endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) who wish to preserve their uterus after complete remission (CR) for primary conservative therapy. METHODS: We performed a retrospective study on recurrent EC or AEH patients who received fertility-sparing re-treatment after achieving CR. Data regarding clinicopathological factors, adverse events, treatment efficacy, tumor prognosis, and reproductive outcome were analyzed. RESULTS: Of the 98 recurrent patients with a median disease-free interval period of 19 (3-96) months, 18 patients decided to receive hysterectomy directly, and 80 patients received fertility-preserving re-treatment. Seventy-one (88.6%) cases achieved CR, 96.0% in AEH and 75.8% in EC patients, with the 6 (3-16) months' median CR time. Seven (8.8%) patients failed to achieve CR and then underwent the hysterectomy: one partial response (PR), four stable disease (SD), and two progressive disease (PD). Forty-nine women attempted to get pregnant after CR, 13 (26.5%) became pregnant, seven (14.3%) successfully delivered, and six (12.2%) miscarried. During the follow-up period, 22 (31.0%) women had developed a second relapse with the median recurrence time of 12 (4-90) months, and 10 patients decided to receive the third round of fertility-sparing treatment. Seven (70.0%) patients, 33.3% in EC and 85.7% in AEH, achieved CR again. Hysterectomy was performed in two (20.0%) patients due to SD. After the third-round treatment, six women had the desire to conceive but no one became pregnant successfully. CONCLUSION: For patients with recurrent EC and AEH after primary conservative treatment, fertility-preserving re-treatment can still achieve a promising response, and patients have possibilities of completing childbirth.

[Comparative study on the effects of LEEP and laser CO(2) vaporization in cervical intraepithelial neoplasia II].

OBJECTIVE: to compare the effect and complications of loop electro-surgical excision procedure (LEEP) and laser CO(2) vaporization in the treatment of cervical intraepithelial neoplasia II. METHODS: a total of 338 CINII women were recruited into this multi-center comparative study. The diagnosis was confirmed by histopathological examination for cervical epithelial cell abnormalities. And colposcopic examination was submitted to LEEP (n = 195) or laser CO(2) vaporization (n = 143) respectively. A post-treatment follow-up of 3, 6 and 12 months was carried out to compare the effect of two methods. RESULTS: among 195 women undergoing LEEP, the frequency of cure, persistent and recurrent CIN was 89.2% (n = 174), 4.1% (n = 8) and 3.6% (n = 7) respectively. And among 143 women receiving laser CO(2) vaporization, the frequency of cure, persistent and recurrent CIN was 86.7% (n = 124), 4.9% (n = 7) and 0.70% (n = 1) respectively. There was no statistical difference in cure rates, persistence or recurrence of CIN (P > 0.05). The recovery time, the operative frequency and intra-operative blood loss were significantly different in two groups. CONCLUSION: both LEEP and CO(2) vaporization are both effective and reliable for the treatment of cervical intraepithelial neoplasia II. However, pathological specimens may be harvested during LEEP. It is of vital importance to conduct preoperative colposcopic assessment and standard postoperative follow-ups.

FIGO Stage IV and Age Over 55 Years as Prognostic Predicators in Patients With Metastatic Malignant Struma Ovarii.

Introduction: Metastatic malignant struma ovarii (MSO) is an extremely rare disease that lacks treatment consensus and accurate prognosis. The objective of this study was to present the clinical, pathological, and treatment characteristics of metastatic MSO, while also investigate the overall survival (OS) rate and factors affecting prognosis in this population. Materials and Methods: A total of 79 cases of metastatic MSO were reviewed, including four cases of metastatic MSO from our hospital and 75 cases selected from the literature. Logistic regression was used to identify potential factors affecting disease free survival (DFS). The Kaplan-Meier method and log-rank test were used to determine OS; further Cox regression was used to evaluate factors affecting OS. Results: The mean age of all the patients at diagnosis was 43.8 years. The most common metastatic sites were peritoneum, bone, liver, omentum and lung in descending order. Only two patients (2.6%) coexisted with local primary thyroid cancer. Follicular carcinoma (41.8%) as the most prevalent subtype, followed by papillary carcinoma, follicular variant of papillary carcinoma, and mixed follicular-papillary carcinoma. 36.7% of the patients received conservative surgery, 43.0% of them underwent aggressive surgery, and 15.2% of them did not receive any surgery. 74.7% of patients who received adjuvant therapy underwent radioiodine therapy (RAI). Logistics regression revealed that FIGO stage IV was the only prognostic factor in predicting DFS (P = 0.002; Odds Ratio [OR] 5.333; 95% confidence interval [CI]: 1.839-15.471). Only seven deaths occurred. The OS rates at 5, 10, 15 years were 89.3, 82.4, 65.9%, respectively. Multivariate analysis showed age over 55 years (P = 0.006; OR 9.362; 95%CI: 1.895-46.246) was the only risk factor for OS. Conclusion: Patients with metastatic MSO have an excellent disease-specific OS rate, FIGO stage IV and age over 55 years were two factors affecting disease prognosis. Conservative surgery with residual ablation by RAI after total thyroidectomy should be preferred since the benefits of aggressive surgery are uncertain.

Ovarian fibrosarcoma: A single-institution experience and a review of the literature.

Ovarian fibrosarcoma is an extremely rare and malignant sex cord-stromal tumor. Due to its low incidence and poor prognosis, until now, very few cases have been reported, and most of the reported cases have been sporadic. Therefore, the treatments and prognostic factors of ovarian fibrosarcoma are still debatable. Here, we report 5 cases of ovarian fibrosarcoma that presented at Peking Union Medical College Hospital over the past 20 years. The 5 patients were 41, 51, 54, 76, and 76 years of age when initial symptoms of pelvic mass or pain appeared. On ultrasound, this disease usually manifests as unilateral pelvic masses, within which uneven echo enhancement and some blood flow signals are observed. No significant increase was observed in the levels of preoperative tumor markers, such as serum CA125 and sex hormones. The final diagnosis depends on postoperative histopathological results since these tumors are easily misdiagnosed when intraoperative frozen sections are used for examination. Pathologic examinations showed that the tumor cells were spindle-shaped with moderate to severe atypia and high mitotic counts. The immunohistochemistry profile is not specific, but the positive rate of Ki-67 was consistent with the degree of malignancy and the prognosis of patients with this tumor. In addition, the tumor may also be positive for Vimentin, α-inhibin, SMA, estrogen receptor and progesterone receptor. Significant differences were observed in the surgical methods used, and no unified chemotherapy regimen has been established. The overall survival was > 15, >7, > 6, <1, and < 1 year for each patient. After reviewing the literature, evidence-based large-scale case studies were lacking. For treatments, complete cytoreductive surgery plus regimens typically used against malignant sex cord-stromal tumors, as described in the NCCN guidelines, are recommended. Due to its low incidence, both multicenter clinical studies and molecular studies are required to provide gynecologists with a better understanding and guidance for future management of patients with ovarian fibrosarcoma.

Intravenous leiomyomatosis is inclined to a solid entity different from uterine leiomyoma based on RNA-seq analysis with RT-qPCR validation.

INTRODUCTION: Intravenous leiomyomatosis (IVL) is currently regarded as a special variant of the common uterine leiomyoma (LM). Though IVL shows a similar histological morphology to LM, IVL is characterized by unique intravenous growth patterns and low-grade malignant potential, which are quite different from LM. There are currently few studies underlying the molecular alterations of IVL, though this information is important for understanding the pathogenesis of the disease, and for identifying potential biomarkers. METHOD: We carried out a high-throughput whole transcriptome sequencing of tumor and normal tissue samples from five IVL patients and five LM patients and compared the differentially expressed genes (DEGs) between IVL and leiomyoma. We performed multiple different enrichment and target analyses, and the expression of selected DEGs was validated using RT-qPCR in formalin-fixed samples. RESULTS: Our study identified substantial different genes and pathways between IVL and LM, and functional enrichment analyses found several important pathways, such as angiogenesis and antiapoptosis pathways, as well as important related genes, including SH2D2A, VASH2, ADAM8, GATA2, TNF, and the lncRNA GATA6-AS1, as being significantly different between IVL and LM (P = .0024, P = .0195, P = .0212, P = .0435, P = .0401, and P = .0246, respectively). CXCL8, LIF, CDKN2A, BCL2A1, COL2A1, IGF1, and HMGA2 were also differently expressed between IVL and LM groups, but showed no statistical difference (P = .2409, P = .1773, P = .0596, P = .2737, P = .1553, P = .1045, and P = .1847, respectively) due to the large differences among individuals. Furthermore, RT-qPCR results for five selected DEGs in IVL tissues and adjacent nontumor tissues were mainly consistent with our sequencing results. CONCLUSION: Our results indicated that IVL may be a solid entity that is unique and different from LM, proving consistent with previous studies. Furthermore, we identified DEGs, particularly within angiogenesis and antiapoptosis pathway-related genes that may play crucial roles in the development and pathogenesis of IVL and may be potential specific biomarkers.