Epithelioid trophoblastic tumor of the lower uterine segment and cervical canal: A case report.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is the rarest type of gestational trophoblastic tumor (GTT). It has been reported that more than 50% of ETTs arise in the uterine cervix or the lower uterine segment. Here, we report a case of ETT within the lower uterine segment and cervical canal and discuss its manifestations, possible causes, and related influencing factors. CASE SUMMARY: A 35-year-old woman (gravida 7, miscarriage 3, induction 2 with 1 being twins, para 2 of cesarean section, live 2), who had amenorrhea for 9 mo after breastfeeding for 22 mo after the last cesarean section, was diagnosed with ETT. The lesion was present in the lower uterine segment and endocervical canal with severe involvement of the anterior wall of the lower uterine segment and the front wall of the lower uterine segment where the cesarean incisions were made. Laboratory tests showed slight elevation of serum beta-human chorionic gonadotropin. Intraoperative exploration showed the presence of a normal-sized uterus body with an enlarged tumor in the lower uterine segment. The surface of the lower uterine segment was light blue, the entire lesion was approximately about 8 cm × 8 cm × 9 cm, with compression and displacement of the surrounding tissue. Histological examination diagnosed ETT. Immunohistochemical analysis showed positive expression of p63, with a Ki-67 proliferation index of 40%. CONCLUSION: A search of the PubMed database using the search terms "cesarean section" and "epithelioid trophoblastic tumor" retrieved nine articles, including 13 cases of ETT and ETT-related lesions, all 13 cases had a history of cesarean section, and the lesions were all located at the cesarean section incision on the anterior wall of the lower uterine segment. The present case is the 14th reported case of ETT after cesarean section. Therefore, we deduced that cesarean section trauma had an important effect on the occurrence of ETT at this site.

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study.

BACKGROUND: Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. METHODS: This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. RESULTS: At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. CONCLUSIONS: Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.

Correlations between alterations of T-helper 17 cells and treatment efficacy after concurrent radiochemotherapy in locally advanced cervical cancer (stage IIB-IIIB): a 3-year prospective study.

BACKGROUND: Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy. METHODS: A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-ß (TGF-ß), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). RESULTS: We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-ß levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-ß level significantly decreased compared with the levels before cCRT (P < 0.05). CONCLUSION: Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.

Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues.

Epithelial ovarian cancer (EOC), the sixth most common cancer in women worldwide, is the most commonly fatal gynecologic malignancy in developed countries. One of the main reasons for this is that relatively little was known about the molecular events responsible for the development of this highly aggressive disease. In the present study, we demonstrated that salt­inducible kinase 1 (SIK1; which is also known as MSK/SIK/SNF1LK) was downregulated in ovarian cancer tissue samples. Using HEY ovarian cancer cells, we noted that SIK1 overexpression inhibited proliferation as well as cancer stem cell-associated traits. Silencing SIK1 promoted the proliferation of the EG ovarian cancer cell line. We performed an analysis of potential microRNAs (miRNAs or miRs) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-141 targets the 3'UTR of SIK1. Subsequent experiments not only confirmed this prediction, but also showed that miR-141 was associated with the progression of this disease. Finally, we found that miR-141 promoted proliferation of EG cells, whereas silencing miR-141 restored SIK1 expression and inhibited the proliferation of the HEY cells. Elucidating the molecular mechanism of ovarian cancer not only enables us to further understand the pathogenesis and progression of the disease, but also provides new targets for effective therapies.

Antibody fragment-armed mesoporous silica nanoparticles for the targeted delivery of bevacizumab in ovarian cancer cells.

In order to enhance the therapeutic efficacy and intracellular concentration of bevacizumab (BVC), we have designed a novel tumor endothelial marker 1 (TEM1)/endosialin (Ab-/scFv)-conjugated mesoporous silica nanoparticles (MSN) to target ovarian cancer cell. The Ab-/scFv-conjugated MSN were prepared by the conjugation of amine functional group of antibody of the carboxyl group of MSN. The resultant MSN was nanosized, spherical shaped, and exhibited a controlled release phenomenon in pH 7.4 conditions. Furthermore, BMSN/Ab was found to increase the cellular uptake and intracellular distribution of BVC in OVCAR-5 cancer cells. The Ab- conjugated MSN exhibited a superior anticancer effect with profound apoptosis in cancer cells in a time- and concentration dependent manner. Consistently, BMSN/Ab effectively inhibited the colony formation in transwell plate. Finally, BMSN/Ab showed a notable increase in the proportion of cells in G2/M phase of cell cycle indicating promising anticancer efficacy profile. Overall, Ab-/scFv-conjugated MSN might provide an effective strategy for the therapeutic management of ovarian cancers.

TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88-positive human ovarian carcinoma in vitro.

In ovarian cancer patients, chemotherapy resistance is the principal factor restricting long-term treatment. Paclitaxel (Pac) has been previously reported to be a ligand to Toll-like receptor 4 (TLR4). It was determined that TLR4 signaling is divided into the following two pathways: Myeloid differentiation factor 88 (MyD88)-dependent and MyD88-independent. The present study investigated the effect of TLR4 ligation by Pac in MyD88-positive (MyD88+) and MyD88-negative (MyD88-) human ovarian cancer cell lines. An RNA interference expression vector was specifically constructed to target TLR4 mRNA, which was stably transfected into the human ovarian cancer cell lines (SKOV3, OVCAR3, A2780 and 3AO). Cytokines, including interleukin (IL)-6 and IL-8, were detected. Cell proliferation and apoptosis were assessed in the cells transfected with scramble control and TLR4 shRNA to explore the possible functions of TLR4 in ovarian cancer cell growth. It was found that lipopolysaccharide and Pac significantly increase the secretion of IL-6 and IL-8 in the SKOV3 cell line. Similarly, Pac resulted in a significant upregulation of IL-6 and IL-8 in OVCAR3 cells, but not in A2780 and 3AO cells. These results suggested that in MyD88+ ovarian cancer cell lines, TLR4 depletion shows increased sensitivity to Pac treatment in inhibiting cell proliferation compared with in cells without TLR4 knockdown. On the contrary, such changes were not found in MyD88- cells (A2780 and 3AO). TLR4 negatively regulates Pac chemotherapy, particularly in terms of cell proliferation, and TLR4 may be a novel treatment target in Pac-resistant ovarian cancer.

[Clinical study of sentinel lymph node detection guided radical abdominal trachelectomy].

OBJECTIVE: To evaluate the clinical value of sentinel lymph nodes (SLN) in predicting pelvic lymph node status for early cervical squamous cell carcinoma, and approach the clinical significance of SLN detection for guiding radical abdominal trachelectomy (RAT).Outcomes of follow up and fertility were also observed. METHODS: A total of 31 patients with stageIa2-Ib1 squamous cell carcinoma planned to be given RAT and pelvic lymphadenectomy were enrolled. (99m)Tc-labeled phytate was injected before surgery.Intraoperatively, SLN were identified, excised, and submitted to fast frozen section.Systematic bilateral pelvic lymphadenectomy was performed, and then RAT was performed in patients with negative SLN. All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases. RESULTS: SLN were detected in all patients (100%,31/31). A total of 109 SLN were identified with a mean number of 3.5 per patient.Of these, SLN of 2 patients were positive on frozen sections and proved to be metastasis by final pathologic examination and quitted the RAT. No missed micrometastasis was found using immunohistochemical staining in SLN and other lymph nodes using histologically node-negative cases. No false negative cases was found and the negative value was 100% (31/31). The sensitivity, accuracy, and false negative rates were 100%, 100%, and 0, respectively. Perioperative complications occurred in 5 patients including 2 cases of bladder injury and 3 cases of uterine artery injury.No relapses occurred during follow-up.Five of 19 patients with procreative desire conceived pregnancies (4 spontaneous abortion and 1 premature birth) after surgery. CONCLUSIONS: The identification of SLN using (99m)Tc-labeled phytate could predict the pelvic lymph node status in early stage cervical cancer. Under the guidance of SLN detection, RAT is a feasible operative modality with well prognosis and low complications for young patients who desire to preserve reproductive function.

[Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer].

OBJECTIVE: To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer. METHODS: Gemcitabine 800 mg/m(2) (day 1, 8), ifosfamide 1.5 g/m(2) (day 1 - 3), adriamycin 40 mg/m(2) or epirubicin 60 mg/m(2) (day 1) or mitoxantrone 10 mg/m(2) (day 1, 8) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days. RESULTS: A total of 60 patients received 172 cycles combined chemotherapy. There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%, 15/60) were observed, with clinical benefit rate 75% (45/60). The median time of progression-free survival was 7 months, and the median overall survival time was 20 months. The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which III-IV accounted for 31% (15/49). Digestive reaction was all in I-II, accounted for 42% (25/60). CONCLUSION: The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.

[Clinicopathological characteristics of hereditary ovarian cancer syndrome].

OBJECTIVE: To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS). METHODS: From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). RESULTS: The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group. CONCLUSION: Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and better prognosis after the comprehensive treated by cytoreductive surgery plus with chemotherapy.

[The rule of metastatic pelvic lymph node distribution in patients with early stage cervical carcinoma].

OBJECTIVE: To investigate the distribution of metastatic pelvic lymph nodes in the women with early stage cervical carcinoma, and the feasibility of dividing these nodes into three stations in those patients. METHODS: (99m)Tc-DX of 2 ml was injected into the cervix to a depth of 5 to 10 mm at 3, 6, 9, 12 o'clock positions preoperatively in 196 patients with early stage cervical cancer. Pelvic lymphadenectomy and radical hysterectomy were performed in all patients. Pelvic lymph nodes were detected by gamma-probe. The sentinel lymph nodes (SLN) were determined if the radioactivity reached 5 times higher than that in the ipsilateral nodes. All resected pelvic lymph nodes were examined by histopathology with HE stained serial sections. RESULTS: Of the 196 patients, 41 were found to have metastasis in 83 lymph nodes. The metastatic rate was 78.3% (65/83) in the parametrial and obturator lymph nodes, 20.5% (17/83)in the internal and external iliac lymph nodes, 1.2% (1/83) in the commmon iliac lymph nodes. Of the 22 patients with metastatic parametrial lymph nodes, metastatic external iliac lymph nodes were detected in 5 patients, and metastatic internal iliac lymph nodes in 3 patients. Among the 19 patients with metastatic obturator lymph nodes, metastatic external iliac lymph nodes were found in 4 patients, and metastatic internal iliac lymph nodes in 3 cases. It was shown by Chi-sqare test that the metastases in parametrial and/or obturator lymph nodes were positively correlated with lymph node metastases in other pelvic sites. Eighty-one SLN were found to have metastasis. The metastatic rate of parametrial and obturator SLN was 79.0% (64/81) versus 21.0% (17/81) of internal and external iliac SLN. No statistically significant difference in 1- and 3-yr survival was observed between the groups with and without metastasis in parametrial and obturator lymph nodes, while the 5-yr survival rate in the patients without metastatic lymph node was 93.2%, significantly higher than that of patients with lymphatic metastasis (65.1%). CONCLUSION: It is feasible for cervical cancer to divide the pelvic lymph nodes into three levels. The level I lymph nodes consist of parametrial and obturator lymph nodes. Internal and external iliac lymph nodes can be considered as level II lymph nodes, and the common iliac and inguinal lymph nodes as level III nodes. A rational treatment plan can be made according to the distribution of metastatic pelvic lymph nodes.

[Intensity modulated radiation therapy for patients with gynecological malignancies after hysterectomy and chemotherapy/radiotherapy].

OBJECTIVE: To investigate the value of intensity modulated radiation therapy (IMRT) for patient with gynecological malignancies after treatment of hysterectomy and chemotherapy/radiotherapy. METHODS: All 32 patients with cervical or endometrial cancer after hysterectomy received full course IMRT after 1 to 3 cycles of chemotherapy (Karnofsky performance status(KPS) > or =70). Seventeen of these patients underwent postoperative preventive irradiation and the other 15 patients were pelvic wall recurrence and/or retroperitoneal lymph node metastasis, though postoperative radiotherapy and/or chemotherapy had been given after operation. RESULTS: The median dose delivered to the PTV was 56.8 Gy for preventive irradiation, and 60.6 Gy for pelvic wall recurrence or retroperioneal lymph node metastasis irradiation. It was required that 90% of iso-dose curve could covere more than 99% of GTV. However, The mean dose irradiated to small intestine, bladder, rectum, kidney and spinal cord was 21.3 Gy, 37.8 Gy, 35.3 Gy, 8.5 Gy, 22.1 Gy, respectively. Fourteen patients presented grade I (11 patients) or II (3 patients) digestive tract side-effects, Five patients developed grade I or II bone marrow depression. Twelve patients had grade I skin reaction. The overall 1-year survival rate was 100%. The 2- and 3- year survival rate for preventive irradiation were both 100%, but which was 5/7 and 3/6 for the patients with pelvic wall recurrence or retroperioneal lymph node metastasis. CONCLUSION: Intensity modulated radiation therapy can provide a better dose distribution than traditional radiotherapy for both prevention and pelvic wall recurrence or retroperioneal lymph node metastasis. The toxicity is tolerable. The adjacent organs at risk can well be protected.

[Clinical significance of sentinel lymph nodes detection in patients with early stage cervical cancer].

OBJECTIVE: To study the value of sentinel lymph nodes (SLN) in prediction of the pelvic lymph nodes status and to determine the significance of SLN detection in pelvic lymph nodes dissection in patients with early stage cervical carcinoma. METHODS: From November 2002 to August 2003, 23 patients with early stage cervical carcinoma planned to undergo radical hysterectomy and extensive pelvic lymph nodes dissection received an intracervical injection of technetium-labeled sulfur colloid as well as blue dye to identify and perform resection of SLNs. The SLNs were pathologically compared with non-SLNs with frozen section, paraffin section, and anti-cytokeratin immunohistochemical staining. RESULTS: Out of 23 patients, SLNs were detected in 19 patients. A total of 59 SLNs were identified and the mean was 3 per patient. The detection rate of SLN was 83%. Sensitivity, specificity and accuracy of the SLN biopsy were 83%, 100% and 95%, respectively. CONCLUSION: SLNs detection can predict the pelvic lymph nodes status in early stage cervical carcinoma, but the feasibility and safety of this technique to substitute conventional surgical modality should be evaluated by large series of prospective studies.