[Gestational trophoblastic diseases in cesarean scar: an analysis of 20 cases].

OBJECTIVE: To analyze the clinical features, diagnosis and treatment of gestational trophoblastic diseases in cesarean scar. METHODS: Clinical data of three cases of gestational trophoblastic diseases in cesarean scar diagnosed in Women's Hospital, Zhejiang University School of Medicine during December 2011 and December 2016 were collected. And literature search was performed in Wanfang data, VIP, CNKI, PubMed, ISI Web of Knowledge and EMbase database. RESULTS: A total of 20 cases of gestational trophoblastic diseases were included in the analysis. Clinical features were mainly abnormal vaginal bleeding after menopause, artificial abortion or medical abortion, which might be accompanied by abdominal pain. Serum ß-human chorionic gonadotropin (ß-hCG) levels were increased in 19 patients. The sonographic features were increase of uterine volume, honeycomb-like abnormal intrauterine echo (or described as multiple cystic dark area, multiple anechoic area and multiple liquid dark area) or heterogeneity echo conglomeration, and no clear bound with muscular layer in some cases. There were abundant blood flow signals inside or around the lesions. The ultrasonography indicated that the lesions were located in the anterior side of the uterine isthmus with the involvement of cesarean section scar. In 12 cases with lesions in cesarean scar shown by preliminary diagnosis, 9 underwent uterine artery embolization (UAE) for pretreatment; the blood loss greater than 1500 mL was observed in only one case without UAE; no patient received hysterectomy. In 8 patients whose lesions were not shown in cesarean scar, only one case received UAE pretreatment, and hysterectomy was performed in 3 cases due to blood loss greater than 1500 mL. Two cases were lost in follow-up and no death was reported in remaining 18 cases. The serum ß-hCG levels returned to normal or satisfactory level during the follow-up in 17 cases with increased ß-hCG levels before treatment and no recurrence was observed. CONCLUSIONS: The misdiagnosis rate and missed diagnosis rate of gestational trophoblastic diseases in cesarean section scar are high. The identification of cesarean section scar involvement and UAE may reduce the bleeding and avoid hysterectomy.

Role of plasmacytoid dendritic cells and inducible costimulator-positive regulatory T cells in the immunosuppression microenvironment of gastric cancer.

Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) play important roles in the immune escape of cancer. In this study, we investigated pDCs and pDC-induced inducible costimulator (ICOS)(+) Treg populations in peripheral blood from gastric cancer (GC) patients and healthy donors by flow cytometry. The distribution of these cells in carcinoma tissue, peritumor tissue, and normal gastric mucosa was detected by immunohistochemistry. Plasma and tissue concentration of the cytokines such as interleukin-10 and transforming growth factor-ß1 were also measured. We found that the numbers of pDCs, Tregs, and ICOS(+) Tregs in peripheral blood were increased in GC patients compared with healthy donors. In tissue, Tregs and ICOS(+) Tregs were found distributing mainly in carcinoma tissue, whereas pDCs were mainly found in peritumor tissue. Moreover, the Foxp3(+) ICOS(+) /Foxp3(+) cell ratio in carcinoma and peritumor tissue were higher than that in normal tissue. There were more ICOS(+) Tregs in tumor and peritumor tissue of late-stage GC patients. There was a positive correlation between pDCs and ICOS(+) Tregs in peripheral blood and peritumor tissue from GC patients. In conclusion, pDCs may play a potential role in recruiting ICOS(+) Tregs, and both participate in the immunosuppression microenvironment of GC.

Anti-tumor effects of Mfn2 in gastric cancer.

Mitofusin-2 (Mfn2) is a mitochondrial outer membrane protein involved in mitochondrial fusion. Its mutation can cause Charcot-Marie-Tooth disease. Recent studies of Mfn2 in cancer research have not included gastric cancer. We confirmed that Mfn2 expression was lower in tumor tissue than in normal gastric mucosal tissue and that it was negatively correlated with tumor size, indicating an anti-tumor role for Mfn2. In vitro experiments showed that Mfn2 overexpression suppressed gastric cancer cell proliferation and colony formation, weakened the invasion and migratory ability of cancer cells by downregulating MMP-2 and MMP-9, halted the cell cycle and induced apoptosis. Western blotting indicated the likely involvement of P21 and PI3K/Akt signaling. Therefore, Mfn2 is a potential anti-tumor gene and a potential therapeutic target for treating gastric cancer. The progress of gastric cancer may be delayed by controlling Mfn2 expression.

Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter.

Immunosuppressive lymphocytes, such as regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs), play crucial roles in tumor escape. To investigate the roles of Tregs and pDCs in papillary thyroid cancer (PTC) plus multinodular non-toxic goiter (MNG), thyroid tissue and blood samples from 30 patients with PTC plus MNG and 30 MNG alone were analyzed for CD4(+) T cell, CD8(+) T cell, FoxP3(+) Treg, ICOS(+)FoxP3(+) Treg, and pDC numbers by immunohistochemistry (IHC), immunofluorescence, and flow cytometry. Plasma concentration of the cytokines interleukin 10 (IL-10) and transforming growth factor ß (TGF-ß) were measured by enzyme-linked immunosorbent assay as well. Both in thyroid tissue and peripheral blood, the numbers of Foxp3(+) Treg were significantly higher in patients with PTC plus MNG compared to patients with MNG alone; and as a prognostic marker, ICOS(+)Foxp3(+) Tregs represent a stronger predictor of disease progression than the total numbers of Foxp3(+) Tregs. Furthermore, a positive correlation between pDC and ICOS(+)Foxp3(+) Treg numbers in tissue of patients with PTC plus MNG was observed, suggesting that PTC-derived pDCs may induce the differentiation of naive CD4(+) T cells into ICOS(+)Foxp3(+)Tregs. This may be one of the mechanisms underlying tumor escape in PTC plus MNG patients. Our results suggest that Tregs and pDCs together contribute to the tumor escape in patients with PTC plus MNG.