Pelvic Exenteration for Recurrent and Persistent Cervical Cancer.

BACKGROUND: Pelvic exenteration (PE) for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution. METHODS: From January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcomes in univariate and Cox hazard regression analysis. RESULTS: There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years (range 29-65 years). Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 (55.3%) patients and 15 (39.5%) patients, respectively. Two (5.3%) patients died due to complications related to surgeries within 3 months after PE. The median overall survival (OS) and disease-free survival (DFS) were 28.5 months (range 9-96 months) and 23 months (range 4-96 months), respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors for OS and DFS. CONCLUSION: In our patients with recurrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03291275; https://clinicaltrials.gov/ct2/show/NCT03291275?term=NCT03291275&rank=1.

[Research advance in antitumor activities of artemisinin and its derivatives].

Artemisinin and its derivatives are highly effective in fighting against malaria. Notably, these drugs have shown potent anti-timor activities by arresting cellular growth, enhancing apoptosis, inhibiting angiogenesis, and regulating the expression of tumor-associated genes, although the underlying mechanisms remain unclear.

Ovarian steroid hormones differentially regulate thrombospondin-1 expression in cultured endometrial stromal cells: implications for endometriosis.

Thrombospondin-1 messenger RNA and protein levels in cultured human endometrial stromal cells (ESCs) treated with 17-beta estradiol (10 nM) were reduced by 47.6% (+/-6.5% SD; P < 0.05) and 49.0% (+/-8.6%; P < 0.05) compared with untreated cells, whereas thrombospondin-1mRNA and protein levels in ESCs treated with progesterone (10 microM) were 2.1-fold (+/-0.4 SD; P < 0.05) and 2.3-fold (+/-0.6; P < 0.05) higher than those in untreated cells. These findings not only provide evidence for the estrogen dependence of endometriosis, but also partly explain the mechanisms by which progestins exert their therapeutic activities in endometriosis.

[Predictors of residual lesion in cervix after conization in patients with cervical intraepithelial neoplasia and microinvasive cervical cancer].

OBJECTIVE: To determine the clinicopathological factors predicting residual lesions after conization in patients with cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma of cervix (MIC). METHODS: The clinical data of 77 patients with CIN3, 20 patients with stage Ia1 cervical cancer, and 8 patients with stage 1a2 cervical cancer, totally 105 patients, aged (43 + 6), who received further surgery within 3 months after conization, 95 receiving hysterectomy, 2 receiving repeated conization, and 8 receiving radical hysterectomy and pelvic lymph node dissection, were evaluated. The demographic features, clinical and pathological parameters, and the correlation thereof with the post-conization residual lesions were analyzed retrospectively. RESULTS: Residual lesions were found in the specimens obtained from hysterectomy or repeated conization of 53 of the 105 patients (50.5%), among which 38 were CIN2 or less severe lesions. Univariate analysis showed that menopausal status, procreation status, cervical cytology, method of conization, and range of resection were not correlated with the presence of post-conization residual lesion, while age < or = 45 (P < 0.05, odd ratio [OR] = 4.68) and positive resection margin (P < 0.05, OR = 5.40) were risk factors of residual lesion. There were no differences in the proportion of post-conization residual lesion among the patients with MIC, CIN 3, CIN2 or less severe lesions. Multivariate logistic analysis showed that only the positive resection margin was an independent risk factor of residual lesion after conization (P < 0.05, OR = 4.20). CONCLUSIONS: Although severity of the cervical disease is the most important factor in determining post-conization treatment, it is not a predicting factor for post-conization residual lesion. Only the positive resection margin was an independent risk factor of residual lesion after conization.

[Complications of hysterectomy: analysis of 162 cases].

OBJECTIVE: To evaluate the complications of different approaches of hysterectomy based on analyzing the records of patients with long post-operative hospitalization. METHODS: The records of 3722 patients undergoing hysterectomy due to benign gynecologic disorders were retrieved. A total of 162 patients with ultra-long post-operative hospitalization (> 9 days defined as delayed discharge) were analyzed to evaluate the complications of hysterectomy. RESULTS: (1) Of 162 patients classified into delayed discharge group, 114 (30.6 per thousand)had post-operative fever in which 82 cases (71.9%) could be explained with complications. (2) The most common procedure-related complications included pelvic hematoma/vaginal stump bleeding (n = 46, 12.4 per thousand), wound dehiscence/infection (n = 24, 6.4 per thousand), organ injury (n = 20, 5.4 per thousand), postoperative urinary retention (n = 20, 5.4 per thousand), postoperative infection(n = 20, 5.4 per thousand)and lower extremity deep venous thrombosis (n = 10, 2.7 per thousand). (3) Organ injury appeared to be relatively more common in abdominal hysterectomy than in laparoscopic and vaginal hysterectomy (7.6 per thousand, 2.1 per thousand and 0 respectively) while pelvic hematoma/vaginal stump bleeding more common in laparoscopic and vaginal hysterectomy than in abdominal hysterectomy (16.5 per thousand, 30.8 per thousand and 7.6 per thousand respectively). (4) Wound dehiscence/infection only occurred in abdominal approach and it was closely related with some concurrent disorders. CONCLUSION: Complications of hysterectomy are related to the approach of surgery, disease characteristics and surgeon experiences. A more accurate evaluation of complications might be performed on the basis of the data of patients with delayed discharge.

[Effects of dihydroartiminisin on the adhesion, migration, and invasion of epithelial ovarian cancer cells].

OBJECTIVE: To investigate the effects of dihydroartiminisin (DHA) on the adhesion, migration, and invasion ovarian cancer cells. METHODS: Human ovarian cancer cells of the lines SKOV3 and OVCAR3 were cultured. Suspensions of SKOV3 and OVCAR3 cells were treated with DHA of the concentrations of 0.5, 2.5, 12.5, and 62.5 micromol/L respectively, and then inoculated on the plate coated with Matrigel. MTT method was used to -determine the adhesion rate. Transwell membrane chamber model was used to evaluate the effect of DHA on the migration and invasion of the SKOV3 and OVCAR3 cells. Western blotting and reverse transcriptase polymerase chain reaction were used to detect the effect of DHA on the phosphorylation of focal adhesion kinase (FAK) and on the effect of expression of metal matrix proteinases (MMPs) and their tissue inhibitors (TIMPs) respectively. RESULTS: (1) Compared to the cells without DHA treatment, the cell adhesion ability levels of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA decreased by 76.1% and 57.9% respectively (P < 0.05), while their migration ability levels decreased by 59.3% and 69.7% respectively (P < 0.05). (2) Both SKOV3 and OVCAR3 showed weak invasion ability, and DHA only showed a slight inhibitory effect on the cell invasion of these 2 lines (both P > 0.05). (3) Compared to the cells without DHA treatment, the phosphorylation level of FAK of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA decreased by 42.9% and 44.8% respectively (both P < 0.05). (4) RT-PCR showed mRNA expression of MMP2, TIMP1, and TIMP2, but not mRNA expression of MMP9 in both SKOV3 and OVCAR3 cells. The mRNA expression levels of the SKOV3 and OVCAR3 cells treated with 12.5 micromol/L DHA increased by 1.5 and 2.6 times respectively (both P < 0.05). CONCLUSION: DHA has inhibitory effects on the adhesion and migration of epithelial ovarian cancer cells, which may be related to its down-regulation of the phosphorylation of FAK in these cells.

[Effects of dihydroartiminisin on proliferation and phosphorylation of mitogen-activated protein kinase in epithelial ovarian cancer cell lines].

OBJECTIVE: To determine the effect of dihydroartiminisin on the proliferation and phosphorylation of mitogen-activated protein kinase (MAPK) in SKOV3 and OVCAR3 ovarian cancer cell lines. METHODS: Methyl thiazolyl tetrazolium assay was performed to evaluate the anti-proliferative effect of dihydroartiminisin in SKOV3 and OVCAR3 cells, and Western blot was used to determine its effect on phosphorylation level of MAPK, including extra-cell regulated kinase (ERK) 1/2 and p38 protein kinase, in the two cell lines. RESULTS: Dihydroartiminisin inhibited the proliferation of ovarian cancer cells in vitro, with a mean of 50% inhibition concentration (IC(50)) at 72 h of (9.0 +/- 1.4) micromol/L for SKOV3 and (5.5 +/- 1.2) micromol/L for OVCAR3 respectively. Compared to cells without dihydroartiminisin treatment, phosphorylation level of ERK 1/2 in SKOV3 and OVCAR3 cells treated with dihydroartiminisin decreased by 64.2% and 75.3% respectively (P < 0.05), while phosphorylation of p38 protein kinase in SKOV3 and OVCAR3 only decreased by 8.5%and 6.4%respectively (P > 0.05). CONCLUSION: Dihydroartiminisin can inhibit the proliferation of ovarian cancer cell in vitro, probably through down-regulation of the phosphorylation of ERK 1/2 in ovarian cancer cells.

[Prognostic value of microvessel density and angiogenesis-related molecules in epithelial ovarian cancer].

OBJECTIVE: To evaluate the correlations of microvessel density (MVD), vascular endothelial growth factor (VEGF), thrombospodin1 (TSP1) and p53 protein with prognosis in epithelial ovarian cancer. METHODS: Samples from 57 patients with primary epithelial ovarian cancer were examined by immunohistochemical staining using anti-VEGF, anti-TSP1, anti-p53 and anti-CD34 antibodies. The correlation of MVD, expression of VEGF, TSP1 and p53 protein with postoperative recurrence and overall survival were analyzed retrospectively. RESULTS: VEGF, TSP1 and p53 protein was positively detected in 40 (70.2%), 27 (47.4%) and 35 (61.4%) of those patients, respectively. The mean MVD in this series was 30.3 +/- 8.5. High MVD, positive VEGF expression and negative TSP1 expression were positively correlated with postoperative recurrence. Univariate analysis showed that patients with high MVD, positive expression of VEGF and p53 had shorter median overall survival time than those with lower MVD, negative expression of VEGF and p53 (P = 0.0187, P = 0.010 and P = 0.005, respectively), while TSP1 expression was revealed as a protective factor for prognosis. Patients with positive expression of TSP1 had longer median overall survival time than those with negative TSP1 expression (P = 0.042). Multivariate analysis showed that MVD and p53 expression were two independent prognostic factors in epithelial ovarian cancer (P = 0.018 and P = 0.009, respectively). CONCLUSION: VEGF, TSP1 and p53 protein may play an important role in the angiogenesis of epithelial ovarian cancer. High MVD level and p53 protein expression are two independent poor prognostic factors.

[Correlation of preoperative serum vascular endothelial growth factor level with CA125 level in patients with epithelial ovarian cancer and its prognostic value].

OBJECTIVE: To analyze the correlation of preoperative serum vascular endothelial growth factor (VEGF) level with serum CA125 level in patients with epithelial ovarian cancer (EOC), and to evaluate the prognostic value of preoperative serum VEGF in these patients. METHODS: Forty-one patients with EOC were included as study group, while 20 healthy women were selected as control group. Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence assay were used to measure serum VEGF and CA125 level respectively. The correlations of serum VEGF with CA125 level, postoperative recurrence rate and survival time were analyzed retrospectively. RESULTS: Serum VEGF levels in patients with EOC were higher than those in healthy women, with the median of 415 and 165 ng/L, range 110-2120 and 100-735 ng/L respectively (P<0.01). No correlation was found between preoperative serum VEGF and CA125 level (Spearman test, P=0.989). High preoperative serum VEGF was positively correlated with postoperative recurrence. Serum VEGF level in patients with postoperative recurrence was higher than that in patients without recurrence, with the median of 490 and 315 ng/L respectively (P=0.035). Univariate analysis showed that higher serum level was reversely correlated with shorter survival. Median overall survival time in patients with higher serum VEGF level and lower serum VEGF level was 18 months and >35 months respectively (P=0.010). Multivariate Cox model analysis showed that high VEGF level was an independent factor for the prognosis of EOC (P=0.042). CONCLUSION: Preoperative serum VEGF level is not correlated with CA125 concentration in patients with EOC, and it is an independent risk factor for prognosis.

[Effects of medical treatment on apoptosis in eutopic endometrium of patients with endometriosis].

OBJECTIVE: To investigate the apoptosis-related mechanisms of levenorgestrel-releasing intrauterine system (LNG-IUS), oral medroxyprogesterone (MPA), and injective gonadotrophic hormone releasing hormone agonist (GnRHa) on eutopic endometrium of patients with endometriosis. Methods We collected the samples of endometrium from patients with endometriosis before operation and after insertion of LNG-IUS, administration of oral MPA, or injection of GnRHa. The ultrastructure of endometria was observed and compared by electron microscopy. Apoptotic cells were assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling (TUNEL) assay, and the expressions of Bax, Fas, and Fas-L mRNA were determined by semi-quantitative reverse transcription-polymerase chain raction. Results After have been exposured to LNG-IUS, the apoptotic rate of endometrial epithelial cells and stromal cells increased from (24. 4 +/- 35.0)% to (51.0 +/- 37.8)% (P = 0.027) and (35.3 +/- 30.2)% to (76.4 +/- 11.2)% (P = 0.008), respectively. The degree of apoptosis under transmission electron microscopy was in an order of GnRHa > LNG-IUS > MPA. The expression of Fas-L mRNA in eutopic endometrium of patients with endometriosis was significantly higher than that of the normal control (P < 0.05). The expressions of three apoptosis-related proteins had no significant difference. CONCLUSION: Medical treatments can increase the apoptosis of eutopic endometrial cells, and such effect was strongest in GnRHa and relatively weaker in LNG-IUS and MPA.

[Effects of progesterone and progestin on expression of regulated on activation, normal T cell expressed and secreted in eutopic endometrium from patients with endometriosis].

OBJECTIVE: To investigate the effects of progesterone and progestin on the expressions of regulated on activation, normal T cell expressed and secreted (RANTES) in eutopic endometrium from patients with endometriosis. METHODS: We collected the samples of endometrium from patients with endometriosis before operation or after insertion of levenorgestrel releasing intrauterine system (LNG-IUS), administration of oral medroxyprogesterone (MPA), or injection of gonadotrophic hormone releasing hormone agonist (GnRHa). Reverse transcription-polymerase chain raction was used to assay the expression of RANTES mRNA. On the other hand, progesterone (Po) and tumor necrosis factor-alpha (TNFalpha) of different concentrations and different manners were used to treat cultured cells in vitro. RANTES secretion was evaluated in the culture medium using ELISA. In order to evaluate the effect of Po on the secretion of RANTES under stimulation of TNFalpha, the cells were cultured in medium containing 100 U/ml TNFalpha and Po of different concentrations for 24 hours. After the pretreatment of Po for 48 hours at different concentrations, TNFalpha (100 U/ml, 16 h) was added to observe whether Po inhibits RANTES or not. RESULTS: The expression of RANTES mRNA in eutopic endometrium of patients with endometriosis was significantly higher than in control group (28.0 +/- 9.0 vs. 22.0 +/- 5.6, P < 0.05). Following the exposures to LNG-IUS (24.0 +/- 4.2 vs. 25.9 +/- 4.2, P > 0.05) or GnRHa (23.0 +/- 12.9 vs. 26.9 +/- 5.2, P > 0.05), the expression of RANTES mRNA had no change. MPA significantly increased the expression of RANTES mRNA (42.6 +/- 3.1 vs. 24.3 +/- 5.7, P < 0.05). Po itself had no significant effect on the secretion of RANTES. Stimulated by Po and TNFalpha at the same time, the secretion of RANTES significantly increased. After pretreatment with Po for 48 hours, the reaction of RANTES to the stimulating effect of TNFalpha was down-regulated. CONCLUSION: The eutopic endometrium of patients with endometriosis has high chemotactic activity. It may be feasible to prevent and treat endometriosis with progestins.

[Operative approaches, indications, and medical economics evaluation of 4180 cases of hysterectomy].

OBJECTIVE: To examine the operative approaches, major indications, and medical economic parameters of the hysterectomy. METHODS: Data on hysterectomy performed due to benign gynecological disorders in Peking Union Medical College Hospital (PUMCH) from 1996 to 2001 were reviewed. The cases were classified into three groups according to the operative approaches: total abdominal hysterectomy (TAH), vaginal hysterectomy (VH), and laparoscopic assisted vaginal hysterectomy (LAVH). The major indications, length of hospital stay, operative cost, and total medical cost were analyzed. RESULTS: Records of 4,180 women who had hysterectomies in PUMCH were examined. Operations included TAH (78.4%), LAVH (13.0%), and VH (8.6%). The use of LAVH increased from 2.4% in 1996 to 17.3% in 2001. The common indications for surgery included uterine leiomyoma (56.2%), adenomyosis (12.2%), benign ovarian tumor (9.2%), genital prolapse (7.7%), endometriosis (6.9%), atypical endometrial hyperplasia (3.0%), and cervical intraepithelial neoplasm (2.0%). The most common indications for TAH and LAVH were uterine leiomyomas and adenomyosis, whereas the most common indication for VH was genital prolapse, followed by uterine leiomyoma. The lengths of hospital stay in TAH, VH, and LAVH were (11.0 +/- 4.9) d, (10.9 +/- 3.9) d, and (8.9 +/- 3.7) d respectively. The total medical cost was (5,666.6 +/- 1,709.4) RMB Yuan for TAH, (5,027.6 +/- 1,067.0) RMB Yuan for VH, and (7,473.8 +/- 1,464.8) RMB Yuan for LAVH. CONCLUSIONS: The use of LAVH has been increasing. Although the direct medical cost for LAVH is higher than that for TAH, its indirect benefit appeares superior to TAH. The major indications for LAVH and TAH are similar, whereas the indications for VH are different from those for TAH and LAVH.

Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis.

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) mRNA and thrombospondin-1 (TSP-1) mRNA in endometriosis. DESIGN: Molecular studies in human tissue. SETTING: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P. R. China. PATIENT(S): Patients undergoing laparoscopy for infertility or other benign gynecologic conditions. INTERVENTION(S): Biopsies were taken from endometriotic lesions (red peritoneal lesion, ovarian endometrioma, and unterosacral ligament nudule) and eutopic endometrium during laparoscopy. MAIN OUTCOME MEASURE(S): mRNA expression from endometriotic lesion and eutopic endometrium was analyzed by reverse transcriptase polymerase chain reaction (PCR) and Northern blotting. RESULT(S): Among the endometriotic lesions, red peritoneal lesions expressed higher levels of VEGF mRNA and lower levels of TSP-1 mRNA, whereas ovarian endometrioma expressed lower levels of VEGF mRNA and higher levels of TSP-1 mRNA. Eutopic endometrium of women with endometriosis had higher expression levels of VEGF mRNA and lower expression levels of TSP-1 mRNA than that of women without endometriosis. CONCLUSION(S): The expression of VEGF and TSP-1 in endometriotic lesions appears to be associated with the extent of their neovascularization. The imbalance in expression of VEGF and TSP-1 in the endometrium may play a role in the development of endometriosis.