Long-Term Effect of Early Post-operative Transcutaneous Electrical Stimulation on Voiding Function After Radical Hysterectomy: A Multicenter, Randomized, Controlled Trial.

Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.

Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer.

BACKGROUND: After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS: A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS: Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION: A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

[Efficacy of postoperative simple chemotherapy and concurrent chemoradiotherapy in FIGO stage IB2-IIB cervical cancer].

OBJECTIVE: To evaluate the effectiveness of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy plus postoperative chemotherapy but no radiotherapy for stage IB2-IIB cervical cancer. METHODS: Seventy-nine patients with stage IB2-IIB cervical cancer were treated with NAC followed by radical hysterectomy. According to different adjuvant therapies, patients were divided into postoperative chemotherapy group (47 cases) and postoperative radiotherapy/concurrent chemoradiotherapy group (32 cases). Regimens for NAC and postoperative chemotherapy were BIP (bleomycin+ ifosfamide+ cisplatin/carboplatin) or TP (paclitaxel+ cisplatin/carboplatin). An average of 1.1±0.3 cycles of NAC and 3.4±1.2 cycles of postoperative chemotherapy were prescribed. RESULTS: Toxicities due to chemotherapy were generally tolerable. Overall response rate of NAC was 88.6%. With a median follow-up period of 42 months, the three-year progression-free survival rates of the two groups were 88.5% and 84.3%, the total survival rates were 90.3% and 86.4%, respectively. There was no statistically significant difference. The recurrent rates were 10.6% and 21.8% in the two groups. In the absence of radiotherapy, pelvic recurrence was observed in two patients; the other three had distant metastases. CONCLUSION: The results indicate that NAC followed by surgery plus postoperative chemotherapy but no radiotherapy offers a viable option in the treatment of stage IB2-IIB cervical cancer. The patients can tolerate the side effects of chemotherapy with better efficacy.

[Results of different postoperative adjuvant therapies for stage Ib-IIa cervical carcinoma with risk factors].

OBJECTIVE: To investigate the effects of postoperative adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) or radiotherapy(RT) for Ib-IIa cervical cancer with risk factors. METHODS: From March 1995 to June 2010, there were 137 patients underwent radical hysterectomy and systematic pelvic lymphadenectomy for stage Ib-IIa cervical cancer admitted at Peking University First Hospital. These patients had risk factors, intermediate risk factors including bulky tumor ( > 4 cm) , lymph vascular space invasion, deep stromal invasion; high risk factors including positive surgical margin, parametrial invasion, lymph node involvement. Of the all patients, 79 cases of them were treated with CT, 58 of them were treated with RT or CRT. The 5-year survival and prognosis factors were analyzed retrospectively, the prognosis was compared between two adjuvant therapy groups. RESULTS: The univariate analysis shown that types of pathology, different grade of risk factors, stroma invasion and lymph node involvement were prognostic factors of 5-year overall survival. Patients with squamous cell carcinoma, intermediate risk factors, no parametrial invasion, and no lymph node involvement had better prognosis(P < 0.05). Whether patients with high-risk factors or intermediate-risk factors, the 5-year overall survival and 3-year disease-free survival had no difference between CT and RCT or RT groups respectively. Cox regression multivariate analysis of survival indicated that clinical stages, types of histology, different grade of risk factors were independent prognostic indicator. Patients with early stage, squamous cell carcinoma, intermediate risk factors had better prognosis. Univariate and multivariate analysis indicated that different postoperative adjuvant therapies had no effects on the prognosis. The 5-year overall survival was 88.6% in patients treated with CT, and 89.7% in patients treated with RT or CRT (P = 0.455) . CONCLUSION: There are equivalent therapeutic results between CT and RT or CRT for patients with risk factors after radical surgery, CT may be as one choice of postoperative adjuvant therapy for stage Ib-IIa cervical carcinoma with risk factors.

[Clinical features and drug resistance characteristics of ovarian clear cell adenocarcinoma and analysis of its prognostic factors].

OBJECTIVE: To investigate the clinical features and factors involved in the drug resistance and prognosis of ovarian clear cell adenocarcinoma (OCCA). METHODS: Forty-seven OCCA patients and 53 ovarian serous cyst adenocarcinoma (OSCA) patients were included in this study. Their clinical characteristics, drug resistance, and prognostic factors were analyzed. RESULTS: The onset age of OCCA was (49.09 + 11.80) years old, and that of OSCA was (55.51 + 1.38) year old. There were 53.3% (24/45) of OCCA and 98.0% (50/51) of OSCA patients who had elevated CA125 levels. There were 46.8% (22/47) of OCCA patients and 7.5% (4/53) of OSCA patients who suffered from endometriosis (EMS). The percentage of early stage (stage I and stage II) OCCA was 80.9% (38/47), and that of OSCA was 11.3% (6/53). A statistically significant difference was observed on all these aspects (P < 0.05). The percentage of drug resistant OCCA was 26.1% (12/46), and that of OSCA was 24.0% (12/50), with a non-significant difference (P = 0.814).Among the patients with advanced stage disease, the percentage of drug resistance was 87.5% (7/8) for OCCA, while that of OSCA was 25.0% (11/44), showing a statistically significant difference (P = 0.003). Multiple logistic regression analysis revealed that OCCA (OR = 21.774, 95%CI: 2.438 to 194.431) and advanced stage (OR = 58.329, 95%CI: 5.750 to 591.703) were independent risk factors of drug resistance in ovarian epithelial cancers. For the advanced stage patients, the median overall survival time of OCCA and OSCA were 11 and 29 months, respectively, with a statistically significant difference (P = 0.000). Cox survival analysis showed that OCCA, advanced stage, suboptimal surgery, fewer than 6 cycles of chemotherapy and drug resistance were all risk factors of OS in ovarian cancer patients (P < 0.05). CONCLUSIONS: The age of onset in OCCA patients is younger than that of OSCA patients. The proportion of combination with endometriosis (EMS) is higher, and more early stage disease is observed in OCCA patients. The percentage of drug resistant in OCCA is higher, especially in advanced stage patients. The prognosis of advanced stage OCCA patients is poorer than that of OSCA patients in advanced stage.

A type IV osteogenesis imperfecta family and pregnancy: a case report and literature review.

Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen is defective and causes osseous fragility. Type IV osteogenesis imperfecta is dominant inheritance. Here, we report a case of type IV osteogenesis imperfecta family and their female member's pregnancy. Abnormal sonographic findings (marked bowing and shortening of long bones) and family history made the diagnosis of fetus with osteogenesis imperfecta. The parents decided to give up rescuing the infant and a caesarean section at 27 weeks of gestation was implemented. In conclusion, it is possible to make a prenatal diagnosis of osteogenesis imperfecta by ultrasound. For the pregnant women with osteogenesis imperfecta, management decision should be made on an individual basis.

[Expression of Notch3 and Notch intracellular domain in ovarian carcinoma and effect of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester on ovarian carcinoma cell].

OBJECTIVE: To study the expression and clinical significance of Notch3 and Notch intracellular domain (NICD) in ovarian carcinoma and the effects of N-[N-(3,5-difluorophenyl) acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a γ-secretase inhibitor on the proliferation and apoptosis in OVCAR3, A2780 ovarian carcinoma cell lines. METHODS: Western blot was used to detect the expression of NICD in the tissues from 58 ovarian carcinomas patients and 21 normal ovarie, who were admitted in Peking University First Hospital from July 2006 to June 2009.Immunohistochemistry was also used to detect the expression of Notch3 in these tissues. The relationship with clinical features of ovarian carcinoma was also analyzed. Proliferation of OVCAR3 and A2780 ovarian cancer cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in OVCAR3 and A2780 cells incubated with DAPT was detected by western blot. RESULTS: (1) The expression level of NICD in ovarian carcinomas was significantly higher than that in normal ovarian tissues (1.64 ± 0.19 vs. 0.98 ± 0.20; P < 0.05). The NICD expression was higher in ovarian cancers with low grade or advanced stage than those in high-middle grade or early stage, respectively (1.90 ± 0.22 vs. 1.25 ± 0.21, 1.80 ± 0.21 vs. 1.21 ± 0.15; all P < 0.05). The Notch3 protein was stained positively in cytoplasm, nuclear and cell membrane. The expression of Notch3 was higher in ovarian carcinomas than that in normal ovaries [78% (45/58) vs. 24% (5/21); P < 0.01]. While, there were no stasistical difference in different pathological types, stages, differentiation of ovarian carcinoma. There was no difference between the patients with adjuvant chemotherapy or not. (2) After OVCAR3 and A2780 cells incubated with DAPT 24, 48, 72 hours, NICD expression was significantly lower than that in control group (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells were depended on the concentrations and times. CONCLUSIONS: Notch3 and NICD may play a key role in the occurrence and progress of ovarian carcinoma. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of OVCAR3 and A2780 cells may be due to decreased the formation of NICD.

[Effects of postoperative chemotherapy on the prognosis of patients with high-risk early stage endometrial cancer].

OBJECTIVE: To investigate the effects of adjuvant chemotherapy for patients with high-risk stage I and II (early stage) endometrial cancer. METHODS: From Jan. 1994 to Jun. 2007, 106 cases with early stage high-risk endometrial cancer were treated in Peking University First Hospital and were divided into two groups based with postoperative adjuvant chemotherapy (ACT group, 66 cases) and without adjuvant chemotherapy (control group, 40 cases). The 5-year survival rates was calculated by Kaplan-Meier method. Prognosis factors were further determined by univariate analysis and Cox proportional hazards models. RESULTS: The 5-year survival rate in the ACT group was significantly higher than that in control group (94% and 81%, P<0.05). On the univariate analysis, the 5-year survival rate of patients received four or more cycles combined chemotherapy was higher than that of cases less than four cycles chemotherapy (100% and 86%, P<0.05). While, it were not significant difference in age, stage, histology, grade, radiotherapy alone, chemotherapy combined radiotherapy or progestin hormonal therapy (P>0.05). On the multivariate analysis, adjuvant chemotherapy was found to affect independent prognostic covariates on early stage cases (P<0.05). CONCLUSION: Postoperative adjuvant chemotherapy maybe improve the prognosis of patients with high-risk early stage endometrial cancer, which need to be further study by prospective randomized trials.

[Expression of Notch intracellular domain in cervical cancer and effect of DAPT on cervical cancer cell].

OBJECTIVE: To study the expression and clinical significance of Notch intracellular domain (NICD) in cervical cancer and the effects of N-[N-(3,5-difluorophenyl)acetyl-L-alanyl]-S-phenyl glycine t-butyl ester (DAPT), a gamma-secretase inhibitor on the proliferation and apoptosis of cervical cancer cell lines. METHODS: Western blot was used to detect the expression of NICD in the tissues of 40 cervical cancers and 21 normal cervix and its relationship with clinical features of cervical cancer was also analyzed. Proliferation of SiHa and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell cycles and apoptosis and index of proliferation were detected by flow cytometry method. The expression of NICD in SiHa and HeLa cells incubated with DAPT was detected by western blot. RESULTS: The expression level of NICD in cervical cancers was significantly higher than that of normal cervical tissues (1.237 +/- 0.353 vs 0.938 +/- 0.105, P < 0.05). The NICD expression was higher in cervical cancers with high grade, lymph node involvement and parametrial invasion than that with low-middle grade (1.496 +/- 0.540 vs 1.150 +/- 0.216), without lymph node involvement (1.419 +/- 0.532 vs 1.159 +/- 0.210) and no parametrial invasion (1.718 +/- 0.710 vs 1.183 +/- 0.258), respectively (all P < 0.05). The expression of NICD in cervical adenocarcinoma was higher than that of squamous cell cancer (1.463 +/- 0.395 vs 1.162 +/- 0.187, P < 0.05). After SiHa and HeLa cells were incubated with DAPT, NICD expression was significantly lower than that in control (P < 0.05). The effects of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells was depended on its concentrations and times. CONCLUSIONS: NICD may play a key role in the occurrence and progress of cervical cancer. The mechanism of DAPT inhibited the proliferation and prompted the apoptosis of SiHa and HeLa cells may be due to decreased the formation of NICD.

[Induction of T cell responses against autologous ovarian cancer by anti-idiotype minibody-pulsed dendritic cells].

BACKGROUND & OBJECTIVE: Immunotherapy of sensitizing dendritic cells (DCs) with antigen,protein,and frozen cancer cell has been widely used in treating various cancers. The 6B11 anti-idiotype-antibody,a fusion protein prepared by our research center,can mimic ovarian cancer-associated antigen OC166-9. This study was to induce T cell cytotoxicity against autologous tumor cells of patients with ovarian cancer by 6B11 anti-idiotype-antibody. METHODS: Peripheral blood samples were collected from 10 patients with epithelial ovarian cancer,Monocytes were isolated and cultured to obtain DCs. Immature DCs were stimulated with 6B11 anti-idiotype-antibody (MINI-DC group); unpulsed DCs (unpulsed-DC group),mouse F(ab) '2 fragments pulsed DCs [F(ab)'2-DC group],and T cells alone (T group) were served as controls. Mature DCs were harvested. (3)H-thymidine ((3)H-TdR) incorporation approach was used to measure effect of DCs on stimulating auto-T cell proliferation. Cytotoxicity of DC-activated T cells against auto-tumor cells was measured with (51)Cr 6-h release test,tumor cell lines,SKOV3,HLE,and K562, were used as controls. RESULTS: In 4 cases,cpm value of (3)H-TdR incorporation,as symbol of auto-T cell proliferation, in MINI-DC group was significantly higher than those in control groups. In 5 cases,specific cytotoxicity effect of T cells on auto-tumor cells was observed in MINI-DC group at effect-target ratio of 20:1,the toxicity effect of T cells in MINI-DC group was 25%-100%,significantly higher than those in F(ab)'2-DC group (18%-40%), unpulsed-DC group (13%-43%),and T group (9%-58%). In 4 cases,the toxicity effect of T cells in MINI-DC group, at effect-target ratio of 20:1,on auto-tumor cells was 25%-100%, higher than those on SKOV3 cells (5%-51%),HLE cells (2%-38%),and K562 cells (2%-25%). Moreover,the toxicity effect of T cells in MINI-DC group on auto-tumor cells can be partially blocked by anti-MHC-I antibody,which indicated that the toxicity was antigen-specific. CONCLUSION: DCs loaded with 6B11 anti-idiotype antibody that mimic ovarian cancer antigen can induce antigen specific T cell cytotoxicity against auto-ovarian tumor cells in vitro.

[Effect of pelvic lymphadenectomy on prognosis of endometrial carcinoma].

OBJECTIVE: To study the associated factors with pelvic lymph node metastasis of endometrial carcinoma and the effect of pelvic lymphadenectomy on prognosis of the disease. METHODS: Totally 102 patients with endometrial carcinoma who underwent pelvic lymphadenectomy (90 patients) or lymph node biopsy (12 patients) in our hospital from Jan 1981 to Dec 2002 were recruited. The relationship between various clinicopathologic factors and pelvic lymph node metastasis was analyzed. Prognosis of ninety patients with pelvic lymphadenectomy was compared with 90 patients without pelvic lymphadenectomy (control group) in the same period. The 5-year survival was calculated by life table method. RESULTS: The incidence of pelvic lymph node metastasis increased in patients with low grade (46%), deep myometrium invasion (42%), cervical involvement (44%), positive peritoneal cytology (52%), adenexal metastasis (75%) and distant spread (100%). The 5-year survival was lower in patients with lymph node metastasis (37%) than that without lymph node metastasis (89%, P < 0.05). Univariate and COX regression analysis demonstrated that pelvic lymphadenectomy did not improve patients' prognosis. The 5-year survival in patients undergoing lymphadenectomy was 78%, and it was 72% in patients without lymphadenectomy. CONCLUSIONS: The high risk factors for pelvic lymph node metastasis in endometrial carcinoma include low grade differentiation deep myometrium invasion, cervical involvement, positive peritoneal cytology, adenexal metastasis and distant spread. The prognosis is poorer in patients with pelvic lymph node metastasis. Pelvic lymphadenectomy could not improve the prognosis of patients with endometrial carcinoma.