[Feasibility of unilateral or bilateral nerve-sparing radical hysterectomy in patients with cervical cancer and evaluation of the post-surgery recovery of the bladder and rectal function].

OBJECTIVE: To investigate the feasibility of unilateral or bilateral nerve-sparing radical hysterectomy and evaluate the recovery of bladder and bowel function postoperatively. METHODS: From August 2008 to October 2009, sixty-one patients with cervical cancer stage Ib1 to IIa underwent radical hysterectomy (33 cases) and nerve-sparing radical hysterectomy (28 cases). Unilateral nerve-sparing radical hysterectomy was performed in 10 patients, and bilateral nerve-sparing radical hysterectomy (BNS) was performed in 18 patients. The data of operation time, blood loss, postoperative hospital stay days, residual urine volume, and postoperative complications were collected. The postoperative recovery of bladder and bowel function was evaluated. RESULTS: There were no significant differences between nerve-sparing radical hysterectomy (NSRH) and radical hysterectomy (RH) groups in operation time [NSRH: (224.5 ± 40.0) min, RH: (176.4 ± 30.0 min)], blood loss [NSRH: (464.3 ± 144.0) ml, RH: (374.2 ± 138.7) ml], postoperative hospital stay days [NSRH: (8.4 ± 2.0) d, RH: (9.2 ± 1.8) d, and residual urine volume [NSRH: (64.8 ± 16.9) ml, RH: (70.6 ± 16.0) ml]. There were also no significant differences between UNSRH and BNSRH groups in operation time [UNSRH: (208.5 ± 28.5) min, BNSRH: (233.3 ± 43.1) min], blood loss [UNSRH: (440.0 ± 104.9) ml, BNSRH: (477.8 ± 162.90) ml], postoperative hospital stay days [UNSRH: 9.1 ± 1.8) d, BNSRH: (8.7 ± 2.1 d], and the residual urine volume [UNSRH: (68.3 ± 12.5) ml, BNSRH: (62.8 ± 20.0) ml]. There was a significant difference in the time of the Foley catheter removal between NSRH [(12.4 ± 5.2) d] and RH [(22.4 ± 9.7) d] groups. There was a significant difference in the time of the Foley catheter removal between UNSRH [(18.2 ± 3.6) d] and BNSRH [(9.1 ± 2.0) d] groups. During the postoperative 3 weeks follow-up, the patients in the NSRH group had a higher rate of satisfaction at urination and defecation (100%, 75%) than the RH group (54.5%, 24.2%). CONCLUSION: UNSRH and BNSRH are safe and feasible techniques for early stage cervical cancer, and may significantly improve the recovery of bladder and rectal function.

[Clinical analysis of 13 cases with vaginal intraepithelial neoplasia].

OBJECTIVE: To investigate the pathogenesis, high risk factors, clinical characteristics, methods of diagnosis and treatment, and prognosis of vaginal intraepithelial neoplasia (VAIN). METHODS: The clinical data of thirteen cases of VAIN treated in Zhejiang Provincial Cancer Hospital dated Mar. 2002 through Dec. 2008 were reviewed and analyzed retrospectively. RESULTS: Twelve of 13 VAIN cases were performed the human papillomavirus (HPV) detection with 92% (11/12) HPV positive rate. None of the cases shown specific clinical manifestation. Among the 13 cases, 6 of them accompanied with cervical cancer, 4 cases with cervical intraepithelial neoplasia (CIN), and 3 cases with vulvar intraepithelial neoplasma (VIN). Five cases synchronously diagnosed with cervical lesion and 3 with vulva lesion were underwent surgery, while the other 5 cases were diagnosed metachronously. Among 8 cases underwent surgery, 1 case with CIN underwent argon plasma coagulation (APC) after surgery, 1 case with the positive edge of VIN underwent APC. During follow up, 1 case with locally advanced cervical cancer underwent radiotherapy again, 3 cases with VAIN received APC, while 1 cervical cancer cases with VAIN received no treatment. The average follow-up time was 25.6 months (range 6-87 months). Two cases died of cervical cancer metastasis. The other 11 cases were normal and still alive. None of them progressed to invasive carcinoma. CONCLUSIONS: The main reason of VAIN is HPV infection. There are not specific clinical manifestations, usually diagnosed when reviewing cervical or vulva lesions and rarely progressed to invasive carcinoma. The main treatment of VAIN is surgery with the adjuvant treatment of APC.

[Analysis of therapeutic result and prognostic factor in primary fallopian tube carcinoma].

OBJECTIVE: To investigate the impact of treatment modality and clinicopathologic profile on prognosis in primary fallopian tube carcinoma. METHODS: The data of 64 cases with primary fallopian tube carcinoma treated between January 1991 and June 2006 were analyzed. The clinicopathological data were retrospectively analyzed. RESULTS: The overall 5-year survival rate of this series was 56.3%. The overall 3- and 5-year survival rate was 84.6% and 65.4% in surgical staging group versus 58.3% and 33.3% in no surgical staging group with a significant difference between two groups (P = 0.0429; P = 0.043), which was 89.5% and 68.4% in optimal cytoreduction group versus 66.7% and 41.7% in suboptimal cytoreduction group (P = 0.0466; P = 0.0444). However, there was no significant difference in 3-year and 5-year survival rate between the group with pelvic lymphadenectomy and the group without (84.2% vs. 69.2%, P = 0.4667; 63.1% vs. 53.8%, P = 0.459), and also between the group treated using CAP/CP regimen and the group by TP regimen for chemotherapy (81.8% vs. 80.0%, P = 0.8946; 59.1% vs. 60.0% P = 0.9582). It was found that the 5-year survival was correlated with FIGO stage (III-IV vs. I - II, P = 0.0197), differentiation grade (G3 vs. G1 + G2, P = 0.003), pathologic type (other type vs. serous, P = 0.0494), lymph nodes status (positive vs. negative, P = 0.0295). CONCLUSION: Surgical staging, optimal cytoreduction, differentiation grade, pathologic type, lymph node status are important factors influencing the 5-year survival in primary fallopian tube carcinoma. Pelvic lymphadenectomy is necessary and feasible to perform during the procedure of surgical staging and cytoreduction. CAP/CP and TP regiment are similarly effective in adjuvant chemotherapy for primary fallopian tube carcinoma.

Pharmacodynamic comparison of prostaglandin E1 administered by different routes to rats.

The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE, was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area under the blood pressure decrease percent-time curves (AUC, % x min) were determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip), and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal approximately = im > ip > sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal > im approximately = ip > sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.

[Combined effect of cosolvent and cyclodextrin on solubilization of insoluble drugs].

AIM: To investigate the combined effect of cosolvent and cyclodextrin (CD) on solubilization of insoluble drugs. METHODS: Phase-solubility method was applied to determine solubilization of two diterpenoids in cosolvent / cyclodextrin combinations. The combined effect was evaluated and explained with an established mathematical model, and the model parameters were calculated by means of nonlinear regression analysis. RESULTS: The strong agreement between the predicted and the observed solubility data supports the validity of the proposed model, with the determination coefficients of two regression models were 0.993 and 0.992, separately. CONCLUSION: The validated mathematical model can be used to explain and predict the combined solubilization of the two insoluble drugs in different cosolvent systems.

[Effect of preparation technique on in vitro release mechanism of huperzine A microspheres].

AIM: To investigate the effect of preparation technique on in vitro release mechanism of huperzine A-PLGA microspheres. METHODS: Huperzine A-PLGA microspheres were prepared by two kinds of O/O emulsion solvent evaporation method (method A and B). In vitro release mechanism was explained by release profile, degradation rate and swelling rate of microspheres in vitro. The microspheres morphology and drug distribution within microspheres were observed in order to explain further the drug release mechanism. RESULTS: The encapsulation efficiency of huperzine A microspheres prepared by method A and B was 47.60% and 83.50% respectively. Microspheres prepared by method A could sustain release for 35 days with nearly no initial burst release. The release profile fitted well to zero order equation and drug release mainly through degradation and diffusion mechanism. Huperzine A microspheres prepared by method B could sustain release for 21 days with some evidence of initial burst release. The release profile fitted well to the Higuchi equation and drug release was mainly through diffusion mechanism. CONCLUSION: Huperzine A microspheres prepared by method A had more desirable release profile.

Preparation of prostaglandin E1-hydroxypropyl-beta-cyclodextrin complex and its nasal delivery in rats.

The potential use of hydroxypropyl-beta-cyclodextrin (HP-betaCD) in the solubilization and stabilization of prostaglandin E(1) (PGE(1)) was investigated. The solubility and chemical stability of PGE(1) were significantly improved upon complexation with HP-betaCD. The nasal delivery of PGE(1) from the complex formulation was also studied in Wistar rats and compared with intravenous administration. PGE(1) complex after nasal administration caused a rapid decrease of blood pressure and exhibited an obvious dose-efficacy relationship, showing results nearly similar to those obtained for intravenous route. The time to reach the peak effect (T(max)) was approximately 3-4 min. Except T(max), other pharmacodynamic parameter values such as the maximal percent of blood pressure decrease (E(max), %), the lasting time of effect (T(d)), and the area under the curve (AUC, blood pressure decrease % min) were increased with increasing the administered doses. The E(max), T(d), and in particular AUC values between doses were significantly different (P < 0.01), but T(max) between doses were not significantly different (P < 0.05). The AUC values per unit dose of PGE(1) for nasal administration, however, were smaller than those for intravenous route, probably due to the incomplete absorption of nasally administered PGE(1). Besides, the in vitro effect of the PGE(1) complex on nasal mucociliary movement was also investigated with a toad palate model. The PGE(1) complex formulation exerted only minor effect on nasal mucociliary movement. These results indicate that the PGE(1)-HP-betaCD complex formulation for nasal delivery is a very promising preparation with advantages such as rapid and effective absorption, good chemical stability, ease of administration, and minor nasal ciliotoxicity.

Preparation and in vivo evaluation of huperzine A-loaded PLGA microspheres.

Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an ONV emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with 10% released per day. Thereafter drug release rate became slow gradually and about 90% drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4 mg/kg and microspheres were intramuscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration (Cmax ) after i.m. microspheres was only 32% of that after i.m. solution. Drug in plasma could be detected until day 14 and about 5% of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was 94.7%. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

Treatment and prognosis of cervical cancer associated with pregnancy: analysis of 20 cases from a Chinese tumor institution.

This study was designed to investigate the therapeutic approaches and prognosis for cervical cancer associated with pregnancy. Clinical information, therapeutic strategies, and follow-up results of 20 patients with cervical cancer associated with pregnancy from Jan. 2000 to June 2009 in the Zhejiang Cancer Hospital were retrospectively analyzed. The International Federation of Gynecology and Obstetrics (FIGO) stages were: in situ (n=1), stage IA1 (n=1), stage IB1 (n=5), stage IB2 (n=1), stage IIA (n=8), stage IIB (n=3), and stage IIIB (n=1). Eight patients were in the first trimester of pregnancy, four in the second, two in the third, and six at postpartum when diagnosed. The therapeutic strategies were either single or combined modalities, including surgery, radiotherapy, and chemotherapy. Fourteen patients survived, five patients died (four of remote metastasis and one of uremia), and one patient was lost to follow-up. One newborn from a patient at stage IIA carcinoma in the third trimester with postponed therapy six weeks after diagnosis survived. Retarded fetal growth was observed in one patient receiving neoadjuvant chemotherapy and cesarean section. Out of the six postpartum patients, three underwent cesarean section and survived, whereas only one out of the three who underwent vaginal delivery survived. The remaining two died of remote metastasis. Therefore, personalized treatment is necessary for cervical cancer associated with pregnancy. Cervical cancer patients in the third trimester of pregnancy can continue the pregnancy for a short period of time. There may be potential risk for the fetus by chemotherapy during pregnancy. Cesarean section is the preferred mode of delivery for pregnant cervical cancer patients.

[The complexation of prostaglandin E1 with hydroxylpropyl-beta-cyclodextrin in aqueous solution].

AIM: To investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process. METHODS: The measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively. RESULTS: That all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy. CONCLUSION: An 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.

Optimization of the preparation of nalmefene-loaded sustained-release microspheres using central composite design.

Nalmefene-loaded poly(lactic-co-glycolic acid) microspheres were prepared by O/O emulsification/solvent evaporation method. The central composite design-response surface methodology was used to optimize and predict the preparation microspheres. Effects of three independent variable variables i.e., Span80 concentration in outer phase, poly(lactic-co-glycolic acid) concentration in inner phase and theoretical drug content were evaluated on a number of response variables. Response variables selected in this study were drug content, encapsulation efficiency, mean diameter, diameter span and the cumulative percentage of the drug released in the first day after incubation (marked as F1d, and it was also calculated as the initial burst). Multiple linear regression and second-order polynomial model were fitted to the data, and the resulting equations were used to produce five dimensional response graphs, by which optimal experimental conditions were selected. The results showed that all response variables were greatly dependent on three independent variables, and the optimal conditions were Span80 concentration 1.5%, poly(lactic-co-glycolic acid) concentration 17.5%, and theoretical drug content 6%. According to the optimal conditions, the drug content, encapsulation efficiency, mean diameter, diameter span and F1d of prepared microspheres were 4.37%, 72.8%, 64.1 microm, 1.36 and 8.93%, respectively.