Wei Chun Chang

Electroacupuncture Reduces Uterine Artery Blood Flow Impedance in Infertile Women

OBJECTIVE To evaluate the effects of electroacupuncture (EA) on pregnancy rate and uterine artery blood flow impedance in patients undergoing in vitro fertilization (IVF). MATERIALS AND METHODS This prospective, randomized trial was carried out in the IVF center of China Medical University Hospital in Taiwan, from February 1, 2004 to January 30, 2005. A total of 44 patients were enrolled in the study. Of these, 30 were allocated to acupuncture, and 14 were allocated to no acupuncture. EA was performed four times, twice a week for 2 weeks, from day 2 of the study to the day before oocyte retrieval. After patients felt the needle reaction, the needles were attached to an electrical stimulator for 30 minutes. Clinical pregnancy and pulsatility index (PI) of right and left uterine arteries before and after EA were measured. RESULTS There was no significant difference in pregnancy rate between the two groups (acupuncture group, 30%; non-acupuncture group, 28.6%). The mean PI of both uterine arteries was significantly reduced after EA (left uterine artery, 2.3 to 2.0; right uterine artery, 2.4 to 2.2). There was no significant change in PI in the group with no acupuncture (left uterine artery, 2.5 to 2.3; right uterine artery, 2.4 to 2.3). CONCLUSION EA could be useful for reducing uterine artery blood flow impedance, but did not increase the pregnancy rate in patients undergoing IVF.

Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway.

OBJECTIVE The anti-proliferation effect of caffeic acid (3,4-dihydroxycinnamic acid), isolated from Ocimum gratissimum Linn, on human cervical cancer cells (HeLa cells) was examined to elucidate the associated mechanism and death mode. MATERIALS AND METHODS Flow cytometry showed that caffeic acid treatment results in dramatically increased apoptosis of HeLa cells. Western blot analysis revealed that caffeic acid activates various processed caspases. RESULTS Caffeic acid significantly reduced proliferation of HeLa cells in a concentration-dependent manner. Morphological evidence of apoptosis, including nuclei fragmentation was clearly observed 24 and 48 hours after exposure to caffeic acid (1 mM and 10 mM) by flow cytometry. Time-dependent inhibition was also observed. Caffeic acid decreased levels of uncleaved caspase-3 and Bcl-2, and induced cleaved caspase-3 and p53. CONCLUSION Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

MicroRNA-21 promotes the ovarian teratocarcinoma PA1 cell line by sustaining cancer stem/progenitor populations in vitro

IntroductionResistance of cancer stem/progenitor cells (CSPCs) to chemotherapy can lead to cancer relapse. Ovarian teratocarcinoma (OVTC) arises from germ cells and comprises pluripotent cells that can be used to study cancer cell stemness. In this study, we evaluated whether microRNA-21 (miR-21) promotes ovarian teratocarcinoma by maintaining cancer stem/progenitor populations.MethodsThe lentiviral delivery system was used to upregulate or to suppress the expression of miR-21 in the human ovarian teratocarcinoma cell line PA1 and cell growth assays were used to monitor the expression of miR-21 at different time points. Antibodies directed toward CD133, a stem cell marker, were used to identify CSPCs in the PA1 cell population, and the level of miR-21 expression was determined in enriched CSPCs. Stem cell functional assays (sphere assay and assays for CD133 expression) were used to assess the effects of miR-21 on progression of the CD133+ population.ResultsKnockdown of miR-21 in PA1 cells attenuated growth of PA1 cells whereas overexpression of miR-21 promoted cell growth. Moreover, knockdown of miR-21 resulted in a marked reduction in the CD133+ population and sphere formation of CSPCs. In contrast, overexpression of miR-21 resulted in a marked increase in the population of CD133+ cells as well as sphere formation of CSPCs.ConclusionsMicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.

The Effect of Physician Experience on Costs and Clinical Outcomes of Laparoscopic-Assisted Vaginal Hysterectomy: A Multivariate Analysis

STUDY OBJECTIVE To evaluate whether or not a physicians experience has an effect on costs and clinical outcomes of an implemented clinical pathway for laparoscopic-assisted vaginal hysterectomy (LAVH). DESIGN Retrospective study (Canadian Task Force classification II-2). SETTING University hospital. PATIENTS One hundred twenty women. INTERVENTION LAVHs, 84 performed by senior physicians and 36 by junior physicians. MEASUREMENTS AND MAIN RESULTS According to results of multiple linear regression analysis, after controlling for other independent variables, senior attending physicians, each with over 6 years of experience, managed to reduce all costs related to LAVH, operating time, and length of stay. Logistic regression analysis revealed no differences in the occurrence of intravenous fluid injection, antibiotic injection more than 2 days after surgery, and complications between physicians with and those without experience. Neither group had blood transfusions, patient mortality, or readmissions within 2 weeks of discharge. CONCLUSION Physician experience reduces medical costs and maintains the quality of care in LAVH. We suggest regular training courses for less-experienced physicians in order to contain costs and maintain quality of care under the quota case-payment system.

Analysis of Caffeic Acid Extraction From Ocimum gratissimum Linn. by High Performance Liquid Chromatography and its Effects on a Cervical Cancer Cell Line

OBJECTIVE Ocimum gratissimum is a herbal medicine and caffeic acid (3,4-dihydroxycinnamic acid) is one of its main components. Caffeic acid is known to control the levels of cholesterol and triglycerides, reduce the activity of cancer cells, and enhance immunity in the human body. The amounts of caffeic acid in herbal medicine and vegetable oils have not been reported in the literature since an analytical method has not yet been established. In this study, we explored the effects of caffeic acid treatment on anti-proliferation in HeLa cells. MATERIALS AND METHODS This paper presents a method of extraction of caffeic acid from O. gratissimum and Ju ZenTa (Ocimum basilicum L.) using high performance liquid chromatography. Treatment of HeLa cells with the extracted caffeic acid (10 mM) was analyzed. RESULTS We showed that caffeic acid isolated from several kinds of vegetables and from the herb of O. gratissimum had anti-proliferative effects on cervical cancer cell lines. Caffeic acid can significantly reduce the proliferation of HeLa cells in a time-dependent manner. CONCLUSION This paper shows that high performance liquid chromatography is a suitable analytical method for determining caffeic acid levels in O. gratissimum, Ju ZenTa, and several vegetable oils. Caffeic acid can suppress the proliferation of HeLa cells.

Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes, and negative para-aortic lymph nodes.

Objective The objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs). Methods Thirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m2. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods. Results Thirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis–free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively. Conclusions Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Clinical implications of elevated pretreatment carcinoembryonic antigen in patients with advanced squamous cell carcinoma of the uterine cervix.

Object: The aim of this study was to investigate the prognostic significance of pretreatment levels of carcinoembryonic antigen (CEA) for treatment outcome in comparison with squamous cell carcinoma antigen (SCC) in cervical cancer patients following concurrent chemoradiotherapy (CCRT). Methods: A total of 148 patients with stage IB2–IVA squamous cell carcinoma of the uterine cervix who were treated with a full course of CCRT were included for analysis. The pretreatment blood samples of tumor markers were obtained before initiation of CCRT. Values for SCC <2 and CEA <5 ng/ml, respectively, were regarded as normal. Cox’s proportional hazards model was performed for risk stratification for disease-free survival (DFS) and cause-specific survival (CSS). Results: Pretreatment CEA and SCC levels were elevated in 37.2 and 64.2% of the patients, respectively. Positive pelvic lymph node, stage and pretreatment CEA levels >10 ng/ml were three independent prognostic factors for DFS and CSS. The 5-year DFS for the low- and high-CEA groups was 80 and 56%, respectively (p = 0.02, hazard ratio 2.6), whereas the 5-year CSS for the low- and high-CEA groups was 84 and 63%, respectively (p = 0.01, hazard ratio 3.2). Conclusion: Despite lower sensitivity, pretreatment CEA levels >10 ng/ml predict a poor outcome in advanced squamous cell carcinoma of the cervix.

Conservative surgical treatment of adenomyosis to improve fertility: Controversial values, indications, complications, and pregnancy outcomes☆

Uterine adenomyosis was first reported in the 19(th) century and early 20(th) century; von Rokitansky described it in 1860. Since then, the general clinical, pathological, and radiologic findings and potentially useful management methods have been reviewed in many studies. Some authors commented that conservative surgical treatment is impracticable as it is not possible to isolate the adenomyotic tissue adequately; therefore, the authors suggested that hysterectomy is the only rational and complete procedure. There is more evidence supporting the advantages of conservative uterine-sparing surgery in providing not only more effective symptom relief, but also longer durable symptom control for symptomatic women with uterine adenomyosis, because the main problem secondary to uterine adenomyosis, dysmenorrhea, can be improved significantly, up to 80%. Menorrhea was also improved in more than two-thirds of patients after type I uterine-sparing surgery, and half of the patients saw benefit in symptom control after type II conservative uterine-sparing surgery. In addition, there was no negative impact on reproductive performance after conservative uterine-sparing surgery, and in fact, reproductive performance seemed to be improved compared with that after medical treatment-not only was there a higher cumulative pregnancy rate, but also a higher cumulative final successful delivery rate. However, there is no doubt that the data supporting the above-mentioned benefits for symptomatic women with uterine adenomyosis after conservative uterine-sparing surgery are limited, suggesting that the benefit may be moderate. In fact, one of the main indications for surgery is temporary pain relief in women seeking spontaneous conception. However, the effect of surgery on pain is usually only temporarily satisfactory, and the risk of complications varies according to the type of lesion extirpated. In light of this, an extensive review of this topic addressing conservative surgical treatment for adenomyosis to improve fertility, including controversial values, indications, complications, and pregnancy outcomes, might be very important, and might help physicians in managing these patients in the future.

Quality-initiated prophylactic antibiotic use in laparoscopic-assisted vaginal hysterectomy.

Background: An evidence‐based initiation of quality improvement activity for reducing the usage of prophylactic antibiotic in laparoscopic‐assisted vaginal hysterectomy (LAVH) in a tertiary hospital.

Risk Stratification for Failure in Patients with Advanced Cervical Cancer after Concurrent Chemoradiotherapy: Another Way to Optimise Treatment Results

AIMS To identify risk factors for disease-free survival (DFS) and para-aortic lymph node (PALN) metastasis in advanced cervical cancer patients after concurrent chemoradiotherapy (CCRT) using risk stratification. MATERIALS AND METHODS In total, 148 patients with stage IB2-IVA cervical cancer without PALN metastasis treated with a full course of CCRT were included for analysis. Radiotherapy consisted of external beam irradiation followed by four courses of high-dose rate intracavitary brachytherapy using 6.0 Gy to point A. Chemotherapy consisted of weekly cisplatin at a dose of 40mg/m(2) for a planned six cycles. Coxs proportional hazards model was used for risk stratification for DFS and PALN relapse-free survival. RESULTS Patients were divided into low- and high-risk groups. The low-risk group was composed of patients with stage IB-IIB disease without enlarged pelvic nodes, whereas the high-risk group was comprised of patients with stage IB2-IIB tumours with enlarged nodes or those with stage III-IVA disease. The 4-year DFS for the low- and high-risk groups was 83 and 52%, respectively (P=0.0001, relative risk 4.51, 95% confidence interval 1.3-10.7), whereas the 4-year PALN metastasis-free survival for the low- and high-risk groups was 92 and 61%, respectively (P=0.0003, relative risk 4.93, 95% confidence interval 1.2-12.5). CONCLUSION The risk of failure in advanced cervical cancer patients treated in the CCRT era can be predicted. For patients with high risk of PALN relapse, this study can provide patient selection criteria when considering prophylactic PALN irradiation.