Jerry Cheng-Yen Lai

Comparison in purity and antitumor effect of brand and generic paclitaxel against human ovarian cancer cells by an in vitro experimental model.

Context: The purity and the therapeutic effectiveness of the generic paclitaxel have not yet been examined and compared to the original brand form. Objective: This study aimed to compare the in vitro purity and biological effects of original brand form (Taxol) and a generic drug of paclitaxel. Materials and Methods: Purity was determined by high-performance liquid chromatography analysis, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay, cell proliferation by clonogenic assay, morphology by Lius staining, and cell cycle distribution by DNA histogram. Results: Taxol and generic paclitaxel shared similar high-performance liquid chromatography profiles with a major peak at the same retention time and ultraviolet spectrum. Generic paclitaxel inhibited the cell viability to an extent greater than Taxol. By assessing the IC50, generic paclitaxel also exhibited a greater inhibitory activity on clonogenicity of human ovarian adenocarcinoma SKOV-3 cells. Although both generic paclitaxel and Taxol arrested SKOV-3 and ES-2 cells at G2/M phase with concurrent development of hypoploid and polyploid cells, Taxol treatment exhibited markedly less extent of these changes. Observation of cellular morphology revealed a greater amount of mitotic catastrophe-like and apoptotic cells in generic paclitaxel-treated cells than Taxol-treated cells. Discussion and Conclusion: The results suggest that generic paclitaxel may possess a greater cell death inducing capacity and clonogenicity inhibitory activity against ovarian cancer cells than the original brand Taxol of the same purity. We conclude that this experimental model for assessing the difference between generic and brand name drugs might be considered as a reference while determining their interchangeability and could be easily established in a hospital-based laboratory.

Trends in bilateral salpingo-oophorectomy among Taiwanese women undergoing benign hysterectomy: a population-based, pooled, cross-sectional study.

ObjectiveThis study aims to examine recent trends in the performance of elective bilateral salpingo-oophorectomy at benign hysterectomy and to identify associated patient and provider-related characteristics from 2000 to 2010. MethodsWe conducted a population-based, pooled, cross-sectional study using claims data from Taiwan’s National Health Insurance program. Women aged 20 years or older who underwent concurrent oophorectomy at benign hysterectomy (n = 26,419) were compared with women who did not undergo concurrent oophorectomy at benign hysterectomy (n = 153,793). A generalized estimating equation model was applied to logistic regressions, and separate models were estimated to account for age interactions. ResultsThe overall oophorectomy rate declined steadily from 22.1% in 2000 to 9.9% in 2010, particularly in women aged 45 to 49 years (decreased by 80%). Women aged 55 years or older who had a comorbid illness or a catastrophic illness, underwent abdominal or laparoscopic surgical operation, and were admitted to regional hospitals or medical centers were more likely to undergo oophorectomy at hysterectomy, whereas women with a preoperative diagnosis of uterine prolapse, with a well-defined monthly wage, and undergoing vaginal hysterectomy were less likely to undergo oophorectomy. ConclusionsAge, socioeconomic status, presence of comorbid illness, hysterectomy approach, hospital accreditation level, and disease diagnosis influence oophorectomy rate in Taiwan, a country with national health insurance. Studies on the possible long-term health risks of elective oophorectomy and the emergence of increasing evidence on ovarian cancers of serous histology (such as tubal carcinoma) since the early 2000s may have influenced patients’ and physicians’ decision-making in favor of ovarian conservation, leading to the observed downward trend among Taiwanese women from 2000 to 2010.

SALVAGE CHEMOTHERAPY IN RECURRENT CERVICAL CANCER WITH BIWEEKLY PEGYLATED LIPOSOMAL DOXORUBICIN (LIPO-DOX)

OBJECTIVE To investigate the objective response rate to and tolerance of biweekly Lipo-Dox (TTY Biopharm Co. Ltd., Taipei, Taiwan) at a dosage of 20 mg/m(2) in previously treated patients with recurrent cervical cancer. MATERIALS AND METHODS This study was performed as a Simons two-stage phase II clinical trial. Ten patients with recurrent cervical cancer were enrolled between April 2003 and December 2005 at the Mackay Memorial Hospital. Lipo-Dox (20 mg/m(2) intravenous) diluted in 250 mL of 5% dextrose solution was administered at 2-weekly intervals. RESULTS The mean age of the patients was 51 +/- 11.1 years. The mean number of cycles of Lipo-Dox injection was 4.6 (range, 1-12 cycles). Nine patients (90%) had disease progression. Only one patient (10%) achieved a partial response, and this was also the only patient who experienced WHO grade 2 palmar-plantar erythrodysesthesia, which led to treatment delay for 2 months. The median survival time was 2 months (range, 2-6 months). The majority of patients experienced grade 1 or 2 anemia (30%), leukopenia (20%) or thrombocytopenia (20%), and others exhibited symptoms of nausea and vomiting (30%). CONCLUSION Salvage chemotherapy with Lipo-Dox at a dose of 20 mg/m(2) administered at 2-weekly intervals produced limited responses in patients with recurrent cervical cancer. This trial will not proceed to the second stage. These results may discourage the management of recurrent cervical cancer with single-agent Lipo-Dox in future clinical trials.

Treatment of gestational trophoblastic neoplasia according to the FIGO 2000 staging and scoring system: a 20 years' experience.

Objective. To reassess the efficacy of the Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system in comparison to the original World Health Organization (WHO) prognostic scoring system (1983) in a single‐institute setting. Design. Retrospective review of the medical records of 89 patients with gestational trophoblastic neoplasia. Setting. Mackay Memorial Hospital, Taipei, a regional referral center for northern Taiwan, over a 20‐year period. Methods. All selected patients were classified retrospectively by the original WHO prognostic scoring system (1983) and the FIGO 2000 system. Main outcome measure. Efficacy as the correlation of risk categorization by percentage of patients between the original WHO scoring system (1983) and the FIGO 2000 system. Results. The correlation was 97%. Only two patients were classified as middle risk group in the original WHO system (1983), but as high‐risk group by the FIGO 2000 system. Conclusion. There was good correlation between the original WHO (1983) and FIGO 2000 systems. Treatment outcomes by FIGO 2000 system were somewhat better than by the original WHO classification.

Development and Validation of a Fertility Intention Scale in Breast Cancer Survivors

Background: Evidence indicates that breast cancer survivors with reproductive concerns have a poorer quality of life than survivors without fertility concerns. There is a lack of reliable and valid assessments of fertility intention among breast cancer survivors. Purpose: The aim of this study was to develop and validate the Fertility Intention Scale (FIS) that is sensitive to the fertility intention of women with breast cancer. Methods: A literature review and a qualitative study were conducted to generate the items in the scale. Content validity was evaluated by 15 experts, and face validity was assessed by 10 patients with cancer. Factor analysis was used to assess construct validity, and criterion validity was evaluated using two percentile items of fertility willingness. We developed and examined the validity and reliability of the FIS using a sample of 178 patients with breast cancer who had completed chemotherapy. Results: The Cronbach’s alpha calculated for the FIS (15 items) was .88. The factor analysis performed for the construct validity of the scale identified four factors that accounted for approximately 68.72% of the total variance. These four factors were pregnancy risk, disease control, social support, and happiness. There was a significant correlation between the total FIS and the level of desiring fertility preservation or pregnancy. Conclusions/Implications for Practice: The FIS has acceptable reliability, content validity, and construct validity. This scale is appropriate for use in research and clinical practice settings to evaluate the risk–benefit perceptions of pregnancy in patients with breast cancer.

Sentinel lymphatic mapping among women with early-stage cervical cancer: A systematic review

The presence of pelvic lymph node metastases is without doubt the most significant prognostic factor that determines recurrences and survival of women with early-stage cervical cancer. To avoid the underdiagnosis of lymph node metastasis, pelvic lymphadenectomy procedure is routinely performed with radical hysterectomy procedure. However, the pelvic lymphadenectomy procedure may not be necessary in most of these women due to the relatively low incidence of pelvic lymph node metastasis. The removal of large numbers of pelvic lymph nodes could also render non-metastatic irreversible damages for these women, including vessel, nerve, or ureteral injuries; formation of lymphocysts; and lymphedema. Over the past decades, the concept of sentinel lymph node biopsy has emerged as a popular and widespread surgical technique for the evaluation of the pelvic lymph node status in gynecologic malignancies. The histological status of sentinel lymph node should be representative for all other lymph nodes in the regional drainage area. If metastasis is non-existent in the sentinel lymph node, the likelihood of metastatic spread in the remaining regional lymph nodes is very low. Further lymphadenectomy is therefore not necessary for a patient with negative sentinel lymph nodes. Since the uterine cervix has several lymphatic drainage pathways, it is a challenging task to assess the distribution pattern of sentinel lymph nodes in women with early-stage cervical cancer. This review article will adapt the methodology proposed in these studies to systematically review sentinel lymphatic mapping among women with early-stage cervical cancer.

The role of sentinel lymph node biopsy in early-stage cervical cancer: A systematic review

Pelvic lymphadenectomy procedure is included as part of the standard protocol of radical hysterectomy for women with early-stage cervical cancer (Stage IA to IB1). However, an important sequel to lymphadenectomy procedure is the possible occurrence of lymphedema in the lower abdomen and lower extremities. Previous researches also find that women with lymphedema experience many emotional impacts, including depression, anxiety, and adjustment problems. Only approximately 10% of women with clinical stage IB cervical carcinoma were involved with metastatic disease. If we could better define the relevant lymphatic nodes that must be removed, it is then possible to limit routinely performed lymphadenectomy for regional nodal metastasis in the pelvis, and hence reduce the need for extended surgical staging (para-aortic lymphadenectomy). We systematically reviewed a body of literature and updated available information concerning the current progress on the application of sentinel lymph node biopsy in women with early-stage cervical cancer. All detection methods (preoperative injection of radiocolloid tracer, intraoperative injection of blue dye, or a combination of both techniques) demonstrated reasonable sensitivity (with a few exceptions), high specificity, low false-negative rate and high negative predictive value. The review of the literature in this paper should convince the readers that sentinel lymph node biopsy has the potential to improve the quality of life and the possibility to maintain relapse-free survival for women with cervical cancer. The proper identification of negative sentinel lymph node allows individualized therapy and may preclude the need of lymphadenectomy procedure in most of these women.

The risk of stroke after bilateral salpingo-oophorectomy at hysterectomy for benign diseases: A nationwide cohort study

OBJECTIVE To assess the risk of stroke (and subtypes of stroke) in women after elective bilateral salpingo-oophorectomy at hysterectomy for benign diseases. STUDY DESIGN We conducted a nationwide population-based, retrospective cohort study using claims data from Taiwans National Health Insurance program between 1997 and 2013. Women aged 20 years or more who underwent bilateral salpingo-oophorectomy at hysterectomy for benign diseases (n = 1083) were compared with women who did not undergo bilateral salpingo-oophorectomy at hysterectomy for benign diseases (n = 3903). The follow-up period ranged from 10 to 16 years. Age-adjusted (or unadjusted) and multivariate Cox proportional hazards regression models were used to estimate the risk of stroke between the two groups. MAIN OUTCOME MEASURES A diagnosis of stroke (and subtypes of stroke). RESULTS We did not find a significant association between bilateral salpingo-oophorectomy and the risk of incident stroke (or subtypes of stroke) over an average follow-up of 13 years. Among women aged 50 years or more who used estrogen therapy, the risk of developing stroke was 64% lower in those who had undergone bilateral salpingo-oophorectomy (hazard ratio, 0.36; 95% confidence interval, 0.16-0.79) than in those who had undergone hysterectomy only. CONCLUSION This study suggests that the use of estrogen after bilateral salpingo-oophorectomy at hysterectomy for benign diseases reduces the risk of stroke in women aged 50 years or more.

In-hospital complications of bilateral salpingo-oophorectomy at benign hysterectomy: a population-based cohort study

Objective: The study compared the in-hospital complications and related outcomes between women who underwent bilateral salpingo-oophorectomy at hysterectomy for benign diseases and those who had hysterectomy only. Methods: We conducted a population-based, retrospective cohort study using data from Taiwans National Health Insurance program. Women who underwent concurrent bilateral salpingo-oophorectomy at hysterectomy for benign indications (n = 34,509) were compared with those who had hysterectomy only (n = 176,305). Separate models were estimated to account for the effect of baseline comorbid condition, age, and hysterectomy approach on the relationship between bilateral salpingo-oophorectomy and study outcomes. A secondary analysis was also performed to evaluate the association of inpatient readmission within 30 days and complications among women who underwent bilateral salpingo-oophorectomy. Results: The addition of a bilateral salpingo-oophorectomy to hysterectomy was associated with a lower risk of surgical complications, a longer length of hospital stay, and an increased risk of inpatient readmission within 30 days. Among women who underwent bilateral salpingo-oophorectomy, women with complications were also more likely to require inpatient readmission within 30 days than those without complications. Our data also suggested that bilateral salpingo-oophorectomy was not associated with an overall risk of medical complications, with the exception of urethral obstruction. The relationships remained even after adjustments by age, surgical indications, hysterectomy approach, and health-related risk factors, such as baseline comorbid condition and status of any prior catastrophic illness. Conclusions: Bilateral salpingo-oophorectomy at hysterectomy for benign conditions is not associated with an increased risk of in-hospital complications.

In-hospital complications of vaginal versus laparoscopic-assisted benign hysterectomy among older women: a propensity score-matched cohort study.

Objective:This investigation compared the outcomes of vaginal and laparoscopic hysterectomies for nonprolapsed benign indications in older women. Methods:We conducted a population-based, retrospective propensity score-matched cohort study using data from the Taiwans National Health Insurance program. Women who were aged 65 years or older with vaginal hysterectomy (n = 290) were compared with women who had laparoscopic hysterectomy for nonprolapsed benign indications (n = 290). Propensity score was calculated based on both patient- (age, socioeconomic status, residential urbanicity, comorbidity, status of any prior catastrophic illness, surgical diagnosis, and year of hysterectomy) and provider-related characteristics (physicians age and sex, hospital accreditation level, and ownership type). Results:Women undergoing laparoscopic hysterectomy were not associated with increased risk of inpatient readmission within 30 days, in-hospital mortality, and in-hospital (including intraoperative) complications when compared with those who had vaginal hysterectomy. Women in the laparoscopic group had significantly shorter hospital stays than those in the vaginal group. The bleeding complications were mostly due to blood transfusion (2.1% in vaginal and 0.7% in laparoscopic hysterectomy groups) and urinary tract infection (1.0% in vaginal and 1.7% in laparoscopic hysterectomy groups). The surgical injury (intraoperative) complications included mostly surgical laceration of the urinary tract (0.7% in vaginal and 0.3% in laparoscopic hysterectomy groups). Conclusions:Advanced age alone should not be the limiting factor for surgical referral of laparoscopic hysterectomy. The shorter hospital stay and low in-hospital complications associated with laparoscopic, as opposed to vaginal hysterectomies, are important attributes of a surgical procedure essential to the postoperative care in older women aged 65 years or more.