Kung-Liahng Wang

Neuroendocrine carcinoma of the uterine cervix : A clinicopathologic retrospective study of 31 cases with prognostic implications

Abstract The present study describes 31 clinical cases of neuroendocrine cervical carcinoma (NECC) treated at Mackay Memorial Hospital between January 1, 1991 and October 31, 2003. There are two cases of atypical carcinoid tumor (ACT), four cases of large-cell neuroendocrine carcinoma (LCNEC), and 25 cases of small-cell neuroendocrine carcinoma (SCNEC). Overall survival did not differ significantly in relation to surgery, tumor histology, age, FIGO stages, chemotherapeutic regimens or lymph node involvement. The specimens available did not permit HPV (human papillomavirus)-DNA analysis in 5 cases (5/31, 9.7%). The HPV viral infection was absent in 8 cases (8/31, 26%); 17 cases of HPV-18 (17/31); and 1 case of HPV-16 (1/31). The prognosis between mixed and pure type histologic patterns is not significant. The mean survival time for all patients was 32.3 months. The 2-year and 5-year survival rates were 54.8% and 31.5% for all patients. The results of this study reaffirm the biologically aggressive nature of this rare malignancy, its low survival rate, and its very unpredictable prognostic factors. Effective treatments of neuroendocrine cervical tumor still remain inconclusive. Further efforts are still required to identify prognostic factors for this uncommon disease.

The psychological impact of illness among women experiencing human papillomavirus-related illness or screening interventions

The present study describes the psychological impact of human papillomavirus (HPV)-related conditions or preventive interventions on Taiwanese women. Women with an HPV-related diagnosis or intervention within the past 3 months were invited to participate in a cross-sectional survey before the receipt of HPV-related diagnostic results. Participants completed a 29-item HPV impact profile (HIP), which was a questionnaire designed to represent the full spectrum of potential HPV-related impacts. The HIP assesses worries and concerns; emotional impact; sexual impact; self-image; partner issues and transmission; interactions with doctors; and control/life impact. The final sample size was 249 women from three hospitals. The mean HIP score (0–100) was normal Pap: 28.2; abnormal Pap: 44.3; CIN: 47.5; genital warts: 62.5; abnormal Pap with high-risk HPV positive: 48.8. This study indicates that significant psychological impact is found in women diagnosed with abnormal Pap, CIN, high-risk HPV test positive and genital wart compared to women with a normal Pap. Women with genital warts had the highest psychological impact scores. This is the first quantitative data that can lay the ground work for future studies that enable the comparison of the effectiveness of different interventions in alleviating the psychological burden of HPV-associated infection and preventive interventions in Taiwan.

Human papillomavirus and vaccination in cervical cancer.

Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN]) evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV) infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA) and bivalent Cervarix (GlaxoSmithKline, London, UK). This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer.

Prenatal diagnosis of otocephaly with microphthalmia/anophthalmia using ultrasound and magnetic resonance imaging

A 30-year-old primigravid woman was referred to hospital at 29 weeks’ gestation because of polyhydramnios and regular uterine contractions. She and her husband were non-consanguineous and healthy. There was no family history of congenital malformations, nor any history of teratogenic medication, recent infection, diabetes mellitus, or hypertension during this pregnancy. A level II, twodimensional (2D) ultrasound examination revealed a single live fetus with a biparietal diameter of 7.99 cm (appropriate for 29 weeks’ gestation), a femur length of 5.4 cm (29 weeks), an abdominal circumference of 24 cm (29 weeks), polyhydramnios with an amniotic fluid index of 45 cm, absence of the mandible, hypotelorism, lowset ventromedially displaced ears, left microphthalmia with an ocular diameter of 1.29 cm (< 5th centile), and right anophthalmia with absence of the right lens (Figure 1). A tentative diagnosis of otocephaly was made. Magnetic resonance imaging (MRI) demonstrated agnathia and right anophthalmia (Figure 2). The other internal organs were unremarkable. A 1404-g female baby (Figure 3) was delivered 1 day later because of premature rupture of the membranes and preterm labor. The proband died shortly after birth. Autopsy confirmed the diagnosis of otocephaly, which was characterized by the isolated agnathia, aglossia, microstomia, and synotia without central nervous system and other organ defects except for the ocular abnormalities of left microphthalmia and absence of the right lens. The karyotype of the proband was 46,XX. Computed tomography (CT) scans following three-dimensional (3D) reconstruction showed a characteristic otocephalic skull (Figure 4). Prenatal diagnosis of otocephaly using 2D and 3D ultrasound has been well described in the literature1–5. To the best of our knowledge, this

Human Papillomavirus Type and Clinical Manifestation in Seven Cases of Large-cell Neuroendocrine Cervical Carcinoma

Large-cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a very rare malignancy. We aimed to investigate the role of human papillomavirus (HPV) on the survival of patients, and its correlation with clinical parameters of HPV status or survival outcomes. Only seven cases of LCNEC were retrospectively collected among 8018 (0.087%) invasive cervical carcinomas from the cancer registry systems at Mackay Memorial Hospital and Veterans General Hospital over a period of 17 years. The median survival time was 17.2 months, including only one long-term survivor (> 5 years). The 2 year and 5-year survival rates after diagnosis were 42% and 30%, respectively. The results indicated that the majority of LCNEC cases were dominated by high-risk HPV-18. No clinical parameters appeared to be associated with HPV-18 or survival outcomes of LCNEC patients. Pelvic lymph node metastasis positivity could also be considered as a prognostic factor for this disease.

Concurrent Cisplatin-Based Chemoradiation for Cervical Carcinoma: Tumor Response, Toxicity, and Serum Cytokine Profiles

Purpose. To evaluate the relation between tumor response, treatment toxicity, and serum cytokine profiles in patients with cervical cancer receiving cisplatin-based chemoradiation. Patients and Methods. Forty-two patients with cervical carcinoma receiving chemoradiation were recruited. Hemogram, biochemistry profile, cytokine levels, tumor size, and toxicity were assessed weekly. Results. The absolute neutrophil count decreased accompanied by an increase in serum levels of G-CSF during chemoradiation. The sudden elevation of serum TGF-β 1 and VEGF levels after the first fraction of brachytherapy accompanied with the development of greater radiation therapy (RT) morbidity. Lower pretreatment TGF-β 1 and VEGF levels are associated with tumor response to chemoradiation. Conclusion. The serial changes in serum cytokines during chemoradiation may correlate with tumor regression and treatment morbidity.

Term pregnancy with umbilical cord prolapse.

OBJECTIVE To investigate the incidence, management, and perinatal and long-term outcomes of term pregnancies with umbilical cord prolapse (UCP) at Mackay Memorial Hospital, Taipei, from 1998 to 2007. MATERIALS AND METHODS For this retrospective study, we reviewed the charts, searched a computerized birth database, and contacted the families by telephone to acquire additional follow-up information. RESULTS A total of 40 cases of UCP were identified among 40,827 term deliveries, an incidence of 0.1%. Twenty-six cases (65%) were delivered by emergency cesarean section (CS). Of the neonates, 18 had an Apgar score of <7 at 1 minute, 10 of these scores being sustained at 5 minutes after birth, and three infants finally died. Eleven UCPs occurred at the vaginal delivery of a second twin, and nine with malpresentation. All of the infants who had good perinatal outcomes also had good long-term outcomes. Poor perinatal outcomes occurred in cases where there was a delayed diagnosis, or an inability to carry out an emergency CS or a prompt vaginal delivery. CONCLUSION Early detection of UCP and expeditious delivery are crucial to good perinatal outcomes. An emergency CS remains the mainstream management. Multiparous women whose cervixes are nearly fully dilated and who are expecting babies relatively smaller than their elder brothers or sisters born vaginally may still have vaginal deliveries managed by well-experienced birth teams, with good perinatal outcomes. Otherwise, vaginal delivery is not recommended and CS is the wiser choice.

Safety and efficacy of unidirectional barbed suture in mini-laparotomy myomectomy.

OBJECTIVE To estimate the safety and effectiveness of unidirectional knotless barbed suture compared to the traditional suture for repair of uterine wall defects through myomectomy via mini-laparotomy. MATERIALS AND METHODS This was a prospective clinical study performed by a single surgeon in a medical center. Sixty-eight women with symptomatic myoma were enrolled. Their uterine wall defects were repaired either by unidirectional knotless barbed suture (Group A) or by traditional suture (Group B). The surgical time, intraoperative blood loss, and number of myomas in the two groups were analyzed by two-sample t test. RESULTS Surgical time required from skin incision to complete closure was significantly lower in Group A than in Group B (50.2 ± 16.49 vs. 69.1 ± 25.33 min) (p = 0.0008). The intraoperative blood loss was also lower in Group A (mean, 260.9 mL; range, 20-850 mL) than in Group B (mean, 394.7 mL; range, 50-2200 mL) but not statistically significant. CONCLUSION The unidirectional knotless barbed suture may facilitate the repair of uterine defects during mini-laparotomy myomectomy by significantly lowering operative time. It may also reduce the intraoperative blood loss.

Survival analysis of Stage IIA1 and IIA2 cervical cancer patients.

OBJECTIVE The aim of this study was to assess the benefits of the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for survival of patients with Stage IIA1 and IIA2 cervical cancer (Cx Ca). MATERIALS AND METHODS A study cohort of 51 patients with Stage IIA Cx Ca was retrospectively collected from the 2004-2009 hospital-based, long-form Cx Ca data registry at Mackay Memorial Hospital (Taipei, Taiwan). The survivorship and overall survival were compared between these two groups (Stages IIA1 and IIA2) using log-rank test. RESULTS Thirty-six and 15 patients were classified into Stages IIA1 and IIA2, respectively. Stage IIA2 patients were younger than those with Stage IIA1 disease (mean age, 47.4 vs. 55.1 years, p = 0.008), but no significant difference was observed in confirmed pelvic lymph node status (21.4% vs. 38.5%, p = 0.280) between them. Although the 2-year and 5-year overall survival was better among Stage IIA1 patients, there was no significant difference in survival between Stage IIA1 and IIA2 groups (2-year, 90.6% vs. 77.8%; 5-year, 86.3% vs. 51.9%, p = 0.218). CONCLUSION Although there was a trend in survival difference between Stage IIA1 and IIA2 patients, the difference was not statistically significant. The revised FIGO 2009 staging system for Cx Ca defines a group of Stage IIA patients with bulky tumor (Stage IIA2) that are generally younger than Stage IIA1 patients. It is sensible to investigate an alternate or enhanced treatment scheme for Stage IIA2 patients. Ideally, the treatment scheme should prevent unnecessary radical surgery if a patient can be exposed to either chemotherapy or radiotherapy, alone or in combination.

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.