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      • Salvage Chemotherapy in Recurrent Platinum-Resistant or Refractory Epithelial Ovarian Cancer with Carboplatin and Distearoylphosphatidylcholine Pegylated Liposomal Doxorubicin (Lipo-Dox<sup>®</sup>)

        Khemapech, Nipon,Oranratanaphan, S.,Termrungruanglert, W.,Lertkhachonsuk, R.,Vasurattana, A. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

        Background: To evaluate the efficacy and safety of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum resistant or refractory epithelial ovarian cancer (EOC) or fallopian tube cancer. Materials and Methods: A retrospective analysis of women who received DPLD with carboplatin for recurrent EOC or fallopian tube cancer in King Chulalongkorn Memorial Hospital Thailand from January 2006 to August 2011 was conducted. Patients were identified from the medical records and data on demographic factors, stage, histology, surgical findings, cytoreduction status, and prior chemotherapies were abstracted. The efficacy and toxicity of DPLD/carboplatin were evaluated. Progression-free (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 65 patients, 64 with platinum resistant or refractory epithelial ovarian cancer and 1 with fallopian tube cancer, were enrolled. DPLD and carboplatin were given for an average of 4.46 cycles per patient with a total of 273 cycles. Among the 65 evaluable patients, 0% achieved CR, 7.69% PR, 15.4% SD and 76.% PD. The overall response rate was 23.1%. With a median follow-up of 27.4 months, the median progression-free and median overall survival in the 36 patients was 4.46 months and 8.76 months respectively. In the aspect of side effects, palmar-plantar erythrodysesthesia (PPE) occurred in 33.3% (Grade I 22.2%, Grade II 11.1%) and mucositis in 41.7% (Grade I 27.8%, Grade II 13.9%) of all treatment cycles, all Grade 1 or 2. Anemia, leukopenia and thrombocytopenia occurred in 58.3% (Grade I 41.7%, Grade II 16.7%), 66.7% (Grade I 47.2%, Grade II 19.4%), and 22.2% (Grade I 16.6%, Grade II 5.56%) of cycle respectively, and were mostly Grade 1 or 2. Conclusions: DPLD, the second-generation PLD drug combined with carboplatin every 4 weeks, is effective and has low toxicity for treatment of patients with recurrent platinum-resistant or refractory epithelial ovarian cancer.

      • Prevalence and Clinical Significance of Mammalian Target of Rapamycin Phosphorylation (p-mTOR) and Vascular Endothelial Growth Factor (VEGF) in Clear Cell Carcinoma of the Ovary

        Khemapech, Nipon,Pitchaiprasert, Sunaree,Triratanachat, Surang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

        Background: To determine the prevalence of mammalian target of rapamycin phosphorylation (p-mTOR) and vascular endothelial growth factor (VEGF) and any correlation with clinical characteristics and prognosis in ovarian clear cell carcinoma patients. Materials and Method: Seventy four paraffin-embedded specimens of such carcinomas frompatients who underwent surgery, received adjuvant chemotherapy and were followed up at King Chulalongkorn Memorial Hospital during January 2002 to December 2008 were stained with rabbit monoclonal IgG p-mTOR and rabbit polyclonal IgG VEGF using immunohistochemical methods. Medical records were reviewed and clinical variables were analysed. Results: The prevalence of positive p-mTOR in ovarian clear cell carcinoma was 87.9% and significantly higher in advance-stage than early-stage patients (100% versus 83.6%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with positive p-mTOR expression were 60% and 69.2% with no differences from patients with negative p-mTOR expression (p>0.05). The prevalence of VEGF expression was 63.5% and significantly higher in chemo-sensitive than chemo-resistant patients (70.7% versus 37.5%, P<0.05). Two-year disease free survival and 2-year overall survival in patients with VEGF expression were 72.3% and 83% respectively which were significantly different from patients with negative VEGF expression (p<0.05). Conclusions: p-mTOR expression in ovarian clear cell carcinoma was significantly correlated with the stage of disease. VEGF expression was significantly correlated with chemosensitivity, and survival. Further studies of related targeted therapy might be promising.

      • Quality of Life in Ovarian Cancer Patients Choosing to Receive Salvage Chemotherapy or Palliative Treatment

        Srisuttayasathien, Manasawee,Khemapech, Nipon Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Background: The hypothesis that patients who primarily progress on two consecutive chemotherapy regimens without evidence of clinical benefit may opt for supportive care was investigated. The purpose was to determine the quality of life in recurrent ovarian cancer patients choosing to receive salvage chemotherapy in addition to supportive care or palliative care alone. A secondary objective was to evaluate factors that affect quality of life in ovarian cancer patients. Materials and Methods: A descriptive study was conducted in patients who had histological confirmed epithelial ovarian cancer and failed to respond to at least one regimen of chemotherapy, coming for treatment at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand over a six-month period from August 2012-March 2013. Each patient was asked to complete the FACT-G and a general personal questionnaire. The median quality of life score was analyzed. The Mann Whitney U Test was used to compare the difference between salvage chemotherapy and palliative care groups, and the Kruskal Wallis was used to evaluate other variables. Results: Thirty-eight ovarian cancer patients were identified who failed to respond to chemotherapy. Of the 38, 30 chose salvage chemotherapy and eight palliative care for further treatment. By histology the carcimnomas were predominantly endometrioid subtype and poorly differentiated. The majority of patients in this study had FIGO stage III, and ECOG status 0-1. The median quality of life score was 76.3 (35.8-94.0), with no significant differences between the groups. Factors associated with the quality of life were the ECOG score and number of chemotherapeutic courses. Conclusions: In the setting of refractory or recurrent epithelial ovarian cancer, patients who receive salvage chemotherapy have comparable quality of life scores with patients treated with palliative care alone, providing a contrast with previous studies.

      • Palliative Care Education in Gynecologic Oncology: a Survey of Gynecologic Oncologists and Gynecologic Oncology Fellows in Thailand

        Ratanakaaew, A,Khemapech, N,Laurujisawat, P Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

        Background: The main purpose of this study was to survey the education and training of certified gynecologic oncologists and fellows in Thailand. A secondary objective was to study the problems in fellowship training regarding palliative care for gynecologic cancer patients. Materials and Methods: A descriptive study was conducted by sending a questionnaire regarding palliative care education to all certified gynecologic oncologists and gynecologic oncology fellows in Thailand. The contents of the survey included fellowship training experience, caring for the dying, patient preparation, attitudes and respondent characteristics. Statistics were analyzed by percentage, mean and standard deviation and chi-square. Results: One hundred seventy completed questionnaires were returned; the response rate was 66%. Most certified gynecologic oncologists and fellows in gynecologic oncology have a positive attitude towards palliative care education, and agree that "psychological distress can result in severe physical suffering". It was found that the curriculum of gynecologic oncology fellowship training equally emphasizes three aspects, namely managing post-operative complications, managing a patient at the end of life and managing a patient with gynecologic oncology. As for experiential training during the fellowship of gynecologic oncology, education regarding breaking bad news, discussion about goals of care and procedures for symptoms control were mostly on-the-job training without explicit teaching. In addition, only 42.9 % of respondents were explicitly taught the coping skill for managing their own stress when caring for palliative patients during fellowship training. Most of respondents rated their clinical competency for palliative care in the "moderately well prepared" level, and the lowest score of the competency was the issue of spiritual care. Conclusions: Almost all certified gynecologic oncologists and fellows in gynecologic oncology have a positive attitude towards learning and teaching in palliative care. In this study, some issues were identified for improving palliative care education such as proper training under the supervision of a mentor, teaching how to deal with work stress, competency in spiritual care and attitudes on responsibility for bereavement care.

      • Characteristics and Treatment Outcomes of Patients with Malignant Transformation Arising from Mature Cystic Teratoma of the Ovary: Experience at a Single Institution

        Oranratanaphan, Shina,Khemapech, Nipon Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

        Background: Malignant transformation arising in mature cystic teratoma (MCT) is one of the most serious complications of MCT. Squamous cell carcinoma is the most common malignant change. Some clinical findings such as advanced age group and large tumor size are significant risk factors of malignant transformation. This study was conducted in order to evaluate characteristics, cell types, treatment and outcome of malignant transformation arising from dermoid cysts in our institution. Materials and Methods: A retrospective chart review was performed. General characteristics, operative data, procedure, operative finding and operative outcome were analyzed. Statistical assessment was performed with SPSS version 17.0, using mean, mode, median and percentage to describe those data. Results: During the 10 years period, 11 cases of malignant transformation from a total of 753 cases (1.46% incidence) of MCT were reviewed. Mean age of the patients was 41.2 years (SD 4.34, range 24-70). The most common presenting symptom was a palpable mass (8 cases; 72.7%). Primary surgical staging was performed in 4 patients (36.4%). Re-staging was conducted in the other 4. Complete cytoreduction was obtained in 45.5% (5 cases) and optimal surgical resection was obtained in 36.4% (4 cases). Mean tumor size was 14.1 cm. (SD 1.55, range 6-20). Squamous cell carcinoma was found in 36.4% (4 cases) and mucinous cancer in the other 4. More than half of them were stage Ia (54.5%, 6 cases). All patients whose stage more than Ia received chemotherapy (45.5%). Mean disease free survival was 5.53 years (1.32, 0.3-10). Conclusion: According to our study, the incidence of malignant transformation was consistent with previous studies. The common malignant transformation histologic types are both squamous and mucinous carcinoma which differed from previous reports. Early detection for early stage disease and optimal surgery are important for long term survival.

      • Acceptability of Self-Sampling HPV Testing Among Thai Women for Cervical Cancer Screening

        Oranratanaphan, Shina,Termrungruanglert, Wichai,Khemapech, Nipon Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

        Background: Acceptability of self-sampling HPV testing is confirmed worldwide. However, some cultural differences may affect this question. Therefore, this study was conducted to evaluate the acceptability of self-sampling HPV testing in Thai women. Materials and Methods: One hundred women aged 30-65 years with an intact cervix were included in this study. The participants were asked to do the Pap test by physicians and then brush type self-sampling instruments were assigned for self-collection and finally completed a questionnaire for acceptability evaluation. The questionnaire contains 2 parts. Part one covered general information of the participants and part two is the acceptability questions. Results: Mean age was 40.6 years. The incidence of high risk HPV detection in this study was 16%. The most common reason for doing Pap smear was for annual checkup. On the topic of ease of use, 85 % of the subjects agreed. Most of the participants (82%) reported that they felt less pain. However, reliability of the result was not satisfactory because 37% of the participants hesitated to rely on the results of the test. According to the price, if the price is less than 1,000 Baht (32.59 Baht = 1USD), 82% of the subjects would use it for their next screening. Conclusions: The acceptability of self-sampling device in this study is quite good but the reliability of the test was questioned by some of the participants. Moreover, the price of the test in Thailand may also influence the acceptability of the test.

      • Incidence and Clinical Characteristic of Venous Thromboembolism in Gynecologic Oncology Patients attending King Chulalongkorn Memorial Hospital over a 10 Year Period

        Oranratanaphan, S,Termrungruanglert, W,Khemapech, N Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

        Background: Venous thromboembolisms (VTEs) constitute a group of diseases including deep vein thrombosis (DVT) and pulmonary embolism (PE). They regarded as the second leading cause of death in cancer patients and several studies have confirmed that VTEs have a negative impact on survival and recurrent rate in both ovarian and endometrial cancer cases. The incidence of VTEs differs worldwide and depends on several risk factors including race, underlying disease, lifestyle, body weight, BMI and genetic risk factors. There is heterogeneity of DVT rates between Asian and Western countries. This study was conducted in order to evaluate the character and incidence of VTEs in gynecologic oncology patients in King Chulalongkorn Memorial Hospital over a 10 year period. Materials and Methods: A retrospective chart review was performed with VTEs defined as objective diagnosis of acute DVT or PE with typical symptoms and signs. Diagnoses were approved byan internist and/or confirmed with imaging studies. Data from both outpatient and inpatient sessions of the affected cases from January 2004 to December 2013 were extracted. General characteristics of the patients were collected with details of the diseases, types of cancer, stage, date of diagnosis of cancer, operative data, treatment outcome, progression free survival and overall survival. Results: Thirty cases of VTEs were identified in a total 2,316 gynecologic oncology cases. The incidence of symptomatic VTEs in total gynecologic oncology patients in our institution is 1.295%. The incidence of VTEs in ovarian cancer patients in our institution was 5.9%. Duration for VTE detection ranged from 13 months before diagnosis of cancer to 33 months after diagnosis of cancer. Most of the VTE cases were detected in ovarian cancer patients (60%). The most common cell type was adenocarcinoma (moderately to poorly differentiated) which accounted for 26.7% of the cases. The second most common cell type was clear cell carcinoma with 23.3% of the cases. Thirty percent of VTE cases developed before cancer was diagnosed, 20% were diagnosed at the same time as cancer detection and fifty percent developed after cancer was diagnosed. Median disease free survival of the gynecologic oncology patients with VTE was 7.5 months. Median overall survival (OS) was 12 months. Median progession free survivals of DVT and PE groups were 11.5 and 5.5 months, respectively. OS of DVT and PE was 12.0 and 11.5 months respectively. Conclusions: The incidence of VTE in Asian countries is believed to be lower than in European or Western countries. From our retrospective review, the incidence of VTEs in all types of gynecologic oncology was 1.295%, much lower than reported in the West. The reason for the lower incidence may genetic differences. Another factor is that VTE in this review was symptomatic, which is less than asymptomatic VTE. More than half of VTEs in this study developed in ovarian cancer patients. The results are compatible with earlier reports that among gynecologic malignancies, the incidence of VTE is highest in ovarian cancer.

      • KCI등재

        Cost effectiveness analysis of HPV primary screening and dual stain cytology triage compared with cervical cytology

        Wichai Termrungruanglert,Nipon Khemapech,Tanitra Tantitamit,Piyalamporn Havanond 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.2

        Objectives: To assess the clinical and cost-effectiveness of human papillomavirus (HPV) primary screening triage with p16/Ki-67 dual stain cytology compared to cytology. Methods: We conducted an Excel®-based budget impact model to estimate the preinvasive and invasive cervical cancer cases identified, mortality rate, direct medical costs, qualityadjusted life years (QALYs) and the incremental cost-effectiveness analysis of two strategies from the healthcare payer perspective. The study population is a cohort of women 30–65 years of age presenting for cervical screening. Results: HPV primary screening triage with p16/Ki-67 dual stain showed higher sensitivity without losing specificity compared to conventional Pap smear. The improving the screening performance leads to decrease the prevalence of precancerous lesion, annual incidence and mortality of cervical cancer. The incidence of cervical cancer case detected by new algorithm compared with conventional method were 31,607 and 38,927, respectively. In addition, the new algorithm was more effective and more costly (average QALY 24.03, annual cost $13,262,693) than conventional cytology (average QALY 23.98, annual cost $7,713,251). The incremental cost-effective ratio (ICER) per QALY gained was $1,395. The sensitivity analysis showed if the cost of cytology and HPV test increased three times, the ICER would fall to $303/QALY gained and increased to $4,970/QALY gained, respectively. Conclusion: Our model results suggest that screening by use of HPV genotyping test as a primary screening test combined with dual stain cytology as the triage of HPV positive women in Thai population 30–65 years old is expected to be more cost-effective than conventional Pap cytology.

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