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Aim: The aim of this study was to explore the effects of ABCB1 and SLCO1B1 gene polymorphisms and the methotrexate (MTX) treatment response in patients with low-risk gestational trophoblastic neoplasia (GTN). Materials & methods: Low-risk GTN patients who received MTX as a first-line single agent were enrolled. DNA was extracted from peripheral blood samples from 18 patients and assessed for ABCB1 C3435T and SLCO1B1 T521C. Results: ABCB1 C3435T and SLCO1B1 T521C polymorphisms were not associated with the MTX response or toxicity in Thai patients Conclusion: The selected ABCB1 and SLCO1B1 polymorphism do not predict the risk of MTX resistance in low-risk GTN.

Objective to evaluate the role of microsatellite genotyping in discordant results between morphologic examination and p57Kip2 staining in hydatidiform mole. Materials and methods 127 cases of hydatidiform mole who had morphologic examination and p57Kip2immunohistochemical staining were evaluated. Six discrepant cases between morphologic examination and p57Kip2 staining were recruited. DNA was extracted from chorionic villi and paired maternal decidual tissue in Formalin fixed paraffin embedded tissue sections. The STR DNA genotyping was performed by Applied Biosystems 3500 Genetic Analyzer. Genetic data analysis was performed by Gene mapper ID-X software. Three concordant cases were used as control. Results were compared to histopathology, p57Kip2 stain and development of post-molar GTN. Results All controlled cases were confirmed PHM. Two cases of histologic CHM with positive p57Kip2and 2 cases of PHM with negative p57Kip2 were reported as PHM from microsatellite. Other 2 cases of histologic diagnosis PHM with negative p57Kip2 reported as CHM from microsatellite test and both of them developed post-molar GTN. Conclusion Microsatellite genotyping is a high accuracy method for differential diagnosis from complete and partial hydatidiform moles. However, cost of microsatellite genotyping is still too high to use routinely. Therefore, selected use in discrepancy cases may be suitable.

Introduction Protein expression in cells are associated with oncogenesis. This study aims to explore proteomic profiles and discover potential biomarkers that can predict malignant transformation of hydatidiform mole. Methods Retrospective analysis was done in 14 cases of remission hydatidiform mole and 14 cases of hydatidiform mole who later developed malignancy (GTN group). Molar tissues were retrieved from −70 °C frozen tissue. Subsequently, a large-scale proteomic analysis was performed to identify proteins and compare their abundance levels in the preserved molar tissues from these two groups using a dimethyl-labeling technique coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results A total of 2,153 proteins were identified from all samples. 22 and 10 proteins were significantly up-regulated and down-regulated, respectively, in the GTN group compared with the mole group. These altered proteins were found in several biological groups such as cell-cell adhesion, secreted proteins, and ribonucleoproteins. Several hormone-related proteins were among the most up-regulated proteins in the GTN group including choriogonadotropin subunit beta (β-hCG) and alpha (α-hCG), growth/differentiation factor 15, as well as both pregnancy-specific beta-1-glycoproteins 2 and 3. In contrast, protein S100-A11 and l -lactate dehydrogenase A chain, were down-regulated in molar tissue from most patients in the GTN group. Discussion This study identified a set of differentially expressed proteins in molar tissues that could potentially be further examined as predictive biomarkers for the malignant transformation of CHMs. A molar proteome database was constructed and can be accessible online at http://sysbio.chula.ac.th/Database/GTD_DB/Supplementary_Data.xlsx .

Background Vulvar lesion is one of the common gynecologic problems. Objective To assess the proportion of vulvar premalignant and malignant lesions in overall vulvar specimens and to evaluate the clinicopathologic features of each vulvar lesion in King Chulalongkorn Memorial Hospital (KCMH). Methods Pathological microscopic slides and medical records of the patients who underwent vulvar-related operations between January 1, 2002 and December 31, 2015 were reviewed. Patients’ clinical characteristics and pathologic features were evaluated and analyzed. Results A total number of 700 patients were included. The proportion of malignant and premalignant lesions in overall vulvar specimens were 16.3% and 8.4%, respectively. Squamous cell carcinoma was the most common malignant vulvar lesion (48.2%), whereas vulvar intraepithelial neoplasia 1 (VIN1) (33.9%) was the most common lesion in the premalignant group. On multivariate analysis, four clinical factors were significantly associated with malignancy risk: increased parity (odds ratio [OR] 1.19, P = 0.010), large tumor size (OR 2.00, P < 0.001), lesion at clitoris (OR 16.67, P = 0.002), and erythematous lesion (OR 2.41, P = 0.026). Conclusions The proportion of malignant and premalignant lesions in overall vulvar specimens was 24.7% in KCMH. Increased parity, large tumor size, clitoris-located lesion, and erythematous lesion were associated with increasing malignancy risk.

Objectives Methotrexate has long been used successfully and is preferred worldwide for the treatment of low-risk gestational trophoblastic neoplasia. However, 26.4% of patients develop resistance and require changes to second-line chemotherapy. In the search for personalised treatment approaches, a link has been found between the pharmacogenomics of methotrexate and the response in various diseases. The aim of this study was to explore the effects of ABCB1 and SCLO1B1 gene polymorphisms and the methotrexate treatment response in patients with low-risk gestational trophoblastic neoplasia. Secondary objectives were to investigate the association of single nucleotide polymorphism (SNP) genotypes with toxicity profiles, and to evaluate other factors associated with the response. Methods Records of all patients with low-risk gestational trophoblastic neoplasia were reviewed and patients who received methotrexate as a single agent were invited to participate in the study. DNA was extracted from peripheral blood samples from 18 patients and assessed for ABCB1 (3435C>T) and SCLO1B1 (521T>C). Results For the ABCB1 polymorphism, CT was the most common genotype (61.1%), followed by CC (27.8%) and TT (11.1%), indicating that TT had a 1.6-fold higher risk of methotrexate-resistance when compared to the wild-type and heterozygous alleles. The risk of methotrexate-related toxicity was 2.67-fold higher in CT/CC patients who showed a better response to methotrexate. The SCLO1B1 polymorphism was not associated with treatment outcomes. Conclusions ABCB1 polymorphism might be useful as a biomarker for predicting the response to methotrexate in patients with low-risk gestational trophoblastic neoplasia.

Purpose To determine the significance of P57KIP2 immunohistochemistry expression in the histopathological diagnosis of hydatidiform mole. Materials and methods Hydatidiform mole patients at King Chulalongkorn Memorial Hospital between January 1999 and December 2011 were recruited. Two gynecologic pathologists reviewed histopathologic slides to confirm diagnosis. Formalin-fixed, paraffin-embedded tissue sections were stained using a bstandard immunostaining system with monoclonal antibodies against P57KIP2 protein. Correlations among pathological features, immunohistochemical expression and clinical data were analyzed. Results One hundred and twenty-seven hydatidiform mole patients were enrolled. After consensus review, 97 cases were diagnosed as complet (CHM) and 30 cases as partial (PHM). Discordance between the first and final H and E diagnoses was found in 19 cases (14.9%, k= 0.578). Significant pathological features to classify the type of hydatidiform mole are central cisterns, trophoblastic proliferation, trophoblastic atypia, two populations of villi, fetal vessels and scalloped borders. After performing immunohistochemistry for P57KIP2, 107 cases were P57KIP2 negative and 20 cases positive. Discordant diagnoses between final H and E diagnosis and P57KIP2 immunohistochemistry was identified in 12 cases (9.4%). Sensitivity of final H and E diagnosis for CHM was 89.7%; specificity was 95.0%. PHM sensitivity and specificity of final H and E diagnosis was 95.0% and 89.7%, respectively. Conclusions Histopathological diagnosis alone has certain limitations in accurately defining types of hydatidiform mole; P57KIP2 immunohistochemistry is practical and can be a useful adjunct to histopathology to distinguish CHM from non-CHM.

ObjectivesStudies have shown improved patient quality of life with supportive care rather than aggressive treatment at the end of life. This study evaluated the symptoms that patients in Thailand with gynecologic cancers experienced and the interventions that they received at the end of life.MethodsThe medical records of patients admitted to a tertiary cancer center in Thailand who died in the hospital from gynecologic malignancies between January 1, 2011 and December 31, 2016 were reviewed. Inclusion criteria were patients who had been been diagnosed with gynecologic cancers (ovarian, endometrial, cervical, vulvar, or peritoneal cancers or uterine sarcomas) and had died in the hospital during that period. Patients whose medical records were incomplete or unavailable were excluded from the study. Data on demographics, symptoms, interventions, and end-of-life care were collected.ResultsA total of 159 patients were included in this analysis. The mean age at death was 54.3 (range 15–91) years. Over half (54.7%) of the patients were diagnosed with ovarian or peritoneal cancer, 26.4% with uterine cancer or sarcoma, 16.4% with cervical cancer, and 1.3% with dual primary cancers. Symptoms at time of admission were poor oral intake (68.6%), abdominal distention or discomfort (63.5%), pain (42.8%), nausea or vomiting (35.2%), and fever or signs of infection (27.0%). The mean number of hospitalizations during the last 6 months was 3.6. Thirty-six patients (22.6%) had major surgery during the last 6 months of life, with 14 patients (8.8%) having it performed during their last admission before death. The mean length of the last hospital stay was 22.3 (range 6–31) days, and 61 patients (38.4%) were admitted to the intensive care unit. Eleven patients (6.9%) had chemotherapy in their last 14 days of life and 10 (6.3%) received cardiopulmonary resuscitation. Almost all patients (153, 96.2%) had do-not-resuscitate (DNR) consents. The mean time between the DNR consent and death was 6.3±9.7 days.ConclusionMultiple hospital admissions, aggressive treatments, and invasive procedures were common among patients with gynecologic cancer at the end of life. Better symptom management, end-of-life preparation, and communication are needed to enhance patients’ quality of life in Thailand.

Background: Adjuvant chemotherapy is a required treatment for most patients with epithelial ovarian cancer (EOC) or peritoneal cancer. However, it has many adverse events which may affect oncologic outcomes. Active hexose correlated compound (AHCC) has been reported to be an immunoenhancer to decrease adverse events of chemotherapy. Materials and Methods: Patients were randomized and allocated to receive either AHCC three grams/day (500mg/ capsule) or placebo. These drugs were administrated as two capsules orally three times a day throughout six cycles of chemotherapy. The primary outcome was a change of CD4+ and CD8+ T cell lymphocytes in peripheral blood samples from baseline to completion of chemotherapy. Secondary outcomes were rate of bone marrow suppression, adverse events and quality of life (QOL) as assessed by Thai version of the Functional Assessment of Cancer Therapy-General (FACT-G). Results: Study outcomes were analyzed in 28 patients, 14 patients in each group. Changes in CD4+ and CD8+ T cell lymphocytes levels were not significantly different between AHCC and placebo group; 43.5/ul (-237.5, 143.3) versus -69.5 /ul (-223.8, 165) for CD4+ level, p=0.61 and 49.5.0 /ul (-80, 153.3) versus 4.0 /ul (-173, 62.5) for CD8+ level, p=0.19. However, CD8+ levels were significantly higher in the AHCC group at the sixth cycle of chemotherapy; 392.5.0 /ul (310.8, 598) versus 259.5 /ul (170.5, 462.3), p=0.03. There was no difference in bone marrow suppression and QOL between the two groups. Adverse events in terms of nausea and vomiting significantly decreased but muscle pain significantly increased in the AHCC group. Conclusions: Changes in CD4+ and CD8+ T cell lymphocytes from baseline were not significantly increased in AHCC group. However, CD8+T cell lymphocytes levels were significantly higher in the AHCC group at the sixth cycle of chemotherapy.

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.

To evaluate changes in treatment outcomes and epidemiologic profiles of gestational trophoblastic neoplasia (GTN) patients over a 20-year period.This retrospective study recruited all GTN patients who were treated at King Chulalongkorn Memorial Hospital during the period January 1994-December 2013. Clinical data were collected. Statistical analyses were performed, with p values0.05 considered statistically significant.There were 183 GTN cases during the study period, resulting in an incidence of 1.03 cases per 1,000 deliveries. Fifty-five cases (30.1%) were diagnosed as GTN following nonmolar pregnancy, and 128 cases were identified as postmolar GTN. A total of 113 cases were diagnosed as stage I, 12 as stage II, 40 as stage III, and 17 as stage IV; 125 cases (68.3%) were clas- sified as low risk, and 57 cases (31.1%) as high risk. Actinomycin D was the most frequently used first-line single-agent chemotherapy (98 cases), and VAC regimen was the most frequently used combination chemotherapy (24 cases). EMACO regimen was the most frequently used second-line chemotherapy (11 cases). The median number of chemotherapy courses was 4.5 courses in the first decade and 6 courses in the second decade of our study (p = 0.005). Median duration of treatment was 72 days (range, 7-491 days). Overall remission rate was 82.6%, with rates of 76% in the first decade and 90.8% in the second decade of the study (p=0.03).Incidence of high-risk GTN increased over the course of the study period at our national referral hospital. Improvement in patient outcomes was observed, being directly associated with improved targeted chemotherapy regimens.

The purpose of this study was to evaluate the incidence of pelvic/para-aortic node metastases and the other pathological characteristics from medical records of patients with endometrial carcinoma treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between1996 and 2005. The records of 213 patients with endometrial carcinoma who had complete surgical staging were reviewed. A particular focus was on clinically early-stage disease. Clinical staging could be determined in 206 patients. Of the 206 patients, 182 (88.3%) presented with clinical stage I disease. However, only 142 (78%) of these patients were confirmed as surgical stage I and 22% were upstaged. Preoperative histologic grade was diagnosed inaccurately in 15.9% of patients and 7.7% were upgraded. Of patients with preoperative histologic grade 1, 33% had deep myometrial invasion, 8.2% had pelvic node metastasis, and 3.3% had para-aortic node metastasis. Even in clinical stage IaG1, pelvic node metastasis occurred in 5.6% and para-aortic node metastasis in 1.3%. It has been suggested that complete surgical staging may not be necessary in patients with low-risk endometrial carcinoma who have disease limited to the uterus without grade 3 or deep myometrial invasion. However, proper selection of such low-risk patients remains problematic. In situations where there is limited preoperative and intraoperative assessment of high-risk factors, particularly radiographic imaging and frozen section assessment, the role of complete surgical staging is beneficial.

BACKGROUND The incidence of hydatidiform mole (HM) differs among regions but has declined significantly over time. In Thailand, the initiation of universal health coverage in 2002 has resulted in a change of medical services countrywide. However, impacts of these policies on gestational trophoblastic disease (GTD) cases in Thailand have not been reported. This study aimed to find the incidence of hydatidiform mole (HM) in King Chulalongkorn Memorial Hospital (KCMH) from 1994-2013, comparing before and after the implementation of the universal coverage health policy. MATERIALS AND METHODS All cases of GTD in KCMH from 1994-2013 were reviewed from medical records. The incidence of HM, patient characteristics, treatment and remission rates were compared over two study decades between 1994-2003 and 2004-2013. RESULTS Hydatidiform mole cases decreased from 204 cases in the first decade to 111 cases in the seond decade. Overall incidence of HM was 1.70 per 1,000 deliveries. The incidence of HM in the first and second decades were 1.70 and 1.71 per 1,000 deliveries, respectively (p=0.65, 95%CI 1.54-1.88). Referred cases of nonmolar gestational trophoblastic neoplasia (GTN) increased from 12 (4.4%) to 23 (14.4%, p

To study the correlation between serum and urine hCG levels in gestational trophoblastic disease (GTD) patients with low hCG level. The correlation between serum hCG and results from urine pregnancy tests are evaluated along with quantitative measurement.In this prospective study, 86 cases of gestational trophoblastic disease patients with positive and low level of serum hCG (100 mIU/ml) were recruited. Quantitative serum hCG urine hCG and urine pregnancy test were performed. The correlation coefficients between serum and urine hCG were then analyzed by SPSS 16.0. Furthermore, the levels of serum hCG were compared to the results of the urine pregnancy test.From February 2006 to June 2008, 86 cases were recruited for this study. The correlation coefficient between serum and urine hCG levels in all cases was 0.44 (using Pearson correlation), p = 0.01. In subgroup analysis, the correlation coefficient between serum and urine hCG levels in chemosensitive gestational trophoblastic neoplasia (GTN) patients (n = 27) was 0.73, p ≤ 0.01. The correlation coefficient in chemoresistant GTN patients (n = 38) was 0.29, p = 0.07; and the correlation coefficient in hydatidiform mole patients (n = 21) was 0.47, p = 0.03. A urine pregnancy test was positive only in 10 of 86 specimens.The correlation coefficient between serum and urine hCG in GTD patients with low hCG level showed significant correlation. However, patients with chemoresistance had less correlation than those with chemosensitivity and hydatidiform mole. Urine pregnancy test had low correlation with urine hCG and was not useful in this group of patients.

Objectives This study aimed to evaluate the efficacy and toxicity of gemcitabine in combination with cisplatin as neoadjuvant therapy in patients with cervical carcinoma stage IB2. Patients and methods Chemotherapy-naive patients with histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were treated with 2 cycles of cisplatin (70 mg/m2 on day 1) and gemcitabine (1000 mg/m2 on days 1 and 8), given every 21 days. After chemotherapy, patients underwent radical hysterectomy and pelvic lymphadenectomy. Patients judged to have a non-resectable disease were treated with standard pelvic radiation. Results Between September 2000 to March 2004, 28 patients were enrolled in the study, of which 27 were evaluable for efficacy and toxicity. The mean age was 39 years (30–55). The overall clinical response rate was 88.9% (24/27), with complete response (CR) in 9/27 patients (33.3%) and partial response in 15/27 patients (55.5%). Three patients (11.1%) did not respond and nobody progressed. A pathological CR was noted in 2 of 24 patients who underwent radical surgery. The 3 non-responding patients were subsequently treated with radiation and achieved CR. Grades 3 or 4 neutropenia, anemia, or thrombocytopenia was observed in 18.5%, 7.4%, and 3.7% patients respectively. Non-hematological toxicity was mild except grade 3 nausea/vomiting in 18.5% patients. At median follow-up time of 36.7 months (range 7–51 months), the 3-year survival was 88.9%. Conclusion Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with cervical cancer (stage IB2) appears encouraging, with manageable and acceptable toxicity profile.

Background Gestational trophoblastic neoplasia (GTN) is a malignant disease which occurs in women of reproductive age. Treatment of GTN has an excellent outcome and further pregnancies can be expected. However, data concerning quality of life in these cancer survivor patients are limited. This study aimed to assess quality of life in women who were diagnosed with GTN and remission after treatment, and to determine factors that may affect quality of life status. Materials and methods This cross sectional study was conducted from July 2013 to May 2014 in the Gestational Trophoblastic Disease Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients who were diagnosed GTN and complete remission were recruited. Data collection was accomplished by interview with two sets of questionnaires, one general covering demographic data and the other focusing on quality of life, the fourth version of Functional Assessment of Cancer Therapy (FACT-G). Descriptive statistics were used to determine general data and quality of life scores. Students t-test and one way ANOVA were used to compare between categorical and continuous data. Results Forty four patients were enrolled in this study. The overall mean quality of life score (FACT-G) was 98.2. The overall FACT-G score was not significantly correlated with age, education level, stage of disease, treatment modalities, and time interval from remission to enrollment. However, patients who needed further fertility showed significant lower FACT-G scores in the emotional well-being domain (p=0.02). Conclusions Overall quality of life scores in post-treatment gestational trophoblastic neoplasia patients are in the mild impairment range. Patients who desire fertility suffer lower quality of life in the emotional well-being domain.

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN).Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN.Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p= 0.003) and theuCuC of LINE-1 increased in the malignant trophoblast group (p≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowestpvalue for distinguishing between the two groups (p< 0.001). The combination of the pretreatmentβ-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively.Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD= 13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

To investigate the role of PTEN and MDM2 expression in hydatidiform mole in the prediction of postmolar gestational trophoblastic neoplasia (GTN).A total of 145 cases of hydatidiform mole were diagnosed at the King Chulalongkorn Memorial Hospital from 1999 to 2010. Patients were classified into 2 groups: spontaneous remission and patients with postmolar GTN. Clinicopathologic features and immunohistochemical staining by PTEN and MDM2 were reviewed. The results were analyzed in correlation to the clinical characteristics and outcomes.Of 145 recruited cases, 128 (88.3%) cases were complete hydatidiform mole (CHM) and 17 (11.7%) cases were partial hydatidiform mole (PHM). Postmolar GTN was clinically diagnosed in 42 cases (28.9%). The incidences of postmolar GTN following CHM and PHM were 29.7% and 23.5%, respectively. Mean age of the postmolar GTN group was significantly older than that of the remission group (31.2 vs. 27.8, p = 0.04). There was no significant difference of pathologic features between cases with remission and postmolar GTN. Immunoreactivity of PTEN and MDM2 were similarly present in trophoblastic cells of both CHM and PHM groups without significantly different patterns.Immunohistochemical expression of PTEN and MDM2 in hydatidiform mole cannot predict molar malignant transformation.

To determine the correlation between serum placental growth factor (PlGF) and human chorionic gonadotropin (hCG) in patients with gestational trophoblastic disease (GTD) and to compare serum levels of PlGF in patients with gestational trophoblastic neoplasia to those of patients with hydatidiform mole.Blood and urine samples were collected from GTD patients. Blood and urine levels for PlGF were processed and quantitated by enzyme-linked immunosorbent assay in parallel with serum levels for hCG. Correlation levels of serum PlGF and hCG were analyzed. Serum levels of PlGF and hCG were correlated with the clinical manifestations of GTD.The correlation between serum levels of PlGF and hCG was not linear (r = 0.274, p = 0.229). The median PlGF levels in benign and malignant groups were 24.0 and 38.3 pg/mL, respectively (p = 0.014). The median serum hCG levels in benign and malignant groups were 7,335.0 and 9,974.5 mlU/mL, respectively (p = 0.942). The linear correlation between urine and serum levels for PlGF was not detected (r = 0.064).Levels of correlation for serum PlGF and hCG in GTD patients were not linear. Median serum levels of PlGF between benign and malignant groups were significantly different. This suggests that there is a higher production of PlGF levels in patients with choriocarcinoma or malignant GTD.

To determine whether teaching skill is associated with knowledge or clinical performance in Obstetrics and Gynecology residents, King Chulalongkorn Memorial Hospital, ThailandA questionnaire evaluating residents' teaching skills was completed by medical students using a global rating scale. The results were compared with the residents' score from in-training examination and clinical performance score from the medical staff Correlation between teaching skill and knowledge, teaching skill, and performance was done by using bivariate correlation.Forty-nine medical-students were enrolled to evaluate residents' teaching skills. Twenty-eight Obstetrics and Gynecology residents were evaluated in the present study. The correlation between teaching skill and knowledge was not significant (r = 0.066; p = 0.25). The correlation between teaching skill and clinical performance was not significant (r = 0.172; p = 0.28). However clinical performance and knowledge showed a significant correlation (r = 0.558; p = 0.002).Clinical performance and knowledge had no correlation with teaching skill in Obstetrics and Gynecology residents. However results of the present study show that clinical performance and knowledge had positive correlation. Training courses are recommended to increase residents' abilities in the range of teaching skills.

To determine outcomes of patients with early stage epithelial ovarian cancer (EOC) who underwent incomplete surgical staging with those who had complete surgical staging.Retrospective chart reviews were performed on early EOC (FIGO Stage I-II) patients who had registered in the Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital between 1994 and 2003. Two groups of patients were identified, patients who underwent incomplete surgical staging (n = 51) and those who had complete surgical staging (n = 50). Recurrence rate and disease free interval were demonstrated. The 5 years survival was estimated using Kaplan-Meire methodBetween 1994 and 2003, 101 patients presented with early EOC. The median age at presentation was 48 years (range, 24-86). Histology distribution showed clear cell carcinoma in 35 cases (34.7%), mucinous carcinoma in 25 cases (24.8%), endometrioid carcinoma in 22 cases (21.8%), mixed epithelial cancer in 10 cases (9.9%), and serous carcinoma in nine cases (8.9%). Fifty-one cases (50.5%) underwent incomplete surgical staging initially. Recurrent rate in the incomplete surgical staging group was 11.8% compared with 14% in complete surgical staging group (p = 0.257). At the median follow up of 60 months, 50.5% of patients survived The 5 years survival rate of incomplete surgical staged was 82.4% and 94.6%, in complete surgical staged (p = 0.404), when focused in the subgroup analysis, incomplete staging group with histology grade 3 compared to complete staging group. They had overall 5 years survival rate 81.1% vs. 88.4% (p = 0.037). Patients with stage II who underwent incomplete staging or complete staging had an overall survival rate 63% vs. 92.3% (p = 0.012).In King Chulalongkorn Memorial Hospital, overall outcome of patients with early stage epithelial ovarian cancer who had incomplete staging was no different from patients who had complete staging. However, patients who had incomplete staging with grade 3 or stage II tended to have less recurrent rate and survival time.

To determine intrauterine pathology in patients with postmolar gestational trophoblastic neoplasia (GTN) and hydatidiform mole after suction curettage. Safety profiles of endometrial sampling in this setting are also evaluated.In this prospective study, 24 cases with persistent GTN or postevacuation hydatidiform mole were recruited. Endometrial pathology was evaluated by Endocell. Clinical characteristics, safety of the instrument and pathology results were analyzed.During August 2006 to July 2007, 15 cases with postmolar GTN and 9 cases of postevacuation mole were recruited. Of 15 cases of postmolar GTN, 2 (13%) showed molar tissue. All 9 cases of postevacuation hydatidiform mole showed benign endometrial tissue or normal trophoblast in endometrial sampling pathology. No patients in this study had severe vaginal bleeding or infection after endometrial sampling. Analysis of endometrial sampling pathology as a diagnostic test for GTN showed a sensitivity of 0.133 (95% CI 0.037-0.379).Endometrial sampling by Endocell is safe in patients with gestational trophoblastic disease. Although the pathology findings from endometrial sampling had low sensitivity in diagnosing GTN, we encourage a larger prospective trial to confirm this result.

A 17 year-old female with stage IIIc endodermal sinus tumor of the ovary developed transient cortical blindness and severe hypertension after 5 cycles of PVB regimen consisting of cisplatin, vinblastine and bleomycin. Clinical and radiological findings were compatible with Posterior LeukoEncephalopathy (PLE). Her visual acuity and blood pressure completely recovered within a few days after supportive treatment with antihypertensive drug. This condition is unpredictable but it can be reversible without long term sequelae. Most reports suggested that this rare toxicity was from cisplatin therapy. However, the exact pathophysiogenesis of this condition was not known precisely. Prompt reduction in blood pressure and withdrawal of immunosuppressive agents might lead to rapid reversal of this syndrome and prevent permanent brain damage.

To determine the frequency, characteristics, treatment and outcome of patients with malignant ovarian germ cell tumor (MOGCT) in King Chulalongkorn Memorial Hospital during the period January 1992 - December 2000.Retrospective descriptive studyAll patients with malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital during the period January 1992 - December 2000 were analyzed by the characteristics of patients, treatment and outcome.Sixty-six patients with MOGCT were demonstrated in that period with a mean age of 22.6 years old. Most of the patients were nulliparous and premenopausal status. Primary surgery was done in all patients. Forty-two patients (63.6%) received conservative surgery. Eight patients received no adjuvant treatment after surgery due to stage 1A dysgerminoma and immature teratoma stage I grade I. Fifty-six patients received chemotherapy for adjuvant treatment. VAC regimen was given in 27 cases (40.9%) and PVB regimen was given in 25 cases (37.9%). Salvage therapy in the patients with persistent and recurrent disease was treated in 9 patients, who received a platinum-base of regimen. Two-year survival was 88% with the median time to follow up 24 months. Overall five-year survival in the present study was 85%.MOGCT in King Chulalongkorn Memorial Hospital had clinical characteristics similar to other studies in malignant ovarian germ cell tumor Treatment by VAC regimen still has benefit in selected group.

Malignant ovarian germ cell tumor has one of the most successful treatment outcomes in gynecological malignancy. More than 80% of the patients can be cured from this rare type of tumor However, patients with recurrent and persistent disease after primary treatment are still the problem of management. The present study has reviewed the treatment outcome of this cancer in King Chulalongkorn Memorial Hospital during the 12 years periodfrom 1993 to 2004. The overall cases of malignant ovarian germ cell tumor were 71 cases, 8 cases had recurrent disease after primary treatment and all cases received platinum-based chemotherapy for the salvage treatment. All patients in this group received long-term survival with median survival time of 87 months. In patients with persistent disease, 10 cases that resisted to first line adjuvant chemotherapy. Cisplatin and Etoposide regimen was applied as second line treatment, but none of these patients received long term response. The survival outcomes in these 2 groups are significantly different. The overall survival from the treatment of malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital was 85.1%. In conclusion, the outcome of treatment in patients with recurrent disease after non-platinum chemotherapy is excellent. Salvage therapy in this group should contain platinum-based regimen. Patients whose disease persisted after platinum-containing regimen had a poor survival outcome.

To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US). All new cases with cytologic smears showing ASC-US that presented in King Chulalongkorn Memorial Hospital from January 2003 to November 2003, excluding known cases of HSILs and pregnancies, were enrolled. Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test. All participants were examined under a colposcope. Then cervicographs were taken before colposcopic-directed cervical biopsies were done. Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%. The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively. Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs. High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.

Pregnancy in the broad ligament is a rare form of ectopic pregnancy, and one type of abdominal pregnancy. The diagnosis is seldom established before surgery. A 38-year-old, 11-week pregnant woman, gravida 3, para 2, presented with vaginal bleeding. She had undergone two cesarean sections 10 and 6 years earlier. Pregnancy in the right broad ligament was diagnosed from clinical and transvaginal ultrasonographic findings. Emergency laparotomy and excision of a pregnancy in the right broad ligament and right salpingectomy were performed. She was well at discharge and at the 6-week follow up. We suggest the use of clinical and ultrasonographic findings for the suspicion of pregnancy in the broad ligament.