Jakkapan Khunnarong

Expressions of estrogen and progesterone receptors in epithelial ovarian cancer: a clinicopathologic study.

Although estrogen (ER) and progesterone (PR) receptors are well recognized as important prognostic indicators of breast and endometrial cancers, their clinical significance in epithelial ovarian cancer is not clear with the limited data from only few immunohistochemical studies. The aim of this study was to evaluate the expressions of ER and PR in patients with epithelial ovarian cancer who were treated in our institution during the period 1996 to 2003. Their associations with clinicopathologic factors of age, stage, histologic subtypes, and grade and their prognostic role to survivals were also examined. Among 106 subjects included in the study, ER and PR expressions were found in 39.6% and 33.0%, respectively, with the corresponding highest expression in serous and endometrioid carcinomas. Estrogen receptor expression had a significant association with age older than 60 years, non-clear cell carcinomas, and high-grade tumors, whereas PR expression showed a significant association with non-clear cell carcinomas and a better response to first-line chemotherapy. Progesterone receptor expression was a favorable prognostic factor to both progression-free and overall survivals from univariable but not multivariable analyses. Expression of ER or any combination of ER/PR subgroups did not have a significant impact on survivals.

Treatment Outcomes of Paclitaxel for Refractory or Recurrent Epithelial Ovarian Cancer Patients in Thailand

BACKGROUND To study the response rate, toxicity profiles, and survival of refractory or recurrent epithelial ovarian cancer (EOC) patients treated with paclitaxel. MATERIALS AND METHODS Patients with refractory or recurrent EOC who were treated with paclitaxel between January 2002 and December 2011 at the Department of Obstetrics and Gynecology, Faculty of Medicine, Vajira Hospital were identified. Clinicopathological features of the patients including detailed data of paclitaxel treatment were collected. RESULTS During the study period, a total of 44 patients were identified, with a mean age of 52.9±8.2 years. Some 13.6% (six patients) had refractory cancer to first-line chemotherapy while 86.4% (38 patients) had recurrent cancer. Among these, 35 (79.6%) and 9 (20.4%) patients were considered as platinum-sensitive and platinum-resistant, respectively. Three patients (6.8%) received fewer than 2 cycles of paclitaxel due to loss to follow-up, leaving 41 patients evaluable for response. The overall response rate observed in all 41 patients was 41.5% (17 patients; 12 complete and five partial responses): 12.5% or 1/8 patients with refractory or platinum-resistant cancer and 48.5% or 16/33 patients with platinum-sensitive disease. Stable disease was demonstrated in 17.0% (seven patients) while progressive disease was apparent in 41.5% (17 patients). Median time to progress was 4.5 months (range, 0.67- 58.6 months). Median progression-free survival was not reached while median overall survival was 16.3 months (95% confidence interval, 11.0 months -21.6 months). Common toxicities were neutropenia, neuropathy, and alopecia. CONCLUSIONS Paclitaxel is an active agent for refractory or recurrent EOC. Neutropenia, neuropathy and alopecia are common side effects.

Medical morbidities in endometrial cancer patients.

Objectives The aim of this study was to evaluate the prevalence and types of medical morbidities in Thai endometrial cancer (EMC) patients and their impact on treatment outcomes. Methods The EMC patients treated in the institution from 1995 to 2012 and with available medical history were identified. Data collected were age; medical morbidities; tumor stage, histopathology, and grade; adjuvant therapy; living status; and cause of death. Results Of the 335 EMC patients included in the study, 77.3% had early-stage diseases, and 46.6% received adjuvant therapy. A total of 220 patients (65.7%) had medical morbidities. Median age of patients with medical morbidities was significantly higher than those without: 59 years (range, 30–84 years) versus 52 years (range, 30–86 years) (P < 0.001). One or more components of metabolic syndrome were the most common: 10.9% had all 4 components, 30.0% had three, and 31.4% had two. Thyroid dysfunction, as the second most common, was found in 8.2%. From a median follow-up of 56.5 months (0.07–234.04 months), 18.5% were dead: 11.6% from EMC, 4.8% from medical conditions, and 2.1% from other causes. Survival of the patients who had or had no medical morbidities was not significantly different: 5-year overall survival and 5-year cancer-specific survival were 84.7% (95% confidence interval [CI], 79.6%–89.8%) versus 84.0% (95% CI, 76.9%–91.0%) (P = 0.918) and 87.3% (95% CI, 82.6%–92.0%) versus 89.3% (95% CI, 83.2%–95.3%) (P = 0.986), respectively. Conclusion This was the first large analysis in South-East Asia showing common incidence of medical morbidities in EMC patients. One or more components of metabolic syndrome were the most common. Some medical illnesses were the causes of death. Comprehensive and continual medical care for EMC patients is important.

Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

BACKGROUND To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. MATERIALS AND METHODS Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. RESULTS We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinum- sensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. CONCLUSIONS Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.

Knowledge, Attitudes and Behavior of Bangkok Metropolitan Women Regarding Cervical Cancer Screening.

PURPOSE To assess knowledge, attitudes and cervical cancer screening behavior of Bangkok Metropolitan women. MATERIALS AND METHODS Thai women, aged 25-to-65 years old, having lived in Bangkok for 5 years or more were invited to participate in the study. After signing informed consent, all women were asked to complete a self-questionnaire (Thai language) with literate assistance if needed. The questionnaire was divided into 3 parts: (I) demographic data; (II) knowledge about cervical cancer screening; and (III) behavior and attitudes, towards cervical cancer screening. Adequate screening was defined as women who had ≥two cervical cancer screening tests except women aged 25-30 years who may have only one screening, and the last screen was within 5 year or had had regular screening. RESULTS Of 4,339 women, there were 1,857 (42.8%) with adequate screening and 2,482 (57.2%) with inadequate screening. Significant factors associated with inadequate screening included age < 45 years, pre-menopausal status, family monthly income <625 USD, no reported sexual intercourse, nulliparous, no knowledge, lack of awareness and poor attitudes. Three major reasons provided by women for inadequate screening were no symptoms (54.4%), fear of pain (33.2%), and embarrassment (34.6%). CONCLUSIONS Personal features, knowledge, and attitudes influence screening behavior of Bangkok Metropolitan women. The three most common reasons of women for not undergoinging screening are no symptoms, fear of pain, and embarrassment. These factors should be the focus of attention to improve coverage of cervical cancer screening in Bangkok.

Patterns of adjuvant therapy for endometrial cancer: single institutional experience in Thailand.

Aim The aim of this study was to evaluate the use of adjuvant therapy and treatment outcomes in patients with endometrial cancer (EMC). Methods Patients with EMC treated in the institution were identified. Data collected were age, stage of disease, histopathology, and adjuvant therapy. Progression-free survival (PFS) and overall survival (OS) were studied. Results The median age of 383 patients was 57 years (30–86 years). Majority had early-stage diseases (76.5%), endometrioid histopathology (87.2%), and high-grade tumors (74.9%). Less than half (44.4%) had adjuvant therapy. Pelvic radiation was the most common type of adjuvant treatment. We found that 25.7% of stages III to IV patients did not have adjuvant therapy (mainly from old age or poor performance status). On the other hand, 21.5% of patients with stage IA had adjuvant treatment (owing to risk factors or other synchronous cancers). The 5-year PFS and 5-year OS (95% confidence interval) were 84.3% (80.5%–88.1%) and 81.2% (77.1%–85.4%), respectively. Significant prognostic factors for survival by univariable analyses were stage, tumor grade, and histopathology. By multivariable analyses, significant prognostic factors were stage, tumor grade (only for OS), histopathology, and adjuvant therapy. Focusing on stage and adjuvant therapy, we found that the PFS and OS of early-stage patients who had or did not have adjuvant therapy were not significantly different, whereas the PFS and OS of advanced-stage patients who had adjuvant treatment were significantly higher than the PFS and OS of those who did not have adjuvant treatment. Conclusions The use of adjuvant therapy for patients with EMC was not according to the standard recommendation in all patients for many reasons. The benefit of adjuvant therapy was demonstrated in advanced- but not in early-stage cancer.

Uterine Sarcoma: Clinical Presentation, Treatment and Survival Outcomes in Thailand

BACKGROUND Uterine sarcoma is a group of rare gynecologic tumors with various natures, and different lines of treatment. Most have a poor treatment outcome. This study targeted clinical characteristics, treatment, overall survival (OS), progression-free survival (PFS), and prognostic factors in uterine sarcoma patients in one tertiary center for cancer care. MATERIALS AND METHODS Uterine sarcoma patients who were treated at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital between January 1994 and December 2014 were identified. Clinico-pathological data were analyzed. Prognostic outcomes were examined by Kaplan-Meier curves and Cox regression analysis. RESULTS We identified 46 uterine sarcoma patients: 25 carcinosarcoma (CS) (54.3%), 15 leiomyosarcoma (LMS) (32.6%), and 6 undifferentiated uterine sarcoma (UUS) (13.1%) cases. Mean age was 54.0±11.9 years (range 25-82 years). Abnormal uterine bleeding was the most common presenting symptom (63.0%). Among 33 patients (71.7%) who had pre-operative tissue collected, diagnosis of malignancy was correct in 29 (87.9%). All patients received primary surgery and retroperitoneal lymph nodes were resected in 34 (73.9%). After surgery, 5 (10.9%) had gross residual tumors. Stage I disease was most commonly found (56.5%). Adjuvant treatment was given to 27 (58.7%), most commonly chemotherapy. After a median follow-up of 16.0 months (range 0.8-187.4 months), recurrence was encountered in 22 patients (47.8%). Median time to recurrence was 5.8 months (range1.0-105.5 months). Distant metastasis was more common than local or loco- regional failure. The 2-year PFS was 45.2% (95% confidence interval [CI], 30.6%-59.7%) and the 2-year OS was 48.3% (95% CI, 33.3%-60.7%). Multivariable analyses found residual disease after surgery as a significant factor only for PFS. CONCLUSIONS Uterine sarcoma is a rare tumor entity. Even with multimodalities of treatment, the prognosis is still poor. Successful cytoreductive surgery is a key factor for a good survival outcome.

Other Gynecologic Pathology in Endometrial Cancer Patients.

BACKGROUND To evaluate the prevalence and features of other gynecologic or surgical lesions in endometrial cancer (EMC) patients. MATERIALS AND METHODS Clinico-pathological data of EMC patients who were treated in the institution from 1995 to 2012 were collected. Data collected were age, stage of disease according to the FIGO 2009 criteria (FIGO), histopathology, tumor grade, adjuvant therapy, other gynecologic or surgical lesions, follow-up period, and living status. RESULTS The mean age of 396 patients was 56.7 ± 10.64 years. Abnormal uterine bleeding was the most common presenting symptom (90.1%). Bleeding was accompanied with pelvic mass in 7.7% and 5.4% had only a pelvic mass. Abnormal cervical cytology was found in 3.8%. Approximately 75% had early stage diseases and 86% had endometrioid histology. We found 55.8% of EMC patients had other gynecologic lesions: 89.6% benign and 9.5% malignant. Some 4.5% had pre-invasive cervical/vulva/vagina lesions. The two most common gynecologic lesions were myoma uteri and ovarian tumors. Focusing on the latter, approximately 14% were benign while 8% were malignant. Among 364 patients with available data, surgical lesions were found in 11.8%, 5.7% benign and 9.2% malignant. The most common benign surgical condition was chronic appendicitis while breast and colon cancers were the two most common malignant lesions found. CONCLUSIONS More than half of EMC patients had other gynecologic lesions including benign and malignant tumors. Surgical lesions were also found in more than one-tenth of patients. Careful pre-operative evaluation and intra-operative inspection are advised for proper management and better prognosis.

Expression of ER, PR and Her-2/neu in Endometrial Cancer: A Clinicopathological Study

OBJECTIVE To determine any association between expression of estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu and clinicopathological features, including survival, of endometrial carcinoma (EMC) patients. METHODS Samples of formalin-fixed, paraffin-embedded tissue of 108 patients with EMC treated at our institution between January 1994 and December 2007 were immunohistochemically studied. RESULTS ER, PR, and Her-2/neu expression were positive in 59.3%, 65.7% and 2.8% of cases, respectively. Positive ER expression was significantly associated with grade I-II tumor while PR expression was linked with endometrioid histology, grade I-II tumor, less myometrial invasion (MI) and negative lymph node involvement. Her-2/neu expression was significantly associated with deep MI, while positive ER and negative Her-2/neu expression in combination was significantly associated with longer disease-free and overall survival. CONCLUSION ER expression is a good prognostic factor while Her-2/neu expression appears to be a poor indicator for both disease-free and overall survival, while PR tended to show favorable influence for only disease-free survival of Thai EMCs.

Abnormal uterine cervical cytology in a large tertiary hospital in Bangkok metropolis: Prevalence, management, and outcomes.

OBJECTIVES To determine the prevalence of abnormal cervical cytology, management, and association with clinical significant histopathology including cervical intraepithelial neoplasia II or adenocarcinoma in situ and more severe lesions. MATERIALS AND METHODS Women with abnormal cervical cytology from January 2005 to December 2009 were identified from the archives of Department of Anatomical Pathology and Department of Obstetrics and Gynecology. Demographic data, type of abnormal cytology, management, and their associated histopathology were collected. RESULTS During the study period: 2533/54,179 women (4.7%) had abnormal cervical Pap test. Squamous lesions were more common than glandular lesions: 2309 (4.3%) compared to 224 (0.4%). Atypical squamous cell (ASC) was most commonly found (1449 or 2.7%), whereas low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intra-epithelial lesion (HSIL), or squamous cell carcinoma (SCC) were found in 648 (1.2%) and 212 (0.4%), respectively. Among abnormal glandular cytology, atypical glandular cell (AGC) was most commonly found (199 women or 0.4%) whereas adenocarcinoma and endometrial cell in woman aged >40 year were found in only 14 (0.02%) and 11 women (0.02%), respectively. Majority (77.3%) underwent further investigations. We found that 13.0% of ASC, 20.3% of LSIL, and 78.7% of HSIL and SCC had clinical significant histopathology. In glandular abnormalities: 14.9% of AGC, 33.3% of women aged >40 years with endometrial cell, and 66.7% of adenocarcinoma were histologically proven to be of clinical significant. CONCLUSIONS ASC was the most common abnormal cervical cytology. Cytology abnormalities of HSIL and SCC had the highest association with clinical significant histopathology.