Management of inoperable endometrial cancer

Some endometrial cancer (EMC) patients are not good candidates for primary surgery. The three major types of treatment for inoperable EMC are radiation therapy, chemotherapy, or their combination as neoadjuvant treatment before surgery. Radiation therapy alone (of different modes) has been used as the sole definitive therapeutic modality, particularly for early-stage disease that is limited to the uterine body and cervix with or without parametrial invasion. The most common treatment modality is neoadjuvant treatment before surgery. Postoperative adjuvant treatment is also occasionally used, depending mainly on the sites of the disease and the results of surgery. Data on neoadjuvant hormonal or radiation therapy are limited, with studies focusing on laboratory outcomes or having only a small number of patients. Most neoadjuvant treatments before surgery involved chemotherapy and fewer combined chemoradiotherapy. Surgery was generally performed, particularly in patients who had shown responses or at least stable disease to neoadjuvant treatment. Perioperative outcomes after neoadjuvant treatment were superior to those after primary surgery, whereas survival data were still inconsistent. Features that had or tended to have a favorable prognosis were younger age, early-stage disease, response to neoadjuvant treatment, low preoperative cancer antigen-125 level, and optimal surgery. Among different modalities of neoadjuvant treatment, which has become a frequent mode of treatment, neoadjuvant chemotherapy was more common than radiation therapy alone or chemoradiation.

Trends of uterine cancer incidence: a projection from the past to the future / 부인종양

No abstract available.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial / 부인종양

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18–70 years who had International Federation of Gynecology and Obstetrics stage IIB–IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82–1.96; p=0.293) and 1.42 (95% CI=0.81–2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164 Thai Clinical Trials Registry Identifier: TCTR 20140106001

Synchronous and metachronous malignancy in endometrial cancer patients treated in a tertiary care center of Thailand / 부인종양

OBJECTIVE: To evaluate the prevalence and features of non-endometrial cancers in Thai endometrial cancer (EC) patients. METHODS: EC patients treated in our institution were identified and the following data were collected: age, EC stage, histopathology, adjuvant therapy, other cancers, living status, and cause of death. RESULTS: The mean age of the 344 patients was 56.8+/-10.8 years. Fifty (14.5%) had other synchronous and metachronous cancers. Mean ages of the patients with or without other cancers were not significantly different, 55.7+/-10.04 years versus 57.1+/-11.0 years, respectively (p=0.358). History of any cancer in the family and tumor in the lower uterine segment were more frequent among the patients with other cancers (6.0% vs. 1.7%, p=0.095; 12.0% vs. 1.0%, p or =2 other cancers. Ovarian, breast, and colon were the three most common other cancers. After a median follow-up of 57.1 months, 18.3% of patients had died: 30.0% of patients with other cancers and 16.3% of those without other cancers. The corresponding EC deaths were 14.0% and 11.2%. The 5-year overall survival was significantly lower in patients who had other cancers: 79.3% (95% confidence interval [CI], 68.3 to 90.3) vs. 86.0% (95% CI, 81.7 to 90.3) than in those without (p=0.023). However, the corresponding disease-specific survival was not significantly different: 85.1% (95% CI, 75.5 to 94.7) compared with 89.0% (95% CI, 85.1 to 92.9), respectively (p=0.514). CONCLUSION: Thai EC patients had a high incidence of other cancers. Overall survival of EC patients who had other cancers was worse than those without, while disease-specific survival was not significantly different.

Cost-utility analysis of treatments for stage IB cervical cancer / 부인종양

OBJECTIVE: To analyze the cost-utility of two common clinical practices for stage IB cervical cancer patients from provider and societal viewpoints. METHODS: A decision tree model was conducted to examine value for expenditure between the following: (1) radical hysterectomy with pelvic lymph node dissection (RHPLND) with or without postoperative adjuvant therapy according to the risk of recurrence and (2) concurrent chemoradiotherapy (CCRT). The relevant studies were identified to extract the probability data, and meta-analysis was performed. Direct medical costs were estimated from hospital database and medical records review. Direct non-medical costs and utility parameters were obtained through interviews with patients to estimate quality-adjusted life years (QALYs) outcome. The time horizon was according to the life expectancy of Thai women. RESULTS: From provider viewpoint, RHPLND and CCRT resulted in approximate costs of US $5,281 and US $5,218, respectively. The corresponding costs from societal viewpoint were US $6,533 and US $6,335, respectively. QALYs were 16.40 years for RHPLND and 15.94 years for CCRT. The estimated incremental cost effectiveness ratio of RHPLND in comparison to CCRT from provider and societal viewpoints were US $100/QALY and US $430/QALY, respectively. RHPLND had more cost-effectiveness than CCRT if patients did not need adjuvant therapy. The most effective parameter in model was a direct medical cost of CCRT. At the current ceiling ratio in Thailand, RHPLND provides better value for money than CCRT, with a probability of 75%. CONCLUSION: RHPLND is an efficient treatment for stage IB cervical cancer. This advantage is only for patients who require no adjuvant treatment.

Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer / 부인종양

OBJECTIVE: To determine whether preoperative platelets to lymphocyte ratio (PLR) could predict disease stage, surgical outcome, and survival in patients with epithelial ovarian cancer (EOC). METHODS: Medical records of EOC patients who had surgery between January 2004 and December 2010 were reviewed. Clinicopathological and complete blood count data were collected. The optimal predictive value of PLR to predict advanced stage, suboptimal surgery, and survival was determined and compared with those of thrombocytosis (> or =400,000 cells/mm3) and neutrophil to lymphocyte ratio (NLR) > or =2.6. RESULTS: A total of 166 EOC patients were included in the study. PLR of 200 yielded better predictive values than those of thrombocytosis and NLR > or =2.6. The area under curve (AUC), sensitivity, specificity, positive and negative predictive values, and accuracy of PLR to predict advanced stage were: 0.66, 59.0%, 72.7%, 65.7%, 66.7%, and 66.3%, respectively. The corresponding values to predict suboptimal surgery were: 0.70, 70.0%, 69.8%, 50.0%, 84.4%, and 69.9%. The patients who had PLR> or =200 had significantly shorter progression-free and overall survivals than those with PLR2.6.

Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer / 부인종양

OBJECTIVE: To determine whether preoperative platelets to lymphocyte ratio (PLR) could predict disease stage, surgical outcome, and survival in patients with epithelial ovarian cancer (EOC). METHODS: Medical records of EOC patients who had surgery between January 2004 and December 2010 were reviewed. Clinicopathological and complete blood count data were collected. The optimal predictive value of PLR to predict advanced stage, suboptimal surgery, and survival was determined and compared with those of thrombocytosis (> or =400,000 cells/mm3) and neutrophil to lymphocyte ratio (NLR) > or =2.6. RESULTS: A total of 166 EOC patients were included in the study. PLR of 200 yielded better predictive values than those of thrombocytosis and NLR > or =2.6. The area under curve (AUC), sensitivity, specificity, positive and negative predictive values, and accuracy of PLR to predict advanced stage were: 0.66, 59.0%, 72.7%, 65.7%, 66.7%, and 66.3%, respectively. The corresponding values to predict suboptimal surgery were: 0.70, 70.0%, 69.8%, 50.0%, 84.4%, and 69.9%. The patients who had PLR> or =200 had significantly shorter progression-free and overall survivals than those with PLR2.6.

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear / 부인종양

OBJECTIVE: To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology. METHODS: Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold. RESULTS: Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively. CONCLUSION: VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.

Accuracy of Frozen Section in Diagnosis of Ovarian Mass

Abstract Accuracy of Frozen Section in Diagnosis of Ovarian Mass Siriwan             Tangjitgamol            MD* Somneuk        Jesadapatrakul         MD** Sumonmal      Manusirivithaya        MD*   *Department of Obstetrics and Gynecology, BMA Medical College and Vajira Hospital **Department of Pathology, BMA Medical College and Vajira Hospital Objective: To determine the accuracy of frozen section compared to permanent section according to status of malignancy and histologic cell type. Study design:  Diagnostic study. Subjects:  Frozen and permanent pathological reports of 212 ovarian masses from 212 women who underwent ovarian resection at BMA Medical College and Vajira Hospital from January 1, 1992 to December 31, 2002 were studied. Methods:  All frozen and subsequent permanent pathological reports of ovarian masses from the studied group were reviewed.  The data of age, tumor size, number of frozen and permanent sections of the ovarian masses, the results of frozen and permanent section were taken from the pathological report.  The pathological slides were reviewed when there was discrepancy of frozen and permanent section diagnosis, in deferred diagnosis for status of malignancy and/ or histologic cell type. Main outcome measures:  Accuracy, sensitivity, specificity, positive predictive value, negative predictive value of frozen section. Results:  From 212 ovarian masses, there were 13 deferred cases which frozen section diagnosis for status of malignancy could not be given. Statistical analysis was then performed in 199 cases..  The overall accuracy was 90.9%.  Sensitivity of frozen section diagnosis was highest in the benign group at 99.1%, next was in the malignant group at 86.1% and lowest in borderline group at 50%.  The specificity were 90.7, 94.6 and 100.0% in the benign, borderline and malignant groups respectively.  Positive and negative predictive values of benign, borderline and malignant groups were 93.3, 41.2, 100.0% and 98.7, 96.2, 92.7%, respectively.  All inaccurate diagnosis were in the common epithelial group.  When the statistical data were analyzed according to histology subgroup of common epithelial tumor, sensitivity in diagnosis malignant and borderline mucinous were lower than non-mucinous tumor, 62.5% and 41.7% compared to 96.9% and 50.0% respectively.  For diagnosis of the histologic cell type, frozen section had 91.9% accuracy.  Thirteen out or 16 incorrect histologic diagnosis cases (81.3%) were in the common epithelial group while only three cases were germ cell tumor.   Conclusion:  The accuracy of frozen section in diagnosis of frozen section in diagnosis of ovarian mass was generally high according to both status of malignancy and histologic cell type.  There were exception in tumors with large size, mucinous or borderline tumor which yielded lower accuracy, sensitivity, specificity and positive predictive value than the other groups.  The surgeon should recognize these limitations and appraise the test result together with other clinical data.  This is to achieve for the correct final diagnosis and the proper management for the patient. Key word:  frozen section, ovarian mass, accuracy, malignancy, histologic cell type Vajira Med J 2003 ; 47 : 17 - 28

Endometrial Cancer: Incidence of Retroperitoneal Lymph Node Metastasis and Clinico-pathological Factors Predicting Retroperitoneal Lymph Node Metastasis

Abstract Endometrial Cancer: Incidence of Retroperitoneal Lymph Node Metastasis and Clinico-pathological Factors Predicting Retroperitoneal Lymph Node Metastasis Surawute    Leelahakorn         MD* Siriwan       Tangjitgamol         MD* Sumonmal Manusirivithaya   MD, MSc (Clinical Epidemiology)* Jakkapan    Khunnarong         MD* * Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, BMA Medical College and Vajira Hospital Objectives: To evaluate the incidence of retroperitoneal lymph node (RLN) metastasis in endometrial carcinoma (EMC) and to assess the clinico-pathological factors predicting RLN metastasis. Study design: Retrospective study. Subjects: Two hundred and twenty five patients with clinical stage I-II EMC who underwent surgical staging at our institute during January 1993 and December 2007. Methods: Medical and pathological records of all EMC patients were reviewed. Clinico-pathological characteristics and other data were extracted and analyzed. Main outcome measures: Retroperitoneal lymph node metastasis. Results: Mean age of the patients was 55.0 ± 9.8 years (30-84 years). All patients had total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node resection. One hundred and seventy seven patients (78.7%) also had para-aortic lymph node resection. The most common histopathologic type was endometrioid adenocarcinoma (90.7%). Mean number of lymph nodes obtained was 23.2 ± 10.6 nodes. Retroperitoneal lymph node metastasis was found in 28 patients (12.4%): pelvic lymph node metastasis in 25 patients (11.1%) and para-aortic lymph node metastasis in 10 patients (4.4%). By univariable analysis, clear cell or papillary serous adenocarcinoma type, high grade (II-III) tumor, tumor size \> 2 cm, tumor located in lower uterine segment, cervical involvement, gross intra-abdominal metastasis, myometrial invasion more than inner half, lymph vascular space invasion and positive peritoneal cytology were significantly associated with RLN metastases. By multivariable analysis, only myometrial invasion more than inner half and lymph vascular space invasion were independently associated with RLN metastasis. Conclusion: RLN metastases were found in 12.4% of patients with clinical stage I and II EMC. Presence of myometrial invasion more than inner half and lymph vascular space invasion were significantly associated with RLN metastasis by multivariable analysis. Vajira Med J 2008 ; 52 : 129 - 138

Liquid-based Cytology for Cervical Cancer Screening

Abstract Liquid-based Cytology for Cervical Cancer Screening Apichote     Khumsangmeun BSc (Biology) Siriwan       Tangjitgamol        MD Sumarin      Pratumkaew        BSc (Biology) Department of Anatomical Pathology, BMA Medical College and Vajira Hospital           Liquid-based cytology is a new method of cervical cells sample collection and cytological slide preparation. This method gains popularity at present because a large number of cervical epithelial cells could be collected, even distribution of cells on the slides, removal and foreign bodies or inflammatory debris were removed or lysis, reduction of equivocal interpretation or false negative results, and less time for interpretation comparing to the Conventional Papanicolaou smear. Furthermore the remaining sample could be submitted for a HPV DNA testing to determine the risk group of virus which is the important etiologic factor for cervical cancer. Vajira Med J 2009 ; 53 : 311-316

Use of Immunohistochemical Study in Pathology

Abstract Use of Immunohistochemical Study in Pathology Unaporn     Trongsakul                     BSc (Biology) Sujitra        Tanvanich                      MSc (Pathobiology) Siriwan       Tangjitgamol                MD Department of Anatomical Pathology BMA Medical College and Vajira Hospital           Immunohistochemistry is the application of immunologic technique used to determine types of antigen in cells or tissue structure. The staining is based on the principle of antigen-antibody binding compound. This compound could be detected by a catalytic chemical reaction of chromogen, producing specific color at specific cellular location. Used of immunohistochemical stain are: to detect the cancer cell origins, to classify the tumors, to demonstrate micrometastatic cancer cells, as a prognostic indicator and to identify microorganisms. Although the physicians who submit a tissue for histologic diagnosis do not require extensive knowledge on immunohistochemistry, basic information of the technique would help them understand the complicated pathological work. Furthermore, the knowledge or familiarity on this special technique would certainly assist them to collaborate with pathologists in making use out of these various immunohistochemistry stainings to facilitate the diagnosis and optimal care for the patients. Vajira Med J 2008 ; 52 : 285-291

Expression of Estrogen Receptor and Progesterone Receptor in Epithelial Ovarian Tumors

Abstract Expression of Estrogen Receptor and Progesterone Receptor in Epithelial Ovarian Tumors Sujitra        Tanvanich               MSc (Pathobiology)* Siriwan       Tangjitgamol         MD*,** Sumonmal Manusirivithaya   MD, MSc (Clinical Epidemiology)** Somneuk    Jesadapatarakul MD* * Department of Anatomical Pathology, BMA Medical College and Vajira Hospital ** Department of Obstetrics and Gynecology, BMA Medical College and Vajira Hospital Objectives: To examine the expression of estrogen receptor (ER) and progesterone receptor (PR) in epithelial ovarian tumors and their associations with status of malignancy, histopathologic subtypes and grading. Study design: descriptive study. Subjects: Tissue of epithelial ovarian tumors resected at the BMA Medical College and Vajira Hospital between 1996-2005. Methods: The patients with epithelial ovarian tumors who were operated in our institution were identified. Samples of formalin-fixed, paraffin-embedded ovarian tumor tissue of patients were retrieved and processed for ER and PR immunohistochemical study. Data collected were: age, status of malignancy, tumor histologic subtype, and grade of malignant tumor. Expression of ER, PR and their associations with these pathological data were studied. Main outcome measures: Immunohistochemical expression of estrogen and progesterone receptors. Results: During the study period, 191 patients with epithelial ovarian tumors who were operated in our institution were identified. Mean age of the patients was 47.7 ± 14.6 years. Positive immunohistochemical expression of ER and PR were found in 29.8% and 34.0% respectively. ER expression was higher in malignant tumors than borderline and benign tumors, 39.6% versus 25.9% and 13.8% respectively while the expression of PR showed no different expression, 33.0% versus 33.3% and 36.2% respectively. Endometrioid tumors showed highest ER and PR expression 57.1% and 66.7% respectively, while clear cell tumors showed lowest expression of ER (5.9%) and mucinous for PR expression (9.6%). Focusing only on the malignant tumors, we found that the expression of ER and PR in mucinous and clear cell carcinomas were significantly lower than other cell types, 6.8% versus 62.9% for ER and 9.1% versus 50.0% for PR expression. Positive ER expression was significantly lower in well differentiated than moderately and poorly differentiated carcinomas, 11.8% versus 48.6% and 42.6% whereas there was no significant association between PR and grade of tumor. Conclusions: We demonstrated 29.8% of ER and 34.0% of PR expression in epithelial ovarian tumors. Expression of ER in malignant tumors was higher than benign and borderline tumors, whereas the expressions of PR of these tumors were nearly the same. Both receptors were lowly expressed in clear cell and mucinous tumors. ER expression was lower in well differentiated than moderately and poorly differentiated tumors while there was no significant association between PR and grade of tumors. Vajira Med J 2008 ; 52 : 249-256