Moon-Hong Kim

Polymorphisms in codon 31 of p21 and cervical cancer susceptibility in Korean women

The aim of this study was to determine whether the codon 31 genotype of p21 might be associated with an increased risk of cervical cancer development in Korean women. We used tissue derived from patients with invasive cervical cancer (ICC) (n=111, composed of two histologic groups: squamous cell carcinoma (n=67) and adenocarcinoma (n=44)), cervical intraepithelial neoplasia (CIN) III (n=101), and non-cancer controls (NCC, n=98). For the determination of p21 polymorphism, genomic DNA was examined by polymerase chain reaction-restriction fragment length polymorphism assay using BsmAI. We compared the distribution of the p21 genotype in ICC, CIN III, and control and also analyzed the association of this polymorphism with the risk of development of cervical cancer, especially in patients with high-risk human papillomavirus (HPV) (16 or 18)-positive cervical cancer. A significant increase of Ser/Ser genotype frequency was found in adenocarcinoma patients with high-risk HPV (16 or 18) compared with the NCC group (P=0.009). The odds ratio was 3.59 (95% CI 1.55-8.31) when comparing adenocarcinoma patients associated with high-risk HPV with NCC. We found that the codon 31 Ser/Ser homozygote of the p21 gene could be a risk factor for the development of cervical adenocarcinoma associated with high-risk HPV.

Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

PURPOSE To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. METHODS AND MATERIALS In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m(2), six cycles) and triweekly (cisplatin 75 mg/m(2) every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. RESULTS All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). CONCLUSIONS Triweekly cisplatin 75-mg/m(2) chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m(2) regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

Is adjuvant chemoradiotherapy overtreatment in cervical cancer patients with intermediate risk factors

PURPOSE To determine whether adjuvant chemoradiotherapy (CRT) improves the outcome of cervical cancer patients with intermediate risk factors. METHODS AND MATERIALS Between January 2000 and June 2006, the medical records of 735 patients who had undergone radical surgery for Stage IB-IIA cervical cancer were reviewed retrospectively. Of the 735 patients, 172 with two or more intermediate risk factors (i.e., lymphovascular space involvement, deep stromal invasion, and tumor size≥2 cm) were grouped as follows according to the adjuvant treatment received: 34 patients, no further treatment; 49 patients, RT; and 89 patients, CRT. The significance of the clinical parameters and recurrence-free survival of each group were analyzed. RESULTS Of the 172 patients with any of the intermediate risk factors, 137 (79.6%) had two or more intermediate risk factors. Of the 172 patients, 12 developed recurrences (6.4%)->(7.0%), with 6 in the pelvis and 6 in distant sites. All 12 recurrences occurred in those who had two or more intermediate risk factors (sensitivity, 100%); however, only six recurrences were detected in patients who met the Gynecologic Oncology Group criteria for the intermediate-risk group (sensitivity, 50%; Z test, p<.05). A statistically significant difference was found in the 3-year recurrence-free survival rate among the no further treatment, RT, and CRT groups (67.5%, 90.5%, and 97.5%, respectively; p<.05). The incidence of Grade 3-4 hematologic and gastrointestinal toxicities was not significantly different statistically between the RT and CRT groups (6.1% and 13.4%, respectively; p > .05). CONCLUSION Postoperative adjuvant CRT can improve the outcome of cervical cancer patients with intermediate risk factors, with low increase in toxicity.

Suppressor of Cytokine Signaling (SOCS) Genes Are Silenced by DNA Hypermethylation and Histone Deacetylation and Regulate Response to Radiotherapy in Cervical Cancer Cells

Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

Detection of Recurrence by 18F-FDG PET in Patients with Endometrial Cancer Showing No Evidence of Disease

This study assessed the feasibility of F-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) in the post-therapy surveillance for patients with endometrial cancer showing no evidence of disease (NED). From April 1997 to June 2007, 127 patients with endometrial cancer showing NED were performed 18F-FDG PET scan. The feasibility of 18F-FDG PET for the early detection of recurrence in patients with endometrial cancer was evaluated retrospectively. Of the 127 patients, 32 patients showed positive lesions on 18F-FDG PET scan. Nineteen (19/127 cases, 15%) of them were confirmed to have a recurrence clinically or histologically. The sensitivity, specificity and positive and negative predictive value of 18F-FDG PET for detecting recurrences in patients with endometrial cancer were 100%, 88%, 59% and 100%, respectively. In conclusion, 18F-FDG PET may be a useful method for the post-therapy surveillance in patients with endometrial cancer.

Characteristics of thyroid incidentalomas detected by pre-treatment [18F]FDG PET or PET/CT in patients with cervical cancer

Objective Considering the increased use of [18F]FDG PET or PET/CT, the clinical significance of thyroid incidentalomas is the subject of controversy. The aim of this study was to determine the incidence of malignancies associated with thyroid incidentalomas detected by pre-treatment PET or PET/CT in patients with cervical cancer. Methods We retrospectively reviewed the medical records of patients with cervical cancer who had thyroid incidentalomas detected by pre-treatment PET or PET/CT and were treated at our institute between January 2001 and December 2009. Results Of 327 patients who underwent pre-treatment PET or PET/CT, 33 patients had thyroid incidentalomas (10.1%) and 4 patients were diagnosed with thyroid malignancies by percutaneous needle aspiration (PCNA) or surgery. To put it concretely, of 33 patients with thyroid incidentaloma, 16 patients had a diffuse uptake and 17 patients had a focal uptake. Four of 17 patients with focal uptake were diagnosed with thyroid malignancies (23.5%). One patient with a focal uptake had an atypical cell based on PCNA, but did not undergo additional studies. The mean SUVmax of thyroid malignancies did not differ from that of benign thyroid diseases. Conclusion Thyroid incidentalomas are frequently detected by pre-treatment PET or PET/CT in patients with cervical cancer. Focal uptake on PET or PET/CT has a high risk of thyroid cancer.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy.

Efficacy of Fibrin Sealant in Reducing Hemorrhage after a Loop Electrosurgical Excision Procedure

Background/Aims: We examined the association of fibrin sealant use with post-operative hemorrhage in patients who underwent a loop electrosurgical excision procedure (LEEP). Methods: We retrospectively collected clinicopathologic data of 344 patients who underwent LEEP at our institute between 2007 and 2009. We defined hemorrhage which occurred between 1 and 30 days after LEEP and required electrocautery to achieve hemostasis as severe secondary hemorrhage (SSH). We determined whether or not the use of fibrin sealant during LEEP was associated with a decreased occurrence of SSH. In addition, we examined the associations of other clinicopathologic variables with SSH and fibrin sealant use. Results: SSH occurred in 6 of 200 patients (3%) with fibrin sealant and in 12 of 144 patients (8%) without fibrin sealant. Based on univariate analysis, the use of fibrin sealant was associated with SSH (p = 0.028). However, age, surgeons and pathologic diagnosis were not associated with SSH. Based on multivariate analysis, the use of fibrin sealant was associated with less SSH (p = 0.033, OR = 0.328, 95% CI 0.117–0.917). Conclusion: Fibrin sealant use reduces the incidence of severe post-operative hemorrhage after LEEP.

Risk of metastatic ovarian involvement in nongynecologic malignancies.

Objective The objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors. Methods The eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test. Results In 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers. Conclusion One hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Prognostic Importance of the site of Recurrence in Patients with Metastatic Recurrent Cervical Cancer

PURPOSE The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. METHODS AND MATERIALS Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board. RESULTS Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group). CONCLUSIONS We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.