Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). METHODS: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). RESULTS: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. DISCUSSION/CONCLUSION: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.

Current status and role of antiphospholipid antibody testing in cryptogenic stroke.

BACKGROUND AND PURPOSE: Although it is not recognized as essential to test for antiphospholipid antibody (aPL) in stroke of unknown cause, aPL-related stroke may account for a considerable number of cryptogenic strokes. We aimed to assess the current status and diagnostic value of aPL testing in cryptogenic stroke patients. METHODS: Consecutive patients admitted with acute ischemic stroke were examined to confirm the factors associated with performing aPL testing and with positive aPL test results in real-world practice. Cryptogenic stroke patients were separately examined in the same manner. The antibody profiles of cryptogenic stroke patients with aPL positivity were compared by age. RESULTS: Among 2947 patients, 606 (20.6%) were tested for aPLs and 129 (21.3%) were positive. Physicians tended to perform aPL testing in patients aged <50 years and in cryptogenic stroke patients. Cryptogenic stroke was a strong predictor of positive aPL results (adjusted odds ratio 3.70, 95% confidence interval 2.38-5.76). However, aPL positivity did not differ by age in stroke patients. Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged <50 years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of >40% (<50 years: 43.2%; ≥50 years: 40.4%; p = 0.92) and their antibody profiles were similar. CONCLUSIONS: A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.

Renal Dysfunction Is Associated with Middle Cerebral Artery Pulsatility Index and Total Burden of Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD. METHODS: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 at admission) and control (eGFR ≥60 mL/min/1.73 m2) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound. RESULTS: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m2 at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85-1.57 vs. controls 0.84, IQR: 0.54-1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1-3 vs. controls median score 1, IQR: 0-2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051-20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038-1.114) as independent predictors of a high PI. CONCLUSIONS: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful.

Glycated Albumin, a Novel Biomarker for Short-Term Functional Outcomes in Acute Ischemic Stroke.

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA < 16% versus GA ≥ 16%). Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02-1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring.

Impact of onset-to-door time on outcomes and factors associated with late hospital arrival in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Previous studies have reported that early hospital arrival improves clinical outcomes in patients with acute ischemic stroke; however, whether early arrival is associated with favorable outcomes regardless of reperfusion therapy and the type of stroke onset time is unclear. Thus, we investigated the impact of onset-to-door time on outcomes and evaluated the predictors of pre-hospital delay after ischemic stroke. METHODS: Consecutive acute ischemic stroke patients who arrived at the hospital within five days of onset from September 2019 to May 2020 were selected from the prospective stroke registries of Seoul National University Hospital and Chung-Ang University Hospital of Seoul, Korea. Patients were divided into early (onset-to-door time, ≤4.5 h) and late (>4.5 h) arrivers. Multivariate analyses were performed to assess the effect of early arrival on clinical outcomes and predictors of late arrival. RESULTS: Among the 539 patients, 28.4% arrived early and 71.6% arrived late. Early hospital arrival was significantly associated with favorable outcomes (three-month modified Rankin Scale [mRS]: 0-2, adjusted odds ratio [aOR]: 2.03, 95% confidence interval: [CI] 1.04-3.96) regardless of various confounders, including receiving reperfusion therapy and type of stroke onset time. Furthermore, a lower initial National Institute of Health Stroke Scale (NIHSS) score (aOR: 0.94, 95% CI: 0.90-0.97), greater pre-stroke mRS score (aOR: 1.58, 95% CI: 1.18-2.13), female sex (aOR: 1.71, 95% CI: 1.14-2.58), unclear onset time, and ≤6 years of schooling (aOR: 1.76, 95% CI: 1.03-3.00 compared to >12 years of schooling) were independent predictors of late arrival. CONCLUSIONS: Thus, the onset-to-door time of≤4.5 h is crucial for better clinical outcome, and lower NIHSS score, greater pre-stroke mRS score, female sex, unclear onset times, and ≤6 years of schooling were independent predictors of late arrival. Therefore, educating about the importance of early hospital arrival after acute ischemic stroke should be emphasized. More strategic efforts are needed to reduce the prehospital delay by understanding the predictors of late arrival.

Effectiveness of mechanical thrombectomy in cancer-related stroke and associated factors with unfavorable outcome.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in cancer-related stroke (CRS) is largely unknown. This study aims to investigate the clinical and radiological outcomes of MT in CRS patients. We also explored the factors that independently affect functional outcomes of patients with CRS after MT. METHODS: We retrospectively reviewed 341 patients who underwent MT after acute ischemic stroke onset between May 2014 and May 2020. We classified the patients into CRS (n = 34) and control (n = 307) groups and compared their clinical details. Among CRS patients, we analyzed the groups with and without good outcomes (3-months modified Rankin scale [mRS] score 0, 1, 2). Multivariate analysis was performed to investigate the independent predictors of unfavorable outcomes in patients with CRS after MT. RESULTS: A total of 341 acute ischemic stroke patients received MT, of whom 34 (9.9%) had CRS. Although the baseline National institute of health stroke scale (NIHSS) score and the rate of successful recanalization was not significantly different between CRS patients and control group, CRS patients showed more any cerebral hemorrhage after MT (41.2% vs. controls 23.8%, p = 0.037) and unfavorable functional outcome at 3 months (CRS patients median 3-month mRS score 4, interquartile range [IQR] 2 to 5.25 vs. controls median 3-month mRS score 3, IQR 1 to 4, [p = 0.026]). In the patients with CRS, elevated serum D-dimer level and higher baseline NIHSS score were independently associated with unfavorable functional outcome at 3 months (adjusted odds ratio [aOR]: 1.524, 95% confidence interval [CI]: 1.043-2.226; aOR: 1.264, 95% CI: 1.010-1.582, respectively). CONCLUSIONS: MT is an appropriate therapeutic treatment for revascularization in CRS patients. However, elevated serum D-dimer levels and higher baseline NIHSS scores were independent predictors of unfavorable outcome. Further research is warranted to evaluate the significance of these predictors.

Triglyceride-glucose index is associated with early neurological deterioration in single subcortical infarction: Early prognosis in single subcortical infarctions.

BACKGROUND: The research about the influence of triglyceride-glucose index on early prognosis in stroke is lacking. AIMS: In this study, we evaluated the association between triglyceride-glucose index and early neurological deterioration in patients with single subcortical infarctions. METHODS: Consecutive patients with single subcortical infarctions within 72 h of symptom onset between 2011 and 2015. Early neurological deterioration was defined as an increase of ≥2 in the total NIHSS score or ≥1 in the motor NIHSS score. The triglyceride-glucose index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. RESULTS: A total of 305 patients with single subcortical infarctions were evaluated. In multivariable analysis, the triglyceride-glucose index (adjusted odds ratio [aOR] = 2.94, 95% confidence interval [CI] = 1.58-5.45) and age (aOR = 1.05, 95% CI = 1.01-1.09) were associated with early neurological deterioration. In subgroup analysis according to the type of single subcortical infarctions, only patients with proximal single subcortical infarctions showed a significant association between the triglyceride-glucose index and early neurological deterioration (aOR = 2.92, 95% CI = 1.35-6.29). On the other hand, there was no statistical significance in patients with distal single subcortical infarctions. Patients with untreated diabetes also showed the close association between the triglyceride-glucose index and early neurological deterioration (aOR = 3.94, 95% CI = 1.47-10.52). CONCLUSIONS: The triglyceride-glucose index was associated with early neurological deterioration in single subcortical infarctions. This association differed depending on the location of lesion and the presence of untreated diabetes.

Modification of Acute Stroke Pathway in Korea After the Coronavirus Disease 2019 Outbreak.

Background: Since the global pandemic of coronavirus disease 2019 (COVID-19), the process of emergency medical services has been modified to ensure the safety of healthcare professionals as well as patients, possibly leading to a negative impact on the timely delivery of acute stroke care. This study aimed to assess the impact of the COVID-19 pandemic on the acute stroke care processes and outcomes in tertiary COVID-19-dedicated centers in South Korea. Methods: We included 1,213 patients with acute stroke admitted to three centers in three cities (Seoul, Seongnam, and Daegu) through the stroke critical pathway between September 2019 and May 2020 (before and during the COVID-19 pandemic). In all three centers, we collected baseline characteristics and parameters regarding the stroke critical pathway, including the number of admitted patients diagnosed with acute stroke through the stroke critical pathway, door to brain imaging time, door to intravenous recombinant tissue plasminogen activator time, door to groin puncture time, and door to admission time. We performed an interrupted time series analysis to determine the impact of the COVID-19 outbreak on outcomes and critical pathway parameters. Results: Three centers modified the protocol of the stroke critical pathway during the COVID-19 pandemic. There was an immediate decrease in the number of patients admitted with acute ischemic stroke after the outbreak of COVID-19 in Korea, especially in the center of Daegu, an epicenter of the COVID-19 outbreak. However, the number of patients with stroke soon increased to equal that before the Covid-19 outbreak. In several critical pathway parameters, door to imaging time showed a temporary increase, and door to admission was transiently decreased after the COVID-19 outbreak. However, there was no significant effect on the timely trend. Moreover, there was no significant difference in the baseline characteristics and clinical outcomes between the periods before and during the COVID-19 pandemic. Conclusion: This study demonstrated that the COVID-19 outbreak immediately affected the management process. However, it did not have a significant overall impact on the trends of stroke treatment processes and outcomes. The stroke management process should be modified according to changing situations for optimal acute management.

Delayed transplantation may affect intellectual ability in children.

BACKGROUND: Decline in neurocognitive function is a reported complication in children with chronic illness. Concerns have been increasing that exposure to a major surgery or trauma may negatively affect cognitive performance in children. This study evaluated cognitive function in 43 Korean children who received organ transplantation (Tx), and sought to identify associated clinical factors. METHODS: Pediatric recipients of kidney (KT) or liver Tx (LT) from 1999 to 2011 were recruited for cognitive tests. Cognitive function was evaluated using intelligence quotient (IQ), social quotient (SQ), and Continuous Performance Test using Advanced Test for Attention scores, which reflect attention ability. Intellectual delay was graded as intellectual disability (ID; IQ <70) or low intelligence (LI; IQ<85). Diagnosis for attention-deficit-hyperactivity disorder (ADHD) was made by pediatric psychiatrists. RESULTS: The subjects consisted of 43 pediatric recipients of 28 LT and 15 KT. There were 20 boys (46.5%). Median age was 3.1 years (range, 0.5-15.3 years) at Tx. Median age at cognitive evaluation was 12.9 years (range, 3.4-18.4 years). Median pre-Tx duration of illness was 1.6 years (range, 0-13.5 years). The prevalence of ID, LI, and ADHD was 11.6%, 32.5%, and 32.5%, respectively. On multivariate analysis, longer pre-Tx duration of illness was a significant factor for LI (OR, 1.263; 95%CI: 1.033-1.544, P = 0.023). CONCLUSION: Longer pre-Tx duration may negatively affect intellectual ability in Korean children. Pre-Tx duration was more significant than the age at Tx or total disease duration per se. Early Tx may be beneficial for cognitive function in children.

Clinical characteristics and precipitating factors of adolescent suicide attempters admitted for psychiatric inpatient care in South Korea.

OBJECTIVE: We aimed to examine the rates, correlates, methods, and precipitating factors of suicide attempts among adolescent patients admitted for psychiatric inpatient care from 1999 to 2010 in a university hospital in Korea. METHODS: The subjects consisted of 728 patients who were admitted for psychiatric inpatient care in a university hospital over a 12-year period and who were aged 10-19 years at the time of admission. We retrospectively investigated the information on suicidal behaviors and other clinical information by reviewing the subjects' electronic medical records. Whether these patients had completed their suicide on 31 December 2010 was determined by a link to the database of the National Statistical Office. RESULTS: Among 728 subjects, 21.7% had suicidal ideation at admission, and 10.7% admitted for suicidal attempts. Female gender, divorced/widowed parents, and the presence of mood disorders were associated with a significantly increased likelihood of suicide attempts. Most common method of suicide attempts was cutting, and most common reason for suicide attempts was relationship problems within the primary support group. A diagnosis of schizophrenia was associated with increased risk of death by suicide after discharge. CONCLUSION: These results highlight the role of specific psychosocial factor (e.g., relational problems) and psychiatric disorders (e.g., mood disorders) in the suicide attempts of Korean adolescents, and the need for effective prevention strategies for adolescents at risk for suicide.

Geographical distribution and oncogenic risk association of human papillomavirus type 58 E6 and E7 sequence variations.

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.

Distribution of human papillomavirus type 16 E6 and E7 gene variants in the progression of cervical dysplasia in Korean women.

AIM: This cross-sectional, hospital-based study examined the distribution of human papillomavirus 16 E6 and E7 gene variants in Korean women with cervical lesions of varying degrees. MATERIAL & METHODS: One hundred and forty-one Korean women (median age 43 years; range 22-65 years) with human papillomavirus 16 single infections were included. The human papillomavirus 16 E6/E7 sequences were amplified from cytology specimens. The distribution of human papillomavirus 16 variations with respect to cervical lesion was examined by the exact Mantel-Haenszel linear trend test (P(trend) ) and Fisher's exact test (P). RESULTS: Human papillomavirus 16 E6 and E7 gene variants were identified in a total of 100 women (70.9%). The most prevalent human papillomavirus 16 variants were E6 Thymine178Guanine (number = 70, 49.6%) and E7 Adenine647Guanine (number = 75, 53.2%). Human papillomavirus 16 E6 Thymine178Guanine and E7 Adenine647Guanine were significantly related to the degree of cervical neoplasia (P(trend) = 0.0002, P< 0.0001; P(trend) < 0.0001, P < 0.0001, respectively). The odds ratio of human papillomavirus 16 E6 Thymine178Guanine to predict progression to cervical intraepithelial neoplasia 2-3 and invasive cancer was 2.37 (95% confidence interval 1.03-5.45) and 9.07 (95% confidence interval 2.86-28.72), respectively. The odds ratio of E7 Adenine647Guanine to predict progression to cervical intraepithelial neoplasia 2-3 and invasive cancer was 3.65 (95% confidence interval 1.16-8.51) and 9.07 (95% confidence interval 2.86-28.72), respectively. CONCLUSION: The distribution of HPV variants appears to be related to geographic difference. Human papillomavirus 16 E6 Thymine178Guanine and E7 Adenine647Guanine can be used as the candidate marker for the progression of the cervical neoplasia.

Identification of human papillomavirus type 58 lineages and the distribution worldwide.

BACKGROUND: Human papillomavirus type 58 (HPV-58) accounts for a much higher proportion of cervical cancers in East Asia than other types. A classification system of HPV-58, which is essential for molecular epidemiological study, is lacking. METHODS AND RESULTS: This study analyzed the sequences of 401 isolates collected from 15 countries and cities. The 268 unique concatenated E6-E7-E2-E5-L1-LCR sequences that comprised 57% of the whole HPV-58 genome showed 4 distinct clusters. L1 and LCR produced tree topologies that best resembled the concatenated sequences and thus are the most appropriate surrogate regions for lineage classification. Moreover, short fragments from L1 (nucleotides 6014-6539) and LCR (nucleotides 7257-7429 and 7540-52) were found to contain sequence signatures informative for lineage identification. Lineage A was the most prevalent lineage across all regions. Lineage C was more frequent in Africa than elsewhere, whereas lineage D was more prevalent in Africa than in Asia. Among lineage A variants, sublineage A2 dominated in Africa, the Americas, and Europe, but not in Asia. Sublineage A1, which represents the prototype that originated from a patient with cancer, was rare worldwide except in Asia. CONCLUSIONS: HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study.

Computed tomography for the preoperative diagnosis of pelvic actinomycosis.

AIMS: The aim of this study was to review the clinical manifestations of pelvic actinomycosis in order to aid clinicians in its diagnosis and treatment. METHODS: We retrospectively reviewed the histopathology and clinical records of all cases confirmed by surgery as pelvic actinomycosis from 1996 to 2006. RESULTS: A total of 16 cases of pelvic actinomycosis were selected and evaluated. The median age was 51 years (range, 36-66 years). All patients experienced childbirth, and had risk factors including use of an intrauterine device (93.8%) or pessary (6.2%), and/or a history of dilatation and curettage (68.8%), or previous abdominal surgery (31.3%). Nine patients (56.3%) were correctly diagnosed before surgery with computed tomography. Other common preoperative diagnoses were intra-abdominal malignancy (18.8%) and tubo-ovarian abscess (25%). The most common initial laboratory abnormalities were anemia (68.8%) and leukocytosis (62.5%). In six patients (37.5%), the preoperative values of carbohydrate antigen-125 were elevated. All patients were cured by surgery and no recurrence or mortality was noted. CONCLUSIONS: The correct initial diagnosis of pelvic actinomycosis is important for decreasing treatment-related morbidity. Imaging studies, especially computed tomography, might have assisted the diagnoses of actinomycosis.

Oral progesterone treatment in a young woman with müllerian adenosarcoma whose ovary was preserved: a case report.

Müllerian adenosarcoma is a rare biphasic tumor in young women. These tumors can recur even after complete resection. We present a patient treated with oral progesterone after hysterectomy with ovary conservation. A 35-year-old woman had a diagnosis of adenosarcoma on hysteroscopic resection, which was estrogen and progesterone receptor positive. She underwent total hysterectomy with ovary conservation and has received oral medroxyprogesterone acetate treatment. At 15 months after surgery, there has been no disease recurrence. Oral medroxyprogesterone acetate therapy can be used effectively in young women with müllerian adenosarcoma whose ovaries are preserved.

Distribution of human papillomavirus type 58 variants in progression of cervical dysplasia in Korean women.

This cross-sectional study examined the distribution of HPV 58 sequence variation in Korean women for the first time. Among 1,750 Korean women, 53 women were positive for HPV 58 single infection, of whom 26 were without disease, 20 were with cervical intraepithelial neoplasia (CIN) 1, and 7 with CIN 2 or 3. Altogether, 36 different nucleotide sequence variations were identified with the L1, 20 within E2, 5 within E6, and 10 within E7. Further studies on variants of oncogenic HPVs are necessary, particularly for the purpose of developing more predictive HPV detection methods.

Clinical characteristics of metastatic tumors to the ovaries.

Approximately 5-30% of the ovarian cancers are metastatic malignancies. The prevalence of metastatic ovarian tumors varies with the incidence rates and spread patterns of primary malignancies. We evaluated the prevalence, pre- and postoperative characteristics of metastatic ovarian cancer in Korean women. We reviewed the records for 821 ovarian malignancies with pathological consultation from 1996-2006 and recorded patient demographical, radiological, histopathological, and survival data. The study included 112 cases of histologically confirmed metastatic ovarian cancer. Metastatic ovarian cancer accounted for 13.6% of all ovarian malignancy, primarily arising from the gastrointestinal tract. The preoperative detection rate with imaging was 75%, and none of the radiological or serological features were useful for differential diagnosis. In multivariate analysis for prognostic variables, the only significant factor was the primary tumor site (p=0.004). Furthermore, extensive resection increased survival for some patients. The differential diagnosis of metastatic ovarian cancer can be problematic, so multiple diagnostic approaches are necessary. The extent of cytoreductive surgery for this type of tumor must be decided on a case-by-case basis.

Anticancer effects on TACC3 by treatment of paclitaxel in HPV-18 positive cervical carcinoma cells.

Previously, we used proteome analysis to identify transforming acidic coiled coil (TACC) 3 as a protein that is down-regulated upon paclitaxel treatment in cervical cancer cells. TACC3 mRNA and protein levels decreased after paclitaxel treatment in a time- and dose-dependent manner, and the transactivation of TACC3 promoter was dramatically diminished by paclitaxel. Importantly, paclitaxel treatment and knockdown of TACC3 by siRNA led to a synergistic enhancement of significant G2/M phase arrest and apoptosis in HeLa cells. In contrast to TACC3-deficient cells, paclitaxel treatment of mTACC3-overexpressing cells failed to induce G2/M phase arrest, cell growth inhibition, and apoptotic cell death. We studied the associated gene in mTACC overexpressed cells using microarray. From these results, numerous genes have been identified as being associated with tumor progression (Ppia, TMSB10, Annexin A2, rab31, prostaglandin E2-EP2, UHRF1), chemoresistance (Akt, Plk-1, MAP kinase) and metastasis (MMP9, PECAM-1) in mTACC3 overexpressed HeLa cells. Thus, TACC3 is thought to be the critical molecule in mediating the anticancer mechanisms of paclitaxel in p53 inactivated cells by inducing G2/M arrest and apoptosis. And our data suggested that the overexpression of TACC3 may be associated with the mechanisms of chemoresistance, tumor progression, cell proliferation and metastasis.

Neoadjuvant cisplatin and etoposide followed by radical hysterectomy for stage 1B-2B cervical cancer.

OBJECTIVES: We aimed to determine the efficacy and feasibility of neoadjuvant chemotherapy (NACT) using cisplatin and etoposide in patients with locally advanced cervical cancer. METHODS: Previously untreated patients with histologically confirmed stage 1B-2B cervical cancer were treated with three courses of NACT (60 mg/m2 cisplatin on days 1 and 2 plus 100 mg/m2 etoposide on day 1) every 10 days. NACT was followed within 2-3 weeks by radical hysterectomy with lymph node dissection. RESULTS: From 1999 to 2004, 112 patients were enrolled and 99 patients were evaluable. All eligible patients had radical surgery after NACT. Hematologic toxicity was the most common side effect, and the level of toxicity was acceptable. The overall pathologic response rate was 69.7% (69/99). The median follow-up period was 49 months, and the 5-year overall and progression-free survival rates were 88.1% and 60.5%, respectively. CONCLUSION: NACT with cisplatin and etoposide for patients with locally advanced cervical cancer is promising and has an acceptable toxicity profile. The regimen timing (every 10 days) did not delay the optimal time for radical treatment.

Human papillomavirus (HPV) type distribution in Korean women: a meta-analysis.

The aim of the present study is to estimate the overall prevalence and type distribution of human papillomavirus (HPV) in Korean women, through literature review and meta-analysis. We searched published data for the period between 1995 and 2007 using the following inclusion criteria; (1) studies using type-specific HPV tests, (2) data from Korean female, (3) with cytologic or pathologic results, (4) having more than 20 cases for each subgroup classified by cytologic results, and (5) HPV detection including types 16, 18, and at least one other type. In total, 18 studies (13,842 cases) published up to April 2007 were identified and selected. Adjusted overall HPV prevalence was 23.9% (95% CI: 23.8-24.1%) in women with normal cytology and 95.8% (95% CI: 95.4-96.2%) in women with cervical cancer. Type 16 was predominant regardless of cervical disease status, and type 58 occupied a significantly larger proportion in high-grade cervical intraepithelial lesions and cervical cancer in Korean women. HPV types 58, 33, and 52 together accounted for about 20% of infections in cervical cancer and high-grade intraepithelial lesions. After introduction of HPV prophylactic vaccines, extended protection, especially against types 58, 33, and 52, will be an important issue for cervical cancer prevention in Korea. The future dominant genotypes will require follow-up epidemiological studies with a large-scale, multicentered, and prospective design.