Comparison of gynecologic cancer risk factors, incidence and mortality trends between South Korea and Israel, 1999-2013.

OBJECTIVE: To discuss possible causes of disparities in incidence and mortality rates of ovarian cancer, uterine cancer and cervical cancer between two diverse populations from east and west Asia. METHODS: Incidence and mortality data from 1999 to 2013 were extracted from Korean and Israeli cancer registries. Age-standardized rates and annual percent changes were calculated. Trends were analyzed using Joinpoint analysis and discussed with respect to risk factor exposure. RESULTS: Age-standardized rate of ovarian cancer significantly increased in Korea (annual percent change 1.7%) but decreased among Jews (annual percent change -2.15%). Age-standardized rate of uterine cancer increased among both Koreans and Israeli Jews (annual percent changes 5.8 and 1.17%, respectively). Incidence of cervical cancer significantly decreased in Korea (annual percent change -3.8%) while remained stable on Israel. Mortality trends paralleled incidence trends with a significant increase in ovarian cancer and uterine cancer mortality in Korea (annual percent changes 1.2 and 4.6%, respectively) and a drop in cervical cancer mortality from 2002 (annual percent change -5.8%). Among Israeli Jews, uterine cancer mortality increased (annual percent change 1.01%), while ovarian cancer mortality decreased (annual percent change -0.58%). Uterine cancer mortality among Arabs declined (annual percent change -0.5%), while cervical cancer mortality remained unchanged. CONCLUSIONS: Gynecologic malignancies show different incidence trends in Korea and Israel. Uterine cancer is rising in both countries and is correlated to changing trends in obesity and dietary habits. Ovarian cancer is rising in Korea but declining among Israeli Jews along with changes in parity, childbearing age, contraceptive use and increasing awareness to BRCA gene carriers and risk reduction salpingo-oophorectomy. Cervical cancer is declining in Korea along with an effective screening program implemented. Mortality trends follow incidence trends in both countries.

Use of Terlipressin in an Elderly Patient With Moderate Aortic Valve Stenosis Accompanied by Episodic Atrial Fibrillation During Liver Transplantation: A Case Report.

Anesthesia for patients with moderate aortic stenosis accompanied by atrial fibrillation during high-risk surgery such as liver transplantation remains a challenge in maintaining control of heart rate and maintenance of cardiac output. The action of terlipressin on vasopressin receptors (mainly V1 receptors) leads to splanchnic vasoconstriction and is the key mechanism responsible for increasing systemic vascular resistance and reducing heart rate. We report successful anesthetic management using low-dose terlipressin infusion in an elderly patient who had moderate aortic stenosis with atrial fibrillation during urgent deceased-donor liver transplantation.

Effect of Perioperative Terlipressin on Postoperative Renal Function in Patients Who Have Undergone Living Donor Liver Transplantation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Recent studies have shown the efficacy of terlipressin on postoperative renal function in patients who have undergone living donor liver transplantation (LDLT). OBJECTIVES: To evaluate the effect of perioperative terlipressin on postoperative renal function in patients who have undergone LDLT and to analyze the hemodynamic data during transplantation surgery. STUDY DESIGN: A meta-analysis. METHODS: We assessed the postoperative peak serum creatinine level and changes in the hemodynamic data (e.g. the mean arterial pressure, heart rate, and systemic vascular resistance). We collected randomized controlled trials from PubMed, EMBASE Drugs and Pharmacology, Cochrane Controlled Trials Register, and Cochrane Database on Systematic Reviews. Analysis was conducted using RevMan 5.2. Data from each trial were pooled and weighted by their mean differences and corresponding 95% confidence intervals (CI). A heterogeneity assessment was performed. RESULTS: Three trials (151 patients) were included. The difference in the mean (95% CI) peak serum creatinine (mg/dL) levels postoperatively was not significant between the intervention and control groups (weighted mean difference [WMD]: -0.27; CI: -0.55-0.01; P = .06). Terlipressin significantly decreased heart rate during the anhepatic phase (WMD: -6.58; 95% CI: -8.85 to -4.31; P < .00001) with a low heterogeneity (I(2) = 41%) and significantly decreased heart rate during the neohepatic phase (WMD: -9.82; 95% CI: -11.96 to -7.68; P < .00001), although the heterogeneity was high (I(2) > 50%). CONCLUSIONS: An intravenous infusion of terlipressin perioperatively for LDLT has no effect on the creatinine values postoperatively. Larger randomized controlled trials on terlipressin infusions during liver transplantation are needed.

Trends in the incidence of and survival rates for oral cavity cancer in the Korean population.

OBJECTIVE: This study assessed trends in the incidence of and survival rates for oral cavity cancer in the Korean population. MATERIALS AND METHODS: Data from the Korea Central Cancer Registry were extracted for 10,282 patients diagnosed with oral cavity cancer (C01-C06) between 1999 and 2010 to evaluate the age-standardised incidence rate, annual percentage change (APC) and 5-year relative survival rate (RSR) according to gender and age. RESULTS: In males, the incidence rate slightly decreased [APC of -0.2% (P = 0.6427)]; in females, the incidence rate increased [APC of 3.1% (P < 0.05)]. In males and females, the incidence of oral tongue cancer (C02) significantly increased [APC of 2.2% and 4.1%, respectively (P < 0.05)]. This increase in oral tongue cancer incidence was most prominent in the younger age group (<40 years, APC = 6.1%, P < 0.05). The incidence of buccal cheek cancer increased only among males [APC of 4.8% (P < 0.05)]. The 5-year RSR improved from 42.7% (1993-1995) to 59.5% (2006-2010), corresponding to an increase of 16.8% from 1993 to 2010 (P < 0.05). CONCLUSION: The incidence of oral cavity cancer in females increased, whereas it stabilised or decreased in males. However, the incidence of oral tongue cancer increased in both males and females, especially in the younger age group.

The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery.

BACKGROUND: We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer patients. METHODS: Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers. RESULTS: Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival [adjusted hazard ratio (aHR) = 1.36-1.86] than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal [aHR = 1.28; 95% confidence interval (CI), 1.17-1.40] and breast (aHR = 1.59; 95% CI, 1.37-1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78-3.81). CONCLUSION: Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.

Cancer survival in Busan, Republic of Korea, 1996-2001.

The Busan cancer registry was established in 1996; cancer registration is done by passive and active methods. The registry contributed survival data for 48 cancer sites or types registered during 1996-2001. Follow-up information has been gleaned predominantly by passive methods with median follow-up ranging between 1-57 months for various cancers. The proportion with histologically verified diagnosis for different cancers ranged between 20-100%; death certificates only (DCOs) comprised 0-53%; 47-100% of total registered cases were included for survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were penis (94%), thyroid (91%), non-melanoma skin (89%), placenta (86%), breast (76%), Hodgkin lymphoma (75%) and testis (72%). Five-year relative survival by age group showed a decreasing trend with increasing age groups for cancers of the nasopharynx, gall bladder, lung, bone, soft tissue, breast, cervix, corpus uteri, thyroid, multiple myeloma, lymphoid leukaemia and myeloid leukaemia or was fluctuating for other cancers.

Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study.

We investigated the risk of gastric cancer by subsite in relation to cigarette smoking and alcohol in a large population-based cohort of 669 570 Korean men in an insurance plan followed for an average 6.5 years, yielding 3452 new cases of gastric cancer, of which 127 were cardia and upper-third gastric cancer, 2409 were distal gastric cancer and 1007 were unclassified. A moderate association was found between smoking, cardia and upper-third (adjusted relative risk (aRR) 2.2; 95% confidence interval (CI) 1.4-3.5) and distal cancers (aRR=1.4; 95% CI=1.3-1.6). We also found a positive association between alcohol consumption and distal (aRR=1.3; 95% CI=1.2-1.5) and total (aRR=1.2; 95% CI=1.1-1.4) gastric cancer. Combined exposure to high levels of tobacco and alcohol increased the risk estimates further; cardia and upper-third gastric cancers were more strongly related to smoking status than distal gastric cancer.British Journal of Cancer (2007) 97, 700-704. doi:10.1038/sj.bjc.6603893 www.bjcancer.com Published online 17 July 2007.

Ovarian cancer incidence and survival in Korea: 1993-2002.

This study examined incidence rates, histologic and stage distribution, and long-term survival rates of patients with ovarian cancer in Korea. A total of 11,404 patients diagnosed with ovarian cancer between 1993 and 2002 were reported to the Korea Central Cancer Registry and the Gynecologic Oncology Committee of Korean Society of Obstetrics and Gynecology. All rates were expressed per 100,000. The age-standardized incidence rates were 3.79 and 4.74 per 100,000 women in 1993 and 2002, respectively. The incidence rates of ovary cancer increased with age in Korea, and over half of the patients were in the stage IA (24.8%) and IIIC (26.8%) in this study. The 5-year relative survival rate was 59.6%. Relative survivals according to the stage of FIGO at 5 years were 91.1%, 75.2%, 46.4%, and 21.2% for stages I, II, III, and IV, respectively. The 5-year relative survivals of germ cell tumors and epithelial ovarian cancer were 89.0% and 58.3%, respectively. Surgical stage and histology were the most important prognostic factors of ovarian cancer. However, the 5-year survival rate of FIGO stage IC was significantly higher than that of stage IB.

Cervical cancer incidence and survival in Korea: 1993-2002.

This study examined the incidence rates, histologic and stage distribution, and long-term survival rates of patients with cervical cancer in Korea. A total of 44,182 patients diagnosed with cervical cancer between 1993 and 2002 were reported to the Korea Central Cancer Registry and the Gynecologic Oncology Committee of Korean Society of Obstetrics and Gynecology. The age-standardized incidence rates were 19.0, 17.8, and 15.1 per 100,000 women in 1993-1995, 1996-1998, and 1999-2002, respectively. The incidence rates of adenocarcinoma (AC) have been in the range between 1.2 in 1993-1995 and 1.4 in 1999-2002, while those of squamous cell carcinoma declined from 15.1 in 1993-1995 to 12.2 in 1999-2002. The 5-year relative survival rate was 79.2%. Relative survival rates, according to stage by the FIGO, at 5 years were 94.2%, 69.7%, 38.9%, and 21.1% for stages I, II, III, and IV respectively. Relative survivals improved between 1993 and 1997, probably due to the introduction of cervical cancer screening and effective treatment. The incidence rates of AC have been constant despite decreased cervical cancer in Korea. Introduction of cervical cancer screening and effective treatment may have contributed to the improved relative survival.

Upregulation of c-Kit receptor and stem cell factor in cerebellar inhibitory synapses in response to kainic acid.

Neuronal stimulation was induced in rats by systemic administration of kainic acid (KA) to determine if such stimulation is responsible for changes in the expression patterns of c-Kit and stem cell factor (SCF) in cerebellar synapses between inhibitory interneurons and Purkinje cells. Using immunocytochemistry and immunoblotting analyses, we demonstrate that c-Kit receptor tyrosine kinase and its ligand SCF are present on the pre- and postsynaptic sides of inhibitory synapses on Purkinje cells. These proteins are upregulated during the first 48 hr after KA treatment, whereas their levels fall below that of the control by 1 week and remain as such thereafter. Expression of both c-Kit and SCF are significantly elevated in the Purkinje cell layer 24 hr after KA administration, and the Purkinje cell layer exhibits a loss of calbindin D-28K immunoreactivity. Expression of c-Kit in basket cell axon terminals is activated until 48 hr after KA treatment, suggesting the transient participation of c-Kit receptor tyrosine kinase in the maintenance of these axonal terminals. Also during the first 48 hr after KA treatment, SCF levels increase in axonal processes of Purkinje cells, and these SCF-positive axons correlate with c-Kit-positive pinceau structures. The increased expression of c-Kit and SCF in response to KA-induced neuronal stimulation may indicate that c-Kit receptor tyrosine kinase and its ligand SCF function in the inhibitory synapse between cerebellar interneurons and Purkinje cells, and that this role is most pronounced during the first 48 hr after KA treatment.

Annual Report of the Central Cancer Registry in Korea-1999: Based on Registered Data from 128 Hospitals.

PURPOSE: The Central Cancer Registry Center in Korea (KCCR) conducted a nationwide hospital-based cancer registry to provide basic statistical data on cancer. MATERIALS AND METHODS: In 1999, 128 hospitals participated in the cancer registry program. All cancer registry data, which was submitted from the participating hospitals by diskettes during the year, were reviewed and analyzed by the committee members who were all Board-qualified clinical oncologists and pathologists. To avoid duplication, every resident registration number was compared by a computer. Cases that had been diagnosed by a histological examination were preferentially chosen for inclusion in this data. RESULTS: Of 94,003 cases that were registered, there was a total of 8,452 (9.0%) duplication cases which were excluded. Of the remaining 85,551 cases, there were 3,231 cases (3.8%) of carcinoma in situ (morphology code/2) which were excluded. A final total of 82,320 cases were analyzed. Of the analyzed cases, 46,908 (57.0%) were males and 35,412 (43.0%) were females. The leading age groups in the order of their relative frequency were those who were 60~64 years of age (15.3%), followed by the 55~59 age group (13.8%). The six leading primary cancer sites in the order of their relative frequency were stomach (20.7%), followed by the bronchus and lung (12.1%), the liver and intrahepatic bile duct (12.0%), the colorectum (9.9%), the breast (6.4%), and then the uterine cervix (5.0%). In males, the five leading primary cancer sites were the stomach (24.2%), the liver and intrahepatic bile duct (16.3%), the bronchus and lung (16.1%), the colorectum (9.7%), and the urinary bladder (3.3%). In females, the stomach (16.2%) was the most common cancer site, followed by the breast (14.7%), the uterine cervix (11.6%), the colorectum (10.2%), and the thyroid (6.8%). Among the 1,077 cases of childhood malignancies, leukemia (35.4%), CNS tumors (16.7%), malignant lymphomas (7.0%), and sympathetic nervous system tumors (6.9%) were the most common cancer types. CONCLUSION: We analyzed and report the KCCR data from 128 nationwide hospitals during 1999.

A PCR analysis of ERalpha and ERbeta mRNA abundance in rats and the effect of ovariectomy.

To study the relative abundance and the changes of both estrogen receptor alpha (ERalpha) and ERbeta mRNA before and after ovariectomy in major organs important to the regulation of calcium homeostasis, we compared the degree of mRNA expression of ERalpha to that of ERbeta in rat tissues by performing competitive reverse transcription polymerase chain reaction (RT-PCR) with internal standards. Both ERalpha and ERbeta were highly expressed in the ovary {ERalpha[(2.2 +/- 0.33) x 10(7) copies/microg of total RNA] > ERbeta[(1.2 +/- 0.33) x 10(5) copies/microg of total RNA]} as we expected. The bone marrow and renal cortex were very important target organs of estrogen because ERalpha was highly expressed approximately 2 x 10(5) copies/microg of total RNA, but marrow cells revealed only a very weak expression of ERbeta [(0.7 +/- 0.21) x 10(2) copies/microg of total RNA]. Both ERalpha and ERbeta were expressed in the trabecular bone [(3.2 +/- 0.56) x 10(3) copy/microg of RNA] and [(2.8 +/- 0.21) x 102 copy/microg of RNA], respectively. However, they were not detected in the cortical bone. In the jejunum, the expression of ERalpha was not detectable, while ERbeta was expressed very weakly [(1.1 +/- 0.24) x 10(2) copies/microg of total RNA]. The thyroid gland expressed low copy numbers of ERbeta [(6.0 +/- 0.23) x 10(2) copies/microg of total RNA], but the parathyroid gland was negative for both ERalpha and ERbeta mRNA. In cultured stromal cells, ERalpha and ERbeta mRNAs were not detected after a 24-h culture; however, the rates of mRNA expression of ERalpha and ERbeta reached approximately 105 copies/microg of total RNA and approximately 10(2) copies/microg of total RNA, respectively, after 9-, 11-, and 13-day cultures. After ovariectomy, the expression of ERalpha mRNA decreased abruptly in the bone marrow and renal cortex, and both ERalpha and ERbeta were barely detected in the trabecular bone. In conclusion, ERalpha might be the main ER in organs important for calcium homeostasis, except in the jejunum. The mRNA expression of ERalpha in the bone marrow and renal cortex decreased abruptly after ovariectomy, which may partially explain why the effect of estrogen deficiency can be amplified and why trabecular bone loss is more predominant than cortical bone loss shortly after surgical or natural menopause.

Germline mutations of the APC gene in Korean familial adenomatous polyposis patients.

We extensively analyzed genomic DNA and messenger RNA (mRNA) from 62 unrelated Korean patients with familial adenomatous polyposis (FAP) for identification of germline adenomatous polyposis coli (APC) gene mutations. We adopted both single-strand conformation polymorphism (SSCP) analysis and a method of analysis involving the reverse transcription-polymerase chain reaction (RT-PCR) followed by a protein truncation test (PTT). DNA sequencing confirmed all alterations represented by aberrant bands. Germline mutations were identified in 38 patients (61%). Nineteen of the detected mutations were presumed to be novel, thus emphasizing the heterogeneity of the mutational spectrum in Korean FAP patients. In the initial 48 patients, SSCP analysis was followed by PTT for those patients for whom no detectable mutations were found by SSCP. Using this combined approach, we identified germline APC gene mutations in 29 of the 48 FAP patients (60%), including 6 patients in whom SSCP analysis failed to distinguish the mutant allele. In the 14 later patients, we identified truncating mutations in 9 patients (64%) using PTT only. Our results confirm that the mutation detection rate with PTT was superior to that with SSCP, and suggest that PTT would be a more practical screening method to detect germline mutations of the APC gene in FAP patients.

Altered hydroxylation of estrogen in patients with postmenopausal osteopenia.

To study the possible contributions of the differences in estrogen metabolism to bone mass in postmenopausal osteopenia, spinal and femoral bone mineral densities (BMD) were measured, and 18 urinary metabolites of estrogen were analyzed by a gas chromatography-mass spectrometry assay system in 59 postmenopausal women (5-10 yr after menopause). The BMD of the spine and femoral neck showed positive correlations with body weight, height, and body mass index as we expected. Compared to nonosteopenic subjects, there were no significant differences in serum estrone (E1) and estradiol (E2) levels in patients with osteopenia. However, the urinary 16 alpha-hydroxyestrone [16 alpha-(OH)E1] level was significantly lower in patients with spinal osteopenia (P < 0.001). Among the 18 urinary metabolites of estrogen, the 16 alpha-(OH)E1 and 16 alpha-(OH)E1/2-hydroxyestrone [2-(OH)E1) ratio showed positive correlations with spinal BMD (P < 0.05), whereas 2-(OH)E2 showed a negative correlation with femoral neck BMD (P < 0.05). The urinary 16 alpha-(OH)E1 level also revealed a positive correlation with the age-matched z score of BMD in the spine (P < 0.05). In multiple stepwise regression analysis, weight, 16 alpha-(OH)E1, interaction between 16 alpha-(OH)E1 and 2-(OH)E2, 2-(OH)E2, and years after menopause were statistically significant for spinal BMD (r2 = 0.4968). For femoral neck BMD and weight, 16 alpha-(OH)E1 and 2-(OH)E2 were the independent determinants (r2 = 0.3369). In conclusion, the activity of estrogen 16 alpha-hydroxylase was decreased and/or the activity of estrogen 2-hydroxylase was enhanced in post-menopausal osteopenia. We speculated that these derangements may serve as contributing factors for the acceleration of bone loss in post-menopausal osteoporosis.

Mutation of p53 gene in hepatocellular carcinoma cell lines with HBX DNA.

It has been known that the incidence of p53 mutation is very rare in HBX-positive primary human hepatocellular carcinoma (HCC) tissues. The frequency of p53 mutation, however, in established cell lines with integrated HBV DNA and/or HBX has not been well studied. To know p53 mutational frequency, and to investigate whether the presence of HBX DNA sequence correlates with the absence of p53 mutation in the established HCC cell lines, we studied the p53 mutation and the presence of HBX sequence in 12 recently characterized HCC cell lines. As a result, all 12 (100%) lines showed mutation in the p53 gene. Three (25%) cell lines had transversion of codon 215 while no mutation of codon 249 was found. In contrast with previous reports, although HBX DNA was present in 11 cell lines, p53 mutation had occurred, indicating that the presence of HBX viral DNA does not correlate with a lack of p53 mutation in established HCC cell lines. Our results suggest that the frequency of p53 mutation is extremely high even in HBX DNA positive HCC cell lines.