PURPOSE: We investigated whether the loss of E-cadherin function was related to the peritoneal seeding in colorectal carcinomas. METHODS: Eleven patients who had undergone a palliative resection for a colorectal carcinoma, with peritoneal seeding, were enrolled onto the study. The primary tumors and seeding nodules were analyzed with regarded to mutations in the expressions of the CDH1 and protein of E-cadherin using SSCP, direct sequencing and immunohistochemical staining. RESULTS: In the primary tumors, the E-cadherin was normally expressed in 9 of the 11 cases, with 2 cases showing a reduced expression. In the seeding nodules, the E-cadherin was normally expressed in 6 of the 11 cases, with 5 cases showing a reduced expression. The degree of E-cadherin expression in the seeding nodules was significantly decreased comparing to that in the primary tumors (P<0.001). In the mutational analysis, there were no pathogenic mutations in either the primary tumors or the seeding nodules, with the exception of two silent changes in the ctgggt>ctaggt (intron 2) and GTG>GTA (codon 782). CONCLUSION: The loss of E-cadherin expression might be related to peritoneal seeding. The functional derangement of E-cadherin in peritoneal seeding could possibly be caused by a mechanism, such as promoter methylation, rather than the mutation of the CDH1.
Cadherins* ; Colorectal Neoplasms* ; Humans ; Methylation ; Polymorphism, Single-Stranded Conformational

BACKGROUND: An aberrant function of the mismatch repair system has been reported to underlie carcinogenesis in several tumors, including colorectal and gastric carcinomas, and to induce the typical genotype of microsatellite instability (MSI). PURPOSE: We aimed to determine the frequency of MSI in early-onset sporadic gastric carcinoma and elucidate the role of promoter methylation in hMLH1 as the mechanism of MSI. MATENRIALS AND METHODS: Thirty-six early-onset sporadic gastric carcinomas were analyzed to determine the status of MSI and the frequency of methylation of the promoter region in hMLH1. MSI was determined using five markers recommended by NCI: MSI-H (high), MSI-L (low), and MSS (Microsatellite stable). Methylation specific PCR (MSP) and direct automated genomic sequencing analysis with DNA modified by sodium bisulfite have been performed to confirm promoter region methylation. All the data were analyzed regarding characteristics of molecular changes, and clinicopathologic variables. RESULTS: The microsatellite status was determined as MSI-H in five cases (13.8%), MSI-L in 13 cases (36.1%), and MSS in 18 cases (50.0%). hMLH1 was methylated in seven cases (19.4%). In all cases of MSI-H, promoter of hMLH1 was methylated, and in two of the 13 cases of MSI-L, hMLH1 promoter methylation was identified. Methylation was not found in any cases of MSS. Promoter methylation in hMLH1 was significantly correlated with MSI status (P<0.001). We could not find any relationship between MSI and clinicopathologic parameters. CONCLUSION: These results suggest that an abnormal function of the mismatch repair system may be associated with gastric carcinogenesis in more than 10% of early-onset gastric carcinomas and MSI appeared to be closely related to the promoter methylation in hMLH1.
Carcinogenesis ; DNA ; DNA Mismatch Repair ; Genotype ; Methylation* ; Microsatellite Instability* ; Microsatellite Repeats* ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Sodium

PURPOSE: The tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined. MATERIALS AND METHODS: A total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies). RESULTS: The mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate. CONCLUSION: MECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.
Biomarkers ; Biopsy ; Cell Count ; Disease-Free Survival ; Drug Therapy ; Gene Expression ; Hematoxylin ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; Pathology ; Polymerase Chain Reaction ; Prognosis ; RNA, Messenger ; Triple Negative Breast Neoplasms* ; Venules*

To determine the role of methylation in colorectal cancer patients with a family history, we enrolled 25 colorectal cancer patients with a family history of colorectal cancer but without a mutation in the hMLH1 and hMSH2 genes. Thirty patients with sporadic colorectal cancer were included as control. The methylation status of COX2, MGMT, hMLH1, TIMP3, p16, and MINT2 in normal mucosa and tumor were assessed using methylation-specific PCR. In patients with a family history, the methylation frequency ranged from 4.0% for TIMP3 to 44.4% for MGMT, whereas, in patients with sporadic colorectal cancer, it ranged from 6.7% for TIMP3 to 50.0% for p16. Nine of the 25 patients with family history (36.0%) were classified as methylation-prone, and nine of the 30 patients with sporadic cancers (30.0%) were as methylation-prone, making their methylation indices 0.19 and 0.16, respectively (p=0.522). As for the individual genes, the methylation rate of MGMT was higher in colorectal cancer patients with family history (44.0% vs. 13.0%, p=0.016), whereas the methylation rate of p16 was higher in sporadic colorectal cancers (50.0% vs. 8.7%, p=0.046). While CpG island methylation of tumor suppressor genes may play a role in colorectal carcinogenesis, the genes involved may be different between tumors of patients with and without a family history of colorectal cancer.
Adenoma/diagnosis/genetics ; Aged ; Carcinoma/diagnosis/genetics ; Colorectal Neoplasms/*diagnosis/*genetics ; *CpG Islands ; *DNA Methylation ; Diagnosis, Differential ; Epigenesis, Genetic ; Family Health ; Female ; Genes, p16 ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction

Infectious esophagitis usually occurs in immunocompromised patients with AIDS, malignancy and those receiving immunosuppresive therapy. Common pathogens causing esophagitis include Candida, Herpes simplex virus and Cytomegalovirus. However simultaneous esophageal infection with both Candida and Herpes simplex virus has rarely been reported. The endoscopic findings of Herpes simplex esophagitis combined with Candida infection does not show typical findings due to diffuse whitish or yellowish plaques; hence, accurate diagnosis can be delayed. We observed concomitant infection of Herpes simplex virus and Candida causing esophagitis in a 45-year-old renal transplant patient who had been receiving immunosuppressive therapy. The patient showed marked reductions in clinical symptoms and in endoscopic findings after anti-fungal and acyclovir therapy.
Acyclovir ; Candida ; Cytomegalovirus ; Esophagitis ; Herpes Simplex ; Humans ; Immunocompromised Host ; Kidney Transplantation ; Methylmethacrylates ; Middle Aged ; Polystyrenes ; Simplexvirus ; Transplants

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) may contribute to the development of sleep disturbance, which may, in turn, provoke or worsen GERD. We evaluated the prevalence of GERD, non-erosive reflux disease (NERD), and extra-esophageal syndrome in subjects with self-reported sleep disturbance. METHODS: Subjects presenting for a health check-up were enrolled. Valid self-administered questionnaires provided information about reflux symptoms and sleep disturbances. We defined insomnia as self-reported sleep disturbance that occurred at least twice a week. GERD was defined as at least weekly symptoms of heartburn or acid regurgitation. Factors affecting sleep disturbance were revealed by a logistic regression analysis. RESULTS: We recruited 1,701 subjects (men 57.5%; mean age 45.0 +/- 15.0 years). The prevalence of sleep disturbance was 16.3%. GERD was reported in 14.8% of the subjects with insomnia and 7.1% of controls (p < 0.001). The prevalence of NERD was 13.7% in subjects with insomnia and 6.2% in controls (p < 0.001). The prevalence of extra-esophageal symptoms was higher in the insomniacs than controls. There was a significant correlation between the number of extra-esophageal symptoms and the frequency of sleep disturbance. Multivariate analysis showed that having GERD, NERD, extra-esophageal symptoms, and high depression and anxiety scores were predictors of sleep disturbance. CONCLUSIONS: The prevalence of GERD is higher in subjects with sleep disturbance. The number of extra-esophageal symptoms was correlated with the severity of poor sleep quality, regardless of the presence of erosive change. These findings have therapeutic implications for GERD, NERD, and extra-esophageal syndrome in patients with sleep disturbance, and future trials are warranted.
Anxiety ; Depression ; Gastroesophageal Reflux ; Heartburn ; Humans ; Logistic Models ; Multivariate Analysis ; Prevalence ; Surveys and Questionnaires ; Sleep Initiation and Maintenance Disorders

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by progressive proximal muscle weakness and atrophy. Given the recent introduction of gene therapies, knowledge of the SMA carrier frequency in various populations has become important for developing screening programs for this disease. In total, 1,581 anonymous DNA samples from an umbilical cord blood bank were tested for SMN1 and SMN2 gene copies using a multiplex ligation-dependent probe amplification assay. Twenty-nine of the 1,581 newborns [1.83%; 95% confidence interval (CI), 1.25–2.66%] were SMA carriers with one copy of SMN1, and no homozygous SMN1 deletion was detected. The carrier frequency in this population was estimated to be 1,834 per 100,000 (95% CI, 1,254–2,659) or 1 in 55 (95% CI, 1/79–1/38). Our data indicate that SMA carriers are not uncommon in the Korean population and may serve as a reference for designing a population screening program in Korea.

Aortic thrombus is a rare but life threatening disorder. The usual causes of aortic thrombus are primary or secondary thrombocythemia, malignancy, atherosclerosis, trauma, and acute infectious disease. Here, we report a case of aortic arch thrombus associated with acute pyelonephritis in a patient with thrombocythemia. A 78-year-old woman was admitted with acute pyelonephritis. A complete blood cell count showed severe thrombocythemia with platelet count of 1, 340, 000/mm3. Chest CT scan demonstrated floating thrombus in the aortic arch. After antibiotic treatement, platelet count decreased to 770, 000/mm3 and aortic thrombus disappeared without thrombolytic therapy.
Aged ; Aorta, Thoracic* ; Atherosclerosis ; Blood Cell Count ; Communicable Diseases ; Female ; Humans ; Platelet Count ; Pyelonephritis* ; Thrombocytosis* ; Thrombolytic Therapy ; Thrombosis* ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Attempts to increase colonoscopy withdrawal time have been the topic of several recent publications. We assessed whether the real-time measurement of withdrawal time affected the withdrawal time and polyp detection rate. METHODS: Real-time colonoscopy withdrawal time was measured in 197 subjects in a study group and 184 subjects comprised a control group without real-time measurements. Colonoscopies were performed by four endoscopy specialists and three fellows during their first year of training. Withdrawal time, clinical features, bowel preparation, and polyp detection rates were comparatively analyzed. RESULTS: No significant differences in age, gender, bowel preparation, or polyp history were found in the two groups. Withdrawal time was significantly higher in the study group than that in the control group when a fellow performed the withdrawal. However, polyp detection rate did not significantly increase in the study group, regardless of physician. CONCLUSIONS: Real-time measurement of colonoscopy withdrawal time did not increase polyp detection rate, but the withdrawal time was significantly higher when a fellow performed the withdrawal phase than when a specialist performed withdrawal. Therefore, the real-time measurement of colonoscopy withdrawal time seems to be a useful tool for fellow training.
Colonoscopy ; Endoscopy ; Polyps ; Quality Control ; Specialization

OBJECTIVES: We investigated the predictors of subjective memory complaints in the community-dwelling normal elderly. METHODS: This study was conducted as a part of Korean Longitudinal Study on Health and Aging (KLoSHA). 747 nondemented community-dwelling elderly aged 65 years or older were recruited. All participants underwent clinical evaluation for dementia and psychiatric disorder conformed to the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) Clinical Assessment Battery and Korean version of Mini-International Neuropsychiatric Interview, respectively. Word list recall test, frontal assessment battery, Mini Mental Status Examination (MMSE-KC) and Korean version of Geriatric depression scale (GDS-K) were administered to evaluate episodic memory, frontal function, global cognition and depression, respectively. Subjective memory complaint was defined in two different ways: worse than one's past (SMC-P) and worse than others of one's age (SMC-O). RESULTS: In highly educated elderly, minor depressive disorder (OR=7.23, 95% C.I.= 2.29-22.86) and frontal dysfunction (OR=2.48, 95% C.I.=1.29-4.77) significantly increased the risk of SMC-O. However, they did not influence the risk of SMC-P. In low educated elderly, both the minor depressive disorder and frontal dysfunction did not influence the risk of SMC-O as well as that of SMC-P. CONCLUSION: SMC-O can be a sensitive subjective recognition of mild depression and/or frontal dysfunction in highly educated normal elderly.
Aged* ; Aging* ; Alzheimer Disease ; Cognition ; Dementia ; Depression ; Depressive Disorder ; Education ; Humans ; Longitudinal Studies* ; Memory* ; Memory, Episodic