Prognostic Value of Progranulin in Patients with Colorectal Cancer Treated with Curative Resection.

Progranulin (PGRN) has been characterized as an autocrine growth and survival factor and is known to stimulate tumorigenesis and proliferation of several types of cancer cell. However, little is known about the prognostic role of PGRN in colorectal cancer (CRC). A retrospective analysis was performed for patients with colorectal cancer who underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semi-quantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+), and high expression was considered for tumors graded ≥2+ staining intensity. A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. Thirty-eight patients (35%) had tumors with high PGRN expression, and there was a trend of elevated pre-operative CEA and CA19-9 levels in patients with high PGRN-expressing tumors compared to those with low PGRN-expressing tumors (CEA, 49% vs. 21%; CA19-9, 21% vs. 7%). The 3-year recurrence-free survival (3Y-RFS) and overall survival rates were 83.7% (95% CI, 76.8-90.6) and 96.0% (95% CI, 92.3-99.7), respectively. Patients with high PGRN-expressing tumors had a worse rate of 3Y-RFS (66.8%) compared to those with low PGRN-expressing tumors (92.4%; p = 0.010). Multivariate analysis showed that high PGRN expression, age (>66 years), stage (III), and perineural invasion (+) were independent prognostic factors associated with poor RFS after adjusting for confounding factors including sex, MSI, tumor location, KRAS, and lympho-vascular invasion. PGRN overexpression was significantly associated with poor RFS in patients with CRC who have undergone curative resection.

Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?

BACKGROUND/AIMS: Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. METHODS: A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy. The methylation status of the SFRP2, TFPI2, NDRG4, and BMP3 promoters was investigated blindly using bisulfate-modified stool DNA obtained from 111 participants. Methylation status was investigated by methylation-specific polymerase chain reaction. RESULTS: Methylated SFRP2, TFPI2, NDRG4, and BMP3 promoters were detected in 60.0%, 31.4%, 68.8%, and 40.0% of CRC samples and in 27.8%, 27.8%, 27.8%, and 33.3% of AA samples, respectively. The sensitivities obtained using 4 markers to detect CRC and AA were 94.3% and 72.2%, respectively. The specificity was 55.0%. CONCLUSIONS: Our results demonstrate that the SFRP2, TFPI2, NDRG4, and BMP3 promoter methylation analysis of stool sample DNA showed high sensitivity but low specificity for detecting CRC and AA. Because of the low specificity, 4 methylated markers might not be sufficient for CRC screening in the Korean population. Further large-scale studies are required to validate the methylation of these markers in the Asian population and to find new markers for the Asian population.

Prospective Analysis of Minor Adverse Events After Colon Polypectomy.

BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP. METHODS: Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR 1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

Erratum: Field Cancerization in Sporadic Colon Cancer.

In the version of this article initially published, the first affiliation (affiliation number 1) was incorrectly stated as "Division of Gastroentorology, Department of Internal Medicine." The correct affiliation is "Department of Internal Medicine."

Field Cancerization in Sporadic Colon Cancer.

BACKGROUND/AIMS: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients. METHODS: We investigated promoter methylation in 34 CRC patients and five individuals with normal colonoscopy results. CRC patients were divided into three tissue groups: tumor tissue, adjacent and nonadjacent normal-appearing tissue. The methylation status (positive: methylation level >20%) of SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters was investigated using methylation-specific PCR. RESULTS: The methylation frequencies of the SFRP2 , TFPI2 , NDRG4 and BMP3 promoters in tumor/adjacent/nonadjacent normal-appearing tissue were 79.4%/63.0%/70.4%, 82.4%/53.6%/60.7%, 76.5%/61.5%/69.2%, 41.2%/35.7%/50.0%, respectively. The methylation levels of the SFRP, TFPI2, NDRG4 and BMP3 promoters in tumor tissues were significantly higher than those in normal-appearing tissue (SFRP2, p=0.013; TFPI2, p<0.001; NDRG4, p=0.003; BMP3, p=0.001). No significant correlation was observed between the methylation levels of the promoters and the clinicopathological variables. CONCLUSIONS: The field effect is present in CRC and affects both the adjacent and nonadjacent normal-appearing mucosa.

Successfully treated infective endocarditis caused by methicillin-resistant Staphylococcus Aureus in extremely low birth weight infant.

Survival rates of preterm infants have improved in the past few decades, and central venous catheters play an important role in the intensive medical treatment of these neonates. Unfortunately, these indwelling catheters increase the risk of intracardiac thrombosis, and they provide a nidus for microorganisms during the course of septicemia. Herein, we report a case of persistent bacteremia due to methicillin-resistant Staphylococcus aureus in an extremely low birth weight (ELBW) infant, along with vegetation observed on an echocardiogram, the findings which are compatible with a diagnosis of endocarditis. The endocarditis was successfully treated with antibiotic therapy, and the patient recovered without major complications. We suggest a surveillance echocardiogram for ELBW infants within a few days of birth, with regular follow-up studies when clinical signs of sepsis are observed.

Effects of short-term potassium iodide treatment for thyrotoxicosis due to Graves disease in children and adolescents.

PURPOSE: Graves disease is the most common cause of hyperthyroidism in children. Inorganic iodide has been used in combination with antithyroid drugs for more effective normalization of thyroid hormones in some cases of severe thyrotoxicosis. This study aimed to investigate clinical characteristics of childhood thyrotoxicosis and effectiveness of inorganic iodide in the early phase of treatment. METHODS: Sixty-seven pediatric patients (53 girls/14 boys, 11.1±3.4 years of age), with newly diagnosed thyrotoxicosis due to Graves disease were recruited. Forty-nine patients were treated with antithyroid drugs alone, while 18 patients were treated with combination of antithyroid drugs and potassium iodide. Initial thyroid function tests and levels of thyroid antibodies were recorded for all patients. Thyroid function tests were repeated 2 and 8 weeks after the initiation of treatment. Measurement thyroid antibodies were done 8 weeks after the initiation of treatment. RESULTS: Mean triiodothyronine and free thyroxine levels were significantly lower (P<0.05) in the group receiving combined therapy of antithyroid drugs and potassium iodide after 2 weeks of treatment compared to the patients receiving antithyroid drugs alone. Eight weeks after the initiation of treatment, thyroid function tests in the two groups did not show significant differences. CONCLUSION: The use of potassium iodide in combination with antithyroid drug is effective for more rapid normalization of thyroid hormones in the early phase treatment of childhood thyrotoxicosis, but larger studies with adequate power are needed in future.