Sun Jin Park

Epigenetic alteration of PRKCDBP in colorectal cancers and its implication in tumor cell resistance to TNFα-induced apoptosis

Purpose: PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis. Experimental Design: Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-κB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays. Results: PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G1 cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFα, and its level correlated with tumor cell sensitivity to TNFα-induced apoptosis. PRKCDBP induction by TNFα was disrupted by blocking NF-κB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFα, and this response was abolished by disruption of a κB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFα-induced apoptosis. Conclusions: PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-κB in response to TNFα. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFα and other stresses, particularly under chronic inflammatory microenvironment. Clin Cancer Res; 17(24); 7551–62. ©2011 AACR.

Clinical Significance of Lymph Node Micrometastasis in Stage I and II Colon Cancer

PURPOSE A 25% rate of recurrence after performing complete resection in node-negative colon cancer patients suggests that their nodal staging is frequently suboptimal. Moreover, the value of occult cancer cells in tumor-free lymph nodes still remains uncertain. The authors evaluated the prognostic significance of the pathologic parameters, including the lymph node occult disease (micrometastases) detected by immunohistochemistry, in patients with node-negative colon cancer. MATERIALS AND METHODS The study included 160 patients with curatively resected stage I or II colon cancer and they were without rectal cancer. 2852 lymph nodes were re-examined by re-do hematoxylin and eosin (H-E) staining and immunohistochemical staining. The detection rates were compared with the clinicopathologic characteristics and with the cancer-specific survival. RESULTS Occult metastases were detected in 8 patients (5%). However, no clinicopathologic parameter was found to be correlated with the presence of micrometastasis. Twenty patients developed recurrence at a median follow-up of 45.7 months: 14 died of colon cancer and 9 died from noncancer-related causes. Univariate analysis showed that lymphatic invasion and the number of retrieved lymph nodes significantly influenced survival, and multivariate analysis revealed that the stage, the number of retrieved lymph nodes and lymphatic invasion were independently related to the prognosis. CONCLUSIONS Inadequate lymph node retrieval and lymphatic invasion were found to be associated with a poorer outcome for node-negative colon cancer patients. The presence of immunostained tumors cells in pN0 lymph nodes was found to have no significant effect on survival, but these tumor were identified by re-do H-E staining. Maximal attention should be paid to the total number of lymph nodes that are retrieved during surgery for colon cancer patients.

Mechanical Bowel Preparation and Prophylactic Antibiotic Administration in Colorectal Surgery: A Survey of the Current Status in Korea

Purpose The usefulness of mechanical bowel preparation (MBP) in colon surgery was recently challenged by many multicenter clinical trials and meta-analyses. The objectives of this study were to investigate current national opinions about MBP and prophylactic antibiotics (PA) and to provide preliminary data for developing future Korean guidelines for MBP and PA administration in colorectal surgery. Methods A questionnaire was mailed to 129 colorectal specialists. The questionnaires addressed the characteristics of the hospital, the MBP methods, and the uses of oral and intravenous antibiotics. Results A total of 73 questionnaires (56.6%) were returned. First, in regard to MBP methods, most surgeons (97.3%) used MBP for a mean of 1.36 days. Most surgeons (98.6%) implemented whole bowel irrigation and used polyethylene glycol (83.3%). Oral antibiotic use was indicated in over half (52.1%) of the responses, the average number of preoperative doses was three, and the mean time of administration was 24.2 hours prior to the operation. Finally, the majority of responders stated that they used intravenous antibiotics (95.9%). The responses demonstrated that second-generation cephalosporin-based regimens were most commonly prescribed, and 75% of the surgeons administered these regimens until three days after the operation. Conclusion The results indicate that most surgeons used MBP and intravenous antibiotics and that half of them administered oral PA in colorectal surgery preparations. The study recommends that the current Korean guidelines should be adapted to adequately reflect the medical status in Korea, to consider the medical environment of the various hospitals, and to establish more accurate and relevant guidelines.

Laparoscopic abdominoperineal resection for rectal cancer in a patient with situs inversus totalis.

Situs inversus totalis (SIT) is a very rare condition. Laparoscopic surgery in a patient with SIT is difficult because the surgeons dexterity is compromised during the procedure, and the patients anatomy is the mirror image of normal. We present a SIT patient who underwent laparoscopic abdominoperineal resection for rectal cancer. The detailed operative procedures and trocar placement considerations are described.

Reduced Raf-1 kinase inhibitor protein expression predicts less favorable outcomes in patients with hepatic colorectal metastasis

Reduced expression of Raf-1 kinase inhibitor protein (RKIP) has been documented in a number of human malignancies, including colorectal carcinoma (CRC). However, despite the importance of hepatic colorectal metastasis (HCM) for the prognosis of CRC patients, no studies have been conducted regarding RKIP expression in HCM tissues or its prognostic significance. The aim of this study was to clarify the relationship between reduced RKIP expression and HCM and to identify independent predictors for recurrent HCM, which will ultimately help identify patients at high risk of developing metastatic recurrence. An immunohistochemical study of RKIP expression was performed using primary CRC and/or corresponding HCM tissue samples obtained from 117 patients. Forty-nine of these patients did not harbor HCM and 68 harbored HCM. RKIP expression was reduced in 24.5% (12/49) of CRCs without HCM, 47.1% (32/68) of CRCs with HCM and 67.6% (46/68) of HCM. This distribution of RKIP downregulation was statistically significant. RKIP expression was found to independently predict recurrent HCM, with a higher relative risk (6.661) compared to that of nodal metastasis (4.690). A reduction of RKIP expression in HCM was a significant predictor of poor prognosis. The median survival of patients with reduced RKIP expression was 35 months, compared with more than 10 years in patients with positive RKIP expression. Multivariate survival analysis demonstrated that RKIP expression in HCM was an independent predictor of overall survival, with a hazard ratio of 5.161, a value comparable to the risk associated with advanced TNM stage (5.247). We demonstrated that a reduction of RKIP expression in HCM had an independent predictive value for metastatic recurrence and less favorable clinical outcomes in patients with HCM. Our results strongly suggest that patients harboring HCM with reduced RKIP expression require careful monitoring after hepatic resection to detect potentially resectable metastatic recurrences.

Influence of Shorter Duration of Prophylactic Antibiotic Use on the Incidence of Surgical Site Infection Following Colorectal Cancer Surgery.

Purpose This study aimed to identify the risk factors for surgical site infections (SSIs) in patients undergoing colorectal cancer surgery and to determine whether significantly different SSI rates existed between the short prophylactic antibiotic use group (within 24 hours) and the long prophylactic antibiotic use group (beyond 24 hours). Methods The medical records of 327 patients who underwent colorectal resection due to colorectal cancer from January 2010 to May 2014 at a single center were retrospectively reviewed, and their characteristics as well as the surgical factors known to be risk factors for SSIs, were identified. Results Among the 327 patients, 45 patients (13.8%) developed SSIs. The patients were divided into two groups according to the duration of antibiotic use: group S (within 24 hours) and group L (beyond 24 hours). Of the 327 patients, 114 (34.9%) were in group S, and 213 (65.1%) were in group L. Twelve patients (10.5%) in group S developed SSIs while 33 patients (15.5%) in group L developed SSIs (P = 0.242). History of diabetes mellitus and lung disease, long operation time, and perioperative transfusion were independent risk factors for SSIs. Conclusion This study shows that discontinuation of prophylactic antibiotics within 24 hours after colorectal surgery has no significant influence on the incidence of SSIs. This study also showed that history of diabetes mellitus and lung disease, long operation time, and perioperative transfusion were associated with increased SSI rates.

Delayed Appendectomy Is Safe in Patients With Acute Nonperforated Appendicitis.

The present study examined whether acute, nonperforated appendicitis is a surgical emergency requiring immediate intervention or a disease that can be treated with a semielective operation. Immediate appendectomy has been the gold standard in the treatment of acute appendicitis because of the risk of pathologic progression. However, this time-honored practice has been recently challenged by studies suggesting that appendectomies can be elective in some cases and still result in positive outcomes. This was a retrospective study using the charts of patients who underwent an appendectomy for acute, nonperforated appendicitis between January 2007 and February 2012. Patients were divided into 2 groups for comparison: an immediate group (those who were moved to an operating room within 12 hours after hospital arrival) and a delayed group (those within 12 to 24 hours after hospital arrival). The end points were conversion rate, operative time, perforation rate, complication rate, readmission rate, length of hospital stay, and medical costs. Of 1805 patients, 1342 (74.3%) underwent immediate operation within 12 hours after hospital arrival, whereas 463 (25.7%) underwent delayed operation within 12 to 24 hours. There were no significant differences in open conversion, operative time, perforation, postoperative complications, and readmission between the 2 groups. Length of hospital stay was significantly greater (3.7 ± 1.7 days) and medical costs were also greater [

Transanal natural orifice transluminal endoscopic surgery total mesorectal excision in animal models: endoscopic inferior mesenteric artery dissection made easier by a retroperitoneal approach

2346.30 ±

Endo-Satinsky Clamp for Rectal Transection During Laparoscopic Total Mesorectal Excision

735.30 (US dollars)] in the delayed group than in the immediate group [3.1 ± 1.9 days; P = 0.000 and

Expression of phosphorylated extracellular signal‑regulated kinase at the invasive front of hepatic colorectal metastasis

2257.80 ±