Sun Il Lee

Multicenter Analysis of Risk Factors for Anastomotic Leakage After Laparoscopic Rectal Cancer Excision The Korean Laparoscopic Colorectal Surgery Study Group

Objective:To assess the risk factors for clinical anastomotic leakage (AL) in patients undergoing laparoscopic surgery for rectal cancer. Background:Little data are available about risk factors for AL after laparoscopic rectal cancer resection. Methods:This was a retrospective analysis of 1609 patients with rectal cancer who had undergone laparoscopic surgery for rectal cancer with sphincter preservation. Clinical data related to AL were collected from 11 institutions. Univariate and multivariate analyses were performed to determine the risk factors for AL. Results:AL was noted in 101 (6.3%) of the patients. The leakage rate ranged from 2.0% to 10.3% for each hospital (P = 0.04). In patients without protective stomas (n = 1187), male sex [hazard ratio (HR), 3.468], advanced tumor stage (HR, 2.520), lower tumor level (HR, 2.418), preoperative chemoradiation (HR, 6.284), perioperative transfusion (HR, 10.705), and multiple firings of the linear stapler (HR, 6.181) were significantly associated with AL. Our theoretical model suggested that the HR for patients with 2 risk factors was significantly higher than that the HR for patients with no or only 1 risk factor. Conclusions:Male sex, low anastomosis, preoperative chemoradiation, advanced tumor stage, perioperative bleeding, and multiple firings of the linear stapler increased the risk of AL after laparoscopic surgery for rectal cancer. A diverting stoma might be mandatory in patients with 2 or more of the risk factors identified in this analysis.

The Prognostic Significance of E-Cadherin and Liver Intestine-Cadherin Expression in Colorectal Cancer

PurposeThe significance of liver intestine-cadherin as a potential marker has been growing in the field of oncology, because of its unique features compared with classic cadherins. We investigated the coexpression patterns of E-cadherin and liver intestine-cadherin in colorectal cancer, and determined whether differences in expression patterns were associated with clinicopathologic parameters and also which relationship between these two adhesion molecules existed in colorectal cancer.MethodsExpression pattern of E-cadherin and liver intestine-cadherin was investigated immunohistochemically in 207 colorectal cancers along with clinicopathologic parameters.ResultsReduced expression of liver intestine-cadherin was detected in 51 percent (n--05) of tumors. Such expression was found to be associated with tumoral dedifferentiation (P--.015) and in a multivariate analysis was associated with a significant worse overall survival after adjustment for tumor stage, differentiation, and E-cadherin status (hazard ratio, 1.951; 95 percent confidence interval, 1.06-.592; P--.032). Fifteen percent (n--2) of tumors showed reduced expression of E-cadherin and had relationship with tumoral dedifferentiation (P-lt;-.001), lymph node metastasis (P--.004), and advanced stage (P--.029). Reduced expression of E-cadherin was associated with short overall survival (P--.028); however, in a multivariate analysis, it was not statistically significant.ConclusionsReduced expression of liver intestine-cadherin had a significant correlation with tumoral dedifferentiation and short overall survival in this series. In addition, early and frequent loss of liver intestine-cadherin expression might be a more sensitive indicator than E-cadherin to predict more aggressive tumoral behavior.

BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres’ cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

Relationship between meat and cereal consumption and colorectal cancer in Korea and Japan

Background and Aim:  The incidence of colorectal cancer in Asian countries is increasing. The change to a more westernized diet is known to be related to these increases, and there are reports on the relationship between meat consumption and colorectal cancer in Japan. The aim of this study was to investigate the relationship between dietary change and colorectal cancer in Korea and Japan.

The Role of Laparoscopic Approach for Anastomotic Leakage After Minimally Invasive Surgery for Colorectal Cancer

OBJECTIVES The objectives of this study were to evaluate the feasibility and safety of a re-laparoscopic approach to manage anastomotic leakage after minimally invasive colorectal resection and to compare its clinical outcomes with those obtained using an open approach. METHODS We retrospectively reviewed clinical data from 1714 patients who underwent colorectal cancer resection from September 2006 to August 2009 at the Korea University Medical Center. Clinical data from a total of 57 surgery patients who developed anastomotic leakage were analyzed. RESULTS Twenty-six leakage cases were managed laparoscopically, whereas the remaining 31 leakage cases were managed using an open approach. There were no significant differences in age, sex, or other clinical features between patients in the two groups. The total operation time was shorter in the laparoscopic group (107.3 ± 68.1 minutes) than in the open group (126.5 ± 50.1 minutes), but this difference was not statistically significant (P = .230). Six cases in each group required additional procedures such as reoperation or percutaneous intervention (P = .126). There was one case of postoperative mortality in the open group. Median (quartiles 25%-75%) number of days required to resume a soft diet tended to be shorter in the laparoscopic group than the open group (5 [3-7] versus 6 [5-10] days; P = .057). Patients in both groups showed similar postoperative complications including intraabdominal abscess; however, the incidence of wound infection was significantly lower in the laparoscopic group than the open group (3.8% versus 25.8%; P = .031). CONCLUSIONS Compared with conventional open treatment of anastomotic leakage, the laparoscopic approach resulted in fewer wound complications and tendency of early recovery of bowel movement without an increase in adverse outcomes. Using a laparoscopic approach, all the advantages of minimally invasive surgery can be realized in patients who develop anastomotic leakage after minimally invasive surgery.

Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells

Metformin is an anti-diabetic drug with a promising anti-cancer potential. In this study, we show that subtoxic doses of metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which induces apoptosis. Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells. CRC cells treated with metformin and TRAIL showed activation of the intrinsic and extrinsic pathways of caspase activation. We attempted to elucidate the underlying mechanism, and found that metformin significantly reduced the protein levels of myeloid cell leukemia 1 (Mcl-1) in CRC cells and, the overexpression of Mcl-1 inhibited cell death induced by metformin and/or TRAIL. Further experiments revealed that metformin did not affect mRNA levels, but increased proteasomal degradation and protein stability of Mcl-1. Knockdown of Mule triggered a significant decrease of Mcl-1 polyubiquitination. Metformin caused the dissociation of Noxa from Mcl-1, which allowed the binding of the BH3-containing ubiquitin ligase Mule followed by Mcl-1ubiquitination and degradation. The metformin-induced degradation of Mcl-1 required E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through Noxa and favors the interaction between Mcl-1 and Mule, which consequently affects Mcl-1 ubiquitination.

Rectal Diverticular Perforation Complicating Diagnostic Colonoscopy: A Case Report and Review of the Literature

Abstract The presence of retroperitoneal, mediastinal, and subcutaneous emphysema due to rectal diverticular perforation during diagnostic colonoscopy has not been reported. Further, the management of colonoscopic perforation remains a controversial issue. In this case report, the authors discuss the importance of recognizing this rare complication after colonoscopy and its response to conservative treatment.

Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells.

Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron-chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation.

Significance of Follow-up in Detection of Pulmonary Metastasis of Colorectal Cancer.

Purpose This study was performed to evaluate the effectiveness of conventional chest radiography, carcinoembrionic antigen (CEA) level and abdominal computed tomography (CT) or chest CT for early detection of pulmonary metastasis after a curative resection of colorectal cancer. Methods We retrospectively reviewed 84 cases of pulmonary metastasis from a group of colorectal cancer patients who had a curative surgical resection from 2000 to 2006 at the Korea University Medical Center. Results Stage I tumors were detected in 4 patients, stage II tumors in 18, stage III tumors in 43 and stage IV tumors in 19. The detection rates for pulmonary metastasis were 28.5% by conventional chest radiography, 40.5% by increased CEA level and 28.5% by abdominal CT or chest CT. Among them, fourteen patients underwent a radical pneumonectomy. After detection of pulmonary metastasis, the survival outcome for the patients who underwent a resection of the lung was superior to the survival outcome of the patients who did not undergo a resection of the lung (43.7 months vs. 17.4 months, P = 0.001). For patients who underwent resections of the lung, pulmonary metastasis was detected by conventional chest radiography in 2 (14%) patients, by elevated CEA level in 6 (42%) patients, and by abdominal CT or chest CT in 6 (42%) patients. Conclusion Conventional chest radiography is no more useful in detecting early pulmonary metastasis after a curative colorectal surgery than a routine chest CT. Thus, we propose the use of routine chest CT for screening for lung metastasis.

The significance of microsatellite instability in colorectal cancer after controlling for clinicopathological factors

Abstract The colorectal cancer (CRC) patients with microsatellite instability (MSI) have distinct clinicopathological characteristics consisting of factors predicting positive and negative outcomes, such as a high lymph node harvest and poor differentiation. In this study, we measured the value of MSI as a prognostic factor after controlling for these discrepant factors. A total of 603 patients who underwent curative surgery for stages I to III colorectal cancer were enrolled. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Propensity score matching was used to match clinicopathological factors between the 2 groups. MSI-H patients had a high lymph node harvest (median: 31.0 vs 23.0, P < .001), earlier-stage tumors (P < .001), advanced T stage (89.3% vs 74.0%, P = .018), and poor differentiation (19.6% vs 2.0%, P < .001). Survival analysis showed better survival in the MSI-H group, but the difference was not statistically significant (P = .126). Propensity score matching was performed for significant prognostic factors identified by Cox hazard regression. After the matching, the survival difference by MSI status was estimated to be larger than before, and reached statistical significance (P = .045). In conclusion, after controlling for pathological characteristics, MSI-H could be a potent prognostic factor regarding patient survival.