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MicroRNA-137 Is Inversely Correlated with DCLK1, Which Is a Potential Distinct Marker for Colon Cancer Stem Cells
Vol. 221, No. 4S1, October 2015
CONCLUSIONS: There is a measured higher mortality in patients with right-sided diverticulitis due to both Asian ethnicity and right-sided disease. Right-sided diverticulitis, especially in Asians, may warrant surgical attention as rigorous as that for left-sided diverticulitis. MicroRNA-137 Is Inversely Correlated with DCLK1, Which Is a Potential Distinct Marker for Colon Cancer Stem Cells Masazumi Sakaguchi, MD, Shigeo Hisamori, MD, Nobu Oshima, MD, PhD, Yoshiharu Sakai, MD, FACS Kyoto University, Kyoto, Japan INTRODUCTION: Cancer stem cells (CSCs) are considered to be a potential therapeutic target. However, most CSC markers are also expressed in normal stem cells (NSCs). DCLK1 has been proposed to be a distinct marker for colon CSCs. Meanwhile, microRNAs are important regulators of CSCs. We aimed to uncover the expression pattern of DCLK1 in colon cancer and normal colon and identify microRNAs that potentially target DCLK1. METHODS: Human colon cancer and normal colon specimens dissociated into single cells were sorted by flow cytometry to concentrate the stem cell (EpCAM+/CD66a-/CD44+) population and the differentiated (EpCAM+/CD66a+/CD44-) population, respectively. Expression patterns of 384 microRNAs and DCLK1 in colon CSCs and NSCs were analyzed using quantitative reverse transcription polymerase chain reaction. Luciferase assay and Western blotting were performed to evaluate the relationship between the microRNA and DCLK1. Lentiviral expression system with SW480 was designed to investigate the phenotype of the microRNA. RESULTS: The mRNA expression of DCLK1 was significantly upregulated in colon CSCs; microRNA-137 was highly expressed in colon NSCs. We confirmed that the activity of the luciferase gene linked to the 3 prime untranslated region of DCLK1 was decreased and that the protein level of DCLK1 was suppressed in the microRNA-137 transduced SW480 cells. Tumor growth in the microRNA-137 transduced SW480 cell-injected mice was markedly suppressed, and organoid growth of the microRNA137 transduced SW480 cells was also inhibited. CONCLUSIONS: These results suggest that microRNA-137 clearly has the potential to suppress a portion of the colon CSC properties by inhibiting the expression of DCLK1. Outcomes Associated with Resident Participation in Laparoscopic Colorectal Surgery: Assessing the “Resident Effect” Grace S Hwang, MD, Zhobin Moghadamyeghaneh, MD, Michael J Phelan, PhD, Steven Mil, MD, Alessio Pigazzi, MD, FACS, Michael J Stamos, MD, FACS, FASCRS, Joseph C Carmichael, MD, FACS, Mark H Hanna, MD University of California-Irvine, Orange, CA INTRODUCTION: The influence of residents on outcomes after specific laparoscopic colorectal surgery has not been analyzed.
Scientific Forum Abstracts
S33
Our purpose was to establish whether resident participation affected outcomes. METHODS: The NSQIP database was used to identify 5 index laparoscopic colorectal procedures of increasing complexity performed between 2005 and 2012. Set 1, right hemicolectomy for cancer; set 2, sigmoidectomy for diverticulitis; set 3, left colectomy for cancer; set 4, total colectomy for ulcerative colitis (UC); and set 5, total proctocolectomy with ileal pouch for UC. Multivariate regression analysis was used to determine potential differences in outcomes based on resident participationdjunior (PGY1-3), senior (PGY4-5) or fellow (PGY>6) residents. RESULTS: A total of 23,277 patients were included in the PGY group and 6,242 in the attending-only group. After adjusting for patient characteristics and admission status, operative time was significantly higher with residents for sets 1-3 (p<0.0001) and similar in sets 4-5 (p>0.05), with shorter OR time with fellows in set 5 (p¼0.03). Postgraduate year >4 was associated with more infection in set 1 (senior p<0.01, fellow p<0.01), longer length of stay in set 1/3 (set 1 senior p¼0.02, fellow p¼0.03; set 3 senior p¼0.01, fellow p¼0.03), more bleeding requiring transfusion in set 3 (senior p¼0.02, fellow p<0.01), and fewer pulmonary emboli in set 5 (p¼0.03). Junior residents were associated with higher rates of infection in set 1 (p<0.01) and more reoperation in set 1 (p¼0.01) (Table). Table. Mean Operative Time (minutes) by Procedure Set
Attending
Fellow
p Value
Set 1 Set 2 Set 3 Set 4 Set 5 Overall (sets 1-5)
121 158 152 233 316 Reference
151 191 194 233 292 29.19
<0.01 <0.01 <0.01 0.68 0.03 <0.0001
CONCLUSIONS: Resident participation in laparoscopic colorectal surgery was independently associated with increased odds of morbidity, longer operative time, and longer length of stay. The “resident effect” generally became smaller with increasing case complexity and increased level of resident training. Pathologic Response to Neoadjuvant Chemoradiation in Rectal Cancer Delineates Prognosis for Stage III Patients Georgios Karagkounis, MD, Leo Thai, MD, Adam G Mace, MD, Homer Wiland, MD, Rish K Pai, MD, PhD, James M Church, MD, FACS, Matthew F Kalady, MD, FACS Cleveland Clinic, Cleveland, OH INTRODUCTION: Response to neoadjuvant chemoradiation has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. We have shown that the recently implemented American Joint Committee on Cancer (AJCC) regression scores correlate with prognosis. The goal of this study
CONCLUSIONS: There is a measured higher mortality in patients with right-sided diverticulitis due to both Asian ethnicity and right-sided disease. Right-sided diverticulitis, especially in Asians, may warrant surgical attention as rigorous as that for left-sided diverticulitis. MicroRNA-137 Is Inversely Correlated with DCLK1, Which Is a Potential Distinct Marker for Colon Cancer Stem Cells Masazumi Sakaguchi, MD, Shigeo Hisamori, MD, Nobu Oshima, MD, PhD, Yoshiharu Sakai, MD, FACS Kyoto University, Kyoto, Japan INTRODUCTION: Cancer stem cells (CSCs) are considered to be a potential therapeutic target. However, most CSC markers are also expressed in normal stem cells (NSCs). DCLK1 has been proposed to be a distinct marker for colon CSCs. Meanwhile, microRNAs are important regulators of CSCs. We aimed to uncover the expression pattern of DCLK1 in colon cancer and normal colon and identify microRNAs that potentially target DCLK1. METHODS: Human colon cancer and normal colon specimens dissociated into single cells were sorted by flow cytometry to concentrate the stem cell (EpCAM+/CD66a-/CD44+) population and the differentiated (EpCAM+/CD66a+/CD44-) population, respectively. Expression patterns of 384 microRNAs and DCLK1 in colon CSCs and NSCs were analyzed using quantitative reverse transcription polymerase chain reaction. Luciferase assay and Western blotting were performed to evaluate the relationship between the microRNA and DCLK1. Lentiviral expression system with SW480 was designed to investigate the phenotype of the microRNA. RESULTS: The mRNA expression of DCLK1 was significantly upregulated in colon CSCs; microRNA-137 was highly expressed in colon NSCs. We confirmed that the activity of the luciferase gene linked to the 3 prime untranslated region of DCLK1 was decreased and that the protein level of DCLK1 was suppressed in the microRNA-137 transduced SW480 cells. Tumor growth in the microRNA-137 transduced SW480 cell-injected mice was markedly suppressed, and organoid growth of the microRNA137 transduced SW480 cells was also inhibited. CONCLUSIONS: These results suggest that microRNA-137 clearly has the potential to suppress a portion of the colon CSC properties by inhibiting the expression of DCLK1. Outcomes Associated with Resident Participation in Laparoscopic Colorectal Surgery: Assessing the “Resident Effect” Grace S Hwang, MD, Zhobin Moghadamyeghaneh, MD, Michael J Phelan, PhD, Steven Mil, MD, Alessio Pigazzi, MD, FACS, Michael J Stamos, MD, FACS, FASCRS, Joseph C Carmichael, MD, FACS, Mark H Hanna, MD University of California-Irvine, Orange, CA INTRODUCTION: The influence of residents on outcomes after specific laparoscopic colorectal surgery has not been analyzed.
Scientific Forum Abstracts
S33
Our purpose was to establish whether resident participation affected outcomes. METHODS: The NSQIP database was used to identify 5 index laparoscopic colorectal procedures of increasing complexity performed between 2005 and 2012. Set 1, right hemicolectomy for cancer; set 2, sigmoidectomy for diverticulitis; set 3, left colectomy for cancer; set 4, total colectomy for ulcerative colitis (UC); and set 5, total proctocolectomy with ileal pouch for UC. Multivariate regression analysis was used to determine potential differences in outcomes based on resident participationdjunior (PGY1-3), senior (PGY4-5) or fellow (PGY>6) residents. RESULTS: A total of 23,277 patients were included in the PGY group and 6,242 in the attending-only group. After adjusting for patient characteristics and admission status, operative time was significantly higher with residents for sets 1-3 (p<0.0001) and similar in sets 4-5 (p>0.05), with shorter OR time with fellows in set 5 (p¼0.03). Postgraduate year >4 was associated with more infection in set 1 (senior p<0.01, fellow p<0.01), longer length of stay in set 1/3 (set 1 senior p¼0.02, fellow p¼0.03; set 3 senior p¼0.01, fellow p¼0.03), more bleeding requiring transfusion in set 3 (senior p¼0.02, fellow p<0.01), and fewer pulmonary emboli in set 5 (p¼0.03). Junior residents were associated with higher rates of infection in set 1 (p<0.01) and more reoperation in set 1 (p¼0.01) (Table). Table. Mean Operative Time (minutes) by Procedure Set
Attending
Fellow
p Value
Set 1 Set 2 Set 3 Set 4 Set 5 Overall (sets 1-5)
121 158 152 233 316 Reference
151 191 194 233 292 29.19
<0.01 <0.01 <0.01 0.68 0.03 <0.0001
CONCLUSIONS: Resident participation in laparoscopic colorectal surgery was independently associated with increased odds of morbidity, longer operative time, and longer length of stay. The “resident effect” generally became smaller with increasing case complexity and increased level of resident training. Pathologic Response to Neoadjuvant Chemoradiation in Rectal Cancer Delineates Prognosis for Stage III Patients Georgios Karagkounis, MD, Leo Thai, MD, Adam G Mace, MD, Homer Wiland, MD, Rish K Pai, MD, PhD, James M Church, MD, FACS, Matthew F Kalady, MD, FACS Cleveland Clinic, Cleveland, OH INTRODUCTION: Response to neoadjuvant chemoradiation has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. We have shown that the recently implemented American Joint Committee on Cancer (AJCC) regression scores correlate with prognosis. The goal of this study