- Email: [email protected]
Predictors of mortality after emergent surgery for complicated acute diverticulitis
Vol. 211, No. 3S, September 2010
Surgical Forum Abstracts
Predictors of mortality after emergent surgery for complicated acute diverticulitis Nikiforos Ballian MBBS, Yin Wan MS, Charles P Heise MD, Eugene F Foley MD, Gregory D Kennedy MD, PhD University of Wisconsin, Madison, WI INTRODUCTION: The surgical treatment of complicated acute diverticulitis is associated with significant morbidity and mortality. However, patient and operative characteristics associated with mortality in this patient population are unclear. We hypothesize that demographic and perioperative variables can be used to predict postoperative mortality. METHODS: Patients with diverticulitis undergoing colostomy and/or partial colectomy with or without primary anastomosis were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database for years 2005 to 2008 inclusive. Only patients undergoing emergent or urgent surgery for acute diverticultis were included. Univariate analyses were performed to compare demographic characteristics, preoperative laboratory values, comorbidities and intraoperative variables. Variables with a significant (p⬍0.05) difference between survivors and non survivors were included in a stepwise logistic regression model to determine pre- and intraoperative predictors of 30-day mortality. Harrell’s concordance index (c-index) was calculated for this model. RESULTS: Two thousand three hundred fifty one patients met inclusion criteria. Mean age was 61.5 years and 50% of patients were male. Thirty-day mortality was 5.4%. Preoperative neurologic disease (p⫽0.014), radiotherapy (p⫽0.028), corticosteroid use (p⬍0.001), hypoalbuminemia (p⬍0.001), recent weight loss (p⫽0.028), age over 80 years (p⫽0.002), American Society of Anesthesiologists class 3 (p⫽0.03) or 4 (p⬍0.001), renal dysfunction (p⬍0.001) and dependent functional status (p⬍0.001) were independent predictors of postoperative mortality. There was a gradual increase in mortality with increasing numbers of risk factors. C-index was 0.90. No, of risk factors
Alive, n (%)
Dead, n (%)
Total, n
0 1 2 3 4 5 6 7
772 (100.0) 605 (98.5) 432 (96.9) 241 (89.6) 127 (79.9) 39 (58.2) 6 (30.0) 0 (0.0)
0 (0.0) 9 (1.5) 15 (3.4) 28 (10.4) 32 (20.1) 28 (41.8) 14 (70.0) 1 (100.0)
772 614 447 269 159 67 20 1
S13
METHODS: This model uses transgenic mice in which the E6 and E7 genes of HPV16 are expressed from the human keratin 14 promoter, which directs expression of these oncogenes to stratified squamous epithelia. To determine that E6 and E7 are functionally expressed, immunohistochemistry for minichromosome maintenance 7 (MCM7) and bromo deoxyuracil (BrdU) was performed on anal tissue harvested from transgenic and nontransgenic mice with or without radiation induced DNA damage. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. RESULTS: Consistent with viral oncogene expression, anal tissue of transgenic mice displayed heightened MCM7 staining, increased cells supporting DNA synthesis(BrdU-positivity), and lacked normal DNA damage response. Nearly 50% of DMBAtreated HPV16 E6/E7 transgenic mice showed overt signs of tumors and upon comprehensive histopathological examination 73% of tumor bearing mice had cancer or atypia. None of the like treated non-transgenic mice showed tumors nor had evidence of cancer or atypia. Biomarker analysis demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in human anal cancer. CONCLUSIONS: E6/E7 transgenic mice express viral oncogenes in the perianus and have heightened susceptibility to anal carcinogenesis. Our mouse model provides an experimental platform for identifying and testing oncogenic pathways and novel treatments for anal cancer.
Molecular diagnosis of pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC) Zhenbin Chen PhD, Wenyan Li BS, Julio Garcia-Aguilar MD, PhD City of Hope, Duarte, CA INTRODUCTION: Up to 25% of patients with LARC have a pCR in response to CRT, raising the question of whether surgery could be avoided in these patients. However, clinical exam or any of the current imaging studies cannot diagnose pCR before surgery.
Marie K Stelzer MD, Henry C Pitot MD, PhD, Paul F Lambert PhD University of Wisconsin, Madison, WI
METHODS: We searched for mutations in the p53, Kras, Braf and APC genes in the pretreatment biopsies and surgical specimens of patients with LARC treated with CRT and total mesorectal excision in a prospective trial. Oligonucleotides specific for those mutations were used to identify tumor DNA in the surgical specimens using Pyrophosphorolysis-Activated PolymerizationAllele specific amplification (PAP-A). Tumor response was defined as pCR when no cancer cells were found in the surgical specimens. Tumor regression grade (TRG) was defined according to standard hystopathologic criteria. PAP-P results were compared to pCR and TRG.
INTRODUCTION: Nearly 80% of anal cancer is associated with Human Papilloma Viruses (HPVs). We describe the initial generation and characterization of a mouse model for human anal cancer.
RESULTS: Mutations were found in at least one gene in 91 of 107 patients (85%). The PAP-A analysis was performed in 48 patients with pCR (13) and non-pCR (35) harboring “indel” and “hotspot”
CONCLUSIONS: Nine readily available pre-operative variables can be used to accurately determine thirty-day mortality after emergent surgery for complicated acute diverticulitis.
Using HPV transgenic mice to model anal carcinoma
Surgical Forum Abstracts
Predictors of mortality after emergent surgery for complicated acute diverticulitis Nikiforos Ballian MBBS, Yin Wan MS, Charles P Heise MD, Eugene F Foley MD, Gregory D Kennedy MD, PhD University of Wisconsin, Madison, WI INTRODUCTION: The surgical treatment of complicated acute diverticulitis is associated with significant morbidity and mortality. However, patient and operative characteristics associated with mortality in this patient population are unclear. We hypothesize that demographic and perioperative variables can be used to predict postoperative mortality. METHODS: Patients with diverticulitis undergoing colostomy and/or partial colectomy with or without primary anastomosis were retrieved from the American College of Surgeons National Surgical Quality Improvement Program database for years 2005 to 2008 inclusive. Only patients undergoing emergent or urgent surgery for acute diverticultis were included. Univariate analyses were performed to compare demographic characteristics, preoperative laboratory values, comorbidities and intraoperative variables. Variables with a significant (p⬍0.05) difference between survivors and non survivors were included in a stepwise logistic regression model to determine pre- and intraoperative predictors of 30-day mortality. Harrell’s concordance index (c-index) was calculated for this model. RESULTS: Two thousand three hundred fifty one patients met inclusion criteria. Mean age was 61.5 years and 50% of patients were male. Thirty-day mortality was 5.4%. Preoperative neurologic disease (p⫽0.014), radiotherapy (p⫽0.028), corticosteroid use (p⬍0.001), hypoalbuminemia (p⬍0.001), recent weight loss (p⫽0.028), age over 80 years (p⫽0.002), American Society of Anesthesiologists class 3 (p⫽0.03) or 4 (p⬍0.001), renal dysfunction (p⬍0.001) and dependent functional status (p⬍0.001) were independent predictors of postoperative mortality. There was a gradual increase in mortality with increasing numbers of risk factors. C-index was 0.90. No, of risk factors
Alive, n (%)
Dead, n (%)
Total, n
0 1 2 3 4 5 6 7
772 (100.0) 605 (98.5) 432 (96.9) 241 (89.6) 127 (79.9) 39 (58.2) 6 (30.0) 0 (0.0)
0 (0.0) 9 (1.5) 15 (3.4) 28 (10.4) 32 (20.1) 28 (41.8) 14 (70.0) 1 (100.0)
772 614 447 269 159 67 20 1
S13
METHODS: This model uses transgenic mice in which the E6 and E7 genes of HPV16 are expressed from the human keratin 14 promoter, which directs expression of these oncogenes to stratified squamous epithelia. To determine that E6 and E7 are functionally expressed, immunohistochemistry for minichromosome maintenance 7 (MCM7) and bromo deoxyuracil (BrdU) was performed on anal tissue harvested from transgenic and nontransgenic mice with or without radiation induced DNA damage. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. RESULTS: Consistent with viral oncogene expression, anal tissue of transgenic mice displayed heightened MCM7 staining, increased cells supporting DNA synthesis(BrdU-positivity), and lacked normal DNA damage response. Nearly 50% of DMBAtreated HPV16 E6/E7 transgenic mice showed overt signs of tumors and upon comprehensive histopathological examination 73% of tumor bearing mice had cancer or atypia. None of the like treated non-transgenic mice showed tumors nor had evidence of cancer or atypia. Biomarker analysis demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in human anal cancer. CONCLUSIONS: E6/E7 transgenic mice express viral oncogenes in the perianus and have heightened susceptibility to anal carcinogenesis. Our mouse model provides an experimental platform for identifying and testing oncogenic pathways and novel treatments for anal cancer.
Molecular diagnosis of pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC) Zhenbin Chen PhD, Wenyan Li BS, Julio Garcia-Aguilar MD, PhD City of Hope, Duarte, CA INTRODUCTION: Up to 25% of patients with LARC have a pCR in response to CRT, raising the question of whether surgery could be avoided in these patients. However, clinical exam or any of the current imaging studies cannot diagnose pCR before surgery.
Marie K Stelzer MD, Henry C Pitot MD, PhD, Paul F Lambert PhD University of Wisconsin, Madison, WI
METHODS: We searched for mutations in the p53, Kras, Braf and APC genes in the pretreatment biopsies and surgical specimens of patients with LARC treated with CRT and total mesorectal excision in a prospective trial. Oligonucleotides specific for those mutations were used to identify tumor DNA in the surgical specimens using Pyrophosphorolysis-Activated PolymerizationAllele specific amplification (PAP-A). Tumor response was defined as pCR when no cancer cells were found in the surgical specimens. Tumor regression grade (TRG) was defined according to standard hystopathologic criteria. PAP-P results were compared to pCR and TRG.
INTRODUCTION: Nearly 80% of anal cancer is associated with Human Papilloma Viruses (HPVs). We describe the initial generation and characterization of a mouse model for human anal cancer.
RESULTS: Mutations were found in at least one gene in 91 of 107 patients (85%). The PAP-A analysis was performed in 48 patients with pCR (13) and non-pCR (35) harboring “indel” and “hotspot”
CONCLUSIONS: Nine readily available pre-operative variables can be used to accurately determine thirty-day mortality after emergent surgery for complicated acute diverticulitis.
Using HPV transgenic mice to model anal carcinoma