Interventional Options for Malignant Upper GI Obstruction, 2nd ed

Background Patients with unresectable cancers of the upper gastrointestinal tract often suffer severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression. Management options vary depending on the site of obstruction, the patient’s functional status, the patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical management options. This Fact Fact reviews interventional approaches for upper GI obstructions, especially when further radiation, chemotherapy, medical management, or curative surgical options are longer helpful. Listed below are treatment options for managing different sites of obstruction (listed from least invasive to most invasive). Management decisions for these problems are complex, requiring a multi-disciplinary approach (involving surgery, gastroenterology, medical and radiation oncology, radiology, and palliative care) to achieve the best possible outcome with minimum morbidity

Interventional Options for Malignant Upper GI Obstruction, 2nd ed

Background Patients with unresectable cancers of the upper gastrointestinal tract often suffer severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression. Management options vary depending on the site of obstruction, the patient’s functional status, the patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical management options. This Fact Fact reviews interventional approaches for upper GI obstructions, especially when further radiation, chemotherapy, medical management, or curative surgical options are longer helpful. Listed below are treatment options for managing different sites of obstruction (listed from least invasive to most invasive). Management decisions for these problems are complex, requiring a multi-disciplinary approach (involving surgery, gastroenterology, medical and radiation oncology, radiology, and palliative care) to achieve the best possible outcome with minimum morbidity

Evaluation of the Charlson-Age Comorbidity Index as a Predictor of Morbidity and Mortality in Patients with Colorectal Carcinoma

The Charlson-Age Comorbidity Index (CACI) is a validated tool used to predict patient outcome based on comorbid medical conditions. We wanted to determine if the CACI would predict morbidity and mortality outcomes in patients undergoing surgery for colorectal carcinoma. Records of 279 consecutive colorectal cancer patients who underwent laparotomy by a single surgical group between 1997 and 2001 were reviewed in a retrospective fashion for patient demographics, stage at diagnosis, operation, surgeon, perioperative complications, tumor characteristics, comorbid diseases, performance status, length of stay (LOS), disposition, and mortality. Using the preoperative history and physical, all patients were assigned a score for the CACI. Perioperative morbidity and mortality were recorded and graded to account for severity. The University Statistical Consulting Center and SPSS software were used to analyze the results. The patients were primarily white (97.1%) with a male-to-female ratio of 1:1.2 and a median age of 72 years. AJCC stage at presentation was stage 0 (3.2%), stage I (28.3%), stage II (24.4%), stage III (24.4%), or stage IV (19.7%). Median LOS was 7.0 days. Perioperative mortality was 17 of 279 (6.1%), and overall mortality was 32.6% at a median follow-up of 18.5 months. Higher CACI scores and AJCC stage at presentation correlated with longer LOS and overall mortality. Only the CACI correlated with perioperative mortality and disposition. No correlation was observed with location of tumor, type of surgery, or surgeon. Patients with higher cumulative number of weighted comorbid conditions as indicated by the CACI are at higher risk for perioperative and overall mortality. This simple scoring system is also a significant predictor of disposition (home versus extended care facility) and LOS. The CACI can be a useful preoperative tool to assess and counsel patients undergoing surgery for colorectal carcinoma

Evaluation of the Charlson-Age Comorbidity Index as a Predictor of Morbidity and Mortality in Patients with Colorectal Carcinoma

The Charlson-Age Comorbidity Index (CACI) is a validated tool used to predict patient outcome based on comorbid medical conditions. We wanted to determine if the CACI would predict morbidity and mortality outcomes in patients undergoing surgery for colorectal carcinoma. Records of 279 consecutive colorectal cancer patients who underwent laparotomy by a single surgical group between 1997 and 2001 were reviewed in a retrospective fashion for patient demographics, stage at diagnosis, operation, surgeon, perioperative complications, tumor characteristics, comorbid diseases, performance status, length of stay (LOS), disposition, and mortality. Using the preoperative history and physical, all patients were assigned a score for the CACI. Perioperative morbidity and mortality were recorded and graded to account for severity. The University Statistical Consulting Center and SPSS software were used to analyze the results. The patients were primarily white (97.1%) with a male-to-female ratio of 1:1.2 and a median age of 72 years. AJCC stage at presentation was stage 0 (3.2%), stage I (28.3%), stage II (24.4%), stage III (24.4%), or stage IV (19.7%). Median LOS was 7.0 days. Perioperative mortality was 17 of 279 (6.1%), and overall mortality was 32.6% at a median follow-up of 18.5 months. Higher CACI scores and AJCC stage at presentation correlated with longer LOS and overall mortality. Only the CACI correlated with perioperative mortality and disposition. No correlation was observed with location of tumor, type of surgery, or surgeon. Patients with higher cumulative number of weighted comorbid conditions as indicated by the CACI are at higher risk for perioperative and overall mortality. This simple scoring system is also a significant predictor of disposition (home versus extended care facility) and LOS. The CACI can be a useful preoperative tool to assess and counsel patients undergoing surgery for colorectal carcinoma

YPEL3, a Novel Inducer of Senescence, is Inhibited by Estrogen in ER+ Mammary Tumor Cells

Abstract It was recently discovered by this laboratory that Yippie-like 3 (YPEL3) is a novel p53 regulated gene that when induced triggers premature senescence in primary and tumor cell lines. Initial screens of human tumor samples uncovered significant decreases in YPEL3 gene expression in ER- verses ER+ breast cancers leading us to believe that estrogen may have a regulatory effect on YPEL3 expression. Using ER+ MCF7 cells, we determined that estrogen is a significant inhibitor of YPEL3 gene expression in cells grown in media with 10% serum verses cells grown in media with charcoal stripped serum (CSS) from which estrogen has been removed. The increase in YPEL3 mRNA expression demonstrated in CSS can be blocked by the addition of estrogen, and as expected tamoxifen competes with this estrogen repressive effect. The effects of estrogen on YPEL3 expression are not observed in MCF10A mammary epithelial cells which are ER negative demonstrating the requirement for the estrogen receptor in the observed effect. Given our observation that YPEL3 induction triggers senescence in breast cancer cells, we employed beta-galactosidase activity as a measurement of senescence and observed an 8-fold increase in senescence in MCF7 cells grown in CSS media. The increase is reduced to less than 3.5-fold with the addition of estrogen to the CSS media, and the increase in cellular senescence is blocked in MCF7 cells stably selected for the loss of YPEL3 (MCF7-shYPEL3) suggesting the need for the absence of estrogen and the presence of YPEL3 in senescence induction. We are currently testing the effects of estrogen on MCF7 cells where p53 has been knocked down using RNAi approaches and are planning to test the effects of RNAi targeting ER-alpha. We believe estrogen is inhibiting YPEL3 expression through its association with the estrogen receptor and their association with p53 thereby inhibiting p53 transactivation of YPEL3. These findings suggest that modulation of YPEL3 by estrogen and its growth suppressive effects may provide a target for future breast cancer therapies. Note: First two authors contributed equally. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3066.</jats:p