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E Christopher Ellison

Publications and source records attributed to E Christopher Ellison.

At least 19 recordsLinked to original sources
PubMed2006

Stromal osteonectin overexpression is associated with poor outcome in patients with ampullary cancer.

BACKGROUND: Osteonectin has been suggested to be important in the progression of pancreatic cancer but has not been correlated with survival. We determined the osteonectin expression and its influence on survival in patients with ampullary carcinoma. METHODS: Tissue microarrays were constructed from the tumors of 56 patients with ampullary cancer undergoing pancreaticoduodenectomy. Immunohistochemical staining for osteonectin was undertaken and compared with staining in chronic pancreatitis (n = 13) and normal pancreas (n = 19). Survival curves were created by the Kaplan-Meier method and compared by log rank analysis. Median follow-up for all living patients with ampullary cancer was 69.6 months. RESULTS: Osteonectin was significantly (P < .05, Fisher's exact test) overexpressed in the stroma of ampullary cancers (90%) relative to chronic pancreatitis (62%) and normal pancreas (0%). Tumors expressing osteonectin were more likely to have nodal metastases than those lacking osteonectin expression (48% vs. 0%, P = .06, Fisher's exact test) and showed decreased survival. Node-negative status, pylorus preservation at the time of pancreaticoduodenectomy, and lack of osteonectin expression were predictors of prolonged survival by multivariate analysis. CONCLUSIONS: Although the importance of tumor-stroma interactions in periampullary cancers is not fully understood, our data suggest that osteonectin is an integral stromal element in ampullary cancers, and its overexpression is associated with decreased survival.

Adenocarcinoma↗
PubMed2006

Differential gene expression in patients genetically predisposed to pancreatic cancer.

BACKGROUND: Nearly 10% of all pancreatic cancer (PCA) results from genetic predisposition. Although abnormalities in sporadic PCA have been described, little is known about the genetics of heritable PCA. The purpose of this study was to identify novel genes expressed in patients with a presumed genetic predisposition or "familial" PCA. PATIENTS AND METHODS: We defined "familial" PCA as patients having one or more first-degree relatives with biopsy-proven adenocarcinoma of the pancreas. Using a PCR-based subtractive and enrichment procedure, representational difference analysis (RDA), pancreatic tumor cDNA was reverse-transcribed from pooled poly(A)+ mRNA from six such patients (tester) and compared to pooled cDNA from five normal pancreata (driver). Tumor-specific gene fragments were identified and confirmed to be overexpressed in familial PCA by comparative RT-PCR. Six PCA cell lines, 11 sporadic tumors, 5 neuroendocrine tumors, and 3 chronic pancreatitis tissues were screened to determine the specificity of these genes. RESULTS: Sequence analysis revealed several sequences of unknown significance and six genes previously described in neoplasia/carcinogenesis: Apolipoprotein A4, CEA, Keratin 19, Stratifin (14-3-3 sigma), Trefoil Factor, and Calcium Binding Protein S100 A6. Screening of cell lines and pancreatic tissue types showed varying degrees of specificity for familial and sporadic PCA. The APO-A4 gene was up-regulated in familial PCA. CONCLUSIONS: The pattern of frequency in all screened tissue suggests that these genes are associated with conditions that produce significant desmoplastic responses and are difficult to differentiate from chronic inflammatory processes. Apolipoprotein A4 is preferentially expressed in familial patients, suggesting that the importance of fatty acid synthesis in carcinogenesis be investigated further.

Adenocarcinoma↗
PubMed2006

Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique.

BACKGROUND: The effect of overexpression of epidermal growth factor receptor (EGFR) in pancreatic carcinoma is not clear. Utilizing tissue microarrays, we evaluated EGFR expression in pancreatic cancer to determine the association of EGFR expression with histopathologic characteristics and patient outcome. METHODS: 71 cases of pancreatic adenocarcinoma and 18 cases of chronic pancreatitis were retrieved from archival files. Tissue cores from donor blocks were arrayed to create a tissue microarray. Sections were stained with EGFR and the intensity of membranous staining and percentage of tumor cells showing immunoreactivity were determined. At least 1% membranous staining and 1+ intensity were considered positive. RESULTS: EGFR was present in 49 of 71 (69%) cases of pancreatic adenocarcinoma and 7 of 18 (39%) cases of chronic pancreatitis (p = 0.03). There was no statistically significant correlation between intensity or extent of EGFR expression and tumor grade, size, or lymph node status. While median survival was nearly twice as long when EGFR was expressed (15.2 vs. 8.3 months), this did not reach statistical significance. CONCLUSIONS: EGFR is overexpressed in pancreatic cancers independent of histopathologic characteristics and does not predict survival. Immunohistochemical analysis of EGFR staining may help in identifying candidates for EGFR inhibitor therapy.

Adenocarcinoma↗
PubMed2006

50-year appraisal of gastrinoma: recommendations for staging and treatment.

BACKGROUND: Gastrinoma is a rare neuroendocrine tumor associated with ulcerogenic syndrome. The purpose of this study was to provide information on current controversies related to treatment, including staging, patient selection, and outcomes for surgical resection. STUDY DESIGN: A retrospective review of 106 patients with gastrinoma. Patients were classified as sporadic gastrinoma (SG) or MEN. End points of analysis included disease-free and disease-specific survival. Kaplan-Meier survival analysis was performed and significance (p < 0.05) was determined by Mantel-Haenszel log-rank test. RESULTS: Gastrinoma can be staged by TNM criteria into four groups (stage 0, I, II, and III), which had notably different survival curves, dependent on tumor size and distant metastases (p < 0.0001), but independent of lymph node metastases (p = 0.324). Surgical resection was possible in 72 patients (SG, n = 50; MEN, n = 22). Durable cure rate for SG was 26%, compared with 4% for MEN-1. Surgical resection achieving gross removal of all tumor resulted in improved survival in both SG and MEN patients (p < 0.0001). Improved survival was independent of a normal postoperative serum gastrin. Stage III was highly predictive of incomplete resection and the associated failure to improve survival (p = 0.0001). CONCLUSIONS: Staging provides a reliable method for the clinician to select patients for operation and to provide a prognosis, and should permit better comparisons of treatment between institutions. In the management of gastrinoma, it is recommended that SG and MEN patients with clinical stage I and II disease have surgical exploration, patients with stage III disease not have mandatory surgical treatment, and some stage 0 patients might not need routine surgical exploration.

Disease-Free Survival↗
PubMed2006

Cytoreduction results in high perioperative mortality and decreased survival in patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas.

We reviewed our experience with pancreatectomy for neuroendocrine tumors (NE) to determine outcomes after R0/R1 or R2 resection and compare them to patients in whom resection was not attempted. Data were reviewed for all patients presenting with NE tumors of the pancreas between 1990 and 2005. Kaplan-Meier survival curves were compared by log-rank analysis. Multivariate analysis was completed using Cox proportional hazards to identify risk factors for poor survival after resection. Of 120 patients, 65 (54%) had functional tumors. Resection was undertaken in 83: distal pancreatectomy in 41, pancreaticoduodenectomy in 27, enucleation in 14, and central pancreatectomy in 1. Survival was significantly longer after resection (91 months versus 24, P<0.001). R0/R1 resection was accomplished in 64 (77%) and resulted in lower perioperative mortality (2% versus 21%, P<0.01) and longer survival (112 months versus 24, P<0.001) compared to R2 resection. Survival after R2 resection was no better than after no resection. Factors predictive of decreased survival were moderate/poor differentiation, R2 resection, and high-risk features. Long-term survival is possible following complete resection for NE tumors of the pancreas. However, cytoreduction resulting in incomplete tumor removal carries significant perioperative mortality without long-term survival benefit and should be discouraged.

Adult↗
PubMed2006

Preoperative carbohydrate antigen 19-9 is most predictive of malignancy in older jaundiced patients undergoing pancreatic resection.

OBJECTIVES: Given the increased detection of occult pancreatic neoplasms with modern imaging modalities, it is often difficult to determine the risk of malignancy before curative pancreatectomy. We reviewed patients who underwent pancreatectomy to determine factors predictive of malignancy with particular attention to the serum marker carbohydrate antigen 19-9 (CA19-9). METHODS: One hundred eighteen patients underwent radical pancreatectomy for malignant (n = 59) or benign (n = 59) pancreatic lesions. Demographic data, preoperative CA19-9 levels (normal, <37 U/mL), and follow-up were obtained from patient charts. Logistic regression analysis was used to determine univariate and multivariate predictors of malignancy. RESULTS: Significant multivariate predictors of malignancy were increased CA19-9, age older than 50 years, and preoperative jaundice. The sensitivity and specificity of increased preoperative CA19-9 alone were 71% and 83%, respectively. The combination of age older than 50 years and jaundice was a more accurate predictor than CA19-9 (sensitivity, 76%; specificity, 92%). Increased CA19-9 was highly specific (97%) for malignancy in older jaundiced patients or when the preoperative level was greater than 150 U/mL. CONCLUSIONS: Age and preoperative jaundice are more predictive of malignancy than CA19-9 alone unless levels are greater than 150 U/mL. Preoperative CA19-9 levels should be interpreted within the context of these other clinical factors.

Adult↗
PubMed2006

Carcinosarcoma of the pancreas arising in a mucinous cystic neoplasm.

We report a carcinosarcoma of the pancreas in a 67-year-old woman who presented with nausea, vomiting, and painless jaundice. A work-up demonstrated a well-circumscribed mass in the head of the pancreas. After pylorus-preserving pancreaticoduodenectomy, the tumor was found to be grossly yellow, and it compressed the common bile duct and pancreatic duct. Histological examination of the neoplasm showed a 4.0 x 4.0 x 3.0-cm mucinous cystadenocarcinoma with invasive poorly differentiated carcinoma, well-differentiated squamous cell carcinoma, and sarcomatous stroma invading into the duodenum. There was no evidence of nodal metastasis (pT3N0M0). Immunohistochemical studies showed that the epithelial cells stained positive for cytokeratin 7, cytokeratin AE1/3, cytokeratin monoclonal antibody 5.2, epithelial membrane antigen, M-carcinoembryonic antigen, and low-molecular-weight kininogen, and the sarcomatous component was immunoreactive with vimentin. The patient had an uneventful recovery, but died 4 months later of rapidly progressive metastatic disease to the liver and peritoneum. To the best of our knowledge, this is the second case of carcinosarcoma with invasive epithelial and sarcomatous areas in the background of a mucinous cystic neoplasm of the pancreas.

Adenocarcinoma, Mucinous↗
PubMed2004

Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesions.

Postoperative peritoneal adhesions are common and serious complications of general abdominal and gynecological surgery that can lead to chronic abdominal pain, small-bowel obstruction and infertility. The specific pathophysiology of peritoneal adhesions remains elusive and current treatment is relegated to prevention through meticulous surgical technique and protective physical barriers, gels and solutions. We have reported that reactive oxygen species (ROS), generated by phagocytic cells at the site of tissue injury, serve as major signaling molecules regulating the expression of vascular endothelial growth factor (VEGF) and subsequent wound repair. We hypothesized that peritoneal adhesions are a product of over-healing surgical wounds and that, like in wound healing, ROS are implicated in their pathogenesis. We examined the presence of footprints of ROS and the ROS-inducible angiogenic factor VEGF in human adhesion tissue. An experimental model of peritoneal adhesion was established in rodents to study of the dynamics of ROS-induced gene expression during de novo adhesion tissue formation. Immunohistochemical analysis demonstrated presence of ROS/oxidant and macrophages in human peritoneal tissue. The presence of ROS and ROS-sensitive transcription factor EGR-1 was also evident in an experimental rodent peritoneal adhesion model. Along with ROS, VEGF, and a large number of mature and immature CD31/vWF positive blood vessels were present in the adhesion tissue. These observations are not consistent with the contention that adhesions are non-functional scar tissue. The newly developed rodent model of adhesion may present a useful approach to reproducibly and objectively study molecular mechanisms underlying the dynamic process of de novo adhesion tissue formation.

Animals↗
PubMed2004

Oxygen: at the foundation of wound healing--introduction.

"Wound Healing: Oxygen & Emerging Therapeutics" Columbus, Ohio, September 12-15, 2002. Sponsored by the National Institutes of Health (R13 AR 049171), International Union of Biochemistry & Molecular Biology and UNESCO-Global Network of Molecular & Cell Biology. Conference co-chairs: Chandan K. Sen, the Ohio State University Medical Center and Thomas K. Hunt, University of California-San Francisco. This congress was conceived for two reasons: to consolidate what is known about oxygen in the repair process and to stimulate discussion about new developments of control of healing by redox regulated signaling processes. A historical and evolutionary perspective on the role of oxygen in wound healing--from the classical physiology of oxygen in the wound to the refined concept of redox signaling--is presented.

Cell Hypoxia↗
PubMed2004

Hepatocellular adenomatosis is a rare entity that may mimic other hepatocellular lesions.

A 14-year-old girl presented to her pediatrician with right lower quadrant pain that progressed to right upper quadrant pain with radiation to her back. Her past medical history included mitral valve prolapse, and she had no history of oral contraceptive use. Abdominal computed tomography revealed a liver mass and multiple smaller areas of low attenuation, too small to characterize. The clinical and radiographic features were suggestive of hepatocellular adenoma, and she underwent a left hepatic lobectomy. The liver contained one 4.2 cm nodule and multiple (10 to 20) smaller nodules that were well-demarcated from the adjacent liver parenchyma. All lesions were histologically hepatocellular adenomas and, therefore, she was diagnosed with hepatocellular adenomatosis. This case is unique because of the small number of cases of hepatocellular adenomatosis diagnosed in teenagers, and little long-term follow-up.

Adenoma, Liver Cell↗
PubMed2004

Microvascular density does not correlate with histopathology and outcome in neuroendocrine tumors of the pancreas.

Microvascular density (MVD), a marker for tumor angiogenesis, has been demonstrated to have prognostic significance in various malignancies. Previous studies have demonstrated that MVD is an independent prognostic factor in pancreatic adenocarcinoma and that longer survival is associated with hypovascular tumors. The prognostic importance of MVD in pancreatic neuroendocrine tumor (NET) has not been documented. We evaluated MVD in pancreatic NET and correlated it with clinicopathologic features and patient outcome to determine whether MVD is a useful prognostic indicator for these patients. Twenty-five pancreatic NETs from our archival files resected between 1981 and 2000 were identified. The mean MVD was determined for each tumor from the 3 most vascularized 200 x fields. Clinical follow-up ranged from 1 to 19 years, with a mean of 4.9 years. At last follow-up, 6 patients were dead of disease, 10 patients were alive without disease, 4 patients were alive with disease, and 5 patients were alive with disease status unknown. Mean MVD ranged from 43 to 527 microvessels per 200 x field. MVD did not correlate with tumor size, the examined histologic parameters, or patient outcome. MVD in pancreatic NET does not correlate with the clinicohistologic features evaluated in this study or with the patient outcome and is not a useful prognostic indicator in these patients. These results suggest that factors other than the simple number of microvessels are important in determining pancreatic NET behavior. However, most tumors were highly vascular, and additional studies may be helpful to clarify further the role of vascularity and assess the utility of antiangiogenic agents in the treatment of pancreatic NET.

Female↗
PubMed2003

Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors?

Effective medical therapy of gastric hypersecretion in Zollinger-Ellison syndrome may delay the diagnosis of gastrinoma. To examine the impact of effective medical therapy on the surgical treatment of gastrinoma we reviewed the records of 108 patients diagnosed between 1948 and 1998 at a single institution. Minimum follow-up was 5 years. The experience was divided into four periods: I, 1955-1965-initial recognition, n = 11; II, 1966-1975-increasing recognition, n = 27; III, 1976-1985-widespread application of gastrin radioimmunoassay, n = 21; and IV, 1986-1998-widespread use of effective medical therapy, n = 49. There was no significant difference in age or sex in the groups. Gastric surgery was less common in period IV (37% compared with 86% to 100% in previous periods) as was total gastrectomy (6% compared with 43% to 78%; P <0.0001). Tumor resection was attempted in a similar percentage of patients in each group (57% to 67%). The incidence of metastatic disease in period III was 19% (P = 0.034 versus period I, 45%, period II, 56%, and period IV, 55%). The 5-year disease-free survival increased in period III to 29% (P = 0.001 versus period I, 0%, period II, 4%, and period IV, 2%). The results support the effectiveness of acid suppressive therapy by H2 antagonists and proton pump inhibitors as evidenced by the decrease in gastric surgery. However, in the era of effective medical therapy, the surgeon sees the patient with more advanced disease and 5-year cure is less likely. Physicians must maintain a high index of suspicion for this disease and not mask a potential malignancy with prolonged control of acid-related symptoms without taking steps to diagnose gastrinoma.

Adult↗
PubMed2003

Recollections of Robert M. Zollinger, M.D.

Remembering Dr. Robert M. Zollinger are Dr. Larry C. Carey, professor of surgery at the University of South Florida, in Tampa, Florida; Dr. Dan W. Elliott, professor emeritus of surgery at Wright State University, in Dayton, Ohio; Dr. E. Christopher Ellison, the Robert M. Zollinger professor and chairman of surgery at Ohio State University, in Columbus, Ohio; Dr. Timothy C. Fabian, professor and chairman of surgery at the University of Tennessee, in Memphis, Tennessee; and Mrs. Letitia Roberts, the widow of Dr. Stuart S. Roberts, the first recipient of the Zollinger Chair of Surgery at Ohio State, of Peoria, Illinois.

General Surgery↗
PubMed2003

A history of the Ohio State University Department of Surgery.

Doctor Robert M. Zollinger wrote this piece prior to his death in 1992. He recounts the history of the Ohio State University Department of Surgery from the evolution of the Ohio State University College of Medicine to the years of the department's reorganization and growth after World War II.

General Surgery↗