Faculty Bibliography

BACKGROUND:Most experts agree that primary hyperaldosteronism (PHA) caused by an aldosterone-producing adenoma (APA) is best treated by adrenalectomy. From a public health standpoint, the cost of treatment must be considered. We sought to compare the current guideline-based (surgical) strategy with universal pharmacologic management to determine the optimal strategy from a cost perspective. METHODS:A decision analysis was performed using a Markov state transition model comparing the strategies for PHA treatment. Pharmacologic management for all patients with PHA was compared with a strategy of screening for and resecting an aldosterone-producing adenoma. Success rates were determined for treatment outcomes based on a literature review. Medicare reimbursement rates were calculated to estimate costs from a third-party payer perspective. RESULTS:Screening for and resecting APAs was the least costly strategy in this model. For a reference patient with 41 remaining years of life, the discounted expected cost of the surgical strategy was $27,821. The discounted expected cost of the medical strategy was $34,691. The cost of adrenalectomy would have to increase by 156% to $22,525 from $8,784 for universal pharmacologic therapy to be less costly. Screening for APA is more costly if fewer than 9.6% of PHA patients have resectable APA. CONCLUSION/CONCLUSIONS:Resection of APAs was the least costly treatment strategy in this decision analysis model.

BACKGROUND:Traditional resections for benign and low-grade malignant neoplasms of the mid pancreas result in loss of normal parenchyma that can cause pancreatic endocrine and exocrine insufficiency. Central pancreatectomy (CP) is a parenchyma-sparing option for such lesions. This study evaluates a single institution's experience with CP and compares outcomes with distal pancreatectomy (DP). METHODS:We retrospectively collected data on CP patients from 1997 through 2009 and evaluated outcomes. In a subset of 50 patients, we performed a matched-pairs analysis to directly compare the short- and long-term outcomes of CP and DP. RESULTS:Seventy-three patients underwent CP with a median operating room time of 254 minutes. Overall morbidity was 41.1% with pancreatic fistula in 20.5%. Mortality was 0%. There were no differences in fistula, morbidity, and mortality rates between the CP and DP groups. The CP group had resected for smaller lesions. CP patients had a lower rate of new-onset and worsening diabetes than DP patients (14% vs 46%; P = .003). Of new-onset and worsening diabetics, only 1 CP patient required insulin compared with 14 DP patients (P = .002). CONCLUSION/CONCLUSIONS:CP is safe and effective for select neoplasms of the mid pancreas. Patients undergoing CP have markedly decreased insulin requirements compared with DP patients.

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is a cell surface receptor implicated in tumor cell proliferation and migration. We hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor growth in murine models of colorectal carcinoma. MATERIALS AND METHODS: Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the C57BL/6 background to generate Apc (1638N/+)/Rage (-/-) mice. Metastasis: BALB/c mice underwent portal vein injection with CT26 cells (syngeneic) and received daily soluble (s)RAGE or vehicle. Rage (-/-) mice and Rage (+/+) controls underwent portal vein injection with MC38 cells (syngeneic). Rage (+/+) mice underwent portal vein injection with MC38 cells after stable transfection with full-length RAGE or mock transfection control. RESULTS: Tumorigenesis: Apc (1638N/+)/Rage (-/-) mice had reduced tumor incidence, size, and histopathologic grade. Metastasis: Pharmacological blockade of RAGE with sRAGE or genetic deletion of Rage reduced hepatic tumor incidence, nodules, and burden. Gain of function by transfection with full-length RAGE increased hepatic tumor burden compared to vector control MC38 cells. CONCLUSION: RAGE signaling plays an important role in tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma. Further work is needed to target the ligand-RAGE axis for possible prophylaxis and treatment of primary and metastatic colorectal carcinoma

BACKGROUND:Uncertainties remain over whether prophylactic surgery or surveillance is the better management option for intraductal papillary mucinous neoplasm of the pancreas. The aim of this preliminary study was to determine if differences in anxiety and quality of life exist between patients who have surgery or undergo surveillance. METHODS:Recruited patients were given the Hospital Anxiety and Depression Scale, a general survey that evaluates anxiety, and the Functional Assessment of Cancer Therapy-Pancreas, a disease-specific survey that assesses quality of life. Questionnaires were scored by standardized algorithms and compared using Student's t test or Wilcoxon rank-sum test. RESULTS:Sixteen patients had surgery and 16 patients were undergoing surveillance. Mean age was 66.8 ± 19.9 years. Responses from both groups were remarkably similar. Surgery patients scored higher on the anxiety questionnaire than surveillance patients, although not statistically significant (p = 0.09). Surgery patients scored lower on the functional well-being domain of the quality-of-life instrument (p = 0.03), though there were no differences in overall quality of life. CONCLUSION/CONCLUSIONS:Prophylactic surgery does not reduce quality of life, and a protocol of surveillance does not appear to generate undue anxiety in this select patient group. Further investigation with more patients is required to validate these findings.

BACKGROUND:Surgery offers the only chance for cure in patients with pancreatic cancer, and a growing number of elderly patients are being offered resection. We examined outcomes after pancreaticoduodenectomy in patients 80 years and older. METHODS:We retrospectively collected data on pancreaticoduodenectomy patients from 1992 to 2009 to compare outcomes between patients older and younger than 80 years. Variables were compared using t-, Wilcoxon rank-sum, or Fisher's exact tests. Survival was compared using Kaplan-Meier analysis and log-rank test. RESULTS:Patients 80 years and older who underwent pancreaticoduodenectomy were similar with respect to sex, race, blood loss, operative times, reoperation, length of stay, and readmission compared to younger patients. There were no differences in overall complications (47% vs. 51%, p = 0.54), major complications (19% vs. 25%, p = 0.25), and mortality (5% vs. 4%, p = 0.53) when comparing older to younger patients. In a subset who underwent pancreaticoduodenectomy for ductal adenocarcinoma, older patients (n = 45) had a median survival time of 11.6 months compared to 18.1 months in younger patients (n = 346; p < 0.01). CONCLUSION/CONCLUSIONS:Pancreaticoduodenectomy can be performed safely in select patients 80 years and older. Age alone should not dissuade surgeons from offering patients resection, though elderly patients with pancreatic ductal adenocarcinoma appear to have shorter survival than younger patients with the same disease.

BACKGROUND:Laparoscopic distal pancreatectomy (LDP) is increasingly performed for lesions of the body and tail of the pancreas. The aim of this study was to investigate short-term outcomes after LDP compared to open distal pancreatectomy (ODP) at a single, high-volume institution. METHODS:We reviewed records of patients who underwent distal pancreatectomy (DP) and compared perioperative data between LDP and ODP. Continuous variables were compared using Student's t or Wilcoxon rank-sum tests. Categorical variables were compared using chi-square or Fisher's exact test. RESULTS:A total of 360 patients underwent DP. Beginning in 2001, 95 were attempted, and 71 were completed laparoscopically with a 25.3% conversion rate. Compared to ODP, LDP had similar rates of splenic preservation, pancreatic fistula, and mortality. LDP had lower blood loss (150 vs. 900 mL, p < 0.01), smaller tumor size (2.5 vs. 3.6 cm, p < 0.01), and shorter length of resected pancreas (7.7 vs. 10.0 cm, p < 0.01). LDP had fewer complications (28.2% vs. 43.8%, p = 0.02) as well as shorter hospital stays (5 vs. 6 days, p < 0.01). CONCLUSIONS:LDP can be performed safely and effectively in patients with benign or low-grade malignant neoplasms of the distal pancreas. When feasible in selected patients, LDP offers fewer complications and shorter hospital stays.

BACKGROUND:Increasingly, surgeons apply minimally invasive and parenchyma-sparing techniques to the management of pancreatic neuroendocrine tumor (PNET). The aim of this study was to evaluate the impact of these approaches on patient outcomes. METHODS:We retrospectively collected data on patients with PNET and compared perioperative and pathologic variables. Survival was analyzed using the Kaplan-Meier method. Factors influencing survival were evaluated using a Cox proportional hazards model. RESULTS:One hundred thirty patients underwent resection for PNET. Traditional resections included 43 pancreaticoduodenectomies (PD), 38 open distal pancreatectomies (DP), and four total pancreatectomies. Minimally invasive and parenchyma-sparing resections included 25 laparoscopic DP, 11 central pancreatectomies, five enucleations, three partial pancreatectomies, and one laparoscopic-assisted PD. Compared to traditional resections, the minimally invasive and parenchyma-sparing resections had shorter hospital stays. By univariate analysis of neuroendocrine carcinoma, liver metastases and positive resection margins correlated with poor survival. There was an increase in minimally invasive or parenchyma-sparing resections over the study period with no differences in morbidity, mortality, or survival. CONCLUSION/CONCLUSIONS:In this series, there has been a significant increase in minimally invasive and parenchyma-sparing techniques for PNET. This shift did not increase morbidity or compromise survival. In addition, minimally invasive and parenchyma-sparing operations yielded shorter hospital stays.