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Walter G Park,
Manhong Wu,
Raffick Bowen,
Ming Zheng,
William L Fitch,
Reetesh K Pai,
Dariusz Wodziak,
Brendan C Visser,
George A Poultsides,
Jeff A Norton,
Subhas Banerjee,
Ann M Chen,
Shai Friedland,
Brennan A Scott,
Pankaj Jay Pasricha,
Anson W Lowe,
Gary Peltz
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ABSTRACT: BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.
Gastrointestinal endoscopy 04/2013; · 6.71 Impact Factor
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George A Poultsides,
Lyen C Huang,
Yijun Chen,
Brendan C Visser,
Reetesh K Pai,
R Brooke Jeffrey, Walter G Park,
Ann M Chen,
Pamela L Kunz,
George A Fisher,
Jeffrey A Norton
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ABSTRACT: Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.
From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.
Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications.
Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.
Annals of Surgical Oncology 03/2012; 19(7):2295-303. · 4.17 Impact Factor
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May T Tun,
Reetesh K Pai,
Shirley Kwok,
Aiwen Dong,
Aparna Gupta,
Brendan C Visser,
Jeff A Norton,
George A Poultsides,
Subhas Banerjee,
Jacques Van Dam,
Ann M Chen,
Shai Friedland,
Brennan A Scott,
Rahul Verma,
Anson W Lowe, Walter G Park
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ABSTRACT: Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.
A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.
Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).
Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.
BMC Gastroenterology 02/2012; 12:15. · 2.42 Impact Factor
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Digestive Diseases and Sciences 07/2011; 57(2):284-7. · 2.12 Impact Factor
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Digestive Diseases and Sciences 01/2011; 56(5):1295-8. · 2.12 Impact Factor
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Walter G Park
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ABSTRACT: Pancreatic cysts are increasingly recognized as a dilemma in clinical practice because of their uncertain risk of malignancy. Because diagnosis by cytology is insensitive, current guidelines suggest using radiographic and clinical criteria to determine the appropriateness of surgery or surveillance, although this is far from perfect. Several cyst fluid biomarkers have been reported to aid diagnosis, and to date, carcinoembryonic antigen is the most accurate in detecting potentially cancerous mucinous cysts, but not in detecting malignant cysts. Recent studies have highlighted novel cyst fluid biomarkers based on DNA analysis, protein expression profiling, and secreted proteins that, if validated, may improve diagnosis and management.
F1000 Medicine Reports 01/2011; 3:3.
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ABSTRACT: Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically.
To determine the feasibility of EUS-guided gold fiducial placement for IGRT.
Prospective case series.
Tertiary medical center.
Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS-guided insertion of gold fiducials from December 2006 to February 2009.
Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case.
Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT.
Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful.
Single-center, nonrandomized study.
EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.
Gastrointestinal endoscopy 03/2010; 71(3):513-8. · 6.71 Impact Factor
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Gastrointestinal endoscopy 07/2009; 69(7):1262-3. · 6.71 Impact Factor
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Gastrointestinal Endoscopy 03/2008; 67(2):313-23. · 4.88 Impact Factor
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Gastrointestinal Endoscopy 02/2008; 67(1):94-6. · 4.88 Impact Factor
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Gastrointestinal Endoscopy 09/2007; 66(2):343-54. · 4.88 Impact Factor
