Faculty Bibliography

PURPOSE/OBJECTIVE:Our goal was to identify circulating micro RNA (miRNA) levels that could distinguish patients with low-stage pancreatic cancer from healthy and disease controls. EXPERIMENTAL DESIGN/METHODS:We measured 735 miRNAs in pancreatic cancer case and control sera by QRTPCR using TaqMan MicroRNA Arrays. After array analysis, we selected 18 miRNA candidates for validation in an independent set of cases and control samples. RESULTS:Of the significantly elevated circulating miRNAs in patients with pancreatic cancer compared with controls, miR-1290 had the best diagnostic performance: receiver operating characteristic (ROC) analysis on miR-1290 serum level yielded curve areas (AUC) of 0.96 [95% confidence interval (CI), 0.91-1.00], 0.81 (0.71-0.91), and 0.80 (0.67-0.93), for subjects with pancreatic cancer (n = 41) relative to healthy controls (n = 19), subjects with chronic pancreatitis (n = 35), and pancreatic neuroendocrine tumors (n = 18), respectively. Serum miR-1290 levels were also significantly higher than healthy controls among patients with intraductal papillary mucinous neoplasm (IPMN; n = 20; AUC = 0.76, 0.61-0.91). Serum miR-1290 levels distinguished patients with low-stage pancreatic cancer from controls better than CA19-9 levels, and like CA19-9, higher miR-1290 levels predicted poorer outcome among patients undergoing pancreaticoduodenectomy. Greater numbers of miR-1290 transcripts were detected by FISH in primary pancreatic cancer and IPMN than normal pancreatic duct cells. miR-1290 influenced in vitro pancreatic cancer cell proliferation and invasive ability. Several other circulating miRNAs distinguished sera of patients with pancreatic cancer from those of healthy controls with AUCs >0.7, including miR-24, miR-134, miR-146a, miR-378, miR-484, miR-628-3p, and miR-1825. CONCLUSIONS:The detection of elevated circulating miR-1290 has the potential to improve the early detection of pancreatic cancer.

BACKGROUND:A computed tomography (CT) scan is often the only study needed prior to surgery for resectable solid pancreas masses. However, many patients are evaluated with multiple studies and interventions that may be unnecessary. METHODS:We conducted a retrospective review of patients who presented to the Johns Hopkins Multidisciplinary Pancreas Cancer Clinic with a clearly resectable solid pancreas mass, >1 cm in size over a 2-year period (6/2007-6/2009) and underwent resection. Pancreas specialists reviewed patient records and identified an index CT with a solid pancreas mass deemed to be resectable for curative intent. Data were collected on all studies and interventions between the index CT and the surgery. RESULTS:A total of 101 patients had an index CT. Following the index CT and before surgery, 78 patients had at least one CT, 19 had magnetic resonance imaging, 9 had a positron emission tomography scan, and 66 underwent pancreatic biopsy. Patients underwent a mean of three studies with a mean added cost of $3,371 per patient. Preoperative tests and interventions were associated with a longer time to definitive surgical intervention. CONCLUSION/CONCLUSIONS:Wide variation exists for evaluation of newly discovered resectable solid pancreas masses, which is associated with delays to surgical intervention and added costs.

BACKGROUND AND AIMS/OBJECTIVE:Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes. PATIENTS AND METHODS/METHODS:This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy. RESULTS:120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p < 0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p = 0.79). Chemotherapy [adjusted hazard ratio (HR) 3 > 0.57, p = 0.04] and radiation therapy (adjusted HR 0.35, p = 0.03) were associated with significantly longer duration of oral intake after ES or GJ. CONCLUSION/CONCLUSIONS:ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.

BACKGROUND:Reliable criteria to predict mortality after hepatectomy remain poorly defined. We sought to identify factors associated with 90-day mortality, as well as validate the "50-50" and peak bilirubin of >7 mg/dL prediction rules for mortality after liver resection. In addition, we propose a novel integer-based score for 90-day mortality using a large cohort of patients. STUDY DESIGN/METHODS:Data from 2,056 patients who underwent liver resection at 2 major hepatobiliary centers between 1990 and 2011 were identified. Perioperative laboratory data, as well as surgical and postoperative details, were analyzed to identify factors associated with liver-related 90-day death. RESULTS:Indications for liver resection included colorectal metastasis (39%), hepatocellular carcinoma (19%), benign mass (17%), or noncolorectal metastasis (14%). Most patients had normal underlying liver parenchyma (71%) and resection involved ≥3 segments (36%). Overall morbidity and mortality were 19% and 2%, respectively. Only 1 patient fulfilled the 50-50 criteria; this patient survived and was discharged on day 8. Twenty patients had a peak bilirubin concentration >7 mg/dL and 5 died within 90 days; the sensitivity and specificity of the >7-mg/dL rule were 25% and 99.3%, respectively, but overall accuracy was poor (area under the curve 0.574). Factors associated with 90-day mortality included international normalized ratio (odds ratio = 11.87), bilirubin (odds ratio = 1.16), and serum creatinine (odds ratio = 1.87) on postoperative day 3, as well as grade of postoperative complications (odds ratio = 5.08; all p < 0.05). Integer values were assigned to each factor to develop a model that predicted 90-day mortality (area under the curve 0.89). A score of ≥11 points had a sensitivity and specificity of 83.3% and 98.8%, respectively. CONCLUSIONS:The 50-50 and bilirubin >7-mg/dL rules were not accurate in predicting 90-day mortality. Rather, a composite integer-based risk score based on postoperative day 3 international normalized ratio, bilirubin, creatinine, and complication grade more accurately predicted 90-day mortality after hepatectomy.

OBJECTIVES/OBJECTIVE:To evaluate the performance characteristics of endoscopic ultrasonography (EUS) compared with computed tomography (CT) and magnetic resonance imaging (MRI) and determine the incremental diagnostic yield and accuracy of EUS with or without fine needle aspiration (FNA) over CT and MRI for prediction of neoplastic pancreatic cysts. METHODS:The EUS database was queried for procedures performed for pancreatic cysts between March 2006 and January 2010. Cystic pancreatic ductal adenocarcinoma, cystic pancreatic neuroendocrine tumor, mucinous cystic neoplasm, intraductal papillary neoplasm, and solid pseudopapillary neoplasm were categorized as neoplastic; pseudocysts and serous cysts were designated as nonneoplastic/low risk. RESULTS:Final diagnoses were established by surgery in 154 patients (mucinous cystic neoplasm/intraductal papillary neoplasm [69.4%], pancreatic neuroendocrine tumor [10%], pancreatic ductal adenocarcinoma [6.4%], solid pseudopapillary neoplasm [0.6%], nonneoplastic/low risk [13.6%]). Endoscopic ultrasonography with or without FNA was superior to CT and MRI in accurately classifying a cyst as neoplastic (P < 0.0001). After CT and MRI, EUS increased the rate of correctly predicting neoplastic cysts in 43 (36%) and 27 (54%) additional cases, respectively. CONCLUSIONS:The incremental increase in diagnostic yield of EUS and fluid analysis over CT and MRI for prediction of a neoplastic cyst is 36% and 54%, respectively. The addition of EUS-FNA to abdominal imaging significantly increases overall accuracy for diagnosis of neoplastic pancreatic cysts.

PURPOSE/OBJECTIVE:To facilitate a better understanding of incidentally noted cystic pancreatic lesions, since these lesions often pose a challenge regarding appropriate management. METHODS:This article reviews pathophysiology, prevalence, significance, and recommendations for management of the various pancreatic cystic lesions. Illustrative cases are demonstrated. RESULTS:Diagnostic benign lesions can be left alone. Cross-sectional imaging can be used to follow-up benign appearing lesions and to stage more aggressive ones. Endoscopic ultrasound with fine needle aspiration and cyst fluid analysis can be performed on certain indeterminate lesions. Lesions with high malignant potential should undergo resection. CONCLUSIONS:A better understanding of the variety of incidentally detected pancreatic cystic lesions can help direct appropriate management.

Pancreatic cysts are being identified with increasing frequency due to a combination of increased awareness and more frequent use of cross sectional imaging. Cystic neoplasms of the pancreas range from completely benign to frankly malignant. Identifying pre-malignant cysts offers the opportunity to prevent the development of pancreatic cancer. This article reviews the presentation, workup, and non-operative and operative management of premalignant and malignant pancreatic cysts.

Although patients with surgically resected noninvasive mucinous cystic neoplasms (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report 16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148 mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.

BACKGROUND:Little is known about the risk of subsequently developing a new or progressive intraductal papillary mucinous neoplasm (IPMN) after partial pancreatic resection of a noninvasive IPMN. STUDY DESIGN/METHODS:One hundred thirty patients with more than 1 year of follow-up after resection were included in this analysis. RESULTS:At a median follow-up of 38 months, 22 (17%) developed imaging evidence of a new or progressive IPMN. Eleven (8%) underwent completion resection. Three of the 11 patients had invasive adenocarcinoma. Two other patients developed metastatic pancreatic adenocarcinoma and did not undergo resection. All 5 patients (4%) with cancer had negative margins at initial operation. Sixteen of 100 patients (16%) with negative margins for IPMN at the initial operation developed a new IPMN vs 6 of 30 patients (20%) with margins positive for IPMN (p = ns). Five of 22 patients (23%) with a new IPMN had a family history of pancreatic cancer, while 8 of 108 patients (7%) without a new IPMN had a family history (p < 0.05). Overall, the chances of developing a new IPMN at 1, 5, and 10 years after the initial surgery were 4%, 25%, and 62%, respectively, and of requiring surgery were 1.6%, 14%, and 18%, respectively. The estimated chances of developing invasive pancreatic cancer were 0%, 7%, and 38% at 1, 5, and 10 years, respectively. CONCLUSIONS:Patients who have undergone resection for noninvasive IPMN require indefinite close surveillance because of the risks of developing a new IPMN, of requiring surgery, and of developing cancer. A family history of pancreatic cancer, but not margin status or degree of dysplasia, is associated with a risk of development of a new or progressive IPMN.