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Pancreatic Neoplasms: HELP
Articles by Dr. C Wolfgang
Based on 239 articles published since 2010
(Why 239 articles?)

Between 2010 and 2020, C. Wolfgang wrote the following 239 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
201 Article Pancreaticobiliary obstruction following duodenal stent placement. 2012

Amateau, S K / Wolfgang, C L / Khashab, M A. ·Department of Internal Medicine, Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, Maryland 21205, USA. ·Endoscopy · Pubmed #22396255.

ABSTRACT: -- No abstract --

202 Article Early mortality risk score: identification of poor outcomes following upfront surgery for resectable pancreatic cancer. 2012

Hsu, Charles C / Wolfgang, Christopher L / Laheru, Daniel A / Pawlik, Timothy M / Swartz, Michael J / Winter, Jordan M / Robinson, Raymond / Edil, Barish H / Narang, Amol K / Choti, Michael A / Hruban, Ralph H / Cameron, John L / Schulick, Richard D / Herman, Joseph M. ·The Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, 410 North Broadway/Suite 1440, Baltimore, MD 21231-2410, USA. ·J Gastrointest Surg · Pubmed #22311282.

ABSTRACT: BACKGROUND: Identifying pancreatic cancer patients at high risk of early mortality following pancreaticoduodenectomy (PD) is important for treatment decisions in a multidisciplinary setting. This study examines the preoperative predictors of early mortality following PD and combines these variables into an early mortality risk score (EMRS). METHODS: Medical records of patients who underwent PD for pancreatic adenocarcinoma at the Johns Hopkins Hospital between 30 August 1993 and 28 February 2005 were reviewed. Cox proportional hazards analysis was performed to identify predictors of early mortality, defined as death at 9 and 12 months. EMRS was constructed from univariate associated risk factors (age >75 years, tumor size ≥ 3 cm, poor differentiation, co-morbid diseases) with each factor assigned 1 point (range of 0-4). EMRS was evaluated as an independent predictor of death at 9 and 12 months. RESULTS: On univariate analysis, risk factors for death at 9 months included age ≥ 75 years (RR, 1.6; p = .009), comorbid disease (RR, 1.5; p = 0.020), tumor ≥ 3 cm (RR, 1.4; P = 0.050), and poor differentiation (RR, 2.1; P < 0.001). EMRS was associated with early mortality among those who did (p = 0.038) and did not receive adjuvant treatment (p < 0.001). A modified EMRS without tumor differentiation was also associated with early mortality (p < 0.001). Results persisted when reanalyzed using death at 12 months. CONCLUSIONS: EMRS may identify patients at risk of early mortality following PD who may be candidates for alternatively sequenced treatment protocols. Prospective validation of this EMRS is needed.

203 Article Factors influencing survival in patients undergoing palliative bypass for pancreatic adenocarcinoma. 2012

Gray, Phillip J / Wang, Jingya / Pawlik, Timothy M / Edil, Barish H / Schulick, Richard / Hruban, Ralph H / Dao, Harry / Cameron, John / Wolfgang, Christopher / Herman, Joseph M. ·Harvard Radiation Oncology Program, Boston, MA, USA. ·J Surg Oncol · Pubmed #22308098.

ABSTRACT: PURPOSE: The purpose of this study is to identify factors predictive of early mortality following palliative bypass in patients with previously unsuspected advanced pancreatic adenocarcinoma to provide a basis for the selection of appropriate therapies. METHODS: All patients with pancreatic adenocarcinoma who underwent a bypass procedure at our institution between 9/30/1994 and 1/31/2006 were reviewed. Patients with peri-operative mortality were excluded from the analysis. Univariate analysis was performed on peri-operative data to identify factors associated with early mortality (death within 6 months of surgery). Patients having multiple risk factors were assigned an overall prognostic score based on the sum of these factors. RESULTS: Of the 397 patients with pancreatic adenocarcinoma analyzed, four factors were found to predict early mortality following palliative bypass: Presence of distant metastatic disease (HR 2.59, P < 0.0001), poor tumor differentiation (HR 1.71, P = 0.009), severe pre-operative nausea and vomiting (HR 1.48, P = 0.013), and lack of previous placement of a biliary stent (HR 1.36, P = 0.048). Patients with a prognostic score of 0 were significantly more likely to survive past 6 months than patients with a prognostic score of 1 (HR 2.71, P < 0.0001), 2 (HR 3.70, P < 0.0001), or ≥3 (HR 5.63, P < 0.0001). CONCLUSIONS: In a cohort of patients undergoing a palliative bypass procedure, specific peri-operative factors can be used to identify patients who are at risk of early mortality. These factors may be helpful in selecting appropriate interventions for this group of patients.

204 Article Analysis of local control in patients receiving IMRT for resected pancreatic cancers. 2012

Yovino, Susannah / Maidment, Bert W / Herman, Joseph M / Pandya, Naimish / Goloubeva, Olga / Wolfgang, Chris / Schulick, Richard / Laheru, Daniel / Hanna, Nader / Alexander, Richard / Regine, William F. ·Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. ·Int J Radiat Oncol Biol Phys · Pubmed #22284684.

ABSTRACT: PURPOSE: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. METHODS AND MATERIALS: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU-based in 72% of patients and gemcitabine-based in 28%. RESULTS: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failure pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1-7.5; HR for death 2.6, 95% CI 1.1-6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. CONCLUSIONS: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial.

205 Article Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. 2012

Yachida, Shinichi / Vakiani, Efsevia / White, Catherine M / Zhong, Yi / Saunders, Tyler / Morgan, Richard / de Wilde, Roeland F / Maitra, Anirban / Hicks, Jessica / Demarzo, Angelo M / Shi, Chanjuan / Sharma, Rajni / Laheru, Daniel / Edil, Barish H / Wolfgang, Christopher L / Schulick, Richard D / Hruban, Ralph H / Tang, Laura H / Klimstra, David S / Iacobuzio-Donahue, Christine A. ·Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. CIACOBU@jhmi.edu ·Am J Surg Pathol · Pubmed #22251937.

ABSTRACT: Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

206 Article Serotonin expression in pancreatic neuroendocrine tumors correlates with a trabecular histologic pattern and large duct involvement. 2012

McCall, Chad M / Shi, Chanjuan / Klein, Alison P / Konukiewitz, Björn / Edil, Barish H / Ellison, Trevor A / Wolfgang, Christopher L / Schulick, Richard D / Klöppel, Günter / Hruban, Ralph H. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ·Hum Pathol · Pubmed #22221702.

ABSTRACT: Pancreatic neuroendocrine tumors with prominent stromal fibrosis are often clinically, radiographically, and grossly indistinguishable from ductal adenocarcinoma. We recently described a small series of fibrotic pancreatic neuroendocrine tumors that express serotonin. To understand better the relationship between histopathologic patterns and serotonin expression, we reviewed 361 pancreatic neuroendocrine tumors to identify those with prominent stromal fibrosis exceeding 30% of total tumor area. We identified 52 cases and immunolabeled these neoplasms with antibodies to serotonin and Ki-67. Two predominant histologic subtypes were identified: 14 (26.9%) of 52 had a trabecular or trabecular-glandular cellular pattern with interspersed fibrosis, whereas 38 (73.1%) of 52 had solid architecture. Of the 52, 14 (26.9%) pancreatic neuroendocrine tumors showed at least focal serotonin immunoreactivity. Tumors with predominantly trabecular architecture were significantly more likely to express serotonin than those with solid architecture (P < .01). Only 2 of 34 pancreatic neuroendocrine tumors with fibrosis less than 30% of total tumor area expressed serotonin. The 14 serotonin-expressing tumors were less likely to have lymph node metastases (P = .016) and more likely to involve large pancreatic ducts (P < .01) than were the 38 serotonin-negative tumors. The serotonin-expressing tumors were also found in a younger patient population (P < .01). There was no significant association of serotonin immunoreactivity with Ki-67 proliferation index, tumor size, or distant metastases. Our data demonstrate a strong correlation between trabecular architecture and serotonin immunoreactivity in pancreatic neuroendocrine tumors with stromal fibrosis. Serotonin-expressing tumors are also less likely to have lymph node metastases and more likely to involve large pancreatic ducts.

207 Article Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. 2012

Matthaei, Hanno / Norris, Alexis L / Tsiatis, Athanasios C / Olino, Kelly / Hong, Seung-Mo / dal Molin, Marco / Goggins, Michael G / Canto, Marcia / Horton, Karen M / Jackson, Keith D / Capelli, Paola / Zamboni, Giuseppe / Bortesi, Laura / Furukawa, Toru / Egawa, Shinichi / Ishida, Masaharu / Ottomo, Shigeru / Unno, Michiaki / Motoi, Fuyuhiko / Wolfgang, Christopher L / Edil, Barish H / Cameron, John L / Eshleman, James R / Schulick, Richard D / Maitra, Anirban / Hruban, Ralph H. ·Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Germany. ·Ann Surg · Pubmed #22167000.

ABSTRACT: OBJECTIVE: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. METHODS: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. RESULTS: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%). CONCLUSIONS: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.

208 Article Vascular invasion in infiltrating ductal adenocarcinoma of the pancreas can mimic pancreatic intraepithelial neoplasia: a histopathologic study of 209 cases. 2012

Hong, Seung-Mo / Goggins, Michael / Wolfgang, Christopher L / Schulick, Richard D / Edil, Barish H / Cameron, John L / Handra-Luca, Adriana / Herman, Joseph M / Hruban, Ralph H. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231-2410, USA. ·Am J Surg Pathol · Pubmed #22082604.

ABSTRACT: Although vascular invasion is a well-established indicator of poor prognosis for patients with infiltrating ductal adenocarcinoma of the pancreas (PDAC), the histopathologic characteristics of vascular invasion are not well described. Hematoxylin and eosin-stained slides from 209 surgically resected infiltrating PDACs were systematically evaluated for the presence or absence of microscopic vascular invasion. For the cases with vascular invasion, we further categorized the histologic pattern of invasion into conventional and pancreatic intraepithelial neoplasia-like (PanIN-like). In addition, several histopathologic factors in the surrounding blood vessels, including lymphocytic infiltration and luminal fibrosis, were carefully assessed. Data were compared with clinicopathologic variables, including patient survival. Microscopic vascular invasion was observed in 136 of the 209 PDACs (65.1%). Vascular invasion mimicking pancreatic intraepithelial neoplasia (PanIN-like invasion) was observed in 94 of the 136 cases (69.1%) with vascular invasion. Microscopic vascular invasion was associated with increased tumor size (P=0.04), higher pT classification (P=0.003), lymph node metastasis (P<0.0001), and perineural invasion (P=0.005). Vascular invasion was inversely correlated with neo-adjuvant therapy (P<0.0001). Examination of adjacent blood vessels revealed that peritumoral blood vessels with intimal lymphocytes (P=0.002), intimal (P=0.007) and medial (P=0.001) fibrosis, and cancer cells in vascular wall (P<0.0001) were all highly associated with the intraluminal vascular invasion. In univariate analysis, patients whose cancers had microscopic vascular invasion (median survival, 15.3 mo) had a significantly worse survival than did patients with carcinomas without vascular invasion (25.1 mo; P=0.01, log-rank test). Microscopic vascular invasion is a poor prognostic indicator and can histologically mimic PanIN.

209 Article Management of patients with pancreatic adenocarcinoma: national trends in patient selection, operative management, and use of adjuvant therapy. 2012

Mayo, Skye C / Gilson, Marta M / Herman, Joseph M / Cameron, John L / Nathan, Hari / Edil, Barish H / Choti, Michael A / Schulick, Richard D / Wolfgang, Christopher L / Pawlik, Timothy M. ·Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ·J Am Coll Surg · Pubmed #22055585.

ABSTRACT: BACKGROUND: Surgical resection remains the only potentially curative option for patients with pancreatic adenocarcinoma (PAC). Advances in surgical technique and perioperative care have reduced perioperative mortality; however, temporal trends in perioperative morbidity and the use of adjuvant therapy on a population basis remain ill-defined. STUDY DESIGN: Using Surveillance, Epidemiology, and End Results-Medicare data, 2,461 patients with resected PAC were identified from 1991 to 2005. We examined trends in preoperative comorbidity indices, adjuvant treatment, type of pancreatic resection, and changes in morbidity and mortality during 4 time intervals (ie, 1991-1996, 1997-2000, 2001-2003, and 2003-2005). RESULTS: The majority of patients underwent pancreaticoduodenectomy (n = 1,945; 79%). There was a temporal increase in mean patient age (p < 0.05) and the number of patients with multiple preoperative comorbidities (Elixhauser comorbidities ≥3: 1991-1996, 10% vs 2003-2005, 26%; p < 0.001). Perioperative morbidity (53%) did not, however, change over time (p = 0.97) and 30-day mortality decreased by half (1991-1996: 6% vs 2003-2005: 3%; p = 0.04). Overall, 51% (n = 1,243) of patients received adjuvant therapy, with the majority receiving chemoradiation (n = 817; 33%). Among patients who received adjuvant therapy, factors associated with receipt of adjuvant chemotherapy alone relative to chemoradiation included older patient age (odds ratio = 1.75; p < 0.001) and ≥3 medical comorbidities (odds ratio = 1.57; p = 0.007). Receipt of adjuvant chemotherapy alone also increased over time (2003-2005 vs 1991-1996, odds ratio = 2.21; p < 0.001). CONCLUSIONS: Perioperative 30-day mortality associated with resection for PAC decreased by one-half from 1991 to 2005. Although patients undergoing resection for PAC were older and had more preoperative comorbidities, the incidence of perioperative complications remained stable. The relative use of adjuvant chemotherapy alone vs chemoradiation therapy for PAC has increased in the United States during the 15 years examined.

210 Article Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas. 2012

Dal Molin, Marco / Hong, Seung-Mo / Hebbar, Sachidanand / Sharma, Rajni / Scrimieri, Francesca / de Wilde, Roeland F / Mayo, Skye C / Goggins, Michael / Wolfgang, Christopher L / Schulick, Richard D / Lin, Ming-Tseh / Eshleman, James R / Hruban, Ralph H / Maitra, Anirban / Matthaei, Hanno. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD 21231, USA. ·Hum Pathol · Pubmed #21940037.

ABSTRACT: A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.

211 Article Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent. 2012

Mayo, Skye C / Nathan, Hari / Cameron, John L / Olino, Kelly / Edil, Barish H / Herman, Joseph M / Hirose, Kenzo / Schulick, Richard D / Choti, Michael A / Wolfgang, Christopher L / Pawlik, Timothy M. ·Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·Cancer · Pubmed #21935914.

ABSTRACT: BACKGROUND: Prognosis after surgery for pancreatic ductal adenocarcinoma (PDAC) is typically reported from the date of surgery. Survival estimates, however, are dynamic and may change based on the time already survived. The authors sought to assess conditional survival among a large cohort of patients who underwent resection of PDAC. METHODS: Between 1970 and 2008, 1822 patients who underwent resection for PDAC with curative intent were identified. Kaplan-Meier and Cox regression analyses were performed to validate established predictors of survival, and results were compared with 2-year conditional survival. RESULTS: Actuarial survival was 18% at 5 years, with a median survival of 18 months. Multivariate analysis revealed that tumor size, lymph node ratio, and positive margins were associated with worse survival (all P < .001). Differences in actuarial versus conditional survival estimates were greater the more years already survived by the patient. The 2-year conditional survival at 3 years-the probability of surviving to postoperative year 5 given that the patient had already survived 3 years-was 66% versus a 5-year actuarial survival calculated from the time of surgery of 18%. Stratification of 2-year conditional survival by lymph node ratio and margin status revealed that patients with high lymph node ratio or positive margins saw the greatest increase in 2-year conditional survival as more time elapsed (both P ≤ .01). CONCLUSIONS: Differences in actuarial versus conditional survival estimates were more pronounced based on the additional years already survived by the patient. Conditional survival may be a helpful tool in counseling patients with PDAC, as it is a more accurate assessment of future survival for those patients who have already survived a certain amount of time.

212 Article Surgical resection of malignant melanoma metastatic to the pancreas: case series and review of literature. 2012

Goyal, Jatinder / Lipson, Evan J / Rezaee, Neda / Edil, Barish H / Schulick, Rich / Wolfgang, Christopher L / Hruban, Ralph H / Antonarakis, Emmanuel S. ·Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-2101, USA. jatinaiims@gmail.com ·J Gastrointest Cancer · Pubmed #21912850.

ABSTRACT: BACKGROUND: Malignant melanoma only rarely metastasizes to the pancreas. As such, there is limited medical literature on the clinical course and outcomes for patients who have undergone surgical management of these tumors. The aim of our study was to review our experience with the surgical resection of melanoma metastatic to the pancreas. METHODS: The records of five patients (four females, one male) with surgically resected melanoma metastatic to the pancreas were retrospectively reviewed. Tumor characteristics, patient presentation, operative details, and follow-up data were evaluated. RESULTS: The primary site of melanoma was known in three cases and unknown in two cases. Four patients were symptomatic at presentation, including abdominal pain (n = 3), jaundice (n = 2), abdominal distension (n = 1), bleeding metastases (n = 1), and fatigue (n = 1). In one patient, the metastasis was an incidental discovery. Surgical resection was accomplished by pylorus-preserving pancreaticoduodenectomy in four patients and distal pancreatectomy in one patient. Single-site resection was done in two patients while the other three underwent synchronous multiple-site resections. Complications developed post-operatively in three patients. Two patients had progression of disease in the form of new metastatic lesions and received subsequent chemotherapy. The median survival was 11.4 months (range, 3-26 months). CONCLUSIONS: Aggressive surgical management of pancreatic metastases provides palliative relief of symptoms and may be considered in appropriately selected candidates.

213 Article Predicting the risk of perioperative mortality in patients undergoing pancreaticoduodenectomy: a novel scoring system. 2011

Venkat, Raghunandan / Puhan, Milo A / Schulick, Richard D / Cameron, John L / Eckhauser, Frederic E / Choti, Michael A / Makary, Martin A / Pawlik, Timothy M / Ahuja, Nita / Edil, Barish H / Wolfgang, Christopher L. ·Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Arch Surg · Pubmed #22106320.

ABSTRACT: OBJECTIVE: To develop and validate a risk score to predict the 30- and 90-day mortality after a pancreaticoduodenectomy or total pancreatectomy on the basis of preoperative risk factors in a high-volume program. DESIGN: Data from a prospectively maintained institutional database were collected. In a random subset of 70% of patients (training cohort), multivariate logistic regression was used to develop a simple integer score, which was then validated in the remaining 30% of patients (validation cohort). Discrimination and calibration of the score were evaluated using area under the receiver operating characteristic curve and Hosmer-Lemeshow test, respectively. SETTING: Tertiary referral center. PATIENTS: The study comprised 1976 patients in a prospectively maintained institutional database who underwent pancreaticoduodenectomy or total pancreatectomy between 1998 and 2009. MAIN OUTCOME MEASURES: The 30- and 90-day mortality. RESULTS: In the training cohort, age, male sex, preoperative serum albumin level, tumor size, total pancreatectomy, and a high Charlson index predicted 90-day mortality (area under the curve, 0.78; 95% CI, 0.71-0.85), whereas all these factors except Charlson index also predicted 30-day mortality (0.79; 0.68-0.89). On validation, the predicted and observed risks were not significantly different for 30-day (1.4% vs 1.0%; P = .62) and 90-day (3.8% vs 3.4%; P = .87) mortality. Both scores maintained good discrimination (for 30-day mortality, area under the curve, 0.74; 95% CI, 0.54-0.95; and for 90-day mortality, 0.73; 0.62-0.84). CONCLUSIONS: The risk scores accurately predicted 30- and 90-day mortality after pancreatectomy. They may help identify and counsel high-risk patients, support and calculate net benefits of therapeutic decisions, and control for selection bias in observational studies as propensity scores.

214 Article Peripancreatic paraganglioma: a potential diagnostic challenge in cytopathology and surgical pathology. 2011

Singhi, Aatur D / Hruban, Ralph H / Fabre, Monique / Imura, Johji / Schulick, Richard / Wolfgang, Christopher / Ali, Syed Z. ·Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·Am J Surg Pathol · Pubmed #21921779.

ABSTRACT: Paragangliomas are rare neuroendocrine neoplasms arising in extra-adrenal chromaffin cells of the autonomic nervous system. In rare instances, paragangliomas present around and involve the pancreas, thereby mimicking one of the more common primary pancreatic lesions. These neoplasms present considerable diagnostic difficulty not only for the clinician and radiologist but also for the pathologist. We have collected a series of 9 peripancreatic paragangliomas clinically simulating a primary pancreatic lesion. The paragangliomas were diagnosed in 4 men and 5 women with an age range of 37 to 78 years (mean, 50 y). Patients presented clinically either with diffuse epigastric and abdominal pain (7 of 9, 78%) or with an incidental mass (2 of 9, 22%) discovered on routine radiographic imaging. All patients were found to have mass lesions suspicious for a primary pancreatic neoplasm on radiographic examination. The lesions were predominantly located in the body of the pancreas (5 of 9, 56%) and ranged in size from 5.5 to 17.0 cm (mean, 10.0 cm). Five of 9 (56%) neoplasms also demonstrated cystic change. Fine-needle aspiration (FNA) was performed on 6 cases; however, the diagnostic accuracy was low, with 3 of 6 (50%) neoplasms misdiagnosed as pancreatic neuroendocrine tumor (PanNET) (n=1), spindle cell neoplasm (n=1), or pseudocyst (n=1). In addition, 2 of 8 (25%) surgically resected tumors were misdiagnosed by the referring pathologist as a PanNET. Immunohistochemistry was performed on all cases, confirming the characteristic 2-cell populations: chief cells (synaptophysin positive and chromogranin A positive) and sustentacular cells (S-100 protein positive). Follow-up information was available for all patients and ranged from 2 months to 11.6 years (mean, 2.7 y). Three of 9 (33%) patients developed metastatic disease, and 2 of these 3 died of their disease at 2.8 and 4.6 years after diagnosis. In summary, in unsuspected cases, interpretation of FNA and surgical pathology resections can be diagnostically challenging. Awareness and proper recognition of this entity, including differential diagnosis, are imperative in establishing the correct diagnosis. Further, close follow-up of these cases should be considered because of the significant risk of metastatic disease.

215 Article Palliative surgical management of patients with unresectable pancreatic adenocarcinoma: trends and lessons learned from a large, single institution experience. 2011

Kneuertz, Peter J / Cunningham, Steven C / Cameron, John L / Torrez, Sergio / Tapazoglou, Nicholas / Herman, Joseph M / Makary, Martin A / Eckhauser, Frederic / Wang, Jingya / Hirose, Kenzo / Edil, Barish H / Choti, Michael A / Schulick, Richard D / Wolfgang, Christopher L / Pawlik, Timothy M. ·Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·J Gastrointest Surg · Pubmed #21913044.

ABSTRACT: INTRODUCTION: Routine palliative bypass has been advocated for palliation of patients with pancreatic adenocarcinoma who have inoperable disease discovered at the time of surgery. We examined trends in the relative use of palliative bypass over time with an emphasis on identifying changes in surgical indications, type of bypass performed, as well as perioperative outcomes associated with surgical palliation. METHODS: Between 1996 and 2010, 1,913 patients with pancreatic adenocarcinoma in the head of the pancreas were surgically explored. Data regarding preoperative symptoms, intraoperative findings, type of surgical procedure performed, as well as perioperative and long-term outcomes were collected and analyzed. RESULTS: Of the 1,913 patients, 583 (30.5%) underwent a palliative procedure. Most patients presented with jaundice (72.2%). The majority of patients were evaluated by CT scan (97.4%), which revealed a median tumor size of 3.2 cm. Most patients who underwent surgical palliation (64.5%) had a double bypass, while a minority had either gastrojejunostomy (28.2%) or hepaticojejunostomy (7.2%) alone. While the number of pancreaticoduodenectomies remained relatively stable over time, there was a temporal decrease in the utilization of palliative bypass (P < 0.001). Unanticipated locally advanced disease vs. liver/peritoneal metastasis as the indication for palliative surgery also changed over time (1996-2001: 47.8% vs. 52.2%; 2002-2007: 49.2% vs. 50.8%; 2008-2010: 17.2% vs. 82.7%) (P = 0.005). Palliative failure rates were 2.3% after hepaticojejunostomy and 3.1% after grastrojejunostomy. Patients with unsuspected metastatic disease had a worse survival compared with patients who had locally unresectable disease (median survival: 5 vs. 8 months, respectively; HR = 1.43, P = 0.001). CONCLUSION: Palliative bypass procedures were less frequently performed over time, probably due to a significant decrease in the rate of unanticipated advanced locoregional disease at the time of exploration. While palliative bypass was effective, survival in the setting of metastatic disease was extremely short.

216 Article Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. 2011

Wu, Jian / Matthaei, Hanno / Maitra, Anirban / Dal Molin, Marco / Wood, Laura D / Eshleman, James R / Goggins, Michael / Canto, Marcia I / Schulick, Richard D / Edil, Barish H / Wolfgang, Christopher L / Klein, Alison P / Diaz, Luis A / Allen, Peter J / Schmidt, C Max / Kinzler, Kenneth W / Papadopoulos, Nickolas / Hruban, Ralph H / Vogelstein, Bert. ·Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA. ·Sci Transl Med · Pubmed #21775669.

ABSTRACT: More than 2% of the adult U.S. population harbors a pancreatic cyst. These often pose a difficult management problem because conventional criteria cannot always distinguish cysts with malignant potential from those that are innocuous. One of the most common cystic neoplasms of the pancreas, and a bona fide precursor to invasive adenocarcinoma, is called intraductal papillary mucinous neoplasm (IPMN). To help reveal the pathogenesis of these lesions, we purified the DNA from IPMN cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. In addition to the expected KRAS mutations, we identified recurrent mutations at codon 201 of GNAS. A larger number (113) of additional IPMNs were then analyzed to determine the prevalence of KRAS and GNAS mutations. In total, we found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. In addition to defining a new pathway for pancreatic neoplasia, these data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.

217 Article Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma. 2011

Ryu, Ji Kon / Matthaei, Hanno / Dal Molin, Marco / Hong, Seung-Mo / Canto, Marcia I / Schulick, Richard D / Wolfgang, Christopher / Goggins, Michael G / Hruban, Ralph H / Cope, Leslie / Maitra, Anirban. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ·Pancreatology · Pubmed #21757972.

ABSTRACT: BACKGROUND: Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer. METHODS: Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The 'mucinous' cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the 'nonmucinous' cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas. RESULTS: Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%. CONCLUSION: This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. and IAP.

218 Article Pulmonary resection for isolated pancreatic adenocarcinoma metastasis: an analysis of outcomes and survival. 2011

Arnaoutakis, George J / Rangachari, Deepa / Laheru, Daniel A / Iacobuzio-Donahue, Chris A / Hruban, Ralph H / Herman, Joseph M / Edil, Barish H / Pawlik, Timothy M / Schulick, Richard D / Cameron, John L / Meneshian, Avedis / Yang, Stephen C / Wolfgang, Christopher L. ·Division of Thoracic Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·J Gastrointest Surg · Pubmed #21725701.

ABSTRACT: OBJECTIVES: This study was conducted to determine if pulmonary metastasectomy (PM) for isolated pancreatic cancer metastases is safe and effective. METHODS: This was a retrospective case-control study of patients undergoing PM at our institution from 2000 to 2009 for isolated lung metastasis after resection for pancreatic cancer. Clinical and pathologic data were compared with a matched reference group. Resected neoplasms were immunolabeled for the Dpc4 protein. Kaplan-Meier analysis compared overall survival and survival after relapse. RESULTS: Of 31 patients with isolated lung metastasis, 9 underwent 10 pulmonary resections. At initial pancreas resection, all patients were stage I or II. Other baseline characteristics were similar between the two groups. Median time from pancreatectomy to PM was 34 months (interquartile range 21-49). During the study, 29/31(90.6%) patients died. There were no in-hospital mortalities or complications after PM. Median cumulative survival was significantly improved in the PM group (51 vs. 23 months, p = 0.04). There was a trend toward greater 2-year survival after relapse in the PM group (40% vs. 27%, p = 0.2). CONCLUSIONS: In patients with isolated lung metastasis from pancreatic adenocarcinoma, this is the first study to show that pulmonary resection can be performed safely with low morbidity and mortality. The improved survival in the PM group may result in part from selection bias but may also represent a benefit of the procedure.

219 Article Hyaline globules in neuroendocrine and solid-pseudopapillary neoplasms of the pancreas: a clue to the diagnosis. 2011

Meriden, Zina / Shi, Chanjuan / Edil, Barish H / Ellison, Trevor / Wolfgang, Christopher L / Cornish, Toby C / Schulick, Richard D / Hruban, Ralph H. ·Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·Am J Surg Pathol · Pubmed #21677537.

ABSTRACT: Distinguishing between solid-pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) may pose a diagnostic dilemma. Both can demonstrate solid growth patterns, and both can be immunoreactive with neuroendocrine markers such as synaptophysin and CD56. One well-established feature of SPNs is the presence of hyaline globules, which in contrast has only rarely been reported in PanNETs. Clinicopathologic features of 361 cases originally classified as PanNETs were examined. Of these, 24 tumors (6.6%) had hyaline globules, raising the possibility of SPN. Immunohistochemistry for β-catenin was performed on these 24 neoplasms, and showed nuclear labeling in 6 cases. These 6 cases, which also demonstrated cytoplasmic CD10 staining, were reclassified as SPNs. The remaining 18 cases maintained their original diagnosis as PanNETs, and the hyaline globules in these cases were periodic acid-Schiff (PAS) positive, diastase resistant, and immunoreactive with α-1-antitrypsin. All 24 cases were histologically re-evaluated, and the pattern of invasion, presence of clear cells, and nuclear grooves were found to be helpful in distinguishing SPNs from PanNETs. We conclude that the presence of hyaline globules should raise SPNs in the differential diagnosis of a solid cellular neoplasm of the pancreas. However, this should not be used as the sole criterion in the diagnosis of SPNs, as hyaline globules may also be seen in 5% of PanNETs. Immunohistochemical and histologic features supporting the diagnosis of SPNs over PanNETs include CD10 and nuclear β-catenin labeling, an insidious pattern of invasion, clear cells, and nuclear grooves.

220 Article Loss of E-cadherin expression and outcome among patients with resectable pancreatic adenocarcinomas. 2011

Hong, Seung-Mo / Li, Ang / Olino, Kelly / Wolfgang, Christopher L / Herman, Joseph M / Schulick, Richard D / Iacobuzio-Donahue, Christine / Hruban, Ralph H / Goggins, Michael. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. ·Mod Pathol · Pubmed #21552209.

ABSTRACT: Only a minority of patients who undergo surgical resection for pancreatic ductal adenocarcinoma are cured. Since patient outcome is not reliably predicted using pathological factors (tumor stage, differentiation, and resection margin status) alone, markers of tumor behavior are needed. One candidate predictor of pancreatic cancer outcome is E-cadherin status. CDH1 is a tumor suppressor gene encoding an important cell adhesion molecule (E-cadherin). The aim of this study was to determine if, among patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, loss of E-cadherin expression was an independent predictor of poor outcome. We examined patterns of loss of E-cadherin by immunohistochemistry in tissue microarrays of 329 surgically resected pancreatic ductal adenocarcinomas. E-cadherin expression was then correlated with outcome. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk. One hundred forty-one pancreatic adenocarcinomas (43%) had partial or complete loss of E-cadherin expression within the analyzed tissue cores. In most instances (134 cases, 41%), this loss was partial. Patients whose pancreatic adenocarcinomas had either complete loss (n=7; median survival, 5.5 months) or partial loss (n=134; 12.7 months) of E-cadherin expression had significantly worse median survival than those with uniformly intact E-cadherin expression (n=188; 18.5 months) by univariate (P=0.002) and multivariate (P=0.006) analyses. In subgroup analysis, patients with poorly differentiated cancers had a worse prognosis if their cancers had partial loss of E-cadherin expression (P=0.02). Among patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, partial loss of tumoral E-cadherin expression is an independent predictor of poor outcome.

221 Article Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. 2011

Matthaei, Hanno / Hong, Seung-Mo / Mayo, Skye C / dal Molin, Marco / Olino, Kelly / Venkat, Raghunandan / Goggins, Michael / Herman, Joseph M / Edil, Barish H / Wolfgang, Christopher L / Cameron, John L / Schulick, Richard D / Maitra, Anirban / Hruban, Ralph H. ·The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD, USA. ·Ann Surg Oncol · Pubmed #21537863.

ABSTRACT: BACKGROUND: Margin status is one of the strongest prognosticators after resection of pancreatic ductal adenocarcinoma (PDAC). The clinical significance of pancreatic intraepithelial neoplasia (PanIN) at a surgical margin has not been established. METHODS: A total of 208 patients who underwent R0 resection for PDAC between 2004 and 2008 were selected. Intraoperative frozen section slides containing the final pancreatic parenchymal transection margin were evaluated for presence or absence, number, and grade of PanINs. Data were compared to clinicopathologic factors, including patient survival. RESULTS: PanIN lesions were present in margins in 107 of 208 patients (51.4%). Median number of PanINs per pancreatic resection margin was 1 (range, 1-11). A total of 72 patients had PanIN-1 (34.6%), 44 had PanIN-2 (21.1%), and 16 had PanIN-3 (7.2%) at their margin. Overall median survival was 17.9 (95% confidence interval, 14-21.9) months. Neither the presence nor absence of PanIN nor histological grade had any significant correlation with important clinicopathologic characteristics. There were no significant survival differences between patients with or without PanIN lesions at the resection margin or among patients with PanIN-3 (carcinoma in situ) versus lower PanIN grades. However, patients with R1 resection had a significantly worse outcome compared with patients without invasive cancer at a margin irrespective of the presence of PanIN (P=0.02). CONCLUSIONS: The presence of PanINs at a resection margin does not affect survival in patients who undergo R0 resection for PDAC. These results have significant clinical implications for surgeons, because no additional resection seems to be indicated when intraoperative frozen sections reveal even high-grade PanIN lesions.

222 Article Tumor size and location correlate with behavior of pancreatic serous cystic neoplasms. 2011

Khashab, Mouen A / Shin, Eun Ji / Amateau, Stuart / Canto, Marcia Irene / Hruban, Ralph H / Fishman, Elliot K / Cameron, John L / Edil, Barish H / Wolfgang, Christopher L / Schulick, Richard D / Giday, Samuel. ·Department of Medicine and Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. ·Am J Gastroenterol · Pubmed #21468008.

ABSTRACT: OBJECTIVES: The majority of pancreatic serous cystic neoplasms (SCNs) are benign. However, these neoplasms can cause symptoms and rarely can be aggressive. Identification of factors associated with symptomatic or aggressive SCNs may aid management decisions. The aim of this study was to identify variables that predict aggressive SCNs. METHODS: Prospective pathology database was queried for SCNs that were surgically resected at Johns Hopkins Hospital. Tumors were considered aggressive if they invaded surrounding structures and/or vessels or if they metastasized to lymph nodes or distant organs. The associations of gender, tumor size, and tumor location, with the presence or absence of symptoms and tumor behavior were examined using Fisher's exact test, logistic regression, and multivariate analyses. RESULTS: A total of 257 patients with SCNs underwent surgical resection. Mean tumor diameter was 4.9 cm. Tumor location in the head of pancreas (HOP) was associated with symptoms (odds ratio (OR) 1.87, 95% confidence interval (CI) 1.1-3.3). Computed tomography (CT) predicted the diagnosis of SCN in approximately a quarter of patients. Thirteen tumors (mean 10.5 cm) were considered aggressive. Multivariate analysis showed that tumor diameter (OR 1.53, 95% CI 1.24-1.89) and location of tumor in pancreatic head (OR 10.44, 95% CI 1.73-63.04) were independently associated with aggressive behavior. CONCLUSIONS: We describe the largest case series of patients with pathologically proven SCNs. CT performed poorly in preoperative diagnosis of SCNs. Large tumor size and head location predicted aggressive behavior. These factors should be considered in the management of patients with SCN.

223 Article Tumour epithelial vimentin expression and outcome of pancreatic ductal adenocarcinomas. 2011

Handra-Luca, A / Hong, S-M / Walter, K / Wolfgang, C / Hruban, R / Goggins, M. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. adriana.handra-luca@avc.aphp.fr ·Br J Cancer · Pubmed #21448168.

ABSTRACT: PURPOSE: Tumour epithelial vimentin expression is a marker of mesenchymal differentiation and may be a useful marker of carcinomas with more aggressive behaviour. The aim of this study was to determine the extent and prognostic significance of vimentin expression in pancreatic ductal adenocarcinomas. METHODS: Vimentin expression was detected by immunohistochemistry on tissue microarrays of surgically resected pancreatic ductal adenocarcinomas from 387 patients. The percentage of vimentin-immunolabelled neoplastic cells was correlated with outcome and with clinico-pathological factors using the Kaplan-Meier method and Cox multivariate survival models. RESULTS: In all, 45% of primary pancreatic adenocarcinomas contained neoplastic cells that expressed vimentin, and in 27.5% of the cancers >10% of cells expressed vimentin. Vimentin expression was correlated with poor histological differentiation. By both uni- and multivariate survival analysis, neoplastic vimentin expression (P<0.01, HR 1.52, 95% confidence interval 1.14-2.04) was an indicator of a shorter postsurgical survival independent of other clinico-pathological variables. CONCLUSION: The presence of vimentin-expressing tumour epithelial cells in surgically resected pancreatic adenocarcinomas independently predicted a shorter postsurgical survival.

224 Article Re-evaluating the impact of tumor size on survival following pancreaticoduodenectomy for pancreatic adenocarcinoma. 2011

de Jong, Mechteld C / Li, Fuyu / Cameron, John L / Wolfgang, Christopher L / Edil, Barish H / Herman, Joseph M / Choti, Michael A / Eckhauser, Frederick / Hirose, Kenzo / Schulick, Richard D / Pawlik, Timothy M. ·Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. ·J Surg Oncol · Pubmed #21283994.

ABSTRACT: BACKGROUND AND OBJECTIVES: Following resection of pancreatic adenocarcinoma, tumor size has been considered a key prognostic feature; however, this remains controversial. We sought to examine the association of size with outcomes following resection of pancreatic adenocarcinoma. METHODS: Between 1970 and 2010, 1,697 patients with pancreatic adenocarcinoma at the Johns Hopkins Hospital underwent curative intent pancreaticoduodenectomy. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: Of 1,697 patients, tumor size was ≤ 2 cm in 418 (24.6%) patients, 2-5 cm in 1,070 (63.1%) patients, and ≥ 5 cm in 209 (12.3%) patients. On univariate analyses, 5-year survival was inversely proportional to tumor size (≤ 2 cm: 28.8% vs. 2-5 cm: 19.4% vs. ≥ 5 cm: 14.2%; P < 0.001). Size correlated with the risk of other adverse factors, with larger tumors being more likely to be associated with nodal disease and poor differentiation (both P < 0.05). On multivariate analysis, the 2 cm cut-off was not associated with survival, while nodal disease (HR = 1.59; P = 0.006) and poor differentiation (HR = 1.59; P = 0.04) remained predictive of outcome, regardless of size. CONCLUSION: The cut-off value of 2 cm is not independently associated with outcome, however, tumor size was strongly associated with the risk of other adverse prognostic factors. The effect of size on prognosis was largely attributable to these other biologic factors rather than tumor size itself.

225 Article DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. 2011

Jiao, Yuchen / Shi, Chanjuan / Edil, Barish H / de Wilde, Roeland F / Klimstra, David S / Maitra, Anirban / Schulick, Richard D / Tang, Laura H / Wolfgang, Christopher L / Choti, Michael A / Velculescu, Victor E / Diaz, Luis A / Vogelstein, Bert / Kinzler, Kenneth W / Hruban, Ralph H / Papadopoulos, Nickolas. ·Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA. ·Science · Pubmed #21252315.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase complex, and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain-associated protein) and ATRX (α thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.

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