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Pancreatic Neoplasms: HELP
Articles by Richard Schulick
Based on 18 articles published since 2008
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Between 2008 and 2019, Richard Schulick wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. 2017

Khorana, Alok A / Mangu, Pamela B / Berlin, Jordan / Engebretson, Anitra / Hong, Theodore S / Maitra, Anirban / Mohile, Supriya G / Mumber, Matthew / Schulick, Richard / Shapiro, Marc / Urba, Susan / Zeh, Herbert J / Katz, Matthew H G. ·Alok A. Khorana and Marc Shapiro, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Jordan Berlin, Vanderbilt University, Nashville, TN · Anitra Engebretson, Pancreatic Cancer Action Network, Manhattan Beach, CA · Theodore S. Hong, Massachusetts General Hospital, Boston, MA · Anirban Maitra and Matthew H.G. Katz, The University of Texas MD Anderson Cancer Center, Houston, TX · Supriya G. Mohile, University of Rochester, Rochester, NY · Matthew Mumber, Harbin Clinic, Rome, GA · Richard Schulick, University of Colorado at Denver, Denver, CO · Susan Urba, University of Michigan, Ann Arbor, MI · and Herbert J. Zeh, University of Pittsburgh, Pittsburgh, PA. ·J Clin Oncol · Pubmed #28398845.

ABSTRACT: Purpose To update the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline published on May 31, 2016. The October 2016 update focuses solely on new evidence that pertains to clinical question 4 of the guideline: What is the appropriate adjuvant regimen for patients with pancreatic cancer who have undergone an R0 or R1 resection of their primary tumor? Methods The recently published results of a randomized phase III study prompted an update of this guideline. The high quality of the reported evidence and the potential for its clinical impact prompted the Expert Panel to revise one of the guideline recommendations. Results The ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy compared gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma. Median overall survival was improved in the doublet arm to 28.0 months (95% CI, 23.5 to 31.5 months) versus 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm. Recommendations All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery. The remaining recommendations from the original 2016 ASCO guideline are unchanged.

2 Editorial Cost-effectiveness of treatment strategies for primary operable pancreatic head adenocarcinoma: do we have more scientific evidence to call for further centralization of care? 2013

Gajdos, Csaba / Schulick, Richard. · ·Ann Surg Oncol · Pubmed #23054108.

ABSTRACT: -- No abstract --

3 Editorial Cost effectiveness of treatment strategies for primary operable pancreatic head adenocarcinoma: do we have more scientific evidence to call for further centralization of care? 2012

Gajdos, Csaba / Schulick, Richard. · ·Ann Surg Oncol · Pubmed #22829004.

ABSTRACT: -- No abstract --

4 Review Update on familial pancreatic cancer. 2010

Hruban, Ralph H / Canto, Marcia I / Goggins, Michael / Schulick, Richard / Klein, Alison P. ·Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, 401 North Broadway, Weinberg 2242, Baltimore, MD 21231, USA. rhruban@jhmi.edu ·Adv Surg · Pubmed #20919528.

ABSTRACT: -- No abstract --

5 Article Evolving Trends Towards Minimally Invasive Surgery for Solid-Pseudopapillary Neoplasms. 2016

Stewart, Camille L / Meguid, Cheryl / Chapman, Brandon / Schulick, Richard / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. Camille.Stewart@ucdenver.edu. · University of Colorado Hospital, Aurora, CO, USA. · Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. ·Ann Surg Oncol · Pubmed #27510845.

ABSTRACT: BACKGROUND: Solid-pseudopapillary neoplasms are rare pancreatic neoplasms with low malignant potential that predominantly arise in young women. We sought to characterize this population and the evolving trend at our institution towards laparoscopic management. METHODS: We identified all patients at our institution that were surgically treated for solid-pseudopapillary neoplasm from 2008-2015. Demographic and clinical information were queried from the medical record, and descriptive statistics were performed. Student's t test and chi-square analysis were used for comparison where appropriate. RESULTS: We identified 11 women and 1 man (average age 26 years; range 14-48 years) who were surgically treated for solid-pseudopapillary neoplasms; 5 with distal pancreatectomy (4 open, 1 laparoscopic), 6 with pancreaticoduodenectomy (3 open, 3 laparoscopic), and 1 open enucleation. From 2008 to 2013, seven of eight (87 %) procedures were performed open. Since 2014, three of four (75 %) procedures have successfully been completed laparoscopically (see video clips). Length of stay was similar for patients who had open versus laparoscopic procedures (8 vs. 9 days, p = 0.61). Two-thirds of patients (5/8) who had open procedures experienced postoperative complications compared with half (2/4) of patients who had laparoscopic procedures (p = 0.28). There have been no recurrences. CONCLUSIONS: Minimally invasive surgical management of solid-pseudopapillary neoplasms is becoming more popular, can be performed safely, and appears to have comparable outcomes to an open approach. Quality of life is an important metric for this relatively young population and may be improved with a laparoscopic approach, which warrants further investigation.

6 Article Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. 2016

Khorana, Alok A / Mangu, Pamela B / Berlin, Jordan / Engebretson, Anitra / Hong, Theodore S / Maitra, Anirban / Mohile, Supriya G / Mumber, Matthew / Schulick, Richard / Shapiro, Marc / Urba, Susan / Zeh, Herbert J / Katz, Matthew H G. ·Alok A. Khorana and Marc Shapiro, Cleveland Clinic, Cleveland, OH · Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA · Jordan Berlin, Vanderbilt University, Nashville, TN · Anitra Engebretson, Patient Representative, Portland, OR · Theodore S. Hong, Massachusetts General Hospital, Boston, MA · Anirban Maitra and Matthew H.G. Katz, The University of Texas MD Anderson Cancer Center, Houston, TX · Supriya G. Mohile, University of Rochester, Rochester, NY · Matthew Mumber, Harbin Clinic, Rome, GA · Richard Schulick, University of Colorado at Denver, Denver, CO · Susan Urba, University of Michigan, Ann Arbor, MI · and Herbert J. Zeh, University of Pittsburgh, Pittsburgh, PA. ·J Clin Oncol · Pubmed #27247221.

ABSTRACT: PURPOSE: To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer. METHODS: ASCO convened a panel of medical oncology, radiation oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. RESULTS: Nine randomized controlled trials met the systematic review criteria. RECOMMENDATIONS: A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki.

7 Article Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer. 2016

Faisal, Farzana / Tsai, Hua-Ling / Blackford, Amanda / Olino, Kelly / Xia, Chang / De Jesus-Acosta, Ana / Le, Dung T / Cosgrove, David / Azad, Nilofer / Rasheed, Zeshaan / Diaz, Luis A / Donehower, Ross / Laheru, Daniel / Hruban, Ralph H / Fishman, Elliot K / Edil, Barish H / Schulick, Richard / Wolfgang, Christopher / Herman, Joseph / Zheng, Lei. ·*Departments of Oncology, Surgery, and Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD †Department of Surgery, University of Colorado School of Medicine, Denver, CO. ·Am J Clin Oncol · Pubmed #24351782.

ABSTRACT: OBJECTIVES: At diagnosis, 30% of patients with pancreatic cancer are unresectable stage 3 locally advanced. The standard treatment for locally advanced pancreatic cancer (LAPC) is not defined. The current study was conducted to assess the roles of chemotherapy and chemoradiation for LAPC treatment. MATERIALS AND METHODS: Between June 2006 and March 2011, 100 patients with LAPC were treated at the Johns Hopkins Hospital. Retrospective analysis was performed to compare cumulative incidence of progression (CIP) and overall survival (OS) among different subgroups. RESULTS: For the 100 patients, the median OS was 15.8 months and the median CIP was 8.4 months. The combination of chemotherapy and chemoradiation before disease progression was significantly associated with improved CIP (P=0.001) and improved OS when compared with chemoradiation alone (median OS: 16.4 vs. 11.1 mo, P=0.03). Among patients receiving combination treatment, patients who received chemotherapy first followed by chemoradiation had a trend toward lower CIP (P=0.09) and improved OS (median OS: 18.1 vs. 11.0 mo, P=0.09). Patients who received >2 cycles of chemotherapy before chemoradiation had a significantly decreased CIP (P=0.008) and a trend toward better OS (median OS: 19.4 vs. 15.7 mo, P=0.10). On multivariate analysis, receiving >2 cycles of chemotherapy before chemoradiation was associated with improved CIP. CONCLUSIONS: Although combination chemotherapy and chemoradiation is favored in the treatment of LAPC, longer induction chemotherapy may play a more important role in sensitization of tumors to subsequent chemoradiation. Our results support treating patients with induction chemotherapy for at least 3 cycles followed by consolidative chemoradiation. These results merit further validation by a prospective study.

8 Article ATM mutations in patients with hereditary pancreatic cancer. 2012

Roberts, Nicholas J / Jiao, Yuchen / Yu, Jun / Kopelovich, Levy / Petersen, Gloria M / Bondy, Melissa L / Gallinger, Steven / Schwartz, Ann G / Syngal, Sapna / Cote, Michele L / Axilbund, Jennifer / Schulick, Richard / Ali, Syed Z / Eshleman, James R / Velculescu, Victor E / Goggins, Michael / Vogelstein, Bert / Papadopoulos, Nickolas / Hruban, Ralph H / Kinzler, Kenneth W / Klein, Alison P. ·Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, USA. ·Cancer Discov · Pubmed #22585167.

ABSTRACT: SIGNIFICANCE: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes.

9 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.

10 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.

11 Article Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. 2012

Canto, Marcia Irene / Hruban, Ralph H / Fishman, Elliot K / Kamel, Ihab R / Schulick, Richard / Zhang, Zhe / Topazian, Mark / Takahashi, Naoki / Fletcher, Joel / Petersen, Gloria / Klein, Alison P / Axilbund, Jennifer / Griffin, Constance / Syngal, Sapna / Saltzman, John R / Mortele, Koenraad J / Lee, Jeffrey / Tamm, Eric / Vikram, Raghunandan / Bhosale, Priya / Margolis, Daniel / Farrell, James / Goggins, Michael / Anonymous3270715. ·Department of Medicine (Division of Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. mcanto@jhmi.edu ·Gastroenterology · Pubmed #22245846.

ABSTRACT: BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs). METHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias. CONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.

12 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.

13 Article Resected pancreatic adenosquamous carcinoma: clinicopathologic review and evaluation of adjuvant chemotherapy and radiation in 38 patients. 2010

Voong, K Ranh / Davison, Jon / Pawlik, Timothy M / Uy, Manuel O / Hsu, Charles C / Winter, Jordan / Hruban, Ralph H / Laheru, Daniel / Rudra, Sonali / Swartz, Michael J / Nathan, Hari / Edil, Barish H / Schulick, Richard / Cameron, John L / Wolfgang, Christopher L / Herman, Joseph M. ·Department of Radiation Oncology and Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Hospital, Baltimore, MD 21231-6681, USA. ·Hum Pathol · Pubmed #19801164.

ABSTRACT: Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (< 30% versus > or = 30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival.

14 Article Elevated cancer mortality in the relatives of patients with pancreatic cancer. 2009

Wang, Li / Brune, Kieran A / Visvanathan, Kala / Laheru, Daniel / Herman, Joseph / Wolfgang, Christoper / Schulick, Richard / Cameron, John L / Goggins, Michael / Hruban, Ralph H / Klein, Alison P. ·1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21231, USA. ·Cancer Epidemiol Biomarkers Prev · Pubmed #19843679.

ABSTRACT: Most inherited cancer syndromes are characterized by the familial clustering of cancers at several organ sites. To determine if cancers, other than pancreatic cancer, cluster in pancreatic cancer kindreds, we examined mortality patterns among the relatives of National Familial Pancreatic Tumor Registry probands. Over 200,000 person-years of follow-up from 8,564 first-degree relatives of probands and 1,007 spouse controls were included in these analyses. We compared mortality rates of National Familial Pancreatic Tumor Registry participants to US population rates using weighed standardized mortality ratios (wSMR). Analyses were stratified by family history of pancreatic cancer (sporadic versus familial), family history of young onset pancreatic cancer (<50 years), and family history score. Cancer mortality was increased in both the relatives of sporadic probands [wSMR 1.55, 95% confidence interval (95% CI) 1.39-1.73] and familial probands (wSMR 1.41, 95% CI 1.26-1.58). Relatives of familial probands had a significantly increased risk of dying from breast (wSMR 1.66, 95% CI 1.15-2.34), ovarian (wSMR 2.05, 95% CI 1.10-3.49), and bile duct cancers (wSMR 2.89, 95% CI 1.04-6.39). Relatives of sporadic probands were at increased risk of dying from bile duct cancer (wSMR 3.01, 95% CI 1.09-6.67). Relatives of young onset probands were at higher risk of dying from cancers of the breast (wSMR 1.98, 95% CI 1.01-3.52), colon (wSMR 2.31, 95% CI 1.30-3.81) and prostate (wSMR 2.31, 95% CI 1.14-4.20). Increased cancer mortality was not observed in the spouse controls. Our results show that relatives of pancreatic cancer patients are at higher risk of developing cancers at other sites and highlight the importance of complete family history in clinical risk assessment.

15 Article SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. 2009

Blackford, Amanda / Serrano, Oscar K / Wolfgang, Christopher L / Parmigiani, Giovanni / Jones, Siân / Zhang, Xiaosong / Parsons, D Williams / Lin, Jimmy Cheng-Ho / Leary, Rebecca J / Eshleman, James R / Goggins, Michael / Jaffee, Elizabeth M / Iacobuzio-Donahue, Christine A / Maitra, Anirban / Cameron, John L / Olino, Kelly / Schulick, Richard / Winter, Jordan / Herman, Joseph M / Laheru, Daniel / Klein, Alison P / Vogelstein, Bert / Kinzler, Kenneth W / Velculescu, Victor E / Hruban, Ralph H. ·Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA. ·Clin Cancer Res · Pubmed #19584151.

ABSTRACT: PURPOSE: Recently, the majority of protein coding genes were sequenced in a collection of pancreatic cancers, providing an unprecedented opportunity to identify genetic markers of prognosis for patients with adenocarcinoma of the pancreas. EXPERIMENTAL DESIGN: We previously sequenced more than 750 million base pairs of DNA from 23,219 transcripts in a series of 24 adenocarcinomas of the pancreas. In addition, 39 genes that were mutated in more than one of these 24 cancers were sequenced in a separate panel of 90 well-characterized adenocarcinomas of the pancreas. Of these 114 patients, 89 underwent pancreaticoduodenectomy, and the somatic mutations in these cancers were correlated with patient outcome. RESULTS: When adjusted for age, lymph node status, margin status, and tumor size, SMAD4 gene inactivation was significantly associated with shorter overall survival (hazard ratio, 1.92; 95% confidence interval, 1.20-3.05; P = 0.006). Patients with SMAD4 gene inactivation survived a median of 11.5 months, compared with 14.2 months for patients without SMAD4 inactivation. By contrast, mutations in CDKN2A or TP53 or the presence of multiple (> or =4) mutations or homozygous deletions among the 39 most frequently mutated genes were not associated with survival. CONCLUSIONS: SMAD4 gene inactivation is associated with poorer prognosis in patients with surgically resected adenocarcinoma of the pancreas.

16 Article Genetic mutations associated with cigarette smoking in pancreatic cancer. 2009

Blackford, Amanda / Parmigiani, Giovanni / Kensler, Thomas W / Wolfgang, Christopher / Jones, Siân / Zhang, Xiaosong / Parsons, D Willams / Lin, Jimmy Cheng-Ho / Leary, Rebecca J / Eshleman, James R / Goggins, Michael / Jaffee, Elizabeth M / Iacobuzio-Donahue, Christine A / Maitra, Anirban / Klein, Alison / Cameron, John L / Olino, Kelly / Schulick, Richard / Winter, Jordan / Vogelstein, Bert / Velculescu, Victor E / Kinzler, Kenneth W / Hruban, Ralph H. ·Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA. ·Cancer Res · Pubmed #19351817.

ABSTRACT: Cigarette smoking doubles the risk of pancreatic cancer, and smoking accounts for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. We previously sequenced >750 million bp DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (discovery screen). In this previous study, the 39 genes that were mutated more than once in the discovery screen were sequenced in an additional 90 adenocarcinomas of the pancreas (validation screen). Here, we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n = 64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n = 50). When adjusted for age and gender, analyses of the discovery screen revealed significantly more nonsynonymous mutations in the carcinomas obtained from ever smokers (mean, 53.1 mutations per tumor; SD, 27.9) than in the carcinomas obtained from never smokers (mean, 38.5; SD, 11.1; P = 0.04). The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head versus tail of the gland. Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.

17 Article New markers of pancreatic cancer identified through differential gene expression analyses: claudin 18 and annexin A8. 2008

Karanjawala, Zarir E / Illei, Peter B / Ashfaq, Raheela / Infante, Jeffrey R / Murphy, Kathleen / Pandey, Akhilesh / Schulick, Richard / Winter, Jordan / Sharma, Rajni / Maitra, Anirban / Goggins, Michael / Hruban, Ralph H. ·The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231-2410, USA. ·Am J Surg Pathol · Pubmed #18223320.

ABSTRACT: BACKGROUND: New markers to distinguish benign reactive glands from infiltrating ductal adenocarcinoma of the pancreas are needed. DESIGN: The gene expression patterns of 24 surgically resected primary infiltrating ductal adenocarcinomas of the pancreas were compared with 18 non-neoplastic samples using the Affymetrix U133 Plus 2.0 Arrays and the Gene Logic GeneExpress Software System. Gene fragments from 4 genes (annexin A8, claudin 18, CXCL5, and S100 A2) were selected from the fragments found to be highly expressed in infiltrating adenocarcinomas when compared with normal tissues. The protein expression of these genes was examined using immunohistochemical labeling of tissue microarrays. RESULTS: Claudin 18 labeled infiltrating carcinomas in a membranous pattern. When compared with normal and reactive ducts, claudin 18 was overexpressed, at least focally, in 159 of 166 evaluable carcinomas (96%). Strong and diffuse claudin 18 overexpression was most often seen in well-differentiated carcinomas (P=0.02). Claudin 18 was overexpressed in 51 of 52 cases (98%) of pancreatic intraepithelial neoplasia. Annexin A8 was at least focally overexpressed in 149 of 154 evaluable infiltrating carcinomas (97%). S100 A2 was at least focally overexpressed in 118 of 154 evaluable infiltrating carcinomas (77%). Non-neoplastic glands also frequently expressed S100 A2 diminishing its potential diagnostic utility. Immunolabeling with antibodies directed against CXCL5 did not reveal any significant differences in protein expression between infiltrating adenocarcinomas and normal pancreatic ducts. CONCLUSIONS: Claudin 18 and annexin A8 are frequently highly overexpressed in infiltrating ductal adenocarcinomas when compared with normal reactive ducts, suggesting a role for these molecules in pancreatic ductal adenocarcinomas. Furthermore, these may serve as diagnostic markers, as screening tests and as therapeutic targets.

18 Minor Surveillance in individuals at high risk of pancreatic cancer: too early to tell? 2010

Harinck, Femme / Canto, Marcia Irene / Schulick, Richard / Goggins, Michael / Poley, Jan-Werner / Fockens, Paul / Kluijt, Irma / Bruno, Marco. · ·Gut · Pubmed #20581252.

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