Ralph H Hruban

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (916)5783.92 Total impact

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    ABSTRACT: The objective of our study was to determine how often symptomatic Meckel diverticulum and asymptomatic Meckel diverticulum are detected on CT in patients with known Meckel diverticulum and to evaluate factors that influence detection. A total of 85 CT examinations of 40 patients (eight pediatric patients and 32 adult patients; 29 male patients and 11 female patients; average age, 46.2 ± 23.7 [SD] years) with a pathologic diagnosis of Meckel diverticulum were retrospectively evaluated. These patients included 26 adult patients with incidentally found asymptomatic Meckel diverticulum and 14 patients (eight pediatric and six adult patients) with symptomatic Meckel diverticulum. The CT technical factors and patients' morphologic factors were compared with the detection of Meckel diverticulum using mixed-effect logistic regression models. Meckel diverticulum was detected on at least one CT examination in eight of 14 (57.1%) symptomatic patients (two of four patients with bleeding, two of six patients with small-bowel obstruction, two of two patients with acute diverticulitis, one of one patient with incisional hernia, and one of one patient with inverted Meckel diverticulum) and in 13 of 23 (56.5%) total CT examinations. Asymptomatic Meckel diverticulum was detected on at least one CT examination in 11 of 26 (42.3%) patients and in 16 of 62 (25.8%) total CT examinations. The amount of peritoneal fat was related to the detection of Meckel diverticula (p = 0.02). Although not statistically significant, the subjective quality of axial CT (p = 0.05) tended to be related to detection, whereas the use of IV (p = 0.59) or positive oral (p = 0.41) contrast material was unrelated to detection. In the original CT reports, none of the asymptomatic cases of Meckel diverticulum was prospectively detected, whereas Meckel diverticulum was detected or mentioned as a possibility in 64% of the symptomatic cases. In patients with known Meckel diverticulum, CT can detect Meckel diverticulum in up to 47.5% of all patients. Meckel diverticulum is more commonly detected in symptomatic patients than in asymptomatic patients, and detection is related to the amount of peritoneal fat.
    American Journal of Roentgenology 08/2015; 205(2):281-91. DOI:10.2214/AJR.14.13898 · 2.74 Impact Factor
  • Marcia I Canto, Ralph H Hruban
    Nature Reviews Gastroenterology &#38 Hepatology 06/2015; DOI:10.1038/nrgastro.2015.112 · 10.81 Impact Factor
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    ABSTRACT: Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile. Biliary intraductal tubulopapillary neoplasms were seen in patients in their 60s (mean 62 years). The tumors were intrahepatic 70%, extrahepatic 10%, and perihilar 20%; mean tumor size was 6.9 cm. Histologically, all intraductal tubulopapillary neoplasms showed, in addition to their typical tubular pattern, solid areas (70%) or abortive papillae (50%). Necrosis was common (85%), predominantly focal (40%), and with 'comedocarcinoma-like pattern' in 40%. Immunohistochemically, these neoplasms were characterized by the expression of MUC1 (80%) and MUC6 (30%) and by the absence of MUC2 and MUC5AC. Associated invasive carcinomas were present in 16 (80%), mainly conventional tubular adenocarcinoma (50%). The molecular alterations observed included CDKN2A/p16 (intraductal components 44%, invasive 33%) and TP53 (intraductal components 17%, invasive 9%). Mutations in KRAS (intraductal 6%, invasive 0%), PIK3CA (intraductal 6%, invasive 0%), and loss of SMAD4/DPC4 (intraductal 7%, invasive 0%) were rare. No alterations/mutations were identified in IDH1/2, BRAF, GNAS, EGFR, HER2, and β-catenin. Follow-up information was available for 17 patients (85%) with mean follow-up 44 months. Overall combined survival rates showed favorable prognosis: 1 year 100%, 3 years 90%, and 5 years 90%. In conclusion, despite the relatively high incidence of invasive carcinoma (80%), available follow-up suggests that biliary intraductal tubulopapillary neoplasms have an indolent behavior. Molecular analyses highlight the low prevalence of alterations of common oncogenic signaling pathways in intraductal tubulopapillary neoplasm. Further studies using whole-exome sequencing are required to discover yet unknown molecular changes and to understand the carcinogenesis of intraductal tubulopapillary neoplasms.Modern Pathology advance online publication, 26 June 2015; doi:10.1038/modpathol.2015.61.
    Modern Pathology 06/2015; DOI:10.1038/modpathol.2015.61 · 6.36 Impact Factor
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    ABSTRACT: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Retrospective multinational study including SCN diagnosed between 1990 and 2014. 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. IRB 00006477. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Gut 06/2015; DOI:10.1136/gutjnl-2015-309638 · 13.32 Impact Factor
  • Pancreatology 06/2015; 15(3):S96. DOI:10.1016/j.pan.2015.05.350 · 2.50 Impact Factor
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    ABSTRACT: Background Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade. Methods We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair-deficient colorectal cancers, patients with mismatch repair-proficient colorectal cancers, and patients with mismatch repair-deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate. Results The immune-related objective response rate and immune-related progression-free survival rate were 40% (4 of 10 patients) and 78% (7 of 9 patients), respectively, for mismatch repair-deficient colorectal cancers and 0% (0 of 18 patients) and 11% (2 of 18 patients) for mismatch repair-proficient colorectal cancers. The median progression-free survival and overall survival were not reached in the cohort with mismatch repair-deficient colorectal cancer but were 2.2 and 5.0 months, respectively, in the cohort with mismatch repair-proficient colorectal cancer (hazard ratio for disease progression or death, 0.10 [P<0.001], and hazard ratio for death, 0.22 [P=0.05]). Patients with mismatch repair-deficient noncolorectal cancer had responses similar to those of patients with mismatch repair-deficient colorectal cancer (immune-related objective response rate, 71% [5 of 7 patients]; immune-related progression-free survival rate, 67% [4 of 6 patients]). Whole-exome sequencing revealed a mean of 1782 somatic mutations per tumor in mismatch repair-deficient tumors, as compared with 73 in mismatch repair-proficient tumors (P=0.007), and high somatic mutation loads were associated with prolonged progression-free survival (P=0.02). Conclusions This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511 .).
    New England Journal of Medicine 05/2015; DOI:10.1056/NEJMoa1500596 · 54.42 Impact Factor
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    ABSTRACT: To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs). FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity. In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen. Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer. FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.
    Annals of surgery 05/2015; DOI:10.1097/SLA.0000000000001156 · 7.19 Impact Factor
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    ABSTRACT: For the majority of patients with pancreas cancer, the high metastatic proclivity is life limiting. Some patients, however, present with and succumb to locally destructive disease. A molecular understanding of these distinct disease manifestations can critically inform patient management. Using genetically engineered mouse models, we show that heterozygous mutation of Dpc4/Smad4 attenuates the metastatic potential of Kras(G12D/+);Trp53(R172H/+) pancreatic ductal adenocarcinomas while increasing their proliferation. Subsequent loss of heterozygosity of Dpc4 restores metastatic competency while further unleashing proliferation, creating a highly lethal combination. Expression levels of Runx3 respond to and combine with Dpc4 status to coordinately regulate the balance between cancer cell division and dissemination. Thus, Runx3 serves as both a tumor suppressor and promoter in slowing proliferation while orchestrating a metastatic program to stimulate cell migration, invasion, and secretion of proteins that favor distant colonization. These findings suggest a model to anticipate likely disease behaviors in patients and tailor treatment strategies accordingly. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 05/2015; 161(6). DOI:10.1016/j.cell.2015.04.048 · 33.12 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is driven by the inactivation of the tumor suppressor genes (TSGs), CDKN2A (P16) and SMAD4 (DPC4), commonly by homozygous deletions (HDs). Using a combination of high density single-nucleotide polymorphism (SNP) microarray and whole genome sequencing (WGS), we fine-mapped novel breakpoints surrounding deletions of CDKN2A and SMAD4 and characterized them by their underlying structural variants (SVs). Only one third of CDKN2A and SMAD4 deletions (6 of 18) were simple interstitial deletions, rather, the majority of deletions were caused by complex rearrangements, specifically, a translocation on one side of the TSG in combination with an inversion on the other side. We designate these as "TransFlip" mutations. Characteristics of TransFlip mutations are: (1) a propensity to target the TSGs CDKN2A and SMAD4 (P < 0.005), (2) not present in the germline of the examined samples, (3) non-recurrent breakpoints, (4) relatively small (47 bp to 3.4 kb) inversions, (5) inversions can be either telomeric or centromeric to the TSG, and (6) non-reciprocal, and non-recurrent translocations. TransFlip mutations are novel complex genomic rearrangements with unique breakpoint signatures in pancreatic cancer. We hypothesize that they are a common but poorly understood mechanism of TSG inactivation in human cancer. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 05/2015; DOI:10.1002/gcc.22258 · 3.84 Impact Factor
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    ABSTRACT: It is estimated that approximately 10% of pancreatic cancers have a familial component. Many inheritable genetic syndromes are associated with increased risk of pancreatic cancer, such as Peutz-Jeghers syndrome, hereditary breast-ovarian cancer and familial atypical multiple mole melanoma, but these conditions account for only a minority of familial pancreatic cancers. Previous studies have identified an increased prevalence of noninvasive precursor lesions, including pancreatic intraepithelial neoplasia, in the pancreata of patients with a strong family history of pancreatic cancer. A detailed investigation of the histopathology of invasive familial pancreatic cancer could provide insights into the mechanisms responsible for familial pancreatic cancer, as well as aid early detection and treatment strategies. We have conducted a blinded review of the pathology of 519 familial and 651 sporadic pancreatic cancers within the National Familial Pancreas Tumor Registry. Patients with familial pancreatic cancer were defined as individuals from families in which at least a pair of first-degree relatives have been diagnosed with pancreatic cancer. Overall, there were no statistically significant differences in histologic subtypes between familial and sporadic pancreatic cancers (p > 0.05). In addition, among surgical resection specimens within the study cohort, no statistically significant differences in mean tumor size, location, perineural invasion, angiolymphatic invasion, lymph node metastasis and pathologic stage were identified (p > 0.05). Similar to sporadic pancreatic cancer, familial pancreatic cancer is morphologically and prognostically a heterogeneous disease. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
    Pancreatology 04/2015; DOI:10.1016/j.pan.2015.04.003 · 2.50 Impact Factor
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    ABSTRACT: Most cancers in humans are large, measuring centimeters in diameter, composed of many billions of cells. An equivalent mass of normal cells would be highly heterogeneous as a result of the mutations that occur during each cell division. What is remarkable about cancers is their homogeneity - virtually every neoplastic cell within a large cancer contains the same core set of genetic alterations, with heterogeneity confined to mutations that have emerged after the last clonal expansions. How such clones expand within the spatially-constrained three dimensional architecture of a tumor, and come to dominate a large, pre-existing lesion, has never been explained. We here describe a model for tumor evolution that shows how short-range migration and cell turnover can account for rapid cell mixing inside the tumor. With it, we show that even a small selective advantage of a single cell within a large tumor allows the descendants of that cell to replace the precursor mass in a clinically relevant time frame. We also demonstrate that the same mechanisms can be responsible for the rapid onset of resistance to chemotherapy. Our model not only provides novel insights into spatial and temporal aspects of tumor growth but also suggests that targeting short range cellular migratory activity could have dramatic effects on tumor growth rates.
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    ABSTRACT: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤0.5, >0.5-≤1, >1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.
    Annals of Surgery 03/2015; DOI:10.1097/SLA.0000000000001173 · 8.33 Impact Factor
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    ABSTRACT: The 2010 World Health Organization (WHO) classification recommends that pancreatic neuroendocrine tumors (PanNETs) be graded on the basis of the mitotic rate and Ki67 index, with grade 2 (G2) PanNETs defined as having a mitotic rate of 2 to 20 mitotic figures/10 high-power fields or a Ki67 index of 3% to 20%. Grade 3 (G3) pancreatic neuroendocrine carcinoma (NEC) is defined as having >20 mitotic figures/10 high-power fields or a Ki67 index of >20%. However, some PanNETs show discordance between the mitotic rate and Ki67 index, usually having a Ki67 index in the G3 range but a mitotic rate suggesting G2, prompting us to examine the clinical significance of the Ki67 index in a large series of clinically well-characterized mitotic G2 PanNETs. Mitotic G2 well differentiated PanNETs, surgically resected at our institutions were reviewed. Of those, 19 cases had a Ki67>20% and were selected as the study group of grade-discordant (mitotic count G2/Ki67 index G3) PanNETs. For comparison, 53 grade-concordant (both mitotic count and Ki67 index G2) PanNETs matched for presenting stage with the discordant group as well as 43 morphologically poorly differentiated (either small cell or large cell type) pancreatic NECs were also included. The percentage of Ki67-positive neoplastic cells was quantified by manual counting of at least 500 cells on printed photographic images of "hot spots." The mean Ki67 index for grade-concordant and grade-discordant PanNETs and poorly differentiated NECs were 8.1% (range, 3% to 20%), 40% (range, 24% to 80%), and 70% (range, 40% to 98%), respectively. Overall, patients with grade-discordant PanNETs had significantly longer survival time compared with the patients with poorly differentiated NEC (median survival of 54.1 vs. 11 mo and 5 y survival of 29.1% vs. 16.1%; P=0.002). In addition, the survival time of the patients with grade-discordant PanNETs was shorter than that of the patients with grade-concordant PanNETs (median survival of 67.8 mo and 5 y survival of 62.4%); however, the difference was not statistically significant (P=0.2). Our data support the notion that the mitotic rate and Ki67 index-based grades of PanNETs can be discordant, and when the Ki67 index indicates G3, the clinical outcome is slightly worse. More importantly, we demonstrate that well differentiated PanNETs that are G3 by Ki67 are significantly less aggressive than bona fide poorly differentiated NECs, suggesting that the current WHO G3 category is heterogenous, contains 2 distinct neoplasms, and can be further separated into well differentiated PanNET with an elevated proliferation rate and poorly differentiated NEC.
    American Journal of Surgical Pathology 02/2015; 39(5). DOI:10.1097/PAS.0000000000000408 · 4.59 Impact Factor
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    ABSTRACT: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.
    Nature 02/2015; 518(7540):495-501. DOI:10.1038/nature14169 · 42.35 Impact Factor
  • Marcia Irene Canto, Ralph H Hruban
    Gastroenterology 02/2015; 148(4). DOI:10.1053/j.gastro.2015.02.033 · 13.93 Impact Factor
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    ABSTRACT: Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in Oncology 02/2015; 42(1):28-39. DOI:10.1053/j.seminoncol.2014.12.004 · 3.94 Impact Factor
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    ABSTRACT: Purpose: The median survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC) is currently <20 months. However, survival ≥10 years is achieved by a small subset of patients who are defined as very long-term survivors (VLTSs). The goal of this study was to determine whether specific genetic alterations in resected PDACs determined very long-term survival. Experimental Design: We sequenced the exomes of 8 PDACs from patients who survived ≥10 years. Based on the results of the exomic analysis, targeted sequencing of selected genes was performed in a series of 27 additional PDACs from VLTSs. Results: KRAS mutations were identified in 33 of 35 (94%) cancers from VLTSs and represented the most prevalent alteration in our cohort. TP53, SMAD4, and CDKN2A mutations occurred in 69%, 26%, and 17%, respectively. Mutations in RNF43, which have been previously associated with intraductal papillary mucinous neoplasms, were identified in 4 of the 35 cancers (11%). Taken together, our data show no difference in somatic mutations in carcinomas from VLTSs compared to available data from PDACs unselected for survival. Comparison of clinico-pathological features between VLTSs and a matching control group demonstrated that younger age, earlier stage, well/moderate grade of differentiation, and negative resection margins were associated with VLTS. However, more advanced stage, poor grade or nodal disease did not preclude long-term survival. Conclusion: Our results suggest that in most patients somatic mutations in commonly mutated genes are unlikely to be the primary determinant of very long-term survival following surgical resection of PDAC. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 01/2015; 21(8). DOI:10.1158/1078-0432.CCR-14-2600 · 8.19 Impact Factor
  • Hanno Matthaei, Alexander Semaan, Ralph H Hruban
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    ABSTRACT: Cancer is caused by the accumulation of inherited and/or acquired alterations in specific genes. The recent decline in the cost of DNA sequencing has allowed tumor sequencing to be conducted on a large scale, which, in turn, has led to an unprecedented understanding of the genetic events that drive neoplasia. This understanding, when integrated with meticulous histologic analyses and with clinical findings, has direct clinical implications. The recent sequencing of all of the major types of cystic and noncystic neoplasms of the pancreas has revealed opportunities for molecular diagnoses and for personalized treatment. This review summarizes the results from these recent studies focusing on the clinical relevance of genomic data.
    Journal of Gastroenterology 01/2015; 50(5). DOI:10.1007/s00535-015-1037-4 · 4.02 Impact Factor
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    ABSTRACT: The significance of indeterminate pulmonary nodules (IPNs) in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) is unknown. We sought to define the prevalence and impact of IPN in such patients. We studied all patients who underwent surgical resection of PDAC between 1980 and 2013. IPN was defined as ≥1 well-defined lung nodule(s) less than 3 cm in diameter. Survival was assessed using univariate and multivariate Cox models. Of the 2306 resected patients, 374 (16.2 %) had a preoperative chest computed tomography (CT) scan. Of these patients, 183 (49 %) had ≥1 IPN. Demographic and clinicopathological characteristics were similar among patients with or without IPN (all P > 0.05). Median survival was comparable among patients who did (15.6 months) or did not (18.0 months) have IPN (P = 0.66). Of the 183 patients with IPN, 29 (16 %) progressed to clinically recognizable metastatic lung disease compared to 13 % without IPN (P = 0.38). The presence of >1 IPN was associated with the development of lung metastasis (relative risk 1.58, 95 % CI 1.03-2.4; P = 0.05). However, lung metastasis was not associated with survival (P = 0.24). An IPN proved to be a lung metastasis in only one of six patients with PDAC undergoing surgical resection in this study. Survival was not impacted, even among patients who developed lung metastasis. Patients with PDAC who have IPN should not be precluded from surgical consideration.
    Journal of Gastrointestinal Surgery 01/2015; 19(5). DOI:10.1007/s11605-014-2740-9 · 2.39 Impact Factor
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    Laura D Wood, Ralph H Hruban
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    ABSTRACT: Pancreatic cancer is a deadly disease with a dismal prognosis. However, recent advances in sequencing and bioinformatic technology have led to the systematic characterization of the genomes of all major tumor types in the pancreas. This characterization has revealed the unique genomic landscape of each tumor type. This knowledge will pave the way for improved diagnostic and therapeutic approaches to pancreatic tumors that take advantage of the genetic alterations in these neoplasms.
    01/2015; 49(1):13-22. DOI:10.4132/jptm.2014.12.26

Publication Stats

57k Citations
5,783.92 Total Impact Points

Institutions

  • 1990–2015
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Surgery
      • • Department of Epidemiology
      • • Department of Medicine
      • • Department of Otolaryngology - Head and Neck Surgery
      Baltimore, Maryland, United States
  • 1984–2015
    • Johns Hopkins Medicine
      • • Department of Surgery
      • • Department of Pathology
      • • Department of Radiology and Radiological Science
      • • Department of Biomedical Engineering
      Baltimore, Maryland, United States
  • 2013
    • Duke University
      Durham, North Carolina, United States
    • University of Colorado
      • Division of GI, Tumor and Endocrine Surgery
      Denver, CO, United States
  • 2011
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 2009
    • Cambridge Institute for Medical Research
      Cambridge, England, United Kingdom
  • 1990–2009
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York City, NY, United States
  • 2007
    • Cold Spring Harbor Laboratory
      Cold Spring Harbor, New York, United States
  • 2006
    • Louisiana State University in Shreveport
      Shreveport, Louisiana, United States
    • Creighton University
      Omaha, Nebraska, United States
  • 2005
    • Sapienza University of Rome
      Roma, Latium, Italy
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
  • 2004
    • Temple University
      Filadelfia, Pennsylvania, United States
    • Kagoshima University
      • Graduate School of Medical and Dental Sciences
      Kagosima, Kagoshima, Japan
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 2003
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, Minnesota, United States
    • Wayne State University
      • Department of Pathology
      Detroit, MI, United States
    • University of Oxford
      • Nuffield Division of Clinical Laboratory Sciences
      Oxford, England, United Kingdom
  • 2000–2003
    • University of Texas Southwestern Medical Center
      • Department of Pathology
      Dallas, Texas, United States
  • 2002
    • Sidney Health Center
      Sydney, New South Wales, Australia
  • 1998–2002
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
    • University of California, San Francisco
      San Francisco, California, United States
  • 1999
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 1995–1999
    • University of Amsterdam
      • Department of Pathology
      Amsterdamo, North Holland, Netherlands
    • University of Chicago
      Chicago, Illinois, United States
  • 1993
    • Greater Baltimore Medical Center
      Baltimore, Maryland, United States
  • 1992
    • University of Massachusetts Boston
      Boston, Massachusetts, United States