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Desolneux G, Castanet F. [Precancerous lesions of the pancreas, prophylactic surgery]. Bull Cancer 2025; 112:263-269. [PMID: 40049795 DOI: 10.1016/j.bulcan.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 05/28/2024] [Accepted: 06/04/2024] [Indexed: 03/15/2025]
Abstract
Pancreatic cancer is a serious pathology whose incidence is increasing. Advances in imaging have made it possible to fortuitously highlight more and more cystic pancreatic lesions, some of which have a malignant potential, leading to the consideration of prophylactic excision. The various known precancerous lesions of the pancreas as well as current management recommendations are here reviewed.
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Affiliation(s)
- Gregoire Desolneux
- Chirurgie digestive oncologique, institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France.
| | - Fanny Castanet
- Chirurgie digestive oncologique, institut Bergonié, 229, cours de l'Argonne, 33076 Bordeaux cedex, France
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A meta-analysis: incidental intraductal papillary mucinous neoplasm and extra-pancreatic malignancy. Langenbecks Arch Surg 2021; 407:451-458. [PMID: 34664122 DOI: 10.1007/s00423-021-02355-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 10/06/2021] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Meta-analysis aimed to quantify the relationship between intraductal papillary mucinous neoplasm (IPMN) and increased incidence of extra-pancreatic malignancy (EPM) previously reported in qualitative observational cohort studies. METHODS Study protocol was registered with PROSPERO (CRD42020169614) and conducted to the Meta-analysis Of Observational Studies in Epidemiology and systematic review reported with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Assessing the Methodological Quality of Systematic Reviews guidelines. RESULTS Sixteen studies (total of 8240 patients) were included in the pooled, and 7399 patients in the subgroup meta-analyses. The odds ratio (OR) for any EPM in the presence of IPMN was 57.9 (95% confidence interval 40.5-82.7), fixed effects, I2 = 59% (p < 0.0014). Subgroup analysis for any gastrointestinal EPM (i.e. oesophagus, stomach, colon and rectum) in the presence of an IPMN estimated an overall OR of 12.9 (95% confidence interval 8.8-19.0), fixed effects, I2 = 64% (p < 0.0004). CONCLUSION Patients with an IPMN are categorically at increased risk for a higher incidence of EPM and particularly the odds of a gastrointestinal malignancy are also increased in comparison with the general population. We advocate that patients presenting with an IPMN should be considered for gastrointestinal screening including colonoscopy, upper gastrointestinal endoscopy or computed tomography.
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Tanaka T, Masuda A, Sofue K, Toyama H, Shiomi H, Sakai A, Kobayashi T, Tanaka S, Nakano R, Yamada Y, Ashina S, Tsujimae M, Yamakawa K, Abe S, Gonda M, Masuda S, Inomata N, Uemura H, Kohashi S, Nagao K, Kanzawa M, Itoh T, Fukumoto T, Kodama Y. Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes. Pancreatology 2021; 21:138-143. [PMID: 33328127 DOI: 10.1016/j.pan.2020.11.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 11/09/2020] [Accepted: 11/15/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN. METHODS This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated. RESULTS AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes. CONCLUSION Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.
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Affiliation(s)
- Takeshi Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Japan
| | - Hirochika Toyama
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Hideyuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Shunta Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Ryota Nakano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Yasutaka Yamada
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Shigeto Ashina
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Masahiro Tsujimae
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Kohei Yamakawa
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Shohei Abe
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Masanori Gonda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Shigeto Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Noriko Inomata
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Hisahiro Uemura
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Shinya Kohashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Kae Nagao
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Maki Kanzawa
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan
| | - Tomoo Itoh
- Division of Diagnostic Pathology, Kobe University Graduate School of Medicine, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
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Intraductal Pancreatic Mucinous Neoplasms: A Tumor-Biology Based Approach for Risk Stratification. Int J Mol Sci 2020; 21:ijms21176386. [PMID: 32887490 PMCID: PMC7504137 DOI: 10.3390/ijms21176386] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 08/27/2020] [Accepted: 09/01/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic ductal adenocarcinoma is one of the most lethal human cancers. Its precursor lesions include pancreatic intra-epithelial neoplasia, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm (IPMN). IPMNs usually present as an incidental finding at imaging in 2.6% of the population and, according to the degree of dysplasia, they are classified as low- or high-grade lesions. Since the risk of malignant transformation is not accurately predictable, the management of these lesions is based on morphological and clinical parameters, such as presence of mural nodule, main pancreatic duct dilation, presence of symptoms, or high-grade dysplasia. Although the main genetic alterations associated to IPMNs have been elucidated, they are still not helpful for disease risk stratification. The growing body of genomic and epigenomic studies along with the more recent development of organotypic cultures provide the opportunity to improve our understanding of the malignant transformation process, which will likely deliver biomarkers to help discriminate between low- and high-risk lesions. Recent insights on the topic are herein summarized.
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Costa DAPD, Guerra JG, Goldman SM, Kemp R, Santos JS, Ardengh JC, Ribas CAPM, Nassif PAN, Ribas-Filho JM. MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MRCP) VERSUS ENDOSONOGRAPHY-GUIDED FINE NEEDLE ASPIRATION (EUS-FNA) FOR DIAGNOSIS AND FOLLOW-UP OF PANCREATIC INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2019; 32:e1471. [PMID: 31859924 PMCID: PMC6918736 DOI: 10.1590/0102-672020190001e1471] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/09/2019] [Indexed: 12/31/2022]
Abstract
BACKGROUND Intraductal papillary mucinous tumor (IPMN) are being diagnosed with increasing frequency. Computerized tomography scanning is commonly used as the primary imaging modality before surgery nonetheless magnetic resonance cholangiopancreatography (MRCP) provides better characterization. Endosonography-guided fine needle aspiration (EUS-FNA) has emerged as a way to reach pathological diagnose. AIM To compare results of both methods with surgical pathology findings for classification of IPMN. METHODS Thirty-six patients submitted to surgical resection with preoperative suspect of IPMN were submitted preoperatively to MRCP and EUS-FNA. Images obtained were analyzed according to a classification determined for each method. ROC curve was used for statistical analysis, that compared the images tests with the purpose of finding the best method for diagnosis and classification of IPMN. RESULTS Sixteen patients underwent pancreatoduodenectomy, 16 to subtotal pancreatectomy and only four laparotomy. Pathological diagnosis was IPMN (n=33) and pancreatic intraepithelial neoplasia type 2 (n=3). Twenty-nine revealed non-invasive neoplasia and invasive form in four patients. MRCP and EUS-FNA have correctly diagnosed and classified (type of IPMN), in 62.5% and 83.3% (p=0.811), the affected segment location in 69% and 92% (p=0.638) and identification of nodules and/or vegetation presence in 45% and 90% (p=0.5). Regarding to histopathological diagnosis by EUS-FNA the sensitivity was 83.3%; specificity was 100%; positive predictive value was 100%; negative predictive value was 33.3% and accuracy was 91.7%. CONCLUSIONS There was no significant difference in the diagnosis of IPMN. However, EUS-FNA showed better absolute results than MRCP to identify nodule and/or vegetation.
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Affiliation(s)
| | - João Guilherme Guerra
- AC Camargo Cancer Center, Endoscopy Service, AC Camargo Hospital, São Paulo, SP, Brazil
| | - Suzan Menasce Goldman
- Department of Diagnostic Imaging, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
| | - Rafael Kemp
- Department of Surgery and Anatomy, Hospital das Clínicas, Ribeirão Preto Medical School, Ribeirão Preto, SP, Brazil
| | - José Sebastião Santos
- Department of Surgery and Anatomy, Hospital das Clínicas, Ribeirão Preto Medical School, Ribeirão Preto, SP, Brazil
| | - José Celso Ardengh
- Department of Diagnostic Imaging, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil
- Department of Surgery and Anatomy, Hospital das Clínicas, Ribeirão Preto Medical School, Ribeirão Preto, SP, Brazil
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"Trivial" Cysts Redefine the Risk of Cancer in Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Potential Target for Follow-Up Discontinuation? Am J Gastroenterol 2019; 114:1678-1684. [PMID: 31449158 DOI: 10.14309/ajg.0000000000000378] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The management of small and incidental branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) still is of concern. The aim is assessing the safety of a surveillance protocol through the evaluation of their progression to malignancy. METHODS All presumed BD-IPMNs observed from 2000 to 2016 were included. Only patients presenting without worrisome features (WFs) and high-risk stigmata (HRS) at diagnosis were included. Development of WF, HRS, pancreatic cancer (PC), and survival were analyzed. BD-IPMNs were defined as trivial in the continuing absence of WF/HRS after 5 years of surveillance. The age-specific standardized incidence ratio of PC in the general population was used for comparison. RESULTS A total of 1,036 BD-IPMNs without WF/HRS at diagnosis were included, 4.2% developed WF or HRS, and 1.1% developed PC after a median of 62 months. The median cyst growth rate was 0 mm/yr. A growth rate ≥2.5 mm/yr and the development of WF resulted independent predictors of PC. The standardized incidence ratio of PC for trivial BD-IPMN (n = 378) was 22.45 (95% confidence interval 8.19-48.86), but considering only patients aged >65 years (n = 198), it decreased to 3.84 (95% confidence interval 0.77-11.20). DISCUSSION Surveillance of the vast majority of presumed BD-IPMNs is safe, as the risk of PC is comparable to postoperative mortality of pancreatic surgery. A growth rate ≥2.5 mm/yr is the main predictor of PC, reinforcing the role of repeated observations. A trivial BD-IPMN in patients aged >65 years might not increase the risk of developing PC compared with general population, identifying potential targets for follow-up discontinuation.
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Patients with a resected pancreatic mucinous cystic neoplasm have a better prognosis than patients with an intraductal papillary mucinous neoplasm: A large single institution series. Pancreatology 2017; 17:490-496. [PMID: 28416122 DOI: 10.1016/j.pan.2017.04.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Revised: 03/16/2017] [Accepted: 04/07/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND/OBJECTIVES Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date. METHODS We compared 142 MCNs and 746 IPMNs resected at a single institution. MCNs were reviewed for confirmation of ovarian-type stroma and reclassified according to current WHO guidelines. RESULTS MCNs presented almost exclusively in middle-aged women (median 47.5 years, 96.5% female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas (92.1%). IPMNs were distributed equally by sex in an older population (median 69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1% vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs (9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs. Patients with an MCN-associated invasive carcinoma had a much better prognosis than did patients with an IPMN-associated invasive carcinoma with 10-year disease-specific survival of 79.6% versus 27.2%, respectively. CONCLUSION MCNs have a stereotypical clinical profile that is readily distinguishable from IPMNs based on demographic features, imaging, and pathology. Most MCNs are noninvasive and curable with surgical resection. Prognosis remains excellent even for invasive disease with 10-year survival approaching 80% following resection.
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Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, Bassi C, Salvia R, Malleo G, Paiella S, Wolfgang CL, Matthaei H, Offerhaus GJ, Adham M, Bruno MJ, Reid M, Krasinskas A, Klöppel G, Ohike N, Tajiri T, Jang KT, Roa JC, Allen P, Castillo CFD, Jang JY, Klimstra DS, Hruban RH, Members of the Verona Consensus Meeting, 2013. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. Ann Surg 2016; 263:162-177. [PMID: 25775066 PMCID: PMC4568174 DOI: 10.1097/sla.0000000000001173] [Citation(s) in RCA: 191] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS (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). CONCLUSIONS 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.
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Affiliation(s)
- Volkan Adsay
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Toru Furukawa
- Department of Pathology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | | | - Claudio Bassi
- Department of Surgery, University of Verona, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, University of Verona, Verona, Italy
| | | | | | - Christopher L. Wolfgang
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Hanno Matthaei
- Department of Surgery, University of Bonn, Bonn, Germany
| | - G. Johan Offerhaus
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Mustapha Adham
- Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Michelle Reid
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Alyssa Krasinskas
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Günter Klöppel
- Department of Pathology, Technical University, München, Germany
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Católica de Chile, Chile
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | - Jin-Young Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - David S. Klimstra
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Ralph H. Hruban
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
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Machado NO, Al Qadhi H, Al Wahibi K. Intraductal Papillary Mucinous Neoplasm of Pancreas. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2015; 7:160-75. [PMID: 26110127 PMCID: PMC4462811 DOI: 10.4103/1947-2714.157477] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are neoplasms that are characterized by ductal dilation, intraductal papillary growth, and thick mucus secretion. This relatively recently defined pathology is evolving in terms of its etiopathogenesis, clinical features, diagnosis, management, and treatment guidelines. A PubMed database search was performed. All the relevant abstracts in English language were reviewed and the articles in which cases of IPMN could be identified were further scrutinized. Information of IPMN was derived, and duplication of information in several articles and those with areas of persisting uncertainties were excluded. The recent consensus guidelines were examined. The reported incidence of malignancy varies from 57% to 92% in the main duct-IPMN (MD-IPMN) and from 6% to 46% in the branch duct-IPMN (BD-IPMN). The features of high-risk malignant lesions that raise concern include obstructive jaundice in a patient with a cystic lesion in the pancreatic head, the findings on radiological imaging of a mass lesion of >30 mm, enhanced solid component, and the main pancreatic duct (MPD) of size ≥10 mm; while duct size 5-9 mm and cyst size <3 mm are considered as “worrisome features.” Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are primary investigations in diagnosing and following up on these patients. The role of pancreatoscopy and the analysis of aspirated cystic fluid for cytology and DNA analysis is still to be established. In general, resection is recommended for most MD-IPMN, mixed variant, and symptomatic BD-IPMN. The 5-year survival of patients after surgical resection for noninvasive IPMN is reported to be at 77-100%, while for those with invasive carcinoma, it is significantly lower at 27-60%. The follow-up of these patients could vary from 6 months to 1 year and would depend on the risk stratification for invasive malignancy and the pathology of the resected specimen. The understanding of IPMN has evolved over the years. The recent guidelines have played a role in this regard.
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Affiliation(s)
| | - Hani Al Qadhi
- Department of Surgery, Sultan Qaboos University Hospital, Muscat, Oman
| | - Khalifa Al Wahibi
- Department of Surgery, Sultan Qaboos University Hospital, Muscat, Oman
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Baiocchi GL, Molfino S, Frittoli B, Pigozzi G, Gheza F, Gaverini G, Tarasconi A, Ricci C, Bertagna F, Grazioli L, Tiberio GAM, Portolani N. Increased risk of second malignancy in pancreatic intraductal papillary mucinous tumors: Review of the literature. World J Gastroenterol 2015; 21:7313-7319. [PMID: 26109820 PMCID: PMC4476895 DOI: 10.3748/wjg.v21.i23.7313] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/12/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the available evidence about the risk of extrapancreatic malignancies and pancreatic ductal adenocarcinoma associated to pancreatic intraductal papillary mucinous tumors (IPMNs). METHODS A systematic search of literature was undertaken using MEDLINE, EMBASE, Cochrane and Web-of-Science libraries. No limitations for year of publication were considered; preference was given to English papers. All references in selected articles were further screened for additional publications. Both clinical series and Literature reviews were selected. For all eligible studies, a standard data extraction form was filled in and the following data were extracted: study design, number of patients, prevalence of pancreatic cancer and extrapancreatic malignancies in IPMN patients and control groups, if available. RESULTS A total of 805 abstracts were selected and read; 25 articles were considered pertinent and 17 were chosen for the present systematic review. Eleven monocentric series, 1 multicentric series, 1 case-control study, 1 population-based study and 3 case report were included. A total of 2881 patients were globally analyzed as study group, and the incidence of pancreatic cancer and/or extrapancreatic malignancies ranged from 5% to 52%, with a mean of 28.71%. When a control group was analyzed (6 papers), the same incidence was as low as 9.4%. CONCLUSION The available Literature is unanimous in claiming IPMNs to be strongly associated with pancreatic and extrapancreatic malignancies. The consequences in IPMNs management are herein discussed.
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MESH Headings
- Carcinoma, Pancreatic Ductal/epidemiology
- Carcinoma, Pancreatic Ductal/pathology
- Humans
- Incidence
- Neoplasms, Cystic, Mucinous, and Serous/epidemiology
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Second Primary/epidemiology
- Neoplasms, Second Primary/pathology
- Pancreatic Neoplasms/epidemiology
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/therapy
- Prevalence
- Prognosis
- Risk Assessment
- Risk Factors
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Ishikawa D, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Arakawa Y, Kanamoto M, Iwahashi S, Saito Y, Yamada S, Miyake H. Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol Hepatol 2014; 29:2032-7. [PMID: 24909638 DOI: 10.1111/jgh.12652] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN. AIM We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN. METHODS Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival. RESULTS Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05). CONCLUSIONS Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.
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Affiliation(s)
- Daichi Ishikawa
- Department of Surgery, The University of Tokushima, Tokushima, Japan
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Klöppel G, Basturk O, Schlitter AM, Konukiewitz B, Esposito I. Intraductal neoplasms of the pancreas. Semin Diagn Pathol 2014; 31:452-466. [DOI: 10.1053/j.semdp.2014.08.005] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Risk Factors for Malignancy in Branched-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas During the Follow-Up Period. World J Surg 2014; 39:244-50. [DOI: 10.1007/s00268-014-2789-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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14
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Sahora K, Fernández-del Castillo C, Dong F, Marchegiani G, Thayer SP, Ferrone CR, Sahani DV, Brugge WR, Warshaw AL, Lillemoe KD, Mino-Kenudson M. Not all mixed-type intraductal papillary mucinous neoplasms behave like main-duct lesions: implications of minimal involvement of the main pancreatic duct. Surgery 2014; 156:611-21. [PMID: 25081232 DOI: 10.1016/j.surg.2014.04.023] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 04/14/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND The malignant potential of intraductal mucinous neoplasm of the pancreas (IPMN) is associated closely with main pancreatic duct (MPD) involvement. Because mixed-type IPMN is thought to have the same malignant potential as that of main-duct (MD)-IPMN, resection is recommended; however, the biological nature of mixed-type IPMN with only minimal involvement of MPD (min-mix-IPMN) may be different. METHODS A prospective database of 404 resected IPMNs was re-reviewed to subclassify mixed-type IPMNs. We defined min-mix-IPMN as absence of gross abnormalities (except for dilatation) of MPD and noncircumferential microscopic involvement of MPD limited to few sections. RESULTS We identified 46 min-mix-IPMNs, 163 IPMNs with extensive involvement of MPD (ex-mix-IPMN), 175 branch-duct (BD)-IPMNs, and 20 MD-IPMNs. The majority of min-mix-IPMNs were found incidentally and increased cyst size on surveillance was the leading operative indication. The median diameter of MPD was 2 mm in min-mix-IPMN versus 9 mm in ex-mix-IPMN (P < .0001), and cysts ≥10 mm were present in 62% of ex-mix-IPMNs versus 93% of min-mix-IPMNs (P < .0001). Most importantly, the vast majority of min-mix-IPMNs exhibited gastric-type epithelium, similar to BD-IPMNs, whereas intestinal-type epithelium was present in half of ex-mix-IPMNs, similar to MD-IPMNs. The prevalence of high-grade lesions was less in min-mix-IPMN than ex-mix-IPMN (P < .0001). These differences were reflected in better disease-specific outcomes of min-mix-IPMN compared with ex-mix-IPMN (P = .046). CONCLUSION Min-mix-IPMN often presents with no MPD dilation and is an incidental finding by microscopic examination. min-mix-IPMN shares the pathologic features and less aggressive biology with BD-IPMN. We propose that min-mix-IPMN be categorized differently than ex-mix-IPMN.
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MESH Headings
- Adenocarcinoma, Mucinous/classification
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adult
- Aged
- Aged, 80 and over
- Carcinoma, Pancreatic Ductal/classification
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Carcinoma, Papillary/classification
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/surgery
- Female
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Pancreatic Ducts/pathology
- Pancreatic Ducts/surgery
- Pancreatic Neoplasms/classification
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
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Affiliation(s)
- Klaus Sahora
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Carlos Fernández-del Castillo
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Fei Dong
- Department of Pathology, Massachusetts General Hospital, Boston, MA
| | - Giovanni Marchegiani
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Sarah P Thayer
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Dushyant V Sahani
- Department of Radiology, Massachusetts General Hospital, Boston, MA; Department of Radiology, Harvard Medical School, Boston, MA
| | - William R Brugge
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA; Department of Internal Medicine, Harvard Medical School, Boston, MA
| | - Andrew L Warshaw
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA; Department of Surgery, Harvard Medical School, Boston, MA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, MA; Department of Pathology, Harvard Medical School, Boston, MA.
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Rebours V, Le Faouder J, Laouirem S, Mebarki M, Albuquerque M, Camadro JM, Léger T, Ruszniewski P, Lévy P, Paradis V, Bedossa P, Couvelard A. In situ proteomic analysis by MALDI imaging identifies ubiquitin and thymosin-β4 as markers of malignant intraductal pancreatic mucinous neoplasms. Pancreatology 2013; 14:117-24. [PMID: 24650966 DOI: 10.1016/j.pan.2013.12.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2013] [Revised: 12/06/2013] [Accepted: 12/09/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE Intraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia. EXPERIMENTAL DESIGN Frozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25). RESULTS BD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2-42) (Omssa score = 1.37 E-9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011). CONCLUSION Ubiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection.
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Affiliation(s)
- Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France.
| | | | | | - Mounya Mebarki
- Inserm U773-CRB3, Paris-Diderot University, Paris, France
| | - Miguel Albuquerque
- Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France
| | - Jean-Michel Camadro
- Mass Spectrometry Facility, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France; Molecular and Cellular Pathology Program, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France
| | - Thibaut Léger
- Mass Spectrometry Facility, Jacques Monod Institute, UMR7592, Paris-Diderot University - CNRS, Paris, France
| | - Philippe Ruszniewski
- Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France; Inserm U773-CRB3, Paris-Diderot University, Paris, France
| | - Philippe Lévy
- Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France
| | - Valérie Paradis
- Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France
| | - Pierre Bedossa
- Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Beaujon Hospital, AP-HP, Clichy, Paris-Diderot University, France
| | - Anne Couvelard
- Inserm U773-CRB3, Paris-Diderot University, Paris, France; Pathology Department, Bichat Hospital, AP-HP, Paris-Diderot University, France
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Sai JK, Nobukawa B, Matsumura Y, Watanabe S. Pancreatic duct lavage cytology with the cell block method for discriminating benign and malignant branch-duct type intraductal papillary mucinous neoplasms. Gastrointest Endosc 2013; 77:726-35. [PMID: 23290718 DOI: 10.1016/j.gie.2012.11.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Accepted: 11/05/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Differentiation between benign and malignant branch-duct type intraductal papillary mucinous neoplasms (IPMNs) remains challenging. OBJECTIVE To examine the usefulness of pancreatic duct lavage cytology with cell block method for discriminating benign and malignant branch-duct type IPMNs. PATIENTS AND METHODS Between December 2007 and April 2011, patients with branch-duct type IPMNs having mural nodules on EUS were examined by pancreatic duct lavage cytology by using the cell block method. Cell block sections underwent hematoxylin and eosin staining and mucin immunostainings (MUCs 1, 2, 5AC, and 6). DESIGN Single-center, prospective study. SETTING Academic medical center. MAIN OUTCOME MEASUREMENTS The sensitivity and specificity of cytology were assessed. The agreement between cytological and histological results for MUC was also examined. RESULTS Cytology with this method was investigated in 44 patients. Cell block diagnosis was cancer positive (class V or IV) in 11 patients and negative (classes I, II, III, and noninformative) in 33. The sensitivity, specificity, and positive and negative predictive values of this method were 92%, 100%, 100%, and 97%, respectively. The cytological and histological results of MUCs 1, 2, 5AC, and 6 agreed in 88% (15/17), 94% (16/17), 88% (15/17), and 100% (17/17), respectively. LIMITATIONS Single center and small number of patients. CONCLUSIONS Pancreatic duct lavage cytology with the cell block method may be useful to differentiate between benign and malignant IPMNs preoperatively and as well as to determine their mucin type.
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Affiliation(s)
- Jin Kan Sai
- Department of Gastroenterology, Juntendo University, Tokyo, Japan.
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Glycemic control after total pancreatectomy for intraductal papillary mucinous neoplasm: an exploratory study. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2012; 2012:381328. [PMID: 22966212 PMCID: PMC3433133 DOI: 10.1155/2012/381328] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Accepted: 07/03/2012] [Indexed: 01/08/2023]
Abstract
Background. Glycemic control following total pancreatectomy (TP) has been thought to be difficult to manage. Diffuse intraductal papillary mucinous neoplasm (IPMN) is a potentially curable precursor to pancreatic adenocarcinoma, best treated by TP. Objective. Compare glycemic control in patients undergoing TP for IPMN to patients with type 1 diabetes mellitus (DM). Design/Setting. Retrospective cohort. Outcome Measure. Hemoglobin A1C(HbA1C) at 6, 12, 18, and 24 months after TP. In the control group, baseline was defined as 6 months prior to the first HbA1c measure. Results. Mean HgbA1C at each point of interest was similar between TP and type I DM patients (6 months (7.5% versus 7.7%, P = 0.52), 12 months (7.3% versus 8.0%, P = 0.081), 18 months (7.7% and 7.6%, P = 0.64), and at 24 months (7.3% versus 7.8%, P = 0.10)). Seven TP patients (50%) experienced a hypoglycemic event compared to 65 type 1 DM patients (65%, P = 0.38). Limitations. Small number of TP patients, retrospective design, lack of long-termfollowup. Conclusion. This suggests that glycemic control following TP for IPMNcan be well managed, similar to type 1 DM patients. Fear of DM following TP for IPMN should not preclude surgery when TP is indicated.
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Intraductal papillary mucinous neoplasms of the pancreas complicated with intraductal hemorrhage, perforation, and fistula formation: CT and MR imaging findings with pathologic correlation. ACTA ACUST UNITED AC 2012; 37:100-9. [PMID: 21394598 DOI: 10.1007/s00261-011-9723-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To correlate the CT and MR images with pathologic findings on intraductal papillary mucinous neoplasms (IPMNs) complicated with intraductal hemorrhage, perforation, and fistula. MATERIALS AND METHODS We retrospectively evaluated the CT (n = 5), MR imaging (n = 4), and pathological features of five IPMN patients complicated with intraductal hemorrhage (n = 5), perforation (n = 1), and fistula into the duodenum and jejunum (n = 1). RESULTS Intraductal hemorrhage could be detected as high attenuation on non-contrast CT in two of the five cases, and as high signal intensity on fat-suppressed T1-weighted MR images in all four of the cases. Perforation and fistula could be recognized on CT images. In all IPMNs, denuded epitheliums were observed pathologically. Dissolution of the duct wall and extension of mucinous materials were seen at the area of denuded epithelium. Perforations and fistula, without evidence of cancer invasion, were recognized in the dissolved duct wall. Pathogenesis of the perforations and fistula formations appeared to be related to excessive pressure in the dilated ducts and autodigestion of enzyme-rich fluids. CONCLUSION Complications with IPMN could be recognized on CT and fat-suppressed T1-weighted MR images. Intraductal hemorrhage might be predictive sign of perforation and fistula formation.
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Rebours V, Couvelard A, Peyroux JL, Sauvanet A, Hammel P, Ruszniewski P, Lévy P. Familial intraductal papillary mucinous neoplasms of the pancreas. Dig Liver Dis 2012; 44:442-6. [PMID: 21824831 DOI: 10.1016/j.dld.2011.07.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2011] [Revised: 06/24/2011] [Accepted: 07/02/2011] [Indexed: 12/11/2022]
Abstract
UNLABELLED The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described. METHODS Three families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for. RESULTS Symptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n=3) or fortuitous discovery (n=5). Number of cystic lesions was ≤3 (n=4) or >3 (n=4). Intraductal papillary mucinous neoplasms involved branch ducts (n=7) or both main pancreatic duct and branch duct (n=1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes). CONCLUSION A familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.
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Affiliation(s)
- Vinciane Rebours
- Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie - Pancréatologie, Hôpital Beaujon, APHP, Université Denis Diderot-Paris VII, 100, boulevard du général Leclerc, 92118 Clichy, France.
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Watanabe Y, Dohke M, Ishimori T, Amoh Y, Oda K, Okumura A, Mitsudo K, Dodo Y. High-Resolution MR Cholangiopancreatography. ACTA ACUST UNITED AC 2011. [DOI: 10.3109/10408379891244181] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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The differences in imaging features of malignant and benign branch duct type of Intraductal Papillary Mucinous Tumor. Eur J Radiol 2011; 80:744-8. [DOI: 10.1016/j.ejrad.2010.09.033] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2010] [Accepted: 09/27/2010] [Indexed: 11/20/2022]
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Abstract
Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.
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Werner JB, Bartosch-Härlid A, Andersson R. Cystic pancreatic lesions: current evidence for diagnosis and treatment. Scand J Gastroenterol 2011; 46:773-788. [PMID: 21288141 DOI: 10.3109/00365521.2011.551892] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Pancreatic cystic neoplasms are detected at an increasing frequency due to an increased use and quality of abdominal imaging. There are well known differential diagnostic difficulties concerning these lesions. The aim is to review current literature on the diagnostic options and the following treatment for cystic lesions in the pancreas focusing on serous cystadenomas, primary mucinous neoplasm of the pancreas and mucinous cystadenocarcinomas, as well as intraductal papillary mucinous neoplasms, starting with excluding pseudocysts. A conservative approach is feasible in patients with a clinical presentation suggestive of an asymptomatic serous cystadenoma. Surgical management, as well as follow-up, is discussed for each of the types of neoplastic lesions, including an uncharacterized cyst, based on patient data, symptoms, serum analysis, cyst fluid analysis and morphological features. Aspects for future diagnostics and management of these neoplasia are commented upon.
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Affiliation(s)
- Josefin Björk Werner
- Department of Surgery, Clinical Sciences Lund, Lund University and Skåne University Hospital Lund, Sweden
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Abstract
This article presents the clinicopathologic characteristics and differential features of pancreatic mucinous tumors. These tumors, which correspond to the most frequent cystic neoplasms, are encountered with increasing frequency. They comprise the mucinous cystic neoplasms and the intraductal papillary mucinous neoplasms. These tumors are known to progress from dysplasia to invasive carcinoma. Thus, it appears important to distinguish them from other cystic neoplasms and non-neoplastic cysts.
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Affiliation(s)
- Benoît Terris
- Pathology Department, Paris Descartes University, Cochin Hospital, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France.
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Fatima Z, Ichikawa T, Motosugi U, Muhi A, Sano K, Sou H, Haradome H, Kiryu S, Araki T. Magnetic resonance diffusion-weighted imaging in the characterization of pancreatic mucinous cystic lesions. Clin Radiol 2011; 66:108-11. [DOI: 10.1016/j.crad.2010.10.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Revised: 10/15/2010] [Accepted: 10/17/2010] [Indexed: 10/18/2022]
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Cyst growth rate predicts malignancy in patients with branch duct intraductal papillary mucinous neoplasms. Clin Gastroenterol Hepatol 2011; 9:87-93. [PMID: 20851216 DOI: 10.1016/j.cgh.2010.09.008] [Citation(s) in RCA: 155] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2010] [Revised: 08/12/2010] [Accepted: 09/04/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little information is available about the clinico-pathologic characteristics of pancreatic branch duct intraductal papillary mucinous neoplasm (Br-intraductal papillary mucinous neoplasm [IPMN]) because of difficulties in diagnosis based on radiologic and tissue information. We investigated the natural history of Br-IPMN using imaging and surgical pathology data from patients. METHODS Data were collected from patients admitted to a single tertiary referral institution from January 2000 to March 2009 (median follow up of 27.9 months); 201 patients were diagnosed with Br-IPMN with an initial cyst less than 30 mm without main pancreatic duct dilatation or mural nodules. The patients were followed for more than 3 months and examined by computed tomography (CT) at least twice. RESULTS The mean size of the patients' initial cysts was 14.7 mm; the mean cyst growth rate was 1.1 mm/year. Thirty-five patients received surgery during follow up and 8 were confirmed to have malignant cysts. The malignant cysts were greater in final size than nonmalignant cysts (24.3 mm vs 16.9 mm; P = .003); they also grew by a greater percentage (69.8% vs 19.4%; P = .046) and at a greater rate (4.1 mm vs 1.0 mm/year; P = .001). The actuarial 5-year risk of malignancy was 41.6% in the group that received surgery and 10.9% for all patients. Cysts that grew more than 2 mm/year had a higher risk of malignancy (5-year risk = 45.5% vs 1.8%; P < .001). CONCLUSIONS In combination with cyst size and the presence of mural nodules, cyst growth rate could be used to predict malignancy in patients with Br-IPMN.
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Acute pancreatitis in patients operated on for intraductal papillary mucinous neoplasms of the pancreas: frequency, severity, and clinicopathologic correlations. Pancreas 2010; 39:658-61. [PMID: 20173669 DOI: 10.1097/mpa.0b013e3181c81b74] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Acute pancreatitis (AP) may reveal intraductal papillary mucinous neoplasms of the pancreas (IPMN). The aims were to describe the characteristics of AP associated with IPMN and to compare patients with AP with those without AP. METHODS All patients who underwent surgery for IPMN between 1995 and 2006 were retrospectively studied. Clinical, imaging, and histological data were collected. The clinical and radiological severity of AP, the number of episodes, and recurrence after surgery were assessed. RESULTS One hundred eighty-five patients were included. Sixty-four (34.6%) had at least 1 AP (median, 2; range, 1-10). The median Balthazar score was 1 (0-6). Imaging analysis showed no difference between the 2 groups except for the presence of a mass. Branch duct IPMNs were more frequent in the AP group (74.4% vs 45.3%, P = 0.001), whereas combined IPMNs were more frequent in the non-AP group (45.3% vs 21.5%, P = 0.001). There was no difference in the grade of dysplasia between AP and non-AP groups: carcinoma, 45.3% versus 56.2%; benign IPMN, 54.7% versus 43.8% (P = NS), respectively. CONCLUSIONS Acute pancreatitis occurs in 34.6% of patients with IPMNs. Acute pancreatitis is not severe and often recurs. Histology showed no difference between the 2 groups.
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Pancreatic and extrapancreatic lesions in patients with intraductal papillary mucinous neoplasms of the pancreas: a single-centre experience. Radiol Med 2010; 115:442-52. [PMID: 20082228 DOI: 10.1007/s11547-010-0502-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2009] [Accepted: 07/19/2009] [Indexed: 02/08/2023]
Abstract
PURPOSE This study was performed to describe the possible presence of extrapancreatic neoplasms in patients with intraductal papillary mucinous neoplasm (IPMN) and to evaluate whether the extrapancreatic tumours were synchronous or metachronous to IPMNs. MATERIALS AND METHODS One hundred and forty-two patients (56 men and 86 women; mean age 69.5 years, range 37-98) with IPMN diagnosed using the Sendai criteria were enrolled. Six patients (4.2%) had type I, 103 (72.5%) type II and 33 (23.2%) type III IPMN. All patients were studied using the following imaging techniques: ultrasonography (US), multidetector computed tomography (MDCT) and magnetic resonance cholangiopancreatography (MRCP). RESULTS Pancreatic IPMN was localised in the head in 43 patients (30.3%), in the body in 13 (9.2%), in the tail in ten (7.0%), in the head-body in 17 (12.0%), in the body-tail in 15 (10.6%) diffuse throughout the gland in 44 (31.0%). The mean size of the cystic lesions was [(mean+/-standard deviation (SD)] 1.9+/-1.9 cm (range 0.5-8.0 cm). Twenty patients (14.1%) had associated pancreatic or extrapancreatic diseases. In evaluating the distribution of pancreatic or extrapancreatic diseases according to IPMN type, we found that this was not significantly different among types I, II and III (p=0.776). CONCLUSIONS The majority of pancreatic and extrapancreatic cancers occur before the diagnosis of IPMNs is made and is not related to the type of IPMN.
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Recurrence patterns of intraductal papillary mucinous neoplasms of the pancreas on enhanced computed tomography. J Comput Assist Tomogr 2010; 33:838-43. [PMID: 19940647 DOI: 10.1097/rct.0b013e3181a7e2a8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To characterize imaging features and findings in recurrent intraductal papillary mucinous neoplasms (IPMN); thereby reconciling the "field defect" theory with the appearance of recurrences distant from the resection margin. METHODS Computed tomography findings were reviewed in 89 patients who were resected with IPMN. At follow-up, the appearance of the pancreatic duct, features of recurrent masses, evidence of enhancement, calcifications, lymphadenopathy, and metastases were recorded. RESULTS Fourteen (16%) of the 89 patients had evidence of recurrence. Nine (64%) of the 14 patients demonstrated evidence for local recurrence. Ten recurrent lesions were noted in 9 patients. Patients with recurrence demonstrated an increase of pancreatic ductal dilatation of 3.3 mm, whereas patients without recurrence either had no dilatation or dilatation which then decreased over time. CONCLUSIONS Computed tomography findings suspicious for tumor recurrence include enlarging mass (either solid, cystic or both), progressive ductal dilatation, or extrapancreatic disease. There was a lack of correlation between margin status and location of recurrence within the pancreas consistent with the global field defect theory of IPMN.
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Diagnostic d’une petite tumeur intracanalaire papillaire et mucineuse du pancréas et surveillance. ACTA ACUST UNITED AC 2009; 33:F88-93. [DOI: 10.1016/j.gcb.2009.07.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Stamatakos M, Sargedi C, Angelousi A, Kontzoglou K, Safioleas P, Petropoulou C, Safioleas M. Management of the rare entity of primary pancreatic cystic neoplasms. J Gastroenterol Hepatol 2009; 24:1203-10. [PMID: 19467142 DOI: 10.1111/j.1440-1746.2009.05855.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Primary cystic neoplasms of the pancreas constitute a rare entity and are composed of a variety of neoplasms with a wide range of malignant potential. Approximately 90% of these lesions are serous cystic neoplasms or mucin-producing neoplasms. In contrast to serous cystadenomas which are nearly always benign, the mucinous cystic neoplasms represent a more diverse, heterogeneous spectrum of related neoplasms. Intraductal papillary mucinous neoplasms manifest a much greater latent or overt malignant potential than other cystic neoplasms of the pancreas. The various subgroups of cystic neoplasms of the pancreas are evaluated and compared through a review of current literature. No symptoms or signs are pathognomonic for the cystic pancreatic neoplasms. While identification of a cystic tumor is relatively easy, the identification of the specific tumor type may be difficult. Most investigators agree that accurate differentiation of benign from malignant neoplasms can be made only at histopathologic examination of the entire resected segment of the pancreas. Because of the low mortality and low postoperative morbidity, surgical resection is indicated in all patients with cystic tumors.
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Affiliation(s)
- Michael Stamatakos
- 4th Department of Surgery, Medical School, University of Athens, Attikon Hospital, Athens, Greece.
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Usefulness of multidetector computed tomography for detecting protruding lesions in intraductal papillary mucinous neoplasm of the pancreas in comparison with single-detector computed tomography and endoscopic ultrasonography. Pancreas 2009; 38:131-6. [PMID: 18981954 DOI: 10.1097/mpa.0b013e31818b0040] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVES To retrospectively evaluate the usefulness of multidetector computed tomography (MDCT) with multiplanar reformations (MPRs) and curved planar reformations (CPRs) for detecting protruding lesions in intraductal papillary mucinous neoplasms of the pancreas (IPMNs) as compared with single-detector CT (SDCT) and endoscopic ultrasonography (EUS). METHODS Eighty-six patients with IPMNs were imaged either with SDCT (n = 52) or MDCT with MPRs/CPRs and EUS (n = 34). The diagnostic accuracy of each imaging modality for identifying protruding lesions was compared with histological samples. RESULTS Among the patients in whom protruding lesions were histopathologically identified, the lesions were detected in 9 of the 33 patients subjected to SDCT (51.9% accuracy), in 17 of the 25 patients subjected to MDCT with MPRs and CPRs (76.5% accuracy), and in 21 of the 25 patients subjected to EUS (70.6% accuracy). Thus, significant difference was observed between MDCT and SDCT regarding accuracy (P < 0.05); however, no significant difference was seen between MDCT and EUS. Protruding lesions of less than 10 mm in height were better visualized with MDCT (53.3%) than with SDCT (13.0%; P < 0.05). CONCLUSIONS Multidetector computed tomography proved more useful than SDCT and equivalent to EUS in detecting protruding lesions in IPMNs.
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Maire F, Voitot H, Aubert A, Palazzo L, O'Toole D, Couvelard A, Levy P, Vidaud M, Sauvanet A, Ruszniewski P, Hammel P. Intraductal papillary mucinous neoplasms of the pancreas: performance of pancreatic fluid analysis for positive diagnosis and the prediction of malignancy. Am J Gastroenterol 2008; 103:2871-7. [PMID: 18775021 DOI: 10.1111/j.1572-0241.2008.02114.x] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The preoperative diagnosis of intraductal papillary mucinous neoplasms (IPMN) of the pancreas must be as reliable as possible because large or even total pancreatectomy may be necessary. Early diagnosis of malignant forms is important to improve prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been confirmed in cystic lesions of the pancreas. It is not known if these results can be applied to IPMN. AIMS To determine the levels of biochemical and tumor markers in fluid from EUS-FNA in patients with IPMN and to assess the impact on the diagnosis of IPMN. PATIENTS AND METHODS In total, 41 patients (14 men, median age 64 yr) underwent EUS-FNA before surgical resection of IPMN in our center. Levels of amylase, lipase, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19.9, and CA 72.4 were measured in the cyst fluid. The performance of the markers was retrospectively evaluated for: (a) a positive diagnosis of IPMN, using cutoffs validated in the literature for mucinous pancreatic lesions and (b) an assessment of malignancy (i.e., high-grade dysplasia or invasive carcinoma) compared with the final pathological examination of the surgical specimen. RESULTS EUS-FNA was performed in dilated branch ducts (BD) in 39 cases and in the main pancreatic duct in 2 cases. No serious complications occurred. The median fluid levels of amylase, lipase, CEA, CA 19.9, and CA 72.4 were 20,155 U/mL, 59,500 U/mL, 173 ng/mL, 6,400 U/mL, and 11.5 U/mL, respectively. A CEA level >200 ng/mL and a CA 72.4 >40 U/mL had a 44% and a 39% sensitivity, respectively, for the diagnosis of IPMN. The levels of CEA, CA 19.9, and CA 72.4 were significantly different between benign and malignant IPMN. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of a CEA level >200 ng/mL for the diagnosis of malignant IPMN were 90%, 71%, 50%, and 96%, respectively. The sensitivity, specificity, PPV, and NPV of a CA 72.4 level >40 U/mL for this purpose were 87.5%, 73%, 47%, and 96%, respectively. CONCLUSION CEA and CA 72.4 in pancreatic cyst fluid have excellent NPVs in the preoperative differential diagnosis of benign versus malignant IPMN, and might reinforce the decision of not to operate on patients with BD-type without predictive factors of malignancy.
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Affiliation(s)
- Frédérique Maire
- Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, AP-HP, Clichy, France
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Sahni VA, Mortele KJ. Magnetic resonance cholangiopancreatography: current use and future applications. Clin Gastroenterol Hepatol 2008; 6:967-77. [PMID: 18774532 DOI: 10.1016/j.cgh.2008.05.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2008] [Revised: 05/13/2008] [Accepted: 05/24/2008] [Indexed: 02/07/2023]
Abstract
Magnetic resonance pancreatography (MRCP) is now established as a robust noninvasive tool for the evaluation of biliary and pancreatic pathology. Its diagnostic performance is comparable with endoscopic retrograde cholangiopancreatography without the associated risks. This article aims to familiarize the reader with the technique, clinical indications, and limitations of the investigation. Common pitfalls in interpretation also are addressed. Emerging applications and techniques are discussed that include recent advances in technology and the development of functional imaging.
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Affiliation(s)
- Vikram A Sahni
- Department of Radiology, Division of Abdominal Imaging and Intervention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
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Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms. ACTA ACUST UNITED AC 2008; 15:169-77. [PMID: 18392710 DOI: 10.1007/s00534-007-1223-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2006] [Accepted: 03/23/2007] [Indexed: 01/12/2023]
Abstract
BACKGROUND/PURPOSE Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs. METHODS Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct's largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations. RESULTS Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2-8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2-5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323). CONCLUSIONS The incidence of K-ras mutation may be associated with the hypersecretion of mucin.
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Kim SC, Park KT, Lee YJ, Lee SS, Seo DW, Lee SK, Kim MH, Jang SJ, Byun JH, Han DJ. Intraductal papillary mucinous neoplasm of the pancreas: clinical characteristics and treatment outcomes of 118 consecutive patients from a single center. ACTA ACUST UNITED AC 2008; 15:183-8. [PMID: 18392712 DOI: 10.1007/s00534-007-1231-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2007] [Accepted: 06/01/2007] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE Appropriate surgical treatment strategies based on clinicopathological findings are unavailable for intraductal papillary mucinous neoplasm (IPMN) of the pancreas. We investigated the clinical features of pancreatic IPMN in a single-center database in order to design an optimal surgical strategy. METHODS The medical records of 118 consecutive patients who had undergone surgical resection between August 1994 and December 2004, in whom IPMN was histologically confirmed, were reviewed retrospectively for radiological and pathological findings. RESULTS Most of the invasive carcinomas in these patients were detected as the main-duct type (88.5%). The type of tumor (main-duct type vs branched-duct type), the tumor size, and the dilated duct size were significant predictive factors associated with malignancy. The relative risk of malignancy was greatest at 13-mm or more ductal dilation in the main-duct type (Odds ratio, 4.1), at 35-mm or more tumor size (Odds ratio, 7.6), and for main-duct type (Odds ratio, 3.9). Major pancreatic resections such as total pancreatectomy and pancreatoduodenectomy were performed in 14.5% and 69% of the patients, respectively. There was a 19.5% rate of incomplete resection, with these patients having a positive resection margin. However, significant recurrence did not occur in patients with a benign IPMN lesion which remained at the resection margin. The overall postoperative survival rate at 5 years was 98.2% for benign IPMN and 65.3% for malignant IPMN. CONCLUSIONS Function-preserving strategies, based on the clinical status of the patient, are necessary in order to avoid possible severe metabolic complications following extended pancreatectomy in patients with benign IPMN because of the low recurrence rate and good prognosis of this entity, irrespective of margin status.
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Affiliation(s)
- Song C Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea
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Abstract
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are now a well-recognized category of slowly growing tumors with a remarkably better prognosis, even when malignant, than pancreatic ductal adenocarcinoma. Their clinical and pathohistologic features have been increasingly attracting the attention of clinicians since their first description 25 years ago. Despite its burgeoning volume recently, accumulated literature devoted to IPMN still provides a low level of evidence with regard to diagnosis, treatment, and prognosis. Therefore, we performed a Medline-based systematic review of the literature aimed at clearly defining the clinicopathologic characteristics of pancreatic IPMN and determining the best currently available evidence-based principles of diagnosis and management of patients with this disease.
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Differential Diagnosis of Benign or Malignant Intraductal Papillary Mucinous Neoplasm of the Pancreas by Multidetector Row Helical Computed Tomography. J Comput Assist Tomogr 2008; 32:191-7. [DOI: 10.1097/rct.0b013e3180676d97] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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CT vs MRCP: optimal classification of IPMN type and extent. J Gastrointest Surg 2008; 12:101-9. [PMID: 17917784 DOI: 10.1007/s11605-007-0367-9] [Citation(s) in RCA: 158] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Accepted: 09/19/2007] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are being diagnosed with increased frequency. CT scanning commonly serves as the primary imaging modality before surgery. We hypothesized MRCP provides better characterization of IPMN type/extent, which more closely matches actual pathology. METHODS Of 214 patients treated with IPMN (1991-2006), 30 had both preoperative CT and MRCP. Of these, 18 met imaging study criteria. Independent readers performed retrospective, blinded analyses using standardized criteria for IPMN type and extent. RESULTS A ductal connection was detected on 73% of MRCP scans and only 18% of CT. IPMN type was classified differently in seven (39%); four (22%) of which were read on CT as having main duct involvement where this was not appreciated on MRCP or found on surgical pathology. MRCP showed multifocal disease in 13(72%) versus only 9(50%) on CT. A different disease distribution was seen in 9(50%). Finally, 101 branch lesions were identified on MRCP compared to 46 on CT. CONCLUSIONS CT falls short of MRCP in detecting a ductal connection, estimating main duct involvement, and identification of small branch duct cysts. These factors influence diagnostic accuracy, cancer risk stratification and operative strategy. MRCP should be employed for optimal management of patients with IPMN.
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A clinical algorithm for the assessment of pancreatic lesions: utilization of 16- and 64-section multidetector CT and endoscopic ultrasound. Clin Radiol 2007; 62:1142-53. [DOI: 10.1016/j.crad.2007.05.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2006] [Revised: 05/01/2007] [Accepted: 05/22/2007] [Indexed: 02/06/2023]
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NAKAZAWA S, YAMAO K. Mucin‐Producing Tumor of the Pancreas —The Proposal of the New Clinical Entity and Its Revision—. Dig Endosc 2007. [DOI: 10.1111/j.1443-1661.1991.tb00511.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Affiliation(s)
- Saburo NAKAZAWA
- Department of Internal Medicine, Second Hospital, Fujita Health University, Aichi, Japan
| | - Kenji YAMAO
- Department of Internal Medicine, Second Hospital, Fujita Health University, Aichi, Japan
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Abstract
OBJECTIVES Hedgehog (Hh) signaling is an important mediator of tumorigenesis of pancreatic ductal adenocarcinoma (PA). It is intriguing to explore whether Hh signaling is also involved in pancreatic cystic neoplasms, which are phenotypically different from PA. METHODS Patients with solid and pseudopapillary tumor (SPT; n = 12), mucinous cystic neoplasm (MCN; n = 18), intraductal papillary mucinous neoplasm (IPMN; n = 18), and PA (n = 20) were studied. Expression of Hh signaling molecules including sonic Hh (sHh), smoothened (Smo), patched 1 (Ptc1), and Gli were determined using immunohistochemistry and/or Western blotting. Cell cycle-regulator genes, including cyclin A, B, C, and D1 messenger RNA, were determined using ribonuclease protection assay. RESULTS Six of 12 SPT, 8 of 18 MCN, 17 of 18 IPMN, and 20 of 20 PA displayed Hh signaling using immunohistochemistry. Sonic Hh was predominantly expressed in stromal cells neighboring to the neoplastic cells of SPT and IPMN; in contrast, sHh was expressed in both stromal cells and neoplastic epithelial cells of MCN and PA. The quantitative expression of sHh signaling detected by Western blotting showed that expression of Ptc1 and Gli, but not Smo, corresponded to the magnitude of sonic hedgehog ligand. The expression of cyclin D1 messenger RNA was highest in PA, followed by MCN, IPMN, and SPT, which matches with Ptc1 and Gli. CONCLUSIONS Hedgehog signaling pathway might play a role during tumorigenesis of SPT, MCN, IPMN, and PA. Mucinous cystic neoplasm and PA exhibit an autocrine regulation of sHh, whereas SPT and IPMN do not. Overexpression of Ptc1 and Gli, reflected by cyclin D1, might represent proliferative potential of various pancreatic neoplasms.
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Affiliation(s)
- Maw-Sen Liu
- Departments of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan
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Gourgiotis S, Ridolfini MP, Germanos S. Intraductal papillary mucinous neoplasms of the pancreas. Eur J Surg Oncol 2007; 33:678-84. [PMID: 17207960 DOI: 10.1016/j.ejso.2006.11.031] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2006] [Accepted: 11/28/2006] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND/AIMS Intraductal papillary mucinous neoplasms (IPMNs) are neoplasms of the pancreatic duct epithelium characterized by intraductal papillary growth and thick mucin secretion. Quantities of mucin fill the main and/or branches of pancreatic ducts and cause ductal dilatation. This review encompasses IPMNs, including symptoms, diagnosis, management, and prognosis. METHODS A Pubmed database search was performed. All abstracts were reviewed and all articles in which cases of IPMNs could be identified were further scrutinized. Further references were extracted by cross-referencing. RESULTS Only one-third of all patients are symptomatic. According to the site of involvement, IPMNs are classified into three types: main duct type, branch duct type, and combined type. Most branch type IPMNs are benign, while the other two types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch type IPMN and marked dilatation of the main duct indicate the existence of adenoma at least. Synchronous or metachronous malignancies may be developed in various organs. Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, while magnetic resonance pancreatography best visualizes the entire outline of IPMNs. CONCLUSIONS Prognosis is excellent after complete resection of benign and non-invasive malignant IPMNs. The extent of pancreatic resection and the intraoperative management of resection margins remain controversial. Total pancreatectomy should be reserved for patients with resectable but extensive IPMNs involving the whole pancreas; its benefits, however, must be balanced against operative and postoperative risks. Regular monitoring for disease recurrence is important after surgery.
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Affiliation(s)
- S Gourgiotis
- Hepatobiliary and Pancreatic Surgery Department, Royal London Hospital, Whitechapel, London E1 1BB, UK.
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Ohuchida K, Mizumoto K, Fujita H, Yamaguchi H, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M. Sonic hedgehog is an early developmental marker of intraductal papillary mucinous neoplasms: clinical implications of mRNA levels in pancreatic juice. J Pathol 2006; 210:42-8. [PMID: 16794990 DOI: 10.1002/path.2019] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are common cystic tumours of the pancreas. Sonic hedgehog (SHH) is involved in gastric epithelial differentiation and pancreatic carcinogenesis. However, a comprehensive analysis of SHH expression in IPMN has not yet been performed. In the present study, one-step quantitative real-time reverse transcription-polymerase chain reaction with gene-specific priming was used to examine mRNA levels in various types of clinical samples. SHH expression in IPMN was measured and the possible association of gastric epithelial differentiation with development of IPMN was evaluated. In bulk tissue analyses (IPMNs, 11 pancreatic cancer, and 20 normal pancreatic tissues), IPMN expressed significantly higher levels of SHH than did normal pancreas (IPMN versus normal pancreas, p = 0.0025; pancreatic cancer versus normal pancreas, p = 0.0132), but SHH expression did not differ between IPMN and pancreatic cancer (p = 0.3409). In microdissection analyses (infiltrating ductal carcinoma cells from 20 sections, IPMN cells from 20 sections, pancreatitis-affected epithelial cells from 11 sections, and normal epithelial cells from 12 sections), IPMN cells expressed significantly higher levels of SHH than did cancer cells, normal cells, or pancreatitis-affected ductal cells (all comparisons, p < 0.008). Pancreatic juice analyses (20 samples from pancreatic cancers, 31 samples from IPMNs, and 27 samples from chronic pancreatitis) revealed that SHH expression differed significantly between IPMN juice and pancreatitis juice (p < 0.0001), and between cancer juice and pancreatitis juice (p = 0.0125). Receiver operating characteristic curve analyses revealed that SHH measurement in pancreatic juice was useful for discriminating IPMN from chronic pancreatitis (area under the curve = 0.915; 95% confidence interval: 0.796-0.976). The data suggest that overexpression of SHH is an early event in the development of IPMN and that SHH measurement in pancreatic juice may provide some advantages for the treatment or follow-up of a subset of patients with IPMN or chronic pancreatitis.
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Affiliation(s)
- K Ohuchida
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan
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Nishikawa N, Kimura Y, Okita K, Zembutsu H, Furuhata T, Katsuramaki T, Kimura S, Asanuma H, Hirata K. Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features. ACTA ACUST UNITED AC 2006; 13:327-35. [PMID: 16858545 DOI: 10.1007/s00534-005-1073-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2005] [Accepted: 11/08/2005] [Indexed: 01/20/2023]
Abstract
BACKGROUND/PURPOSE The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs. METHODS Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded. RESULTS Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05). CONCLUSIONS Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.
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Affiliation(s)
- Noriko Nishikawa
- First Department of Surgery, Sapporo Medical University School of Medicine, S-1, W-16, Sapporo, Hokkaido 060-8543, Japan
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Kawamoto S, Lawler LP, Horton KM, Eng J, Hruban RH, Fishman EK. MDCT of intraductal papillary mucinous neoplasm of the pancreas: evaluation of features predictive of invasive carcinoma. AJR Am J Roentgenol 2006; 186:687-95. [PMID: 16498096 DOI: 10.2214/ajr.04.1820] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE The purpose of our study was to evaluate factors predictive of the presence of invasive carcinoma associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas on MDCT. MATERIALS AND METHODS Preoperative MDCT of 36 consecutive patients (23 men, 13 women; mean age, 66.6 years) who had undergone surgical resection and had a pathologic diagnosis of IPMN were retrospectively assessed. CT was performed with a 4-MDCT scanner with 120 mL of IV contrast material at an injection rate of 3 mL/sec. Arterial and venous phase images were acquired at 25 and 50-60 sec from the start of IV contrast administration. Type of ductal involvement, location, tumor size in branch duct type and combined type lesions, caliber of the main pancreatic duct, caliber of the common bile duct or common hepatic duct, and solid appearance of the lesion were assessed on CT and correlated with pathologic findings for invasive carcinoma. RESULTS Pathologic analysis revealed carcinoma in situ in seven patients (19%) and invasive carcinoma in 15 patients (42%) arising from the IPMN. With invasive carcinoma, the size of the tumor in branch duct type and combined type, and the caliber of the main pancreatic duct were significantly larger compared with the lesions without invasive carcinoma (4.7 +/- 1.7 cm vs 2.6 +/- 1.4 cm [p = 0.0007] and 9.3 +/- 5.5 mm vs 4.6 +/- 4.1 mm [p = 0.006], respectively). A solid mass (p < 0.001), dilatation of the common bile duct or common hepatic duct (> or = 15 mm), and the presence of a stent (p = 0.0004) were correlated with the presence of associated invasive carcinoma. CONCLUSION MDCT helped to predict invasive carcinoma associated with IPMN.
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Affiliation(s)
- Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, 600 N Wolfe St., Baltimore, MD 21287, USA.
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Abstract
Reports of intraductal papillary mucinous tumors of the pancreas have become substantially more frequent in the literature in the past several years. This increased prevalence is due, among other things, to improved screening techniques, especially high-resolution spatial imaging. These tumors are characterized by proliferation of the intraductal epithelium, mucin production, and ductal dilatation. They grow slowly. Their potential for malignancy is high (although the precise risk remains difficult to assess), but their prognosis, when identified during the first stage of neoplastic transformation (before invasion), is far better than that of 'pancreatic ductal adenocarcinoma. Early diagnosis allows patients to be treated before carcinomatous degeneration. Specific diagnosis makes it possible to define an appropriate treatment strategy - either surgery or monitoring, especially when only the intralobular ducts are affected. In that case, the risk of malignant degeneration is much lower than with lesions in the pancreatic duct or in combined forms.
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MESH Headings
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Cholangiopancreatography, Endoscopic Retrograde
- Cystadenocarcinoma, Mucinous/diagnosis
- Cystadenocarcinoma, Mucinous/pathology
- Cystadenocarcinoma, Mucinous/surgery
- Cystadenoma, Mucinous/diagnosis
- Cystadenoma, Mucinous/pathology
- Cystadenoma, Mucinous/surgery
- Diagnosis, Differential
- Humans
- Magnetic Resonance Imaging
- Palliative Care
- Pancreas/pathology
- Pancreatectomy
- Pancreatic Ducts/pathology
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Prognosis
- Tomography, X-Ray Computed
- Ultrasonography
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Affiliation(s)
- Olivier Jean-Yves Monneuse
- Service de Chirurgie Digestive et d'Urgence, Pavillon G Viscéral, Hospices civils de Lyon, Hôpital Edouard Herriot
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Ftériche FS, Chebbi F, Bedioui H, Kchir N, Ammous A, Ksantini R, Jouini M, Kacem M, Ben Safta Z. Tumeur intracanalaire papillaire mucineuse du pancréas dégénérée et fistulisée dans l'estomac, le duodénum, et le côlon. ACTA ACUST UNITED AC 2006; 131:118-20. [PMID: 16182226 DOI: 10.1016/j.anchir.2005.08.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2005] [Accepted: 08/08/2005] [Indexed: 11/25/2022]
Abstract
We report a case of intraductal papillary mucinous tumor of the pancreas (IPMT) degenerated and fistulized into the stomach, the duodenum and the colon. Diagnoses of malignancy and fistulization were proven preoperatively. Pancreaticoduodenectomy extended to the body was performed. Pathological examination revealed a malignant IPMT with an invasive component. Of the 3 fistulizations tracts, both gastric and duodenal ones were malignant. To our knowledge, this is the first reported case of IPMT with colonic fistulization. Twelve months later, the patient is alive without signs of recurrence.
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Affiliation(s)
- F S Ftériche
- AHU, Service de Chirurgie A, Hôpital La-Rabta, 1004 Jabbari, Tunis, Tunisie
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