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Smith SR, Sarmiento JM. Cost-effectiveness of Operative Intervention for Mucinous Cystic Neoplasm: The Role of Postoperative Diabetes. Pancreas 2025; 54:e23-e29. [PMID: 39259844 DOI: 10.1097/mpa.0000000000002389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
OBJECTIVES Small mucinous cystic neoplasms (MCNs) of the pancreas are managed with operative resection in otherwise healthy patients; however, postoperative diabetes development is not considered in recommendations for resection. MATERIALS AND METHODS Via probabilistic microsimulation Markov modeling, we assessed clinical and economic implications of laparoscopic distal pancreatectomy (LDP) versus surveillance for non-diabetes mellitus (DM) patients with suspected MCN of 2 cm without high-risk or worrisome features. Primary outcomes included quality-adjusted life years (QALYs), medical costs (2021 USD), and incremental cost-effectiveness ratios. We conducted sensitivity analyses to evaluate the robustness of our model to changes in input parameters. All analyses were repeated for a population with pre-DM. RESULTS Surveillance resulted in 6.52 QALYs and $61,200, while LDP accumulated 6.12 QALYs and $63,700. Almost 20% of the LDP cohort developed DM over the first 10 years, compared with 11% of the surveillance cohort. In a pre-DM cohort, LDP remained dominated in the base case, with over 40% developing DM postoperatively. In sensitivity analyses, surveillance remained the preferred strategy in most iterations for both cohorts. CONCLUSIONS Surveillance for small suspected MCNs without high-risk features is the preferred strategy from a clinical and economic standpoint. Consensus guidelines should consider the long-term implications of postoperative diabetes development after LDP.
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Biswas S, Afrose S, Mita MA, Hasan MR, Shimu MSS, Zaman S, Saleh MA. Next-Generation Sequencing: An Advanced Diagnostic Tool for Detection of Pancreatic Disease/Disorder. JGH Open 2024; 8:e70061. [PMID: 39605899 PMCID: PMC11599877 DOI: 10.1002/jgh3.70061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 11/05/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
The pancreas is involved in digestion and glucose regulation in the human body. Given the recognized link between chronic pancreatitis and pancreatic cancer, addressing pancreatic disorders and pancreatic cancer is particularly challenging. This review aims to highlight the limitations of traditional methods in diagnosing pancreatic disorders and cancer and explore several next-generation sequencing (NGS) approaches as a promising alternative. There are distinct clinical symptoms that are shared by a number of clinical phenotypes of pancreatic illness induced by particular genetic mutations. Traditional diagnostic methods encompass computed tomography, magnetic resonance imaging, contrast-enhanced Doppler ultrasound, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, transabdominal ultrasound, laparoscopy, and positron emission tomography have a prognostic ability of only 5% or less and a 5-year survival rate. Genetic sequencing can be employed as an alternative to conventional diagnostic techniques. Sanger sequencing and NGS are currently largely operated genome analysis, with no exception for pancreatic disease diagnosis. The NGS methods can sequence millions to billions of short DNA fragments, enabling enormous sample screening in a short amount of time with low-abundance detection, like in 0.1%-1% mutation prevalence declining approximate cost. Whole-genome sequencing, whole-exome sequencing, RNA sequencing, and single-cell NGS are a few NGS methods utilized to diagnose pancreatic disease. For both research and clinical applications, the NGS techniques can provide a precise diagnosis of pancreatic disorders in a short amount of time at a reasonable expenditure.
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Affiliation(s)
- Suvro Biswas
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
| | - Shamima Afrose
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | - Mohasana Akter Mita
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | - Md. Robiul Hasan
- Department of Genetic Engineering and BiotechnologyUniversity of RajshahiRajshahiBangladesh
| | | | - Shahriar Zaman
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
| | - Md. Abu Saleh
- Miocrobiology Laboratory, Department of Genetic Engineering and BiotechnologyUniversity of RajshahiBangladesh
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de Jesus VHF, Donadio MDS, de Brito ÂBC, Gentilli AC. A narrative review on rare types of pancreatic cancer: should they be treated as pancreatic ductal adenocarcinomas? Ther Adv Med Oncol 2024; 16:17588359241265213. [PMID: 39072242 PMCID: PMC11282540 DOI: 10.1177/17588359241265213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 06/13/2024] [Indexed: 07/30/2024] Open
Abstract
Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.
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Affiliation(s)
- Victor Hugo Fonseca de Jesus
- Oncoclínicas, Department of Gastrointestinal Medical Oncology, Santos Dumont St. 182, 4 floor, Florianópolis, Santa Catarina 88015-020, Brazil
- Department of Medical Oncology, Centro de Pesquisas Oncológicas, Florianópolis, Santa Catarina, Brazil
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Dahiya DS, Shah YR, Ali H, Chandan S, Gangwani MK, Canakis A, Ramai D, Hayat U, Pinnam BSM, Iqbal A, Malik S, Singh S, Jaber F, Alsakarneh S, Mohamed I, Ali MA, Al-Haddad M, Inamdar S. Basic Principles and Role of Endoscopic Ultrasound in Diagnosis and Differentiation of Pancreatic Cancer from Other Pancreatic Lesions: A Comprehensive Review of Endoscopic Ultrasound for Pancreatic Cancer. J Clin Med 2024; 13:2599. [PMID: 38731128 PMCID: PMC11084399 DOI: 10.3390/jcm13092599] [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: 03/21/2024] [Revised: 04/17/2024] [Accepted: 04/21/2024] [Indexed: 05/13/2024] Open
Abstract
Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Pancreatic lesions consist of both neoplastic and non-neoplastic lesions and often pose a diagnostic and therapeutic challenge due to similar clinical and radiological features. In recent years, pancreatic lesions have been discovered more frequently as incidental findings due to the increased utilization and widespread availability of abdominal cross-sectional imaging. Therefore, it becomes imperative to establish an early and appropriate diagnosis with meticulous differentiation in an attempt to balance unnecessary treatment of benign pancreatic lesions and missing the opportunity for early intervention in malignant lesions. Endoscopic ultrasound (EUS) has become an important diagnostic modality for the identification and risk stratification of pancreatic lesions due to its ability to provide detailed imaging and acquisition of tissue samples for analysis with the help of fine-needle aspiration/biopsy. The recent development of EUS-based technology, including contrast-enhanced endoscopic ultrasound, real-time elastography-endoscopic ultrasound, miniature probe ultrasound, confocal laser endomicroscopy, and the application of artificial intelligence has significantly augmented the diagnostic accuracy of EUS as it enables better evaluation of the number, location, dimension, wall thickness, and contents of these lesions. This article provides a comprehensive overview of the role of the different types of EUS available for the diagnosis and differentiation of pancreatic cancer from other pancreatic lesions while discussing their key strengths and important limitations.
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Affiliation(s)
- Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology and Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA
| | - Yash R. Shah
- Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, USA
| | - Hassam Ali
- Division of Gastroenterology, Hepatology & Nutrition, East Carolina University/Brody School of Medicine, Greenville, NC 27858, USA
| | - Saurabh Chandan
- Division of Gastroenterology and Hepatology, Creighton University School of Medicine, Omaha, NE 68178, USA
| | - Manesh Kumar Gangwani
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, The University of Utah School of Medicine, Salt Lake City, UT 84132, USA
| | - Umar Hayat
- Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes Barre, PA 18711, USA
| | - Bhanu Siva Mohan Pinnam
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, IL 60612, USA
| | - Amna Iqbal
- Department of Internal Medicine, University of Toledo Medical Center, Toledo, OH 43614, USA
| | - Sheza Malik
- Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, USA
| | - Sahib Singh
- Department of Internal Medicine, Sinai Hospital, Baltimore, MD 21215, USA
| | - Fouad Jaber
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA
| | - Saqr Alsakarneh
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA
| | - Islam Mohamed
- Division of Hepatology, University of Missouri School of Medicine, Columbia, MO 64108, USA
| | - Meer Akbar Ali
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, University of Jordan, 11942 Amman, Jordan
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
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Elahabadi I, Rahnama A, Bazmandegan G, Kamiab Z. Mucinous non neoplastic cyst of the pancreas: a case report. J Surg Case Rep 2023; 2023:rjad633. [PMID: 38026749 PMCID: PMC10663063 DOI: 10.1093/jscr/rjad633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 10/31/2023] [Indexed: 12/01/2023] Open
Abstract
The aim of this study was to introduce a patient with mucinous nonneoplastic cyst (MNNC) at an unusual age. MNNCs of the pancreas are uncommon primary tumors, which affect middle-aged women in their fifth decade of life and have significant malignant potential. Therefore, it is important to accurately diagnose and remove them. This case is a 28-year-old woman patient who presented with a pain in the right and upper abdomen from 3 months ago and worsened at night. A cystic lesion was observed near the upper bridge of the left kidney in abdominal ultrasonography. Contrast-enhanced abdominal computed tomography (CT) scan showed a cystic lesion in the trunk and umbilical cord of the pancreas. The patient underwent surgery and the mass was removed and the MNNC was diagnosed.
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Affiliation(s)
- Ismail Elahabadi
- Department of Surgery, Ali Ibn Abi Talib Hospital, School of Medicine, Rafsanjan University of Medical Sciences, Imam Ali Boulevard, Rafsanjan 7717933777, Iran
| | - Amir Rahnama
- Department of Pathology, School of Medicine, Rafsanjan University of Medical Sciences, Imam Ali Boulevard, Rafsanjan 7717933777, Iran
| | - Gholamreza Bazmandegan
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Imam Ali Boulevard, Rafsanjan 7717933777, Iran
- Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Imam Ali Boulevard, Rafsanjan 7717933777, Iran
| | - Zahra Kamiab
- Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Imam Ali Boulevard, Rafsanjan 7717933777, Iran
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Kawasaki K, Yoshitomi H, Furukawa K, Takayashiki T, Kuboki S, Takano S, Kagawa S, Ohtsuka M. Lymph node involvement is rare in mucinous cystic neoplasms of the pancreas: Role of minimally invasive surgery. Mol Clin Oncol 2023; 19:92. [PMID: 37854330 PMCID: PMC10580257 DOI: 10.3892/mco.2023.2688] [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: 05/31/2023] [Accepted: 08/21/2023] [Indexed: 10/20/2023] Open
Abstract
Mucinous cystic neoplasm (MCN) is a premalignant cystic tumor of the pancreas. Resection of MCN in the distal pancreas is a standard treatment; however, at present, there is no consensus on the necessity or extent of lymph node dissection, and minimally invasive pancreatectomy is commonly the preferred surgical technique. Thus, the present study aimed to assess the efficacy of minimally invasive surgery and the extent of lymph node metastasis as factors in determining an appropriate surgical treatment for MCN. The present study retrospectively analyzed 21 consecutive patients who underwent distal pancreatectomy (DP) for MCN under general anesthesia at Chiba University Hospital (Chiba, Japan) between April 2011 and July 2019. All 21 patients were female. DP with a splenectomy was performed in all the patients. A total of 14 patients underwent laparoscopic DP (LDP). No lymph node metastasis was found in any of the patients. The minimally invasive surgery group had lower operative blood loss and a shorter hospital stay than the open surgery group. There was no significant difference in the number of dissected lymph nodes between the open surgery group and the minimally invasive surgery group. Preoperative findings of malignancy in MCN included solid components on enhanced CT and endoscopic ultrasonography, high carbohydrate antigen 19-9 values and large tumor size. In conclusion, DP with spleen preservation, which is minimally invasive, may be preferentially considered as a surgical technique for MCN without malignant findings because lymph node metastases are rare in MCN and were not observed in the present study.
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Affiliation(s)
- Keishi Kawasaki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
- Department of Surgery, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama 343-8555, Japan
| | - Hideyuki Yoshitomi
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
- Department of Surgery, Dokkyo Medical University Saitama Medical Center, Koshigaya, Saitama 343-8555, Japan
| | - Katsunori Furukawa
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
| | - Tsukasa Takayashiki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
| | - Satoshi Kuboki
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
| | - Shigetsugu Takano
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
| | - Shingo Kagawa
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Chiba 260-0856, Japan
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7
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Søreide K. Burgeoning rise in intraductal papillary mucinous neoplasia (IPMN) - a blessing in disguise. Scand J Gastroenterol 2023; 58:1101-1104. [PMID: 37022179 DOI: 10.1080/00365521.2023.2197095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/21/2023] [Accepted: 03/23/2023] [Indexed: 04/07/2023]
Affiliation(s)
- Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
- Gastrointestinal Translational Research Group, Laboratory for Molecular Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- SAFER Surgery, Surgical Research Group, Stavanger University Hospital, Stavanger, Norway
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8
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Xia Q, Li F, Min R, Sun S, Han YX, Feng ZZ, Li N. Malignancy risk factors and prognostic variables of pancreatic mucinous cystic neoplasms in Chinese patients. World J Gastroenterol 2023; 29:3119-3132. [PMID: 37346158 PMCID: PMC10280801 DOI: 10.3748/wjg.v29.i20.3119] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 04/21/2023] [Accepted: 05/04/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Pancreatic mucinous cystic neoplasms (MCNs) represent one of the precursor lesions of pancreatic ductal adenocarcinoma, and their detection has been facilitated by advances in preoperative imaging. Due primarily to the rarity of MCNs, however, there is limited knowledge regarding the prognostic variables and high-risk factors for malignant transformation. A more comprehensive and nuanced approach is necessary to fill this gap and provide a basis for improved treatment decisions and patient outcomes.
AIM To investigate the high-risk factors associated with malignant MCNs and to explore the prognostic factors of MCN with associated invasive carcinoma (MCN-AIC).
METHODS All cases of resected MCNs from a single high-volume institution between January 2012 and January 2022 were retrospectively reviewed. Only cases with ovarian-type stroma verified by progesterone receptor staining were included. Preoperative features, histological findings and postoperative course were documented. Multivariate logistic regression was employed to investigate variables related to malignancy. Survival analysis was performed using the Kaplan-Meier curve, and the prognostic factors were assessed to evaluate the postoperative course of patients with MCN-AIC.
RESULTS Among the 48 patients, 36 had benign MCNs, and 12 had malignant MCNs (1 high-grade atypical hyperplasia and 11 MCN-AIC). Age, tumour size, presence of solid components or mural nodules and pancreatic duct dilatation were identified as independent risk factors associated with malignancy. The follow-up period ranged from 12 mo to 120 mo, with a median overall survival of 58.2 mo. Only three patients with MCN-AIC died, and the 5-year survival rate was 70.1%. All 11 cases of MCN-AIC were stage I, and extracapsular invasion was identified as a prognostic factor for poorer outcomes.
CONCLUSION The risk factors independently associated with malignant transformation of MCNs included age, tumour size, presence of solid components or mural nodules, and pancreatic duct dilatation. Our study also revealed that encapsulated invasion was a favourable prognostic factor in MCN-AIC patients.
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MESH Headings
- Humans
- Carcinoma, Pancreatic Ductal/epidemiology
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- East Asian People
- Neoplasms, Cystic, Mucinous, and Serous/epidemiology
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/surgery
- Pancreatic Neoplasms/epidemiology
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Prognosis
- Receptors, Progesterone
- Retrospective Studies
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Affiliation(s)
- Qing Xia
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu 233004, Anhui Province, China
| | - Fan Li
- Department of Pathology, Bengbu Medical College, Bengbu 233030, Anhui Province, China
| | - Rui Min
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu 233004, Anhui Province, China
| | - Shuai Sun
- Department of Pathology, Bengbu Medical College, Bengbu 233030, Anhui Province, China
| | - Yue-Xin Han
- School of Clinical Medicine, Bengbu Medical College, Bengbu 233030, Anhui Province, China
| | - Zhen-Zhong Feng
- Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Nan Li
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu 233004, Anhui Province, China
- Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Vieira RMF, Souza Junior ASD, Kerche LE. CYSTIC PANCREATIC LESIONS: IMAGING VERSUS ANATOMOPATHOLOGICAL FINDINGS-HOW TO IMPROVE DIAGNOSTIC ACCURACY? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1735. [PMID: 37255104 DOI: 10.1590/0102-672020230017e1735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 01/15/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Pancreatic cystic lesions are a group of pancreatic neoplasms with different behavior and risk of malignancy. Imaging diagnosis and differentiation of these lesions remain a challenge. AIMS The aim of this study was to evaluate the agreement between computed tomography and/or magnetic resonance imaging and post-operative pathologic diagnoses of Pancreatic cystic lesions in a University Hospital of São Paulo State. METHODS A total of 39 patients with surgically diagnosed Pancreatic cystic lesions were enrolled, as a study cohort from 2009 to 2019. Preoperative radiological and final pathological diagnosis was correlated to measure computed tomography and/or magnetic resonance imaging diagnostic. Pancreatic adenocarcinoma, choledochal pancreatic cyst, mucinous cystadenoma, serous cystadenoma, intraductal papillary mucinous neoplasms, and pancreatic pseudocyst were classified as neoplastic cysts. RESULTS It was noted that 27 patients (69.23%) had preoperative computed tomography and magnetic resonance imaging, 11 patients (28.20%) had preoperative computed tomography only, and 1 patient had preoperative magnetic resonance imaging only. The values for diagnoses made only with computed tomography (p=0.47) and from the combination of computed tomography+magnetic resonance imaging (p=0.50) did also point to moderate agreement with the anatomopathological findings. The values pointed to a fair agreement for the diagnosis of mucinous cystadenoma (p=0.3), moderate agreement for intraductal papillary mucinous neoplasms (p= 0.41), good agreement for serous cystadenoma (p=0.79), and excellent agreement for choledochal pancreatic cyst (p=1), pancreatic pseudocyst (p=0.84), and Frantz tumor (p=1) (p<0.05). CONCLUSIONS The findings of computed tomography and/or magnetic resonance imaging have an equivalent diagnostic agreement with an anatomopathological diagnosis for differentiating benign from malignant Pancreatic cystic lesions and in suggesting a specific diagnosis. There is no statistical difference between the use of computed tomography alone and computed tomography+magnetic resonance imaging in the improvement of diagnostic accuracy.
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Affiliation(s)
- Rafael Mello Fontolan Vieira
- Cancer Regional Hospital, Hepatobiliopancreatic Oncological Digestive Surgery - Presidente Prudente (SP), Brazil
| | | | - Leandra Ernst Kerche
- Faculty of Medicine of Oeste Paulista, Functional Sciences Department - Presidente Prudente (SP), Brazil
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Chen W, Ahmed N, Krishna SG. Pancreatic Cystic Lesions: A Focused Review on Cyst Clinicopathological Features and Advanced Diagnostics. Diagnostics (Basel) 2022; 13:65. [PMID: 36611356 PMCID: PMC9818257 DOI: 10.3390/diagnostics13010065] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/13/2022] [Accepted: 12/19/2022] [Indexed: 12/28/2022] Open
Abstract
Macroscopic, endomicroscopic, and histologic findings and correlation are an integral part of the diagnostic evaluation of pancreatic cystic lesions (PCLs), as complementing morphologic features seen by different specialties are combined to contribute to a final diagnosis. However, malignancy risk stratification of PCLs with worrisome features can still be challenging even after endoscopic ultrasound guided-fine needle aspiration (EUS-FNA) with cytological evaluation. This review aims to summarize cyst clinicopathological features from the pathologists' perspective, coupled with knowledge from advanced diagnostics-confocal laser endomicroscopy and cyst fluid molecular analysis, to demonstrate the state-of-art risk stratification of PCLs. This review includes illustrative photos of surgical specimens, endomicroscopic and histologic images, and a summary of cyst fluid molecular markers.
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Affiliation(s)
- Wei Chen
- Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Nehaal Ahmed
- School of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Somashekar G. Krishna
- Division of Gastroenterology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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11
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Wang R, Su D, Liu Y, Qiu J, Cao Z, Yang G, Luo W, Tao J, Zhang T. Cancer-specific survival and metastasis in pancreatic mucinous cystadenocarcinoma: A SEER-based cohort study. Front Oncol 2022; 12:985184. [PMCID: PMC9631930 DOI: 10.3389/fonc.2022.985184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 10/03/2022] [Indexed: 11/13/2022] Open
Abstract
Aims This study aimed to investigate the prognostic value of clinical features for cancer-specific survival (CSS) and metastasis in patients with pancreatic mucinous cystadenocarcinoma (MCAC). We further constructed and validated an effective nomogram to predict CSS. Methods We screened patients diagnosed with pancreatic MCAC from Surveillance Epidemiology and End Results (SEER) database. Kaplan-Meier curves were used to determine the CSS time. Univariate and multivariate Cox and logistic regression analyses were conducted to identify the prognostic factors for CSS and metastasis. The nomogram was constructed to predict the prognosis of pancreatic MCAC based on the results from the multivariate analysis. We used the concordance index (C-index), the area under the curve (AUC), and the calibration plots to determine the predictive accuracy and discriminability of the nomogram. Results Multivariate Cox analysis revealed that age, primary site, grade, and radiotherapy were independent prognostic factors associated with CSS. Multivariate logistic regression analysis revealed that surgery and grade were independent risk factors associated with metastasis. The independent risk factors were included to construct a prognosis prediction model for predicting CSS in patients with pancreatic MCAC. The concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots of the training cohort and the validation cohort showed that the nomogram had an acceptable predictive performance. Conclusion We established a nomogram that could determine the 3- and 5-year CSS, which could evaluate individual clinical outcomes and provide individualized clinical decisions.
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Affiliation(s)
- Ruobing Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dan Su
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yueze Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiangdong Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhe Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gang Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenhao Luo
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jinxin Tao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Taiping Zhang,
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12
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Bell PD, Singhi AD. Integrating Molecular Analysis into the Pathologic Evaluation of Pancreatic Cysts. Surg Pathol Clin 2022; 15:455-468. [PMID: 36049828 DOI: 10.1016/j.path.2022.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
The development of cross-sectional imaging techniques has enhanced the detection of pancreatic cystic lesions (PCLs). PCLs are found in approximately 2% of the general population, often as incidentally detected lesions on computed tomography or MRI during the evaluation of other medical conditions. Broadly, PCLs are classified as mucinous or nonmucinous. Mucinous PCLs include mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Nonmucinous PCLs include pseudocysts, serous cystadenomas, solid pseudopapillary neoplasms, and cystic pancreatic neuroendocrine tumors, as well as cystic acinar cell carcinoma, cystic degeneration of pancreatic ductal adenocarcinoma, lymphoepithelial cyst, and others.
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Affiliation(s)
- Phoenix D Bell
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA.
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA
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13
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Tezuka S, Ueno M, Kobayashi S, Fukushima T, Nasu R, Washimi K, Yamamoto N, Morinaga S, Morimoto M, Maeda S. A case of pancreatic mucinous cystadenocarcinoma with malignant ascites without recurrence for more than 8 years after surgery. Clin J Gastroenterol 2022; 15:834-839. [PMID: 35546381 PMCID: PMC9334409 DOI: 10.1007/s12328-022-01639-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/25/2022] [Indexed: 11/04/2022]
Abstract
Mucinous cystadenocarcinoma (MCAC) with malignant ascites is rare. We report a case of a 28-year-old woman who presented with epigastric pain. The ascites in the Douglas fossa was identified at a nearby gynecology clinic. Computed tomography showed a multiloculated cystic lesion (9.5 × 6.4 cm) in the tail of the pancreas, which was diagnosed as mucinous cystic neoplasm on imaging. Staging laparoscopy was performed, and rapid cytology of ascites revealed adenocarcinoma, leading to a diagnosis of unresectable MCAC. Subsequently, combination chemotherapy with gemcitabine plus S-1 was initiated. Although there were no remarkable changes in the imaging findings, the peritoneal dissemination node was not consistently recognized in any of the imaging findings, and distal pancreatectomy was performed. A peritoneal dissemination node was not observed in the laparotomy findings, but the peritoneal lavage cytology was positive. The postoperative pathological result was non-invasive MCAC, and the ascites was suspected to be caused by cyst rupture. The patient has been recurrence-free, including the reappearance of ascites, for > 8 years after adjuvant therapy with S-1. Although careful follow-up will be required in the future, the very good prognosis in this case suggests that MCAC with malignant ascites without obvious peritoneal dissemination should be considered for surgical resection.
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Affiliation(s)
- Shun Tezuka
- Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama City, 241-8515, Japan.
| | - Makoto Ueno
- Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama City, 241-8515, Japan
| | - Satoshi Kobayashi
- Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama City, 241-8515, Japan
| | - Taito Fukushima
- Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama City, 241-8515, Japan
| | - Ryuji Nasu
- Department of Clinical Laboratory, Kanagawa Cancer Center, Yokohama, Japan
| | - Kota Washimi
- Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan
| | - Naoto Yamamoto
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Soichiro Morinaga
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Manabu Morimoto
- Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama City, 241-8515, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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14
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Okasha HH, Abdellatef A, Elkholy S, Mogawer MS, Yosry A, Elserafy M, Medhat E, Khalaf H, Fouad M, Elbaz T, Ramadan A, Behiry ME, Y William K, Habib G, Kaddah M, Abdel-Hamid H, Abou-Elmagd A, Galal A, Abbas WA, Altonbary AY, El-Ansary M, Abdou AE, Haggag H, Abdellah TA, Elfeki MA, Faheem HA, Khattab HM, El-Ansary M, Beshir S, El-Nady M. Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions. World J Gastrointest Endosc 2022; 14:402-415. [PMID: 35978716 PMCID: PMC9265252 DOI: 10.4253/wjge.v14.i6.402] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/28/2021] [Accepted: 05/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions.
AIM To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-β), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions.
METHODS This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs.
RESULTS The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions.
CONCLUSION EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.
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Affiliation(s)
- Hussein Hassan Okasha
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Abeer Abdellatef
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Shaimaa Elkholy
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Mohamad-Sherif Mogawer
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Ayman Yosry
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Magdy Elserafy
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Eman Medhat
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Hanaa Khalaf
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Magdy Fouad
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Tamer Elbaz
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Ahmed Ramadan
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Mervat E Behiry
- Department of Internal Medicine, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
| | - Kerolis Y William
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Ghada Habib
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Mona Kaddah
- Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
| | - Haitham Abdel-Hamid
- Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
| | - Amr Abou-Elmagd
- Department of Gastroenterology, Armed forces College of Medicine, Cairo 11451, Egypt
| | - Ahmed Galal
- Endoscopy and Internal Medicine Consultant at Dr/Ahmed Galal Endoscopy Center, Alexandria 35516, Egypt
| | - Wael A Abbas
- Department of Internal Medicine, Faculty of Medicine, Assuit University, Assuit 71111, Egypt
| | | | - Mahmoud El-Ansary
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo 11451, Egypt
| | - Aml E Abdou
- Department of Microbiology and Immunology, Faculty of Medicine for girls Al-Azhar University, Cairo 11451, Egypt
| | - Hani Haggag
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
| | - Tarek Ali Abdellah
- Department of Internal Medicine, Faculty of Medicine, Ain shams University, Cairo 11451, Egypt
| | - Mohamed A Elfeki
- Department of Internal Medicine, Bani-suef University, Bani-suef, Bani-suef 62511, Egypt
| | - Heba Ahmed Faheem
- Department of Internal Medicine, Faculty of Medicine, Ain shams University, Cairo 11451, Egypt
| | - Hani M Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
| | - Mervat El-Ansary
- Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
| | - Safia Beshir
- Department of Environmental Medicine & Clinical Pathology, National Research Centre, Cairo 11451, Egypt
| | - Mohamed El-Nady
- Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
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15
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Facility Type Affects Treatment Outcomes for Patients With Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas. Pancreas 2021; 50:1422-1426. [PMID: 35041342 DOI: 10.1097/mpa.0000000000001948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Academic centers report better outcomes for pancreatic ductal adenocarcinoma. We hypothesized that treatment outcomes for mucinous cysts differ according to institution type. METHODS Using the National Cancer Data Base, we analyzed data on patients with mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). RESULTS Of 3278 identified patients, 2622 (80%) had IPMNs and 656 (20%) had MCNs. While most academic/research programs (ARCPs, 84.9%) treated more than 10 patients/year, this was true for only 59% of integrated network cancer programs, 37.3% of comprehensive community cancer programs, and 0% of community cancer programs (P < 0.001). Surgery was used more often in ARCPs and for smaller tumors. The ARCPs had higher rates of margin negative resections with retrieval of 15 or more nodes with the lowest 30- and 90-day mortality rates. The median overall survival was better in ARCPs (110.3 months) than comprehensive community cancer programs (75.1 mo), community cancer programs (75.1 mo), or integrated network cancer programs (100.8 mo, P < 0.001). CONCLUSIONS Treatment of MCNs and IPMNs of the pancreas at academic centers is associated with a higher probability of pancreatectomy, disease identification in a noninvasive stage, and better overall survival. Centralization of care for mucinous pancreatic cysts will lead to improved outcomes.
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16
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Cai J, Chen H, Lu M, Zhang Y, Lu B, You L, Zhang T, Dai M, Zhao Y. Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett 2021; 520:1-11. [PMID: 34216688 DOI: 10.1016/j.canlet.2021.06.027] [Citation(s) in RCA: 193] [Impact Index Per Article: 48.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 06/09/2021] [Accepted: 06/25/2021] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer.
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Affiliation(s)
- Jie Cai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Hongda Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Ming Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Yuhan Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Bin Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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17
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Marchegiani G, Andrianello S, Crippa S, Pollini T, Belfiori G, Gozzini L, Cassalia F, Caravati A, Luchini C, Doglioni C, Bassi C, Falconi M, Salvia R. Actual malignancy risk of either operated or non-operated presumed mucinous cystic neoplasms of the pancreas under surveillance. Br J Surg 2021; 108:1097-1104. [PMID: 34059873 DOI: 10.1093/bjs/znab131] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 03/25/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Despite the low malignant potential of pancreatic mucinous cystic neoplasms (MCNs), surgery is still performed. The aim of this pragmatic study was to assess the outcome of surgery and surveillance for patients presenting with a presumed MCN at the first evaluation. METHODS Data for patients with a presumed MCN observed from 2000 to 2016 at the Verona Pancreas Institute and San Raffaele Hospital were extracted from prospective databases. The endpoints were risk of malignancy at pathology and rate of misdiagnosis for the surgical series, expressed as an odds ratio (OR) with 95 per cent confidence interval, and disease-specific survival (DSS) for the surveillance cohort investigated by the Kaplan-Meier method. RESULTS A total of 424 patients were identified. In the surgical series (229 patients), the rate of misdiagnosis was 19.2 per cent. The rate of malignant MCNs was 10.9 per cent (25 patients). The overall rate of malignancy, including misdiagnoses, was 11.3 per cent (26 patients). Predictors of malignancy were mural nodules (OR 27.75, 95 per cent c.i. 4.44-173.61; P < 0.001), size at least 50 mm (OR 13.39, 2.01 to 89.47; P = 0.007), and carbohydrate antigen 19.9 level (OR 3.98, 1.19 to 13.30; P = 0.025). In the absence of mural nodules and enhancing walls, none of the resected presumed MCNs smaller than 50 mm were malignant. Only patients with high-risk stigmata undergoing surgery experienced a significantly reduced 5-year DSS compared with all other patients (88 versus 100 per cent; P = 0.031). CONCLUSION Presumed MCNs with mural nodules, enhancing walls or cysts of 50 mm or larger should be considered for upfront surgical resection owing to the high risk of malignancy. In the absence of these features, the incidence of malignancy is negligible, favouring surveillance in selected patients given the low risk of malignancy and the high rate of misdiagnosis. GRAPHICAL ABSTRACT Pancreatic mucinous cystic neoplasms (MCNs) are well known preneoplastic lesions. Despite the low rate of cancer, lesions without radiological features of malignancy are resected systematically. In the absence of mural nodules, enhancing walls or cyst size 50 mm or more, the incidence of malignancy is negligible. Given the high risk of misdiagnosis, in the absence of such radiological features, surveillance of presumed MCNs seems safer.
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Affiliation(s)
- G Marchegiani
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - S Andrianello
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - S Crippa
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - T Pollini
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - G Belfiori
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - L Gozzini
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - F Cassalia
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - A Caravati
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - C Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University of Verona Hospital Trust, Verona, Italy
| | - C Doglioni
- Department of Pathology, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - C Bassi
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - R Salvia
- General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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18
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Shyu S, Singhi AD. Cystic biliary tumors of the liver: diagnostic criteria and common pitfalls. Hum Pathol 2020; 112:70-83. [PMID: 33383041 DOI: 10.1016/j.humpath.2020.12.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 02/08/2023]
Abstract
With major advancements and frequent use of abdominal imaging techniques, hepatic cysts are increasingly encountered in clinical practice. Although the majority of cysts are benign, a small subset represents neoplastic precursors to cholangiocarcinoma. These cystic precursors include intraductal papillary neoplasms of the bile duct (IPNB) and mucinous cystic neoplasms of the liver (MCN-L), and bear striking pathologic resemblance to corresponding cystic neoplastic precursors within the pancreas. This review examines the salient clinical, gross, microscopic and molecular features of IPNBs and MCN-Ls, and, in particular, provides histopathologic comparison to their pancreatic counterparts. Considering these neoplasms may be diagnostically challenging, we also discuss other hepatic lesions within the differential diagnosis, and the potential for molecular methods to improve their preoperative evaluation and the early detection of cholangiocarcinoma.
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Affiliation(s)
- Susan Shyu
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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19
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Höhn P, Soydemir MA, Luu AM, Janot-Matuschek M, Tannapfel A, Uhl W, Belyaev O. It's not all about the size-characteristics and risk factors for malignancy of mucinous cystic neoplasms of the pancreas. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1572. [PMID: 33437771 PMCID: PMC7791201 DOI: 10.21037/atm-20-4774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background Mucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN. Methods All resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ2 and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni- and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test. Results A total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5-18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd's ratio 33.600; 7.000-161.270); P<0.001 and odd's ratio 19.250; 3.370-109.970; P<0.001). Other factors associated with malignancy were preoperative weight loss (P=0.015) and higher age (P=0.048). Tumor size, abdominal or back pain or jaundice showed no significant correlation to malignancy in our cohort. Conclusions Malignant potential of MCN should not be underestimated and a close clinical and radiological follow-up is mandatory in all suspected cases. This is especially important for small lesions. Risk assessment should not rely only on tumor size but consider all clinical, radiological and laboratory findings of each case. Follow-up should be performed by experienced surgeons and radiologists in high volume centers for pancreatic surgery. Surgery should be performed in all cases in which malignancy is suspected.
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Affiliation(s)
- Philipp Höhn
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | | | - Andreas Minh Luu
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Monika Janot-Matuschek
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | | | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Orlin Belyaev
- Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
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20
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Yadav RK, Jiang X, Chen J. Differentiating benign from malignant pancreatic cysts on computed tomography. Eur J Radiol Open 2020; 7:100278. [PMID: 33163586 PMCID: PMC7607418 DOI: 10.1016/j.ejro.2020.100278] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/11/2020] [Accepted: 09/23/2020] [Indexed: 12/19/2022] Open
Abstract
CT can distinguish between benign and premalignant or malignant pancreatic cysts. Solid component and septation were the only CT features that could differentiate benign from malignant cysts. Cyst wall enhancements on CT were more commonly observed in premalignant or malignant cysts than in benign cysts. CT is a necessary diagnostic modality to preoperatively detect and characterize pancreatic lesions. Purpose It is important to identify features on computed tomography (CT) that can distinguish between benign and premalignant or malignant pancreatic cysts to avoid unnecessary surgeries. This study investigated the preoperative diagnostic evaluation of cystic pancreatic lesions to determine how advanced imaging and clinical factors should guide management. Methods In total, 53 patients with 27 benign and 26 premalignant or malignant cysts were enrolled. CT features of the cysts were compared using univariate and multivariate analyses. Results On univariate analysis, a solid component (p < 0.01), septation (p < 0.01), location (p < 0.01), border (p < 0.01), wall enhancement (p = 0.01), lesion margins (p < 0.01), pancreatic atrophy (p = 0.04), and a cystic wall (p < 0.01) were all significantly different between benign and premalignant or malignant cysts. On multivariate analysis, only a solid component (p < 0.01) and septation (p < 0.01) were significant. Conclusion A thin cystic wall, uniform homogeneity, a clear border, the presence of septation, pancreatic atrophy, and the absence of both wall enhancements and solid components were more frequently seen in benign cysts. A thick wall, lack of homogeneity, the presence of wall enhancements and solid components, absence of septation, only a small degree of pancreatic atrophy, and unclear borders were more frequent among premalignant or malignant cysts. The only CT features to differentiate benign from premalignant or malignant cysts were a solid component and septation.
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Key Words
- CEA, Carcinoembryonic antigen
- CPR, Curved planar reformation
- CTA, CT angiography
- DWI, Diffusion-weighted imaging
- ERCP, Endoscopic retrograde cholangiopancreatography
- FDG PET, Fluorodeoxyglucose PET
- FNA, Fine-needle aspiration
- HASTE, Half-Fourier acquisition single-shot turbo spin-echo
- IPMN, Intraductal papillary mucinous neoplasia
- MCA, Mucinous cystadenoma
- MCB, Mucinous cystic borderline tumor
- MCC, Mucinous cystadenocarcinoma
- MCN, Mucinous cystic neoplasm
- MPD, Main pancreatic duct
- MPR, Multi-planar reformation
- MRA, MR angiography
- MRCP, MR cholangiopancreatography
- MRI, Magnetic resonance imaging
- MSCT, Multi-slice helical computed tomography
- PACS, Picture archiving and communicating system
- PCN, Cystic neoplasms of the pancreas
- PDAC, Pancreatic ductal adenocarcinoma
- PET, Positron emission computed tomography
- Pancreatic cystic lesions
- Pancreatic ductal adenocarcinoma
- Pancreatic neoplasm
- ROI, Region of interest
- SCA, Serous cystadenoma
- SMA, Serous microcystic adenoma
- US, Ultrasonography
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Affiliation(s)
- Rajesh Kumar Yadav
- Second Affiliated Hospital, Department of Radiology, Sun Yat-sen University, Guangzhou 510000, China
- Corresponding author: Current Address: Novus Health Wellness, 4808 Munson St NW, OH 44718 USA.
| | - Xinhua Jiang
- Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Jianyu Chen
- Second Affiliated Hospital, Department of Radiology, Sun Yat-sen University, Guangzhou 510000, China
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21
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Guo C, Peng X, Song L, Ying M, Wu Y, Chang R, Li J, Feng D, Zhan L, Zhan X. Autophagy promotes malignant migration and invasion via miR-224-5p/BCL2 in pancreatic mucinous cystadenocarcinoma MCC1 cells. Oncol Lett 2020; 20:276. [PMID: 33029204 PMCID: PMC7530886 DOI: 10.3892/ol.2020.12139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 10/10/2019] [Indexed: 12/19/2022] Open
Abstract
The prognosis of invasive pancreatic mucinous cystadenocarcinoma (MCC) is poor, and the molecular mechanism underlying its development remains unclear. The present study aimed to explore the potential role of autophagy in pancreatic MCC. The results demonstrated an increase in autophagy signaling in pancreatic MCC tissues and the MCC1 cell line compared with adjacent tissues and normal human pancreatic ductal epithelium (HPDE) cells. In addition, abnormal autophagy activation facilitated the migration and invasion of MCC1 cells. MicroRNA (miR)-224-5p expression levels were significantly higher in MCC1 cells compared with those in HPDE cells. Treatment with rapamycin further demonstrated that high levels of autophagy elevated miR-224-5p expression in MCC1 cells in a time-dependent manner. BCL2 was identified as a downstream target gene of miR-224-5p, which binds to the 3′-untranslated region of BCL2. In addition, the results of the present study demonstrated that BCL2 knockdown reversed the inhibition of autophagy mediated by the miR-224-5p inhibitor. To the best of our knowledge, this is the first study to evaluate the role of autophagy in pancreatic MCC. Thus, these results suggested that autophagy may be hyperactivated in pancreatic MCC. In addition, the present study identified a positive feedback loop between autophagy signaling and miR-224-5p, which may promote the aggressive migration and invasion of MCC1. These results may provide a new insight into the relationship between autophagy and tumor metastasis in pancreatic MCC.
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Affiliation(s)
- Chengtao Guo
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
| | - Xiaobo Peng
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
| | - Lele Song
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
| | - Mingzhen Ying
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
| | - Yanjun Wu
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
| | - Renxu Chang
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
| | - Jie Li
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
| | - Dan Feng
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
| | - Lixing Zhan
- Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
| | - Xianbao Zhan
- Department of Oncology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, P.R. China
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22
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Lanke G, Lee JH. Similarities and differences in guidelines for the management of pancreatic cysts. World J Gastroenterol 2020; 26:1128-1141. [PMID: 32231418 PMCID: PMC7093312 DOI: 10.3748/wjg.v26.i11.1128] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 02/21/2020] [Accepted: 02/29/2020] [Indexed: 02/06/2023] Open
Abstract
Accurate diagnosis of Pancreatic cysts (PC) is key in the management. The knowledge of indications for surgery, the role of endoscopic ultrasound-guided fine needle aspiration, cyst fluid analysis, imaging, and surveillance of PC are all important in the diagnosis and management of PC. Currently, there are many guidelines for the management of PC. The optimal use of these guidelines with a patient-centered approach helps diagnose early cancer and prevent the spread of cancer.
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Affiliation(s)
- Gandhi Lanke
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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23
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Din NU, Zubair M, Abdul-Ghafar J, Ahmad Z. Pancreatic mucinous cystic neoplasms: a clinicopathological study of 11 cases and detailed review of literature. SURGICAL AND EXPERIMENTAL PATHOLOGY 2020. [DOI: 10.1186/s42047-020-0059-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Mucinous cystic neoplasms (MCNs) of pancreas are relatively rare, occur almost exclusively in middle-aged females, and are overwhelmingly located in the body and tail of the pancreas, histologically show an ovarian type stroma. MCNs are premalignant, low aggressive tumors. Here we describe the clinicopathologic and radiologic features and follow up of cases diagnosed in our practice. We also present a detailed review of recent literature.
Materials and methods
Based on strict criteria, 11 cases diagnosed between 2002 and 2016 were included in the study.
Results
All cases were reviewed histologically. Mean and median age was 46.7 and 46 years respectively. All patients were females and 9 out of 11 cases were located in the body and/or tail of the pancreas. Mean tumor size was 8 cm. Grossly, cysts were uni or multilocular and ranged from a few millimeters to several centimeters in diameter. Microscopically, all cases showed characteristic tall columnar, mucin producing epithelium and ovarian type stroma. Atypia was mild in 8 cases and severe in 3 cases. The latter 3 cases were classified as non-invasive MCNs with high grade dysplasia (2 cases) and MCN with an associated invasive carcinoma (1 case). On immunohistochemistry, all cases showed epithelial positivity for cytokeratin AE1/AE3 and stromal positivity for vimentin and smooth muscle actin. Follow up was available in 7 cases. All patients were alive and well with no recurrence.
Conclusions
Our cases show features similar to those described in other published studies although cases in our series tended to be larger in number. Since these tumors are relatively rare, premalignant and have strict diagnostic criteria, they must always be considered in the differential diagnosis of pancreatic mucinous cystic lesions. Larger studies incorporating greater number of patients and more detailed follow up will help in increasing our understanding of MCNs.
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van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 2019; 16:676-689. [PMID: 31527862 DOI: 10.1038/s41575-019-0195-x] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/31/2019] [Indexed: 12/11/2022]
Abstract
Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed.
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Affiliation(s)
- Nadine C M van Huijgevoort
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
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Carmicheal J, Patel A, Dalal V, Atri P, Dhaliwal AS, Wittel UA, Malafa MP, Talmon G, Swanson BJ, Singh S, Jain M, Kaur S, Batra SK. Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s). Biochim Biophys Acta Rev Cancer 2019; 1873:188318. [PMID: 31676330 DOI: 10.1016/j.bbcan.2019.188318] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/25/2019] [Accepted: 10/25/2019] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an increased likelihood of future pancreatic cancer in patients placing them in a high-risk category. Discerning concurrent malignancy and risk of future PCL progression to cancer must be carefully and accurately determined to improve survival outcomes and avoid unnecessary morbidity of pancreatic resection. Unfortunately, current image-based guidelines are inadequate to distinguish benign from malignant lesions. There continues to be a need for accurate molecular and imaging biomarker(s) capable of identifying malignant PCLs and predicting the malignant potential of PCLs to enable risk stratification and effective intervention management. This review provides an update on the current status of biomarkers from pancreatic cystic fluid, pancreatic juice, and seromic molecular analyses and discusses the potential of radiomics for differentiating PCLs harboring cancer from those that do not.
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Affiliation(s)
- Joseph Carmicheal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Asish Patel
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Vipin Dalal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Pranita Atri
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Amaninder S Dhaliwal
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Uwe A Wittel
- Department of General- and Visceral Surgery, University of Freiburg Medical Center, Faculty of Medicine, Freiburg, Germany
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Geoffrey Talmon
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Benjamin J Swanson
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shailender Singh
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
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26
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Dalal V, Carmicheal J, Dhaliwal A, Jain M, Kaur S, Batra SK. Radiomics in stratification of pancreatic cystic lesions: Machine learning in action. Cancer Lett 2019; 469:228-237. [PMID: 31629933 DOI: 10.1016/j.canlet.2019.10.023] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/03/2019] [Accepted: 10/15/2019] [Indexed: 12/15/2022]
Abstract
Pancreatic cystic lesions (PCLs) are well-known precursors of pancreatic cancer. Their diagnosis can be challenging as their behavior varies from benign to malignant disease. Precise and timely management of malignant pancreatic cysts might prevent transformation to pancreatic cancer. However, the current consensus guidelines, which rely on standard imaging features to predict cyst malignancy potential, are conflicting and unclear. This has led to an increased interest in radiomics, a high-throughput extraction of comprehensible data from standard of care images. Radiomics can be used as a diagnostic and prognostic tool in personalized medicine. It utilizes quantitative image analysis to extract features in conjunction with machine learning and artificial intelligence (AI) methods like support vector machines, random forest, and convolutional neural network for feature selection and classification. Selected features can then serve as imaging biomarkers to predict high-risk PCLs. Radiomics studies conducted heretofore on PCLs have shown promising results. This cost-effective approach would help us to differentiate benign PCLs from malignant ones and potentially guide clinical decision-making leading to better utilization of healthcare resources. In this review, we discuss the process of radiomics, its myriad applications such as diagnosis, prognosis, and prediction of therapy response. We also discuss the outcomes of studies involving radiomic analysis of PCLs and pancreatic cancer, and challenges associated with this novel field along with possible solutions. Although these studies highlight the potential benefit of radiomics in the prevention and optimal treatment of pancreatic cancer, further studies are warranted before incorporating radiomics into the clinical decision support system.
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Affiliation(s)
- Vipin Dalal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Joseph Carmicheal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Amaninder Dhaliwal
- Department of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA; The Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA; The Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
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Srivastava S, Koay EJ, Borowsky AD, De Marzo AM, Ghosh S, Wagner PD, Kramer BS. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nat Rev Cancer 2019; 19:349-358. [PMID: 31024081 PMCID: PMC8819710 DOI: 10.1038/s41568-019-0142-8] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods of progression and death. Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours. In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms). More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers. In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.
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Affiliation(s)
- Sudhir Srivastava
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alexander D Borowsky
- Department of Pathology and Laboratory Medicine, University of California Davis Health, Sacramento, CA, USA
| | - Angelo M De Marzo
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
| | - Sharmistha Ghosh
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Paul D Wagner
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Barnett S Kramer
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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Keane MG, Shamali A, Nilsson LN, Antila A, Millastre Bocos J, Marijinissen Van Zanten M, Verdejo Gil C, Maisonneuve P, Vaalavuo Y, Hoskins T, Robinson S, Ceyhan GO, Abu Hilal M, Pereira SP, Laukkarinen J, Del Chiaro M. Risk of malignancy in resected pancreatic mucinous cystic neoplasms. Br J Surg 2018; 105:439-446. [PMID: 29488646 DOI: 10.1002/bjs.10787] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/12/2017] [Accepted: 11/16/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND Pancreatic mucinous cystic neoplasms (MCNs) are rare mucin-producing cystic tumours defined by the presence of ovarian-type stroma. MCNs have a malignant potential and thus surgery is frequently performed. The aim of this cohort study was to define better the criteria for surgical resection in patients with MCN. METHODS This multicentre retrospective study included all resected MCNs between 2003 and 2015 in participating centres. Lesions without ovarian-type stroma were excluded. Patient characteristics, preoperative findings, histopathology findings and follow-up data were recorded. RESULTS The study included 211 patients; their median age was 53 (range 18-82) years, and 202 (95·7 per cent) were women. Median preoperative tumour size was 55 (range 12-230) mm. Thirty-four of the 211 (16·1 per cent) were malignant, and high-grade dysplasia (HGD) was found in a further 13 (6·2 per cent). One-third of MCNs in men were associated with invasive cancer, compared with 15·3 per cent in women. Five cases of malignant transformation occurred in MCNs smaller than 4 cm. All cases of malignancy or HGD were associated with symptoms or features of concern on preoperative cross-sectional imaging. In multivariable analysis, raised carbohydrate antigen 19-9 (odds ratio (OR) 10·54, 95 per cent c.i. 2·85 to 218·23; P < 0·001), tumour size (OR 4·23, 3·02 to 11·03; P = 0·001), mural nodules (OR 3·55, 1·31 to 20·55; P = 0·002) and weight loss (OR 3·40, 2·34 to 12·34; P = 0·034) were independent factors predictive of malignant transformation. CONCLUSIONS Small indeterminate MCNs with no symptoms or features of concern may safely be observed as they have a low risk of malignant transformation.
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Affiliation(s)
- M G Keane
- Institute for Liver and Digestive Health, University College London, London
| | - A Shamali
- Department of Surgery, Southampton University Hospital, Southampton, UK
| | - L N Nilsson
- Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - A Antila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - J Millastre Bocos
- Department of Gastroenterology, Miguel Servet University Hospital, Zaragoza, Spain
| | | | - C Verdejo Gil
- Department of Gastroenterology, Ciudad Real University Hospital, Ciudad Real, Spain
| | | | - Y Vaalavuo
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - T Hoskins
- Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - S Robinson
- Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle upon Tyne, UK
| | - G O Ceyhan
- Surgical Clinic, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - M Abu Hilal
- Department of Surgery, Southampton University Hospital, Southampton, UK
| | - S P Pereira
- Institute for Liver and Digestive Health, University College London, London
| | - J Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - M Del Chiaro
- Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
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30
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Berevoescu N, Scăunașu R, Berevoescu M, Croitoru A. Mucinous cystadenoma of the pancreas associated with pregnancy. Case report and review of the literature. JOURNAL OF CLINICAL AND INVESTIGATIVE SURGERY 2018. [DOI: 10.25083/2559.5555/3.2/88.94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective. We present a rare pathology with uncommon onset. Background. Mucinous cystic pancreatic neoplasms (MCNs) are rare tumors, which generally occur in the fifth and sixth decades of women. Although some tumours are frankly malignant, all are in fact considered to be potentially malignant. Case report. We present the case of a 30-year-old patient, with a 16/11 cm tumor located in the pancreas body, which was diagnosed 8 months after birth. The preoperative assessment of the pancreatic lesion suggested the diagnosis of mucosal cyst neoplasm, without being able to determine its benign or malignant nature. Central pancreatectomy was performed with a good postoperative evolution. Histopathologic result was represented by mucinous pancreatic chistadenoma. Two years after surgical intervention, the patient presented no signs of recurrence or pancreatic (exocrine or endocrine) secretion deficiency. Conclusions. Preoperative imaging evaluation could be suggestive for mucinous cystic tumour, but this cannot specify however the nature of the tumor. The postpartum occurrence could establish a possible relationship between hormonal levels encountered during pregnancy and the development of this tumor, taking into considerations the ovarian-type stroma and the presence of hormone (estrogen and progesterone) receptors in this neoplasm. Central pancreatectomy without anastomosis preserves the functions of pancreas, and also decreases morbidity.
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31
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Kim JY, Hong SM. Precursor Lesions of Pancreatic Cancer. Oncol Res Treat 2018; 41:603-610. [DOI: 10.1159/000493554] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 09/07/2018] [Indexed: 12/18/2022]
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33
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Gerosa M, Chiarelli M, Guttadauro A, De Simone M, Tagliabue F, Costa M, Terragni S, Cioffi U. Wirsung atraumatic rupture in patient with pancreatic pseudocysts: a case presentation. BMC Gastroenterol 2018; 18:52. [PMID: 29685110 PMCID: PMC5913810 DOI: 10.1186/s12876-018-0781-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 04/17/2018] [Indexed: 01/02/2023] Open
Abstract
Background Pancreatic duct disruption is a challenging condition leading to pancreatic juice leakage and consequently to pancreatic fluid collections. The manifestations of pancreatic main duct leak include pseudocysts, walled-off necrosis, pancreatic fistulas, ascites, pleural and pericardial effusions. Pseudocyst formation is the most frequent outcome of a pancreatic duct leak. Case presentation We describe a case of a 64-year old man with large multiple pancreatic cysts discovered for progressive jaundice and significant weight loss in the absence of a previous episode of acute pancreatitis. Computed tomography scan showed lesion with thick enhancing walls. The main cyst dislocated the stomach and the duodenum inducing intra and extrahepatic bile ducts enlargement. Magnetic resonance cholangiopancreatography revealed a communication between the main pancreatic duct and the cystic lesions due to Wirsung duct rupture. Endoscopic ultrasound guided fine needle aspiration cytology did not show neoplastic cells and cyst fluid analysis revealed high amylase concentration. Preoperative exams were suggestive but not conclusive for a benign lesion. Laparotomy was necessary to confirm the presence of large communicating pseudocysts whose drainage was performed by cystogastrostomy. Histology confirmed the inflammatory nature of the cyst wall. Subsequently, the patient had progressive jaundice resolution. Conclusion Pancreatic cystic masses include several pathological entities, ranging from benign to malignant lesions. Rarely pseudocysts present as complex cystic pancreatic lesions with biliary compression in absence of history of acute pancreatitis. We describe the rare case of multiple pancreatic pseudocysts due to Wirsung duct rupture in absence of previous trauma or acute pancreatitis. Magnetic resonance showed the presence of communication with the main pancreatic duct and endoscopic ultrasound fine needle aspiration suggested the benign nature of the lesion.
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Affiliation(s)
- Martino Gerosa
- Department of Surgery, ASST Lecco, Via dell'Eremo 9/11, 23900, Lecco, Italy
| | - Marco Chiarelli
- Department of Surgery, ASST Lecco, Via dell'Eremo 9/11, 23900, Lecco, Italy
| | - Angelo Guttadauro
- Department of Surgery, University of Milan-Bicocca, Istituti Clinici Zucchi, Via Zucchi 24, 20900, Monza, Italy
| | - Matilde De Simone
- Department of Surgery, University of Milan, Via F. Sforza 35, 20122, Milan, Italy
| | - Fulvio Tagliabue
- Department of Surgery, ASST Lecco, Via dell'Eremo 9/11, 23900, Lecco, Italy
| | - Melchiorre Costa
- Department of Surgery, ASST Lecco, Via dell'Eremo 9/11, 23900, Lecco, Italy
| | - Sabina Terragni
- Department of Surgery, University of Milan-Bicocca, Istituti Clinici Zucchi, Via Zucchi 24, 20900, Monza, Italy
| | - Ugo Cioffi
- Department of Surgery, University of Milan, Via F. Sforza 35, 20122, Milan, Italy.
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Lan C, Li X, Wang X, Hao J, Ren H. A new combined criterion to better predict malignant lesions in patients with pancreatic cystic neoplasms. Cancer Biol Med 2018; 15:70-78. [PMID: 29545970 PMCID: PMC5842337 DOI: 10.20892/j.issn.2095-3941.2017.0152] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective: Cystic lesions of the pancreas have been increasingly recognized. Some lesions exhibit benign behavior, while others have unequivocal malignant potential. Thus, accurate identification of malignancy in patients diagnosed with pancreatic cystic neoplasms (PCNs) remains a major challenge. The aim of this study was to define a combined criterion to better predict malignant lesions in patients with PCNs. Methods: We retrospectively analyzed 165 patients who underwent resection of PCNs from October 2011 to May 2017. The relationship among malignancy and serum carbohydrate antigen 19-9 (CA19-9), preoperative neutrophil-to-lymphocyte ratio (NLR), and the presence of enhanced solid component on imaging was analyzed. Results: NLR before surgery in patients with malignant PCNs (2.81±2.14) was significantly higher than that in patients diagnosed with pancreatic neuroendocrine tumor (1.90±0.69, P=0.013) or healthy volunteers (1.40±0.48; P<0.001). Serum CA19-9 ≥39 U/mL, NLR >1.976 and presence of enhanced solid component were independent predictors of PCN malignancy. A combined criterion meeting any two or more of the three elements including CA19-9 ≥39 U/mL, NLR >1.976, and presence of enhanced solid component on computed tomography imaging is an indicator with a high positive predictive value of 80.5% and a high negative predictive value of 87.9%, and thus, represents a highly accurate test (86.1%).
Conclusions: The new combined criterion is an effective predictor of tumor malignancy in patients with PCNs.
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Affiliation(s)
- Chungen Lan
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Xin Li
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Xiuchao Wang
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jihui Hao
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - He Ren
- Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
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35
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Moutinho-Ribeiro P, Macedo G, Melo SA. Pancreatic Cancer Diagnosis and Management: Has the Time Come to Prick the Bubble? Front Endocrinol (Lausanne) 2018; 9:779. [PMID: 30671023 PMCID: PMC6331408 DOI: 10.3389/fendo.2018.00779] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 12/11/2018] [Indexed: 02/01/2023] Open
Abstract
Pancreatic cancer (PC) is associated with poor prognosis and very dismal survival rates. The most effective possibility of cure is tumor resection, which is only possible in about 15% of patients diagnosed at early stages of disease progression. Recent whole-genome sequencing studies pointed genetic alterations in 12 core signaling pathways in PC. These observations hint at the possibility that the initial mutation in PC might appear nearly 20 years before any symptoms occur, suggesting that a large window of opportunity may exist for early detection. Biomarkers with the potential to identify pre-neoplastic disease or very early stages of cancer are of great promise to improve patient survival. The concept of liquid biopsy refers to a minimally invasive sampling and analysis of liquid biomarkers that can be isolated from body fluids, primarily blood, urine and saliva. A myriad of circulating molecules may be useful as tumor markers, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), circulating tumor proteins, and extracellular vesicles, more specifically exosomes. In this review, we discuss with more detail the potential role of exosomes in several aspects related to PC, from initiation to tumor progression and its applicability in early detection and treatment. Exosomes are small circulating extracellular vesicles of 50-150 nm in diameter released from the plasma membrane by almost all cells and exhibit some advantages over other biomarkers. Exosomes are central players of intercellular communication and they have been implicated in a series of biological process, including tumorigenesis, migration and metastasis. Several exosomal microRNAs and proteins have been observed to distinguish PC from benign pancreatic diseases and healthy controls. Besides their possible role in diagnosis, understanding exosomes functions in cancer has clarified the importance of microenvironment in PC progression as well as its influence in proliferation, metastasis and resistance to chemotherapy. Increasing knowledge on cancer exosomes provides valuable insights on new therapeutic targets and can potentially open new strategies to treat this disease. Continuous research is needed to ascertain the reliability of using exosomes and their content as potential biomarkers, so that, hopefully, in the near future, they will provide the opportunity for early diagnosis, treatment intervention and increase survival of PC patients.
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Affiliation(s)
- Pedro Moutinho-Ribeiro
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal
- Faculty of Medicine of the University of Porto, Porto, Portugal
- *Correspondence: Guilherme Macedo
| | - Sónia A. Melo
- Faculty of Medicine of the University of Porto, Porto, Portugal
- Institute for Research Innovation in Health (i3S), Porto, Portugal
- Institute of Pathology and Molecular Immunology of the University of Porto, Porto, Portugal
- Sónia A. Melo
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36
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Kang CM, Matsushita A, Hwang HK, Matsuda Y, Kim H, Nakamura Y, Lee WJ. Experience-based surgical approach to pancreatic mucinous cystic neoplasms with ovarian-type stroma. Oncol Lett 2017; 15:2451-2458. [PMID: 29434957 DOI: 10.3892/ol.2017.7627] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 08/08/2017] [Indexed: 12/19/2022] Open
Abstract
The present study aimed to elucidate the clinicopathological characteristics of resected mucinous cystic neoplasm (MCN) with ovarian-type stroma and identify a surgical approach for MCN treatment, on the basis of Republic of Korean (Yonsei University College of Medicine, Seoul, South Korea) and Japanese (Nippon Medical School, Tokyo, Japan) bi-institutional collaboration. The present study retrospectively reviewed 55 MCNs with ovarian-type stroma using pathological re-examination. Clinicopathological features and preoperative clinical parameters were evaluated to predict malignant alterations in MCNs. The proportion of surgically treated MCNs has recently been increasing. All patients included in the present study were female, with a mean age of 47.9±13.3 years. Mural nodules were noted in 8 patients (14.5%) and the mean cyst size was 6.1±4.2 cm. A total of 9 patients (16.4%) were identified to exhibit non-invasive mucinous cystadenocarcinoma. The number of patients with small tumors (R2=-0.079, P=0.038) and asymptomatic pancreatic MCNs (P=0.022) was significantly increased (P<0.05), which resulted in the more frequent application of minimally invasive surgery (P<0.001). During the follow-up period (mean, 51.6 months; range, 1.1-242.8 months), no recurrence or tumor-associated mortality was identified. The presence of mural nodules (P=0.002) and a tumor size ≥4.5 cm (P=0.027) were identified as potential clinical parameters for predicting malignant transformation. The significance of mural nodules in predicting malignant transformation was increased in large MCNs (≥4.5 cm) of the pancreas compared with small MCNs (<4.5 cm) (P=0.002). Overall, non-invasive pancreatic MCNs are not aggressive, and minimally invasive pancreatectomy may be an effective approach for suitable patients.
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Affiliation(s)
- Chang Moo Kang
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.,Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Akira Matsushita
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8603, Japan
| | - Ho Kyoung Hwang
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.,Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Yoko Matsuda
- Department of Integrative Oncological Pathology, Nippon Medical School, Tokyo 113-8603, Japan
| | - Hyunki Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Yoshiharu Nakamura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8603, Japan
| | - Woo Jung Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.,Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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37
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Pittman ME, Rao R, Hruban RH. Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant Lesions of the Pancreas. Arch Pathol Lab Med 2017; 141:1606-1614. [PMID: 29189063 DOI: 10.5858/arpa.2016-0426-ra] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT - Invasive pancreatic ductal adenocarcinoma has a greater than 90% mortality rate at 5 years. Understanding noninvasive, curable precursor lesions gives us the best hope for reducing mortality from pancreatic ductal adenocarcinoma. The 3 pancreatic precursor lesions that have been well studied include intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. OBJECTIVE - To give an update on the latest clinical, molecular, and pathologic advances in intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia for the general surgical pathologist. DATA SOURCES - The current literature was analyzed and the authors' experiences with institutional and consult material were incorporated. CONCLUSIONS - Our understanding of the molecular alterations that lead from pancreatic precursor lesion to invasive carcinoma continues to evolve. These advances aid clinicians in their treatment decisions and researchers in their search for actionable, druggable targets.
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38
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Tamura S, Yamamoto H, Ushida S, Suzuki K. Mucinous cystic neoplasms in male patients: two cases. Rare Tumors 2017; 9:7096. [PMID: 29081929 PMCID: PMC5643879 DOI: 10.4081/rt.2017.7096] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 05/24/2017] [Accepted: 08/17/2017] [Indexed: 11/23/2022] Open
Abstract
Mucinous cystic neoplasms (MCNs) of the pancreas in male patients are very rare. Though few cases of MCNs in male patients have been reported, it is difficult to reveal them preoperatively. The first patient was a 50-year-old man and was incidentally found to have a cystic mass of 51 mm in the tail of the pancreas. We performed a distal pancreatectomy. The second patient was a 73-year-old man, incidentally found to have a cystic mass of 25 mm in diameter in the tail of the pancreas and a carcinoma of the bile duct. We performed a subtotal stomachpreserving pancreaticoduodenectomy and distal pancreatectomy. In both cases, the cystic lesion was diagnosed pathologically as MCNs. Since MCNs have the risk of malignancy, a resection is recommended. Cases of MCNs in male patients exhibit features that are similar to MCNs in women. We should recognize that MCNs of the pancreas in male patients exists.
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Affiliation(s)
| | | | | | - Kazufumi Suzuki
- Department of Gastrointestinal Surgery, Seirei Hamamatsu General Hospital, Shizuoka, Japan
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Ridtitid W, Al-Haddad MA. Endoscopic Ultrasound Imaging for Diagnosing and Treating Pancreatic Cysts. Gastrointest Endosc Clin N Am 2017; 27:615-642. [PMID: 28918802 DOI: 10.1016/j.giec.2017.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Cystic pancreatic lesions are increasingly diagnosed owing to the abundant use of cross-sectional imaging. Given their malignant potential, true pancreatic cysts should be considered for resection or periodic follow-up. Cystic lesions of the pancreas (CLPs) require further evaluation and management. Therefore, it is important to establish a solid diagnosis at the time of detection. Endoscopic ultrasound examination is the imaging modality of choice. Fine needle aspiration provides fluid for cytologic, biochemical, and molecular assays to classify lesions and predict biological behavior. This review provides an overview of the diagnosis and management of various types of commonly encountered true CLPs.
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Affiliation(s)
- Wiriyaporn Ridtitid
- Division of Gastroenterology and Hepatology, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Mohammad A Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 550 North University Boulevard, Suite 4100, Indianapolis, IN 46202, USA.
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40
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Moutinho-Ribeiro P, Coelho R, Giovannini M, Macedo G. Pancreatic cancer screening: Still a delusion? Pancreatology 2017; 17:754-765. [PMID: 28739291 DOI: 10.1016/j.pan.2017.07.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 06/17/2017] [Accepted: 07/05/2017] [Indexed: 12/11/2022]
Abstract
Pancreatic adenocarcinoma represents the fourth most common cause of cancer mortality and death due to pancreatic cancer (PC) have increased since 2003. Its incidence has also raised about 30% in the past decade and it is expected to become the second cause of cancer mortality by 2020 in the USA. Most PC present with metastatic disease and improvements in treatment outcomes for this group have been disappointing. These observations support the idea that screening to identify patients at an earlier stage might be an important strategy in improving overall PC outcomes. Many protocols have been tested, nevertheless, by now there is no effective screening program. Given the overall low incidence of disease and the current lack of accurate, inexpensive and noninvasive screening tests, the consensus is that widespread population-based screening for PC in the general population or in patients with only one affected first-degree relative is neither practicable nor indicated in most countries. However, a different scenario is screening patients with higher risk for PC, most of them with hereditary conditions predisposing the development of this neoplasia. In fact, some guidelines are now available helping to select these individuals at risk and to screen them, in order to achieve early detection of PC.
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Affiliation(s)
- Pedro Moutinho-Ribeiro
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; Faculty of Medicine, University of Porto, Portugal.
| | - Rosa Coelho
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal
| | - Marc Giovannini
- Endoscopic Unit, Paoli-Calmettes Institute, Marseilles, France
| | - Guilherme Macedo
- Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; Faculty of Medicine, University of Porto, Portugal
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41
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Paniccia A, Torphy R, Devaraj K, Schulick RD. Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature. J Pancreat Cancer 2017; 3:40-45. [PMID: 30631840 PMCID: PMC5933473 DOI: 10.1089/pancan.2017.0004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy-morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma-were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions.
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Affiliation(s)
- Alessandro Paniccia
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Robert Torphy
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Kalpana Devaraj
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Richard D Schulick
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Abstract
Pancreatic cystic neoplasms are discovered with increasing frequency. Accurate knowledge of the natural history of cystic neoplasms is crucial to develop useful and cost-effective strategies for surveillance and surgical resection. To date, the natural history of cystic neoplasms is still incomplete due to lack of adequate diagnostic accuracy in the absence of surgical pathology. Nevertheless, current evidence points to risk factors for malignant transformation to help clinical management. New biomarkers that accurately distinguish cyst neoplasms and those most likely to progress to cancer would help clarify the natural history of cystic neoplasms.
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Affiliation(s)
- Alexander Larson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Richard S Kwon
- Division of Gastroenterology and Hepatology, University of Michigan, 1500 E. Medical Center Drive, Taubman 3912, Ann Arbor, MI, 48109-5362, USA.
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43
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Postlewait LM, Ethun CG, McInnis MR, Merchant N, Parikh A, Idrees K, Isom CA, Hawkins W, Fields RC, Strand M, Weber SM, Cho CS, Salem A, Martin RCG, Scoggins C, Bentrem D, Kim HJ, Carr J, Ahmad S, Abbott DE, Wilson GC, Kooby DA, Maithel SK. Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study. JAMA Surg 2017; 152:19-25. [PMID: 27760255 DOI: 10.1001/jamasurg.2016.3598] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN. Objectives To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma. Design, Setting, and Participants Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma. Main Outcomes and Measures Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy. Results A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years. Conclusions and Relevance Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.
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Affiliation(s)
- Lauren M Postlewait
- Winship Cancer Institute, Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Cecilia G Ethun
- Winship Cancer Institute, Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Mia R McInnis
- Winship Cancer Institute, Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Nipun Merchant
- Division of Surgical Oncology, Department of Surgery, University of Miami, Miami, Florida
| | - Alexander Parikh
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Chelsea A Isom
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - William Hawkins
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Matthew Strand
- Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | - Sharon M Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
| | - Clifford S Cho
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
| | - Ahmed Salem
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
| | - Robert C G Martin
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky
| | - David Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Hong J Kim
- Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill
| | - Jacquelyn Carr
- Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill
| | - Syed Ahmad
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, Ohio
| | - Daniel E Abbott
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, Ohio
| | - Gregory C Wilson
- Division of Surgical Oncology, Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, Ohio
| | - David A Kooby
- Winship Cancer Institute, Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Shishir K Maithel
- Winship Cancer Institute, Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
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Paniccia A, Torphy R, Devaraj K, Schulick RD. Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature. J Pancreat Cancer 2017. [DOI: 10.1089/crpc.2017.0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Alessandro Paniccia
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Robert Torphy
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Kalpana Devaraj
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Richard D. Schulick
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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Roch AM, Bigelow K, Schmidt CM, Carr RA, Jester AL, Ceppa EP, House MG, Zyromski NJ, Nakeeb A, Schmidt CM. Management of Undifferentiated Solitary Mucinous Cystic Lesion of the Pancreas: A Clinical Dilemma. J Am Coll Surg 2017; 224:717-723. [PMID: 28126546 DOI: 10.1016/j.jamcollsurg.2016.12.045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 12/22/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Management of solitary mucinous cystic lesions of the pancreas (MCLs) relies on correct differentiation between branch duct intraductal papillary mucinous neoplasm (BD-IPMN) and mucinous cystic neoplasm (MCN). Current international consensus guidelines recommend resection for MCN, and unifocal BD-IPMN can be followed in the absence of worrisome features/high-risk stigmata. We hypothesized that preoperative differentiation of solitary MCLs is suboptimal, and that all solitary MCLs should be treated similarly. STUDY DESIGN A retrospective review of an institutional database (2003 to 2016) identified 711 patients who underwent resection for pancreatic cyst. Only lesions that met cytologic or biochemical criteria for diagnosis of MCLs were included. Mucinous cystic neoplasms were defined by presence of ovarian stroma on pathology. Patients with formal preoperative diagnosis of BD-IPMN (multifocality, GNAS mutation) were excluded. RESULTS One hundred and eighty solitary MCLs were identified on preoperative imaging (mean age 54 years, 24% men). On surgical pathology, 108 were MCNs and 72 BD-IPMNs. There was no difference in invasive rate (7 of 108 [6.5%] MCNs vs 4 of 72 [5.6%] BD-IPMN; p ≈ 1). Pancreatic ductal connectivity was reported on imaging/endoscopy in 10 of 108 (9%) MCNs and 22 of 72 (31%) BD-IPMNs, representing 67% accuracy in differentiating MCNs from BD-IPMNs. On multivariate analysis, typical risk factors failed to predict invasiveness in either MCNs or BD-IPMNs. When all undifferentiated solitary MCLs were analyzed together, older age (p = 0.03) and cyst size (p = 0.04) were associated with increased invasive rate in multivariate analysis. CONCLUSIONS Unreliable differentiation and limited ability to predict invasiveness make solitary MCLs clinically challenging. With similar invasive rates, MCN and unifocal BD-IPMNs should be merged into one new entity for management, the undifferentiated solitary MCL.
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Affiliation(s)
- Alexandra M Roch
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Katherine Bigelow
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Christian M Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Rosalie A Carr
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Andrea L Jester
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Eugene P Ceppa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Nicholas J Zyromski
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Attila Nakeeb
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.
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46
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Moris M, Wallace MB. Intraductal papillary mucinous neoplasms and mucinous cystadenomas: current status and recommendations. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:358-367. [PMID: 28112959 DOI: 10.17235/reed.2017.4630/2016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The real prevalence of pancreatic cystic lesions remains unknown. The malignant potential of some of these lesions remains a cause for significant concern. Thus, it is mandatory to develop a strategy to clearly discriminate those cysts with a potential for malignant transformation from those that do not carry any significant risk. Intraductal papillary mucinous neoplasms and mucinous cystadenomas are mucinous cystic neoplasms with a known malignant potential that have gained greater recognition in recent years. However, despite the numerous studies that have been carried out, their differential diagnosis among other cysts subtypes and their therapeutic approach continue to be a challenge for clinicians. This review contains a critical approach of the current recommendations and management strategies regarding intraductal papillary mucinous neoplasms and mucinous cystadenomas, as well as highlighting the limitations exposed in current guidelines.
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Greer JB, Ferrone CR. Spectrum and Classification of Cystic Neoplasms of the Pancreas. Surg Oncol Clin N Am 2016; 25:339-50. [PMID: 27013368 DOI: 10.1016/j.soc.2015.11.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
As patients are living longer and axial imaging is more widespread, increasing numbers of cystic neoplasms of the pancreas are found. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common. The revised Sendai guidelines provide a safe algorithm for expectant management of certain cystic neoplasms; however, studies are ongoing to identify further subgroups that can be treated nonoperatively. For those patients with high-risk clinical features or symptoms, surgical resection can be performed safely at high-volume pancreatic centers. Accurate diagnosis is critical for accurate decision making.
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Affiliation(s)
- Jonathan B Greer
- General Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRB-425, Boston, MA 02114, USA
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
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Cao S, Hu Y, Gao X, Liao Q, Zhao Y. Serum Carbohydrate Antigen 19-9 in Differential Diagnosis of Benign and Malignant Pancreatic Cystic Neoplasms: A Meta-Analysis. PLoS One 2016; 11:e0166406. [PMID: 27835676 PMCID: PMC5105948 DOI: 10.1371/journal.pone.0166406] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 10/30/2016] [Indexed: 12/12/2022] Open
Abstract
Background Using serum carbohydrate antigen 19–9 (CA 19–9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19–9 in predicting malignant pancreatic cystic lesions. Methods Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. Results A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35–0.59), and 0.88(95% CI: 0.86–0.91), respectively, and the AUC was 0.87(95% CI, 0.84–0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. Conclusions Serum CA 19–9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods.
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Affiliation(s)
- Shaobo Cao
- Department of General Surgery, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, 100730, China
| | - Ya Hu
- Department of General Surgery, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, 100730, China
| | - Xiang Gao
- Department of General Surgery, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, 100730, China
| | - Quan Liao
- Department of General Surgery, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, 100730, China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, 100730, China
- * E-mail:
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Nilsson LN, Keane MG, Shamali A, Millastre Bocos J, Marijinissen van Zanten M, Antila A, Verdejo Gil C, Del Chiaro M, Laukkarinen J. Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature. Pancreatology 2016; 16:1028-1036. [PMID: 27681503 DOI: 10.1016/j.pan.2016.09.011] [Citation(s) in RCA: 82] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Revised: 09/17/2016] [Accepted: 09/20/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management. METHODS A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015. RESULTS MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%. CONCLUSIONS Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.
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Affiliation(s)
| | - Margaret G Keane
- Institute for Liver and Digestive Health, University College London, UK
| | | | | | | | - Anne Antila
- Tampere University Hospital, Tampere, Finland
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Pancreatic mucinous cystadenocarcinoma: Epidemiology and outcomes. Int J Surg 2016; 35:76-82. [PMID: 27638187 DOI: 10.1016/j.ijsu.2016.09.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 08/30/2016] [Accepted: 09/11/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Pancreatic mucinous cystadenocarcinoma is a rare malignancy. Our aim was to investigate the demographic, pathological characteristics, treatment modalities and survival of patients with mucinous cystadenocarcinoma via the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database analysis. MATERIALS AND METHODS This was a retrospective study of SEER database's records on patients with mucinous cystadenocarcinoma diagnosed from 1988 to 2012. Primary outcome measures were clinico-pathological characteristics, observed and disease-specific survival. RESULTS A total of 507 patients were identified. Median age at diagnosis was 67 years and most patients were female (68.4%). The tumors were mainly low grade (82.9%, grade I-II) and frequently localized (42.8%) in the body/tail of the pancreas (45.6%). According to Kaplan-Meier curves observed survival was 111 months (95%CI: 82.5, 139.5) vs 14 months (95% CI: 10.9, 17.1) vs 4 months (95%CI: 2.9, 5.1) for patients with localized, regional and distant disease, respectively. One-year disease-specific survival for patients with localized disease was 90.1%, vs. 56.7% for those with regional and 18.7% with distant tumor spread. CONCLUSIONS Mucinous cystadenocarcinomas tend to be low grade tumors, localized to the pancreatic body/tail. Surgery as the primary therapeutic intervention and tumor stage are independent predictors of disease-specific survival.
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