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Rahmatullah ZF, Nia IY, Afghani E, Zaheer A. Exploring the new Kyoto guidelines for managing pancreatic cysts: an overview and comparison with previous guidelines. Abdom Radiol (NY) 2024:10.1007/s00261-024-04665-2. [PMID: 39611939 DOI: 10.1007/s00261-024-04665-2] [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: 09/19/2024] [Revised: 10/26/2024] [Accepted: 10/28/2024] [Indexed: 11/30/2024]
Abstract
The rising use of diagnostic imaging has led to an increase in the incidental detection of pancreatic cysts, with reported incidences of 1.2-2.6% on Computed Tomography and 2.4-49.1% on Magnetic Resonance Imaging. While many of these cysts are asymptomatic and benign, the enhanced imaging techniques have also revealed malignant and premalignant lesions. Mucinous neoplasms, including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms, are particularly concerning due to their potential for malignant transformation. Recent studies highlight significant variations in dysplasia across IPMN types, with main duct IPMNs showing a higher likelihood of high-grade dysplasia or invasive carcinoma compared to branch duct IPMNs. Management and follow-up of these lesions remain controversial due to inconsistent guidelines. This article reviews and compares six major guidelines: the 2015 American Gastroenterological Association guidelines, the 2017 International Association of Pancreatology (IAP/Fukuoka) guidelines, the 2017 American College of Radiology guidelines, the 2018 American College of Gastroenterology guidelines, the 2018 European Study Group guidelines, and the newly released, 2024 Kyoto guidelines. We summarize key differences in risk factors, surveillance protocols, and surgical referral criteria, with a focus on the updated 2024 Kyoto guidelines and the implications of recent research advancements.
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Affiliation(s)
- Zahra Fatima Rahmatullah
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Iman Yazdani Nia
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, USA
- Department of Radiology, University of Pennsylvania, Philadelphia, USA
| | - Elham Afghani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Atif Zaheer
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, USA.
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Hernandez-Barco YG, Fernandez-Del Castillo C, Fradelos E, Matos Ruiz PM, Bazerbachi F, Dhandibhotla S, Lillemoe KD, Casey BW, Kambadakone A, Qadan M. The multidisciplinary pancreatic cyst clinic: A collaborative approach to streamlined management. Pancreatology 2024; 24:764-770. [PMID: 38796308 DOI: 10.1016/j.pan.2024.05.525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 05/10/2024] [Accepted: 05/18/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. METHODS To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. CLINIC INFRASTRUCTURE The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. RESULTS A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. CONCLUSIONS The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.
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Affiliation(s)
- Yasmin G Hernandez-Barco
- Pancreas and Biliary Program, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | | | - Evangelos Fradelos
- Pancreas and Biliary Program, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | | | - Fateh Bazerbachi
- CentraCare, Interventional Endoscopy, St. Cloud Hospital, St. Cloud, MN, USA
| | - Sarvani Dhandibhotla
- Pancreas and Biliary Program, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Keith D Lillemoe
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Brenna W Casey
- Pancreas and Biliary Program, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | | | - Motaz Qadan
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
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Tzadok R, Kessner R, Ritter E, Aizic A, Yashar H, Lazar S, Katz Y, Ronen-Amsalem Z, Chernomorets A, Shibolet O, Ben-Ami Shor D. Utility of Radiological Follow Up of Main-Duct Intraductal Papillary Mucinous Neoplasms and Mixed-Type Intraductal Papillary Mucinous Neoplasms. Biomedicines 2024; 12:1437. [PMID: 39062014 PMCID: PMC11274131 DOI: 10.3390/biomedicines12071437] [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: 06/02/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms (IPMNs) have the potential to evolve into pancreatic adenocarcinoma (PDAC). While main-duct IPMNs (MD-IPMNs), involving the main pancreatic duct (MPD), are less common than side-branch IPMNs (SB-IPMNs) or mixed-type IPMNs (mixed-IPMNs), their malignant transformation potential is far greater. Controversy exists between different guidelines in terms of recommended management strategies. This study was aimed at assessing the utility of the radiological follow up of MD-IPMNs and mixed-type IPMNs, including prevalence of worrisome radiological findings as well as clinical and laboratory parameters, and their correlation with the development of progression or pancreatic adenocarcinoma. METHODS Eighty-four patients with MD-IPMNs or mixed-type IPMNs who underwent at least one magnetic resonance cholangiopancreatography (MRCP) were included. Clinical and laboratory data were obtained retrospectively. A cross-sectional analysis was carried out to establish clinical and laboratory parameters associated with development of PDAC. A retrospective cohort analysis was performed on 44 patients who had at least six months of follow up, trying to identify factors correlating with worrisome radiological features. RESULTS Nine cases (10.7%) of PDAC were recorded in this cohort. The laboratory and imaging factors associated with cyst size progression greater than 5 mm during follow up were elevated alanine transaminase (ALT) levels, the maximal cyst size, and the MPD diameter. Cross-sectional analysis indicated that PDAC was associated with nausea (p = 0.01), as well as increased levels of aspartate aminotransferase (AST) (p = 0.05), gamma glutamyl transpeptidase (GGT) (p = 0.01), and alkaline phosphatase (ALP) (p = 0.01). CONCLUSIONS Elevated levels of liver enzymes were associated with IPMN progression and, subsequently, the development of PDAC. ALT levels, maximal cyst size, and MPD diameter are associated with the progression of cyst size. These data may aid in risk-stratifying patients when determining the follow up approach for IPMNs.
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Affiliation(s)
- Roie Tzadok
- Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (R.T.); (E.R.)
| | - Rivka Kessner
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Einat Ritter
- Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (R.T.); (E.R.)
| | - Asaf Aizic
- Department of Pathology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Hila Yashar
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Sapir Lazar
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Yuval Katz
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Zur Ronen-Amsalem
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Arthur Chernomorets
- Department of Radiology, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Oren Shibolet
- Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (R.T.); (E.R.)
| | - Dana Ben-Ami Shor
- Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; (R.T.); (E.R.)
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Sekine K, Nagata N, Hisada Y, Yamamoto K, Mukai S, Tsuchiya T, Machitori A, Kojima Y, Yada T, Yamamoto N, Uemura N, Itoi T, Kawai T. Identifying predictors for comorbidities related mortality versus pancreatic cancer related mortality in patients with intraductal papillary mucinous neoplasm. United European Gastroenterol J 2024; 12:614-626. [PMID: 38367226 PMCID: PMC11176910 DOI: 10.1002/ueg2.12540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 12/11/2023] [Indexed: 02/19/2024] Open
Abstract
BACKGROUNDS Few data are available for surveillance decisions focusing on factors related to mortality, as the primary outcome, in intraductal papillary mucinous neoplasm (IPMN) patients. AIMS We aimed to identify imaging features and patient backgrounds associated with mortality risks by comparing pancreatic cancer (PC) and comorbidities. METHODS We retrospectively conducted a multicenter long-term follow-up of 1864 IPMN patients. Competing risk analysis was performed for PC- and comorbidity-related mortality. RESULTS During the median follow-up period of 5.5 years, 14.0% (261/1864) of patients died. Main pancreatic duct ≥5 mm and mural nodules were significantly related to all-cause and PC-related mortality, whereas cyst ≥30 mm did not relate. In 1730 patients without high-risk imaging features, 48 and 180 patients died of PC and comorbidity. In the derivation cohort, a prediction model for comorbidity-related mortality was created, comprising age, cancer history, diabetes mellitus complications, chronic heart failure, stroke, paralysis, peripheral artery disease, liver cirrhosis, and collagen disease in multivariate analysis. If a patient had a 5 score, 5- and 10-year comorbidity-related mortality is estimated at 18.9% and 50.2%, respectively, more than 7 times higher than PC-related mortality. The model score was also significantly associated with comorbidity-related mortality in a validation cohort. CONCLUSIONS This study demonstrates main pancreatic duct dilation and mural nodules indicate risk of PC-related mortality, identifying patients who need periodic examination. A comorbidity-related mortality prediction model based on the patient's age and comorbidities can stratify patients who do not require regular tests, especially beyond 5 years, among IPMN patients without high-risk features. CLINICAL TRIAL REGISTRATION T2022-0046.
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Affiliation(s)
- Katsunori Sekine
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineKohnodai HospitalIchikawaChibaJapan
| | - Naoyoshi Nagata
- Department of Gastroenterological EndoscopyTokyo Medical UniversityTokyoJapan
| | - Yuya Hisada
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineTokyoJapan
| | - Kenjiro Yamamoto
- Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyoJapan
| | - Shuntaro Mukai
- Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyoJapan
| | - Takayoshi Tsuchiya
- Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyoJapan
| | - Akihiro Machitori
- Department of RadiologyNational Center for Global Health and MedicineKohnodai HospitalIchikawaChibaJapan
| | - Yasushi Kojima
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineTokyoJapan
| | - Tomoyuki Yada
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineKohnodai HospitalIchikawaChibaJapan
| | - Natsuyo Yamamoto
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineTokyoJapan
| | - Naomi Uemura
- Department of Gastroenterology and HepatologyNational Center for Global Health and MedicineKohnodai HospitalIchikawaChibaJapan
| | - Takao Itoi
- Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyoJapan
| | - Takashi Kawai
- Department of Gastroenterological EndoscopyTokyo Medical UniversityTokyoJapan
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Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, Hijioka S, Jang JY, Lennon AM, Miyasaka Y, Ohno E, Salvia R, Wolfgang CL, Wood LD. International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology 2024; 24:255-270. [PMID: 38182527 DOI: 10.1016/j.pan.2023.12.009] [Citation(s) in RCA: 76] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/14/2023] [Accepted: 12/22/2023] [Indexed: 01/07/2024]
Abstract
This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.
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Affiliation(s)
- Takao Ohtsuka
- Department of Digestive Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
| | | | - Toru Furukawa
- Department of Investigative Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Jin-Young Jang
- Division of Hepatobiliary-Pancreatic Surgery, Departments of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Anne Marie Lennon
- Division of Gastroenterology and Hepatology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Yoshihiro Miyasaka
- Department of Surgery, Fukuoka University Chikushi Hospital, and Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Roberto Salvia
- Department of Surgery, Dentistry, Paediatrics and Gynaecology University of Verona, Verona, Italy
| | | | - Laura D Wood
- Departments of Pathology and Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Chon HK, Song TJ, Yoo KH, Hwang JS, Kim MH, Choi EK, Kim TH. Enhancing Mural Nodules in the Main Pancreatic Duct of Main and Mixed Types of Intraductal Papillary Mucinous Neoplasms: Does Size Matter in Malignancy Risk? Gut Liver 2023; 17:942-948. [PMID: 37317514 PMCID: PMC10651374 DOI: 10.5009/gnl220378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/15/2022] [Accepted: 11/29/2022] [Indexed: 06/16/2023] Open
Abstract
Background/Aims Most guidelines recommend surgical resection of all main duct (MD) and mixed-type (MT) intraductal papillary mucinous neoplasms (IPMNs) in suitable patients. However, there is little evidence regarding the malignancy risk of enhancing mural nodules (EMNs) that are present only in the main pancreatic duct (MPD) in patients with MD- and MT-IPMNs. Therefore, this study aimed to identify the clinical and morphological features associated with malignancy in MD- and MT-IPMNs with EMNs only in the MPD. Methods We retrospectively enrolled 50 patients with MD- and MT-IPMNs with EMNs only in the MPD on contrast-enhanced magnetic resonance imaging. We evaluated the clinical characteristics and preoperative radiologic imaging results of MPD morphology and EMN size and analyzed the risk factors associated with malignancy. Results Histological findings of EMNs were low-grade dysplasia (38%), malignant lesions (62%), high-grade dysplasia (34%), and invasive carcinoma (28%). On the receiver operating characteristic curve, the cutoff value of EMN size on magnetic resonance imaging for best predicting malignancy was 5 mm (sensitivity, 93.5%; specificity, 52.6%; area under the curve, 0.753). Multivariate analysis showed that only EMN >5 mm (odds ratio, 27.69; confidence interval, 2.75 to 278.73; p=0.050) was an independent risk factor for malignancy. Conclusions EMNs of >5 mm are associated with malignancy in patients with MD- and MT-IPMNs with EMNs that are present only in the MPD, in accordance with the international consensus guidelines.
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Affiliation(s)
- Hyung Ku Chon
- Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea
- Institution of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Tae Jun Song
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoung-Hoon Yoo
- Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea
| | - Jun Seong Hwang
- Center of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Changwon Hanmaeum Hospital, Hanyang University College of Medicine, Changwon, Korea
| | - Myung-Hwan Kim
- Center of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Changwon Hanmaeum Hospital, Hanyang University College of Medicine, Changwon, Korea
| | - Eun Kwang Choi
- Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Korea
| | - Tae Hyeon Kim
- Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea
- Institution of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea
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Schleimer LE, Chabot JA, Kluger MD. Innovation in the Surgical Management of Pancreatic Cystic Neoplasms: Same Operations, Narrower Indications, and an Individualized Approach to Decision-Making. Gastrointest Endosc Clin N Am 2023; 33:655-677. [PMID: 37245941 DOI: 10.1016/j.giec.2023.03.003] [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: 05/30/2023]
Abstract
Historically, the management of pancreatic cystic neoplasms (PCN) has been operative. Early intervention for premalignant lesions, including intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN), offers an opportunity to prevent pancreatic cancer-with potential decrement to patients' short-term and long-term health. The operations performed have remained fundamentally the same, with most patients undergoing pancreatoduodenectomy or distal pancreatectomy using oncologic principles. The role of parenchymal-sparing resection and total pancreatectomy remains controversial. We review innovations in the surgical management of PCN, focusing on the evolution of evidence-based guidelines, short-term and long-term outcomes, and individualized risk-benefit assessment.
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Affiliation(s)
- Lauren E Schleimer
- Department of Surgery, Columbia University Irving Medical Center, 177 Fort Washington Avenue, 8 Garden South, New York, NY 10032, USA. https://twitter.com/lschleim
| | - John A Chabot
- Division of GI/Endocrine Surgery, Department of Surgery, Herbert Irving Pavilion, Columbia University Irving Medical Center, Columbia University, Vagelos College of Physicians & Surgeons, 161 Fort Washington Avenue, Suite 819, New York, NY 10032, USA
| | - Michael D Kluger
- Division of GI/Endocrine Surgery, Department of Surgery, Herbert Irving Pavilion, Columbia University Irving Medical Center, Columbia University, Vagelos College of Physicians & Surgeons, 161 Fort Washington Avenue, Suite 823, New York, NY 10032, USA.
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Hamada T, Oyama H, Nakai Y, Tange S, Arita J, Hakuta R, Ijichi H, Ishigaki K, Kanai S, Kawaguchi Y, Kogure H, Mizuno S, Saito K, Saito T, Sato T, Suzuki T, Takahara N, Tanaka M, Tateishi K, Ushiku T, Hasegawa K, Fujishiro M. Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct. Clin Gastroenterol Hepatol 2023; 21:1792-1801.e3. [PMID: 36787835 DOI: 10.1016/j.cgh.2023.01.032] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/14/2023] [Accepted: 01/30/2023] [Indexed: 02/16/2023]
Abstract
BACKGROUND & AIMS Dilatation of the main pancreatic duct (MPD) has been a surgical indication for intraductal papillary mucinous neoplasms (IPMNs). Few studies have investigated long-term outcomes of IPMNs with MPD dilatation. METHODS Among 3610 patients diagnosed with pancreatic cysts between 1994 and 2021, we identified 2829 IPMN patients, including 282 patients with MPD ≥5 mm, and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma. Utilizing competing risks proportional hazards models, we estimated subdistribution hazard ratios for incidence of pancreatic carcinoma with adjustment for potential confounders. RESULTS In analyses of short-term outcomes of the 282 patients with MPD dilatation, 72 (26%) patients were diagnosed with pancreatic carcinoma based on surgical or nonsurgical exploration. During long-term follow-up of 168 patients, we documented 24 (14%) patients diagnosed with pancreatic carcinoma (18 with IPMN-derived carcinoma and 6 with concomitant ductal adenocarcinoma). The patients with the MPD = 5-9.9 mm had cumulative incidence rates of pancreatic carcinoma diagnosis of 8.1% (95% confidence interval [CI], 4.3%-13.5%) and 10.0% (95% CI, 5.5%-15.9%) at 2 and 5 years, respectively; and the patients with the MPD ≥10 mm had the corresponding rates of 16.0% (95% CI, 3.6-36.5%) and 33.3% (95% CI, 10.3%-58.8%). The multivariable subdistribution hazard ratios were 2.78 (95% CI, 1.57-4.90) and 7.00 (95% CI, 2.58-19.0) for the MPD = 5-9.9 mm and ≥10 mm (vs <5 mm), respectively. CONCLUSIONS IPMNs with MPD dilatation at baseline were associated with higher prevalence and incidence of pancreatic carcinoma compared with IPMNs with no MPD dilatation.
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Affiliation(s)
- Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Hiroki Oyama
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
| | - Shuichi Tange
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryunosuke Hakuta
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hideaki Ijichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sachiko Kanai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kei Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsunori Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mariko Tanaka
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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He X, Fan R, Sun J, Ren Y, Zhao X, Rui W, Yuan Y, Zou D. A model for predicting degree of malignancy in patients with intraductal papillary mucinous neoplasm. Front Oncol 2023; 13:1087852. [PMID: 36761937 PMCID: PMC9902908 DOI: 10.3389/fonc.2023.1087852] [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: 11/02/2022] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
Background/Objectives There is no predictive model available to address early stage malignant intraductal papillary mucinous neoplasm (IPMN) including high grade dysplasia (HGD) and pT1a (invasive component≤0.5 cm). The aim of this study was to establish an objective and sufficient model to predict the degree of malignancy in patients with IPMN, which can be easily applied in daily practice and adopted for any type of lesion. Methods A retrospective cohort study of 309 patients who underwent surgical resection for IPMN was performed. Members of the cohort were randomly allocated to the training or testing set. A detection tree model and random forest model were used for a 3-class classification to distinguish low grade dysplasia (LGD), HGD/pT1a IPMN, and invasive intraductal papillary mucinous cancer (I-IPMC) beyond pT1a. Results Of the 309 patients, 54 (17.4%) had early stage malignancy (19 HGD, 35 pT1a), 49 (15.9%) had I-IPMC beyond pT1a, and 206 (66.7%) had LGD IPMN. We proposed a 3-class classification model using a random forest algorithm, and the model had an accuracy of 99.5% with the training set, and displayed an accuracy of 96.0% with the testing set. We used SHAP for interpretation of the model and showed the top five factors (mural nodule size, main pancreatic duct diameter, CA19-9 levels, lesion edge and common bile duct dilation) were most likely to influence the 3-class classification results in terms of interpretation of the random forest model. Conclusions This predictive model will help assess an individual's risk for different stages of IPMN malignancy and may help identify patients with IPMN who require surgery.
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Affiliation(s)
- Xiangyi He
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rong Fan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Sun
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanhao Ren
- School of Mathematical Sciences, Fudan University, Shanghai, China
| | - Xuesong Zhao
- Departments of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Rui
- Departments of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
| | - Duowu Zou
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,*Correspondence: Yaozong Yuan, ; Duowu Zou,
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Zhou H, Li X, Wang Y, Wang Z, Zhu J, Wang Z, Chen X. Threshold of main pancreatic duct for malignancy in intraductal papillary mucinous neoplasm at head-neck and body-tail. BMC Gastroenterol 2022; 22:473. [PMCID: PMC9675150 DOI: 10.1186/s12876-022-02577-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 11/14/2022] [Indexed: 11/21/2022] Open
Abstract
Background Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD diameter in predicting malignancy may be related to the lesion location. This study aimed to separately identify the thresholds of MPD for malignancy of IPMNs separately for the head-neck and body-tail. Materials and methods A total of 185 patients with pathologically confirmed IPMNs were included. Patient demographic information, clinical data, and pathological features were obtained from the medical records. Those IPMNs with high-grade dysplasia or with associated invasive carcinoma were considered as malignant tumor. Radiological data including lesion location, tumor size, diameter of the MPD, mural nodule, and IPMN types (main duct, MD; branch duct, BD; and mixed type, MT), were collected on computed tomography or magnetic resonance imaging. Serum carbohydrate antigen 19-9 levels, serum carcinoembryonic antigen levels, and the medical history of diabetes mellitus, chronic cholecystitis, and pancreatitis were also collected. Results Malignant IPMNs were detected in 31.6% of 117 patients with lesions in the pancreatic head-neck and 20.9% of 67 patients with lesions in the pancreatic body-tail. In MPD-involved IPMNs, malignancy was observed in 54.1% of patients with lesions in the pancreatic head-neck and 30.8% of patients with lesions in the pancreatic body-tail (p < 0.05). The cutoff value of MPD diameter for malignancy was 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail in all type of IPMNs. In MPD-involved IPMNs, the threshold was 8.2 mm for lesion in pancreatic head-neck and 7.7 mm for lesions in the body-tail. Multivariate analysis confirmed that MPD diameter ≥ 6.5 mm (pancreatic head-neck) and MPD diameter ≥ 7.7 mm (pancreatic body-tail) were independent predictors of malignancy (p < 0.05). Similar results were observed in MPD-involved IPMNs using 8.2 mm as a threshold. Conclusion The thresholds of the dilated MPD may be associated with IPMNs locations. Thresholds of 6.5 mm for lesions in the head-neck and 7.7 mm for lesions in the body-tail were observed. For MPD-involved IPMNs alone, threshold for lesions in the head-neck was close to that in the body-tail. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02577-3.
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Affiliation(s)
- Hao Zhou
- grid.410745.30000 0004 1765 1045Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 China
| | - Xiaoshuang Li
- grid.452511.6Department of Radiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210000 China
| | - Yajie Wang
- grid.410745.30000 0004 1765 1045Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 China
| | - Zhiyue Wang
- grid.452511.6Department of Radiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210000 China
| | - Jingrong Zhu
- grid.410745.30000 0004 1765 1045Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 China
| | - Zhongqiu Wang
- grid.410745.30000 0004 1765 1045Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 China
| | - Xiao Chen
- grid.410745.30000 0004 1765 1045Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029 China
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Fujita Y, Hirono S, Kawai M, Okada KI, Miyazawa M, Kitahata Y, Ueno M, Hayami S, Kobayashi R, Yanagisawa A, Yamaue H. Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1054-1061. [PMID: 34933794 DOI: 10.1016/j.ejso.2021.11.137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 11/03/2021] [Accepted: 11/29/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND As the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. METHODS From 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. RESULTS The rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). CONCLUSIONS Measurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.
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Affiliation(s)
- Yoichi Fujita
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Seiko Hirono
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan.
| | - Manabu Kawai
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Motoki Miyazawa
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Yuji Kitahata
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Masaki Ueno
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Shinya Hayami
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Ryohei Kobayashi
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
| | - Akio Yanagisawa
- Department of Pathology, Japanese Red Cross Kyoto Daiichi Hospital, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Japan
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Jung HS, Han Y, Kang JS, Sohn H, Lee M, Lee KB, Kim H, Kwon W, Jang JY. Prediction of malignancy in Main duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Pancreas. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1014-1024. [PMID: 35451206 DOI: 10.1002/jhbp.1161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 02/20/2022] [Accepted: 03/27/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND/PURPOSE Surgical indications of main-duct involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9mm, remain controversial. We aimed to predict malignancy risk of main-duct involved IPMN. METHODS Total 258 patients with main-duct involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main-duct IPMN was classified into segmental and diffuse type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed. RESULTS Among 258, 47 and 211 had pure main-duct (segmental:27, diffuse-type:20) and mixed-type. Malignant IPMN presented higher in main-duct type (66.0%) compared to mixed-type (46.9%). The diffuse-type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5≤MPD <10mm vs. 10≤MPD<15mm vs. MPD≥15mm; 23.4% vs. 40.0% vs. 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9mm with at least one predictive factor had 35.0% of malignancy risk. CONCLUSIONS The invasive IPMN risk was different according to the dilated main-duct pattern. Patients with main-duct type, diffuse-type, MPD ≥10mm, and MPD 5-9mm with at least one predictive factor should be candidates for immediate surgery.
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Affiliation(s)
- Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Heeju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Perioperative risk of pancreatic head resection-nomogram-based prediction of severe postoperative complications as a decisional aid for clinical practice. Langenbecks Arch Surg 2022; 407:1935-1947. [PMID: 35320379 PMCID: PMC9399026 DOI: 10.1007/s00423-021-02426-z] [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: 05/10/2021] [Accepted: 12/29/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE To develop nomograms for pre- and early-postoperative risk assessment of patients undergoing pancreatic head resection. METHODS Clinical data from 956 patients were collected in a prospectively maintained database. A test (n = 772) and a validation cohort (n = 184) were randomly generated. Uni- and multi-variate analysis and nomogram construction were performed to predict severe postoperative complications (Clavien-Dindo Grades III-V) in the test cohort. External validation was performed with the validation cohort. RESULTS We identified ASA score, indication for surgery, body mass index (BMI), preoperative white blood cell (WBC) count, and preoperative alkaline phosphatase as preoperative factors associated with an increased perioperative risk for complications. Additionally to ASA score, BMI, indication for surgery, and the preoperative alkaline phosphatase, the following postoperative parameters were identified as risk factors in the early postoperative setting: the need for intraoperative blood transfusion, operation time, maximum WBC on postoperative day (POD) 1-3, and maximum serum amylase on POD 1-3. Two nomograms were developed on the basis of these risk factors and showed accurate risk estimation for severe postoperative complications (ROC-AUC-values for Grades III-V-preoperative nomogram: 0.673 (95%, CI: 0.626-0.721); postoperative nomogram: 0.734 (95%, CI: 0.691-0.778); each p ≤ 0.001). Validation yielded ROC-AUC-values for Grades III-V-preoperative nomogram of 0.676 (95%, CI: 0.586-0.766) and postoperative nomogram of 0.677 (95%, CI: 0.591-0.762); each p = 0.001. CONCLUSION Easy-to-use nomograms for risk estimation in the pre- and early-postoperative setting were developed. Accurate risk estimation can support the decisional process, especially for IPMN-patients with an increased perioperative risk.
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Margonis GA, Andreatos N, Wang J, Weiss MJ, Wolfgang CL. Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms: a narrative review and discussion of conceptual similarities in tumor progression and recurrence. JOURNAL OF PANCREATOLOGY 2022; 5:36-40. [PMID: 39640535 PMCID: PMC11619816 DOI: 10.1097/jp9.0000000000000083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ("field defect") in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect"may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression; thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.
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Affiliation(s)
| | - Nikolaos Andreatos
- Department of Internal Medicine and Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
| | - Jane Wang
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Matthew J. Weiss
- Department of Surgery, Northwell Health Cancer Institute and Zucker School of Medicine at Hofstra, Lake Success
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Zhuge X, Zhou H, Chen L, Chen H, Chen X, Guo C. The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms. BMC Cancer 2021; 21:1253. [PMID: 34800987 PMCID: PMC8606075 DOI: 10.1186/s12885-021-08986-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). METHODS A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. RESULTS Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p < 0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01-1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78-17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19-9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19-9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). CONCLUSIONS Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.
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Affiliation(s)
- Xiaoling Zhuge
- Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun road, Hangzhou, 310003, China
| | - Hao Zhou
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, Nanjing, 210029, China
| | - Liming Chen
- Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun road, Hangzhou, 310003, China
| | - Hui Chen
- Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun road, Hangzhou, 310003, China
| | - Xiao Chen
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, Nanjing, 210029, China.
| | - Chuangen Guo
- Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun road, Hangzhou, 310003, China.
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Bicu F, Rink JS, Froelich MF, Cyran CC, Rübenthaler J, Birgin E, Röhrich M, Tollens F. Supplemental 18F-FDG-PET/CT for Detection of Malignant Transformation of IPMN-A Model-Based Cost-Effectiveness Analysis. Cancers (Basel) 2021; 13:1365. [PMID: 33803522 PMCID: PMC8002963 DOI: 10.3390/cancers13061365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/15/2021] [Accepted: 03/16/2021] [Indexed: 12/26/2022] Open
Abstract
Accurate detection of malignant transformation and risk-stratification of intraductal papillary mucinous neoplasms (IPMN) has remained a diagnostic challenge. Preliminary findings have indicated a promising role of positron emission tomography combined with computed tomography and 18F-fluorodeoxyglucose (18F-FDG-PET/CT) in detecting malignant IPMN. Therefore, the aim of this model-based economic evaluation was to analyze whether supplemental FDG-PET/CT could be cost-effective in patients with IPMN. Decision analysis and Markov modeling were applied to simulate patients' health states across a time frame of 15 years. CT/MRI based imaging was compared to a strategy with supplemental 18F-FDG-PET/CT. Cumulative costs in US-$ and outcomes in quality-adjusted life years (QALY) were computed based on input parameters extracted from recent literature. The stability of the model was evaluated by deterministic sensitivity analyses. In the base-case scenario, the CT/MRI-strategy resulted in cumulative discounted costs of USD $106,424 and 8.37 QALYs, while the strategy with supplemental FDG-PET/CT resulted in costs of USD $104,842 and a cumulative effectiveness of 8.48 QALYs and hence was cost-saving. A minimum specificity of FDG-PET/CT of 71.5% was required for the model to yield superior net monetary benefits compared to CT/MRI. This model-based economic evaluation indicates that supplemental 18F-FDG-PET/CT could have a favorable economic value in the management of IPMN and could be cost-saving in the chosen setting. Prospective studies with standardized protocols for FDG-PET/CT could help to better determine the value of FDG-PET/CT.
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Affiliation(s)
- Felix Bicu
- Department of Nuclear Medicine, University Hospital Heidelberg, D-68120 Heidelberg, Germany; (F.B.); (M.R.)
| | - Johann S. Rink
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany; (M.F.F.); (F.T.)
| | - Matthias F. Froelich
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany; (M.F.F.); (F.T.)
| | - Clemens C. Cyran
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, D-81377 Munich, Germany; (C.C.C.); (J.R.)
| | - Johannes Rübenthaler
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, D-81377 Munich, Germany; (C.C.C.); (J.R.)
| | - Emrullah Birgin
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany;
| | - Manuel Röhrich
- Department of Nuclear Medicine, University Hospital Heidelberg, D-68120 Heidelberg, Germany; (F.B.); (M.R.)
| | - Fabian Tollens
- Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany; (M.F.F.); (F.T.)
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Sakai A, Masuda A, Eguchi T, Anami T, Nishi K, Furumatsu K, Okabe Y, Kakuyama S, Sato Y, Nishioka C, Sanuki T, Yagi Y, Kobayashi T, Shiomi H, Kodama Y. Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation. J Gastroenterol 2021; 56:285-292. [PMID: 33112991 DOI: 10.1007/s00535-020-01739-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 10/15/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.
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Affiliation(s)
- Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan.
| | - Takaaki Eguchi
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Takahiro Anami
- Department of Gastroenterology, Yodogawa Christian Hospital, Osaka, Japan
| | - Katsuhisa Nishi
- Department of Gastroenterology, Hyogo Prefectural Awaji Medical Center, Sumoto, Japan
| | - Keisuke Furumatsu
- Department of Gastroenterology, Akashi Medical Center, Akashi, Japan
| | - Yoshihiro Okabe
- Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Saori Kakuyama
- Department of Gastroenterology, Takatsuki General Hospital, Takatsuki, Japan
| | - Yu Sato
- Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Tamba, Japan
| | | | - Tsuyoshi Sanuki
- Department of Gastroenterology, Kita-harima Medical Center, Ono, Japan
| | - Yosuke Yagi
- Department of Internal Medicine, Shiso Municipal Hospital, Shiso, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan
| | - Hideyuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan
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Giuffrida P, Biagiola D, Ardiles V, Uad P, Palavecino M, de Santibañes M, Clariá RS, Pekolj J, de Santibañes E, Mazza O. Long-term follow-up of Branch-Duct Intraductal Papillary Mucinous Neoplasms with negative Sendai Criteria: the therapeutic challenge of patients who convert to positive Sendai Criteria. HPB (Oxford) 2021; 23:290-300. [PMID: 32709558 DOI: 10.1016/j.hpb.2020.06.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 04/15/2020] [Accepted: 06/19/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The management of Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) is still controversial. Our objective was to assess the long-term follow-up (FU) of patients with "low-risk" BD-IPMN according to the Sendai-International Consensus Guidelines (ICG-I). METHODS We retrospectively analyzed a cohort of patients with BD-IPMN and Negative Sendai-Criteria (NSC) from January 2004 to October 2019. A univariate analysis was performed to determine factors associated with conversion to Positive Sendai-Criteria (PSC) and malignancy. Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the IGC-I were assessed for the development of malignancy. RESULTS A total of 219 patients were selected and underwent a median 58-month FU. Thirty-seven (17%) patients developed PSC during FU including 12 (5.5%) with malignant lesions. Conversely, 182 patients (83%) did not develop malignancy. The NPV and PPV of ICG-I for malignancy were 100% and 32.4%, respectively. Among patients who developed PSC, those with cancer were >65years (OR = 3.57;p = 0.015) and had significantly higher serum CA-19-9 levels (OR = 5.27;p = 0.007). CONCLUSION The ICG-I is a safe strategy for FU of patients with BD-IPMN. The absence of PSC exclude malignancy. Among patients who develops PSC, the risk of cancer remains low and surgery should be decided according to their surgical risk and life expectancy.
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Affiliation(s)
- Pablo Giuffrida
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - David Biagiola
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Victoria Ardiles
- HPB Surgery Section and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Pedro Uad
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Martin Palavecino
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Martín de Santibañes
- HPB Surgery Section and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Rodrigo S Clariá
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Juan Pekolj
- HPB Surgery Section and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Eduardo de Santibañes
- HPB Surgery Section and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina
| | - Oscar Mazza
- HPB Surgery Section, Department of General Surgery, Hospital Italiano de Buenos Aires, Tte. Gral. Juan Domingo Perón 4190, C1199ABD, Buenos Aires, Argentina.
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Vaalavuo Y, Siiki A, Antila A, Rinta-Kiikka I, Sand J, Laukkarinen J. The European evidence-based guidelines on pancreatic cystic neoplasms (PCN) in clinical practice: The development of relative and absolute indications for surgery during prospective IPMN surveillance. Pancreatology 2020; 20:1393-1398. [PMID: 32938553 DOI: 10.1016/j.pan.2020.09.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 08/26/2020] [Accepted: 09/01/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The European evidence-based guidelines on PCN recommend surveillance for IPMN patients who are fit for surgery but who have no indication for immediate surgery. Our aim was to demonstrate the feasibility of the new guidelines in clinical practice. METHODS This is a prospective cohort study of patients included in the IPMN register in Tampere University Hospital, Finland. IPMN was diagnosed from January 1, 2013 to December 31, 2018. Patients were analyzed for surveillance and indications for surgery according to the European guidelines on PCN. RESULTS Out of 128 patients in register 23 was decided to operate upfront and 105 patients were included in the surveillance programme. Invasive carcinoma was found in 4/23 of operated patients. Median follow-up time was 26 months (6-69). Median size of the cyst at the beginning and end of the surveillance was 16 mm (4-58 mm). During surveillance 0/105 (0.0%) patients had or developed an absolute indication for surgery. Relative indication for surgery was present in 8/105 (7.6%) patients in the beginning surveillance and 9/105 (8.6%) patients developed at least one relative indication for surgery during surveillance. From the surveillance cohort 2/105 patients were operated. Surveillance was abandoned in 15/105 (14.1%) patients all due to poor general condition or other medical conditions. CONCLUSIONS In clinical practice, surveillance of IPMN according to the European guidelines on PCN is feasible. Among our patients 16% were detected to have relative indications for surgery during the median 26 (range 3-135) months of surveillance. Nearly 15% became surgically unfit during surveillance period.
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Affiliation(s)
- Yrjö Vaalavuo
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Antti Siiki
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anne Antila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Irina Rinta-Kiikka
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Dept. of Radiology, Tampere University Hospital, Tampere, Finland
| | - Juhani Sand
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
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Ohno E, Kawashima H, Ishikawa T, Iida T, Suzuki H, Uetsuki K, Yashika J, Yamada K, Yoshikawa M, Gibo N, Aoki T, Kataoka K, Mori H, Hirooka Y, Fujishiro M. Can contrast-enhanced harmonic endoscopic ultrasonography accurately diagnose main pancreatic duct involvement in intraductal papillary mucinous neoplasms? Pancreatology 2020; 20:887-894. [PMID: 32651080 DOI: 10.1016/j.pan.2020.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/02/2020] [Accepted: 06/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Main pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS). METHODS This study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis. RESULTS A total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45-8.98), age (OR, 5.70; 95% CI: 1.47-22.2), cyst size (OR, 2.45; 95% CI:1.04-5.78) and MN size (OR, 7.05; 95% CI:2.48-20.0) were significant for malignant BD-IPMNs. CONCLUSIONS MPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.
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Affiliation(s)
- Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hirotaka Suzuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kota Uetsuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Jun Yashika
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Yamada
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masakatsu Yoshikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Noriaki Gibo
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshinori Aoki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kunio Kataoka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroshi Mori
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Gastroenterological Oncology, Fujita Health University, Fujita Health University of Medicine, Toyoake, Aichi, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Hirono S, Yamaue H. Surgical strategy for intraductal papillary mucinous neoplasms of the pancreas. Surg Today 2020; 50:50-55. [PMID: 31807871 PMCID: PMC6923258 DOI: 10.1007/s00595-019-01931-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 10/08/2019] [Indexed: 12/17/2022]
Abstract
The current treatment strategy for intraductal papillary mucinous neoplasms (IPMNs), based on the international consensus guideline, has been accepted widely. However, reported outcomes after surgical resection for IPMN show that once the tumor progresses to invasive intraductal papillary mucinous carcinoma (IPMC), recurrence is not uncommon. The surgical treatment for IPMN is invasive and sometimes followed by complications. Therefore, the best timing for resection might be at the point when high-grade dysplasia (HGD) is evident. According to previous reports, main duct type IPMN has a high malignant potential and its surgical resection is universally accepted, whereas, the incidence of HGD/invasive IPMC in branch duct and mixed type IPMNs is thought to be lower. In addition to mural nodules and a dilated main pancreatic duct, cytology and measurement of the carcinoembryonic antigen level in the pancreatic juice might be useful to differentiate HGD/invasive IPMC from low-grade dysplasia. The nomogram proposed recently to predict the risk of HGD/invasive IPMC in IPMN patients might help surgeons decide on the best treatment strategy, depending on the patient's age and general condition. Second resection for high-risk lesions in the remnant pancreas might improve the survival of IPMN patients.
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Affiliation(s)
- Seiko Hirono
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
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22
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Main duct and mixed type intraductal papillary mucinous neoplasms without enhancing mural nodules: Duct diameter of less than 10 mm and segmental dilatation of main pancreatic duct are findings support surveillance rather than immediate surgery. Pancreatology 2019; 19:1054-1060. [PMID: 31611130 DOI: 10.1016/j.pan.2019.09.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 09/14/2019] [Accepted: 09/22/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN. METHODS We performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions. RESULTS The rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155-5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152-8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928-23.833, P < 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of <10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001). CONCLUSIONS MD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation <10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.
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23
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Carcinoembryonic antigen level in the pancreatic juice is effective in malignancy diagnosis and prediction of future malignant transformation of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 2019; 54:1029-1037. [PMID: 31111221 DOI: 10.1007/s00535-019-01592-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 05/09/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND The present study aimed to determine the ability of diagnosing malignancy and predicting malignant transformation in patients with IPMN using carcinoembryonic antigen (CEA) level in the pancreatic juice. METHODS We enrolled patients with IPMN who underwent endoscopic retrograde pancreatography (ERP) between 2002 and 2018. We examined the ability of diagnosing malignancy in 63 patients who underwent surgery (surgical group). Furthermore, we examined the value of predicting malignant transformation in 52 patients who underwent follow-up for over 1 year after ERP (follow-up group). RESULTS In the surgical group, the overall sensitivity and specificity of CEA level (≥ 97 ng/ml) in the pancreatic juice for diagnosing malignancy were 45% and 100%, respectively. The specificity was excellent for all IPMN types; however, the sensitivity was highest in main duct type, followed by mixed type and branch duct type. In the follow-up group, malignant transformation was observed in four patients (7.7%) during the follow-up, and the median time until malignant transformation was 58 months. High CEA level in the pancreatic juice demonstrated a statistically significant difference in multivariate analysis and was found to be an independent predictor of malignant transformation (hazard ratio 17; P = 0.02). The cumulative malignant transformation rate was significantly higher in the high CEA group than that in the low CEA group (5-year cumulative malignant transformation rates, 69% vs. 0%, P < 0.001). CONCLUSIONS Carcinoembryonic antigen level in the pancreatic juice is useful not only in diagnosing malignancy but also in predicting future malignant transformations in IPMN patients receiving follow-up.
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Tanaka M, Heckler M, Liu B, Heger U, Hackert T, Michalski CW. Cytologic Analysis of Pancreatic Juice Increases Specificity of Detection of Malignant IPMN-A Systematic Review. Clin Gastroenterol Hepatol 2019; 17:2199-2211.e21. [PMID: 30630102 DOI: 10.1016/j.cgh.2018.12.034] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can progress to cancer. Biomarkers have been identified that were reported to increase the accuracy of identification of malignant lesions; we performed a systematic review of the accuracy of these markers. METHODS We performed a systematic review of published studies on biomarkers of malignant IPMNs by searching MEDLINE and Web of Science databases from January 2005 through December 2017. Our methods were developed based on the Meta-analysis Of Observational Studies in Epidemiology guidelines. Pooled sensitivity, specificity, receiver operating characteristic curves, and their respective areas under the curve (AUC) were calculated from groups of markers (cell-, protein-, or DNA-based) measured in samples collected before and after surgery. A hypothetical test model was developed to determine how to meaningfully amend the revised Fukuoka guidelines, focusing on increasing test specificity for patients with IPMNs that have worrisome features. RESULTS We collected data from 193 published studies, comprising 12,297 patients, that analyzed 7 preoperative and 21 postoperative markers of IPMNs. The 3 biomarkers that identified malignant IPMNs with the largest AUC values were pancreatic juice cytology (AUC, 0.84; sensitivity, 0.54; specificity, 0.91), serum protein carbohydrate antigen 19-9 (AUC, 0.81; sensitivity, 0.45; specificity, 0.90), and cyst fluid cytology (AUC, 0.82; sensitivity, 0.57; specificity, 0.84). A combination of cytologic and immunohistochemical analysis of MUC1 and MUC2 in pancreatic juice samples identified malignant IPMNs with the largest AUC and sensitivity values (AUC, 0.85; sensitivity, 0.85; specificity, 0.65). In a test model, inclusion of cytologic analysis of pancreatic juice in the guideline algorithm significantly increased the specificity of detection of malignant IPMNs. CONCLUSIONS In a systematic review, we found cytologic analysis of pancreatic juice to have the greatest effect in increasing the specificity of detection of malignant IPMNs. We propose addition of this test to the Fukuoka guidelines for assessment of patients with IPMNs with worrisome features.
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Affiliation(s)
- Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Bing Liu
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany.
| | - Christoph W Michalski
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld, Germany; Department of Surgery, Halle University Hospital, Martin Luther University Halle-Wittenberg, Halle, Germany
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25
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Multi-institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis for Prediction of High-risk Intraductal Papillary Mucinous Neoplasms of the Pancreas. Ann Surg 2019; 268:340-347. [PMID: 28700444 DOI: 10.1097/sla.0000000000002421] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Preliminary work by our group suggested that proteins within the pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought to externally validate these markers and determine whether their inclusion in a preoperative clinical nomogram could increase diagnostic accuracy. SUMMARY BACKGROUND DATA IPMN is the most common radiographically identifiable precursor to pancreatic cancer; however, the timing and frequency of its malignant progression are unknown, and there are currently no reliable preoperative tests that can determine the grade of dysplasia in IPMN. METHODS Clinical and radiographic data, as well as CF samples, were obtained from 149 patients who underwent resection for IPMN at 1 of 3 institutions. High-risk disease was defined as the presence of high-grade dysplasia or invasive carcinoma. Multianalyte bead array analysis (Luminex) of CF was performed for 4 protein markers that were previously associated with high-risk disease. Logistic regression models were fit on training data, with and without adjustment for a previously developed clinical nomogram and validated with an external testing set. The models incorporating clinical risk score were presented graphically as nomograms. RESULTS Within the group of 149 resected patients, 89 (60%) had low-risk disease, and 60 (40%) had high-risk disease. All 4 CF markers (MMP9, CA72-4, sFASL, and IL-4) were overexpressed in patients with high-risk IPMN (P < 0.05). Two predictive models based on preselected combinations of CF markers had concordance indices of 0.76 (Model-1) and 0.80 (Model-2). Integration of each CF marker model into a previously described clinical nomogram leads to increased discrimination compared with either the CF models or nomogram alone (c-indices of 0.84 and 0.83, respectively). CONCLUSIONS This multi-institutional study validated 2 CF protein marker models for preoperative identification of high-risk IPMN. When combined with a clinical nomogram, the ability to predict high-grade dysplasia was even stronger.
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Circulating Leptin and Branched Chain Amino Acids-Correlation with Intraductal Papillary Mucinous Neoplasm Dysplastic Grade. J Gastrointest Surg 2019; 23:966-974. [PMID: 30215202 PMCID: PMC6416083 DOI: 10.1007/s11605-018-3963-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Accepted: 08/31/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND The most common type of mucinous pancreatic cyst that may progress to pancreatic cancer is intraductal papillary mucinous neoplasm (IPMN). Low-risk IPMN with low-/moderate-grade dysplasia may be safely watched, whereas high-risk IPMN with high-grade dysplasia or invasive components should undergo resection. However, there is currently no reliable means of making this distinction. We hypothesize that blood concentrations of insulin resistance biomarkers may aid in the differentiation of low- and high-risk IPMN. METHODS Plasma/serum was collected from consented patients undergoing pancreatic resection. IPMN diagnosis and dysplastic grade were confirmed by surgical pathology. The study included 235 IPMN (166 low/moderate grade, 39 high grade, 30 invasive). Circulating levels of leptin, branched chain amino acids (BCAA), and retinol-binding protein-4 (RBP-4) were measured by enzyme-linked immunoassay and correlated with surgical pathology. RESULTS Circulating leptin levels (mean ± SE) were significantly higher in patients with low/moderate IPMN than in high-grade/invasive IPMN (15,803 ± 1686 vs. 10,275 ± 1228 pg/ml; p = 0.0086). Leptin levels were positively correlated with BMI (r = 0.65, p < 0.0001) and were higher in females (p < 0.0001). Stratified analysis showed that mean leptin levels were significantly different between low/moderate and high/invasive IPMNs only in females (24,383 ± 2748 vs. 16,295 ± 2040 pg/ml; p = 0.020). Conversely, circulating BCAA levels were lower in low/moderate IPMN than in high-grade/invasive IPMN (0.38 ± 0.007 vs. 0.42 ± 0.01 mM; p = 0.011). No significant differences in RBP-4 levels were observed. CONCLUSIONS Circulating leptin in females and BCAA correlates with IPMN dysplastic grade and, if combined with clinical characteristics, have the potential to improve clinical decision-making.
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Simpson RE, Cockerill NJ, Yip-Schneider MT, Ceppa EP, House MG, Zyromski NJ, Nakeeb A, Al-Haddad MA, Schmidt CM. Clinical criteria for integrated molecular pathology in intraductal papillary mucinous neoplasm: less is more. HPB (Oxford) 2019; 21:574-581. [PMID: 30293868 DOI: 10.1016/j.hpb.2018.09.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 08/13/2018] [Accepted: 09/03/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND For pancreatic cysts with negative cytology, Integrated Molecular Pathology (IMP) is a malignancy risk score integrating clinical criteria with pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD) diameter, integrated clinical criteria are not International Consensus Guidelines High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD diameter could simplify the IMP and better distinguish invasive/malignant disease. METHODS Records of >1100 patients with IPMN were reviewed retrospectively. Sensitivity, specificity, and accuracy of conventional IMP for invasive/malignant disease was compared to DNA profile including only MPD ≥10mm (IMP-10.) Invasive outcomes were invasive-IPMN/adenocarcinoma on surgical pathology, pathologic or radiographic evidence of invasive/metastatic disease during surveillance. Malignant outcomes included high grade dysplastic IPMN (HGD-IPMN). RESULTS 225 patients who met study criteria underwent 283 IMP evaluations: 98 followed by surgery, 185 followed by ≥ 23 months surveillance. IMP-10 had greater specificity (90.1% vs. 73.7%) and accuracy (89.8% vs. 74.2%) for invasive disease compared to IMP in surgery + surveillance patients, but lower sensitivity (77.8% vs. 88.9%). Trends were similar in surgery patients alone and malignant outcome analyses. CONCLUSION IMP-10 excludes less-reliable clinical factors resulting in greater accuracy in predicting invasive/malignant disease and fewer patients with benign disease being recommended for surgery.
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Affiliation(s)
- Rachel E Simpson
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Nathan J Cockerill
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Michele T Yip-Schneider
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA
| | - Eugene P Ceppa
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA
| | - Michael G House
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Nicholas J Zyromski
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Attila Nakeeb
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA
| | - Mohammad A Al-Haddad
- Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA; Indiana University School of Medicine, Department of Medicine, Division of Gastroenterology, 702 Rotary Cir., Suite 225, Indianapolis, IN 46202, USA
| | - C M Schmidt
- Indiana University School of Medicine, Department of Surgery, 545 Barnhill Dr., Indianapolis, IN 46202, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, 550 University Blvd., Indianapolis, IN 46202, USA; Indiana University School of Medicine, Department of Biochemistry/Molecular Biology, 635 Barnhill Dr., Medical Sciences Building Rm 4053, Indianapolis, IN 46202, USA; Walther Oncology Center, 950 W. Walnut St., Indianapolis, IN 46202, USA; Indiana University Simon Cancer Center, 535 Barnhill Dr., Indianapolis, IN 46202, USA.
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Abstract
Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.
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Schmidt CR, Cloyd J. What is the Incidence of Malignancy in Resected IPMN? An Analysis of Over 100 U.S. Institutions in a Single Year. Ann Surg Oncol 2018; 25:1797-1798. [PMID: 29675763 DOI: 10.1245/s10434-018-6478-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Indexed: 11/18/2022]
Affiliation(s)
- Carl R Schmidt
- Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
| | - Jordan Cloyd
- Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA
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Vanella G, Crippa S, Archibugi L, Arcidiacono PG, Delle Fave G, Falconi M, Capurso G. Meta-analysis of mortality in patients with high-risk intraductal papillary mucinous neoplasms under observation. Br J Surg 2018; 105:328-338. [PMID: 29405253 DOI: 10.1002/bjs.10768] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 06/25/2017] [Accepted: 10/26/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Although consensus guidelines suggest that patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) should have surgery, a non-operative strategy is often selected in patients who are poor surgical candidates. The aim was to determine the risk of disease-related death from IPMN in patients with worrisome features or high-risk stigmata who were kept under observation. METHODS A PubMed literature search was undertaken of articles published from August 1992 to June 2016 (updated October 2017). The methodology was developed from PRISMA and MOOSE checklists. Incidence proportions and rates of overall and IPMN-related deaths were calculated, with subgroup analyses for main-duct/mixed-type and branch-duct IPMNs. Quality of the studies, publication bias and heterogeneity were explored. RESULTS Six studies reported data on overall mortality and eight described disease-specific mortality for 556 patients during follow-up ranging from 24·9 to 60·0 months. Pooled rates of overall and IPMN-related mortality were 30·9 (95 per cent c.i. 19·6 to 45·1) and 11·6 (6·0 to 21·2) per cent respectively. The pooled incidence rate for overall mortality was substantially higher than that for IPMN-related mortality: 78 (95 per cent c.i. 44 to 111) and 23 (9 to 37) per 1000 patient-years respectively. The pooled incidence rate for disease-specific mortality was considerably lower for branch-duct than for main-duct or mixed-type IPMNs: 5 (0 to 10) and 32 (12 to 52) per 1000 patient-years respectively. CONCLUSION In patients unfit for surgery, IPMN-related mortality among patients with worrisome features and high-risk stigmata is low, and the risk of death from other causes much higher.
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Affiliation(s)
- G Vanella
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
| | - S Crippa
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - L Archibugi
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
| | - P G Arcidiacono
- Pancreato-Biliary Endoscopy Division and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, Milan, Italy
| | - G Delle Fave
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy
| | - G Capurso
- Digestive and Liver Disease Unit, Sant'Andrea Hospital, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy
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31
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Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas: A Report from The Pancreatic Surgery Consortium. Ann Surg 2017; 267:157-163. [PMID: 28079542 DOI: 10.1097/sla.0000000000002015] [Citation(s) in RCA: 109] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. SUMMARY BACKGROUND DATA IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. METHODS Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. RESULTS We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. CONCLUSIONS For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.
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Tanaka M, Fernández-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 2017; 17:738-753. [PMID: 28735806 DOI: 10.1016/j.pan.2017.07.007] [Citation(s) in RCA: 1110] [Impact Index Per Article: 138.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 07/12/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023]
Abstract
The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found. Whether or not it is safe to do so, as well as the method and interval of surveillance, has generated substantial debate. Based on a consensus symposium held during the meeting of the International Association of Pancreatology in Sendai, Japan, in 2016, the working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN. As the working group did not recognize the need for major revisions of the guidelines, we made only minor revisions and added most recent articles where appropriate. The present guidelines include updated information and recommendations based on our current understanding, and highlight issues that remain controversial or where further research is required.
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Affiliation(s)
- Masao Tanaka
- Department of Surgery, Shimonoseki City Hospital, Shimonoseki, Japan.
| | | | - Terumi Kamisawa
- Department of Gastroenterology, Komagome Metropolitan Hospital, Tokyo, Japan
| | - Jin Young Jang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Philippe Levy
- Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hopital Beaujon, Clichy Cedex, France
| | - Takao Ohtsuka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Yasuhiro Shimizu
- Dept. of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | - Minoru Tada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Christopher L Wolfgang
- Cameron Division of Surgical Oncology and The Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
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33
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Abstract
Management of pancreatic cystic lesions relies on patients' clinical presentation, imaging, and endoscopic ultrasound. Current research in basic science, radiology, and endoscopy is evolving and making progress in this condition which is relatively common in the general population. This review focuses on the recent endoscopic ultrasound approaches to the diagnosis of these pancreatic disorders.
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Affiliation(s)
- Michael J Bartel
- Department of Medicine, Section of Gastroenterology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA
| | - Massimo Raimondo
- Department of Gastroenterology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
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Crippa S, Bassi C, Salvia R, Malleo G, Marchegiani G, Rebours V, Levy P, Partelli S, Suleiman SL, Banks PA, Ahmed N, Chari ST, Fernández-Del Castillo C, Falconi M. Low progression of intraductal papillary mucinous neoplasms with worrisome features and high-risk stigmata undergoing non-operative management: a mid-term follow-up analysis. Gut 2017; 66:495-506. [PMID: 26743012 DOI: 10.1136/gutjnl-2015-310162] [Citation(s) in RCA: 140] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 11/15/2015] [Accepted: 11/16/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To evaluate mid-term outcomes and predictors of survival in non-operated patients with pancreatic intraductal papillary mucinous neoplasms (IPMNs) with worrisome features or high-risk stigmata as defined by International Consensus Guidelines for IPMN. Reasons for non-surgical options were physicians' recommendation, patient personal choice or comorbidities precluding surgery. METHODS In this retrospective, multicentre analysis, IPMNs were classified as branch duct (BD) and main duct (MD), the latter including mixed IPMNs. Univariate and multivariate analysis for overall survival (OS) and disease-specific survival (DSS) were obtained. RESULTS Of 281 patients identified, 159 (57%) had BD-IPMNs and 122 (43%) had MD-IPMNs; 50 (18%) had high-risk stigmata and 231 (82%) had worrisome features. Median follow-up was 51 months. The 5-year OS and DSS for the entire cohort were 81% and 89.9%. An invasive pancreatic malignancy developed in 34 patients (12%); 31 had invasive IPMNs (11%) and 3 had IPMN-distinct pancreatic ductal adenocarcinoma (1%). Independent predictors of poor DSS in the entire cohort were age >70 years, atypical/malignant cyst fluid cytology, jaundice and MD >15 mm. Compared with MD-IPMNs, BD-IPMNs had significantly better 5-year OS (86% vs 74.1%, p=0.002) and DSS (97% vs 81.2%, p<0.0001). Patients with worrisome features had better 5-year DSS compared with those with high-risk stigmata (96.2% vs 60.2%, p<0.0001). CONCLUSIONS In elderly patients with IPMNs that have worrisome features, the 5-year DSS is 96%, suggesting that conservative management is appropriate. By contrast, presence of high-risk stigmata is associated with a 40% risk of IPMN-related death, reinforcing that surgical resection should be offered to fit patients.
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Affiliation(s)
- Stefano Crippa
- Division of Pancreatic Surgery, Università Politecnica delle Marche, Ancona, Italy.,Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giuseppe Malleo
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy.,Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Vinciane Rebours
- Service de Gastroenterologie-Pancreatologie, Hopital Beaujon, APHP, Université Paris Diderot, DHU UNITY, Clichy, France
| | - Philippe Levy
- Service de Gastroenterologie-Pancreatologie, Hopital Beaujon, APHP, Université Paris Diderot, DHU UNITY, Clichy, France
| | - Stefano Partelli
- Division of Pancreatic Surgery, Università Politecnica delle Marche, Ancona, Italy.,Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy
| | - Shadeah L Suleiman
- Center for Pancreatic Disease, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Peter A Banks
- Center for Pancreatic Disease, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Nazir Ahmed
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
| | - Suresh T Chari
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Massimo Falconi
- Division of Pancreatic Surgery, Università Politecnica delle Marche, Ancona, Italy.,Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy
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35
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The Clinical Indications for Limited Surgery of Intraductal Papillary Mucinous Neoplasms of the Pancreas. World J Surg 2016; 41:1358-1365. [DOI: 10.1007/s00268-016-3824-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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36
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Affiliation(s)
- Alexandra M Roch
- Department of Surgery, Indiana University School of Medicine, 980 W Walnut Street R3-C541, Indianapolis, IN 46202, USA
| | - Christian Max Schmidt
- IU Health Pancreatic Cyst and Cancer Early Detection Center, Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, EH 129, Indianapolis, IN 46202, USA.
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Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current State of the Art and Ongoing Controversies. Ann Surg 2016; 263:908-17. [PMID: 26727096 DOI: 10.1097/sla.0000000000001567] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms.
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38
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Risk Factors for Progression or Malignancy in Main-Duct and Mixed-Type Intraductal Papillary Mucinous Neoplasm of the Pancreas. Pancreas 2016; 45:1027-31. [PMID: 26692447 DOI: 10.1097/mpa.0000000000000592] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy. METHODS Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion. RESULTS Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy. CONCLUSIONS A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.
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Park JS, Seo DW, Song TJ, Park DH, Lee SS, Lee SK, Kim MH. Endoscopic ultrasound-guided ablation of branch-duct intraductal papillary mucinous neoplasms: Feasibility and safety tests using porcine gallbladders. Dig Endosc 2016; 28:599-606. [PMID: 26856542 DOI: 10.1111/den.12628] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Revised: 01/19/2016] [Accepted: 02/03/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Radiofrequency ablation (RFA) and ethanol ablation are accepted methods of tissue destruction for treating cystic tumors. The aim of the present study was to evaluate the feasibility, efficacy, and safety of endoscopic ultrasound (EUS)-guided ablation using normal porcine gallbladders as a substitute model for branch-duct intraductal papillary mucinous neoplasms (BD-IPMN). METHODS Six adult mini pigs were included in this prospective study. EUS-guided RFA with or without ethanol ablation of the gallbladder was carried out using a prototype 18-gauge endoscopic RFA electrode, and RFA and ethanol ablation were done in a single session. Outcomes were assessed in terms of macroscopic and microscopic evaluations of the treated gallbladders. RESULTS The prototype RFA electrode was used for ablation of the mucosa, aspiration of the internal contents of the gallbladder, and ethanol injection. RFA plus ethanol lavage resulted in a greater mean percentage of denuded gallbladder mucosa (97.5%) than RFA alone (55.8%). Effects of ablation extending to the cystic duct and partially denuded cystic duct mucosae were detected in five of the six pigs. There were no major procedure-related adverse events. CONCLUSIONS EUS-guided ablation of the gallbladder mucosa was feasible and effective in the porcine model. Additional studies will be required to fully assess the risk of procedure-related damage to the main pancreatic duct before using this technique in a clinical setting.
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Affiliation(s)
- Jin-Seok Park
- Digestive Disease Center, Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea
| | - Dong-Wan Seo
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Tae Jun Song
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Do Hyun Park
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sang Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sung Koo Lee
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Myung-Hwan Kim
- Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Shimura T, Kofunato Y, Okada R, Yashima R, Okada K, Araki K, Hosouchi Y, Kuwano H, Takenoshita S. MIB-1 labeling index, Ki-67, is an indicator of invasive intraductal papillary mucinous neoplasm. Mol Clin Oncol 2016; 5:317-322. [PMID: 27446570 DOI: 10.3892/mco.2016.908] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 05/09/2016] [Indexed: 01/25/2023] Open
Abstract
Despite strict criteria for the observation of intraductal papillary mucinous neoplasm (IPMN), it remains difficult to distinguish invasive IPMN from non-invasive IPMN. The aim of the present study was to identify an indicator of invasive IPMN. The present study retrospectively evaluated 53 patients (28 with non-invasive and 25 with invasive IPMN) who underwent resection of IPMN, and examined the usefulness of the MIB-1 labeling index as an indicator of invasive IPMN. The MIB-1 labeling indexes in patients with invasive IPMN were significantly higher compared with those with non-invasive IPMN (P<0.001). A receiver operating characteristic curve revealed that the area under the curve was 0.822. These results suggested that a cut-off level for the MIB-1 labeling index should be set to 15.5% to distinguish invasive from non-invasive IPMN. A multivariate analysis using a logistic regression model revealed the MIB-1 labeling index (hazard ratio, 18.692; 95% confidential interval, 4.171-83.760; P<0.001) and the existence of mural nodules (hazard ratio, 6.187, 95% confidential interval, 1.039-36.861; P=0.045) were predictive factors for invasive IPMN. However, no statistically significant differences were observed between patients with a lower MIB-1 labeling index and patients with a higher MIB-1 labeling index (P=0.798). The MIB-1 labeling index must be considered as a candidate for the classification of IPMN.
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Affiliation(s)
- Tatsuo Shimura
- Department of Cancer Biology and Electronics, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Yasuhide Kofunato
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Ryo Okada
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Rei Yashima
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| | - Koji Okada
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
| | - Kenichiro Araki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
| | - Yasuo Hosouchi
- Department of Surgery and Laparoscopic Surgery, Gunma Prefecture Saiseikai-Maebashi Hospital, Maebashi, Gunma 371-0821, Japan
| | - Hiroyuki Kuwano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan
| | - Seiichi Takenoshita
- Department of Organ Regulatory Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
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Main-duct Intraductal Papillary Mucinous Neoplasm: High Cancer Risk in Duct Diameter of 5 to 9 mm. Ann Surg 2016; 262:875-80; discussion 880-1. [PMID: 26583679 DOI: 10.1097/sla.0000000000001462] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The 2012 international consensus guidelines for the management of intraductal papillary mucinous neoplasms (IPMN) recommend surgical treatment in main-duct IPMN patients with a main pancreatic duct (MPD) diameter of ≥10 mm. Aim of the present study was to analyze cancer risk in patients with an MPD diameter of less than 10 mm. METHODS All consecutive patients (prospective data protocol) with histological proof of IPMN who underwent surgery between January 2004 and December 2013 were included in the study. Clinical characteristics, particularly preoperative imaging with regard to morphology of the MPD, were correlated with final histopathology. RESULTS Among a total of 605 patients who underwent surgery for IPMN, there were 320 patients with MPD involvement, 238 patients with mixed-type IPMN, and 82 patients with main-duct IPMN alone. The total malignancy rate including high-grade dysplasia and invasive carcinoma in IPMNs with MPD involvement was 68%. When the MPD diameter was 5 to 9 mm, malignancy rate was 59%, whereas in MPD diameter more than 10 mm, it was 73%. No statistical correlations were observed between MPD diameter and clinical and/or IPMN features such as age, cyst location, mural nodules, serum tumor markers, or bilirubin. CONCLUSIONS Main-duct IPMNs with a MPD between 5 and 9 mm already bear a significant risk of malignancy. Therefore, surgical treatment is clearly indicated in patients with a MPD diameter of ≥5 mm and the 2012 guidelines should be discussed and adapted with regard to this topic.
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Follow-up of asymptomatic pancreatic cysts in clinical practice: A vignette questionnaire. Pancreatology 2016; 16:416-22. [PMID: 26973156 DOI: 10.1016/j.pan.2016.02.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 02/11/2016] [Accepted: 02/12/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES In absence of evidence-based guidelines of pancreatic cystic neoplasms (PCN), the management might vary among physicians. The aim of this survey was to assess the attitude of Dutch gastroenterologists (GE) towards the management of asymptomatic PCNs. METHODS An anonymous online questionnaire was distributed to all practicing GE (n = 381) in The Netherlands, in which four vignette patients with PCN were presented. RESULTS In total 45% of GE responded. Most respondents would perform surveillance for a 10 mm PCN (78%) mainly with an interval of one year (57%). A shorter interval of three (26%) or six (57%) months was chosen for a 25 mm BD-IPMN. Ultrasound was recommended for surveillance by 19% for a 10 mm cyst. GE with EUS experience were more likely to apply EUS for surveillance of 10 mm cyst than those without (56% vs 28%; p < 0.001). The presence of a branch-duct intraductal mucinous neoplasm (BD-IPMN) with a mural nodule, dilated pancreatic duct (8 mm) or increased serum CA 19.9 (300 U/ml) were considered an indication for resection by respectively 88%, 68% and 51% of respondents. CONCLUSION Dutch GE demonstrate substantial variability in the management of asymptomatic PCNs. A significant proportion of general GE still use ultrasound for surveillance of small PCNs, while GE with EUS experience were more likely to perform EUS. The presence of risk factors for malignant degeneration of IPMN were not recognized by a substantial proportion of GE. Data on the natural history of PCNs is required to provide input for evidence-based guidelines, which should lead to a more uniform approach.
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Pulvirenti A, Marchegiani G, Malleo G, Borin A, Allegrini V, Bassi C, Salvia R. Cystic Neoplasm of the Pancreas. Indian J Surg 2016; 77:387-92. [PMID: 26722201 DOI: 10.1007/s12262-015-1363-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 09/30/2015] [Indexed: 01/04/2023] Open
Abstract
Cystic neoplasms of the pancreas (CNPs) are not considered as rare entities any more. Imaging-based population studies attested an overall prevalence of 2 %, but that becomes five times higher on individuals of more than 70 year old. This family of neoplasms includes a wide spectrum of benign, borderline, and malignant lesions whose actual biological behavior has not been completely clarified yet. Moreover, the management of CNPs still represents a challenge for gastrointestinal (GI) specialists. While many CNPs have an indolent behavior that justifies surveillance, others should be resected because of the risk of progression to invasive cancer. Due to the high morbidity related to pancreatic resections, the surgeon should balance very carefully the advantages of a radical resection with the risks of an unrequested dangerous procedure. We reviewed the current issues regarding CNPs, with a particular focus on the clinical and radiological features that are integrated in the current guidelines and that drive the management of these patients.
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Affiliation(s)
- Alessandra Pulvirenti
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Giuseppe Malleo
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Alex Borin
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Valentina Allegrini
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, The Pancreas Institute, G.B. Rossi Hospital, University of Verona Hospital Trust, P. Le L.A. Scuro 10, Verona, 37134 Italy
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Nagata N, Kawazoe A, Mishima S, Wada T, Shimbo T, Sekine K, Watanabe K, Imbe K, Kojima Y, Kumazawa K, Mihara F, Tokuhara M, Edamoto Y, Igari T, Yanase M, Mizokami M, Akiyama J, Uemura N. Development of Pancreatic Cancer, Disease-specific Mortality, and All-Cause Mortality in Patients with Nonresected IPMNs: A Long-term Cohort Study. Radiology 2016; 278:125-34. [DOI: 10.1148/radiol.2015150131] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Ceppa EP, Roch AM, Cioffi JL, Sharma N, Easler JJ, DeWitt JM, House MG, Zyromski NJ, Nakeeb A, Schmidt CM. Invasive, mixed-type intraductal papillary mucinous neoplasm: Superior prognosis compared to invasive main-duct intraductal papillary mucinous neoplasm. Surgery 2015; 158:937-44; discussion 944-5. [DOI: 10.1016/j.surg.2015.06.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 05/01/2015] [Accepted: 06/03/2015] [Indexed: 01/27/2023]
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Abstract
PURPOSE OF REVIEW Our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has remarkably grown within the last decade; nonetheless there is still an ongoing controversy if the majority of these potentially malignant neoplasms need to be resected or if observation in a subset is well tolerated. RECENT FINDINGS Novel cyst fluid biomarkers, like Gnas mutations or mab DAS-1, could play a pivotal role in the distinction of IPMN vs. other cystic lesions, in the sub-classification of IPMN and in the detection of IPMN with high-grade dysplasia or invasive cancer. Other recent studies focused on natural history of minimal- and extensive-mixed IPMN and the safety of the 2012 AIP guidelines. Small series also described that observation can be an option in selected frail patients with MD-IPMN. Further, data from a large European multicenter study analysis indicated that patients with IPMN do not have an increased frequency of extrapancreatic malignancies. SUMMARY Increasing knowledge about the nature of IPMN and their subtypes has resulted in an individualized approach in diagnosis and treatment. Owing to the availability of accurate diagnostic instruments, timing and indication for pancreatic resection have become more selective, sparing patients with harmless IPMN from major surgery.
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Fritz S, Lerch MM. Natural History and Management of Intraductal Papillary Mucinous Neoplasms: Current Evidence. VISZERALMEDIZIN 2015; 31:25-30. [PMID: 26288612 PMCID: PMC4433132 DOI: 10.1159/000375186] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background With the use of modern cross-sectional abdominal imaging modalities, an increasing number of cystic pancreatic lesions are identified incidentally. Although there is no pathological diagnosis available in most cases, it is believed that the majority of these lesions display small branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) of the pancreas. Even though a number of large clinical series have been published, many uncertainties remain with regard to this entity of mucinous cystic neoplasms. Methods Systematic literature review. Results Main-duct (MD) and mixed-type IPMNs harbor a high risk of malignant transformation. It is conceivable that most IPMNs with involvement of the main duct tend to progress to invasive carcinoma over time. Thus, formal oncologic resection is the treatment of choice in surgically fit patients. In contrast, the data regarding BD-IPMN remain equivocal, resulting in conflicting concepts. To date, it is not clear whether and which BD-IPMNs progress to carcinoma and how long this progression takes. Conclusion While patients with MD-IPMNs should undergo surgical resection if comorbidities and life expectancy permit this, the management of small BD-IPMNs remains controversial. Population-based studies with long-term follow-up are needed to define which cohort of patients can be observed safely without immediate resection.
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Affiliation(s)
- Stefan Fritz
- Department of General, Visceral and Transplantation Surgery, Ruprecht-Karls University of Heidelberg, Heidelberg, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
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Machado NO, Al Qadhi H, Al Wahibi K. Intraductal Papillary Mucinous Neoplasm of Pancreas. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2015; 7:160-75. [PMID: 26110127 PMCID: PMC4462811 DOI: 10.4103/1947-2714.157477] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are neoplasms that are characterized by ductal dilation, intraductal papillary growth, and thick mucus secretion. This relatively recently defined pathology is evolving in terms of its etiopathogenesis, clinical features, diagnosis, management, and treatment guidelines. A PubMed database search was performed. All the relevant abstracts in English language were reviewed and the articles in which cases of IPMN could be identified were further scrutinized. Information of IPMN was derived, and duplication of information in several articles and those with areas of persisting uncertainties were excluded. The recent consensus guidelines were examined. The reported incidence of malignancy varies from 57% to 92% in the main duct-IPMN (MD-IPMN) and from 6% to 46% in the branch duct-IPMN (BD-IPMN). The features of high-risk malignant lesions that raise concern include obstructive jaundice in a patient with a cystic lesion in the pancreatic head, the findings on radiological imaging of a mass lesion of >30 mm, enhanced solid component, and the main pancreatic duct (MPD) of size ≥10 mm; while duct size 5-9 mm and cyst size <3 mm are considered as “worrisome features.” Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are primary investigations in diagnosing and following up on these patients. The role of pancreatoscopy and the analysis of aspirated cystic fluid for cytology and DNA analysis is still to be established. In general, resection is recommended for most MD-IPMN, mixed variant, and symptomatic BD-IPMN. The 5-year survival of patients after surgical resection for noninvasive IPMN is reported to be at 77-100%, while for those with invasive carcinoma, it is significantly lower at 27-60%. The follow-up of these patients could vary from 6 months to 1 year and would depend on the risk stratification for invasive malignancy and the pathology of the resected specimen. The understanding of IPMN has evolved over the years. The recent guidelines have played a role in this regard.
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Affiliation(s)
| | - Hani Al Qadhi
- Department of Surgery, Sultan Qaboos University Hospital, Muscat, Oman
| | - Khalifa Al Wahibi
- Department of Surgery, Sultan Qaboos University Hospital, Muscat, Oman
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Daudé M, Muscari F, Buscail C, Carrère N, Otal P, Selves J, Buscail L, Bournet B. Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas. World J Gastroenterol 2015; 21:2658-2667. [PMID: 25759534 PMCID: PMC4351216 DOI: 10.3748/wjg.v21.i9.2658] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/12/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas (IPMN).
METHODS: Over a 14-year period, 50 patients who did not undergo surgery for resectable main-duct or mixed IPMN, for reasons of precluding comorbidities, age and/or refusal, were compared with 74 patients who underwent resection to assess differences in rates of survival, recurrence/occurrence of malignancy, and prognostic factors. All study participants had dilatation of the main pancreatic duct by ≥ 5 mm, with or without dilatation of the branch ducts. Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration. For the surgical patients, pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct. Clinical and biologic follow-ups were conducted for all patients at least annually, through hospitalization or consultation every six months during the first year of follow-up, together with abdominal imaging analysis (magnetic resonance cholangiopancreatography or computed tomography) and, if necessary, endoscopic ultrasound with or without fine needle aspiration.
RESULTS: The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients (74% vs 58%; P = 0.019). The parameters of age (< 70 years) and absence of a nodule were associated with better survival (P < 0.05); however, the parameters of main pancreatic duct diameter > 10 mm, branch duct diameter > 30 mm, or presence of extra pancreatic cancers did not significantly influence the prognosis. In the nonsurgical patients, pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo (median: 29 mo; range: 8-141 mo). Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age, sex, symptoms, subtype of IPMN, or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups, with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis (> 10 mm).
CONCLUSION: Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.
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MESH Headings
- Adenocarcinoma, Mucinous/mortality
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adenocarcinoma, Mucinous/therapy
- Adenocarcinoma, Papillary/mortality
- Adenocarcinoma, Papillary/pathology
- Adenocarcinoma, Papillary/surgery
- Adenocarcinoma, Papillary/therapy
- Adult
- Aged
- Aged, 80 and over
- Cholangiopancreatography, Endoscopic Retrograde
- Cholangiopancreatography, Magnetic Resonance
- Disease Progression
- Endoscopic Ultrasound-Guided Fine Needle Aspiration
- Endosonography
- Female
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Neoplasm Recurrence, Local
- Pancreatectomy/adverse effects
- Pancreatectomy/mortality
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Pancreatic Neoplasms/therapy
- Predictive Value of Tests
- Proportional Hazards Models
- Retrospective Studies
- Risk Factors
- Time Factors
- Tomography, X-Ray Computed
- Treatment Outcome
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