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Bui NT, Dalvin LA, Howard SL, Hall JP, Sit AJ, Zhang X. A noninvasive ultrasound vibro-elastography technique for assessing ocular lesions. ULTRASONICS 2025; 147:107525. [PMID: 39571472 DOI: 10.1016/j.ultras.2024.107525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 11/15/2024] [Accepted: 11/16/2024] [Indexed: 12/14/2024]
Abstract
OBJECTIVE This research aims to develop a noninvasive ultrasound vibro-elastography technique for assessing ocular lesions including intraocular melanoma and nevus lesions. METHOD Wave speed (WS) was noninvasively measured in the lesions at three different frequencies (i.e., 100 Hz, 150 Hz, and 200 Hz). The nearby normal tissue of choroid and sclera was also analyzed as controls. Viscoelasticity of these tissues was analyzed using the wave speed dispersion curve and the Voigt model. RESULTS In this pilot study of 10 cases (5 melanomas vs. 5 nevus) with ages (mean ± SD) of (53.2 ± 6.82) vs. (72.2 ± 7.71) yo, the WS (m/s), elasticity (kPa) and viscosity (Pa.s) of lesion (melanoma vs. nevus) locations of the eye (i.e., WS @100 Hz: 3.63 vs. 3.09 (m/s), @150 Hz: 4.10 vs. 3.66 (m/s), @200 Hz: 4.78 vs. 4.07 (m/s); elasticity: 9.59 vs. 6.89 (kPa); viscosity: 12.46 vs. 9.26(Pa.s)) were analyzed. There were significant differences of WS ratio (WS close to the surface and WS inside the tumor) between the nevus and melanoma of all three frequencies (i.e., nevus vs. melanoma; @100 Hz: 1.59 vs. 2.95, p = 0.0285; @150 Hz: 1.58 vs. 3.53, p = 0.0054; @200 Hz: 1.70 vs. 3.31, p = 0.0124). The melanoma lesions are stiffer than the nevus lesions. It also shows that the lesion tissues are stiffer than the control tissues. However, there were no significant differences in WS, elasticity, viscosity among melanoma lesions, nevus lesions, and control tissues. CONCLUSIONS We demonstrate for the first time that noninvasive ultrasound vibro-elastography can be used for assessing ocular lesions. The results show that lesion tissues are stiffer than control tissues. They also show that melanoma lesions are stiffer than the nevus lesions. We plan to study more ocular lesion patients and improve the specificity and sensitivity of wave speed or viscoelasticity between lesions and controls. SIGNIFICANCE Ultrasound vibro-elastography is an innovative and noninvasive technique for assessing ocular lesions.
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Affiliation(s)
- Ngoc Thang Bui
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Lauren A Dalvin
- Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA
| | | | - Jason P Hall
- Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA
| | - Arthur J Sit
- Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA
| | - Xiaoming Zhang
- Department of Radiology, Mayo Clinic, Rochester, MN, USA; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA.
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Mazor N, Dar G, Lederman R, Lev-Cohain N, Sosna J, Joskowicz L. MC3DU-Net: a multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI. Int J Comput Assist Radiol Surg 2024; 19:423-432. [PMID: 37796412 DOI: 10.1007/s11548-023-03020-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/12/2023] [Indexed: 10/06/2023]
Abstract
PURPOSE Radiological detection and follow-up of pancreatic cysts in multisequence MRI studies are required to assess the likelihood of their malignancy and to determine their treatment. The evaluation requires expertise and has not been automated. This paper presents MC3DU-Net, a novel multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI studies consisting of coronal MRCP and axial TSE MRI sequences. METHODS MC3DU-Net leverages the information in both sequences by computing a pancreas Region of Interest (ROI) segmentation in the TSE MRI scan, transferring it to MRCP scan, and then detecting and segmenting the cysts in the ROI of the MRCP scan. Both the voxel-level ROI of the pancreas and the segmentation of the cysts are performed with 3D U-Nets trained with Hard Negative Patch Mining, a new technique for class imbalance correction and for the reduction in false positives. RESULTS MC3DU-Net was evaluated on a dataset of 158 MRI patient studies with a training/validation/testing split of 118/17/23. Ground truth segmentations of a total of 840 cysts were manually obtained by expert clinicians. MC3DU-Net achieves a mean recall of 0.80 ± 0.19, a mean precision of 0.75 ± 0.26, a mean Dice score of 0.80 ± 0.19 and a mean ASSD of 0.60 ± 0.53 for pancreatic cysts of diameter > 5 mm, which is the clinically relevant endpoint. CONCLUSION MC3DU-Net is the first fully automatic method for detection and segmentation of pancreatic cysts in MRI. Automatic detection and segmentation of pancreatic cysts in MRI can be performed accurately and reliably. It may provide a method for precise disease evaluation and may serve as a second expert reader.
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Affiliation(s)
- Nir Mazor
- School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Gili Dar
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Richard Lederman
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Naama Lev-Cohain
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Jacob Sosna
- Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Leo Joskowicz
- School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
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Aleotti F, Crippa S, Belfiori G, Tamburrino D, Partelli S, Longo E, Palumbo D, Pecorelli N, Lena MS, Capurso G, Arcidiacono PG, Falconi M. Pancreatic resections for benign intraductal papillary mucinous neoplasms: Collateral damages from friendly fire. Surgery 2022; 172:1202-1209. [PMID: 35667898 DOI: 10.1016/j.surg.2022.04.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/05/2022] [Accepted: 04/28/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Surgical resection of intraductal papillary mucinous neoplasms is based on preoperative high-risk stigmata/worrisome features, but the risk of overtreatment remains high. The aim of this study was to evaluate surgical indications and perioperative and long-term complications in patients with low-grade intraductal papillary mucinous neoplasms. METHODS Patients who underwent surgical resection between 2009 and 2018 with a final histology of low-grade intraductal papillary mucinous neoplasms were included. Surgical indications, type of surgery, and short- and long-term outcomes were evaluated. RESULTS A significant decrease in the rate of patients resected for low-grade intraductal papillary mucinous neoplasms was observed (43.6% in 2009-2012 vs 27.8% in 2013-2018; P = .003), and 133 patients were finally included (62 women, median age: 68 years). Of these, 24.1% had 1 worrisome feature, 39.8% had ≥2 worrisome features, 18.8% had ≥1 high-risk stigmata, and 15.8% had ≥1 worrisome features + 1 high-risk stigmata. Overall surgical morbidity was 55.6%, 15.8% had Clavien-Dindo ≥3 complications, reoperation rate was 3.8%, and 90-day postoperative mortality was 1.5%. After a median follow-up of 60 months, 13 patients (11.5%) had a recurrence of benign intraductal papillary mucinous neoplasm in the pancreatic remnant, and 2 patients (1.8%) developed pancreatic ductal adenocarcinoma. After partial pancreatectomy, 51.3% of patients were taking pancreatic enzyme replacement therapy. Among nondiabetics, 26% developed diabetes after partial pancreatectomy, of which 38% were insulin-dependent. Eighteen patients (13.7%) developed incisional hernia. CONCLUSION Given the rates of morbidity and long-term complications after pancreatic resections, surgeons should attentively balance the true risks of intraductal papillary mucinous neoplasm degeneration with the risks of surgical resection in each patient.
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Affiliation(s)
- Francesca Aleotti
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Crippa
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Giulio Belfiori
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy. http://www.twitter.com/spartelli
| | - Enrico Longo
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Diego Palumbo
- Division of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Nicolò Pecorelli
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy. http://www.twitter.com/nicpecorelli
| | - Marco Schiavo Lena
- Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreas-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, Università Vita-Salute, IRCCS San Raffaele Scientific Institute, Milan, Italy. http://www.twitter.com/lelecapurso
| | - Paolo Giorgio Arcidiacono
- Pancreas-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, Università Vita-Salute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Crippa S, Aleotti F, Longo E, Belfiori G, Partelli S, Tamburrino D, Di Salvo F, De Cobelli F, Romano L, Arcidiacono PG, Petrone MC, Zamboni G, Lena MS, Doglioni C, Falconi M. Main Duct Thresholds for Malignancy Are Different in Intraductal Papillary Mucinous Neoplasms of the Pancreatic Head and Body-Tail. Clin Gastroenterol Hepatol 2022; 20:390-399.e7. [PMID: 33385536 DOI: 10.1016/j.cgh.2020.12.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 12/22/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The risk of malignancy is uncertain for intraductal papillary mucinous neoplasms (IPMNs) with main pancreatic duct (MPD) of 5-9 mm. No study has correlated MPD size and malignancy considering the anatomic site of the gland (head versus body-tail). Our aim was to analyze the significance of MPD in pancreatic head/body-tail as a predictor of malignancy in main-duct/mixed IPMNs. METHODS Retrospective analysis of resected patients between 2009-2018 was performed. Malignancy was defined as high-grade dysplasia and invasive carcinoma. MPD diameter was measured with magnetic resonance imaging. Receiver operating characteristic curve (ROC) analysis was utilized to identify optimal MPD cut-off for malignancy. Independent predictors of malignancy were searched. RESULTS Malignancy was detected in 74% of 312 identified patients. 213 patients (68.3%) had IPMNs of the pancreatic head and 99 (31.7%) of the body-tail. ROC analysis identified 9 and 7 mm as the optimal MPD cut-offs for malignancy in IPMNs of head and body-tail of the pancreas, respectively. Multivariate analysis confirmed that MPD ≥9 mm (pancreatic head) and ≥7 mm (body-tail) were independent predictors of malignancy along with macroscopic solid components, positive cytology and elevated CA 19-9. The risk of malignancy was low for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) unless high-risk stigmata or multiple worrisome features were present. CONCLUSIONS Different thresholds of MPD dilation are associated with malignancy in IPMNs of the head and body-tail of the pancreas. The risk of malignancy for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) lacking high-risk stigmata or multiple worrisome features is low.
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Affiliation(s)
- Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan
| | - Francesca Aleotti
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan
| | - Enrico Longo
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan
| | - Giulio Belfiori
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan
| | - Francesca Di Salvo
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan; Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan
| | - Luigi Romano
- Department of Radiology, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar (VR)
| | - Paolo Giorgio Arcidiacono
- Vita-Salute San Raffaele University, Milan; Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan
| | - Maria Chiara Petrone
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan
| | - Giuseppe Zamboni
- Department of Pathology, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar (VR)
| | - Marco Schiavo Lena
- Department of Pathology, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Doglioni
- Vita-Salute San Raffaele University, Milan; Department of Pathology, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan; Vita-Salute San Raffaele University, Milan.
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Khalaf N, Abrams HR, Eke C, Kanwal F, El-Serag HB. Why Do Small Intraductal Papillary Mucinous Neoplasms Create Such a Huge Management Challenge?: How International Classification of Diseases Codes Have Failed Us. Pancreas 2022; 51:e13-e15. [PMID: 35404900 PMCID: PMC10127940 DOI: 10.1097/mpa.0000000000001989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Pulvirenti A, Margonis GA, Morales-Oyarvide V, McIntyre CA, Lawrence SA, Goldman DA, Gonen M, Weiss MJ, Ferrone CR, He J, Brennan MF, Cameron JL, Lillemoe KD, Kingham TP, Balachandran V, Qadan M, D’Angelica MI, Jarnagin WR, Wolfgang CL, Castillo CFD, Allen PJ. Intraductal Papillary Mucinous Neoplasms: Have IAP Consensus Guidelines Changed our Approach?: Results from a Multi-institutional Study. Ann Surg 2021; 274:e980-e987. [PMID: 31804389 PMCID: PMC8503800 DOI: 10.1097/sla.0000000000003703] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes. BACKGROUND Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease. METHODS Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000-2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006-2012), Fukuoka (FCG, after 2012)]. RESULTS The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63). CONCLUSION Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnostic imaging
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adenocarcinoma, Papillary/diagnostic imaging
- Adenocarcinoma, Papillary/pathology
- Adenocarcinoma, Papillary/surgery
- Adult
- Aged
- Aged, 80 and over
- Carcinoma, Pancreatic Ductal/diagnostic imaging
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Female
- Humans
- Male
- Middle Aged
- Neoplasm Grading
- Neoplasm Staging
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Practice Guidelines as Topic
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Affiliation(s)
| | - Georgios A Margonis
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Caitlin A McIntyre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sharon A Lawrence
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Debra A Goldman
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Matthew J Weiss
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jin He
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Murray F Brennan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - John L Cameron
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Vinod Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Duke, University School of Medicine, Durham, NC
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Dbouk M, Brewer Gutierrez OI, Lennon AM, Chuidian M, Shin EJ, Kamel IR, Fishman EK, He J, Burkhart RA, Wolfgang CL, Hruban RH, Goggins MG, Canto MI. Guidelines on management of pancreatic cysts detected in high-risk individuals: An evaluation of the 2017 Fukuoka guidelines and the 2020 International Cancer of the Pancreas Screening (CAPS) consortium statements. Pancreatology 2021; 21:613-621. [PMID: 33593706 DOI: 10.1016/j.pan.2021.01.017] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 01/10/2021] [Accepted: 01/26/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI. METHODS Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts. RESULTS 356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria. CONCLUSIONS In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.
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Affiliation(s)
- Mohamad Dbouk
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Olaya I Brewer Gutierrez
- Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Anne Marie Lennon
- Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Miguel Chuidian
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Eun Ji Shin
- Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Ihab R Kamel
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Elliot K Fishman
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Richard A Burkhart
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Michael G Goggins
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Marcia Irene Canto
- Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
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Djordjevic V, Grubor N, Kovac JD, Micev M, Milic N, Knezevic D, Gregoric P, Lausevic Z, Kerkez M, Knezevic S, Radenkovic D. Comparison of Preoperative Evaluation with the Pathological Report in Intraductal Papillary Mucinous Neoplasms: A Single-Center Experience. J Clin Med 2021; 10:678. [PMID: 33578680 PMCID: PMC7916322 DOI: 10.3390/jcm10040678] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/05/2021] [Accepted: 02/07/2021] [Indexed: 12/17/2022] Open
Abstract
The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neoplasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 patients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy.
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Affiliation(s)
- Vladimir Djordjevic
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
| | - Nikica Grubor
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
| | - Jelena Djokic Kovac
- Centre for Radiology and Magnetic Resonance Imaging, Clinical Centre of Serbia, 11000 Belgrade, Serbia;
- Department for Radiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Marjan Micev
- Department of Histopathology, Clinical Centre of Serbia, 11000 Belgrade, Serbia;
| | - Natasa Milic
- Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; or
- Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, NY 55905, USA
| | - Djordje Knezevic
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
| | - Pavle Gregoric
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
- Centre for Emergency Surgery, Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Zeljko Lausevic
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
- Centre for Emergency Surgery, Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Mirko Kerkez
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
| | - Srbislav Knezevic
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
| | - Dejan Radenkovic
- Clinic for Digestive Surgery, First Surgical Clinic, Clinical Centre of Serbia, 11000 Belgrade, Serbia; (N.G.); (D.K.); (M.K.); (S.K.); (D.R.)
- Department for Surgery, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (P.G.); (Z.L.)
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9
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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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10
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Intraductal papillary mucinous neoplasm of the pancreas: diagnostic performance of the 2017 international consensus guidelines using CT and MRI. Eur Radiol 2021; 31:4774-4784. [PMID: 33409798 DOI: 10.1007/s00330-020-07583-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/30/2020] [Accepted: 12/01/2020] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To assess the diagnostic performance of the 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas and to compare the diagnostic performance and intermodality agreement between contrast-enhanced CT and MRI. METHODS We retrospectively evaluated patients with surgical resection of IPMN of the pancreas who underwent preoperative CT and MRI between 2009 and 2019. Two radiologists evaluated the clinical and imaging features of IPMN of pancreas according to the 2017 international consensus guideline. Univariable and multivariable analyses were performed to identify significant predictors of malignancy in IPMN. The diagnostic abilities of CT and MRI were compared, and their intermodality agreement was determined. RESULTS Of 175 patients (mean age, 64 years; 116 males), 88 (50.3%) had malignant IPMN. On multivariable analysis, all three high-risk stigmata (main pancreatic duct [MPD] ≥ 10 mm, mural nodule ≥ 5 mm, and obstructive jaundice) and two worrisome features (MPD 5-9 mm and elevated carbohydrate antigen 19-9) were associated with malignant IPMN on CT and MRI (p < 0.05). A mural nodule < 5 mm on MRI was also associated with malignant IPMN (OR 5.3, p = 0.009). The diagnostic accuracy of high-risk stigmata showed no difference between CT and MRI (73.7% vs. 75.4%, p = 0.505), with good to excellent intermodality agreement. CONCLUSIONS Current high-risk stigmata had the strongest association with malignant IPMN on CT and MRI. Although MRI is superior to CT for identifying mural nodules, diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI. KEY POINTS • The current high-risk stigmata in the 2017 International Consensus Guidelines had the strongest association with malignant IPMN on CT and MRI. • MRI is better than CT for identifying enhancing mural nodule. • Diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI.
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11
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Goh BKP, Park RHS, Koh YX, Teo JY, Tan EK, Cheow PC, Thng CH, Low AS, Tan DM, Chow PKH, Chan CY, Chung AYF, Ooi LLPJ. Changing trends in the clinicopathological features, practices and outcomes in the surgical management for cystic lesions of the pancreas and impact of the international guidelines: Single institution experience with 462 cases between 1995-2018. Pancreatology 2020; 20:1786-1790. [PMID: 33008749 DOI: 10.1016/j.pan.2020.09.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/08/2020] [Accepted: 09/23/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice. METHODS 462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998-2006, 2007-2012 and 2013 to 2018. RESULTS Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HRSG06 and HRFG12 CLP with a corresponding lower proportion of LRSG06 and LRFG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated. CONCLUSIONS Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HRSG06 and HRFG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment.
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Affiliation(s)
- Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore.
| | - Rachel H S Park
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Ek-Khoon Tan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Choon-Hua Thng
- Department of Oncologic Imaging, National Cancer Center Singapore, Singapore
| | - Albert S Low
- Department of Radiology, Singapore General Hospital, Singapore
| | - Damien M Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke National University of Singapore Medical School, Singapore
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12
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Assessment of malignant potential in intraductal papillary mucinous neoplasms of the pancreas using MR findings and texture analysis. Eur Radiol 2020; 31:3394-3404. [PMID: 33140171 DOI: 10.1007/s00330-020-07425-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/25/2020] [Accepted: 10/14/2020] [Indexed: 12/18/2022]
Abstract
OBJECTIVES To investigate the utility of MR findings and texture analysis for predicting the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs). METHODS Two hundred forty-eight patients with surgically confirmed IPMNs (106 malignant [invasive carcinoma/high-grade dysplasia] and 142 benign [low/intermediate-grade dysplasia]) and who underwent magnetic resonance imaging (MRI) with MR cholangiopancreatography (MRCP) were included. Two reviewers independently analyzed MR findings as proposed by the 2017 international consensus guidelines. Texture analysis of MRCP was also performed. A multivariate logistic regression analysis was used to identify predictors for malignant IPMNs. Diagnostic performance was also analyzed using receiver operating curve analysis. RESULTS Among MR findings, enhancing mural nodule size ≥ 5 mm, main pancreatic duct (MPD) ≥ 10 mm or MPD of 5 to 9 mm, and abrupt change of MPD were significant predictors for malignant IPMNs (p < 0.05). Among texture variables, significant predictors were effective diameter, surface area, sphericity, compactness, entropy, and gray-level co-occurrence matrix entropy (p < 0.05). At multivariate analysis, enhancing mural nodule ≥ 5 mm (odds ratios (ORs), 6.697 and 6.968, for reviewers 1 and 2, respectively), MPD ≥ 10 mm or MPD of 5 to 9 mm (ORs, 4.098 and 4.215, and 2.517 and 3.055, respectively), larger entropy (ORs, 1.485 and 1.515), and smaller compactness (ORs, 0.981 and 0.977) were significant predictors for malignant IPMNs (p < 0.05). When adding texture variable to MR findings, diagnostic performance for predicting malignant IPMNs improved from 0.80 and 0.78 to 0.85 and 0.85 in both reviewers (p < 0.05), respectively. CONCLUSIONS MRCP-derived texture features are useful for predicting malignant IPMNs, and the addition of texture analysis to MR features may improve diagnostic performance for predicting malignant IPMNs. KEY POINTS • Among the MR imaging findings, an enhancing mural nodule size ≥ 5 mm and dilated main pancreatic ducts are independent predictors for malignant IPMNs. • Greater entropy and smaller compactness on MR texture analysis are independent predictors for malignant IPMNs. • The addition of MR texture analysis improved the diagnostic performance for predicting malignant IPMNs from 0.80 and 0.78 to 0.85 and 0.85, respectively.
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13
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Park RHS, Lim GRS, Wu JJY, Koh YX, Teo JY, Cheow PC, Chan CY, Ooi LLPJ, Chung AYF, Goh BKP. Validation of the clinical utility of 4 guidelines in the initial triage of mucinous cystic lesions of the pancreas based on cross-sectional imaging: Experience with 188 surgically-treated patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:2114-2121. [PMID: 32828582 DOI: 10.1016/j.ejso.2020.07.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/10/2020] [Accepted: 07/19/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN. METHODS One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma. RESULTS Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively. CONCLUSIONS All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnostic imaging
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/physiopathology
- Adenocarcinoma, Mucinous/surgery
- Adult
- Aged
- Aged, 80 and over
- Biopsy, Fine-Needle
- CA-19-9 Antigen/metabolism
- Dilatation, Pathologic
- Female
- Humans
- Jaundice, Obstructive/physiopathology
- Lymphadenopathy/diagnostic imaging
- Male
- Middle Aged
- Neoplasms, Cystic, Mucinous, and Serous/diagnostic imaging
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/physiopathology
- Neoplasms, Cystic, Mucinous, and Serous/surgery
- Pancreatic Ducts/diagnostic imaging
- Pancreatic Intraductal Neoplasms/diagnostic imaging
- Pancreatic Intraductal Neoplasms/pathology
- Pancreatic Intraductal Neoplasms/physiopathology
- Pancreatic Intraductal Neoplasms/surgery
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/physiopathology
- Pancreatic Neoplasms/surgery
- Pancreatitis/physiopathology
- Retrospective Studies
- Risk Assessment
- Triage
- Tumor Burden
- Young Adult
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Affiliation(s)
- Rachel H S Park
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Grace R S Lim
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Jania J Y Wu
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
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14
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Sharib J, Esserman L, Koay EJ, Maitra A, Shen Y, Kirkwood KS, Ozanne EM. Cost-effectiveness of consensus guideline based management of pancreatic cysts: The sensitivity and specificity required for guidelines to be cost-effective. Surgery 2020; 168:601-609. [PMID: 32739138 PMCID: PMC8754171 DOI: 10.1016/j.surg.2020.04.052] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 03/25/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Detection of cystic lesions of the pancreas has outpaced our ability to stratify low-grade cystic lesions from those at greater risk for pancreatic cancer, raising a concern for overtreatment. METHODS We developed a Markov decision model to determine the cost-effectiveness of guideline-based management for asymptomatic pancreatic cysts. Incremental costs per quality-adjusted life year gained and survival were calculated for current management guidelines. A sensitivity analysis estimated the effect on cost-effectiveness and mortality if overtreatment of low-grade cysts is avoided, and the sensitivity and specificity thresholds required of methods of cyst stratification to improve costs expended. RESULTS "Surveillance" using current management guidelines had an incremental cost-effectiveness ratio of $171,143/quality adjusted life year compared with no surveillance or operative treatment ("do nothing"). An incremental cost-effectiveness ratio for surveillance decreases to $80,707/quality adjusted life year if the operative overtreatment of low-grade cysts was avoided. Assuming a societal willingness-to-pay of $100,000/quality adjusted life year, the diagnostic specificity for high-risk cysts must be >67% for surveillance to be preferred over surgery and "do nothing." Changes in sensitivity alone cannot make surveillance cost-effective. Most importantly, survival in surveillance is worse than "do nothing" for 3 years after cyst diagnosis, although long-term survival is improved. The disadvantage is eliminated when overtreatment of low-grade cysts is avoided. CONCLUSION Current management of pancreatic cystic lesions is not cost-effective and may increase mortality owing to overtreatment of low-grade cysts. The specificity for risk stratification for high-risk cysts must be greater than 67% to make surveillance cost-effective.
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Affiliation(s)
- Jeremy Sharib
- Department of Surgery, University of California San Francisco, Helen Diller Cancer Center, San Francisco, CA
| | - Laura Esserman
- Department of Surgery, University of California San Francisco, Helen Diller Cancer Center, San Francisco, CA
| | - Eugene J Koay
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Anirban Maitra
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Yu Shen
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kimberly S Kirkwood
- Department of Surgery, University of California San Francisco, Helen Diller Cancer Center, San Francisco, CA.
| | - Elissa M Ozanne
- Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT
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15
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Gillies RJ, Schabath MB. Radiomics Improves Cancer Screening and Early Detection. Cancer Epidemiol Biomarkers Prev 2020; 29:2556-2567. [PMID: 32917666 DOI: 10.1158/1055-9965.epi-20-0075] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/18/2020] [Accepted: 08/31/2020] [Indexed: 11/16/2022] Open
Abstract
Imaging is a key technology in the early detection of cancers, including X-ray mammography, low-dose CT for lung cancer, or optical imaging for skin, esophageal, or colorectal cancers. Historically, imaging information in early detection schema was assessed qualitatively. However, the last decade has seen increased development of computerized tools that convert images into quantitative mineable data (radiomics), and their subsequent analyses with artificial intelligence (AI). These tools are improving diagnostic accuracy of early lesions to define risk and classify malignant/aggressive from benign/indolent disease. The first section of this review will briefly describe the various imaging modalities and their use as primary or secondary screens in an early detection pipeline. The second section will describe specific use cases to illustrate the breadth of imaging modalities as well as the benefits of quantitative image analytics. These will include optical (skin cancer), X-ray CT (pancreatic and lung cancer), X-ray mammography (breast cancer), multiparametric MRI (breast and prostate cancer), PET (pancreatic cancer), and ultrasound elastography (liver cancer). Finally, we will discuss the inexorable improvements in radiomics to build more robust classifier models and the significant limitations to this development, including access to well-annotated databases, and biological descriptors of the imaged feature data.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."
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Affiliation(s)
- Robert J Gillies
- Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. .,Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| | - Matthew B Schabath
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.,Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
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16
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Advances in the management of pancreatic cystic neoplasms. Curr Probl Surg 2020; 58:100879. [PMID: 34144739 DOI: 10.1016/j.cpsurg.2020.100879] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 08/09/2020] [Indexed: 12/11/2022]
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17
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Kanani T, Isherwood J, Chung WY, Dennison A. Diagnostic approaches for pancreatic cystic lesions. ANZ J Surg 2020; 90:2211-2218. [PMID: 32815222 DOI: 10.1111/ans.16251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/23/2020] [Accepted: 07/26/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Cystic lesions of the pancreas (PCLs) may be inflammatory or proliferative and making an accurate and timely pre-operative diagnosis remains a significant clinical challenge. This is principally due to the heterogeneity of the pathological processes involved. PCLs constitute an entity with diverse histology and although infrequent, the possible potential for malignant transformation of these lesions and the opportunity for curative surgery mandates that our diagnostic approaches are up to date and evidence based. In addition, improved diagnostic accuracy is crucial to prevent unnecessary surgical procedures with the inevitable associated morbidity. METHODS This narrative review examines the current diagnostic benchmarks and identifies novel diagnostic techniques that warrant further consideration, a number of which are beginning to be included in routine clinical practice when these PCLs are being investigated. A computerized search was made of MEDLINE, EMBASE and PubMed using the search words 'diagnostic approaches to pancreatic cystic lesions'. All relevant articles in English language or with an English abstract were retrieved and additionally cross referenced. CONCLUSION The increasing accuracy of available imaging techniques together with the wider availability of endoluminal ultrasound and the development of additional novel methods to assess PCLs presents an opportunity to significantly improve the pre-operative diagnosis rate. This is essential to classify the type of PCL and hence guide the management particularly with lesions where there is a likelihood of progression to more serious pathology. We have highlighted the need for a comprehensive and standardized algorithm for the diagnosis and management of PCLs.
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Affiliation(s)
- Trisha Kanani
- Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University of Leicester, Leicester, UK
| | - John Isherwood
- Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University of Leicester, Leicester, UK
| | - Wen Yuan Chung
- Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University of Leicester, Leicester, UK
| | - Ashley Dennison
- Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, University of Leicester, Leicester, UK
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18
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Management of Incidental Pancreatic Cystic Lesions: Integrating Novel Diagnostic and Prognostic Factors With Current Clinical Guidelines. J Clin Gastroenterol 2020; 54:415-427. [PMID: 32011401 DOI: 10.1097/mcg.0000000000001310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Owing to increased detection rates, the diagnosis and management of incidental pancreatic cysts has become a common predicament. Up to 13% of patients undergoing cross-sectional imaging studies for other indications are found to have pancreatic cystic lesions. Although most cystic lesions are benign, the malignant potential of several types of pancreatic cysts makes accurate classification vital to directing therapy. To this end, advances in the last decade led to better characterization of pancreatic cyst morphology and hence enhanced the ability to predict underlying histopathology, and biological behavior. Although accurate classification remains a challenge, the utilization of complementary diagnostic tools is the optimal approach to dictate management. The following review includes a description of pancreatic cysts, a critical review of current and emerging diagnostic techniques and a review of recent guidelines in the management of incidental pancreatic cysts.
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Sidhu H, Maher S, Bleszynski MS, Chen L, Farnell D, Gan I, Segedi M. Determining when endoscopic ultrasound changes management for patients with pancreatic cystic neoplasms. Am J Surg 2020; 221:813-818. [PMID: 32334802 DOI: 10.1016/j.amjsurg.2020.03.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 03/29/2020] [Accepted: 03/30/2020] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Pancreatic cystic neoplasms (PCNs) are being incidentally detected at an increased rate due to increased CT and MRI usage. EUS is an emerging tool that can differentiate between benign and malignant features of pancreatic cysts. We hoped to identify the specific cross-sectional imaging findings and patient characteristics that warrant EUS referral. METHODS We conducted a retrospective case-control chart review, evaluating patients, who were diagnosed with pancreatic cysts and underwent EUS between January 1, 2010 and December 31, 2017. RESULTS EUS was found to change management when CT imaging found cyst size > 4 cm (OR = 4.07, p < 0.01), cyst size > 3 cm (OR = 3.79, p < 0.001) and associated solid component to the cyst (OR = 5.95, p < 0.01). Additionally, patient characteristics, including age less than 50 years, male sex and 10-pack year smoking history were significantly associated with EUS change in management. DISCUSSION Our findings suggest that EUS referral should be coordinated based on the findings of specific HRFs, with support from high risk patient characteristics, rather than the accumulation of multiple HRFs, as suggested by existing guidelines.
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Affiliation(s)
- Hasrit Sidhu
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Safia Maher
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Michael S Bleszynski
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Leo Chen
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Dave Farnell
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Ian Gan
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
| | - Maja Segedi
- University of British Columbia, 2329, West Mall, Vancouver, BC, V6T 1Z4, Canada.
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Hua J, Zhang B, Yang XJ, Zhang YY, Wei MY, Liang C, Meng QC, Liu J, Yu XJ, Xu J, Shi S. Validation and head-to-head comparison of four models for predicting malignancy of intraductal papillary mucinous neoplasm of the pancreas: A study based on endoscopic ultrasound findings. World J Gastrointest Oncol 2019. [DOI: 10.4251/wjo.v11.i11.1043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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Hua J, Zhang B, Yang XJ, Zhang YY, Wei MY, Liang C, Meng QC, Liu J, Yu XJ, Xu J, Shi S. Validation and head-to-head comparison of four models for predicting malignancy of intraductal papillary mucinous neoplasm of the pancreas: A study based on endoscopic ultrasound findings. World J Gastrointest Oncol 2019; 11:1043-1053. [PMID: 31798784 PMCID: PMC6883176 DOI: 10.4251/wjgo.v11.i11.1043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 09/06/2019] [Accepted: 09/13/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking. AIM To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN. METHODS A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests. RESULTS Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model. CONCLUSION The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.
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Affiliation(s)
- Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Xiu-Jiang Yang
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Yi-Yin Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Miao-Yan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Qing-Cai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Fudan University Shanghai Medical College, Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
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Wu J, Wang Y, Li Z, Miao H. Accuracy of Fukuoka and American Gastroenterological Association Guidelines for Predicting Advanced Neoplasia in Pancreatic Cyst Neoplasm: A Meta-Analysis. Ann Surg Oncol 2019; 26:4522-4536. [PMID: 31617119 DOI: 10.1245/s10434-019-07921-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND A differential diagnosis of advanced pancreatic cystic neoplasms (PCNs) is critical to determine optimal treatment. The Fukuoka and American Gastroenterological Association (AGA) guidelines are the most widely accepted criteria for the management of PCNs. OBJECTIVE This study aimed to evaluate the diagnostic value of these guidelines in predicting advanced neoplasia (AN). METHODS A comprehensive electronic search of the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases was conducted to identify all relevant studies evaluating the Fukuoka and AGA guidelines in surgically resected and histologically confirmed PCNs. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated as compound measures of diagnostic accuracy using the random-effects model. Summary of receiver operating characteristic (SROC) curves and the area under the curve (AUC) were also performed. RESULTS A total of 21 studies with 3723 patients were included in this meta-analysis. Of these studies, 15, 4, and 2 evaluated the Fukuoka guidelines, the AGA guidelines, and both guidelines, respectively. For AN prediction, the Fukuoka guidelines had a pooled sensitivity of 0.67 (95% confidence interval [CI] 0.64-0.70), pooled specificity of 0.64 (95% CI 0.62-0.66), and pooled DOR of 6.28 (95% CI 4.38-9.01), with an AUC of the SROC of 0.78. AGA guidelines showed a pooled sensitivity of 0.59 (95% CI 0.52-0.65), pooled specificity of 0.77 (95% CI 0.74-0.80), and pooled DOR of 5.84 (95% CI 2.60-13.15), with an AUC of 0.79 (95% CI 0.70-0.88). CONCLUSION When used alone, the Fukuoka and AGA guidelines showed similar but unsatisfactory diagnostic accuracy in the risk stratification of malignant potential of PCN. Thus, we recommend that they be applied only as a broad framework in clinical practice.
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Affiliation(s)
- Jiayuan Wu
- Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China.
| | - Yufeng Wang
- School of Public Health, Guangdong Medical University, Zhanjiang, People's Republic of China
| | - Zitao Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China
| | - Huilai Miao
- Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People's Republic of China. .,Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
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Ivry SL, Knudsen GM, Caiazza F, Sharib JM, Jaradeh K, Ravalin M, O’Donoghue AJ, Kirkwood KS, Craik CS. The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts. Biol Chem 2019; 400:1629-1638. [DOI: 10.1515/hsz-2019-0103] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 05/27/2019] [Indexed: 12/15/2022]
Abstract
Abstract
Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers.
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Affiliation(s)
- Sam L. Ivry
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
- Pharmaceutical Sciences and Pharmacogenomics Graduate Program , University of California , San Francisco, San Francisco, CA , USA
| | - Giselle M. Knudsen
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Francesco Caiazza
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Jeremy M. Sharib
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Katrin Jaradeh
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Matthew Ravalin
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
| | - Anthony J. O’Donoghue
- Skaggs School of Pharmacy and Pharmaceutical Chemistry , University of California , San Diego, La Jolla, CA , USA
| | - Kimberly S. Kirkwood
- Department of Surgery , University of California , San Francisco, San Francisco, CA , USA
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry , University of California , San Francisco, 600 16th Street , San Francisco, CA 94143 , USA
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Srinivasan N, Koh YX, Goh BK. Systematic review of the utility of 18-FDG PET in the preoperative evaluation of IPMNs and cystic lesions of the pancreas. Surgery 2019; 165:929-937. [DOI: 10.1016/j.surg.2018.11.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 11/01/2018] [Accepted: 11/08/2018] [Indexed: 02/07/2023]
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Sharib JM, Fonseca AL, Swords DS, Jaradeh K, Bracci PM, Firpo MA, Hatcher S, Scaife CL, Wang H, Kim GE, Mulvihill SJ, Maitra A, Koay EJ, Kirkwood KS. Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making? Surgery 2018; 164:1178-1184. [DOI: 10.1016/j.surg.2018.07.014] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 06/24/2018] [Accepted: 07/10/2018] [Indexed: 12/17/2022]
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Abstract
PURPOSE OF REVIEW The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging. RECENT FINDINGS Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.
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Affiliation(s)
- Jennifer Phan
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Suite 330-37, Los Angeles, CA, 90095, USA
| | - V Raman Muthusamy
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Suite 330-37, Los Angeles, CA, 90095, USA.
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Srinivasan N, Teo JY, Chin YK, Hennedige T, Tan DM, Low AS, Thng CH, Goh BKP. Systematic review of the clinical utility and validity of the Sendai and Fukuoka Consensus Guidelines for the management of intraductal papillary mucinous neoplasms of the pancreas. HPB (Oxford) 2018; 20:497-504. [PMID: 29486917 DOI: 10.1016/j.hpb.2018.01.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 12/16/2017] [Accepted: 01/03/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN). METHODS A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs. RESULTS Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign. CONCLUSION The FCG had a higher positive predictive value (PPV) compared to the SCG. However, the negative predictive value (NPV) of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines.
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Affiliation(s)
- Nandhini Srinivasan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Yung-Ka Chin
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Tiffany Hennedige
- Department of Oncologic Imaging, National Cancer Center Singapore, Singapore; Duke-NUS Medical School Singapore, Singapore
| | - Damien M Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Albert S Low
- Department of Diagnostic Radiology, Singapore General Hospital, Singapore
| | - Choon Hua Thng
- Department of Oncologic Imaging, National Cancer Center Singapore, Singapore; Duke-NUS Medical School Singapore, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore; Duke-NUS Medical School Singapore, Singapore.
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Evaluation of the International Consensus Guidelines for the Surgical Resection of Intraductal Papillary Mucinous Neoplasms. Dig Dis Sci 2018; 63:860-867. [PMID: 28667432 DOI: 10.1007/s10620-017-4667-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 06/26/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND International consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) were revised in 2012. AIMS We aimed to evaluate the clinical utility of each predictor in the 2006 and 2012 guidelines and validate the diagnostic value and surgical indications. METHODS Forty-two patients with surgically resected IPMNs were included. Each predictor was applied to evaluate its diagnostic value. RESULTS The 2012 guidelines had greater accuracy for invasive carcinoma than the 2006 guidelines (64.3 vs. 31.0%). Moreover, the accuracy for high-grade dysplasia was also increased (48.6 vs. 77.1%). When the main pancreatic duct (MPD) size ≥8 mm was substituted for MPD size ≥10 mm in the 2012 guidelines, the accuracy for high-grade dysplasia was 80.0%. CONCLUSIONS The 2012 guidelines exhibited increased diagnostic accuracy for invasive IPMN. It is important to consider surgical resection prior to invasive carcinoma, and high-risk stigmata might be a useful diagnostic criterion. Furthermore, MPD size ≥8 mm may be predictive of high-grade dysplasia.
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Intraductal Papillary Mucinous Neoplasms of the Pancreas: Current Understanding and Future Directions for Stratification of Malignancy Risk. Pancreas 2018; 47:272-279. [PMID: 29424809 PMCID: PMC5808987 DOI: 10.1097/mpa.0000000000000999] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.
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Permuth JB, Choi J, Balarunathan Y, Kim J, Chen DT, Chen L, Orcutt S, Doepker MP, Gage K, Zhang G, Latifi K, Hoffe S, Jiang K, Coppola D, Centeno BA, Magliocco A, Li Q, Trevino J, Merchant N, Gillies R, Malafa M. Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms. Oncotarget 2018; 7:85785-85797. [PMID: 27589689 PMCID: PMC5349874 DOI: 10.18632/oncotarget.11768] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 07/14/2016] [Indexed: 12/21/2022] Open
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cancer precursors incidentally discovered by cross-sectional imaging. Consensus guidelines for IPMN management rely on standard radiologic features to predict pathology, but they lack accuracy. Using a retrospective cohort of 38 surgically-resected, pathologically-confirmed IPMNs (20 benign; 18 malignant) with preoperative computed tomography (CT) images and matched plasma-based ‘miRNA genomic classifier (MGC)’ data, we determined whether quantitative ‘radiomic’ CT features (+/- the MGC) can more accurately predict IPMN pathology than standard radiologic features ‘high-risk’ or ‘worrisome’ for malignancy. Logistic regression, principal component analyses, and cross-validation were used to examine associations. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were estimated. The MGC, ‘high-risk,’ and ‘worrisome’ radiologic features had area under the receiver operating characteristic curve (AUC) values of 0.83, 0.84, and 0.54, respectively. Fourteen radiomic features differentiated malignant from benign IPMNs (p<0.05) and collectively had an AUC=0.77. Combining radiomic features with the MGC revealed an AUC=0.92 and superior sensitivity (83%), specificity (89%), PPV (88%), and NPV (85%) than other models. Evaluation of uncertainty by 10-fold cross-validation retained an AUC>0.80 (0.87 (95% CI:0.84-0.89)). This proof-of-concept study suggests a noninvasive radiogenomic approach may more accurately predict IPMN pathology than ‘worrisome’ radiologic features considered in consensus guidelines.
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Affiliation(s)
- Jennifer B Permuth
- Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.,Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jung Choi
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Yoganand Balarunathan
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jongphil Kim
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Dung-Tsa Chen
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Lu Chen
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Sonia Orcutt
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Matthew P Doepker
- Department of Clinical Surgery/Surgical Oncology, Palmetto Health/USC School of Medicine, Columbia, South Carolina, USA
| | - Kenneth Gage
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Geoffrey Zhang
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.,Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Kujtim Latifi
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.,Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Sarah Hoffe
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.,Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Kun Jiang
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Domenico Coppola
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Barbara A Centeno
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Anthony Magliocco
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Qian Li
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.,Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jose Trevino
- Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA
| | - Nipun Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Robert Gillies
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Mokenge Malafa
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
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El Gammal AT, Izbicki JR. Incidental Intraductal Papillary Mucinous Neoplasm, Cystic or Premalignant Lesions of the Pancreas. Surg Clin North Am 2018; 98:141-155. [DOI: 10.1016/j.suc.2017.09.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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32
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Duconseil P, Adham M, Sauvanet A, Autret A, Périnel J, Chiche L, Mabrut JY, Tuech JJ, Mariette C, Turrini O. Fukuoka-Negative Branch-Duct IPMNs: When to Worry? A Study from the French Surgical Association (AFC). Ann Surg Oncol 2018; 25:1017-1025. [PMID: 29392508 DOI: 10.1245/s10434-017-6318-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND This study analyzed the pathologic findings for patients with Fukuoka-negative branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) who theoretically were eligible for surveillance care with follow-up assessment, but instead underwent resection. METHODS From January 2005 to December 2012, 820 patients underwent evaluation for IPMN. At initial staging, 319 patients had BD-IPMN, and 89 of these patients presented with Fukuoka-negative criteria. These 89 patients were included in this study. RESULTS Of the 89 patients, 55 (62%) underwent pancreatectomy. After pathologic examination, the ultimate diagnosis was MT-IPMN for 20 (36%) of these patients (the MT group) and BD-IPMN for 35 (64%) of these patients (the BD group). The remaining 34 patients (38%) underwent enucleation. The patients in the MT group were more likely to be male (P = 0.01) and to have a higher rate of recent (< 1 year) diabetes mellitus diagnosis (P = 0.007) than the patients in the BD group. In the multivariate analysis, diabetes mellitus was independently associated with involvement of the main pancreatic duct (P = 0.05). Malignancy was diagnosed for 14 (16%) of the 89 patients. The rate of invasive IPMN was higher in the MT group than in the BD group (20% vs. 0%, P = 0.02). The 5-year overall survival rate was 100% for the BD group and 84% for the MT group (P = 0.02). For the male patients with diabetes mellitus, the rate of malignancy rose to 67%. CONCLUSIONS For patients with a diagnosis of Fukuoka-negative BD-IPMN, resection should be considered primarily for male patients with a recent diabetes mellitus diagnosis.
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Affiliation(s)
- Pauline Duconseil
- Department of Surgery, Hôpital Nord, Marseille, France. .,Department of Digestive Surgery, Hôpital Nord, Marseille, France.
| | - Mustapha Adham
- Department of Surgery, Hôpital Edouard-Herriot, Lyon, France
| | | | - Aurélie Autret
- Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France
| | - Julie Périnel
- Department of Surgery, Hôpital Edouard-Herriot, Lyon, France
| | - Laurence Chiche
- Department of Surgery, Maison du Haut-Lévêque, Bordeaux, France
| | | | | | | | - Olivier Turrini
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
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Jee KN. Mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm: A case report. World J Gastroenterol 2018; 24:297-302. [PMID: 29375215 PMCID: PMC5768948 DOI: 10.3748/wjg.v24.i2.297] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 11/15/2017] [Accepted: 11/21/2017] [Indexed: 02/06/2023] Open
Abstract
Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the pathologic findings of focal inflammatory fibrosis without evidence of tumor in pancreas. A 34-year-old man presented with right upper abdominal pain for a few weeks and slightly elevated bilirubin level on clinical findings. Radiological findings of multidetector-row computed tomography, magnetic resonance (MR) imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed focal branch pancreatic duct dilatation with surrounding delayed enhancing solid component at uncinate process and head of pancreas, suggesting branch duct type intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I would like to report the first case report of mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm.
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MESH Headings
- Adult
- Biopsy
- Cholangiopancreatography, Magnetic Resonance
- Diagnosis, Differential
- Endosonography
- Humans
- Male
- Multidetector Computed Tomography
- Neoplasms, Cystic, Mucinous, and Serous/diagnostic imaging
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/pathology
- Pancreaticoduodenectomy
- Pancreatitis, Alcoholic/diagnostic imaging
- Pancreatitis, Alcoholic/pathology
- Pancreatitis, Alcoholic/surgery
- Pancreatitis, Chronic/diagnostic imaging
- Pancreatitis, Chronic/pathology
- Pancreatitis, Chronic/surgery
- Predictive Value of Tests
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Affiliation(s)
- Keum Nahn Jee
- Department of Radiology, Dankook University Hospital, Chungcheongnam-do 330-715, South Korea
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Penheiter AR, Deelchand DK, Kittelson E, Damgard SE, Murphy SJ, O'Brien DR, Bamlet WR, Passow MR, Smyrk TC, Couch FJ, Vasmatzis G, Port JD, Marjańska M, Carlson SK. Identification of a pyruvate-to-lactate signature in pancreatic intraductal papillary mucinous neoplasms. Pancreatology 2018; 18:46-53. [PMID: 29170050 PMCID: PMC6139027 DOI: 10.1016/j.pan.2017.11.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 11/03/2017] [Accepted: 11/13/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We used transcriptomic profiling and immunohistochemistry (IHC) to search for a functional imaging strategy to resolve common problems with morphological imaging of cystic neoplasms and benign cystic lesions of the pancreas. METHODS Resected pancreatic cancer (n = 21) and normal pancreas were laser-capture micro-dissected, and transcripts were quantified by RNAseq. Functional imaging targets were validated at the protein level by IHC on a pancreatic adenocarcinoma tissue microarray and a newly created tissue microarray of resected intraductal papillary mucinous neoplasms (IPMNs) and IPMN-associated adenocarcinomas. RESULTS Genes encoding proteins responsible for cellular import of pyruvate, export of lactate, and conversion of pyruvate to lactate were highly upregulated in pancreatic adenocarcinoma compared to normal pancreas. Strong expression of MCT4 and LDHA was observed by IHC in >90% of adenocarcinoma specimens. In IPMNs, the pyruvate-to-lactate signature was significantly elevated in high grade dysplasia (HGD) and IPMN-associated adenocarcinoma. Additionally, cores containing HGD and/or adenocarcinoma exhibited a higher number of peri-lesional stromal cells and a significant increase in peri-lesional stromal cell staining of LDHA and MCT4. Interestingly, the pyruvate-to-lactate signature was significantly upregulated in cores containing only low grade dysplasia (LGD) from patients with histologically confirmed IPMN-associated adenocarcinoma versus LGD cores from patients with non-invasive IPMNs. CONCLUSION Our results suggest prospective studies with hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging are warranted. If these IHC results translate to functional imaging findings, a positive pyruvate-to-lactate imaging signature might be a risk factor for invasion that would warrant resection of IPMNs in the absence of other worrisome features.
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Affiliation(s)
- Alan R Penheiter
- Department of Molecular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Dinesh K Deelchand
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA
| | - Emily Kittelson
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA
| | - Sibel Erdogan Damgard
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Stephen J Murphy
- Department of Molecular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Daniel R O'Brien
- Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - William R Bamlet
- Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Marie R Passow
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Thomas C Smyrk
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Fergus J Couch
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - George Vasmatzis
- Department of Molecular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - John D Port
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
| | - Małgorzata Marjańska
- Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, 2021 6th Street SE, Minneapolis, MN 55455, USA
| | - Stephanie K Carlson
- Department of Molecular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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Zhou W, Rong Y, Kuang T, Xu Y, Shen X, Ji Y, Lou W, Wang D. The value of systemic inflammatory markers in identifying malignancy in mucinous pancreatic cystic neoplasms. Oncotarget 2017; 8:115561-115569. [PMID: 29383181 PMCID: PMC5777793 DOI: 10.18632/oncotarget.23310] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 12/04/2017] [Indexed: 12/12/2022] Open
Abstract
The treatment decision-making of mucinous pancreatic cystic neoplasm (PCN) has become a common clinical problem since the diagnostic accuracy of current tests in identifying malignancies in pancreatic cysts is limited. In this study, we aimed to validate the predictive value of systemic inflammatory factors in detecting malignant PCNs. Two hundred and forty-five patients with pathologically confirmed mucinous PCNs in a single Chinese institution were retrospectively analyzed. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cut-off values and measure the diagnostic value. The results showed that neutrophil count (P = 0.009), lymphocyte count (P = 0.002), neutrophil-to-lymphocyte ratio (NLR, P < 0.001), platelet-to-lymphocyte ratio (PLR, P < 0.001) and lymphocyte-to-monocyte ratio (LMR, P < 0.001) were distributed differently among the various differentiation groups of PCN. The univariate analyses indicated that a neutrophil count ≥ 2.8 × 109/L (P = 0.024), lymphocyte count ≤ 1.9 × 109/L (P < 0.001), PLR ≥ 125 (P < 0.001), NLR ≥ 1.96 (P < 0.001), and LMR ≤ 4.29 (P < 0.001) were significantly associated with invasive carcinomas in PCN patients. In addition, the multivariate analyses demonstrated that PLR ≥ 125 and LMR ≤ 4.29 were independent predictors of invasive malignancies. The ROC curves exhibited the malignant detection utility of the independent factor-based predictive model with an area under the curve (AUC) of 0.858 (P < 0.001). In conclusion, systemic inflammatory markers provide a supportive and easily accessible tool for the preoperative diagnoses of malignant PCNs.
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Affiliation(s)
- Wentao Zhou
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yefei Rong
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Tiantao Kuang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yadong Xu
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Xiaojing Shen
- Department of Pathology, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
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Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas. Ann Surg 2017; 266:1062-1068. [PMID: 27607098 DOI: 10.1097/sla.0000000000001985] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. BACKGROUND Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. METHODS Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. RESULTS The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. CONCLUSION A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.
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37
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Validation of the 2012 International Consensus Guidelines Using CT and MRI: Branch Duct and Main Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas. Ann Surg 2017; 266:e51-e52. [PMID: 29136961 DOI: 10.1097/sla.0000000000001382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Zhou W, Xu Y, Rong Y, Wu W, Kuang T, Xin B, Zhu H, Lou W, Wang D. Validation of Sendai and Fukuoka consensus guidelines in predicting malignancy in patients with preoperatively diagnosed mucinous pancreatic cystic neoplasms. J Surg Oncol 2017; 117:409-416. [PMID: 29044541 DOI: 10.1002/jso.24882] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 09/18/2017] [Indexed: 01/04/2023]
Affiliation(s)
- Wentao Zhou
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yadong Xu
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yefei Rong
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Wenchuan Wu
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Tiantao Kuang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Baobao Xin
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Hongxu Zhu
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
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Impact of MUC1 Expression on the Progression of Intraductal Papillary Mucinous Neoplasm With Worrisome Features During Follow-up. Pancreas 2017; 46:1127-1132. [PMID: 28902782 DOI: 10.1097/mpa.0000000000000902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES The aim of this study was to investigate whether MUC1 expression is associated with progression of intraductal papillary mucinous neoplasms with worrisome features during follow-up. METHODS Fifteen patients positive for MUC1 and negative for MUC2 (MUC1 group) and 16 patients negative for MUC1 and MUC2 (control group) were followed up and examined for changes in diameters of the main and ectatic branches of pancreatic ducts, enlargement of mural nodules, and appearance of a solid mass, by imaging studies. All of them presented worrisome features, and none had "high-risk stigmata." RESULTS The sizes of the main and ectatic branches of pancreatic ducts increased in 8 (53.3%) and 8 (53.3%) patients, respectively, of the MUC1 group and in 1 (6.3%) and 1 (6.3%) patients, respectively, of the control group (P = 0.0059 and 0.0059, respectively). A solid mass developed in 6 patients (33.3%) of the MUC1 group but in none of the control group patients (P = 0.0373). CONCLUSIONS Positive MUC1 expression in cell block cytology specimens may be associated with progressive dilation of the main and ectatic branches of pancreatic ducts and appearance of a solid mass in patients with intraductal papillary mucinous neoplasm with worrisome features during follow-up.
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40
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Lensing RJ, Bipat S. Incidences of Pancreatic Malignancy and Mortality in Patients With Untreated Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Surveillance: A Systematic Review. Pancreas 2017; 46:1098-1110. [PMID: 28902778 DOI: 10.1097/mpa.0000000000000907] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of this study was to pool incidences of increased cyst size, malignant branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs), pancreatic malignancy, and pancreatic malignancy-related death during follow-up (FU) of BD-IPMN patients. METHODS Searches were performed from January 2010 to April 2016. All hits were checked on inclusion criteria, and outcomes were extracted. Incidences were pooled. Three subgroups were defined: (1) including only BD-IPMN patients, (2) short-interval FU (maximum 6 months), and (3) long-interval FU (>6 months). RESULTS Thirty-one articles were enrolled, including 8455 patients (mean age, 66.4 years). Twenty-two studies included subgroup 1; 10 and 6 studies included, respectively, subgroups 2 and 3. Incidence of increased cyst size was 17.4%. In subgroups 1, 2, and 3, incidences were, respectively, 20.0%, 17.2%, and 31.7%. Incidence of malignant BD-IPMN was 2.5. In subgroups 1, 2, and 3, incidences were, respectively, 3.0%, 2.4%, and 3.3%. Incidence of pancreatic malignancy was 2.6%. In subgroups 1, 2, and 3, incidences were, respectively, 2.3%, 1.2%, and 4.0%. Incidence of death was 0.5%. In subgroups 1, 2, and 3, incidences were, respectively, 0.4%, 0.04%, and 0.12%. CONCLUSIONS Although not significant, all incidences on long-interval FU were higher; therefore, short-interval FU seems necessary to find resectable lesions.
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Affiliation(s)
- Rutger J Lensing
- From the Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
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41
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Permuth JB, Chen DT, Yoder SJ, Li J, Smith AT, Choi JW, Kim J, Balagurunathan Y, Jiang K, Coppola D, Centeno BA, Klapman J, Hodul P, Karreth FA, Trevino JG, Merchant N, Magliocco A, Malafa MP, Gillies R. Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas. Sci Rep 2017; 7:10484. [PMID: 28874676 PMCID: PMC5585319 DOI: 10.1038/s41598-017-09754-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 07/31/2017] [Indexed: 12/20/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5 and SRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (including ADARB2-AS1, ANRIL, GLIS3-AS1, LINC00472, MEG3, PANDA, PVT1, and UCA1) had greater accuracy than standard clinical and radiologic features in distinguishing 'aggressive/malignant' IPMNs that warrant surgical removal from 'indolent/benign' IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative 'radiomic' imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.
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Affiliation(s)
- Jennifer B Permuth
- Departments of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. .,Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
| | - Dung-Tsa Chen
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Sean J Yoder
- Molecular Genomics Core Facility, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jiannong Li
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Andrew T Smith
- Molecular Genomics Core Facility, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jung W Choi
- Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jongphil Kim
- Biostatistics and Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Yoganand Balagurunathan
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Kun Jiang
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Domenico Coppola
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Barbara A Centeno
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jason Klapman
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Pam Hodul
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Florian A Karreth
- Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Jose G Trevino
- Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville, Florida, USA
| | - Nipun Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Anthony Magliocco
- Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Mokenge P Malafa
- Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Robert Gillies
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
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Surveillance and Outcomes of Nonresected Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Meta-analysis. Pancreas 2017; 46:927-935. [PMID: 28697134 DOI: 10.1097/mpa.0000000000000858] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Guidelines regarding the surveillance of intraductal papillary mucinous neoplasms (IPMNs) are controversial because of uncertain risk of malignancy, agnosticism regarding the use of endoscopic ultrasound, and their recommendation to stop surveillance after 5 years. We present a systematic review and meta-analysis of the risk of malignancy and other end points and estimate the value of endoscopic ultrasound for surveillance. METHODS We systematically searched MEDLINE for studies with a cohort of patients with presumed branch-duct IPMN who initially were managed nonsurgically. Data regarding study characteristics, surveillance, and outcomes were extracted. Incidence rates of morphologic progression, malignancy, surgery, and death were calculated with a random effects model. RESULTS Twenty-four studies with 3440 patients and 13,097 patient-years of follow-up were included. Rates of morphologic progression, surgery, malignancy, and death were 0.0379, 0.0250, 0.0098, and 0.0043 per patient-year, respectively. Endoscopic ultrasound was not associated with significantly different rates of these outcomes. CONCLUSIONS The risk of malignancy calculated in this study was low and in line with recent systematic reviews. Endoscopic ultrasound does not have marginal use in surveillance. Given the limitations of a systematic review of nonrandomized studies, further studies are needed to determine the optimal surveillance of branch-duct IPMNs.
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Abstract
With increased utilization and ongoing advancements in cross-sectional abdominal imaging, the identification of a pancreatic cyst has become a frequent finding. While many pancreatic cysts are associated with a benign clinical course, others may transform into pancreatic ductal adenocarcinoma. However, distinguishing a benign from a malignant pancreatic cyst or pancreatic cyst with malignant potential on the basis of standard clinical findings, imaging parameters and ancillary studies can be challenging. Hence, a significant interest within the past decade has been the identification of novel biomarkers to accurately classify and prognosticate a pancreatic cyst. Within this review, we discuss novel DNA, miRNA, protein and metabolite biomarkers, and their relevance in clinical practice. In addition, we focus on future areas of research that have the potential to change pancreatic cyst management.
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Abstract
Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.
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Affiliation(s)
- James J Farrell
- Yale Center for Pancreatic Diseases, Interventional Endoscopy, Yale School of Medicine, New Haven, CT, USA. .,Section of Digestive Diseases, Yale University School of Medicine, LMP 1080, 15 York Street, New Haven, CT, 06510-3221, USA.
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45
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Nentwich M, Menzel K, Reeh M, Uzunoglu F, Ghadban T, Bachmann K, Schrader J, Bockhorn M, Izbicki J, Perez D. Blood fibrinogen levels discriminate low- and high-risk intraductal papillary mucinous neoplasms (IPMNs). Eur J Surg Oncol 2017; 43:758-762. [DOI: 10.1016/j.ejso.2016.12.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 12/05/2016] [Accepted: 12/16/2016] [Indexed: 01/26/2023] Open
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Re. Validation of the 2012 International Consensus Guidelines Using Computed Tomography and Magnetic Resonance Imaging. Ann Surg 2017; 266:e51. [PMID: 28257323 DOI: 10.1097/sla.0000000000001378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Moris M, Wallace MB. Intraductal papillary mucinous neoplasms and mucinous cystadenomas: current status and recommendations. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:358-367. [PMID: 28112959 DOI: 10.17235/reed.2017.4630/2016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The real prevalence of pancreatic cystic lesions remains unknown. The malignant potential of some of these lesions remains a cause for significant concern. Thus, it is mandatory to develop a strategy to clearly discriminate those cysts with a potential for malignant transformation from those that do not carry any significant risk. Intraductal papillary mucinous neoplasms and mucinous cystadenomas are mucinous cystic neoplasms with a known malignant potential that have gained greater recognition in recent years. However, despite the numerous studies that have been carried out, their differential diagnosis among other cysts subtypes and their therapeutic approach continue to be a challenge for clinicians. This review contains a critical approach of the current recommendations and management strategies regarding intraductal papillary mucinous neoplasms and mucinous cystadenomas, as well as highlighting the limitations exposed in current guidelines.
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Permuth JB, Choi JW, Chen DT, Jiang K, DeNicola G, Li JN, Coppola D, Centeno BA, Magliocco A, Balagurunathan Y, Merchant N, Trevino JG, Jeong D. A pilot study of radiologic measures of abdominal adiposity: weighty contributors to early pancreatic carcinogenesis worth evaluating? Cancer Biol Med 2017; 14:66-73. [PMID: 28443205 PMCID: PMC5365183 DOI: 10.20892/j.issn.2095-3941.2017.0006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Objective: Intra-abdominal fat is a risk factor for pancreatic cancer (PC), but little is known about its contribution to PC precursors known as intraductal papillary mucinous neoplasms (IPMNs). Our goal was to evaluate quantitative radiologic measures of abdominal/visceral obesity as possible diagnostic markers of IPMN severity/pathology. Methods: In a cohort of 34 surgically-resected, pathologically-confirmed IPMNs (17 benign; 17 malignant) with preoperative abdominal computed tomography (CT) images, we calculated body mass index (BMI) and four radiologic measures of obesity: total abdominal fat (TAF) area, visceral fat area (VFA), subcutaneous fat area (SFA), and visceral to subcutaneous fat ratio (V/S). Measures were compared between groups using Wilcoxon two-sample exact tests and other metrics. Results: Mean BMI for individuals with malignant IPMNs (28.9 kg/m2) was higher than mean BMI for those with benign IPMNs (25.8 kg/m2) (P=0.045). Mean VFA was higher for patients with malignant IPMNs (199.3 cm2) compared to benign IPMNs (120.4 cm2),P=0.092. V/S was significantly higher (P=0.013) for patients with malignant versus benign IPMNs (1.25vs. 0.69 cm2), especially among females. The accuracy, sensitivity, specificity, and positive and negative predictive value of V/S in predicting malignant IPMN pathology were 74%, 71%, 76%, 75%, and 72%, respectively.
Conclusions: Preliminary findings suggest measures of visceral fat from routine medical images may help predict IPMN pathology, acting as potential noninvasive diagnostic adjuncts for management and targets for intervention that may be more biologically-relevant than BMI. Further investigation of gender-specific associations in larger, prospective IPMN cohorts is warranted to validate and expand upon these observations.
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Affiliation(s)
| | - Jung W Choi
- Diagnostic Imaging and Interventional Radiology
| | | | | | - Gina DeNicola
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa 33612, FL, USA
| | | | | | | | | | - Yoganand Balagurunathan
- Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa 33612, FL, USA
| | - Nipun Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami 33136, FL, USA
| | - Jose G Trevino
- Department of Surgery, Division of General Surgery, University of Florida Health Sciences Center, Gainesville 32611, FL, USA
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Outcome of long interval radiological surveillance of side branch pancreatic duct-involved intraductal papillary mucinous neoplasm in selected patients. HPB (Oxford) 2016; 18:879-885. [PMID: 27591177 PMCID: PMC5094481 DOI: 10.1016/j.hpb.2016.06.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 06/05/2016] [Accepted: 06/13/2016] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Side branch IPMN (SB-IPMN) of the pancreas has a malignancy rate between 10 and 20%. We hypothesized that surveillance at longer intervals on selected patients with SB-IPMN might be indicated. METHODS This is a retrospective study of prospectively collected data of 276 patients presenting from 2000 to 2010. After 2007, we opted to screen our patients with longer intervals, initially at 12 months then 24 months using MR if no "worrisome features" were present. RESULTS Complete data sets for 261 patients were analysed and patients were aged 78 (40-91) years. 232 patients had sole SB-IPMN while 92% were incidental (n = 209) and 8% were symptomatic (n = 24). Single SB-IPMN accounted for 84% (n = 195) of all cases; maximum diameter of 15.5 (5-60) mm. The median follow up duration was 46 (32-53) months. Short interval radiological surveillance (3-9 months) was 39% (n = 90), while long interval surveillance (12-36 months) was performed in 61% (n = 142). The rate of pancreatic resection, due to concern for the development of pancreatic cancer, in the short and long interval surveillance groups was 4.4% (n = 4) and 3.5% (n = 5) respectively; p = 0.78. CONCLUSION Our data suggests no difference in outcome between long and short interval MR surveillance of SB-IPMN patients.
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Goh BKP, Teo JY, Allen JC, Tan DMY, Chan CY, Lee SY, Tai DWM, Thng CH, Cheow PC, Chow PKH, Ooi LLPJ, Chung AYF. Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms. Pancreatology 2016; 16:888-892. [PMID: 27421563 DOI: 10.1016/j.pan.2016.06.660] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 06/08/2016] [Accepted: 06/24/2016] [Indexed: 12/11/2022]
Abstract
INTRODUCTION To determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients. METHODS 318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index. RESULTS The optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICG(HR) group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740-0.829) vs AUC 0.822 (95% CI: 0.772-0.872) (p = 0.0032)]. CONCLUSIONS High PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Consensus
- Female
- Guidelines as Topic
- Humans
- Jaundice, Obstructive/complications
- Lymphocyte Count
- Male
- Middle Aged
- Neoplasm Invasiveness/pathology
- Neoplasms, Cystic, Mucinous, and Serous/blood
- Neoplasms, Cystic, Mucinous, and Serous/diagnosis
- Neoplasms, Cystic, Mucinous, and Serous/surgery
- Neutrophils
- Pancreatic Neoplasms/blood
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/surgery
- Platelet Count
- Predictive Value of Tests
- Prognosis
- Retrospective Studies
- Triage/methods
- Young Adult
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Affiliation(s)
- Brian K P Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore.
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | | | - Damien M Y Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Ser-Yee Lee
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - David W M Tai
- Division of Medical Oncology, National Cancer Centre, Singapore
| | - Choon-Hua Thng
- Department of Diagnostic Imaging, National Cancer Centre, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Pierce K H Chow
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
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