Will Ipmn Pancreas Continue to Grow

Intraductal papillary mucinous neoplasms (IPMNs) are commonly found, and management is difficult because of the lack of consensus and limited data on long-term surveillance outcomes. Studies investigating the natural history of IPMNs have shown a high overall prevalence of carcinoma. Malignancy has been identified in 60–90% of resected main pancreatic duct IPMNs and 6–29% of side-branch IPMNs [1–8]. The risk of progression and malignant transformation varies depending on IPMN type (main duct versus side branch), lesion size, and complexity. Although size is the most reproducible imaging characteristic [9, 10], features including enhancing solid components, 5-mm or greater pancreatic duct dilatation, thick cyst walls, and mural nodules are better predictors of malignant transformation and considered high-risk stigmata [11].

Multiple guidelines have been established in an attempt to risk stratify pancreatic cysts and establish a surveillance framework. Guidelines (established in 2006 and revised in 2012) have been proposed by the International Association of Pancreatology, the American College of Radiology (ACR), and the American Gastroenterological Association (AGA) [12–14]. Although these management guidelines are generally comparable for cysts with high-risk features, controversy continues regarding management of small (< 3 cm) incidental pancreatic cysts that do not exhibit worrisome features.

Multiple studies have shown the growth and malignant potential of these low-risk cysts at 1–3 years of surveillance. Frequently cited ranges are that approximately 10–30% of simple unilocular cysts exhibit significant growth during surveillance [15, 16]. As many as 5% of small (< 20 mm), simple-appearing cystic lesions develop worrisome features detected at imaging performed years after the initial diagnosis [16], and approximately 11% exhibit delayed growth after an initial 1-year period of stability [15]. Malignant transformation may occur as late as 3–5 years after the initial imaging diagnosis [17]. However, few studies thus far have shown outcomes of surveillance beyond 4 years, especially exclusively in a population at low risk [18, 19].

According to ACR recommendations for the management of incidental findings, surveillance imaging of small (< 20 mm) stable asymptomatic pancreatic cysts should cease at 1 year [14]. Recent AGA guidelines echo conservative management and recommend that patients with low- to intermediate-risk cysts undergo maximum surveillance of 5 years if during that surveillance period, there is no change in cyst size or characteristics [12]. Although the Fukuoka (revised from the Sendai guidelines of the International Association of Pancreatology), AGA, and ACR guidelines are attempts to standardize surveillance for low-risk cysts, they represent conditional recommendations based on the low quality of evidence and have proved controversial in clinical practice [12–14].

The long-term natural history of low-risk pancreatic cysts is an active area of research. The optimal length of surveillance has yet to be identified. Recommendations for long-term follow-up guidelines are lacking, as are data regarding predictors of progression and malignant transformation. The primary aims of this study were to determine rate of growth and interval progression of presumed low-risk branch duct IPMNs with more than 4 years of follow-up, identify predictors of progression, and understand the timeline of progression.

Study Population

This HIPAA-compliant institutional review board–approved study was conducted with a waiver of the requirement for informed consent. A retrospective review of clinical, radiologic, and endoscopic databases over the period January 2001–December 2013 was performed. A keyword search of the electronic medical chart system was performed with the following terms: pancreatic cyst, pancreatic cystic lesion, IPMN, IPMT, intraductal papillary tumor, intraductal papillary neoplasm, intraductal papillary mucinous tumor, intraductal papillary mucinous neoplasm, and pancreatic pseudocyst.

Inclusion and Exclusion Criteria

The inclusion criteria were as follows: age older than 18 years, presumed branch duct IPMN but without Fukuoka high-risk stigmata (jaundice, enhancing solid components, main pancreatic dilatation ≥ 10 mm) or worrisome features (thick cyst walls, mural nodules, pancreatic duct dilatation of 5–9 mm, or abrupt changes in pancreatic duct size with distal pancreatic atrophy) at initial radiologic or endoscopic imaging. Cysts with a baseline size of 30 mm or larger were included if they had no additional high-risk stigmata or worrisome features. Cysts were identified as branch duct IPMN based on the presence of unilocular or multilocular cysts without main pancreatic duct dilatation and without the features considered exclusion criteria, which would make an alternative diagnosis overwhelmingly likely (Fig. 1 ). Visualization of the branch duct was not an absolute criterion for classifying a lesion as IPMN. Minimum interval follow-up of 4 years with either cross-sectional imaging (CT or MRI) or endoscopic ultrasound was also required.

View larger version (312K)

Fig. 1A —53-year-old woman with intraductal papillary mucinous neoplasm. A, Axial T2-weighted (A), coronal T2-weighted (B), and coronal 3D MRCP (C) images obtained with 1.5-T MRI system show multilocular cyst in pancreatic body without high-risk stigmata or worrisome features.

View larger version (272K)

Fig. 1B —53-year-old woman with intraductal papillary mucinous neoplasm. B, Axial T2-weighted (A), coronal T2-weighted (B), and coronal 3D MRCP (C) images obtained with 1.5-T MRI system show multilocular cyst in pancreatic body without high-risk stigmata or worrisome features.

View larger version (193K)

Fig. 1C —53-year-old woman with intraductal papillary mucinous neoplasm. C, Axial T2-weighted (A), coronal T2-weighted (B), and coronal 3D MRCP (C) images obtained with 1.5-T MRI system show multilocular cyst in pancreatic body without high-risk stigmata or worrisome features.

We excluded patients if they had evidence of high-risk stigmata or worrisome features. Patients were also excluded if they had any of the following: a history of chronic pancreatitis or pancreatic cancer, cysts with morphologic characteristics consistent with serous cystadenoma or pseudocyst, or spontaneous cyst resolution or cyst resection before the end of the minimum 48-month surveillance period. Duplicate patient data and patients without pancreatic cystic lesions were also excluded after the keyword search (Fig. 2 ).

View larger version (76K)

Fig. 2 —Patient selection and flow diagram. Other cystic lesions include cystic degeneration of carcinoma, duplication cysts, and phlegmon gastrointestinal stromal tumor with cystic component. BD-IPMN = branch duct intraductal papillary mucinous neoplasm, SC = serous cystadenoma, NET = neuroendocrine tumor.

Data Collection

Two resident physicians (one postgraduate year 2 in internal medicine, one postgraduate year 3 in diagnostic radiology) reviewed medical charts, imaging reports, and images when reports were incomplete. The following demographic and clinical data were collected: age, sex, symptoms (abdominal pain, steatorrhea, weight loss, jaundice) and length of follow-up. The following cyst characteristics were collected: location, number (unifocal vs multifocal), morphologic features, initial and serial sizes, main pancreatic duct communication, pancreatic duct size, initial presence or interval development of associated solid components, thickened septation, or change in pancreatic duct with distal atrophy. Endoscopic records were examined for cytopathologic results and cyst fluid carcinoembryonic antigen (CEA) and amylase, if the tests were available. Cyst size was documented as the maximum observed cyst diameter in any plane. The size of the largest discrete cyst was used for analysis.

Assessment of Interobserver Variability, Cyst Measurement, and Definition of Progression

The minimum growth threshold for progression was established by assessment of the interreader variability of cyst measurement. Forty patients with pancreatic cysts of varying sizes (mean, 14.3 mm; range, 3–34 mm) were randomly selected by an author not involved in the image interpretation to be reviewed by radiologists. A postgraduate year 3 diagnostic radiology resident and a board-certified radiologist with more than 10 years of experience blinded to the imaging reports independently reviewed the serial imaging and performed serial measurements for each patient. Images were interpreted at a commercially available radiology PACS workstation, and if needed integrated 3D reconstruction software (Aquarius iNtuition, verson 4.4.11, TeraRecon) was used. MRI and MRCP were performed with a 1.5-T system (Signa, GE Healthcare). The greatest cyst diameter (outer wall to outer wall) in any plane was measured on axial (thickness, 5–8 mm) and coronal (5 mm) single-shot fast spin-echo, 2D thick slab MRCP (40 mm), and 3D MRCP (1.4 mm) images. The pancreatic neck and linear connections to the pancreatic duct were not included. Cysts were also measured with MDCT in the axial or coronal plane with slice thickness ranging from 1.25 to 5 mm. The methods used to measure the maximal cyst size in any dimension were similar to those described in other publications [19, 20]. Initially, a sample of 10 test cases, excluded from the interobserver variability analysis, were reviewed by both readers independently to ensure interpretation criteria and measurement guidelines were followed.

Comparison was made between the two readers' measurements and those recorded in the original radiology report to assess interobserver variability between the three readers. Cyst progression was defined as an increase of greater than 1 SD in intraobserver variability or the development of worrisome features, such as pancreatic duct dilatation, solid components, thickened or enhancing cyst walls, or abrupt change in pancreatic duct with distal atrophy. Nonprogression was defined as a lack of size change or any decrease in cyst size.

Statistical Analysis

Descriptive statistics were prepared for all data, including frequencies and percentages for categoric variables and means and SD for quantitative variables. Kaplan-Meier curves were generated to evaluate time to cyst progression and linear mixed models to evaluate rate of growth.

Patient Demographics and Baseline Characteristics of Branch Duct Intraductal Papillary Mucinous Neoplasms

A total of 2423 patients were identified in the electronic medical record keyword search. Among these, 2263 patients were identified as having pancreatic cysts, but only 1063 patients had undergone more than one surveillance study. Two hundred twenty-eight patients had more than 48 months of follow-up and had no previous pancreatic surgery. Of these, 131 patients with presumed branch duct IPMNs without high-risk stigmata or worrisome features at baseline were identified (Fig. 2 ). Patients underwent follow-up for a mean period of 74.5 months. The mean age of the study patients was 72 (SD, 13) years.

Interobserver Variability and Minimum Growth Threshold for Progression

Intraclass correlation was 0.88 mm (95% CI, 0.77–0.94 [SD, 1.2] mm), indicating nearly perfect agreement between all readers. A progression threshold of 2 mm or greater or 20% or greater was therefore considered an acceptable threshold for the imaging data in this study. Development of worrisome features was also considered progression, regardless of cyst size change.

Prevalence of Progression

The mean initial size of the 131 presumed branch duct IPMNs was 13.8 ± 9 mm; 10 cysts had an initial size of 30 mm or larger. Among the 131 cysts, 76 (58.0%) were located in the pancreatic body or tail, and 55 (42.0%) were located in the uncinate process or head of the pancreas. Seventy-one of the 131 (54.2%) cysts were multifocal (more than two cysts in the pancreas), and 60 (45.8%) were unifocal (Table 1).

TABLE 1: Cyst Characteristics

Among the 131 patients with branch duct IPMNs, 73 (55.7%) of cysts progressed, and 58 (44.3%) did not. The mean initial cyst size was 13.0 ± 7 mm for cysts that progressed and 14.7 ± 11 mm for those that did not. Overall, 61 of the 131 (46.6%) cysts increased in size without interval development of worrisome features, 10 (7.6%) increased in size and developed worrisome features, and two (1.5%) developed worrisome features only. Within the subset of 73 cysts that progressed, 61 (83.6%) of the cysts increased 2 mm or more or 20% or more in maximum cyst diameter with a mean cyst size increase of 7.4 (SD, 6) mm. Only 12 of the 73 (16.4%) cystic lesions that progressed developed worrisome features (10 with concurrent size increase, two without a change in size).

Among the 12 cysts that developed worrisome features, three had a change in pancreatic duct caliber with distal atrophy, two developed pancreatic duct dilatation of 5 mm or more, and two cysts developed thick or enhancing septations (Table 2). Five of 12 patients had more than one worrisome feature, most commonly pancreatic duct dilatation accompanied by distal atrophy and thick septations. Two patients had high-risk features warranting surgery. The first of these patients was 85 years old with cyst size increasing from 22 to 49 mm and greater than 10-mm dilatation of the main pancreatic duct over a surveillance period of 102 months. The second patient was 71 years old with an increase in cyst size from 23 to 42 mm and interval development of greater than 10-mm main pancreatic duct dilatation over 156 months. Because of comorbid conditions identified at the time of last surveillance, neither patient underwent resection. None of the 131 patients with presumed branch duct IPMNs had pancreatic adenocarcinoma.

TABLE 2: Criteria for Progression (n = 73)

Risk Factors for Progression

Age was the only patient demographic noted to be significantly different between cysts that progressed and those that did not. The mean age of patients with cysts that progressed was 75 years compared with 70 years for those with cysts that did not progress (p = 0.03). There were no significant differences in sex, baseline symptoms, initial cyst size, or location or number of cysts (unifocal vs multifocal) (Table 1).

Cysts that progressed were stratified by baseline size into two groups. In the first group, baseline cyst size was stratified into three subgroups (< 10 mm, 10–20 mm, and > 20 mm). In the second group, it was stratified into two subgroups (≤ 20 mm and > 20 mm). The interval time points of these cysts were plotted, and Kaplan-Meier curves were constructed. Overall, there was no significant difference in risk of progression among cysts of different baseline sizes (three-size group, p = 0.19; two-size group, p = 0.74) (Fig. 3 ).

View larger version (36K)

Fig. 3A —Kaplan-Meier survival estimates of risk of progression stratified by baseline cyst size at diagnosis. A, Graph shows risk stratified by baseline cyst size < 10 mm, 10–20 mm, and > 20 mm.

View larger version (29K)

Fig. 3B —Kaplan-Meier survival estimates of risk of progression stratified by baseline cyst size at diagnosis. B, Graph shows risk stratified by baseline cyst size ≤ 20 mm and > 20 mm.

Rate and Timing of Progression of Branch Duct Intraductal Papillary Mucinous Neoplasms

Fifty of 71 (70.4%) cysts increased in size within the first 5 years of surveillance. Size progression occurred with a nearly even distribution per year within this time period. This finding suggests that progression may be as likely in the first 2–3 years as in subsequent years. The mean annual rate of change was 0.8 mm/y for cysts with a baseline size less than 10 mm, 1.0 mm/y for cysts measuring 10–20 mm, and 1.3 mm/y for cysts larger than 20 mm. Twenty-one of the 71 (29.6%) cysts did not increase in size until after 5 years of surveillance. Among these patients, 18 of 21 (85.7%) underwent at least one imaging study at least 2 years after the previous one within the first 5 years of surveillance. There were no significant differences in the growth rates of cysts with different baseline sizes (stratified as < 10 mm, 10–20 mm, > 20 mm) during up to 50 months of surveillance. After 50 months of surveillance, however, cysts with a baseline size of 20 mm or smaller reached a plateau in growth, but cysts with baseline size larger than 20 mm continued to show significant increases in size (p < 0.05) and rates of change (Fig. 4 ).

View larger version (90K)

Fig. 4 —Graph shows cumulative linear fit of plotted progression time points stratified by baseline cyst size before and after initial 50-month surveillance period.

Cytopathologic Assessment

Eighty-five of the 131 patients (64.9%) had accompanying fine-needle aspiration (FNA) and cytopathologic data. The percentage of atypical cyst aspirate cytologic features was significantly greater for the cysts that progressed (23.4%) than for those that did not (7.9%) (p = 0.02). Otherwise, there were no significant differences in mean cyst CEA level or percentage of patients with worrisome features seen at endoscopic ultrasound (Table 3). Of the 12 lesions that developed worrisome features, four were evaluated with FNA, all with negative results. Thirty-three of 73 (45.2%) cysts that progressed were evaluated with FNA, and only one lesion (3.0%) exhibited high-grade dysplasia, in a cyst with a size increase of 3 mm.

TABLE 3: Baseline Endoscopic Ultrasound Characteristics

The long-term natural history of low- to intermediate-risk branch duct IPMNs is not well understood. Previous studies of long-term outcomes of branch duct IPMNs have shown favorable results for patients enrolled in surveillance programs, but limitations have prohibited generalizability [21–23]. Our retrospective review represents one of the larger IPMN cohorts with long-term surveillance and adds a number of cases to the literature.

Within our cohort of low- to intermediate-risk branch duct IPMNs, more than one-half of them (55.7%) increased in size. This rate is higher than previously reported ranges (12–47%) [9, 18, 19, 24, 25]. Our mean follow-up time (74.5 months) is similar to that in previous studies (77–96 months) in which increase in overall cyst size along the higher end of the percentage range (38–41%) was reported [18, 24]. The study showing the highest percentage of cysts that underwent interval growth (47%) [25] had a shorter mean follow-up time (30.6 months), included cysts measuring 8–40 mm, and used a threshold of 1 mm instead of 2 mm to define size progression. Our overall patient cohort is larger than that in most of the previous studies, and approximately 30% of the pancreatic cysts exhibited progression after only 5 years of imaging surveillance. Therefore, with a shorter mean follow-up time, a number of cysts that progress may be missed.

In addition, among the patients who had multifocal pancreatic cystic lesions (two or more), only the largest cyst was measured according to the methods in this study. None of the nondominant cysts in these patients developed adenocarcinoma, had worrisome features, or became larger than the originally identified dominant cyst. If these additional cysts were included in our study population, it is likely that the overall percentage of cysts showing progression would fall within the range reported in previous studies.

Despite the higher incidence of cyst growth in our cohort, the increase in size did not portend worse outcome than for cystic lesions that did not grow. Less than 10% (9.1%) of the cysts in this study developed worrisome features, and only a single lesion (3.0% of all cysts that progressed) had high-grade dysplasia, and in no patient did adenocarcinoma develop. These results are in keeping with a recent report [25] of 1.0% mortality due to progression of branch duct IPMN to cancer and 0.5% mortality secondary to concomitant pancreatic cancer separate from known branch duct IPMN. Overall, morbidity and mortality due to these asymptomatic cystic pancreatic lesions appear to be very small.

Our definition of progression (increase in size ≥ 2 mm or ≥ 20% of the largest cyst dimension) is based on clinical relevance and considered an appropriate threshold given that the interreader variability in our study was below this measurement threshold. This definition has been increasingly applied to clinical practice and was most recently used in a large multicenter trial in which it was proved to be effective in differentiating cysts that progressed from cysts that did not [26]. In addition, our method of measuring cysts was similar to that used by Nougaret et al. [19], who evaluated the additive value of gadolinium contrast enhancement in MRI follow-up of pancreatic cysts.

Though there was no statistical significance and a large overlap in mean baseline cyst size between cysts that progressed and those that did not, cysts larger than 2 cm in maximum single dimension at baseline continued to increase in size, as found at surveillance imaging after more than 50 months, and 30% did not exhibit progression until after 5 years of surveillance. This is particularly relevant given newer AGA guidelines calling for less surveillance of stable cysts. If these same guidelines had been applied to the treatment of the patients in our study population, approximately 30% of lesions with interval growth would have been missed, illustrating the challenges of appropriate patient follow-up. Until more data become available, it may be prudent to extend surveillance guidelines beyond those of the current ACR, Fukuoka, and AGA guidelines, past 5 years, perhaps adding one additional imaging study at 10 years if the patient remains a good surgical candidate.

Most of our patients underwent baseline endoscopic ultrasound and FNA evaluation. The presence of cellular atypia but not CEA was associated with risk of progression. A 2011 study of the predictive value of cyst fluid markers in diagnosing malignancy [27] showed no significant difference in CEA levels between benign and malignant mucinous cysts.

Most of the limitations of this study arose from the retrospective nature of our review, the lack of histopathologic confirmation of the diagnosis of branch duct IPMN, and variable timing of imaging follow-up. The keyword search may not have been all-encompassing, such that some cases of cystic pancreatic masses may have been missed, potentially introducing selection bias. Selection bias also may have ben present in the choice of patients with more than 4 years of follow-up, who may be more likely to survive or less likely to have progression early on. We have not provided information on the patients we excluded because of lack of long-term (> 4 year) follow-up and the low rate of high-grade lesions in this cohort.

The inclusion of cysts with baseline size greater than 3 cm without high-risk stigmata (n = 10) in our cohort is contrary to management guidelines, yet our data suggest that baseline cyst size alone is not predictive of cyst progression or development of high-risk features. Thus, we believe that including these lesions in our study population was merited. Although we acknowledge that surveillance of cysts larger than 3 cm is not recommended under current guidelines because of the increased risk of malignancy [11], we included these patients in this study because it was a unique opportunity to observe the natural history of the disease.

The lack of standardized surveillance protocols and uniform time intervals were particular limitations for assessing growth rate. Despite these biases, we believe the cohort of patients we included represents a highly clinically relevant patient population that is the target of guidelines on long-term surveillance.

We did not evaluate volumetric analysis of pancreatic cystic lesions in this patient cohort because of technical limitations (3D MRCP data not available for all patients, 2D imaging slice thickness ranging from 5 to 8 mm, and motion as a limitation to performing segmentation in the smaller lesions). Instead we measured the greatest dimension, because it is the current standard of practice and more reproducible in clinical practice. Though cystic pancreatic segmentation remains challenging to routinely reproduce, studies of CT texture analysis show promise for determining the histologic grade of IPMN [28, 29].

The results of our study suggest that over long-term surveillance, increase in cyst size among low-risk IPMNs is common, that development of worrisome features is uncommon, and that even fewer cysts meet high-risk surgical criteria. The timeline of size progression in our cohort suggests that most low-risk IPMNs will exhibit progression within the first 5 years of surveillance and that as many as 30% will exhibit progression after 5 years of follow-up. The rate and likelihood of progression in our study cohort would support extending surveillance intervals to at least every 2 years for low-risk IPMN. Although 5 years of surveillance may be sufficient for low-risk branch duct IPMNs measuring 20 mm or smaller, extended surveillance (perhaps to 10 years) should be considered for IPMNs larger than 20 mm if the patient remains a surgical candidate.

1. Choi BS, Kim TK, Kim AY, et al. MR cholangiopancreatography and MR angiography. Korean J Radiol 2003; 4:157–162 [Google Scholar]

2. Doi R, Fujimoto K, Wada M, Imamura M. Surgical management of intraductal papillary mucinous tumor of the pancreas. Surgery 2002; 132:80–85 [Google Scholar]

3. Kitagawa Y, Unger TA, Taylor S, Kozarek RA, Traverso LW. Mucus is a predictor of better prognosis and survival in patients with intraductal papillary mucinous tumor of the pancreas. J Gastrointest Surg 2003;7:12–18; discussion, 18–19 [Google Scholar]

4. Kobari M, Egawa S, Shibuya K, et al. Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: differences in clinical characteristics and surgical management. Arch Surg 1999; 134:1131–1136 [Google Scholar]

5. Matsumoto T, Aramaki M, Yada K, et al. Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas. J Clin Gastroenterol 2003; 36:261–265 [Google Scholar]

6. Sohn TA, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity. Ann Surg 2001; 234:313–321; discussion, 321–322 [Google Scholar]

7. Sugiyama M, Suzuki Y, Abe N, Mori T, Atomi Y. Management of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 2008; 43:181–185 [Google Scholar]

8. Terris B, Ponsot P, Paye F, et al. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 2000; 24:1372–1377 [Google Scholar]

9. Lee SH, Shin CM, Park JK, et al. Outcomes of cystic lesions in the pancreas after extended follow-up. Dig Dis Sci 2007; 52:2653–2659 [Google Scholar]

10. Nagai K, Doi R, Ito T, et al. Single-institution validation of the international consensus guidelines for treatment of branch duct intraductal papillary mucinous neoplasms of the pancreas. J Hepatobiliary Pancreat Surg 2009; 16:353–358 [Google Scholar]

11. Tanaka M. International consensus on the management of intraductal papillary mucinous neoplasm of the pancreas. Ann Transl Med 2015; 3:286 [Google Scholar]

12. Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee American Gastroenterology Association. American Gastroenterological Association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015;148:819–822 [Google Scholar]

13. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12:183–197 [Google Scholar]

14. Berland LL, Silverman SG, Gore RM, et al. Managing incidental findings on abdominal CT: white paper of the ACR incidental findings committee. J Am Coll Radiol 2010; 7:754–773 [Google Scholar]

15. Brook OR, Beddy P, Pahade J, et al. Delayed growth in incidental pancreatic cysts: are the current American College of Radiology recommendations for follow-up appropriate? Radiology 2016; 278:752–761 [Google Scholar]

16. Tanno S, Nakano Y, Nishikawa T, et al. Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results. Gut 2008; 57:339–343 [Google Scholar]

17. Yamada Y, Mori H, Matsumoto S, Kamei N, Hongo N. Invasive carcinomas derived from intraductal papillary mucinous neoplasms of the pancreas: a long-term follow-up assessment with CT imaging. J Comput Assist Tomogr 2006; 30:885–890 [Google Scholar]

18. Handrich SJ, Hough DM, Fletcher JG, Sarr MG. The natural history of the incidentally discovered small simple pancreatic cyst: long-term follow-up and clinical implications. AJR 2005; 184:20–23 [Abstract] [Google Scholar]

19. Nougaret S, Reinhold C, Chong J, et al. Incidental pancreatic cysts: natural history and diagnostic accuracy of a limited serial pancreatic cyst MRI protocol. Eur Radiol 2014; 24:1020–1029 [Google Scholar]

20. Sainani NI, Saokar A, Deshpande V, Fernandezdel Castillo C, Hahn P, Sahani DV. Comparative performance of MDCT and MRI with MR cholangiopancreatography in characterizing small pancreatic cysts. AJR 2009; 193:722–731 [Abstract] [Google Scholar]

21. Baiocchi GL, Portolani N, Grazioli L, et al. Management of pancreatic intraductal papillary mucinous neoplasm in an academic hospital (2005–2010): what follow-up for unoperated patients? Pancreas 2013; 42:696–700 [Google Scholar]

22. Cauley CE, Waters JA, Dumas RP, et al. Outcomes of primary surveillance for intraductal papillary mucinous neoplasm. J Gastrointest Surg 2012; 16:258–267; discussion, 266 [Google Scholar]

23. Khannoussi W, Vullierme MP, Rebours V, et al. The long term risk of malignancy in patients with branch duct intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2012; 12:198–202 [Google Scholar]

24. Arlix A, Bournet B, Otal P, et al. Long-term clinical and imaging follow-up of nonoperated branch duct form of intraductal papillary mucinous neoplasms of the pancreas. Pancreas 2012; 41:295–301 [Google Scholar]

25. Del Chiaro M, Ateeb Z, Hansson MR, et al. Survival analysis and risk for progression of intraductal papillary mucinous neoplasia of the pancreas (IPMN) under surveillance: a single-institution experience. Ann Surg Oncol 2017; 24:1120–1126 [Google Scholar]

26. Kwong WT, Lawson RD, Hunt G, et al. Rapid growth rates of suspected pancreatic cyst branch duct intraductal papillary mucinous neoplasms predict malignancy. Dig Dis Sci 2015; 60:2800–2806 [Google Scholar]

27. Park JA, Kim YE, Seok HJ, Park WY, Kwon HJ, Lee Y. Differentiation and upregulation of heat shock protein 70 induced by a subset of histone deacetylase inhibitors in mouse and human embryonic stem cells. BMB Rep 2011; 44:176–181 [Google Scholar]

28. Hanania AN, Bantis LE, Feng Z, et al. Quantitative imaging to evaluate malignant potential of IPMNs. Oncotarget 2016; 31:1–9 [Google Scholar]

29. Permuth JB, Choi J, Balarunathan Y, et al. Combining radiomic features with a miRNA classifier may improve prediction of malignant pathology for pancreatic intraductal papillary mucinous neoplasms. Oncotarget 2016; 7:85785–85797 [Google Scholar]

thigpencoad1951.blogspot.com

Source: https://www.ajronline.org/doi/full/10.2214/AJR.16.17249

Share this post