Abstract
Objectives:
The natural course of pancreatic cysts in inflammatory bowel disease (IBD) is unknown. We aim to describe the natural course of pancreatic cysts in IBD and evaluate long-term outcomes.
Methods:
A database of patients with abdominal imaging diagnosis of pancreatic cysts (2008–2019) was reviewed. Patients with IBD and pancreatic cysts (study group) and pancreatic cysts without IBD (controls) were selected. Outcomes were measured at 1, 3, 5, and 10 years. Several logistic regression models were used for analysis.
Results:
Of the 1789 patients evaluated, 1690 had pancreatic cysts without IBD, and 78 had IBD and pancreatic cysts. Majority of cysts were intraductal papillary mucinous neoplasms. Patients with IBD and pancreatic cysts were more likely to be diagnosed with pancreatic cysts at a younger age (P < 0.001) and were more likely to undergo surgical intervention at a younger age (P < 0.001).
Conclusions:
This is the first study to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in long-term outcomes. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD.
Keywords: Crohn disease, cystic, lesions, neoplasm, pancreas, ulcerative colitis
It is estimated that the incidence and the prevalence of pancreatic cysts are as high as 40% and 49.1%, respectively, in patients who undergo magnetic resonance imaging (MRI). Age is considered a risk factor for increased prevalence, number, and size of pancreatic cysts. The high rates of pancreatic cysts in the general population are thought to be due to the use of more sophisticated imaging modalities.1–6 In the past decade, there has been an increased interest in describing the natural course of these cysts and identifying predictors for unfavorable outcomes. Multiple societies have provided recommendations on the optimal diagnostic modality, long-term surveillance, and indications for surgery.4,6,7 Although chronic inflammation, autoimmunity, and genetic predisposition have been suggested to contribute to the etiology of pancreatic cysts, very limited studies have examined or identified underlying risk factors.8–21 It is also unknown if other chronic medical conditions or certain medications contribute to the development of pancreatic cysts or alter their natural course.17,18,20,21
Inflammatory bowel disease (IBD) is a chronic inflammatory process, with most patients presenting at an age younger than 30 years.22,23 Although a number of studies have evaluated several pancreatic manifestations in IBD, there is paucity of data on pancreatic cysts in IBD.17,21,22,24 One study suggested an increased detection of pancreatic cysts in IBD patients.17 However, it is unclear if this association is incidental because of increased abdominal imaging in this cohort or if there is an underlying pathophysiological etiology. Furthermore, there are no studies evaluating the natural course and outcomes of pancreatic cysts in IBD. Hence, we aim to describe the natural course of pancreatic cysts in IBD and identify long-term outcomes over a 10-year period. Outcomes include rate of growth over time, high-risk transformation, malignant transformation, and surgical intervention.
MATERIALS AND METHODS
This is a retrospective cohort study that was carried out at a tertiary referral center. A prospectively maintained database of patients with pancreatic cysts diagnosed on computed tomography (CT) scan or MRI was used as the source population. Records between 2008 and 2019 were reviewed. Patients with a diagnosis of IBD and pancreatic cysts were identified as the study cohort. Patients with pancreatic cysts and without IBD were used as the control group. Baseline characteristics including age, sex, race, body mass index, Charlson comorbidity index (CCI), and selected medical conditions were collected. Smoking status, history of pancreatitis, alcohol use, and drug use were also identified. Medication use including nonsteroidal anti-inflammatory drugs, immunosuppressants (azathioprine, methotrexate, sulfasalazine, cyclosporine, tacrolimus, infliximab, adalimumab, certolizumab, etanercept, golimumab, tofacitinib, vedolizumab, natalizumab, ustekinumab, 6-mercaptopurine, mycophenolate mofetil), aspirin, and statins was evaluated. Initial pancreatic cyst diagnosis and morphology were reviewed, including type, location, communication with pancreatic duct (PD), dilation of PD, enhanced solid component, cyst size in millimeters (long and short axis), number of cysts, thickened cyst wall, nonenhanced mural nodules, distal pancreatic atrophy, and abrupt change in main pancreatic diameter size. Patients were then retrospectively followed up at 1, 3, 5, and 10 years. Abdominal imaging at these intervals was reviewed. Magnetic resonance imaging was the preferred imaging modality for follow-up, and CT scan was used only when MRI follow-up was not available. Endoscopic ultrasound (EUS) data and cyst sampling analysis were also collected if present. All study data were collected and managed using Research Electronic Data Capture, which is a secure Web-based software platform designed to support data capture for research studies.25,26 An institutional review board approval was obtained before data collection.
Pancreatic Cyst Diagnosis
Pancreatic cyst diagnosis was based on MRI findings, reviewed by a radiologist, and EUS features, reviewed by an advanced endoscopist, when available. This was also confirmed by fine-needle aspiration or surgical pathology when present. Computed tomography scan findings were used only when MRI was not available. A breakdown of the diagnostic modality is presented in the Results section (Table 1).
TABLE 1.
Modality of Pancreatic Cyst Diagnosis in the IBD
| Modality | n (%) |
|---|---|
|
| |
| MRI or EUS | 66 (85) |
| MRI only | 32 (41) |
| EUS only | 8 (10.3) |
| MRI and EUS | 27 (34.6) |
| CT only | 11 (14.1) |
| CT and EUS | 8 (10.3) |
| Fine-needle aspiration | 23 (29.5) |
| Surgical pathology | 4 (5.1) |
Outcomes
Four outcomes were measured at 1, 3, 5, and 10 years. These included rate of growth, surgical intervention, high-risk transformation, and malignant transformation. Growth rate was defined by change in size in millimeters of the long axis and/or change in the number of pancreatic cysts. Changes in size and number were analyzed separately. Surgical intervention was defined as the enucleation or excision of pancreatic cysts through pancreaticcoduodenectomy, distal pancreatectomy, central pancreatectomy, or total pancreatectomy. High-risk transformation was defined by 10 variables, including new communication with PD or new dilation, change in size of previous dilation, extension of cyst location, cyst ≥3 cm, new thickened enhanced cyst wall, new nonenhanced mural nodule, new distal pancreatic atrophy, new abrupt change in main PD size, and new lymphadenopathy. Pancreatic duct dilation was defined as an increase in PD diameter by 1 to 4.9, 5 to 9.9, or more than 10 mm. Lastly, malignant transformation was defined by the presence of dysplasia or malignant cells on cytology or pathology.
Statistical Analysis
Categorical variables were described using frequencies and percentages, and the relationship between these variables was assessed using Pearson χ2 tests. Continuous variables were described using means and standard deviations (SD), and the relationship between these variables was assessed using t tests. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses of the first high-risk transformation, malignant transformation, and surgery. Mixed-effect logistic regression models were fit to predict increases in size and number increase in cysts. Univariable analyses were performed. Multivariable models were then fit, again adjusting for factors that differed across groups. Analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC).
RESULTS
A total of 1789 patients with pancreatic cysts were evaluated from the database. There were 1690 patients who had pancreatic cysts without IBD and 78 (4.4%) patients who had IBD and pancreatic cysts. The remaining 21 patients were excluded because of incomplete medical records. Eighty-five percent of the IBD group had pancreatic cysts detected on MRI and/or EUS, and 10.3% were detected on an abdominal CT scan and confirmed by EUS (Table 1).
In the IBD cohort, there were 29 patients (37.2%) with ulcerative colitis, 43 (55.1%) with Crohn disease, 4 (5.1%) with indeterminate colitis, and 2(2.6%) with microscopic colitis. There were 65 (83.3%) intraductal papillary mucinous neoplasms (IPMNs), 4 (5.1%) mucinous cystic neoplasms, 2 (2.6%) serous cystadenomas, 6 (7.7%) pseudocysts, and 1 (1.3%) neuroendocrine tumor.
The mean age of patients with IBD and pancreatic cysts was 60.8 years, with 62% females and 93.2% White. The mean CCI was 4.2. Forty-three percent of the study cohort had a history of smoking, and 44.7% had a history of alcohol use. In comparison to pancreatic cyst patients without IBD, those with IBD with pancreatic cysts were overall younger. They were also more likely to be White with a lower CCI and body mass index. There were no statistically significant differences in sex, alcohol use, smoking status, or drug use. Baseline characteristics are presented in Table 2. Inflammatory bowel disease medications, location, and phenotype of ulcerative colitis and Crohn disease in the study cohort are presented in Table 3.
TABLE 2.
Baseline Characteristics of Control and Study Cohorts
| Variable | No IBD (n = 1690) | IBD (n= 78) | P |
|---|---|---|---|
|
| |||
| Age, mean (SD), y | 67.1 (13.8) | 60.8 (14.2) | <0.001 |
| Sex, n (%) | |||
| Male | 665 (39.4) | 30 (38.5) | |
| Female | 1024 (60.6) | 48 (61.5) | |
| Body mass index, mean (SD), kg/m2 | 29.7 (33.3) | 26.9 (7.0) | 0.014 |
| Charlson score, mean (SD) | 5.1 (3.1) | 4.2 (2.8) | 0.017 |
| Ever smoker, n (%) | 739 (45.7) | 34 (43.6) | 0.65 |
| Alcohol use, n (%) | 780 (49.2) | 34 (43.6) | 0.45 |
| White, n (%) | 1283 (84.7) | 68 (93.2) | 0.049 |
| Diabetes without complications, n (%) | 333 (19.7) | 17 (21.8) | 0.69 |
| Diabetes with end organ failure, n (%) | 136 (8.0) | 5 (6.4) | 0.58 |
| Drug abuse, n (%) | 61 (3.6) | 1 (1.3) | 0.27 |
| History of acute pancreatitis, n (%) | 232 (13.7) | 13 (16.7) | 0.49 |
| History of chronic pancreatitis, n (%) | 148 (8.8) | 8 (10.3) | 0.67 |
| Extrapancreatic cancer, n (%) | 621 (37.0) | 25 (32.1) | 0.34 |
| Maximum cyst size, mean (SD), mm | 4.4 (71.7) | 1.5 (2.1) | 0.11 |
| No. cysts, mean (SD) | 1.8 (1.6) | 1.9 (1.3) | 0.50 |
| Location, n (%) | |||
| Head | 714 (42.2) | 26 (33.3) | 0.10 |
| Neck | 209 (12.4) | 13 (16.6) | 0.28 |
| Body | 696 (41.2) | 35 (44.9) | 0.58 |
| Tail | 600 (35.5) | 27 (34.6) | 0.81 |
| Involving >1 site | 171 (10.1) | 11 (14.1) | 0.28 |
| Morphology, n (%) | |||
| Unilocular | 361 (21.4) | 17 (21.7) | 0.97 |
| Multilocular | 259 (15.3) | 12 (15.3) | 0.97 |
| Dilation of the PD | 88 (5.2) | 5 (6.4) | 0.66 |
| High-risk stigmata | 111 (6.6) | 5 (6.4) | 0.93 |
| High-risk stigmata, n (%) | |||
| Enhanced solid component | 16 (0.95) | 0 (0.00) | 0.38 |
| Cyst ≥3 cm | 51 (3.0) | 2 (2.6) | 0.80 |
| Thickened enhanced cyst wall | 13 (0.77) | 0 (0.00) | 0.43 |
| Nonenhanced mural nodules | 2 (0.12) | 0 (0.00) | 0.76 |
| Distal pancreatic atrophy | 24 (1.4) | 1 (1.3) | 0.91 |
| Abrupt change in main pancreatic diameter size | 4 (0.24) | 0 (0.00) | 0.67 |
| Lymphadenopathy | 16 (0.95) | 2 (2.6) | 0.17 |
| IPMN type, n (%) | 0.22 | ||
| All others | 27 (2.8) | 0 (0.00) | |
| Side-branch location | 930 (97.2) | 53 (100.0) | |
P values in bold font are statistically significant.
TABLE 3.
IBD Medications, Location, and Phenotype of Ulcerative Colitis and Crohn Disease in the Study Cohort
| Ulcerative Colitis | Crohn Disease | |||
|---|---|---|---|---|
|
| ||||
| Medications | Azathioprine | 1 (3.4) | Azathioprine | 6 (14) |
| Methotrexate | 1 (3.4) | Methotrexate | 3 (7) | |
| 6-Mercaptopurine | 3 (10.3) | 6-Mercaptopurine | 3 (7) | |
| Sulfasalazine | 5 (17.2) | Sulfasalazine | 11 (25.6) | |
| Infliximab | 1 (3.4) | Infliximab | 10 (23.3) | |
| Adalimumab | 0 (0) | Adalimumab | 4 (9.3) | |
| Ustekinumab | 0 (0) | Certolizumab | 2 (4.7) | |
| Vedolizumab | 1 (3.4) | Vedolizumab | 3 (7) | |
| Ustekinumab | 2 (4.7) | |||
| Location | Ulcerative proctitis | 3 (10.3) | Ileal | 9 (20.9) |
| Left-sided ulcerative colitis | 9 (31) | Colonic | 10 (23.3) | |
| Extensive | 17 (58.6) | Ileocolonic | 24 (55.8) | |
| Isolated upper disease | 0 (0) | |||
| Phenotype | — | Nonstricturing, nonpenetrating | 21 (48.8) | |
| Stricturing | 15 (34.9) | |||
| Penetrating | 10 (23.3) | |||
| Perianal disease | 7 (16.3) | |||
Values are presented as n (%).
Baseline Cyst Morphology and Characteristics of the Study Group
Most pancreatic cysts in IBD patients occurred in the body of the pancreas (44.3%). They had a mean maximum cyst size of 1.5 cm at the time of diagnosis. There were 5 (6.4%) pancreatic cysts with high-risk stigmata at baseline in the IBD cohort. These included 2 cysts ≥3 cm, 1 with distal pancreatic atrophy and 2 with associated lymphadenopathy. There were no statistically significant differences between the study and control cohorts (Table 2).
Univariable and Multivariable Analyses of Predictors of High-Risk Transformation, Malignant Transformation, Rate of Growth, and Surgical Intervention
In univariable analysis, younger age was a predictor of surgical intervention in pancreatic cyst patients with IBD (odds ratio [OR], 0.975; 95% confidence interval [CI], 0.964–0.987). White race was a significant predictor of increased rate of growth. In multivariable analysis, younger age remained a significant predictor of surgical intervention (OR, 0.97; 95% CI, 0.96–98; P < 0.001). There were no other statistically significant predictors of the measured outcomes in both univariable and multivariable analyses (Tables 4 and 5).
TABLE 4.
Multivariable Analysis of IBD as a Predictor of High-Risk Transformation, Malignant Transformation, and Surgical Intervention Over Time*
| High-Risk Transformation |
Malignant Transformation |
Surgery |
||||
|---|---|---|---|---|---|---|
| OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | |
|
| ||||||
| IBD as a predictor | 1.03 (0.29–3.60) | 0.97 | 0.81 (0.24–2.75) | 0.74 | 0.47 (0.14–1.58) | 0.23 |
| IBD cohort | ||||||
| Age | 0.99 (0.96–1.01) | 0.25 | 0.98 (0.97–1.00) | 0.08 | 0.97 (0.96–0.99) | <0.001 |
| CCI | 1.06 (0.96–1.18) | 0.25 | 1.06 (0.97–1.15) | 0.17 | 0.99 (0.91–1.07) | 0.71 |
| White | 0.96 (0.42–2.17) | 0.92 | 0.99 (0.51–1.90) | 0.97 | 1.15 (0.64–2.08) | 0.64 |
| Immunosuppressants | 1.09 (0.40–2.99) | 0.87 | 0.89 (0.36–2.20) | 0.80 | 0.75 (0.31–1.182) | 0.53 |
Multivariable analysis of predictors of aforementioned outcomes in the IBD cohort is also presented.
TABLE 5.
Summary of Changes in Mean of Pancreatic Cysts Size Over 10 Years Using Mixed-Effects Model
| Time, y | IBD Mean Size (95% CI), cm | IBD Change in Size (95% CI), cm | IBD P | No IBD Mean Size (95% CI), cm | No IBD Change in Size (95% CI), cm | No IBD P | Group Size P | Change P |
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| 0 | 1.54 (1.05–2.02) | — | 1.81 (1.71–1.90) | — | 0.28 | — | ||
| 1 | 1.69 (1.19–2.19) | 0.15 (−0.00 to 0.31) | 0.052 | 1.95 (1.85–2.05) | 0.14 (0.10–0.17) | <0.001 | 0.32 | 0.86 |
| 3 | 1.76 (1.25–2.27) | 0.22 (0.04–0.41) | 0.019 | 2.03 (1.93–2.13) | 0.22 (0.18–0.26) | <0.001 | 0.31 | 0.99 |
| 5 | 1.69 (1.16–2.21) | 0.15 (−0.08 to 0.38) | 0.21 | 2.07 (1.96–2.18) | 0.27 (0.21–0.32) | <0.001 | 0.16 | 0.33 |
| 10 | 2.01 (1.42–2.60) | 0.48 (0.12–0.83) | 0.009 | 2.05 (1.88–2.22) | 0.24 (0.10–0.38) | <0.001 | 0.90 | 0.23 |
Multivariable Analysis of IBD as a Predictor of High-Risk Transformation, Malignant Transformation, Rate of Growth, and Surgical Intervention Over Time
Although both study and control groups had significant increase in size relative to baseline over time, there were no statistically significant differences in size changes over time between the study and control groups (Table 5, Fig. 1). Moreover, IBD was not associated with increased risk of high-risk transformation (OR, 1.03; 95% CI, 0.29–3.60; P = 0.97), malignant transformation (OR, 0.81; 95% CI, 0.24–2.75; P = 0.74), or surgical intervention (OR, 0.47; 95% CI, 0.14–1.58; P = 0.23) (Table 3).
FIGURE 1.
Pancreatic cyst size measures over time. Means in centimeters.
Malignancy, Mortality, and Surgical Intervention
There was 1 patient (1.3%) IBD with pancreatic cysts who had malignant cells on cytology on fine-needle aspiration as compared with 19 (1.1%) in the control group (OR, 1.28; 95% CI, 0.15–8.53; P = 0.91). Four IBD patients (5.1%) with pancreatic cysts underwent pancreatic surgery with a total of 1 (1.3%) who had evidence of pancreatic malignancy on surgical pathology as compared with 98 (5.80%) undergoing surgery (OR, 0.88; 95% CI, 0.31–2.45; P = 0.88) with a total of 24 (1.42%) who had evidence of pancreatic malignancy on surgical pathology (OR, 0.90; 95% CI, 0.12–6.75; P = 0.92) in the control group. Lastly, there were 10 patients (12.82%) with IBD and pancreatic cysts who died with deaths 3 (3.8%) related to pancreatic malignancy. This was not statistically significant when compared with 307 patients (18.17%) (OR, 0.66; 95% CI, 0.34–1.30; P = 0.23) who died with 29 deaths (1.72%) related to pancreatic malignancy (OR, 2.29; 95% CI, 0.68–7.69; P = 0.18) in the control group. Diagnostic workup, type of surgery, and pathology results of IBD patients with pancreatic cysts who underwent surgical intervention are presented in Table 6.
TABLE 6.
Diagnostic Workup, Type of Surgery, and Pathology Results of IBD Patients With Pancreatic Cysts Who Underwent Surgical Intervention
| Indication for CT | CT | Indication for MRI | MRI | Indication for EUS | EUS | Fine-Needle Aspiration | Indication for Surgery | Type of Surgery | Age at Time of Surgery, y | Pathology | |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||
| Patient A | Crohn disease | 1.1-cm cystic lesion | Cyst seen on CT | 1-cm solid enhancing lesion consistent with neuroendocrine tumor | Pancreatic cyst concerning for neuroendocrine tumor | 1.2-cm cystic lesion (anechoic with hyperechoic shadowing | Cytology: negative for malignant cells. Mucin: negative |
Pancreatic cyst concerning for neuroendocrine tumor | Central pancreatectomy and pancreatojejunostomy | 56 | Well-differentiated pancreatic endocrine neoplasm of uncertain behavior |
| Patient B | Abdominal pain and acute pancreatitis | 0.6-cm low-density lesion | History of chronic pancreatitis | Multiple cystic lesions (0.9-cm largest) | Multiple cysts seen on MRI and CT | Hyperechoic foci, calcifications. Main duct narrowed with hyperechoic walls and dilation to 3.9 mm | Not done | Chronic pancreatitis | Total pancreatectomy with islet cell transplant | 52 | Fibrodense tissue with granulation tissue and acute inflammation |
| Patient C | Abdominal aortic aneurysm | 4.5-cm cyst | Not applicable | Not done | Large pancreatic cyst | 4.5-cm unilocular cyst | Carcinoembryonic antigen: 29445 Cytology: negative | 4.5-cm cyst, high carcinoembryonic antigen level | Distal pancreatectomy | 73 | Side-branch intraductal papillary mucinous adenoma without dysplasia |
| Patient D | Nephrolithiasis | 1-cm cystic lesion | Pancreatic cyst | 1.5-cm cystic mass with PD dilation to 0.5 cm | Pancreatic cyst with PD dilation | 1.1-cm cyst with mural nodule and PD dilation | Cytology: atypical cells | Pancreatic cyst with mural nodule, PD dilation, and atypical cells | Open distal pancreatectomy | 81 | IPMN, low-grade dysplasia |
DISCUSSION
In this retrospective cohort study, we evaluated the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age and were more likely to undergo surgery at a younger age. Despite the early presentation, there was no increase in high-risk transformation, malignant transformation, rate of growth over time, or surgical intervention rates.
Although a few number of studies have evaluated the development of several pancreatic manifestations in IBD, there is a paucity of data on the association between IBD and pancreatic cysts.17,20,21,24 Roch et al17 demonstrated a higher incidence of pancreatic cysts in IBD. It is unclear, however, if this increased association is incidental or if IBD is an independent risk factor of pancreatic cysts. The impact of chronic inflammation and the medications used in IBD on the natural course of pancreatic cysts is also unknown. The underlying pathophysiology of this association can only be postulated and inferred from previous studies. The genetic makeup of pancreatic cysts is increasingly being recognized to play a role in the development and growth of pancreatic cysts.8–12 The genetic profile of cystic fluid and surgically excised IPMNs was analyzed for 169 cancer-related mutations by Wu et al.8 The most common mutations identified involved the KRAS and GNAS pathways. Inactivation mutations of TP53, BRAF, SMAD4, and CDKN2A/p16 were also observed in several other studies of IPMNs.8–12 Those same variants were also found in mucinous cystic neoplasms.8–12 It is known that the most common dysplasia-related mutations in IBD involve the KRAS and TP53 pathways.27 Furthermore, multiple studies have linked inflammation to increased risk of pancreatic cysts.13–15 Sadotetal15 demonstrated high neutrophil count in cystic fluid of IPMNs, whereas several others provided evidence of high cytokine levels and other inflammatory markers in IPMNs. Furthermore, several case reports and case series have linked autoimmune pancreatitis and immunoglobulin G4–related disease to the increased risk of pancreatic cysts, suggesting a role for autoimmunity.28–32
Although it is plausible that the interplay between chronic inflammation, genetic alterations, and autoimmune process in IBD patients contributes to the development of pancreatic cysts in IBD, the findings of the current study are suggestive of incidental detection of pancreatic cysts in IBD rather than IBD being a risk factor for pancreatic cyst development. It is known that IBD patients have higher health care utilization rates than the general population, with up to 53.5% likelihood of hospitalization within 5 years of diagnosis.33 They also undergo numerous abdominal imaging with CT and MRI at a younger age than the general population.34 This increases the likelihood of detection of pancreatic cysts in IBD patients at a younger age. As demonstrated by this study as well, IBD patients with pancreatic cysts have a lower CCI and body mass index, making them a better fit for surgical intervention, and thus, they are more likely to undergo surgery at a younger age. Most notably, IBD does not seem to alter the natural course of pancreatic cysts based on our findings, further supporting the incidental nature of pancreatic cyst detection in IBD.
There are very limited data on the correlation between IBD medications and pancreatic cysts. Roch et al17 evaluated the relationship between immunosuppressants and IPMN and found no effect on the “invasiveness” of IPMNs or rate of malignant transformation. Other studies had conflicting results, with some suggesting an increased risk of pancreatic malignancy.18–20 In the current study, immunosuppressant medications, including biologic agents, steroids, and immunomodulators, had no statistically significant impact on the measured outcomes.
In regard to cyst characteristics in IBD patients, none is currently reported in the literature. We found that the most common cyst type in IBD patients is IPMN, which is similar to the general population. There were no significant differences between baseline cyst morphology of patients with IBD and patients without IBD. Patients with IBD with pancreatic cysts were more likely to be female and White when compared with pancreatic cyst patients without IBD. The increased prevalence in female and White patients is consistent with the epidemiology of IBD.
The most clinically relevant finding of the current study is that despite the early detection of pancreatic cysts in IBD, there were no statistically significant differences between the study and cohort groups in high-risk and malignant transformation. There were also no differences in surgery rates or development of pancreatic malignancy on pathology or differences in overall mortality rates. These findings are especially relevant, given that it is not uncommon for gastroenterologists to encounter pancreatic cysts in IBD patients. The current literature does not allow for guidelines and society recommendations to identify patients at risk of developing pancreatic cysts and does not evaluate the impact of chronic medical conditions such as IBD on pancreatic cysts course. The current approach to IBD patients with pancreatic cysts is similar to that of the general population, and this study validates the current approach as it demonstrates that this cohort of patients is not at increased risk of unfavorable outcomes. This serves as a reassurance to both physicians and patients. It also shows that despite surgery at a younger age, there were no differences on surgical pathology, suggesting that watchful waiting and continued surveillance may be more appropriate than early surgical intervention.
There are several limitations to this study. The detection, description, and measurements of pancreatic cysts vary between MRI and CT scans. Few patients did not have an MRI on initial diagnosis, and few did not have an MRI follow-up. To overcome this heterogeneity, MRI was favored when present, and the same imaging modality was used for comparison on follow-up. It is important to note also that 85% of the cohort had an MRI and/or EUS, and 10.3% had CT scan and EUS. Also, it is challenging to ascertain the adherence and length of exposure to IBD medications of our current cohort. The methodology that was followed helps confirm with certainty the exposure to infusion medications, but orally administered or self-administered medications were confirmed based on pharmacy refills. Lastly, data are obtained from a tertiary referral center and thus are at risk of selection bias of more complicated pancreatic cysts and IBD cases.
In conclusion, this is the first study to date to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in rate of growth, high-risk malignant transformation, or overall risk of surgery. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD and in accordance with society recommendations and guidelines.
Abbreviations:
- CT
computed tomography
- IBD
inflammatory bowel disease
- IPMN
intraductal papillary mucinous neoplasms
- MRI
magnetic resonance imaging
- PD
pancreatic duct
Footnotes
F.R. is on consulting or AdBoard of Agomab, Allergan, AbbVie, Boehringer-Ingelheim, Celgene, CDISC, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Jannsen, Koutif, Metacrine, Morphic, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Takeda, Techlab, Theravance, Thetis, UCB. M.R. has unrestricted educational grants from Abbvie, Janssen, UCB, Pfizer, Takeda, Celgene, Genentech, Gilead; is on advisory boards for and a consultant to Abbvie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, S.p.A., Bristol Meyer Squibb (BMS); CME companies: CME Outfitters, Imedex, GI Health Foundation (GiHF), Cornerstones, Remedy, MJH Life Science; and royalties: Wolters Kluwer Health as author/editor of UpToDate. The other authors declare no conflict of interest.
M.A.S. worked on conceptualization, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, writing original draft, review, and editing. M.A.: conceptualization, data curation, formal analysis, methodology, project administration, supervision, writing original draft, review, and editing. A.H.: data curation, formal analysis, methodology, project administration, supervision, writing original draft, review, and editing. A.A.: data curation, formal analysis, methodology, validation, writing original draft, review, and editing. F.Q.: conceptualization, data curation, formal analysis, methodology, validation, review, and editing. W.K.: data curation, formal analysis, methodology, validation, review, and editing. J.B.: data curation, formal analysis, investigation, and methodology. C.M.: data curation, project administration, supervision, validation, review, and editing. M.R.: methodology, project administration, supervision, review, and editing. F.R.: methodology, supervision, validation, review, and editing. C.R.S.-L.: data curation, methodology, supervision, validation, review, and editing. P.C.: conceptualization, formal analysis, investigation, methodology, project administration, validation, writing original draft, review, and editing.
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