Pancreatic Cysts and Pancreatitis in the Older Adult

Incidence of both pancreatic cysts and acute pancreatitis increases with age. Appropriate management of these conditions in older adults (at least 65 years of age) is multifaceted and include considerations of age-related changes, comorbidities, age-specific implications of various management options and patient preferences. We review these incidental pancreatic cystic lesions and acute pancreatitis as well as chronic and autoimmune pancreatitis below with focus on specific considerations in older adults. Other important topics including the approach to patients at higher risk of pancreatic cancer and pancreatic cancer screening are beyond the scope of this review. PANCREATIC CYSTS Epidemiology Pancreatic cysts appear ubiquitous and in fact, have been identified in up to 50% of autopsies while appearing incidentally in anywhere from 15% to 75% of cross-sectional imaging studies with a recent global MRI study showing 16% prevalence (1–4). Similar to other findings, incidence of pancreatic cystic lesions rises with age, occurring nearly 3 times as commonly in patients in their 70 s (26%) compared to those in their 50 s (9%) and found in 38% of people over 80 years old (4–6). The main concern over these cystic lesions is the malignant potential in some forms. Pancreatic cancer has a poor prognosis with few acceptable treatment options. Therefore, early detection remains a cornerstone to improving survival rates of patients with pancreatic cancer. Unfortunately, older adult patients with pancreatic cancer have worse outcomes given undertreatment and underrepresentation in studies which lead to a lack of understanding of unique therapeutic and deleterious effects on older adults especially due to issues with cognition, depression, nutrition, functional status, polypharmacy, falls, incontinence, and frailty (7). Benign pancreatic cysts Broadly, pancreatic cysts are grouped into benign and premalignant/malignant cysts (Table 2, Figure 4). Pseudocysts and serous cystadenomas are the more common benign cysts. Approximately two-thirds to three-quarter of serous cystadenomas occur in older women in their sixties (8). They typically appear multiseptated, lobular with a minority containing a central scar that is pathognomonic for the cyst (2). Some of these tend to grow over time and rarely may require surgical resection due to large size causing extrinsic compression upon surrounding structures. Pseudocysts occur in the setting of acute or chronic pancreatitis, usually with a thick wall and cola colored, amylase-rich fluid.Table 2.: Common types of pancreatic cystsFigure 4.: (a) MRI of serous cystadenoma with central scar. (b) MRI of mucinous cystic neoplasm in tail of pancreas. (c) MRI showing branch duct IPMN. (d) MRI of main duct IPMN with diffusely dilated main pancreatic duct.Premalignant/malignant pancreatic cysts Mucinous cysts are typically premalignant and mainly consist of mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasms (IPMN). MCNs are not common and tend to occur in younger women, found in the body-tail of the pancreas with a thick wall and single compartment. IPMNs arise from within the pancreatic duct and occur in 3 varieties which correlate with their malignant potential. BD-IPMNs have the lowest malignant potential (3%–12%) while main duct IPMN (MD-IPMN) and mixed type IPMN carry significantly higher risk of malignant transformation (30%–50%). The most common type of cyst is branch duct (BD) IPMN with average age at diagnosis in sixties. Given the widespread occurrence of BD-IPMNs, risk stratification of these cysts is important, relies on identifying worrisome and high-risk stigmata (Table 3), and is similar for older adult and younger patients (8). Those with high-risk stigmata have significantly worse 5-year survival compared with having worrisome stigmata (9). Another consideration in patients with IPMNs is the increased risk of concomitant pancreatic ductal adenocarcinoma (PDAC) which is 3–5 times higher than age-matched controls (10,11).Table 3.: Worrisome and high-risk stigmata (8)Older adults with pancreatic cysts may have additional factors increasing their risk of pancreatic cancer including significant family history of pancreatic cancer (at least 2 first-degree relatives with history of pancreatic cancer) or personal history of genetic mutations such as BRCA1, BRCA2, PALB2, ATM, or genetic syndromes including Lynch and Peutz-Jeghers syndromes. These patients are managed differently with intensive screening for pancreatic cancer consisting of magnetic resonance imaging (MRI) alternating with endoscopic ultrasound (EUS) annually. Whether and when to stop screening in these patients remains uncertain but should incorporate the patient's wishes, comorbidities, and life expectancy. New onset diabetes over the age of 60 as a significant risk factor associated with PDAC (12). Whether all these patients should undergo imaging and what type of imaging to look for pancreatic cancer remains unclear and requires further study. However, older adults with pancreatic cysts and new onset diabetes or worsening glycemic control should undergo at least MRI pancreas for further evaluation. Approach to older adults with incidental pancreatic cysts Especially in the older adult, assessment of comorbidities and overall health status is important to guide appropriate evaluation and management of incidental pancreatic cysts. Studies have shown that older patients with multiple comorbidities have much higher risk of dying from other causes (13–15). One of the initial studies assessing this noted that patients with Charlson comorbidity index greater than 7 had an 11 times higher chance of dying from a non-pancreatic cyst reason within 3 years of cyst diagnosis than those with a lower index (13). Therefore, it is reasonable in non-surgical and sicker patients to discuss not continuing with further work up and surveillance. The approach with other patients, whether older adult or younger, focuses on the following: identifying malignant cysts, diagnosing mucinous cysts, and understanding the malignant potential of the cyst. Typically, this involves obtaining good quality MRI pancreas with MRCP if possible or pancreatic protocol CT and reviewing any prior abdominal imaging with your radiologist to search for evidence of pancreatic cysts. MRI is superior to CT scan for identifying IPMNs, detecting ductal involvement, nodules, and small masses (16). The Kyoto guidelines also suggest considering serum CA 19-9 and hemoglobin A1C to help risk stratify patients. Only a subset of patients will need EUS for further evaluation. EUS is indicated if worrisome or high-risk stigmata are identified or management would change based on EUS results. Furthermore, if high-risk stigmata are present, the patient should be referred to a pancreatic surgeon and/or a multidisciplinary pancreas center for further evaluation. Patients with worrisome findings do not necessarily require immediate surgery, however, likely would also benefit from referral to a pancreas center. Other patients without worrisome or high-risk stigmata should be enrolled into a surveillance program unless the patient definitely has an asymptomatic pseudocyst or serous cystadenoma. Surveillance Given the high prevalence of incidental pancreatic cystic lesions, indefinite surveillance of all these patients is not economically or practically feasible especially as the population of older adult patients grows. Several guidelines suggest stopping surveillance after 5 or 10 years of stability on imaging (8,17,18). Studies reported that during long-term follow-up of presumed low risk BD-IPMNs, malignancy develops in approximately 2% while worrisome or high-risk stigmata occur in up to 20% of patients (10,11,19,20). An interesting study suggested stopping surveillance in 2 groups of older patients after 5 years due to very low risk of developing malignancy (<0.5%) or high-risk stigmata (<2%): those at least 75 years old with cysts 3 cm or smaller and patients at least 65 years old with cysts 1.5 cm or smaller (21). However, Japanese literature suggests higher risk of malignant transformation over time, up to 15% risk at 15 years (10). Whether this reflects differences in the patient population or other factors remains unclear. Further study is needed although conversations around stopping surveillance are reasonable in older adult patients with low-risk cysts, especially those that are subcentimeter. Another issue is the necessity of contrast with surveillance MRIs. Increasing number of studies have demonstrated deposition of gadolinium in healthy tissue including brain which remains of unclear clinical significance (22). This observation as well as decreased cost and increased speed of exams without contrast make non-contrast MRI appealing. Faster MRIs are likely easier for older adults to tolerate. Only a few studies have examined this question but suggest that important findings (such as nodules, masses) and advanced neoplasia were not missed with non-contrast MRIs and management was not changed by the addition of contrast imaging (2,23). Therefore, performing surveillance MRI without contrast seems reasonable in low-risk patients with low-risk lesions. Surveillance interval varies depending on cyst size with the general principle being more frequent MRI for larger cysts. The updated Kyoto guidelines suggest repeat MRI in 6 months for all cystic lesions to ensure the cyst is not changing rapidly. Afterwards, small cysts may be followed every 1–2 years while larger cysts should be followed every 6–12 months. Diagnostic EUS Very few studies have examined the safety of EUS with or without tissue acquisition in older adults although these studies suggest that complication rates are not higher in the older adult (24,25). This may partially reflect selection bias as typically the decision to perform procedures in older adults is made after careful consideration of the pros and cons considering their age, life expectancy and comorbidities. Sedation with anesthesia is usually used although intravenous conscious sedation may be administered around the world especially for diagnostic EUS procedures. Older adult patients are more sensitive to the effects of sedatives and anesthesia due to physiologic changes associated with aging, should be given lower doses, and experience greater adverse events (24,26). During EUS, careful inspection of the cyst as well as the rest of the pancreas is performed, especially with increased risk of concomitant PDAC in IPMNs. The cyst should be characterized in addition to evaluating for nodule, mass, duct communication and dilation. Contrast-enhanced EUS aids in diagnosing nodules as well as high-risk nodules and may be used as an adjunct if available although further data is necessary to understand its role and impact (27). EUS imaging findings are at most 50% accurate for differentiating mucinous from non-mucinous cysts (28). Cyst fluid analysis should be performed for string sign, carcinoembryonic antigen (CEA), glucose, amylase and cytology (29). DNA analysis can be helpful for diagnosing mucinous cysts and identifying cysts with high-grade dysplasia and invasive carcinoma although suffer from high cost, lack of widespread availability and lower sensitivity. More recent studies suggest improved sensitivity with certain mutation panels (30). Approaches for incorporating DNA analysis include sending in all cyst fluid samples or selectively using in patients with indeterminate cysts and/or worrisome or high-risk features. With the shortcomings of cyst fluid analysis, new EUS-guided techniques have garnered interest including microbiopsy forceps and needle-based confocal endomicroscopy (nCLE). Microbiopsy forceps ideally obtain small samples of the epithelial lining, septa, or nodules but carry significantly higher risk of pancreatitis ranging from 2% to 8% including several reported deaths (31). Highest risk (28% adverse events) included patients with IPMN undergoing more than 1 biopsy followed by age over 64 years old (32). Therefore, the potential added value of microbiopsy forceps should be carefully considered before using in older adult patients. On the other hand, nCLE appears safer with good accuracy for diagnosing serous cystadenoma (29). Widespread adoption of this technology has not occurred due to expense required for equipment, the learning curve, and its reliance on visual images without tissue diagnosis. Management of high-risk lesions Unlike with EUS, mortality and morbidity following pancreatic surgery appear higher in older adult patients (33–35). Therefore, surgical resection must be carefully considered in high-volume centers to minimize issues postoperatively with cognition, depression, nutrition, polypharmacy, falls, incontinence, constipation, and deconditioning. Minimally invasive approaches appear beneficial to older adults. Importantly, surgery should not be denied to patients simply due to their chronological age. Typical indications for surgery include concern for symptoms from the cyst (e.g., pancreatitis, obstructive jaundice), invasive cancer or high-grade dysplasia, MD-IPMN, mixed type IPMN, BD-IPMN with high-risk features, and all or higher risk MCNs (8,36). For non-surgical candidates without malignancy and older adults at higher risk for surgery, EUS-guided ablation (chemoablation and radiofrequency ablation) is another option. These techniques are not widely available and require further study. However, cyst ablation with chemotherapeutics including paclitaxel and gemcitabine appear safe unlike with ethanol ablation leading to pancreatitis and have comparable long-term cyst resolution in approximately two-thirds of patients with no progression to high-grade pathology (37). Summary: Pancreatic cysts Incidence of pancreatic cysts increases with age. Endoscopic ultrasound is only needed in select patients with pancreatic cysts and appears safe in older adult patients. New onset diabetes in older adults with pancreatic cysts should lead to MRI pancreas and/or endoscopic ultrasound. Surveillance can likely be stopped in older patients with small pancreatic cysts that have remained stable for at least 5 years. ACUTE PANCREATITIS Incidence, morbidity and mortality Acute pancreatitis remains an often devastating inflammatory illness with significant morbidity and mortality (38). In older adult patients both the severity and mortality associated with acute pancreatitis is higher than in younger populations. In addition, the incidence of acute pancreatitis is higher in older adult patients (39). Multiple studies in geographically diverse patients indicate that older age results in longer lengths of hospital stay, higher requirements for ICU admission, interventional procedures, and organ failure (40–42). There does appear to be a linear correlation with advancing age, as patients of the oldest old (>80 years) have worse clinical outcomes than those in younger elderly cohorts (43,44). Mortality rates range from 3% to 21%, with 1 retrospective study from the Mayo Clinic demonstrating in-hospital mortality in the older adult (>70 y/o) was 3-fold greater than in controls (21.4 vs. 7.1%, P = 0.028), as was the development of organ failure (41,45). Increasing underlying morbidity inherent in the older adult, combined with the decreased tolerance of inflammatory stress and subsequent promotion of pre-inflammatory mediators are postulated to be main contributors to worsening severity in the older adult (46). In fact, advanced age is such a predictor of poor outcomes that it is used as metric in several acute pancreatitis scoring systems, such as the BISAP and APACHE-2 score (47,48). Etiology The causes of acute pancreatitis in the older adult are not considerably different than those in younger patients. Biliary lithiasis and alcohol use remain by far the most common etiologies, with biliary disease becoming relatively more common with advancing age (49). Older adult women, however, have a much greater risk of biliary lithiasis as the cause of acute pancreatitis compared to older adult men (50). Whereas hyperlipidemia-induced pancreatitis rates are lower in the older adults compared to younger patients, drug-induced pancreatitis rates are higher (51). Medications including ACE-inhibitors, statins and dipeptidyl peptidase 4 inhibitors are all more commonly used in older adult patients, and thus portend higher risks to be the etiologic agent (52). Clinical presentation The clinical triad for diagnosing acute pancreatitis—biochemical elevations in amylase and/or lipase >3 times the upper limit of normal, classic and/or diagnostic cross-sectional not be in older adult patients abdominal are commonly especially in patients over 80 In addition, older adult patients are more to which can scoring on status such as the BISAP Older adult patients are also more likely to have other disease that can acute pancreatitis, such as which may require more frequent and use of cross-sectional imaging Management There is no available to acute is with on fluid and appropriate of The the of in acute pancreatitis, although not this treatment in older adult patients However, studies of fluid in an appropriate for the inflammatory in acute pancreatitis, the impact of on the older adults Older adult patients may with use and consideration of other such as is should be as as especially given the risk of in older adult patients, with over if In patients with biliary pancreatitis, of and subsequent biliary is careful should be to early endoscopic in older adult patients with but without due to the increased in early (38). In addition, older adult patients are at high risk for subsequent biliary if their is not prior to hospital no data to if is benefit to with biliary over in some for an endoscopic all older adult patients should be for the development of diabetes as with this have a much higher subsequent risk of mortality and from all causes compared to patients with underlying type diabetes Summary: Acute pancreatitis in the older adult is more with higher mortality than in younger populations. age (>70 years results in higher morbidity and Older adult patients are especially to fluid leading to such as and PANCREATITIS Etiology and history There is data chronic pancreatitis in the older most history data from retrospective In however, older adult patients with chronic pancreatitis tend to have a higher incidence of and autoimmune disease compared to younger patients, although and disease the leading Approximately 1 in 10 patients has which is a higher than younger patients and are also more commonly the cause of mortality in older adult patients Clinical presentation are with those in younger patients. patients have which can be and and will not necessarily with time is usually in the with to the and a or Approximately 20% of patients with chronic pancreatitis will have clinical symptoms of pancreatic abdominal although of and are common Management Management of chronic pancreatitis in the older adult focuses on control treatment of pancreatic and of most This is especially important as older adult patients also are more likely to such as and pancreatitis and have a higher risk of underlying disease management should clinical in management of this in a from a low approach to higher as the need should be to if although in some patients their use may be necessary should be to older adult patients prior to the of and is not a for patients over 70 years old due to the morbidity associated with the of to but also to in the of and is for older adult patients with chronic pancreatitis Older adult patients will typically require a lower of pancreatic for although older adult patients with chronic pancreatitis are likely to be given pancreatic than younger patients associated with due to chronic pancreatitis are higher in older adult patients, and thus and management are Summary: pancreatitis Older adult patients are likely to have but more likely to have than younger patients. combined with pancreatic the older adult at high risk for PANCREATITIS pancreatitis is a subset of chronic pancreatitis with 2 very different both of these types have a prevalence autoimmune pancreatitis, is due to an in older adult pancreatic epithelial lesions, often in younger patients with inflammatory More than of patients with type autoimmune pancreatitis are older than age it the most type of chronic pancreatitis in the older adult patients often with and abdominal it is that pancreatitis be from pancreatic malignancy of malignancy in the of autoimmune pancreatitis, and the has been well the treatment for both and autoimmune pancreatitis is should be to use the lowest possible and for and are all more common in older adult patients using which is by a lower of in this age The treatment in older adult patients should be of in early use of such as to and consideration of such as for treatment failure CT imaging of an older adult patient with demonstrating (a) An pancreas prior to treatment and (b) the pancreas following treatment with pancreatitis autoimmune pancreatitis is by far the most common type if in the older should be in their use of in the older options are more With the prevalence of acute pancreatitis, type 1 autoimmune pancreatitis and pancreatic cysts increasing in older understanding appropriate evaluation and management in this specific population is Further is needed to understand the impact of chronic pancreatitis in older adults as well as management of pancreatic cysts. will have an important role in and of cystic lesions. considerations must be when older adult patients by to their comorbidities, functional status, and other syndromes including and Further studies should the role of over fluid in older adults as well as the increased risks of in this population and its role in morbidity and Acute pancreatitis morbidity and mortality is more in the older Medications used to pancreatic disease in the older adult, such as for chronic pancreatitis and for autoimmune pancreatitis, should be used in older adult patients. Older adult patients with multiple comorbidities and decreased life expectancy likely will not benefit from further evaluation or surveillance of their incidental pancreatic cysts. Older adults with high-risk pancreatic cysts should not be denied surgery simply of their chronological age although must be referred to a high-volume center.