Clinical features and outcomes of total pancreatic lipomatosis with chronic pancreatitis: a case series

Introduction

There have been numerous terminologies for the accumulation of fat in the pancreatic gland: pancreatic lipomatosis (PL), fatty infiltration, fatty replacement, fatty pancreas, lipomatous pseudohypertrophy, nonalcoholic fatty pancreatic disease, nonalcoholic fatty pancreato-steatosis, and pancreatic steatosis [1]. The term PL has been used to describe fatty replacement of exocrine pancreatic tissue and fat infiltration [1]. The fatty replacement could be either focal or total, with focal replacement being the most common. Total PL is a very rare condition in which there is complete fatty replacement of the pancreatic parenchyma, and this may result in pancreatic exocrine insufficiency [2-4].

The exact etiopathogenesis of PL is unclear, but several predisposing factors have been described, including metabolic diseases (diabetes mellitus, obesity, dyslipidemia, severe malnutrition, Cushing syndrome), congenital anomalies of the pancreas, cystic fibrosis, iron overload conditions such as hemochromatosis, drugs, viral infections (hepatitis B virus, reoviruses, human immunodeficiency virus), chronic pancreatitis and pancreatic duct blockage [5]. Most patients with PL remain asymptomatic, but extensive fat replacement, as in total PL, can result in impairment of pancreatic exocrine or endocrine function [4].

Total or extensive PL has rarely been reported following pancreatic duct obstruction by calculi or carcinoma [6-8]. There is a paucity of literature on the clinical features and outcomes of total PL associated with chronic pancreatitis. In the current case series, we retrospectively analyzed the clinical and imaging features, as well as the treatment outcomes, in 8 patients with chronic pancreatitis and total PL.

Results

Over the last 15 years, 8 patients (mean age: 37.1±5.5 years; 5 male) with total PL and chronic pancreatitis were seen in our unit (Table 1). Two (25%) patients had a history of significant alcohol consumption, whereas in 6 (75%) patients no underlying etiology could be identified (idiopathic chronic pancreatitis). One patient with underlying alcohol-related chronic pancreatitis also had a history of significant smoking. All patients presented with chronic upper abdominal pain of 3-26 months duration. None of the patients had a history of prior acute pancreatitis. Two (25%) patients were overweight and 3 (37.5%) patients were obese, as per the Indian Consensus Group 2009 criteria [14]. Pre-existing hypertension was recorded in 4 (50%) patients, whereas 5 (62.5%) patients had pre-existing diabetes. Steatorrhea at presentation was observed in 1 (12.5%) patient.

Table 1 Characteristics of the patients included in the present case series

Six (75%) patients had elevated serum triglyceride levels (>150 mg/dL) at presentation. Seven (87.5%) patients had low fecal elastase, while 3/8 (37.5%) patients had severe exocrine insufficiency (fecal elastase <100 μg/g of stool). Seven (87.5%) patients had pancreatic calcification, and all 8 patients had a dilated main pancreatic duct observed on the abdominal CT. All 8 patients had complete replacement of the pancreatic parenchyma by fat (low attenuation value), with no demonstrable pancreatic parenchyma on CT (Fig. 1, 2). Magnetic resonance imaging (MRI) was performed in 3 patients and revealed a hyperintense pancreas on T2-weighted images, suggestive of total PL, along with a dilated main pancreatic duct. EUS revealed an echogenic pancreas (Fig. 1) in all the patients. The pancreatic duct was well visualised on EUS in 5/8 (62.5%) patients, while pancreatic calcification could be detected in 3 patients. No other EUS features of chronic pancreatitis could be identified in these patients.

Figure 1 (A) Computed tomography (CT) of abdomen: complete replacement of pancreas by fat (low attenuation value*). (B) CT abdomen: calcification in head of pancreas (arrow). (C) Endoscopic ultrasound: increased echogenicity of pancreas

Figure 2 Computed tomography (CT) of abdomen: complete replacement of pancreas by fat with scattered islands of pancreatic parenchyma in body and tail. Calcification also noted in head (arrow)

Fatty liver was detected on imaging in 3 patients, of whom 2 had elevated liver enzymes. However, both these patients also had a history of significant alcohol consumption. The abdominal pain was successfully managed with medical therapy in 2 (25%) patients, while 6 (75%) patients were successfully managed with pancreatic endotherapy. No adverse effects of pancreatic endotherapy were encountered in these patients. None of the patients required surgery and none developed pancreatic malignancy on follow up. The patient with steatorrhea was successfully managed with pancreatic enzyme replacement. Two patients with diabetes required insulin therapy, while 3 patients were managed with oral hypoglycemic drugs.

Discussion

Total PL is a rare condition of the pancreas that results in its complete fatty replacement; it has been infrequently reported in patients with chronic pancreatitis. In the current case series, we report the clinical profile as well as treatment outcomes in 8 patients who had total PL coexistent with chronic pancreatitis. The majority of our patients (5/8) were males and the mean age was 37 years. In addition, the majority of our patients had a coexistent component of metabolic syndrome, such as hypertension, diabetes, obesity or dyslipidemia. Sepe et al also reported that the presence of any metabolic syndrome components, such as a body mass index (BMI) ≥30 kg/m², hyperlipidemia, diabetes or hypertension, increased the prevalence of fatty pancreas by 37% (odds ratio 1.37, P=0.01), while factors independently associated with fatty pancreas on multivariate analysis were an elevated BMI and the presence of fatty liver [15]. In our case series, one third of our patients had coexistent fatty liver. Alcohol consumption and smoking have also been reported to be risk factors for a fatty pancreas [16,17]. Two of the 8 patients with total PL in our case series had a history of significant alcohol consumption, while 1 of them also had a history of significant smoking.

Whether chronic pancreatitis precedes fatty changes in the pancreas, or is an effect of obstruction of the pancreatic duct, cannot be ascertained with certainty. It has been postulated that long-standing obstruction to the pancreatic duct leads to lipomatous changes, but the exact mechanisms need to be elucidated. An animal study on the effects of ductal ligation reported that the volume of the pancreas increased in the first 2 days, as a result of interstitial edema, followed by a rapid decrease due to atrophy of the exocrine tissue [18]. The ductal cells, however, proliferated, with mitotic figures forming duct-like structures lacking in the acinar cells. After 2 weeks, the ductal cells also started decreasing in number, and the pancreas then showed intralobular fatty replacement, resulting in its gradual enlargement to a size approximating normal 8 weeks after duct ligation.

The symptoms of PL range from none, to non-specific abdominal pain, to severe pancreatic exocrine insufficiency presenting as chronic diarrhea [3]. In our series, all the patients had presented with abdominal pain, while only 1 patient had symptomatic exocrine insufficiency in the form of steatorrhea, which responded to pancreatic enzyme replacement therapy. Despite the absence of symptoms, 7 (87.5%) patients had low fecal elastase and 3 (37.5%) patients had very low fecal elastase levels (<100 μg/g of stool). The abdominal pain present in our patients was due to coexistent chronic pancreatitis resulting in ductal hypertension, and fatty replacement of the pancreas was probably not responsible for the abdominal pain. Fatty replacement of the pancreas has also been associated with reduced insulin secretion and the development of diabetes mellitus [19,20]. A study has shown that the presence of >25% fat infiltration of the pancreas is associated with a significantly increased risk of diabetes as well as atherosclerosis [21,22].

Ultrasound findings in fatty pancreas are often nonspecific and inconclusive, because the fatty change results in increased echogenicity and hence a hyper-reflective pancreas, making sonographic assessment difficult. In addition, the overlying bowel gas and abdominal fat cause difficulty in visualizing the pancreas [2,3]. Non-contrast CT can diagnose total PL by revealing specific fat density in the pancreatic bed, and demonstrating a negative attenuation value of pancreatic parenchyma that is replaced by the fat. However, the pancreatic parenchyma trapped between fatty tissues can show enhancement on contrast CT, simulating a pancreatic mass [23]. In these situations, MRI has the advantage over CT of demonstrating uneven fatty replacement of the pancreas [3]. In our series, all 8 patients had complete replacement of the pancreatic parenchyma by fat (low attenuation value), with no demonstrable pancreatic parenchyma on CT, and MRI revealed a hyperintense pancreas on T2-weighted images, suggestive of total PL, along with a dilated main pancreatic duct in 3/3 patients.

Because of its rarity, there are no consensus treatment guidelines or any specific treatment for total PL associated with chronic pancreatitis [1,3]. While lifestyle modifications have been shown to reduce the extent of pancreatic steatosis, their effect on total PL is unclear. There is also a paucity of prospective studies on the long-term follow up of patients with total PL. Their management revolves around the improvement of maldigestion, as well as nutrient deficiencies, treatment of diabetes and the management of chronic pancreatitis and its local complications, including control of pain. Oral pancreatic enzyme replacement therapy is effective for the management of maldigestion. Patients with coexistent metabolic syndrome can benefit from weight reduction, control of diabetes/blood pressure, regular exercise and management of dyslipidemia [3,24]. In our series, exocrine and endocrine insufficiency was successfully managed with pancreatic enzyme replacement and oral hypoglycemic drugs/insulin, respectively. The abdominal pain was successfully managed with medical therapy in 2 (25%) patients and by pancreatic endotherapy in 6 (75%) patients, and the presence of PL did not appear to impact the response to pancreatic endotherapy.

Our case series had important limitations, including a small sample size, its retrospective and single-center design, and the potential for selection bias.

In conclusion, total PL associated with chronic pancreatitis is a rare condition, and these patients have a high frequency of both pancreatic exocrine and endocrine insufficiency. Pancreatic endotherapy is safe and effective in the treatment of abdominal pain in patients who have chronic pancreatitis with total PL.