PANCREATIC STEATOSIS: A NEW DIAGNOSIS AND THERAPEUTIC CHALLENGE IN GASTROENTEROLOGY

Esteatose pancreática: um novo diagnóstico e desafio terapêutico na Gastroenterologia

Jayanta PAUL Ambalathu Veettil Hussain SHIHAZ About the authors

ABSTRACT

Fat infiltration in the pancreas is called pancreatic steatosis and it has several synonyms such as pancreatic lipomatosis, non-alcoholic fatty pancreatic disease, lipomatous pseudohypertrophy, fatty replacement, fatty pancreas and fatty infiltration. Pancreatic steatosis describes a disease ranging from infiltration of fat in the pancreas to pancreatic inflammation, and development of pancreatic fibrosis. There are multiple aetiologies of this condition, such as metabolic syndrome, alcohol intake, viral infections, toxins, congenital syndromes, etc. Pancreatic steatosis is usually diagnosed by trans-abdominal ultrasound, computed tomography scan and magnetic resonance imaging. Fatty infiltration in pancreas may lead to pancreatitis, diabetes mellitus and may be a predisposing cause of pancreatic cancer. Now a day, pancreatic steatosis is a common incidental finding during abdominal ultrasonography for other reasons and is a new challenge in Gastroenterology. But there is no guideline for pancreatic steatosis till now. In this review article, we are trying to give an overall idea (aetiologies, diagnosis, management, clinical significances) on pancreatic steatosis.

HEADINGS:
Pancreas; Pancreatic diseases; Lipomatosis; Magnetic resonance imaging; Endosonography; Ultrasonography; Review

RESUMO

A infiltração de gordura no pâncreas é chamada de esteatose pancreática ou lipomatose pancreática e tem vários sinônimos tais como: doença pancreática gordurosa não alcoólica, pseudo hipertrofia lipomatosa, reposição gordurosa, pâncreas gorduroso e infiltração gordurosa. A esteatose pancreática descreve uma doença que vai desde a infiltração de gordura no pâncreas até a inflamação pancreática com o desenvolvimento de fibrose pancreática. Existem múltiplas causas dessa condição, como síndrome metabólica, ingestão de álcool, infecções virais, toxinas, síndromes congênitas, etc. A esteatose pancreática é geralmente diagnosticada por ultrassom trans-abdominal, tomografia computadorizada ou ressonância magnética. A infiltração gordurosa no pâncreas pode levar à pancreatite e pode ser uma causa predisponente ao câncer de pâncreas. Hoje em dia, a fibrose pancreática é um achado incidental comum durante a ultrassonografia abdominal realizada por outras razões e é um novo desafio na Gastroenterologia. Mas não há diretriz para esteatose pancreática até agora. Neste artigo de revisão, objetivamos dar uma ideia geral sobre esteatose pancreática.

DESCRITORES:
Pâncreas; Pancreatopatias; Lipomatose; Imagem por ressonância magnética; Endossonografia; Ultrassonografia; Revisão

INTRODUCTION

Pancreatic steatosis (PS) is the most common benign pathologic condition of the pancreas in adult11. Ozbulbul NI, Yurdakul M, Tola M. Does the visceral fat tissue show better correlation with the fatty replacement of the pancreas than with BMI? Eurasian J Med. 2010;42:24-7. and commonly related to obesity and associated insulin resistance22. van Geenen EJ, Smits MM, Schreuder TC, van der Peet DL, Bloemena E, Mulder CJ. Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease. Pancreas. 2010;39:1185-90.. PS (used for all forms of pancreatic fat accumulation) has several synonyms such as: pancreatic fatty infiltration (pancreatic fatty infiltration due to obesity, reversed by weight reduction and medications), pancreatic lipomatosis (used for all forms of fatty infiltration of pancreas), fatty replacement (irreversible damage of pancreatic acinar cells and replacement by adipocytes), non-alcoholic fatty pancreatic disease (obesity and metabolic syndrome causing pancreatic fat accumulation), lipomatous pseudohypertrophy (when pancreas is uniformly or focally enlarged and/or the pancreatic exocrine system is altered by fat accumulation, and not related to obesity), fatty pancreas (used for all types of pancreatic fat accumulation)33. Pezzilli R, Calculli L. Pancreatic steatosis: Is it related to either obesity or diabetes mellitus? World J Diabetes. 2014;5:415-9.,44. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8:169-77.. Pancreatic fat accumulation increases with age and replacement of more than 25% of pancreas by fat is associated with severe generalized atherosclerosis and increased risk of development of diabetes mellitus type 255. Stamm BH. Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Hum Pathol. 1984;15:677-83.. On abdominal computed tomography scan, pancreas becomes hypodense and on ultrasound (US) examination it shows typical hyperechogenicity. Pancreatic steatosis is the commonly identifying pancreatic pathology during radiological examination but there is no guideline for PS till now. This article is trying to describe pancreatic steatosis in details including aetiology, diagnosis, clinical significance and management.

Definition of pancreatic steatosis

Pancreatic steatosis (PS) is defined by fat accumulation in pancreas and when there is presence of obesity or metabolic syndrome; it is called “non-alcoholic fatty pancreas disease” (NAFPD) and usually associated with NAFLD (non-alcoholic fatty liver disease)44. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8:169-77.. In 1933, Ogilvie first described pancreatic steatosis in literature44. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8:169-77..

Aetiologies of pancreatic steatosis

There are several causes of pancreatic steatosis (Figure 1). Similar to NAFLD, advanced age, obesity, metabolic syndrome and insulin resistance are the common risk factors of pancreatic steatosis. Pancreatic fat content is significantly associated with greater body mass index (BMI) and advanced age66. Rosso E, Casnedi S, Pessaux P, Casnedi S, Pessaux P, Oussoultzoglou E, Panaro F, Mahfud M, et al. The role of “fatty pancreas” and of BMI in the occurrence of pancreatic fistula after pancreaticoduodenectomy. J Gastrointest Surg. 2009;13:1845-51.. Prevalence is extremely low in women with age less than 50 years, but increases progressively after 50 years of age77. Wong VW, Wong GL, Yeung DK, et al. Fatty pancreas, insulin resistance, and β-cell function: a population study using fat-water magnetic resonance imaging. Am J Gastroenterol. 2014;109:589-97.. Some medications are also responsible for pancrea­tic steatosis such as steroid hormones66. Rosso E, Casnedi S, Pessaux P, Casnedi S, Pessaux P, Oussoultzoglou E, Panaro F, Mahfud M, et al. The role of “fatty pancreas” and of BMI in the occurrence of pancreatic fistula after pancreaticoduodenectomy. J Gastrointest Surg. 2009;13:1845-51., antiretroviral therapy88. Villarroya F, Domingo P, Giralt M. Drug-induced lipotoxicity: lipodystrophy associated with HIV-1 infection and antiretroviral treatment. Biochim Biophys Acta. 2010;1801:392-9., rosiglitazone99. Fernandes-Santos C, Evangelista Carneiro R, de Souza Mendonca L, Barbosa Aguila M, Mandarim-de-Lacerda CA. Rosiglitazone aggravates nonalcoholic fatty pancreatic disease in C57BL/6 mice fed high-fat and high-sucrose diet. Pancreas. 2009;38:e80-e86., gemcitabine chemotherapy1010. Makay O, Kazimi M, Aydin U, Nart D, Yilmaz F, Zeytunlu M, et al. Fat replacement of the malignant pancreatic tissue after neoadjuvant therapy. Int J Clin Oncol. 2010;15:88-92. and octreotide1111. Yu T, Liu R, Li M, Li X, Qiang O, Huang W, Tang C. Effects of octreotide on fatty infiltration of the pancreas in high-fat diet induced obesity rats. Wei Sheng Yan Jiu. 2014;43:186-92.. The presence of one or more component of metabolic syndrome, such as diabetes, BMI ≥30, hypertension or hyperlipidemia is associated with 37% increased prevalence of pancreatic steatosis1212. Sepe PS, Ohri A, Sanaka S, Berzin TM, Sekhon S, Bennett G, et al. A prospective evaluation of fatty pancreas by using EUS. Gastrointest Endosc. 2011;73:987-93.. Chronic alcohol abuse increases pancreatic cholesteryl ester accumulation and induces pancreatic steatosis1313. Wilson JS, Colley PW, Sosula L, Pirola RC, Chapman BA, Somer JB. Alcohol causes a fatty pancreas. A rat model of ethanol-induced pancreatic steatosis. Alcohol Clin Exp Res. 1982;6:117-21. and usually is seen when person consuming more than 30 gram/day of ethanol1414. Noronha M, Salgadinho A, Ferreira De Almeida MJ, Dreiling DA, Bordalo O. Alcohol and the pancreas. I. Clinical associations and histopathology of minimal pancreatic inflammation. Am J Gastroenterol . 1981;76:114-9.. Several infections such as acquired immunodeficiency syndrome (AIDS)1515. Oliveira NM, Ferreira FA, Yonamine RY, Chehter EZ. Antiretroviral drugs and acute pancreatitis in HIV/AIDS patients: is there any association? A literature review. Einstein (Sao Paulo). 2014;12:112-9., chronic hepatitis B1616. Sasaki M, Nakanuma Y, Ando H. Lipomatous pseudohypertrophy of the pancreas in a patient with cirrhosis due to chronic hepatitis B. Pathol Int. 1998;48:566-8. and reovirus infection1717. Walters MN, Leak PJ, Joske RA, Stanley NF, Perret DH. Murine infection with reovirus 3. pathology of infection with types 1 and 2. Br J Exp Pathol. 1965;46:200-12. can produce fatty pancreas. Haemochromatosis44. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8:169-77. and malnutrition state such as kwashiorkor1818. Diamond I, Vallbona C. Kwashiorkor in a North American white male. Pediatrics. 1960;25:248-57. can also be responsible NAFPD.

Diagnosis of pancreatic steatosis

Pancreatic steatosis (PS) is most commonly diagnosed by using different imaging techniques11. Ozbulbul NI, Yurdakul M, Tola M. Does the visceral fat tissue show better correlation with the fatty replacement of the pancreas than with BMI? Eurasian J Med. 2010;42:24-7.,33. Pezzilli R, Calculli L. Pancreatic steatosis: Is it related to either obesity or diabetes mellitus? World J Diabetes. 2014;5:415-9.,77. Wong VW, Wong GL, Yeung DK, et al. Fatty pancreas, insulin resistance, and β-cell function: a population study using fat-water magnetic resonance imaging. Am J Gastroenterol. 2014;109:589-97. (Figure 1). When using any imaging technique to identify pancreatic steatosis, we should know that there is up to 6.2% fatty infiltration of the pancreas in normal individuals. But specificity and sensitivity of different imaging modalities has not been clearly mentioned in several articles on PS.

FIGURE 1
Aetiologies of pancreatic steatosis.

Ultrasonography in diagnosis of pancreatic steatosis

Ultrasonography (USG) is widely available to detect PS but obesity and bowel gas may cause invisibility of pancreas. To diagnose pancreatic steatosis, pancreas echogenicity is traditionally compared with kidney echogenicity. Hyperechogenic pancreas can be seen in both pancreatic fibrosis and in fatty pancreas. Pancreatic steatosis can be classified into four grades by identifying patterns of pancreas echogenicity in abdominal USG (Figure 2); grade 0: when pancreas and renal echogenicity are similar; grade 1: when pancreas echogenicity is increased and is slightly higher than in the kidney; grade 2: when substantial increase in pancreas echogenicity than renal echogenicity but the retroperitoneal fat echogenicity is more than pancreatic echogeni­city; and grade 3: the pancreas echogenicity is ≥ retroperitoneal fat echogenicity1919. Lee JS, Kim SH, Jun DW, Han JH, Jang EC, Park JY, et al. Clinical implications of fatty pancreas: correlations between fatty pancreas and metabolic syndrome. World J Gastroenterol. 2009;15:1869-75.,2020. Marks WM, Filly RA, Callen PW. Ultrasonic evaluation of normal pancreatic echogenicity and its relationship to fat deposition. Radiology. 1980;137:475-9..

Computed tomography (CT) in diagnosis of pancreatic steatosis

Focal pancreatic steatosis can be presented as a hypo attenuating mass lesion on CT scan2121. Hague J, Amin Z. Focal pancreatic lesion: can a neoplasm be confidently excluded? Br J Radiol. 2006;79:627-9.. Non contrast computed tomography (CT) can be used to diagnose PS. Disadvantages of CT scan are exposure to radiation, high cost and can miss focal fatty replacement of pancreas. Fatty pancreas can be classified by CT scan into five grades depending on site of pancreatic involvement (Figure 2); Grade 0- normal appearance without fatty replacement, Grade 1- fatty infiltration involving less than 25% of given pancreatic region, Grade 2- fatty replacement that involved 25%-50% of a given pancreatic region, Grade3- fatty replacement involving 50%-75% of a given pancreatic regions; and Grade 4 corresponded to fatty infiltration which involves more than 75% of a given pancreatic region2222. Soyer P, Spelle L, Pelage JP, Dufresne AC, Rondeau Y, Gouhiri M, et al. Cystic fibrosis in adolescent and adults: Fatty replacements of the pancreas CT evaluation and functional correlation. Radiology. 1999;210:611-5.. Fat concentration in pancreas is positively correlated with attenuation indexes in CT scan; this finding suggests that unenhanced CT is useful non-invasive assessment of pancreatic fat2323. Kim SY, Kim H, Cho JY, Lim S, Cha K, Lee KH, et al. Quantitative assessment of pancreatic fat by using unenhanced CT: pathologic correlation and clinical implications. Radiology. 2014;271:104-12..

FIGURE 2
Pancreatic steatosis grading by trans abdominal ultrasonography (UGS) and abdominal computed tomography (CT).

Endoscopic ultrasonography in diagnosis of pancreatic steatosis

Diagnostic accuracy of pancreatic steatosis by endoscopic ultrasound (EUS) is superior to CT scan and magnetic resonance imaging (MRI). The disadvantages are invasive procedure, risk of complications and needs of sedation. EUS is still the most sensitive investigation for pancreas screening but till now pancreatic biopsy is the best method to measure pancreatic fat concentration2424. Lesmana CRA, Ho KY, Lesmana LA. Impact of endoscopic ultrasound procedures in various pancreatobiliary disorders in Indonesia based on a case series in a private hospital. Case Rep. Gastroenterol. 2015;9:206-14.. However, it is unethical to use EUS as a screening tool2525. Larghia A, Petroneb MC, Galassoa D, Arcidiacono PG. Endoscopic ultrasound in the evaluation of pancreatobiliary disorders. Dig Liver Dis. 2010;42:6-15.. EUS grading system adapted from radiology incorporating the echo-texture of the pancreas relative to the spleen as well as the ability to visualize the main pancreatic duct and “salt and pepper” dots in the parenchyma has been suggested to assess fatty pancreas1212. Sepe PS, Ohri A, Sanaka S, Berzin TM, Sekhon S, Bennett G, et al. A prospective evaluation of fatty pancreas by using EUS. Gastrointest Endosc. 2011;73:987-93..

Magnetic resonance imaging for diagnosis of PS

Magnetic resonance imaging (MRI) can estimate fat concentration in pancreas with high accuracy. MRI may be the test of choice for detection of intrapancreatic fat but available data is little to correlate pancreatic steatosis on MRI or EUS with histology. During MRI, commonly three methods are used to measure the fat in the pancreas. Advanced chemical shift-based gradient echo magnetic resonance imaging technique that measures the proton-density-fat-fraction (PDFF) has been shown to accurately quantify liver fat fraction when compared with the magnetic resonance spectroscopy (MRS) technique2626. Kang GH, Cruite I, Shiehmorteza M, Wolfson T, Gamst AC, Hamilton G, et al. Reproducibility of MRI determined proton density fat fraction across two different MR scanner platforms. J Magn Reson Imaging. 2011;34:928-34. and reliably measures pancreatic fat content when compared with other MRI imaging techniques2727. Schwenzer NF, Machann J, Martirosian P, Stefan N, Schraml C, Fritsche A, et al. Quantification of pancreatic lipomatosis and liver steatosis by MRI: comparison of in/opposed-phase and spectral-spatial excitation techniques. Invest Radiol. 2008;43:330-7..

Pathological classification

Pathologically pancreatic steatosis is classified into homogenous pancreatic lipomatosis and non homogenous pancreatic lipomatosis. Again non homogenous lipomatosis is classified into four types; type 1a: head is usually replaced by fat, type 1b: head, neck and body are replaced by fat, type 2a: head and uncinate process replaced by fat, type 2b: most of the pancreas except the peribiliary region is replaced by fat2828. Mortelé KJ, Rocha TC, Streeter JL, Taylor AJ. Multimodality imaging of pancreatic and biliary congenital anomalies. Radiographics. 2006;26:715-31.. However, histological examination is not recommended for only diagnosis of pancreatic steatosis.

Clinical significances

Development of diabetes mellitus: Wang et al. (2014) in their study found that the patients with fatty pancreas has an higher risk of development of diabetes than patients without fatty pancreas2929. Wang CY, Ou HY, Chen MF, Chang TC, Chang CJ. Enigmatic ectopic fat: prevalence of non-alcoholic fatty pancreas disease and its associated factors in a Chinese population. J Am Heart Assoc. 2014;3:e000297. and newly diagnosed patients with type 2 diabetes mellitus (DM2) have significantly greater pancreatic fat content3030. Chai J, Liu P, Jin E, Su T, Zhang J, Shi K, et al. MRI chemical shift imaging of the fat content of the pancreas and liver of patients with type 2 diabetes mellitus. Exp Ther Med. 2016;11:476-80.. Pancreatic islets cell fat infiltration leads to a reduced insulin secretion and increases development of DM23131. Lameloise N, Muzzin P, Prentki M, Assimacopoulos-Jeannet F. Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes. 2001;50:803-9.. Presence of >25% pancreatic fatty infiltration is associated with significantly increased risk of development of type 2 diabetes mellitus and generalized atherosclerosis3232. Stamm BH. Incidence and diagnostic significance of minor pathologic changes in the adult pancreas at autopsy: a systematic study of 112 autopsies in patients without known pancreatic disease. Hum Pathol. 1984;15:677-83..

Post operative pancreatic fistula: developing a pancreatic fistula is significantly increased after pancreatic surgery in patients with pancreatic steatosis3333. Mathur A, Marine M, Lu D, Swartz-Basile DA, Saxena R, Zyromski NJ, Pitt HA. Nonalcoholic fatty pancreas disease. HPB (Oxford) 2007;9:312-8.,3434. Tranchart H, Gaujoux S, Rebours V, Vullierme MP, Dokmak S, Levy P, et al. Preoperative CT scan helps to predict the occurrence of severe pancreatic fistula after pancreaticoduodenectomy. Ann Surg. 2012;256:139-45., and have a ten times higher risk of incidence of fistula formation in pancreas than those with fibrotic pancreas3535. Patel AC, Yagnik VD. Evaluation of risk factors for postoperative pancreatic fistula following pancreaticoduodenectomy. Formos J Surg. 2019;52:76-83..

Carotid atherosclerosis: pancreatic steatosis is an independent risk factor for the development of carotid atherosclerosis in non-obese subjects with type 2 diabetes mellitus. So, it could be a marker of higher risk of cardiovascular disease, especially in non-obese individuals3636. Kim MK, Chun HJ, Park JH, Yeo DM, Baek KH, Song KH, et al. The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes. Diabetes Res Clin Pract. 2014;106:590-6..

Pancreatitis: risk factors of pancreatic steatosis such as obesity and components of metabolic syndrome are known risk factors for acute pancreatitis. When acute pancreatitis due to any aetiology affects fatty pancreas, it is usually severe in intensity3737. Van Geenen EJ, Smits MM, Schreuder TC, van der Peet DL, Bloemena E, Mulder CJ. Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease. Pancreas. 2010;39:1185-90. and also is a significant risk factor for developing subclinical chronic pancreatitis3838. Fujii M, Ohno Y, Yamada M, Kamada Y, Miyoshi E. Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical check up. Environ Health Prev Med. 2019; 24:10..

Pancreatic carcinoma: fatty pancreas is independently associated with an increased risk of development of pancreatic carcinoma33. Pezzilli R, Calculli L. Pancreatic steatosis: Is it related to either obesity or diabetes mellitus? World J Diabetes. 2014;5:415-9.,3939. Hori M, Takahashi M, Hiraoka N, Yamaji T, Mutoh M, Ishigamori R, et al. Association of pancreatic Fatty infiltration with pancreatic ductal adenocarcinoma. Clin Transl Gastroenterol. 2014;5:e53.. PS promotes dissemination and lethality of pancreatic carcinoma by alteration of tumour microenvironment, enhanced tumour spread4040. Mathur A, Hernandez J, Shaheen F, Shroff M, Dahal S, Morton C, et al. Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma. HPB (Oxford). 2011;13:404-10.. Patients with increased pancreatic fat have a poor outcome than those who develop cancer in a pancreas without steatosis. Chronic inflammation with excessive fat accumulation might be the cause of cell injury and development of pancreatic carcinoma4141. Jeannet FA. Fat storage in pancreas and in insulin-sensitive tissues in pathogenesis of type 2 diabetes. Int. J. Obes. 2004;28:53-57.. But another study found that there is no association between fatty pancreas and chronic pancreatitis or carcinoma of pancreas1212. Sepe PS, Ohri A, Sanaka S, Berzin TM, Sekhon S, Bennett G, et al. A prospective evaluation of fatty pancreas by using EUS. Gastrointest Endosc. 2011;73:987-93.. Non alcoholic fatty liver disease (NAFLD) is positively correlated with pancreatic cancer in these patients and NAFLD patients with pancreatic cancer have poorer outcome than patients without NAFLD4242. Chang CF, Tseng YC, Huang HH, Shih YL, Hsieh TY, Lin HH. Exploring the relationship between nonalcoholic fatty liver disease and pancreatic cancer by computed tomographic survey. Intern Emerg Med. 2018;13:191-7.. Pathophysiology of development of pancreatic cancer in NAFPD is similar to how NAFLD causes liver cancer 44. Smits MM, van Geenen EJ. The clinical significance of pancreatic steatosis. Nat Rev Gastroenterol Hepatol. 2011;8:169-77..

Pancreatic exocrine insufficiency: pancreatic steatosis can lead to exocrine pancreatic insufficiency (EPI) by (1) fat droplet accumulation in pancreatic acinar cells and consequent lipotoxicity, (2) destruction of acinar cells by both inflammation and fatty replacement, (3) by negative paracrine effect of adipocytes. Exocrine function in NAFPD patients has never been extensively investigated. In few case reports, patients with weight loss and massive steatorrhea were found to have severe pancreatic steatosis diagnosed by abdominal computed tomograms (CT scan) in whom the administration of pancreatic extracts improved symptoms4343. Lozano M, Navarro S, Perez-Ayuso R, Llach J, Ayuso C, Guevara MC, Ros E. Lipomatosis of the pancreas: an unusual cause of massive steatorrhea. Pancreas. 1988;3:580-2.,4444. Aubert A, Gornet JM, Hammel P, Lévy P, O’Toole D, Ruszniewski P, et al. Diffuse primary fat replacement of the pancreas: an unusual cause of steatorrhea. Gastroenterol Clin Biol. 2007;31:303-6..

Cardiovascular risk: risk factors of fatty pancreas are also risk factors of cardiovascular accident. The presence of NAFPD on ultrasonography is associated with increased aortic intima media thickness and epicardial adipose tissue4545. Selim Kul S, Ayşegül Karadeniz A, Dursun I, Şahin S, Faruk Çırakoğlu Ö, Raşit Sayın M, et al. Non-Alcoholic Fatty Pancreas Disease is Associated with Increased Epicardial Adipose Tissue and Aortic Intima-Media Thickness. Acta Cardiol Sin. 2019;35:118-25.. Therefore, it could be a marker of a higher risk of cardiovascular disease.

Pancreatic enzymes level in PS: few study4646. Wu WC, Wang CY. Association between non-alcoholic fatty pancreatic disease (NAFPD) and the metabolic syndrome: casecontrol retrospective study. Cardiovasc Diabetol 2013;12:77. showed that serum amylase value is significantly lower in patients with fatty pancreas compared to normal pancreas individuals but another study indicates that there is no association between fatty pancreas and serum amylase or lipase concentrations1212. Sepe PS, Ohri A, Sanaka S, Berzin TM, Sekhon S, Bennett G, et al. A prospective evaluation of fatty pancreas by using EUS. Gastrointest Endosc. 2011;73:987-93.. Benign pancreatic hyperenzymemia (BPH) or Gullo’s syndrome is a diagnosis of exclusion and diagnosed by persistently elevated pancreatic enzymes without any clinical or pathological evidence of pancreatic disease. There is no relationship between NAFPD and Gullo’s syndrome.

Correlation between non-alcoholic fatty liver and non-alcoholic fatty pancreas

Pancreatic steatosis is common in patients with NAFLD, and pancreatic fat content positively correlates with liver steatosis grading determined by histology4646. Wu WC, Wang CY. Association between non-alcoholic fatty pancreatic disease (NAFPD) and the metabolic syndrome: casecontrol retrospective study. Cardiovasc Diabetol 2013;12:77.,4747. Nacif LS, Rocha-Santos V, Claro LCL, Vintimilla A, Ferreira LA, Arantes RM, et al. Liver biopsy may facilitate pancreatic graft evaluation: Positive association between liver steatosis and pancreatic graft adipose infiltration. Clinics (Sao Paulo). 2018; 73:e49.. Patients with histology-determined liver fibrosis have significantly less pancreatic fat infiltration than those without evidence of liver fibrosis4848. Patel NS, Peterson MR, Brenner DA, Heba E, Sirlin C, Loomba R. Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;37:630-9.. Fatty infiltration in pancreas causes β-cell dysfunction, which may also lead to hepatic steatosis4949. Hannukainen JC, Borra R, Linderborg K, Kallio H, Kiss J, Lepomäki V, et al. Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity. J Hepatol. 2011;54:545-52. and pancreatic fat also may play a role in the development of non alcoholic steatohepatitis (NASH)3737. Van Geenen EJ, Smits MM, Schreuder TC, van der Peet DL, Bloemena E, Mulder CJ. Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease. Pancreas. 2010;39:1185-90..

Differential diagnosis

Pancreatic steatosis of the dorsal caudal pancreas must be distinguished from dorsal pancreatic agenesis. Lipomatous pseudohypertrophy of the pancreas has probably been considered as a differential diagnosis of pancreatic steatosis5050. Yasuda M, Niina Y, Uchida M, Fujimori N, Nakamura T, Oono T, et al. A case of lipomatous pseudohypertrophy of the pancreas diagnosed by typical imaging. JOP. 2010;11:385-8.,5151. Shimada M, Shibahara K, Kitamura H, Demura Y, Hada M, Takehara A, et al. Lipomatous pseudohypertrophy of the pancreas taking the form of huge massive lesion of the pancreatic head. Case Rep Gastroenterol. 2010;4:457-6..

Management of pancreatic steatosis (Figure 3)

There is no specific treatment for fatty pancreas. Until now there are no approved drugs for NAFPD treatment. Treatment of PS depends on the underlying cause and if it is correctable, it may reduce pancreatic fat infiltration. If patient is having metabolic syndrome then tight diabetes control, diet restriction, physical exercise and weight reduction may improve condition. Pancreatic steatosis can be treated with a healthy diet, exercise, less meat consumption, and smoking cessation5252. Ramkissoon R, Gardner TB. Pancreatic Steatosis: An Emerging Clinical Entity. Am J Gastroenterol . 2019;114:1726-34..

FIGURE 3
Flow chart of a practical approach of pancreatic steatosis (aetiology, diagnosis, clinical significance and management).

CONCLUSION

In majority cases, pancreatic steatosis is an incidental finding during trans-abdominal ultrasonography. It is commonly associated with metabolic syndrome, alcohol abuse and patients with non alcoholic fatty liver disease. NAFPD is usually diagnosed by radiological investigations such as abdominal USG, abdominal CT scan or abdominal MRI. Fatty pancreas has an increased risk of development of diabetes, pancreatic fistula after pancreatic surgery, development of carotid atherosclerosis in non-obese individuals, risk of development of pancreatic carcinoma, developing subclinical chronic pancreatitis and exocrine pancreatic insufficiency. Therefore early diagnosis and interventions for predisposing factors of pancreatic steatosis such as each component of metabolic syndrome can improve quality of life and prevent complications. But Until now there are no approved specific drugs for NAFPD treatment.

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  • Disclosure of funding: no funding received

Publication Dates

  • Publication in this collection
    20 May 2020
  • Date of issue
    Apr-Jun 2020

History

  • Received
    21 Oct 2019
  • Accepted
    20 Feb 2020
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