The relationship between triglycerides and pancreatic damage has been studied over the years. It is now known that Hypertriglyceridemia (HTG) is the 3rd leading cause of acute pancreatitis (less prevalent only than biliary and alcoholic causes). However, the presence of HTG is common in all etiologies of acute pancreatitis.

How do you know if triglycerides (TG) are the cause or just an epiphenomenon present in an acute pancreatitis of another etiology?

Concept

Hypertriglyceridemia is defined as an increase in serum triglyceride levels above 150 mg/dL. This increase can be categorized into:

• Mild HTG: 150-199 mg/dL
• Moderate HTG: 200-999 mg/dL
• Severe HTG: 1000-1999 mg/dL
• Very severe HTG: > 2000 mg/dL

HTGs are classified into:

• Primary – patients with genetic alterations that do not allow the correct metabolism of triglycerides. These causes were cataloged by Friderickson into types I to V. The types most associated with acute pancreatitis are: types I, IV and V.
• Secondary: some patients raise TG due to: obesity, poorly controlled diabetes, hypercaloric and hyperlipidic diet, pregnancy and alcohol use. In addition, some medications are known to cause HTG and should be researched in this context (eg: retinoids, protease inhibitors, anti-psychotics, calcineurin inhibitors, diuretics and estrogens)

The risk of acute pancreatitis (PA) occurring in individuals with HTG is considered when TG rises > 1000 mg/dL (around 5%) and increases greatly when TG > 2000 mg/dL (risk becomes 10-20%). When analyzing the population with severe hypertriglyceridemia, about 20% reported a previous history of acute pancreatitis, a value much higher than the prevalence found in the population.

Pathophysiology

The pathophysiology of pancreatitis by HTG is complex, and to this day not completely understood. It is known that TG in the microcirculation induces the release of pancreatic lipase, which cleave the molecules into free fatty acids (which are lipotoxic to pancreatic cells). These, in turn, lead to endothelial injury with capillary extravasation. TG also activate substances such as tramboxane, phospholipase A and prostaglandins that lead to vasoconstriction and pancreatic ischemia.

Triglycerides and free fatty acids also tend to group together in the form of micelles, which increases plasma viscosity and leads to gland ischemia.

Added to this we also have the imbalance in intracellular calcium, oxidative stress in organelles, which also precipitate the early activation of trypsin, still within the pancreas.

Diagnosis

The diagnosis of PA by HTG is given in the same way as other etiologies, with the Atlanta criteria, when 2 of the 3 criteria are present (upper abdominal pain, elevation of pancreatic enzymes > 3 the limit of the method and compatible imaging exam) associated with elevation of TG > 1,000 mg/dL.

Here it is important to remember that PAs originating from other causes (biliary, alcoholic and drug) can raise TG in the acute phase, but rarely at levels > 1000 mg/dL. This elevation is seen as an epiphenomenon.

As for severity, in studies conducted, it was observed that PA by HTG tends to be more severe compared to other etiologies. In meta-analyses and systematic reviews, it was observed that these patients evolved with higher severity scores, higher recurrence rates, more ICU admissions, and higher mortality.

Treatment

The initial treatment is based on support, as in any pancreatitis: hydration, analgesia and nutritional support (especially for severe PAs).

Among the specific approaches, the following stand out:

• Heparin pump: heparin can be used in monotherapy or associated with other modalities (such as the insulin pump). The anticoagulant initially increases the degradation of TG into free fatty acids. This effect, however, is temporary and hepatic consumption of plasma lipoprotein lipase causes a rebound increase in TG after discontinuation of the infusion. In addition, heparin infusion increases hemorrhagic events, especially in severe PAs with local complications.
• Insulin pump: continuous insulin infusion also increases the activation of lipoprotein lipase and decreases the release of free fatty acids by adipocytes and promotes the metabolism of these fatty acids by hormone-sensitive cells. It can be used in conjunction with heparin therapy, but the studies that evaluated the results are small. This modality has the potential to reduce TG levels by 50-75% in 3 days.
• Plasmapheresis: this therapy mechanically removes excess chylomicrons from the bloodstream. Similarly, it appears to reduce the levels of pro-inflammatory cytokines, which are determinants for severity in the initial phase of PA. However, the results regarding relevant outcomes (multiple organ dysfunction, mortality) did not favor plasmapheresis over supportive therapy. In addition, these patients had higher ICU admission rates (since it is a procedure performed in an intensive care unit), always need central catheter placement and may present an infusion reaction to plasma. It is a safe therapy to be performed in pregnant women.
• Hemofiltration: this is another controversial therapy, which tends to remove lipids and cytokines from plasma. Although it removes TG quickly and effectively, there was no difference in relevant clinical outcomes, in addition to having a high cost.

Follow-up

Patients who have already had PA by HTG need follow-up after discharge to reduce the risks of recurrence. The use of hypolipidemic agents (such as fibrates) is recommended as soon as the patient is already able to resume the diet orally, still in the hospital. The goal in outpatient treatment is to keep TG levels < 500 mg/dL.

Patients with primary HTGs should be followed by specialists in the lipid area.

In summary, HTG is a relevant cause of PA, especially in patients with primary hypertriglyceridemias. Triglyceride dosage should be done in the first few hours, as levels tend to drop significantly with fasting. The therapeutic approach is similar to that of other pancreatitis, and specific therapies can be associated for short-term TG reduction. Patients should always be referred for follow-up post discharge, to reduce the risk of a new event.

References

1. Yang, AL & McNabb-Blatar, J. Hypertriglyceridemia and acute pancreatitis. Pancreatology 20 (2020) 795-800
2. Qiu, M et al. Comprehensive review on the pathogenesis of hypertriglyceridaemia associated acute pancreatitis. Annals of Medicine 2023, VOL. 55, No. 2, 2265939
3. de Pretis, N et al. Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical management. United European Gastroenterology Journal 2018, Vol. 6(5) 649–655
4. Bálint, ER et al. Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta?analysis. Sci Rep 2020 Oct 21;10(1):17936.

How to cite this article

Marzinotto M. Acute Pancreatitis by Hypertriglyceridemia Gastropedia 2024, vol 1. Available at: gastropedia.com.br/gastroenterology/pancreas/acute-pancreatitis-by-hypertriglyceridemia/

The term chronic pancreatitis (CP) is used to define a fibro-inflammatory disease of the pancreas, of a progressive and irreversible nature, which can present with abdominal pain as a symptom and loss of the exocrine and endocrine functions of the gland.

Causes of chronic pancreatitis

What is currently being discussed in the literature are the possible causes for this pathology. Alcohol is already well established as the main environmental risk factor for the onset of CP (42-77% of cases). Patients considered moderate or severe drinkers (35-48 drinks per week) have a relative risk of 2.7 to 3.3 for the development of the disease in a Danish observational study.

Another environmental risk factor is smoking, which is very prevalent in patients with CP, and is currently considered an independent risk factor for the onset of the pathology. It is a potent risk factor, including, for cases of recurrent acute pancreatitis, which sometimes culminate in the appearance of CP. In the case of smoking, the relative risk is 1.93 for current smokers compared to people who have never smoked.

Other causes of CP include autoimmune etiologies (both type I autoimmune pancreatitis – IgG4-related disease – and type II autoimmune pancreatitis are considered etiologies of chronic pancreatitis), obstructive etiologies (as in cases of neoplasms, cysts, scarring stenoses of the main pancreatic duct, oddi sphincter dysfunctions and pancreas divisum), Recurrent Acute Pancreatitis (RAP) and genetic etiologies.

Even after genetic study, about 10-15% of CPs still remain idiopathic, suggesting that there is much unknown in this field.

Pancreatic genetics and risk of neoplasia

The genetics of pancreatic pathologies is extremely complex, with several genes possibly involved in the phenotypes presented. Many mutations can lead to a RAP picture, which culminates with gland fibrosis, and other mutations or polymorphisms that lead directly to the appearance of CP.

The main genes involved in the pathogenesis of CP are listed below:

• PRRS-1: cationic trypsinogen gene – autosomal dominant inheritance mutation, responsible for Hereditary Chronic Pancreatitis.
• SPINK-1: gene that, in the absence of pathogenic mutations, prevents the activation of trypsinogen.
• CFTR: gene that encodes the chloride channels in the membrane of ductal cells – mutations in this gene can result in the phenotypes of Cystic Fibrosis
• CTRC: gene that promotes the degradation of trypsinogen and that mutated loses this protection mechanism

There are several other genes listed as coadjuvants in the pathological processes of the pancreas, and probably others that we are not yet aware of. The fact is that, in pancreatitis associated with one or more genetic mutations, the risk of Ductal Adenocarcinoma of the Pancreas is higher than other pancreatitis and much higher than the population risk. Patients with PRRS-1 and SPINK-1 mutations have a cumulative risk of 53% of pancreatic neoplasia at 75 years of age, while alcoholic CPs have this same calculated risk of 4%.

However, it was observed that this risk may be even higher in smoking patients. Cigarette smoking is the main risk factor for pancreatic neoplasia not associated with CP, and when the risks of mutated genes are added to smoking

Other mutations (such as CFTR and CTRC) do not seem to contribute to a significant increase in the incidence of pancreatic cancer. Just as other causes of CP, such as autoimmune pancreatitis or rarer causes, also do not confer a significant additional risk of neoplasia.

Although there is a higher incidence of ductal adenocarcinoma of the pancreas in the population with CP, there are no studies suggesting an efficient screening strategy for all patients. For patients with PRSS-1 mutations (or with suspicion of the mutation, in cases with more than two family members affected by CP) the international group recommends annual screening with imaging examination (computed tomography or magnetic resonance imaging). The use of echoendoscopy was not recommended, as it can be falsified by inflammation, fibrosis or calcifications. More studies are needed for recommendations regarding other mutations and other etiologies.

Despite recent advances, there is still a vast unknown field regarding the etiology and risk factors for CP, and more studies are needed so that we can unravel all the mysteries about this topic.

References

1. Singh, VK et al. Diagnosis and Management of Chronic Pancreatitis A Review. JAMA. 2019;322(24):2422-2434.
2. Hart, PA et al. Chronic Pancreatitis: Managing a Difficult Disease. Am J Gastroenterol. 2020 January ; 115(1): 49–55.
3. Aune, D et al. Tobacco smoking and the risk of pancreatitis: a systematic review and meta-analysis of prospective studies. Pancreatology, 2019 Dec;19(8):1009-1022.
4. Gardner, TB et al. ACG Clinical Guideline: Chronic Pancreatitis. Am J Gastroenterol 2020;115:322–339.
5. Le Cosquer, G et al. Pancreatic Cancer in Chronic Pancreatitis: Pathogenesis and Diagnostic Approach. Cancers 2023, 15, 761.
6. Greenhalf, G et al. International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 2020, 20, 910-918

How to cite this article

Marzinotto M. Chronic Pancreatitis – main etiologies and associated risk of Pancreatic Neoplasia Gastropedia 2023, vol 2. Available at: gastropedia.com.br/gastroenterologia/pancreatite-cronica-principais-etiologias-e-risco-associado-de-neoplasia-pancreatica/

When we think of Exocrine Pancreatic Insufficiency – EPI (decrease in the activity of pancreatic enzymes in the intestinal lumen, below the values for normal digestion) we automatically relate it to primary pancreas problems, such as chronic pancreatitis or pancreatic neoplasia. And that’s correct, these pathologies are indeed a cause of EPI. However, we have several other causes that should be remembered by the gastroenterologist.

To understand correctly, let’s turn to pancreatic physiology. The production of digestive enzymes by the pancreas is not only dependent on the morphology of the gland. Initially, the pancreas is stimulated by neural pathways derived from the vagus nerve, and later has its main stimulation pathway through the passage of chyme through the duodenum. At this stage, the release of secretin and cholecystokinin (CCK) is responsible for about 70% of all pancreatic juice production for that meal. Therefore, it is correct to say that any failure in this circuit can be the cause of EPI.

Today we classify the etiologies of EPI as pancreatic and extra-pancreatic causes:

Among the pancreatic causes, we have:

• Chronic pancreatitis
• Pancreatic neoplasms
• Cystic Fibrosis
• Pancreatic Resections
• Hemochromatosis
• Severe acute pancreatitis, with extensive necrosis of the glandular parenchyma

And among the extra-pancreatic causes, we can list:

• Celiac Disease
• Crohn’s disease of high small intestine involvement
• Type I and II Diabetes
• Pancreatic aging
• Gastroduodenal surgeries

Pancreatic causes are better known, and are caused by diseases that lead to progressive fibrosis of the pancreas, such as chronic pancreatitis; pancreatic atrophy combined with obstruction of the main pancreatic duct (such as neoplasms, especially of the cephalic region) and loss of pancreatic parenchyma, secondary to acute pancreatitis or pancreatic resections. In addition to these, cystic fibrosis is the main genetic cause and causes liposubstitution of the pancreatic parenchyma, as well as alteration in the transport of pancreatic juice through the ducts.

The most well-established non-pancreatic causes are: celiac disease (due to duodenal atrophy and loss of stimulation by duodenal hormones – secretin and CCK), diabetes mellitus and derivative surgeries.

In more recent studies, diabetes has been pointed out as a cause of EPI, both DM-1 and DM-2. The reasons for this are diverse and involve:

• Atrophy of the exocrine parenchyma due to lack of insulin: the hormone produced by pancreatic endocrine cells exerts a paracrine trophic action on acinar cells. The decrease in insulin causes a decrease in the trophism of the exocrine parenchyma.
• Diabetes can lead to autonomic neuropathy, impairing vagal pathways and the stimulation of acetylcholine on pancreatic cells.
• The microangiopathy that leads to a course of chronic ischemia in the gland, decreasing enzymatic production.
• The infiltration of adipocytes in the pancreas, in addition to lymphocytes, increases the action of fibroblasts and causes a greater deposition of collagen in the organ.

The frequency of EPI in diabetics is still uncertain, and it seems to be higher in patients with DM-1 (30-56%) and lower in patients with DM-2 (30-40%). Despite the heterogeneity of the studies, the prevalence of EPI in diabetic patients should not be underestimated.

In relation to upper abdomen surgical procedures, we observe an increasing frequency of EPI in gastrectomies, duodenopancreatectomies and derivative surgeries, such as gastrojejunal bypass.

• In partial or total gastrectomies we have studies showing 30-73% of EPI after 3 months of surgery.
• After duodenopancreatectomies this percentage can reach 100%, however the average post-procedure indicated by pancreatic or periampullary neoplasia was 74%.
• This percentage is higher than that found in duodenopancreatectomies for benign diseases (53%).
• There is a study that shows 16% of EPI post esophagectomy, although it has a small N.

Finally, the frequency of EPI post gastrojejunal bypass has been shown to be a concern in the follow-up of these patients. Especially after a few years of surgery, a percentage of these patients may present EPI. In a retrospective cohort, 20.6% of patients had steatorrhea, but only 10.3% of them were diagnosed with EPI post bypass with Y-Roux reconstruction. However, despite the frequency not being high, the treatment of patients diagnosed with EPI is crucial for satisfactory nutritional evolution.

As we can see, the causes of Exocrine Pancreatic Insufficiency go beyond structural problems in the gland. It is imperative that the gastroenterologist remember EPI in the contexts presented above, and that he does not miss the opportunity for correct treatment of these patients.

References

1. Vikesh K Singh, Mark E Haupt, David E Geller, Jerry A Hall, Pedro M Quintana Diez. Less common etiologies of exocrine pancreatic insufficiency. World J Gastroenterol 2017 October 21; 23(39): 7059-7076
2. Martha Campbell-Thompson, Teresa Rodriguez-Calvo, and Manuela Battaglia. Abnormalities of the Exocrine Pancreas in Type 1 Diabetes. Curr Diab Rep. 2015 October ; 15(10): 79.
3. J. R. Huddy, F. M. S. Macharg, A. M. Lawn, S. R. Preston. Exocrine pancreatic insufficiency following esophagectomy. Diseases of the Esophagus (2013) 26, 594–597
4. Miroslav Vujasinovic, Roberto Valente, Anders Thorell, Wiktor Rutkowski, Stephan L. Haas, Urban Arnelo, Lena Martin and J.-Matthias Löhr. Pancreatic Exocrine Insufficiency after Bariatric Surgery. Nutrients 2017, 9, 1241;
5. Joshua Y Kwon , Alfred Nelson , Ahmed Salih , Jose Valery, Dana M Harris, Fernando Stancampiano , Yan Bi. Exocrine pancreatic insufficiency after bariatric surgery. Pancreatology, 2022 Nov;22(7):1041-1045.

How to cite this article

Marzinotto M. Exocrine Pancreatic Insufficiency: a look beyond the obvious. Gastropedia 2023, vol 1. Available at: https://gastropedia.com.br/sem-categoria/insuficiencia-pancreatica-exocrina-um-olhar-alem-do-obvio

A topic that has been gaining attention from pancreas scholars lately is pancreatic steatosis. This is a generic term that infers the accumulation of fat in the pancreas. However, there are 2 main mechanisms to justify pancreatic steatosis:

• The first is called “fatty replacement”, that is, the replacement of pancreatic cells by adipocytes after the death of acinar cells. This occurs in genetic and congenital syndromes, such as Cystic Fibrosis, Shwachman-Diamond and Johanson-Blizzard, in addition to alcohol abuse, use of some medications (such as corticosteroids, gencitabine, octreotide and rosiglitazone), viral infections, malnutrition and post necrotizing acute pancreatitis (the area of necrosis is often replaced by adipocytes).
• The second mechanism is fatty infiltration (or “fatty infiltration”), in which adipocytes accumulate in the gland, without loss of acinar cells. Unlike what happens with liver fat, which is intracellular, pancreatic fat accumulates in the interlobular region, both of the exocrine parenchyma and of the islets of endocrine parenchyma. This mechanism is most associated with obesity, DM-2 and with Metabolic Syndrome.

Epidemiology

Data on the incidence and prevalence of pancreatic steatosis are still scarce, especially in the west. In the east, 16-35% of people have this finding on imaging exams. In individuals undergoing endoscopic ultrasound, the finding of pancreatic steatosis was in 27% of patients.

In a meta-analysis conducted by Singh and collaborators of 11 studies with 12,675 patients, the global prevalence was 33%. These patients had a 67% higher risk of hypertension, a 108% higher risk of diabetes and a 137% higher risk of Metabolic Syndrome.

Obesity proved to be the main risk factor for the finding of pancreatic steatosis. And some studies also related the finding of non-alcoholic fatty liver disease (NAFLD) with pancreatic steatosis, although the accumulation of pancreatic fat precedes the appearance of liver fat.

Diagnosis

The definitive diagnosis of pancreatic steatosis is with histological analysis, however it is rare to have pancreatic biopsies in the context of benign diseases. Therefore, it is necessary to use non-invasive imaging exams, such as:

• Trans-abdominal ultrasound: it is a very available exam that does not use radiation or contrast. However, being the pancreas a retro-peritoneal organ, the evaluation of the gland is impaired by gas interposition and by the patient’s own biotype. The ultrasonographic characteristic is of a hyperechoic pancreas, compared to the hepatic and splenic parenchyma.
• Endoscopic ultrasound: the most used method for diagnosis and grading of pancreatic steatosis (which can vary from I to IV, with types I and II considered normal pancreas, and types III and IV considered steatotic pancreas). The grading is done in comparison with the spleen parenchyma. However, there is still little inter-observer agreement, and multicenter studies with a larger number of participants are needed for this grading to be validated.
• Abdominal tomography: in abdominal tomography without contrast, we can observe a hypoattenuating pancreas in relation to the splenic parenchyma. There is a good correlation between tomographic attenuation indices and histology. In the study without contrast, however, the diagnosis of pancreatic masses that can also present as hypoattenuating may be missed.
• Magnetic resonance imaging: a safe and effective method in diagnosing pancreatic steatosis, as it has greater accuracy for evaluating soft parts. More studies are needed, however, to determine the “normal” amount of fat in healthy individuals

Clinical impact

Some situations related to pancreatic steatosis are being raised in the most recent studies. There are still many doubts about the real clinical impact of this finding, but what we have positive so far is:

• Relationship of pancreatic steatosis with obesity: there is a correlation of pancreatic steatosis and obesity, as well as a reduction of steatosis with weight loss. In individuals undergoing bariatric surgery (by-pass or vertical gastrectomy) there was a significant decrease in pancreatic fat, regardless of weight loss or control of comorbidities (such as diabetes, for example).
• Relationship of pancreatic steatosis with Diabetes mellitus: in diabetic individuals, the finding of pancreatic steatosis is common, and increases with the duration of the disease. However, there are doubts whether the presence of pancreatic steatosis can potentiate the dysfunction of pancreatic beta cells, and contribute to a worsening of glycemic control.
• Relationship of pancreatic steatosis and Non-alcoholic fatty liver disease (NAFLD): it seems that pancreatic steatosis precedes hepatic steatosis in patients with Metabolic Syndrome. Almost all individuals with NAFLD (97%) have concomitant pancreatic fat infiltration.
• Relationship of pancreatic steatosis and pancreatic cancer: it is known that obesity is considered a risk factor for pancreatic adenocarcinoma and, it seems, fatty infiltration in the pancreas plays a role in carcinogenesis, regardless of obesity. This finding is due to lipotoxicity and the release of substances resulting from oxidative stress, such as oxygen free radicals. In the fatty pancreas, the incidence of intraepithelial neoplasia (PanIN) and invasive ductal adenocarcinoma is higher. It is even suggested that patients with pancreatic steatosis would have a greater severity of the disease, with more lymph node metastases.

Other associations are not possible to be made at the moment, such as: association with acute pancreatitis, chronic pancreatitis or pancreatic fibrosis, exocrine pancreatic insufficiency or appearance of pancreatic fistula in the postoperative period. These relationships are still controversial, and require further studies.

References

1. Sepe, PS et al. A prospective evaluation of fatty pancreas by using EUS. Gastrointestinal Endoscopy, 2011. doi:10.1016/j.gie.2011.01.015
2. Majumder, S et al. Fatty Pancreas: Should We Be Concerned? Pancreas. 2017 ; 46(10): 1251–1258. doi:10.1097/MPA.0000000000000941.
3. Catanzaro, R et al. Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease. World J Gastroenterol 2016 September 14; 22(34): 7660-7675. DOI: 10.3748/wjg.v22.i34.7660
4. Chang, ML. Fatty Pancreas-Centered Metabolic Basis of Pancreatic Adenocarcinoma: From Obesity, Diabetes and Pancreatitis to Oncogenesis. Biomedicines 2022, 10, 692. https://doi.org/10.3390/biomedicines10030692.

How to cite this article

Marzinotto, M. Pancreatic Steatosis – Where are we? Gastropedia 2021, vol. 1. Available at: https://gastropedia.com.br/gastroenterology/pancreas/pancreatic-steatosis-where-are-we

The mucinous cystadenoma (MCN) is a cystic lesion, mucin-producing, almost exclusively found in women, in a ratio of 20:1. The peak incidence is in the 5th decade of life.

The cyst is preferentially located in the body and tail of the pancreas. The main characteristic, in addition to the thick content, rich in mucin, is the ovarian stroma found in the lesion, with receptors for estrogens and progestogens. In the presence of female hormones, the lesion tends to grow in size. In addition, it is a lesion that does not communicate with the pancreatic duct, differentiating them from IPMNs.

The cyst epithelium is composed of columnar cells, mucin-producing. There is a risk of malignant transformation that varies in studies from 0-34%, however there are still no faithful markers that predict the risk of the lesion becoming malignant. What exists are image characteristics that can signal malignant transformation:

• lesions > 3 cm
• presence of mural nodules
• dilation of the main pancreatic duct (> 6mm)
• peripheral calcifications

Diagnosis

The diagnosis of MCNs can be given with a good imaging exam, such as a tomography or magnetic resonance imaging. However, if there is diagnostic doubt, there is the possibility of fine needle aspiration (FNA) via Echoendoscopy. In this case it is important to request biochemical markers such as: amylase (tends to be low), CEA (in mucinous lesions CEA is usually > 190 ng/ml, with an accuracy of 79%) and glucose (usually low in mucinous cysts < 66 mg/dl). When combined, the dosage of CEA and intracyst glucose has an accuracy of 93% for the diagnosis of mucinous lesions.

In doubt of malignant transformation, cytology of the cyst is requested, although the sensitivity is low for the evaluation of dysplasia (about 58%), although the specificity is 96%.

Treatment

MCNs that do not have high risk stigmas for malignancy can be followed with imaging exams (in the first year, an exam every 6 months, and after this period, an annual exam), although it is not possible to exclude the possibility of neoplasia without surgical resection.

When opting to follow up with images, we can delay the treatment of a resectable lesion. Therefore, this decision should take into account the risk of the patient evolving with pancreatic malignancy, as well as his age, life expectancy and other risk factors, such as obesity and smoking. In addition, another alarm sign is recent onset diabetes.

As MCNs are lesions that affect the body and tail of the pancreas (preferably) the resection of this portion of the pancreas tends to be less morbid to the patient. In addition, it is possible to perform the enucleation of the lesion, without necessarily requiring pancreatectomy.

Still as therapeutic alternatives we have the ablation of the lesion with ethanol or paclitaxel, or even radiofrequency ablation. However, these procedures have many adverse effects, and are proposed for patients not candidates for surgery. More studies are needed to indicate ablation as a routine procedure.

Prognosis

The prognosis of the patient who had the MCN resected before malignant transformation is very good, with survival around 100% in 5 years. Patients operated with invasive MCNs, have about 60% survival in 5 years. Lesions < 4 cm without high risk stigmas, have malignancy rates of < 0.05%

See also our article on Serous Cystadenoma of the Pancreas by clicking this link

Bibliography

1. Lopes CV. Cyst fluid glucose: An alternative to carcinoembryonic antigen for  pancreatic mucinous cysts. World J Gastroenterol 2019 May 21; 25(19): 2271-2278
2. Nilsson, LN et al. Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature. Pancreatology 2016. 1-9.
3. Elta, GH et al. ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts. Am J Gastroenterol 2018; 113:464–4
4. The European Study Group on Cystic Tumours of the Pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018;67:789–804

How to cite this file

Marzinotto M., MUCINOUS CYSTADENOMA (MCN). Gastropedia, 2022. Available at: https://gastropedia/gastroenterology/pancreas/mucinous-cystadenoma-mcn

Pancreatic cysts are, in most cases, incidental findings of imaging exams.

It is estimated that about 3-14% of people undergoing abdominal exams have some pancreatic cystic lesion as a finding. In autopsy studies, this finding can reach 24%. There is a clear increase in prevalence in older age groups.

Cystic lesions can be divided into:

• benign cysts: pseudocysts, simple cysts, serous cystadenomas
• malignant cysts: cystadenocarcinomas, cystic neuroendocrine tumors, solid-cystic pseudopapillary neoplasia
• cysts with potential for malignancy: IPMNs and mucinous cystadenomas

In this article we will talk a little about serous cystadenoma.

SEROUS CYSTADENOMA (SCA)

Serous cystadenoma is a lesion that affects more women than men (2:1), in the 6th or 7th decade of life.

It is a lesion that has no preference for any pancreatic region, being able to affect the head, body or tail of the gland.

Radiological aspect

The most striking characteristic of serous cystadenoma is the finding of a polycystic lesion, with fibrous septa between them, forming a microcystic aspect (70% of SCA). In about 20-30% of cases, the septa converge to the center of the lesion, forming a central fibrous scar (most typical sign of SCA). In 20% of cases we observe a honeycomb aspect, with multiple microcysts and thin septa between them.

Figure 1: Serous Cystadenoma of the pancreas head – lobular lesion with septa converging to the central location of the lesion. (personal file)

In about only 10% of cases SCA can be oligocystic, making the radiological diagnosis more challenging. In these cases, other exams are often necessary for diagnostic confirmation, such as Echoendoscopy with puncture and analysis of the intracystic fluid.

Fluid characteristics

The cytological characteristic of serous cystadenoma are cuboidal cells, with cytoplasm rich in glycogen, although the sensitivity for cytology with FNA is very low.

The biochemical analysis of the fluid can help in cases of uncertain diagnosis. The characteristic of SCA is to have the Carcino-Embryonic Antigen (CEA) below 192 ng/ml, which is associated with non-mucinous lesions. In addition, as there is no communication with the pancreatic ducts, the amylase in the intra-cystic fluid is low.

More recently, with the advancement of confocal endoscopy, it is possible to visualize the vascularization pattern (in SCA, it is subepithelial – accuracy 87%) and allows biopsies of the cyst epithelium. This procedure is still performed in few centers, and although it improves the accuracy of the diagnosis, it brings higher risks of adverse effects (acute pancreatitis and intracystic hemorrhage).

Prognosis

The prognosis of SCA is excellent, with less than 1% mortality. Few cases in the literature have evolved to malignancy, and there is no agreement on the periodicity of follow-up. For many authors, it is a benign lesion.

Although it is a lesion with a low chance of malignant transformation, there is the possibility of lesion growth in up to 40% of SCAs.

The last recommendation from the European group is for a new imaging exam in 1 year, and afterwards, only if there are symptoms (abdominal pain, jaundice or nausea and vomiting).

How to cite this file

Marzinotto M., SEROUS CYSTADENOMA OF PANCREAS. Gastropedia, 2022. Available at: https://gastropedia/gastroenterology/pancreas/serous-cystadenoma-of-pancreas

References

1. Sakorafas, GH et al. Primary pancreatic cystic neoplasms revisited. Part I: Serous cystic neoplasms. Surgical Oncology, 2011
2. Tirkes, T et al. Cystic neoplasms of the pancreas; findings on magnetic resonance imaging with pathological,surgical, and clinical correlation. Abdom Imaging, 2014
3. Larson, A et al. Natural History of Pancreatic Cysts. Dig Dis Sci, 2017

Autoimmune Pancreatitis (AIP) is one of the possible causes of chronic pancreatitis, which presents with inflammatory infiltrate in the gland and progressive fibrosis, which can lead to pancreatic insufficiency (1).

The observation of the clinical picture allows us to classify AIP into 2 subtypes (2,3):

• Autoimmune Pancreatitis type 1: the pancreatic involvement is part of a systemic condition, which affects various organs, related to infiltration by immune cells rich in IgG4 (a sub-fraction of IgG). The main characteristic is the lympho-plasmacytic infiltrate in the pancreas, with more than 10 cells / CGA positive for IgG4, storiform fibrosis and the absence of granulocytic lesions.
• Autoimmune Pancreatitis type 2: it is an exclusively pancreatic disease, which can present with episodes of Recurrent Acute Pancreatitis, and which is characterized by the granulocytic infiltrate in the pancreas and the absence of cells positive for IgG4. The diagnosis of AIP type 2 can only be confirmed with pancreatic histology. Despite being a disease restricted to the pancreas, it is associated with other autoimmune conditions, such as Inflammatory Bowel Diseases (especially UC).

Clinical picture

• The clinical picture typical of AIP (in either subtype) is abdominal pain, obstructive jaundice and elevation of pancreatic and canalicular enzymes in the blood. Weight loss is also common.
• In some cases, pancreatic or biliary masses may be found, which require differential diagnosis with neoplasms.
• Less common is the occurrence of repeated acute pancreatitis, especially in AIP type 2 (4, 5).
• The dosage of IgG4 > 140 mg/dl, hypergammaglobulinemia and FAN + can be secondary markers of systemic disease (AIP type 1).

Radiological Findings

Associated with the clinical picture, radiological findings can corroborate the diagnosis. About 85% of patients with AIP have compatible radiological changes. The most typical finding is edema and pancreatic enlargement (pancreas “in sausage”) and loss of lobulations, often associated with a hypoattenuating halo on contrast-enhanced abdominal tomography or resonance in 15-40% of cases (6,7).

                                                                      * Own archive images

Less frequent is the focal involvement, with the presence of nodules in the gland, which can mimic neoplasia. This form is more common in AIP type 2 (35-80% incidence) and it is essential to make the differential diagnosis with mitotic processes. (7) In this context, the use of exams such as Endoscopic Ultrasound or Endoscopic Retrograde Cholangiopancreatography can be useful in an attempt to rule out the diagnosis of neoplastic processes, as they allow the collection of material for histopathological evaluation. (8)

Treatment

The initial treatment is with corticosteroids, and both forms of the disease have a good response to the corticosteroid course. Treatment is indicated in cases that present with obstructive jaundice and abdominal pain, nodular form (pancreatic or biliary masses), cases simulating sclerosing cholangitis or extra-pancreatic disease. The initial dose can be a fixed 40mg/day of prednisone (or around 0.6 mg/kg/day) for a period of 4 weeks. After this period, a clinical, laboratory and imaging reassessment is recommended. In case of improvement, a reduction in the dose of 5mg per week is indicated until the complete suspension of the medication. (5, 9)

In the patient who has a contraindication to the use of corticosteroids (especially patients with uncontrolled diabetes mellitus) Rituximab (anti CD-20) can also be used as a first-line agent for induction of remission. (9, 10)

Despite showing a good response to treatment with corticosteroids, the recurrence rate of symptoms is approximately 30%. Predictors for recurrence of the condition are: high levels of IgG4 at diagnosis and involvement of other organs, especially the biliary tree. In these cases, it is still not clear whether adjuvant treatment with immunomodulators (Cyclosporine, Azathioprine, Rituximab) is necessary or whether a longer therapy with corticosteroids is necessary. (1, 2, 5, 9).

How to cite this article

Marzinotto M. Autoimmune Pancreatitis. Gastropedia, 2022. Available at: https://gastropedia.com.br/gastroenterology/pancreas/autoimmune-pancreatitis/

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