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/

Bibliographic references

• Mahdani, K. Farrel, J. Management of Autoimmune Pancreatitis. Gastrointest Endoscopy Clin N Am 28, 2018, 493–519
• Shimosegawa, T. et al. International Consensus Diagnostic Criteria for Autoimmune Pancreatitis Guidelines of the International Association of Pancreatology. Pancreas 2011; 40: 352-358
• Sah, R.P., Chari, S.T. Autoimmune Pancreatitis: An Update on Classification, Diagnosis, Natural History and Management. Curr Gastroenterol Rep, 2012 14:95–105
• Hart, P.A. et al. Recent Advances in Autoimmune Pancreatitis. Gastroenterology 2015;149:39–51
• Nagpal, S.J.S. et al. Autoimmune Pancreatitis. Am J Gastroenterol (2018) 113:1301–1309
• Raina A, Yadav D, Krasinskas AM, et al. Evaluation and management of autoimmune pancreatitis: experience at a large US center. Am J Gastroenterol 2009; 104(9):2295–306.
• Sandrasegaran, K. Menias, C.O. Imaging in Autoimmune Pancreatitis and Immunoglobulin G4–Related Disease of the Abdomen. Gastroenterol Clin N Am 47 (2018) 603–619
• Fujii-Lau, L.L.. Levy, M.J. The Role of Endoscopic Ultrasound in the Diagnosis of Autoimmune Pancreatitis. Gastrointest Endoscopy Clin N Am, 2017.
• Kamisawa, T. et al. Advances in IgG4-related pancreatobiliary diseases. Lancet Gastroenterol Hepatol, 2018; 3: 575–85
• Okazaki, K. Uchida, K. Current perspectives on autoimmune pancreatitis and IgG4-related disease. Jpn. Acad., Ser. B 94 (2018) 412-427.

The Endoflip^TM is an innovative technique that uses impedance planimetry technology to assess the distensibility of gastrointestinal organs.

Despite being developed in 2009, its use is still restricted to research environments due to high costs and the need for more evidence for better standardization of the method.

It consists of a catheter that has at its distal end a distensible balloon of 8 or 16 cm (Figures 1 and 2). In this balloon, there are 16 pairs of impedance planimetry sensors, which are capable of measuring the cross-sectional area of a plane of the organ (planimetry) using the electrical resistance (impedance) of the fluid in the balloon.

At the distal end of the catheter, there is also a pressure transducer, which is responsible for measuring the pressure inside the balloon. Thus, by dividing the cross-sectional area by the pressure, we can determine the Distensibility Index in response to volume-controlled distension.

Most of the studies with Endoflip^TM have been carried out for esophageal evaluation. For this, the catheter is introduced with the patient sedated, usually after upper digestive endoscopy.

With the introduction of Endoflip^TM 2.0 in 2017, a topography system was also associated, which allows the evaluation of esophageal motility (whether absence of waves, whether abnormal retrograde contractions or normal anterograde contractions) – Figure 3.

The potential applications of the method are:

1. Evaluation of dysphagia and achalasia

• Highlight in those patients with clinical suspicion of achalasia, but diagnostic doubt due to normal relaxation of the esophagogastric junction (EGJ) in manometry exam;
• Usefulness in patients who cannot perform manometry due to not tolerating the discomfort of the probe (Endoflip^TM is performed sedated);
• Distensibility index of the EGJ > 3 mm²/mmHg and anterograde contractions suggest normality (Figure 3);
• Distensibility index £ 1.6 mm²/mmHg of the EGJ, as well as absence of contractions (figure 4) or repetitive retrograde contractions (figure 5) suggest achalasia.
• In cases of manometric diagnosis of EGJ flow obstruction, the Distensibility Index of the EGJ < 2 mm²/mmHg is associated with better symptomatic response to therapies similar to achalasia, while values > 3 mm²/mmHg are favorable to conservative follow-up.

2. Intraoperative use to guide adjustments in myotomies and fundoplications

• In myotomies, values of Distensibility Index of the EGJ between 4.5 and 8.5 mm²/mmHg suggest better results (Figure 6);
• In fundoplications, values of Distensibility Index of the EGJ between 2 and 3.5 mm²/mmHg were associated with lower index of dysphagia and reflux after procedure.

3. Evaluation in eosinophilic esophagitis

• Identify esophageal distensibility, in order to identify fibrostenotic narrowings that are not always well evaluated by endoscopy.
• Potential benefit in patients who persist with dysphagia despite histological remission, possibly guiding possible dilations.

4. Other potential uses

• Evaluate pyloric distensibility in patients suspected of gastroparesis
• Evaluate anal canal in patients with incontinence.

How to cite this article

Lages RB., Endoluminal Functional Lumen Imaging Probe (EndoflipTM): getting to know the technology and its potential uses. Gastropedia, 2022. Available at: https://gastropedia.com.br/gastroenterologia/esofago/endoluminal-functional-lumen-imaging-probe-endofliptm-conhecendo-tecnologia-e-seus-potenciais-usos/

Bibliographic References

1. Dorsey YC, Posner S, Patel A. Esophageal Functional Lumen Imaging Probe (FLIP): How Can FLIP Enhance Your Clinical Practice? Dig Dis Sci 2020. Online ahead of print. doi:10.1007/s10620-020-06443-8.
2. Hirano I, Pandolfino JE, Boeckxstaens GE. Functional Lumen Imaging Probe for the Management of Esophageal Disorders: Expert Review From the Clinical Practice Updates Committee of the AGA Institute. Clin Gastroenterol Hepatol 2017;15:325–34. doi:10.1016/j.cgh.2016.10.022.
3. Su B, Novak S, Callahan ZM, Kuchta K, Carbray JA, Ujiki MB. Using impedance planimetry (EndoFLIP^TM) in the operating room to assess gastroesophageal junction distensibility and predict patient outcomes following fundoplication. Surg Endosc 2020;34:1761–8. doi:10.1007/s00464-019-06925-5.
4. Su B, Dunst C, Gould J, Jobe B, Severson P, Newhams K, et al. Experience-based expert consensus on the intra-operative usage of the endoflip impedance planimetry system. Surg Endosc 2020. doi:10.1007/s00464-020-07704-3.

Fecal microbiota transplantation (FMT) or fecal transplant involves the infusion of feces from a healthy donor into the gastrointestinal tract of a patient who has a disease related to alteration of the intestinal flora.

The first reports of FMT are from 1700 years ago when a Chinese doctor administered suspensions of human feces orally to patients with food poisoning and/or severe diarrhea. In 2013, the first well-designed study on the success of FMT in infections by Clostridium difficile was published in the New England Journal of Medicine and has since motivated numerous other works related to the topic.

The formal indication of FMT currently is in recurrent infections by Clostridium difficile with a cure rate of up to 90%.

There are ongoing studies of FMT in other gastrointestinal diseases (inflammatory bowel disease, irritable bowel syndrome) as well as in endocrine (obesity, metabolic syndrome), neurological (Parkinson’s, multiple sclerosis), hematological (ITP, GVHD) and psychiatric (autism) diseases.

For the smooth running of the FMT, a multidisciplinary team (attending physician whether it is the clinician, gastroclinician or geriatrician, infectious disease specialist and the endoscopist) aligned and with a well-established protocol in the service is necessary.

STAGES OF THE PROCEDURE

1. CHOICE OF DONOR

The donor can be related or not. This person will have to go through a rigorous infectious screening and a questionnaire regarding the presence of other diseases that may make donation unfeasible.

2. COLLECTION, PREPARATION AND ADMINISTRATION OF MATERIAL

The donor should arrive at the laboratory on the day of the procedure and the ideal time between the collection of feces and the infusion of the material is 6 hours. The fecal weight should be at least 50g and the total volume of the suspension is 100 to 200ml, which will be infused depending on the chosen route. There is also the option to freeze the material but it is preferable to use fresh feces (see image below).

3. ROUTE OF ADMINISTRATION

According to the articles published so far, all 5 routes studied show similar results. In this way, FMT can be performed by:

• Upper digestive endoscopy with nasogastric/nasoenteral tube
• Anterograde enteroscopy
• Colonoscopy
• Rectosigmoidoscopy
• Enema

What will determine the choice of method will be the clinical condition of the patient and experience of the endoscopist. In the upper route, it is suggested to infuse up to 100ml slowly through the nasoenteral tube or through the accessory channel or by a spray catheter. In the lower route, it is suggested to infuse as much of the material as possible (average of 200ml) in the terminal ileum and right colon.

4. PRE, PERI AND POST FMT CARE

The preparation of the exam is the adequate fasting and in cases where the chosen route is low, intestinal preparation can be performed with mannitol solution or polyethylene glycol.

Some precautions can be taken, however, still nothing consensual, such as:

• Use of proton pump inhibitors
• Use of prokinetics
• Use of antidiarrheals (loperamide)

It is recommended to infuse about 100ml of the fecal material slowly when the upper route is used, while when FMT is done by the lower route, slightly larger volumes are used (about 200ml).

5. ADVERSE EVENTS

Adverse events can occur in up to 30% of cases, usually in the first 48 hours post procedure and treated conservatively. The most common are fever, diarrhea, abdominal cramps and belching. Rare cases of death have been described due to regurgitation with bronchoaspiration of fecal material and perforation due to toxic megacolon.

FINAL CONSIDERATIONS

So far, the only indication of FMT with proven scientific evidence is in severe infections by Clostridium difficile. Due to the increase in incidence and morbidity and mortality related to infection by C difficile, fecal microbiota transplantation has been a good therapeutic option in selected cases. In Brazil, there is still no well-defined regiment for the procedure and there are few centers that have performed FMT. However, with recent discoveries of the influence of intestinal microbiota on immune response, it may be that in the future new indications will emerge and FMT will be a widely used procedure in our country.

HOW TO CITE THIS ARTICLE

Carlos A. Fecal Microbiota Transplantation. Gastropedia 2022. Available at: https://gastropedia.com.br/gastroenterology/intestine/fecal-microbiota-transplantation

BIBLIOGRAPHIC REFERENCES

1. Bennet JD, et al. Lancet. 1989 Jan 21;1(8630):164.
2. Zhang F, et al. Am J Gastroenterol. 2012 Nov;107(11):1755
3. Van Nood E, et al. N Engl J Med. 2013 Jan 31;368(5):407-15
4. Cammarota G, et al. Gut 2017;66:569–580
5. Mullish BH, et al. Gut 2018;0:1–22
6. Choi HH, et al. Clin Endosc. 2016 May;49(3):257-65

Introduction

The incidence of neuroendocrine tumors of the pancreas is increasing, possibly due to more frequent imaging tests and the quality of these tests. However, their prevalence is fortunately still rare. This post from Therapeutic Endoscopy is intended to serve as a reference guide when we eventually come across one of these situations in our daily lives. If you want to know about duodenal neuroendocrine tumors check out this other article.

Important general concepts about neuroendocrine tumors of the gastrointestinal tract

The NETs correspond to a heterogeneous group of neoplasms that originate from neuroendocrine cells (enterochromaffin-like cells), with secretory characteristics.

All gastroenteropancreatic (GEP) NETs are potentially malignant and behavior and prognosis are correlated with histological types.

The NETs can be sporadic (90%) or associated with hereditary syndromes (10%), such as multiple endocrine neoplasia type 1 (MEN-1), SD von Hippel-Lindau, neurofibromatosis and tuberous sclerosis.

The NETs are mostly indolent, but can determine symptoms. Thus, they can be divided into functioning and non-functioning:

• Functioning: secretion of active hormones or neurotransmitters: serotonin, glucagon, insulin, somatostatin, gastrin, histamine, VIP or catecholamines. They can cause a variety of symptoms
• Non-functioning: they may not secrete any peptide/hormones or secrete non-active peptides or neurotransmitters, so as not to cause clinical manifestations.

Pancreatic neuroendocrine tumors (TNE-P)

The functioning TNEs of the pancreas are: insulinoma, gastrinoma, glucagonoma, vipoma and somatostatinoma.

Most TNE-Ps are malignant, except for insulinomas and TNE-NFs smaller than 2 cm.

Surgery is the only curative modality for sporadic TNE-P, and resection of the primary tumor in patients with localized, regional and even metastatic disease, can improve patient survival.

In general, functioning TNEs of the pancreas should be resected to control symptoms whenever possible. TNE-NF depends on size (see below).

Multiple pancreatic tumors are rare and should raise suspicion of MEN1.

NEXT WE WILL SEE THE MAIN CHARACTERISTICS OF EACH HISTOLOGICAL SUBTYPE

INSULINOMAS

• It is the most frequent TNE of the pancreatic islets.
• 90% are benign, but they are symptomatic even when small.
• About 10% are associated with MEN.
• They are hypervascularized and solitary lesions, often < 2 cm.
• Whipple’s triad:
  • hypoglycemia (< 50)
  • neuroglycopenic symptoms (blurred vision, weakness, fatigue, headache, drowsiness)
  • disappearance of symptoms with glucose replacement
• serum insulin > 6 IU/ml
• C-peptide > 0.2 mmol/l
• Pro-insulin > 5 IU/ml
• Positive prolonged fasting test (99% of cases)
• Learn more about insulinoma in this other article

GASTRINOMAS

• It is more common in the duodenum, but 30% of cases are in the pancreas
• They are the most frequent TNEs of the pancreas after insulinomas.
• They are associated with MEN 1 syndrome in 30%, and in these cases they present as small and multifocal lesions.
• They cause hypergastrinemia and Zollinger-Ellison syndrome.
• 60% are malignant.
• Treatment: surgical in sporadic cases (DPT).
• In MEN 1, there is controversy in the surgical indication, since gastrinemia may not be controlled even with DPT (tumors are usually multiple)

GLUCAGONOMAS

• Rare; most are sporadic.
• They are usually large and solitary, with a size between 3-7 cm occurring mainly in the tail of the pancreas.
• Symptoms: migratory necrolytic erythema (80%), DM, malnutrition, weight loss, thrombophlebitis, glossitis, angular cheilitis, anemia
• Slow growth and long survival
• Lymph node or hepatic metastasis occurs in 60-75% of cases.

VIPOMAS

• Extremely rare
• Like glucagonomas, located in the tail, large and solitary.
• Most are malignant and metastatic
• In 10% of cases it can be extra-pancreatic.
• Clinical picture related to VIP secretion (vasoactive intestinal peptide):
  • diarrhea (more than 3L liters per day) – rice washing water
  • Hydro-electrolyte disorders: hypokalemia, hypochloridria, metabolic acidosis
  • Blushing
• Excellent response to treatment with somatostatin analogues.

SOMATOSTATINOMAS

• It is the least common of all
• Somatostatin leads to inhibition of endocrine and exocrine secretion and affects intestinal motility.
• Solitary lesion, large, sporadic, mostly malignant and metastatic
• Clinical picture:
  • Diabetes (75%)
  • Gallstones (60%)
  • Steatorrhea (60%)
  • Weight loss

NON-FUNCTIONING PANCREATIC TNE

• 20% of all pancreatic TNEs.
• 50% are malignant.
• The main differential diagnosis is with adenocarcinoma

Well-differentiated TNE-NF smaller than 2 cm: two societies (ENETS and NCCN) suggest observation if it is well differentiated. However, the North American society NETS recommends observation in tumors smaller than 1 cm and individualized conduct, between 1-2 cm.

PANCREATIC TNE RELATED TO HEREDITARY SYNDROMES

• 10% of TNE-Ps are related to MEN-1
• Often multicentric,
• Usually affecting younger people.
• Usually of benign behavior, but they present malignant potential
• Gastrinoma 30-40%; Insulinoma 10%; TNE-NF 20-50%; others 2%
• Surgical treatment is controversial, because sometimes it does not control gastrinemia (multiple tumors)

The multiple endocrine neoplasia (MEN) syndromes comprise 3 genetically distinct familial diseases involving adenomatous hyperplasia and malignant tumors in several endocrine glands. They are autosomal dominant diseases.

MEN-1

• Autosomal dominant disease
• Predisposes to TU (3Ps): Parathyroid; Pituitary (pituitary); Pancreas,
• Usually of benign behavior, but they present malignant potential
• Gastrinoma 30-40%; Insulinoma 10%; TNE-NF 20-50%; others 2%
• Surgical treatment is controversial, because sometimes it does not control gastrinemia (multiple tumors)

MEN-2A:

• Medullary thyroid carcinoma,
• Pheochromocytoma,
• Hyperplasia or adenomas of the parathyroid glands (with consequent hyperparathyroidism).

MEN-2B:

• Medullary thyroid carcinoma,
• Pheochromocytoma
• Multiple mucous and intestinal neuromas

References:

1. Pathology, classification, and grading of neuroendocrine neoplasms arising in the digestive system – UpToDate ; 2021
2. Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group. ecancer 2017,11:716 DOI: 10.3332/ecancer.2017.716

How to cite this article:

Martins BC, de Moura DTH. Pancreatic neuroendocrine tumors. Gasstropedia. 2022; vol I. Available at: gastropedia.com.br/surgery/pancreatic-neuroendocrine-tumors