The Helicobacter pylori (H. pylori) is the most prevalent chronic bacterial infection in the world, affecting more than half of the population. It is associated with chronic gastritis, which can progress to serious complications such as peptic ulcer, adenocarcinoma, and MALT lymphoma.

Based on current evidence, its eradication has been more broadly recommended, even in the absence of symptoms in many situations. The main references that guide the conduct of H. pylori in Brazil are:

• IV Brazilian Consensus (2018)
• Maastricht VI / Florence Consensus (2022)

One of the most important causes of failure to eradicate H. pylori is the increase in resistance to clarithromycin and levofloxacin. Resistance to nitroimidazoles is also common. On the other hand, resistance to amoxicillin and tetracycline is low and stable. These concepts are important both when we think about first-line schemes and retreatment schemes.

The choice of the initial treatment scheme for H pylori considers two main aspects:

• Local rate of resistance to clarithromycin
• History of drug allergy

It would be interesting to perform a susceptibility test (molecular or culture) before prescribing antibiotics, but we know that these methods are still extremely scarce (or even almost non-existent) in our daily Brazilian practice.

In areas where there is low resistance to clarithromycin (< 15%), the first-line empirical treatment should be triple therapy with clarithromycin or quadruple therapy with bismuth. A few studies have evaluated the resistance profile of H. pylori in Brazil, identifying resistance of 2.5 to 16.9% to clarithromycin, 5 to 23% to fluoroquinolones, approximately 50% to metronidazole and double resistance to clarithromycin and metronidazole from 7.5 to 10%. Given this, the trend of the Brazilian Consensus is still to consider Brazil as a low resistance area to clarithromycin.

Since Maastricht V (2017) and the IV Brazilian Consensus (2018), an important change in treatment recommendations for H. pylori was the increase in duration from 7 to 14 days in an attempt to increase the eradication rate in the face of the growing increase in bacterial resistance.

The first-line schemes proposed in our country, therefore, are the following:

• Recommended scheme: OAC – Standard triple therapy with clarithromycin

• Alternative scheme: BOTM – Quadruple therapy with bismuth

• Another alternative scheme: OACM – Concomitant quadruple therapy without bismuth. It is an option in areas of higher proven resistance to clarithromycin when bismuth is not available.

Speaking of the availability of colloidal bismuth subcitrate, this medication has been very little available in our country. Currently, it can only be obtained through compounding (and even then with some difficulty). This reminds us of furazolidone, which has been widely used in schemes for the treatment of H. pylori, but which has not been marketed for years in our country.

Penicillin allergy

The eradication of H. pylori in patients with penicillin allergy (reported in up to 3 to 10% of people) is a challenge. Ideally, this allergy should really be proven to have the schemes with amoxicillin available.

According to the Brazilian Consensus, there are two main schemes:

• Triple therapy with levofloxacin in substitution for amoxicillin (OCL)
• Quadruple therapy with bismuth (BOTM), as previously mentioned

Adverse effects

Unfortunately, up to 50% of patients experience side effects with H. pylori treatment. In less than 10%, these effects are limiting and lead to therapy interruption. It is therefore always important to properly inform patients about the most common side effects to increase adherence:

• Amoxicillin: Diarrhea, skin rash
• Clarithromycin: Nausea, vomiting, abdominal pain, metallic taste, rarely QT prolongation

Do probiotics help?

Probiotics (such as Lactobacilli and Saccharomyces boulardii) reduce the side effects associated with eradication therapy and, with this, can increase adherence. There are studies on direct effects on H. pylori, but more data are still needed.

It is necessary to check curability? When?

Yes. It should be performed at least 4 weeks after treatment. Ideally, non-invasive methods should be preferred, reserving endoscopy only if indicated for another reason (e.g., gastric ulcer cure control).

Conclusion

The H. pylori is extremely common and its eradication can often be a challenge. The standard triple therapy (OAC) in Brazil provides cure rates above 80% and is still the most used. However, we must be aware of the growing levels of bacterial resistance to constantly update our recommendations.

How to cite this article

Lages RB. How to treat Helicobacter pylori? Understanding how to choose the first-line scheme. Gastropedia 2022. Available at https://gastropedia.pub/en/gastroenterology/how-to-treat-helicobacter-pylori-understanding-how-to-choose-the-first-line-scheme

References

[1] Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022;71:1724–62. doi:10.1136/gutjnl-2022-327745.
[2] Coelho LGV, Marinho JR, Genta R, Ribeiro LT, Passos M CF, Zaterka S, et al. IVth Brazilian Consensus Conference on Helicobacter pylori infection. Arq Gastroenterol 2018;55:97–121. doi:10.1590/s0004-2803.201800000-20.

When we come across an ultrasound (USG) describing a focal liver lesion, we should organize the reasoning of when and how to investigate the described lesion: is it a focal cystic lesion, with regular walls, anechoic content and without signs of complexity (septa, calcifications, irregular margins)?

If yes and the exam is done by an experienced radiologist, no further investigation is necessary. However, if there is a complex cystic focal lesion or a solid focal lesion, these have an indication for investigation with contrasted imaging exam (computed tomography or upper abdomen magnetic resonance).

Figure 1. Abdominal ultrasound showing a solid, hyperechoic nodule, measuring approximately 1.0 cm, circumscribed, located in the right lobe, hepatic segment VII. Source: personal file.

It is essential to order the exam correctly, that is, to describe in the exam order that it is directed to the investigation of focal liver lesion. This will be fundamental to align the correct protocol on the day of the exam, especially, of abdominal tomography with intravenous contrast (iodine) with triphasic protocol – in addition to the pre-contrast phase, there will be the arterial, portal and balance phases.

The abdominal resonance exam with intravenous contrast (gadolinium) performs the contrasted phases (arterial, portal, balance) usually, in addition to having additional sequences that assist in the evaluation of the focal lesion (T1 pre-contrast sequences; in-phase and out-of-phase for fat evaluation; T2 and diffusion).

It is strongly recommended to mention in the exam order the most significant clinical data of the patient, such as age, symptoms, absence/presence of chronic liver disease and/or liver cirrhosis, use of anabolic steroids or contraceptives and previous or current oncological disease.

Note 1: The presence of liver cirrhosis is the most relevant clinical data and the most significant risk factor for the development of hepatocellular carcinoma (HCC), so that cirrhosis is present in approximately 90% of patients with HCC. Therefore, a hepatic nodule in cirrhotic liver, the main suspicion will be of HCC; already a hepatic nodule in non-cirrhotic liver, there will be a greater chance of benign focal lesion.

Among the benign focal liver lesions, the following stand out: hemangioma, focal nodular hyperplasia and adenoma. Such lesions present different echogenicity patterns to USG, being able to be hyperechoic, isoechoic or hypoechoic and their particularities will be themes of future posts

A differential diagnosis to be remembered is the possibility of area spared from steatosis, when the liver as a whole becomes hyperechoic due to fat deposition and a specific area is spared from this, generating the false impression of hypoechoic nodular focal lesion. There are also cases of focal steatosis, when fat deposition occurs locally, simulating a hyperechoic nodule.

Note 2: Except for simple hepatic cysts, solid hepatic focal lesions deserve dynamic investigation with intravenous contrasted exam for the evaluation of their behavior in the different phases of filling and vascular emptying, even if they are suggestive of benign lesion to abdominal ultrasound.

            Most of the time, the identification of benign focal liver lesion will be incidental, in routine exams, without clinical repercussion (symptoms or complications) and without laboratory alterations. After the initial contrasted exam (CT/MRI), selected cases will be candidates for abdominal resonance with hepatospecific contrast (gadoxetic acid – Primovist), biopsy of the hepatic nodule or even referred for surgical approach.

Thus, doctors from different specialties should have the discernment to investigate appropriately the finding of hepatic nodule in routine exam or choose to refer the patient for specialized evaluation with gastro-hepatologist.

Learn more about the evaluation of liver lesions in this other article

How to cite this article

Oti, KST. Hepatic nodule detected by ultrasound: step by step of when and how to investigate. Gastropedia 2022. Available at: https://gastropedia.com.br/gastroenterologia/figado/nodulo-hepatico-detectado-pela-ultrassonografia-passo-a-passo-de-quando-e-como-investigar/

References

1. Haring MPD, Cuperus FJC, Duiker EW, de Haas RJ, de Meijer VE. Scoping review of clinical practice guidelines on the management of benign liver tumours. BMJ Open Gastroenterol. 2021 Aug;8(1):e000592. doi: 10.1136/bmjgast-2020-000592. PMID: 34362758; PMCID: PMC8351490.
2. Strauss E, Ferreira AdeSP, França AVC, et al. Diagnosis and treatment of benign liver nodules: Brazilian Society of hepatology (SBH) recommendations. Arq Gastroenterol 2015;52:47–54.
3. Marrero JA, Ahn J, Rajender Reddy K, Reddy RK, et al. Acg clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol 2014;109:1328–47.
4. European Association for the Study of the Liver (EASL). EASL clinical practice guidelines on the management of benign liver tumours. J Hepatol 2016;65:386–98.

Non-alcoholic steatohepatitis (NASH) corresponds to the group of patients with non-alcoholic fatty liver disease (NAFLD) who present, in addition to predominantly macrovesicular steatosis, with hepatocyte ballooning, lobular inflammation, liver fibrosis, cirrhosis and risk of progression to hepatocellular carcinoma (HCC). Learn more in this other article.

About 30-40% of adults have NAFLD and of these, 3-12% evolve with NASH, with prevalence in progression in recent years, especially due to the strong association with metabolic factors such as obesity. Thus, NASH has become in recent years the main cause of liver transplantation in the world

In the evaluation of patients with NAFLD, it is essential to assess which non-invasive tests (NIT) can contribute to the investigation. Although abdominal ultrasound is the first-line examination in the initial evaluation of patients with NAFLD, it is operator-dependent and has low sensitivity for mild hepatic steatosis: typically, steatosis needs to affect more than 30% of hepatocytes to be detectable by this method.

Among the NITs available in our environment, transient hepatic elastography (FibroScan®, Echosens, Paris, France; TE) is the most commonly used by hepatologists. The technology was approved in 2013 by the Food and Drug Administration in the United States and quickly incorporated in the evaluation of patients with hepatopathy of different etiologies, including those with NAFLD.

Advantages of the method

Through the appropriate selection of one of the probes (Small, Medium and XL) by age, physical type and skin-liver distance, the examination is performed non-invasively and quickly, allowing the quantification of liver fat by CAP (controlled attenuation parameter) and liver fibrosis by assessing liver stiffness (liver stiffness measurement; LSM).

The reference point is guided by anatomical markers (meeting of the mid-axillary line with transverse and parallel line to the costal margins, at the level of the xiphoid appendix).

LSM

Through vibrations of low amplitude and low frequency (50Hz) emitted by the probe at the reference point, a shear wave propagates through the liver tissue at a certain speed (m/s): the stiffer the tissue, the faster the propagation of the wave. The LSM ranges from 1.5 to 75 kilopascals (kPa) and assesses liver stiffness in a volume 100 times larger than a liver biopsy.

The values of LSM vary according to the etiology of the hepatopathy, with the values of AUROC for F1, F2, F3 and F4 of 0.82, 0.85, 0.94 and 0.96, respectively, being reported in NAFLD. For advanced fibrosis (F3-F4), the cut-offs range from 8-12kPa, with a sensitivity of 84-100% and specificity of 83-97%.

Note 1: Some cross-sectional studies and head-to-head comparison indicated better accuracy of MR elastography in the evaluation of liver fibrosis compared to TE, in the identification of fibrosis (F1-F4) with specificity (F4, 94.5% vs 75.9%), however, the factors cost, availability and examination time (duration) are limiting factors of elastoRM in clinical practice.

CAP

An AUROC of 81-84% ?E1 (steatosis in at least 5-10% of hepatocytes); 85-88% for ?E2 (33%) and 86-91% for E3 (66%), with sensitivity for ?E1, ?E2 and E3 of 60-75%, 69-84% and 77-96%, respectively. The cut-offs for CAP is 248 dB/m for E1, 268 dB/m for E2 and 280 dB/m for E3.

Note 2: Although abdominal resonance with proton density fat fraction (MR-PDFF) has better sensitivity and specificity for the quantification of liver fat fraction compared to CAP, the factors cost and availability are the major limitations in clinical practice.

Reliability criteria

According to the manufacturer’s recommendations, during TE, 10 valid measurements should be obtained, with a success rate >60% and an interquartile range (IQR) ?30%.
Some studies have shown that IQR > 40 dB/m of CAP with M probe was associated with lower reliability for the diagnosis of liver steatosis, but additional studies are needed for validation as a criterion.

Limitations and considerations of the method

One of the biggest challenges of TE is the lower success rate in obese patients. While the M probe is indicated for adults with normal weight (BMI <25kg/m²) and the S probe for children and adolescents, the XL probe is indicated for obese patients or those with skin-liver distance greater than 3.5cm, as this probe allows greater depth in the evaluation of liver stiffness (35-75 vs 25-65mm) and CAP.

Prospective studies indicate that the XL probe estimates higher liver stiffness value than the M probe when applied in the same patient, however, high BMI tends to overestimate the LSM, thus, the effects of obesity and the XL probe tend to cancel each other out.

Other factors that impair LSM are: liver congestion, biliary obstruction, amyloidosis, focal liver lesions, increased transaminases (1-5xLSN) and ascites.

It is essential to instruct the patient to fast for 3-4 hours before the examination, as increased portal flow can increase the LSM by 1-5kPa (peak at 20-40 minutes, with duration of up to 180 minutes, on average).

Clinical application

In addition to the evaluation of liver stiffness and quantification of steatosis, TE has an important role in predicting complications of compensated advanced chronic liver disease (cACLD), such as esophageal varices (EV), HCC and liver-related death.

According to Baveno VII, in general:

1. LSM ?15kPa and platelets ? 150,000 excludes clinically significant portal hypertension (CSPH, sensitivity and negative predictive value >90%) in patient with cACLD;
2. LSM <20kPa and platelets > 150,000 allows to avoid performing EDA screening of EV;
3. In patients of viral, alcoholic and non-obese NASH etiology (BMI <30kgm/²), LSM ? 25 is sufficient to exclude CSPH (sensitivity and positive predictive value >90%).
4. In patients with cACLD due to NASH, the ANTECIPATE model can be used to predict the risk of CSPH, but additional validation is needed.

Guidelines Recommendations

TE is a validated NIT and recommended by the AASLD and EASL guidelines and, according to its availability, should be incorporated as a tool in the evaluation of patients with NAFLD in clinical practice.

References

1. Zhang X, Wong GL, Wong VW. Application of transient elastography in nonalcoholic fatty liver disease. Clin Mol Hepatol. 2020 Apr;26(2):128-141. doi: 10.3350/cmh.2019.0001n. Epub 2019 Nov 8. PMID: 31696690; PMCID: PMC7160347.
2. Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Goodman ZD, Chalasani NP, Kowdley KV, George J, Lindor K. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology. 2018 Jul;68(1):349-360. doi: 10.1002/hep.29721. PMID: 29222917; PMCID: PMC6511364.
3. Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, Hooker J, Sy E, Savides MT, Alquiraish MH, Valasek MA, Rizo E, Richards L, Brenner D, Sirlin CB, Loomba R. Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017 Feb;152(3):598-607.e2. doi: 10.1053/j.gastro.2016.10.026. Epub 2016 Oct 27. PMID: 27911262; PMCID: PMC5285304.
4. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII – Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30. Erratum in: J Hepatol. 2022 Apr 14;: PMID: 35120736.

How to cite this file

Oti KST., What should we know about transient hepatic elastography and its application in non-alcoholic fatty liver disease?. Gastropedia, 2022. Available at: https://gastropedia.com.br/gastroenterologia/figado/o-que-devemos-saber-sobre-a-elastografia-hepatica-transitoria-e-sua-aplicacao-na-doenca-hepatica-gordurosa-nao-alcoolica/

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

Gastroesophageal Reflux Disease (GERD) is quite common in the general population, with a prevalence of 10 to 20%. In patients with obesity, this prevalence can be double.

The mechanisms involved in the increased risk of GERD in obesity are due to increased abdominal pressure, leading to:

• Increased transient relaxation of the lower esophageal sphincter
• Hiatal hernia
• Decreased esophageal clearance

The prevalence of GERD is directly related to the severity of obesity and BMI (Body Mass Index). Patients with obesity (BMI > 30) have more episodes of reflux and worse DeMeester score than those who are overweight (BMI > 25). In candidates for bariatric surgery, those with BMI > 50 have erosive esophagitis with higher prevalence than those with BMI > 40 and so on. Despite this, it is uncommon to find severe esophagitis (C/D) or even the diagnosis of Barrett’s Esophagus.

How should GERD investigation be in the preoperative period of bariatric surgery?

Although it is routine in most bariatric services in Brazil, until recently there was great controversy in the international literature regarding Upper Digestive Endoscopy (EDA) in preparation for bariatric surgery.

The current recommendation according to international society consensus is as follows:

• EDA should be considered for all patients with gastrointestinal symptoms who plan to undergo bariatric surgery due to the frequency of findings that can change conduct
• EDA should also be considered for those without symptoms due to the chance of 25% of incidental endoscopic findings that can change conduct or even contraindicate bariatric surgery

How does the presence of GERD influence the technical choice of bariatric surgery?

Currently, Vertical Gastrectomy (GV) is the most performed bariatric surgery in the world. However, with long-term follow-up, we have seen more frequently cases with GERD postoperatively. In some situations, very symptomatic and refractory to clinical treatment, with the need for revision surgery for conversion to Roux-en-Y Gastric Bypass (BGYR).

There is no conduit, strong evidence regarding preoperative risk factors that can predict which patients will evolve with de novo reflux. We only know that those with pathological GERD, according to Lyon criteria, tend to worsen after GV.

For all this, the presence of GERD should be weighed in the joint decision with the patient between GV or Bypass. In general, but not necessarily, we should favor Gastric Bypass in case of:

• Los Angeles grades C or D Erosive Esophagitis
• Barrett’s Esophagus
• Hiatal hernia
• Esophageal motor alterations

How to cite this article

Dantas, A. Gastroesophageal reflux disease in the patient with obesity. Gastropedia; 2022 Available at: https://gastropedia.com.br/cirurgia/obesidade/doenca-do-refluxo-gastroesofagico-no-paciente-com-obesidade/

References:

1. Ayazi S, Hagen JA, Chan LS, DeMeester SR, Lin MW, Ayazi A, Leers JM, Oezcelik A, Banki F, Lipham JC, DeMeester TR, Crookes PF. Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms. J Gastrointest Surg. 2009 Aug;13(8):1440-7.
2. Derakhshan MH, Robertson EV, Fletcher J, Jones GR, Lee YY, Wirz AA, McColl KE. Mechanism of association between BMI and dysfunction of the gastro-oesophageal barrier in patients with normal endoscopy. Gut. 2012 Mar;61(3):337-43.
3. Brown WA, Johari Halim Shah Y, Balalis G, Bashir A, Ramos A, Kow L, Herrera M, Shikora S, Campos GM, Himpens J, Higa K. IFSO Position Statement on the Role of Esophago-Gastro-Duodenal Endoscopy Prior to and after Bariatric and Metabolic Surgery Procedures. Obes Surg. 2020 Aug;30(8):3135-3153. doi: 10.1007/s11695-020-04720-z. PMID: 32472360.
4. Bolckmans, R., Roriz-Silva, R., Mazzini, G.S. et al. Long-Term Implications of GERD After Sleeve Gastrectomy. Curr Surg Rep 9, 7 (2021).
5. Sebastianelli L, Benois M, Vanbiervliet G, Bailly L, Robert M, Turrin N, Gizard E, Foletto M, Bisello M, Albanese A, Santonicola A, Iovino P, Piche T, Angrisani L, Turchi L, Schiavo L, Iannelli A. Systematic Endoscopy 5 Years After Sleeve Gastrectomy Results in a High Rate of Barrett’s Esophagus: Results of a Multicenter Study. Obes Surg. 2019 May;29(5):1462-1469.

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/

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