Gallbladder polyps are common findings in abdominal ultrasound exams, appearing in about 4.5% of adults. While most of them do not have malignant potential, a small percentage – between 4% and 10% – are adenomas, which can become malignant.

Studies show that the size of the polyp is the main risk factor for the development of cancer, especially when adenomatous polyps are 10 millimeters or more, presenting a chance of malignancy between 37% and 55%.

However, it is difficult to differentiate between adenomatous polyps and polyps without malignant potential in preoperative exams. Therefore, it is important for the gastroenterologist to know the correct indication for surgery in patients with gallbladder polyps in order to avoid an unnecessary surgical procedure in patients without risk and, mainly, correctly indicating the procedure in the population with a higher risk of malignancy.

In this article, we will summarize the indications for follow-up and treatment of gallbladder polyps.

SYMPTOMATIC PATIENTS

Gallbladder polyps rarely cause symptoms, however some studies have reported an association between gallbladder polyps and undetected stones on ultrasound and/or cholecystitis. The joint European guideline of 2022 recommends cholecystectomy for patients who present symptoms such as biliary colic or complications (example: pancreatitis) and who have favorable clinical conditions for surgery [1]. The rate of symptom improvement is variable in the literature (40-90% improvement).

Patients with nonspecific dyspeptic symptoms without biliary colic should be treated conservatively (unless there are other indications for polyp removal), since the pathogenesis of these symptoms is not clear and cholecystectomy may not relieve symptoms. These patients should be treated symptomatically, as with other patients with functional dyspepsia.

ASYMPTOMATIC PATIENTS WITH RISK FACTORS FOR GALLBLADDER CANCER

Risk factors for gallbladder cancer include:

• age >60 years
• primary sclerosing cholangitis
• Asian ethnicity
• sessile polyps with focal gallbladder wall thickness >4 mm

The approach will depend on the size of the polyp:

• Polyps ≤5 mm: surveillance ultrasound at 6 months, 1 year, and 2 years. Follow-up can be discontinued if there is no growth during this period.
• Polyps 6 to 9 mm: cholecystectomy is recommended if the patient is clinically fit and accepts surgery.
• Polyps 10 to 20 mm: Polyps 10 to 20 mm should be considered as possibly malignant. Laparoscopic cholecystectomy is recommended.
• Polyps >20 mm: are generally malignant. Patients should undergo preoperative staging with computed tomography or endoscopic ultrasound. Radical treatment consists of extended cholecystectomy with lymph node dissection and partial hepatic resection at the gallbladder bed.

ASYMPTOMATIC PATIENTS WITHOUT RISK FACTORS FOR GALLBLADDER CANCER

In asymptomatic patients without risk factors for gallbladder cancer, surveillance recommendations vary according to the size of the polyp.

• For polyps ≤ 5 mm: no follow-up is necessary. *
• For polyps 6 to 9 mm: perform abdominal ultrasound at 6 months, 1 year, and 2 years. Surveillance can be discontinued if there is no growth during this period.

* This strategy is aligned with the practices of the American College of Radiology [2] and the Canadian Association of Radiologists Incidental Findings Working Group [3], which recommend that polyps smaller than 7 mm do not require follow-up.

IMPORTANT CONSIDERATIONS IN PATIENTS UNDERGOING SURVEILLANCE

1. Increase in polyp size

The joint European guideline of 2017 recommended that:

• An increase in size greater than 2 mm in the images probably represents a clinically significant increase and should prompt referral to a surgeon for cholecystectomy.

The update of this guideline in 2022 recommends that:

• If the polypoid lesion grows 2 mm or more during the 2-year follow-up period, then the current size of the polypoid lesion should be considered along with the patient’s risk factors. Multidisciplinary discussion should be held to decide whether to continue surveillance or if cholecystectomy is indicated.

An important retrospective study published in 2019 including more than 600,000 adults undergoing cholecystectomy showed that:

• The growth of 2 mm or more seems to be part of the natural history of gallbladder polyps.
  • The likelihood of a polyp growing at least 2 mm in 10 years was 66% for polyps smaller than 6 mm and 53% for polyps between 6-10mm.
  • Important: this growth does not seem to be associated with future gallbladder cancer. None of the 507 patients with polyps that grew to 10 mm or more were subsequently diagnosed with cancer.
• The first year is the most important:
  • Most cases of gallbladder cancer were diagnosed in the first year, probably representing neoplasms already present at the time of diagnosis.
  • Polyps initially smaller than 10 mm were almost never associated with future cases of gallbladder cancer (rate 1.05 per 100,000 person-years)
  • Polyps with ≥ 10 mm at diagnosis were rarely associated with gallbladder cancer after the first year.

The cherry on top of this study:

• In addition, we observed that similar proportions of adults were diagnosed with gallbladder Ca (0.053% vs. 0.054%), whether an initial ultrasound showed a gallbladder polyp or not. These findings suggest that there may not be a general link between gallbladder polyps and gallbladder neoplasia, and that gallbladder polyps are an incidental finding.

2. Duration of surveillance

The duration of surveillance in patients with gallbladder cancer is not clear. The updated joint European guidelines recommend discontinuing surveillance in two years if there is no growth of the polyps. Some authors recommend maintaining surveillance for at least five years. However, in patients with risk factors for gallbladder cancer, we should maintain surveillance for gallbladder cancer with abdominal USG indefinitely.

3. Adenomyomatosis

Patients with typical features of adenomyomatosis on ultrasound do not require surveillance or cholecystectomy.

4. If the gallbladder polyp disappears during follow-up

If the gallbladder polyp disappears during follow-up, the follow-up surveillance can be discontinued.

References

1. Foley KG, Lahaye MJ, Thoeni RF, Soltes M, Dewhurst C, Barbu ST, Vashist YK, Rafaelsen SR, Arvanitakis M, Perinel J, Wiles R, Roberts SA. Management and follow-up of gallbladder polyps: updated joint guidelines between the ESGAR, EAES, EFISDS and ESGE. Eur Radiol. 2022 May;32(5):3358-3368. doi: 10.1007/s00330-021-08384-w. Epub 2021 Dec 17. PMID: 34918177; PMCID: PMC9038818.
2. Sebastian S, Araujo C, Neitlich JD, Berland LL (2013) Manag- ing incidental findings on abdominal and pelvic CT and MRI, Part 4: white paper of the ACR Incidental Findings Commit- tee II on gallbladder and biliary findings. J Am Coll Radiol 10(12):953–956
3. Bird JR, Brahm GL, Fung C, Sebastian S, Kirkpatrick IDC (2020) Recommendations for the management of incidental hepatobiliary findings in adults: endorsement and adaptation of the 2017 and 2013 ACR Incidental Findings Committee White Papers by the Canadian Association of Radiologists Incidental Findings Working Group. Can Assoc Radiol J 71(4):437–447
4. Szpakowski JL, Tucker LY. Outcomes of Gallbladder Polyps and Their Association With Gallbladder Cancer in a 20-Year Cohort. JAMA Netw Open. 2020 May 1;3(5):e205143. doi: 10.1001/jamanetworkopen.2020.5143. PMID: 32421183; PMCID: PMC7235691.

How to cite this article

Martins BC. Management of Gallbladder Polyps: When to Follow Up and When to Recommend Cholecystectomy? Gastropedia 2024; vol 1. Available at: https://gastropedia.pub/en/surgery/management-of-gallbladder-polyps-when-to-follow-up-and-when-to-recommend-cholecystectomy

Introduction

Gallbladder polyps are usually incidental findings diagnosed during abdominal ultrasound exams or during cholecystectomy. They usually do not present symptoms, but occasionally they can cause discomforts similar to those caused by gallstones.

Most of these lesions are not neoplastic, but rather hyperplastic or represent lipid deposits.

With the widespread use of ultrasound, polypoid lesions in the gallbladder are being increasingly detected. However, often the image is not enough to rule out the possibility of neoplasia or pre-malignant adenomas. In this article, we will review the clinical importance and differential diagnosis of gallbladder polyps.

Classification

Polypoid lesions in the gallbladder can be categorized as benign or malignant. Benign lesions can be subdivided into neoplastic and non-neoplastic.

Non-neoplastic benign polyps

The most common benign non-neoplastic lesions are cholesterol polyps, followed by adenomyomatosis and inflammatory polyps.

• Cholesterol polyps and cholesterosis:
  • it is a benign condition characterized by the accumulation of lipids in the mucosa of the gallbladder wall.
  • they are the most common types of gallbladder polyps, reaching up to 10% or more.
  • It can be of the diffuse or polypoid type.
  • The term cholesterosis refers to the diffuse type, which is usually diagnosed incidentally during cholecystectomy, causing the appearance of a “strawberry gallbladder” due to the contrast it makes with the gallbladder mucosa.
  • Cholesterol polyps are the polypoid form of cholesterosis, being the most common gallbladder polyp, usually diagnosed incidentally on ultrasound.
  • Although usually asymptomatic, in some patients it can cause symptoms and complications similar to those caused by gallstones.
• Adenomyomatosis:
  • it is an abnormality of the gallbladder characterized by excessive growth of the mucosa, thickening of the muscular wall and intramural diverticula.
  • The prevalence of gallbladder adenomyosis is low, but it appears to have a higher prevalence in women than in men.
• Inflammatory polyps
  • Inflammatory polyps are the least common non-neoplastic polyps.
  • They appear as sessile or pedunculated and are composed of granulation and fibrous tissue with plasma cells and lymphocytes.
  • The polyps are usually 5 to 10 mm in diameter, although inflammatory polyps larger than 1 cm have been described

Neoplastic benign polyps

• Adenomas:
  • Adenomatous polyps of the gallbladder are the most common benign neoplastic lesions. Although the true incidence is unknown, in most series it is less than 0.5 percent.
  • Gallbladder adenomas are benign epithelial tumors composed of cells that resemble the epithelium of the bile ducts.
  • The risk of cancer increases with the size of the polyp, with larger adenomatous polyps having a risk of malignancy.
• Others — Other neoplastic lesions of the gallbladder such as fibromas, lipomas and leiomyomas, are rare. The natural history of these polyps is not well defined.

Malignant polyps:

• Most malignant polyps in the gallbladder are adenocarcinomas.
• The adenocarcinomas of the gallbladder are much more common than gallbladder adenomas, unlike the colon, where adenomas are much more common than adenocarcinomas.
• Squamous cell carcinoma, mucinous cystadenoma and gallbladder adenoacanthomas are rare

CANCER RISK

Most gallbladder polyps are benign, and most benign polyps, with the exception of adenomas, do not have malignant potential. The overall risk of gallbladder cancer in patients with gallbladder polyps appears to be low.

• In a large cohort study with over 35,000 adults with gallbladder polyps diagnosed by USG, 0.053% had gallbladder cancer, similar to the population without polyps (0.054%). [ref]
• The risk of progression to neoplasia varies according to the size of the polyps, occurring in 128/100,000 people for polyps > 10mm, but only in 1.3/100,000 people for polyps < 6mm.

Established risk factors for cancer

• Polyp size — The incidence of gallbladder cancer varies from 43 to 77% in polyps larger than 1 cm and 100% in polyps larger than 2 cm.
• Sessile polyp — sessile polyps are an independent risk factor for malignancy, with a 7x higher risk of gallbladder cancer. [ref]
• Age > 60 years: this is the cut-off adopted in guidelines for risk stratification and treatment guidance.
• Others: Indian ethnicity, primary sclerosing cholangitis

Conditions with uncertain risk

• Concomitant gallstones
• Adenomyomatosis — There is no evidence that the presence of adenomyosis increases the risk of gallbladder cancer. If the risk is increased, the magnitude of the increase appears to be small.

DIAGNOSIS

Gallbladder polyps are usually discovered incidentally on abdominal ultrasound exams. None of the available imaging modalities can unequivocally distinguish benign from malignant polyps. This can only be confirmed by histopathology after cholecystectomy.

Characteristics of gallbladder polyps on abdominal ultrasound:

• They can be single or multiple
• Sensitivity 84% and specificity 96% (meta-analysis with 16,260 patients)
• CHOLESTEROL POLYPS are usually multiple, homogeneous, polypoid and pedunculated, with echogenicity greater than the liver parenchyma.
  • They may or may not contain hyperechoic points.
  • Cholesterol polyps usually measure less than 1 cm.
  • In contrast to cholesterol polyps, diffuse cholesterosis does not have specific ultrasonographic findings, and its diagnosis is usually made after surgery.
• ADENOMAS are homogeneous lesions, isoechoic in relation to the liver parenchyma, have a smooth surface and usually do not have a pedicle.
  • The sessile morphology and focal thickening of the gallbladder wall greater than 4 mm are risk factors for malignancy.
• ADENOCARCINOMAS are homogeneous or heterogeneous polypoid structures that are usually isoechoic in relation to the liver parenchyma.
• The ADENOMYOMATOSIS can also cause a diffuse thickening with round anechoic f

Treating and caring for an oncology patient should go beyond the knowledge of high complexity and evidence-based that is updated every day. A solid doctor-patient relationship with expectation management and a lot of trust is expected.

The situation I want to put here is that of a patient with cholestatic syndrome due to non-biopsied periampullary malignant neoplasia. He had a very good status, a totally independent athlete for daily activities and with little weight loss even in the presence of symptoms of food intolerance.

Not meeting criteria for neoadjuvant (borderline)¹ and without evidence of metastatic lesions in the staging performed, a resection was chosen as the first treatment (upfront) which took place about 1 month after the first contact with the surgeon.

I expose the intraoperative photo:

The subcentimetric lesion highlighted was resected and sent for freezing biopsy. The finding was malignant neoplasia in the sample sent.

There are several factors at this decision-making moment that induce us to proceed with the surgery: the fallibility of intraoperative freezing, the fact that this patient – the exception of most cases attended in this context – is so physically and nutritionally fit for surgery, the confidence and optimism transmitted in consultation to the patient and family in the face of the precocity of surgical treatment, the experience of previous cases that were “successful”.

For this reason, I share the following studies that aimed to define the real prognosis of this patient.

What do the studies say?

In the first² patients undergoing pancreatectomies associated with hepatic resections at an internationally renowned center were retrospectively analyzed.

The sample size (22 patients) is criticizable and is probably a consequence of high patient selection. This selection is also proven in the sample details: average size of the metastasis (0.6 cm), hepatic resections were mostly nodulectomies. In addition, all cases were similar to ours, an incidental intraoperative finding.

For control, two groups were designated: 1 – conventional resection with the same primary site without association with hepatic metastasis and 2 – palliative surgery performed in the face of hepatic metastasis (bili-digestive + food diversion). The comparison showed interesting but not unexpected results: at a cost of a higher rate of complications, bleeding and length of stay, there was no benefit in the survival of these patients in the long term compared to palliative surgery. It is worth noting that, as in our situation, we are comparing a group selected by optimism, by the expectation of better evolution compared to the usual.

I also highlight this more recent systematic review³ showing a similar survival between patients who underwent combined surgery in the proposed context and patients referred for palliative chemotherapy after metastasis detection in staging (not submitted to surgery). In selected patients, after chemotherapy and systemic control, the survival provided by the same surgery was 3 to 4 times greater.

Conclusion

As seen above, we are not lacking examples that in a few patients the surgery initially thought (resection of hepatic metastasis + duodenopancreatectomy) can bring benefit in survival⁴. However, at the time of surgery this individual has not yet gone through this selection of systemic treatment and, therefore, we do not yet know if he is – or better – will be one of these cases. Therefore, on that day, we proceeded with the bili-digestive diversion – thus solving the biliary obstruction – associated with food diversion due to the food symptoms alleged.

For those who would choose to proceed with the procedure, I invite you to reflect: no matter how optimistic our expectation, our intention and attitude remain subject to data and statistics. Our main function during our patient’s journey is to advise him to take the most advantageous path and not just hope for the best result.

After all, there are less risky surgeries that relieve symptoms and provide a systemic treatment without complications for our patient. In this way, in the light of current knowledge, he will remain with a higher quality of life and for a longer time outside the hospital environment. Remembering that definitive treatment will not cease to be an option if it proves adequate over its evolution.

References

1. Isaji, S. et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology 18, 2–11 (2018).
2. Gleisner, A. L. et al. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer 110, 2484–2492 (2007).
3. Crippa, S. et al. A systematic review of surgical resection of liver-only synchronous metastases from pancreatic cancer in the era of multiagent chemotherapy. Updates Surg. 72, 39–45 (2020).
4. Nagai, M. et al. Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients. J. Hepatobiliary. Pancreat. Sci. 1–11 (2023) doi:10.1002/jhbp.1303.

How to cite this article

Magalhães DP. Periampullary neoplasia with isolated hepatic metastasis: what would you do? Gastropedia, vol. 2 Available at: gastropedia.com.br/cirurgia/neoplasia-periampular-com-metastase-hepatica-isolada-o-que-voce-faria/

Insulinoma is the most frequent functioning pancreatic neuroendocrine tumor (55%), with its peak occurrence in patients in their fifth decade of life (between 40 and 50 years) and a slight predominance among women (1.4:1)¹.

The symptoms associated with the tumor are divided between adrenergic – anxiety, tremors and agitation – and neuroglycopenic such as disorientation, visual alterations and seizures². Due to frequent food intake to avoid severe hypoglycemia during fasting, it is common for patients to present with obesity/overweight at diagnosis.

In 1938, the Whipple triad was described: documented hypoglycemia (<50mg/dL), symptomatic and relieved after caloric intake. Currently, diagnostic confirmation is given with a clinical fasting test of 48 to 72 hours in which laboratory tests are collected periodically. The laboratory profile will show low blood sugar in opposition to high levels of insulin, pro-insulin and C-peptide³. It is essential for diagnosis to ensure that the patient does not use oral antidiabetics such as sulfonylureas or injectable insulin.

The relationship of insulinoma in endocrine syndromes (MEN-1 and tuberous sclerosis) is known and brings propaedeutic particularities due to a higher risk of multiple neuroendocrine tumors or malignant insulinomas⁴.

The recommended treatment is surgical excision of the tumor. Enucleation, as well as segmental pancreatectomies, are recognized treatments since the vast majority of tumors are benign. Thus, lymphadenectomy becomes less relevant than the preservation of pancreatic parenchyma in order to avoid exocrine or endocrine insufficiency¹.

Therefore, this article aims to bring an analysis of the different diagnostic tests used in insulinoma cases and their applications, in addition to a list of specific perioperative care for these patients.

Diagnostic methods by image

Axial methods with contrast are the most used for the anatomical study of the pancreas and its vascular relations. Among them, magnetic resonance, when available, has proven to be more sensitive to locate insulinomas that present as hypervascular nodules in the arterial phase, with hyperintensity in T2 and hypointensity in T1 in relation to the pancreatic parenchyma. Smaller lesions can be located more easily in diffusion phases⁵.

A specific exam for neuroendocrine tumors that uses their somatostatin receptors, the PET Gallium 68 can assist in cases of clinical suspicion without diagnosis by the methods above. It is an appropriate exam for the location of ectopic insulinomas that were not visualized in the upper abdomen⁵.

Invasive diagnostic methods

Echoendoscopy: Exam for evaluation of the pancreatic parenchyma in search of subcentimetric lesions, used by some authors as the first exam to locate the insulinoma. It offers even greater sensitivity in lesions of the head of the pancreas and uncinate process.

In the report of a suspected insulinoma, it is important to include, if possible, the measurement of the tumor, its location and the distance from relevant vascular structures (spleno-mesenteric junction), and the proximity of the main pancreatic duct (to assist the operative decision to enucleate the lesion).¹

Needle puncture is dispensable in the vast majority of cases. The symptomatic patient with sporadic lesion does not need histopathological confirmation for treatment. In endocrine syndromes, both functioning and non-functioning neuroendocrine tumors can express immunohistochemical markers for insulin. Thus, this exam is not suitable to differentiate them. ⁶

In non-peripheral or intrapancreatic lesions of difficult location, the surgeon may request a tattoo with methylene blue to facilitate intraoperative location.

Selective pancreatic arterial catheterization (SACS)

The exam consists of positioning a collector catheter in the right hepatic vein to collect the blood level of insulin after arterial stimuli.

Then, after selective arterial catheterization, calcium gluconate is injected into the peripancreatic arteries with the power to topograph the lesion if insulinemia doubles within 3 minutes after injection.

• Tumor in the body/tail of the pancreas: Positive after injection in the splenic artery
• Tumor in the pancreatic head or uncinate process: Positive after injection in the gastroduodenal or superior mesenteric artery
• Hidden hepatic metastasis: Positive after injection in the proper hepatic artery

The exam is used mainly in cases of endocrine syndromes and multiple neuroendocrine tumors in which it is desired to identify which lesion is metabolically active.¹

Surgical treatment

The definition of surgical route depends on the surgeon’s expertise. It is important to note that for laparoscopic access, especially for nodulectomies and distal pancreatectomies, a detailed planning of the location of the pancreatic section is necessary. Conversion to open surgery is justified in cases of imprecision.⁷

Intraoperative ultrasonography is an ally of the liver and pancreas surgeon and, in this context, certifies the tumor location and proximity to pancreatic ducts in cases where enucleation is considered. Thus, the exam provides greater safety to the procedure, reducing the risk of pancreatic fistula and allowing preservation of pancreatic parenchyma when possible.

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