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

Anorectal manometry is an examination used to evaluate the function of the rectum and sphincter apparatus. Its utility is mainly valued in patients who present functional disorders, such as intestinal constipation and fecal incontinence, assisting in the management of these patients. In this article we will learn about the concepts, the main indications and the technique of execution.

Introduction

The pelvic floor is a peculiar muscular structure, with an important function in maintaining anal continence and influence on defecation, and its dysfunction, whether for functional, anatomical and/or neurological reasons, results in morbidities with significant social, emotional, psychological and economic impact. Urinary incontinence, prolapse of pelvic organs, anal incontinence, evacuatory dysfunction and sexual disorders, among others, are considered abnormalities of the pelvic floor.

The evacuation disorders, whether fecal incontinence (FI) or chronic intestinal constipation (CIC), represent alterations of the pelvic floor quite frequent in the general population more commonly in those with risk factors, that is, elderly, women with obstetric past, comorbidities (such as scleroderma, hypothyroidism, diabetes mellitus), history of pelvic radiotherapy, bedridden patients or with locomotion deficits, history of orificial surgeries, chronic use of analgesics, opioids and psychiatric medications, among others.

Fecal incontinence has a very variable incidence and fundamentally dependent on the age of the study population, so that the incidence oscillates between 1.4 to 18%, with an average of 2 to 8.4%. On the other hand, chronic intestinal constipation (CIC) is one of the most common functional gastrointestinal disorders with high prevalence in the population, affecting 16% of adults and up to 33% of those over 60 years of age, more specifically females with a prevalence of 2 to 3:1 when compared to males.

Anorectal manometry can assist the attending physician, whether he is a gastroenterologist, digestive tract surgeon, coloproctologist or other medical specialty to better understand the disorder being evaluated and assist in its management. We will discuss the indications, concepts and techniques of anorectal manometry below.

Indications

Anorectal manometry (MNAR) can be indicated mainly for cases of:

• fecal incontinence (FI);
• intestinal constipation;
• dysinergia of the pelvic floor;
• prolapse of pelvic organs: rectocele, enterocele, mucosal prolapse, rectal procidence and cystocele;
• chronic pelvic pain: endometriosis, proctalgia fugax;
• pre-operative of orificial surgeries and reconstruction of intestinal transit;
• post-operative of colorectal surgery, notably in patient with the syndrome of anterior resection of the rectum.

Technique for execution

About 2-3 hours before the exam, retrograde intestinal preparation is indicated with a bottle of phosphoenema® or two of Minilax® (evacuatory enemas). No dietary restriction is necessary. At the time of the exam, the patient is positioned in left lateral decubitus with the lower limbs semi-flexed (Simms position) and then anal inspection is performed followed by rectal touch with the aim of:

• assessing whether there is an excess of feces in the rectal ampulla;
• measuring subjectively the tone of the internal and external sphincters of the anus, respectively during rest and anal contraction;
• assessing the relaxation of the puborectal muscle and the force of rectal propulsion;

In addition, the rectal touch has the final purpose of guiding the adequate and careful insertion of the anorectal manometry catheter.

Parameters evaluated

The following data are evaluated during the MNAR:

• Resting pressure: provided fundamentally by the action of the internal anal sphincter muscle (EAI – values in mmHg);
• Functional anal canal length: normally between 2-3 cm in females and a little longer in males;
• Contraction pressure: action performed by the anorectal striated musculature, that is, by the external anal sphincter (EAE) and puborectal muscle (PR – values in mmHg);
• Action of the sphincter musculature during the Valsalva maneuver or evacuatory effort in order to observe adequate relaxation of the same or signs suggestive of paradoxical contraction of the PR muscle, also described as pelvic floor dysinergia;
• Ability to sustain contraction: corresponds to the fatigue index during 30 seconds of the anorectal striated musculature with measurement in percentage and in duration time;
• Rectoanal inhibitory reflex: demonstrates the relaxation of the EAI to the stimulation of the nerve receptors in the anorectal ring from the stepped insufflation of air in the balloon, positioned at the distal end of the manometry catheter (it can be positive, negative or indeterminate);
• Sensitivity and capacity of the rectum: measurement made with the instillation of water inside this same balloon (values measured in ml);
• Sphincter asymmetry index at rest and during contraction: measures the symmetry of the anorectal sphincter complex in its circumference, in percentage.

After obtaining these data, it is recommended to perform the rectal balloon expulsion test, primarily in patients with clinical symptoms of intestinal constipation and those with manometric signs suggestive of paradoxical contraction of the puborectal muscle to MNAR.

For this, about 50 to 60 ml of water is left inside the rectal balloon with the probe positioned just above the anorectal ring and the patient is asked, mainly in the sitting position on a toilet, to eliminate the balloon, simulating an evacuation. The test is considered negative if there is elimination in up to three attempts with a maximum time of 60 seconds each. If the balloon containing water is not eliminated after 3 attempts, the test is positive, and may corroborate with pelvic floor dysinergia.

Conventional x High resolution

The conventional MNAR had, in our environment, its dissemination and execution methodology from 1993. For this, a probe with eight radial holes located at its end is used and through which the sphincter pressures are measured through the resistance offered to the flow of water at 0.3-0.5 ml/minute/channel. For its execution, the probe is inserted up to 6 cm from the anal edge and the catheter is pulled at each centimeter in a stationary manner.

On the other hand, the most recent MNAR devices, known as high resolution, have 24 or 36 channels, distributed radially and staggered from 1 to 6 cm from the end of the catheter. For its execution, the probe is inserted 6 cm from the anal edge, leaving it static with successive measurements of the above mentioned data, following a specific protocol known as the London Protocol, which better standardized the high resolution MNAR in relation to the conventional one.

This new MNAR execution technology has as main advantages:

• graphs with better spatial visualization;
• less discomfort to the patient, notably those with anal pain, such as chronic fissure;
• better technical standardization;
• less need for the participation of the nursing technician who assists the exam;

However, despite these advantages and a greater performance of the technological system in the preparation of reports, any of the available techniques does not replace the importance of the correct execution and interpretation of the data by the doctor who performs the exam.

Conclusion

The anorectal manometry exam, whether conventional or high resolution, is an important propaedeutic resource in the approach of patients with pelvic floor disorders, especially in anal incontinence and refractory intestinal constipation, and can also be used as a method in the pre-operative of colorectal and/or orificial surgeries in specific situations.

Also read: Screening for anal intraepithelial neoplasia and prevention of anal cancer

How to cite this article

Pinto RA, Neto IJFC, Marques CFS. Anorectal Manometry: concepts, indications and technique Gastropedia 2023, vol. 2. Available at: https://gastropedia.com.br/cirurgia/manometria-anorretal-conceitos-indicacoes-e-tecnica

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/

Unfortunately, many patients at the time of diagnosis already have locally advanced gastric tumors, which cannot be removed by surgical procedure, or signs of systemic disease. In Brazil, this number may represent more than 25% of cases. Distal gastric obstruction (gastric outlet obstruction) occurs in about 30% of distal gastric tumors. In these situations, the main non-curative therapeutic modality for the treatment of GC remains the resection of the tumor, but without the need for associated lymphadenectomy.

However, some patients have locally advanced tumors that cannot be resected. The incidence of these varies in the literature from 5 to 30% of GC cases. In these cases, gastrointestinal bypass procedures or the use of endoscopic prostheses may be indicated to improve quality of life, relieve symptoms of gastric obstruction, and thus enable the administration of palliative treatment.

The use of endoscopic prostheses has gained popularity for the palliation of digestive tract obstructions, as it has the advantage of being a less invasive option and without the need for use of the operating room with general anesthesia. However, the multicenter randomized study (Sustent Study) reported worse long-term results with the use of the prosthesis compared to gastrojejunostomy. Factors such as prosthesis migration, tumor growth causing new obstruction, and gastric wall erosion, are long-term complications that impair the observed results. Another aggravating factor refers to the cost and immediate unavailability of prostheses by the public system in our country. Currently, the prosthesis is mainly indicated in patients with low clinical performance by the Eastern Cooperative Oncology Group (ECOG) scale, and with a life expectancy of less than 2 months.

Regarding bypass surgical procedures, the most used is gastrojejunostomy, also called gastroentero anastomosis. Gastrojejunostomy consists of performing anastomosis with a wide extension of the posterior wall of the stomach with the first jejunal loop that reaches the stomach without tension (Figure 1). The anastomosis can be performed manually or mechanically, with the use of surgical staplers.

Despite the technical simplicity of performing gastrojejunostomy, a major inconvenience observed in practice is the difficulty of gastric emptying through the anastomosis after the procedure. Literature data refer that 10 to 26% of patients present this complication, as shown in Figure 1. Such occurrence can lead to an increase in hospitalization time and delay the start of palliative chemotherapy, fundamental to prolong survival.

Another inconvenience of this procedure is the maintenance of the tumor in contact with the food ingested by the patient, since the exposure of the tumor predisposes the occurrence of tumor bleeding. Finally, there is also the risk of obstruction of the gastrojejunostomy by the growth of the tumor that is located near the anastomosis, and can thus invade it. This fear can lead the surgeon to perform the anastomosis in a more proximal portion of the gastric body, which further impairs gastric emptying.

With the aim of overcoming these inconveniences, the performance of a partial partition of the stomach associated with gastrojejunostomy in the proximal gastric chamber has been indicated for non-resectable obstructive distal tumors. The rationale for performing the partition involves creating a gastric chamber of smaller dimensions facilitating emptying by gastrojejunostomy and excluding the tumor in the distal chamber reducing the risk of bleeding and preventing the infiltration of the anastomosis by the tumor.

Technical steps of gastric partition

After identifying the proximal limits of the lesion, a point located 3 to 5 cm proximal to the lesion on the greater curvature is selected to start the partition (Figure 2).

A Faucher tube nº 32 or a large nasogastric tube is passed and maintained along the lesser gastric curvature to maintain communication between the two gastric chambers created by the partition (Figure 3). The partial partition of the stomach is performed using a cutting linear stapler.

Subsequently, the gastrojejunostomy is performed in a position anterior to the colon, isoperistaltic in the posterior wall of the stomach with at least 5 cm of extension, using the first jejunal loop about 30-40 cm from the Treitz angle (Figure 4).

The anastomosis can be performed manually or with the use of a cutting linear stapler. The access route can be conventional or laparoscopic, according to the surgeon’s preference.

It is important to note that in cases of proximal tumors or with involvement of the proximal lesser curvature to the angular incisura the partition should be avoided due to the risk of obstruction of the communication between the gastric chambers.

How to cite this article

Ramos MFKP, Gastric partition for the treatment of non-resectable obstructive distal gastric tumors. Gastropedia 2023 Vol 1. Available at: gastropedia.com.br/sem-categoria/particao-gastrica-para-tratamento-de-tumores-gastricos-distais-obstrutivos-nao-ressecaveis/

Incidence of anal and anal canal cancer

Squamous cell carcinoma of the anus and anal canal has a low incidence in the general population (1-2/100,000 people-year). However, when associated with risk factors such as co-infection with HIV, men who have sex with men (MSM), presence of high-grade lesions or carcinoma in the genitals and immunosuppression, this risk can increase considerably:

Anus and anal canal cancer can be screened with a complete proctological examination, with inspection and rectal touch, followed by anoscopy with biopsy in suspicious lesions (3).

High-grade anal intraepithelial lesions (high-grade AIN), as occurs in the cervix, can be identified through exams such as oncotic cytology or genotyping for high-risk oncogenic HPV obtained through the anal smear (Anal-Pap).

When these results come altered, the patient should be referred for a high-resolution anoscopy examination or anoscopy with image magnification, which resembles a colposcopy examination of the anus and anal canal region. Through this examination, it is possible to identify lesions suspicious for high-grade AIN, which, when identified through a biopsy, should be treated, through chemical cauterization or electrocautery or with infrared laser (4)

ANCHOR trial

• Until recently, there was not a robust degree of evidence to indicate the screening and treatment of high-grade anal intraepithelial lesions as a method of prevention for anal and anal canal cancer (2).
• However, in 2022 the results of the ANCHOR trial, (Anal Cancer HSIL Outcomes Research) (5) a prospective multicenter randomized study that evaluated 4446 people living with HIV who were followed up with cytology exams and high-resolution anoscopy were published in the NEJM.
• When high-grade anal intraepithelial lesions (AIN 2 p16+ or AIN3) were identified, the participants were randomized into two groups: one in which these lesions would be treated and another in which these lesions would be followed up every 6 months.
• The rate of progression to anal cancer was 53% lower in the treated group than in the group only followed up (p= 0.03).

Conclusion

• Anus and anal canal cancer is quite rare and should not be screened in the general population.
• Its incidence increases considerably in certain populations such as: people living with HIV, men who have sex with men, women with a history of cancer or high-grade lesions in the genitals and diseases or treatments that course with immunosuppression, which justifies screening in these groups.
• The identification and treatment of high-grade anal intraepithelial lesions in people living with HIV has proven effective in preventing anal and anal canal cancer.

References

1. Clifford, Gary M., et al. “A meta-analysis of anal cancer incidence by risk group: toward a unified anal cancer risk scale.” International journal of cancer 148.1 (2021): 38-47.
2. Stewart, David B., et al. “The American Society of Colon and Rectal Surgeons clinical practice guidelines for anal squamous cell cancers (revised 2018).” Diseases of the Colon & Rectum 61.7 (2018): 755-774.
3. Hillman, Richard John, et al. “International Anal Neoplasia Society guidelines for the practice of digital anal rectal examination.” Journal of lower genital tract disease 23.2 (2019): 138-146.
4. Hillman, Richard John, et al. “2016 IANS international guidelines for practice standards in the detection of anal cancer precursors.” Journal of lower genital tract disease 20.4 (2016): 283-291
5. Palefsky, Joel M., et al. “Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer.” New England Journal of Medicine 386.24 (2022): 2273-2282.

How to cite this article

Ribeiro VL. Screening of anal intraepithelial neoplasia and prevention of anal cancer. Gastropedia 2023, vol. 1. Available at: https://gastropedia.com.br/sem-categoria/rastreamento-de-neoplasia-intrapeitelial-anal-e-prevencao-de-cancer-de-anus/

Gastric cancer (GC) is the fifth most common cancer in the world. It is estimated that over one million new cases of GC occur annually.

Remnant gastric cancer, or gastric stump cancer, was defined as a tumor that develops in the gastric remnant more than 5 years after previous gastrectomy.

Its reported incidence in the literature varies between 2 to 6% of all patients with GC. It can occur in the remaining stomach either after previous resection for benign or malignant lesion. However, these tumors seem to have different behaviors and etiologies. Due to its rarity and diversity, the characteristics of remnant gastric cancer, prognostic factors and survival, remain uncertain.

Context

Gastric resection for benign disease was commonly performed until the late 1980s and created a large cohort of patients with gastric remnant at risk of developing tumors. The introduction of H2 receptor antagonists and proton pump inhibitors in the 1980s drastically reduced the number of gastric resections due to peptic disease. However, as the disease development period is long, the occurrence of remnant tumors is still part of the current reality due to the past use of gastric resection for peptic ulcer treatment. On the other hand, the improvement in the treatment results of GC has increased the survival of patients undergoing gastric resection, also increasing the population susceptible to the development of new neoplasia in the gastric remnant. Therefore, a change in this benign/malignant ratio related to previous indications of gastric resection is expected in the future.

Long-term endoscopic surveillance is recommended for early detection of lesions in patients who have undergone previous distal gastrectomy. Even with these recommendations, there is a common sense that remnant tumors usually present at a more advanced clinical stage and with a worse prognosis. The longer period of carcinogenic effect after resection, as well as the patients’ perception that they had benign disease, makes them less likely to continue monitoring the gastric remnant for early detection.

Carcinogenesis

The carcinogenesis of GC is a multi-step process that involves the interaction of several genetic, epigenetic and environmental factors. The risk factors commonly associated with the development of GC include chronic infection by H. pylori, low intake of fruits and vegetables, high salt intake, smoking and alcohol consumption.

• After previous gastric resection for malignant disease, this cumulative carcinogenic effect on the gastric mucosa is maintained. For this reason, patients with previous gastrectomy for cancer develop tumors in the remnant in a significantly shorter period than patients with previous benign lesions.
• After gastric resection for benign disease, environmental changes begin to induce chronic damage in a previously normal gastric mucosa of the remnant, initiating a de novo carcinogenic pathway with a longer period for the development of the tumor in the remnant. The reported time required to transform this remaining inflamed mucosa into a neoplastic epithelium is over 20 years.

Another factor contributing to remnant carcinogenesis is the vagotomy performed in the previous procedure, which causes denervation of the gastric mucosa leading to hypochlorhydria. On the other hand, the frequency of H. pylori infection decreases in the remnant mucosa, leading to a protective effect.

Whether these changes actually lead to a higher incidence of GC in the remnant mucosa, or just reflect the normal risk of GC in the general population, is still under discussion. This discrepancy in reports may result from the difference in GC incidence rates in the general population of different countries. Regions with low incidence of GC tend to have a higher proportion of remnant tumors compared to regions with high incidence of GC.

Type of reconstruction and risk of carcinogenesis

The relationship between type of reconstruction and risk of RGC remains uncertain.

• The Billroth I (BI) reconstruction maintains the flow of ingested food from the remaining stomach to the duodenum, but due to pyloric resection the duodeno-gastric bile reflux is increased.
• The Billroth II (BII) reconstruction allows the influx of bile from the afferent jejunal branch to the remaining stomach. This constant flow makes alkaline gastritis more common and severe after BII. This leads to inflammation and regeneration of the mucosa, which may be associated with a higher risk of remnant tumors. Despite some reports in the literature, this association is not yet a consensus.
• On the other hand, the Roux-en-Y reconstruction avoids bile reflux to the remaining stomach, but is rarely performed for benign resections.

Access the Gastropedia surgical video library to see the types of reconstruction

Characteristics and staging

In most cases the remnant tumor is located at the previous anastomosis (Figure 1). Patients usually have a more advanced age which reflects the long period of inflammatory gastritis necessary to induce carcinogenesis in the gastric mucosa. Although the TNM system is applied to all gastric tumors, the staging system for remnant tumors has not been established. For adequate final pathological staging, it is recommended to recover at least 15 lymph nodes to avoid stage migration due to underestimation.

Surgical treatment

Complete total gastrectomy with radical lymphadenectomy is the cornerstone of the treatment of remnant tumors. Adhesion to adjacent organs and displacement of anatomical structures are common difficulties during the procedure, making it longer and more prone to combine repair or resection of other organs. Normally, the surgical procedure is performed by conventional open approach, but recently minimally invasive laparoscopic and robotic approaches are increasing (access gastropedia surgical video library).

It has been suggested that the characteristics of lymph node metastasis in remnant tumors are different due to the interruption of the lymphatic pathway in the first procedure. The type of reconstruction and the previous indication of the first gastrectomy do not seem to influence the incidence of lymph node metastasis, but rather its location. This can lead to a greater involvement of the splenic artery, splenic hilum, lower mediastinum and jejunal mesentery. However, the standard extent of lymphadenectomy is not yet defined. Similar to GC, splenic hilum lymphadenectomy is indicated only if the tumor invades the greater curvature.

The presence of lymph node metastasis in the jejunal mesentery has a poor prognosis. It is known that extended lymphadenectomy in the area can severely affect postoperative quality of life. Therefore, the extent of lymphadenectomy in the mesentery should be determined based on the extent of lymph node involvement, considering a balance between risk and benefit.

References

1. Ramos MFKP, Pereira MA, Dias AR, Dantas ACB, Szor DJ, Ribeiro U Jr, Zilberstein B, Cecconello I. Remnant gastric cancer: An ordinary primary adenocarcinoma or a tumor with its own pattern? World J Gastrointest Surg. 2021 Apr 27;13(4):366-378. doi: 10.4240/wjgs.v13.i4.366.
2. Ramos MFKP, Pereira MCM, Oliveira YS, Pereira MA, Barchi LC, Dias AR, Zilberstein B, Ribeiro Junior U, Cecconello I. Surgical results of remnant gastric cancer treatment. Rev Col Bras Cir. 2020 Nov 30;47:e20202703. doi: 10.1590/0100-6991e-20202703.

How to cite this article

Ramos MFKP, Remnant gastric tumors. Gastropedia 2023 Vol 1. Available at: https://gastropedia.com.br/cirurgia/tumores-do-remanescente-gastrico/

Colorectal tumor has a major impact on global health and, according to INCA data, it ranked second in incidence in both sexes in our country in 2020. Complications resulting from colorectal tumor rank second in cancer mortality worldwide⁶. At diagnosis, about 20% of these patients already present with hepatic metastases.⁴

With the advancement of oncological treatments and better understanding of the disease, a greater number of treatments are available for these patients, including: surgery, chemotherapy, immunotherapy, radiotherapy and radio interventional treatments. Although patients with hepatic metastases are considered stage IV, they are still cases eligible for curative treatment.

Faced with several therapeutic options and with the increase in survival, complex cases have become more common, which requires us to have a deep knowledge of the different therapeutic options. Recognizing this difficulty, oncology hospitals organize specialized multidisciplinary committees that discuss the particularities of each patient with the intention of obtaining the best results. It is in these meetings that we outline the therapeutic planning and the best time for reassessment and action of each team.

Figure 1 – Performing radiofrequency ablation guided by simultaneous ultrasound to hepatic surgery for multimodal treatment of colorectal tumor metastases

Given the epidemiological importance of the diagnosis that frequently presents in clinics and in emergency situations – where we do not always have access to multidisciplinary opinion in a timely manner – this article aims to show the benefits and disadvantages of each available strategy to offer to the patient with colorectal tumor and synchronous hepatic metastasis.

The studies on hepatic metastases from colorectal tumors are numerous and there is often a regional difference in terminology on the subject. This article applies to patients with hepatic metastasis already existing or identified at the staging of the primary tumor.

Figure 2 – Magnetic resonance imaging showing synchronous hepatic metastasis (yellow arrow) to a right colon adenocarcinoma (blue arrow).

Patients with asymptomatic colorectal tumor and resectable hepatic metastases

Most clinical and surgical specialists recommend preoperative chemotherapy – for about 02 months – followed by surgical treatment if good response¹. Surgery can involve resection of the primary in association with hepatectomy as long as the surgeons are qualified for this and that both are medium-sized surgeries. Casuistics have already shown a higher rate of perioperative complications and mortality in cases of combined surgery involving major hepatectomies².

It is also possible to perform resection of the primary followed by chemotherapy in the interval between surgeries; with hepatic resection scheduled for after about 2 to 3 months. During the first surgery, the evaluation of hepatic disease and histopathological confirmation of metastases can be performed, if necessary.

Figure 3 – Intraoperative laparoscopic ultrasound. Valid resource in the identification and intraoperative planning of hepatic resections.

There was no difference in survival over a 5-year period when analyzing the options; however, we highlight that these are data from retrospective studies in which there may have been a bias in the indication of primary surgery for patients with better performance and less volume of oncological disease. Therefore, the consensus among specialized centers is to indicate chemotherapy as the first treatment¹.

Patients with asymptomatic colorectal tumor and unresectable hepatic metastases

It is common for cases of colorectal tumors in patients with good performance to undergo surgery as the first treatment regardless of the presence of hepatic metastases. However, it is observed that the limiting factor for the possible curative treatment of these patients is the systemic disease manifested in the liver³.

Therefore, it is recommended to perform chemotherapy as the first treatment, with reassessment of the response after 2 months and programming of the hepatectomy, if feasible. In 1996, Bismuth already demonstrated a conversion rate of unresectable hepatic metastases to resectable in 16% with impact on prognosis (survival rate of 40% in 05 years). More recent results show conversion rates of up to 30%².

The literature shows that the outcome of patients who, in the end, underwent both surgeries is similar whether for those who started treatment with chemotherapy, or for those who started with colectomy. This data gives us confidence to keep the primary lesion under treatment with chemotherapy and, at the same time, pursue the possibility of surgical treatment – simultaneous or in stages – of all lesions¹.

Figure 4 – In addition to the reduction in dimensions after chemotherapy, there is a change in signal (scar aspect) and better delimitation of the lesion limits; factors that favor the surgical procedure

Patients with symptomatic colorectal tumor and hepatic metastases

It is estimated that about 20% of colorectal tumor cases have their diagnosis and treatment started in an emergency.⁵ In this context, it is important to highlight the impact of complete staging in the face of clinical suspicion of colorectal tumor. If it is safe for the patient, performing contrast-enhanced abdominal and thoracic tomography and carcinoembryonic antigen dosage before a possible resection of the primary tumor will be fundamental during oncological therapeutic planning.

The main complications that lead the patient with colorectal tumor to emergency are intestinal obstruction, perforation or bleeding. Even in the face of a metastatic patient, we need to consider the patient as potentially treatable and, therefore, offer a surgery with oncological principles or a derivation that allows to delay the treatment with curative intentions¹.

There is consensus among specialists that during the symptomatic context with obstruction or perforation there is no room to involve any approach to hepatic metastases.¹

Bleeding in colorectal tumor rarely requires emergency surgery. In general, bleeding can be solved with transfusion therapy followed by early chemotherapy with good response. Once the bleeding is resolved, these patients can be managed according to the strategies above.

The different surgical treatment strategies

• Traditional

The strategy of the traditional approach consists in performing colectomy as the first treatment, followed by chemotherapy and hepatic surgery in 2-3 months². On the one hand, this path is safer with the reduction of the risk of complications of the primary tumor. On the other hand, it is important to pay attention to the risk of complication during the resection of the primary that can, and often exceeds, the risk of intercurrences if we keep it under chemotherapy treatment.

A perioperative complication will delay the treatment of the patient’s systemic metastases, which is what will actually define his prognosis. Therefore, in cases of unresectable hepatic lesion, strongly consider starting with chemotherapy that may provide the opportunity for a complete treatment¹.

• Simultaneous surgery

There are clear benefits to offering a combined treatment during just one surgical act. Being subjected to a single anesthetic act and a shorter hospital stay is an inviting possibility for the surgeon and the patient. However, prolonged operative time and a higher risk of perioperative complications are disadvantages already demonstrated and that, when they occur, nullify these benefits.

Currently, combined resection is reserved for cases of simple colectomy and minor hepatectomies that can be performed at the same surgical time by conventional or videolaparoscopic approach. The right subcostal incision of the hepatectomy allows the performance of oncological right colectomy, being this the most frequent indication. For cases of left colectomy, the laparoscopic approach with resection of smaller and peripheral nodules is the most used.

Increased mortality and morbidity have already been demonstrated in the association of large oncological colectomies (mesorectum approach or multivisceral) and/or major hepatectomies (resection of more than 3 segments); suggesting the limits of this type of strategy.⁵

Figure 5 – The simultaneous approach of primary tumor (right colon) and hepatic metastasis.

• Liver-first or Reverse Approach

Approach is increasingly used and reserved for cases where the complete oncological treatment will depend on a major hepatectomy and/or response of the lesions to chemotherapy.

Very applied in cases of medium/low rectal tumors where neoadjuvant chemotherapy and radiotherapy will be performed. In this interval, it is possible to start the treatment of hepatic disease over the time of response of the primary to chemoradiotherapy¹.

The disadvantage of this strategy is the attention and monitoring of the symptoms of the primary tumor or its complications, such as intestinal obstruction and perforation. Studies show that the incidence of these local complications in asymptomatic patients during chemotherapy is low, but not null.⁷

References

1. Adam, R. et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus. 41, 729–741 (2022).
2. Lillemoe, H. A. & Vauthey, J. Surgical approach to synchronous colorectal liver metastases: staged, combined, or reverse strategy. 9, 25–34 (2020).
3. Siriwardena, A. K., Mason, J. M., Mullamitha, S. & Hancock, H. C. Management of colorectal cancer presenting with synchronous liver metastases. Nat. Publ. Gr. 11, 446–459 (2014).Borner MM. Neoadjuvant chemotherapy for unresectable liver metastases of colorectal cancer–too good to be true?. Ann Oncol. 10(6):623-626. (1999)
4. Reddy SK, Pawlik TM, Zorzi D, et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: A multi-institutional analysis. Ann Surg Oncol. 14:3481-91 (2007)
5. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 71(3):209-249. (2021)
6. Tebbutt NC, Norman AR, Cunningham D, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 52(4):568-573 (2003)

How to cite this article

Magalhães DP. Synchronous colorectal hepatic metastasis – How to program the treatment

Obesity is a public health problem with increasing incidence. In this article we will discuss its concept, etiology, classification and consequences.

1. Concept and epidemiology
2. Consequences of obesity
   • Metabolic syndrome
3. Classification
4. Etiology

1. Concept and epidemiology

Obesity can be defined by the accumulation of localized or generalized fatty tissue, caused by nutritional imbalance, associated or not with genetic or endocrine-metabolic disorder.

Obesity is a chronic disease whose prevalence is increasing in adults, children and adolescents and is currently considered a global epidemic. Once considered a problem of developed countries, obesity is now becoming a major health problem also in developing countries.

Obesity in adults is related to reduced life expectancy

The sedentary lifestyle associated with diets high in calories including not only carbohydrates, but also saturated fats, sugar and salt, has contributed to the increase in obesity, especially after the 80s.

• According to the WHO, in 2015 there were 600 million adults with obesity.

• In the USA, 9.2% of the population are morbidly obese (class III), (BMI > 40 kg/m2).

• In Brazil obesity affected 12.2% of the adult population in 2002-2003 and rose to 26.8% in 2020, according to IBGE

• 29.5% of women are obese — practically one in three — compared to 21.8 of men.

• Overweight, on the other hand, was found in 62.6% of women and 57.5% of men.

2. Consequences of obesity

Severe obesity (type III) is associated with a significant increase in morbidity and mortality. On the other hand, weight loss is associated with a reduction in morbidity associated with obesity.

These are pathological states aggravated by the presence of obesity and that are improved by its control, among the most frequent:

• HAS
• DM II
• Peripheral vascular insufficiency
• Cholelithiasis
• Arthropathies
• Coronary insufficiency
• Dyslipidemias
• Hepatic steatosis
• Sleep apnea
• Urinary incontinence
• GERD
• Physical limitation conditions and others.

The mortality of severe obese is 250% higher than non-severe.

Mortality from cancer, especially endometrial, is also increased for obese.

Metabolic syndrome

Metabolic Syndrome corresponds to a set of diseases whose basis is insulin resistance. When present, Metabolic Syndrome is related to a general mortality twice as high as in the normal population and cardiovascular mortality three times higher.

According to Brazilian Consensus, Metabolic Syndrome occurs when three of the five criteria below are present:

• Central obesity – waist circumference greater than 88 cm in women and 102 cm in men;
• Arterial Hypertension – systolic blood pressure ? 130 and/or diastolic blood pressure ? 85 mmHg;
• Altered glycemia (glycemia ? 110 mg/dl) or diagnosis of Diabetes;
• Triglycerides ? 150 mg/dl;
• HDL cholesterol ? 40 mg/dl in men and ? 50 mg/dl in women

* If BMI >30, the abdominal circumference does not need to be determined as central obesity is presumed.

3. Classification

The main index to measure and classify the degree of obesity is the BMI, due to its ease of application and correlation with morbidity and mortality risks.

Another useful measure, especially in Asians and patients with BMI between 25-35 is the measurement of abdominal circumference, since central obesity (associated with higher cardiometabolic risks) may not be captured in these patients.

• AC > 102 cm male sex
• AC > 88 cm female sex

Note: Asian population admits > 90 (male) and >80 (female)

4. Etiology

There are multiple factors that can contribute to the development of obesity

• Genetics: child with an obese parent has a 3-4 x higher risk of developing obesity. Two obese parents, the risk is 10 x higher
• Age: tendency to weight gain
• Habits and lifestyle: consumption of caloric, fatty foods, salt, sugar, sedentary lifestyle
• Medications: some antidepressants, antipsychotics, anticonvulsants, hypoglycemic agents (insulin and sulfonylureas), contraceptive hormones
• Comorbidities: hypothyroidism, cushing’s syndrome
• Intestinal microbiota: increasing evidence of the role of the microbiota

How to cite this article

Martins BC. Obesity: concept, consequences and classification. Gastropedia, vol I, 2023. Available at: gastropedia.com.br/cirurgia/obesidade/obesidade-conceito-consequencia-classificacao

Risk factors commonly associated with the development of gastric cancer (GC) include chronic infection with Helicobacter pylori (H. pylori), low intake of fruits and vegetables, high salt consumption, smoking, and alcohol consumption.

Another known but rarely mentioned risk factor is the presence of Primary Immunodeficiencies (PID), which not only increase the risk of developing GC but also cause its manifestation at earlier ages than in the general population.

PIDs are a set of diseases that encompass more than 300 innate immunity defects, most of which are of unknown cause. PID carriers have an increased risk of recurrent and chronic infections, autoimmune diseases, and neoplasms throughout life.

Following infections, the occurrence of neoplasms is the second most common cause of death in this population. It is estimated that 4 to 25% of PID carriers will develop some neoplasm. Specifically, the risk of developing GC is around 3 to 4 times higher in this population.

Regarding patients with PID, the presence of gastrointestinal disorders is quite frequent, occurring in 5% to 50% of cases. This occurs, in part, because the intestine is the largest lymphoid organ in the human body, containing most of the lymphocytes and producing large amounts of Immunoglobulins. Gastrointestinal manifestations can be related to infection, inflammation, autoimmune diseases, and neoplasms.

Common Variable Immunodeficiency (CVID)

Common Variable Immunodeficiency (CVID) is the most common form of PID, and its prevalence is estimated at 1 in every 25,000 to 50,000 people.

Its pathogenesis has not yet been fully clarified, however mutations of various genes related to the development of B cells into immunoglobulin-producing plasma cells and memory B cells have been described.

Affected individuals commonly present with recurrent bacterial infections of the upper and lower respiratory tract, autoimmune diseases, granulomatous infiltrative disease, and neoplasms. The most common tumors are lymphoma, gastric cancer, and breast cancer.

The diagnosis is based on a significant reduction in serum levels of IgG, IgA and/or IgM, in addition to reduced antibody production after the application of vaccines. Most patients are diagnosed between the ages of 20 and 40, and treatment consists of monthly administration of immunoglobulin.

CVID and Gastric Cancer

The increased risk of GC in patients with CVID varies according to the incidence rate of GC in patients without CVID in the country evaluated. In this sense, a Scandinavian study estimated a 10-fold increased risk, while an Australian study showed a 7.23-fold increased risk.

Although there is no conclusive evidence, the most accepted mechanism for the increased risk of GC in the presence of CVID is due to the reduction in the production of gastric IgA and hydrochloric acid – factors that promote chronic gastritis and facilitate colonization by H. pylori, triggering the carcinogenesis process. This mechanism is supported by the finding that patients with pernicious anemia, who also have achlorhydria and chronic gastritis, have a three times higher risk of developing GC. The decrease in local immune response is also a factor that may play a role in neoplastic development, due to the lower presence of B cells in the gastric mucosa of patients with CVID.

The age of cancer diagnosis in patients with CVID usually occurs at an earlier age, on average 15 years earlier than in the general population.

In relation to the histological diagnosis of the tumor, the Intestinal type of Lauren is usually the most frequent, presenting moderate or poorly differentiated degree. In addition, atrophic pangastritis with little presence of plasma cells, nodular lymphoid aggregates, and apoptotic activity are usually present due to the associated autoimmune gastritis.

Given the evidence of a higher risk of developing GC, it is important that patients with CVID are included in screening programs. Dutch data showed that there is a high incidence of pre-malignant histological and/or endoscopic lesions in patients with CVID, such as atrophic gastritis, intestinal metaplasia, and dysplasia, even in those who are asymptomatic. Up to 88% of CVID patients with no previous gastrointestinal history may present pre-malignant lesions on endoscopy. The rates of progression of these lesions to GC vary from 0–1.8% per year in atrophic gastritis; from 0–10% per year for intestinal metaplasia; and from 0–73% per year when there is already presence of dysplasia.

Intervals between follow-up exams normally employed may not be appropriate for patients with CVID, as the development of GC may occur more quickly. Indeed, there is no standardized screening protocol, and its use should take into account the regional incidence of GC. Patients with CVID can develop high-grade cancer 12 to 14 months after an endoscopy without signs of dysplasia. This justifies the proposal to at least perform EGD in all patients with CVID at the time of diagnosis; repeat it every 24 months in patients with normal histology; every 12 months in patients with atrophic gastritis or intestinal metaplasia; and every 6 months in patients with dysplasia. Routine eradication of H. pylori is also recommended.

Treatment

There are no specific protocols for the treatment of cancer in patients with CVID. Once the diagnosis of GC is made, these patients should undergo standard treatment – the same offered to the immunocompetent population.

Preoperative nutritional support and administration of Immunoglobulin are recommended measures. Patients with CVID can receive the same chemotherapy protocols used in immunocompetent patients. However, short-duration protocols are preferable to long-duration regimes, with special attention to infection control. When possible, the chemotherapy regimen should be adapted according to individual risk factors and tolerance.

Reference

Krein P, Yogolare GG, Pereira MA, Grecco O, Barros MAMT, Dias AR, Marinho AKBB, Zilberstein B, Kokron CM, Ribeiro-Júnior U, Kalil J, Nahas SC, Ramos MFKP. Common variable immunodeficiency: an important but little-known risk factor for gastric cancer. Rev Col Bras Cir. 2021 Dec 15;48:e20213133. English, Portuguese. doi: 10.1590/0100-6991e-20213133. PMID: 34932733.

How to cite this article

Ramos MFKP. Common Variable Immunodeficiency and Gastric Cancer. Gastropedia 2023 vol. 1. Available at: https://gastropedia.com.br/gastroenterology/strongcommon-variable-immunodeficiency-and-gastric-cancer/