clinical study small intestinal tumours · 2019. 7. 31. · to access for endoscopic investigation...

Hindawi Publishing CorporationGastroenterology Research and PracticeVolume 2013, Article ID 702536, 7 pageshttp://dx.doi.org/10.1155/2013/702536

Clinical StudySmall Intestinal Tumours

Marcela KopáIová, Stanislav Rejchrt, Jan Bureš, and Ilja Tachecí

2nd Department of Medicine, Charles University in Praha, Faculty of Medicine at Hradec Kralove, University Teaching Hospital,Sokolska 581, 500 05 Hradec Kralove, Czech Republic

Correspondence should be addressed to Marcela Kopacova; [email protected]

Received 17 February 2013; Accepted 21 October 2013

Academic Editor: Antonin Vavrecka

Copyright © 2013 Marcela Kopacova et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Objective. Balloon enteroscopy (BE) and capsule enteroscopy (CE) are enteroscopy methods that allow examination and treatmentof the small bowel. Before the CE and BE era, the small intestine was difficult to access for investigation. Small intestinal tumoursare infrequent conditions, but about half of them are malignant. Materials and Methods. A total of 303 BEs were performed in179 patients. Oral insertion was performed in 240 and anal in 63 BEs. Indications for the procedure in our patients with smallbowel tumours were anaemia and/or bleeding, obstruction, suspicion of carcinoid tumour, or suspicion of Peutz-Jeghers syndrome.Results. In 50 of our 179 patients (28%), we diagnosed some small intestinal tumours: hamartomas in Peutz-Jeghers syndrome in16 patients, adenocarcinoma in 7, lymphoma in 6, carcinoid tumour in 4, melanoma and stromal tumour in 3, adenoma, lipoma,and inflammatory polyps in 2, and granular cell tumour, cavernous lymphangioma, fibrolipoma, Cronkhite-Canada polyps, andmetastatic involvement in individual cases.Conclusion. BE facilitates exploration and treatment of the small intestine.Theprocedureis generally safe and useful. BE and CE are essential modalities for the management of small intestinal diseases.

1. Introduction

The small intestine is the longest part of the digestive tractaccounting for 75% of its total length and 90% of the wholemucosal surface of alimentary tract. It is not a common sitefor the development of neoplasms, accounting for only 3–6% of all gastrointestinal neoplasms and 1–3% of all primarygastrointestinal malignancies [1–3].

Multiple factors are considered to influence the relativeinfrequency of tumourigenesis in the small bowel: the mostimportant are rapid small bowel transit time allowing onlyshort contact of possible carcinogens from food with theintestinal mucosa; a high concentration of the enzymes andintestinal juices decreasing the concentration of irritatingagents (benzpyrene, a known carcinogen present in food, isconverted into less toxic metabolites by benzpyrene hydroxy-lase, which is present in higher concentrations in the smallintestine compared to the stomach and colon); the highconcentration of gastrointestinal lymphoid tissue and highlevel of immunoglobulins (IgA) exert an effective immunesurveillance; a decrease in mechanical and/or chemicalinflammation of the mucosa because of liquidity and alkaline

pH of the small bowel contents; low bacterial load (especiallyanaerobic bacteria) in the small intestine processing theintestinal content produces a low amount of carcinogens; andrapid turnover of intestinal mucosa (epithelial cells) shoulddecrease the potential growth and development of neoplasticcells [2–5].

The diagnosis of small intestinal tumours is difficult dueto the rarity of these lesions and the nonspecific and vari-able nature of the presented symptoms. The most commonsymptom isGI bleeding,more often obscure. Apart from this,patients may be presented with nonspecific complaints suchas abdominal pain, anaemia, nausea and vomiting, weightloss, malabsorption, diarrhoea, intestinal obstruction, andperforation. However, many patients are asymptomatic untilthe late stages of disease [5–8].

Small intestinal tumours are also difficult to identify bymeans of diagnostic imaging. Until recently, barium entero-clysis has been used as the best radiological possibility fordetection of small bowel malignancies. Not only is the inves-tigation time consuming and poorly tolerated by patientsbut it is also limited in its ability to accurately representthe mural and extramural portion of tumour and contribute

2 Gastroenterology Research and Practice

Figure 1: Jejunal lipoma.

to a high miss rate for small and/or flat lesions. Contem-porary modern alternatives for investigation of small boweltumours are multidetector CT andMRI techniques [5]. Withthe development of multislice spiral computed tomographyand magnetic resonance imaging, computed tomographyenteroclysis and magnetic resonance enteroclysis are widelyused in the examination of the small bowel and diagnosisof small bowel tumours. Both, computed tomography andmagnetic resonance enteroclysis, with three-dimensionalimaging capabilities and excellent soft-tissue contrast cananalyze the abnormalities of peripheral intestinal structureas well as the tunica mucosa. These two methods are evenable to clearly reveal the localization, appearance, degree ofmesenteric infiltration, and remote tumourmetastasis, whichincreases our cognition of the imaging diagnosis for intestinaltumours [1, 5].

Endoscopy is the best method for investigation of the gas-trointestinal tract. It has the advantage of direct visualisationof the mucosa, histology, and even therapeutic possibilities.Upper GI endoscopy performed to the ligament of Treitzis optimal for identifying duodenal tumours; colonoscopycould examine the area of the terminal ileum. However,lesions located between these points were a diagnosticchallenge. Push enteroscopy is an effective diagnostic andtherapeutic procedure, but only for examination of thedistal duodenum and proximal jejunum to approximately50–70 cm past the ligament of Treitz. Sonde enteroscopywas a demanding method, both for the patient and forthe physician and has been completely abandoned. Intra-operative enteroscopy is the complete investigation of thesmall bowel with possibilities for therapy at the same time,but it is invasive and, nowadays, is reserved for multi-ple transmural small lesions of small intestine alone (bluerubber bleb nevus syndrome, multiple carcinoids, etc.)[9, 10].

The development and the introduction in the clini-cal practice of the capsule enteroscopy (CE) and balloonenteroscopy (BE) were a great boom in investigation of thesmall bowel. Bothmethods allowed for complete enteroscopy,in the case of BE with sampling biopsies and therapeuticpotential.

Figure 2: Jejunal hamartoma.

2. Materials and Methods

A total of 303 double balloon enteroscopies (DBE) wereperformed in 179 patients (87 men, 92 women, mean age 48years, range 12–86) using Fujinon EN 450T5 and EN 450P5enteroscopes. Oral insertion was performed in 240 pro-cedures and an anal approach was taken in 63 DBEs. Mostof our patients with the anal approach primarily underwentthe oral procedure. Indications for the procedure in all ofour patients with small bowel tumour were anaemia and/orbleeding, obstruction, suspicion of carcinoid tumour, orsuspicion of Peutz-Jeghers syndrome.

3. Results and Discussion

We found some small bowel tumours (both, benign or malig-nant) in 74 of our 303 DBEs in 50 patients; 17 men, 33 wom-en, mean age 41 years. Capsule enteroscopy preceded DBEin 21 cases and suspicion of tumour was expressed in 20cases (one tumour was missed by capsule enteroscopy). Finaldiagnosis was specified using DBE in all cases. Twenty-oneof our 50 patients (42%) had malignant tumours: 7 wereadenocarcinomas, 6 lymphomas, 4 carcinoids, 3 melanomas,and multiple metastatic involvement of the small bowelwith renal carcinoma was found once. Another 29 hadbenign tumours: 16 patients with Peutz-Jeghers syndromeand multiple hamartomas, 3 patients with GISTs, 2 inflam-matory polyps in NSAIDs patients, 2 adenomas, 2 lipomas,1 cavernous lymphangioma, 1 fibrolipoma, 1 granular celltumour, and 1 time polyps in Cronkhite-Canada syndromeFigures 1–9.

We performed 40 DBEs in our 16 patients with Peutz-Jeghers syndrome; 34 with oral and 6 with anal approach. Atotal number of 502 polyps were removed. One to 48 polypswere removed per session (mean 13, median 15). The largesthamartoma measured 6 cm in diameter on CT scan.

Of our six patients with lymphoma, one suffered from T-cell lymphoma and celiac disease, onewithMALT-lymphomaand Crohn’s disease, one with T-cell rich B-cell lymphoma,and the last three with large B-cell lymphoma. The patientwith T-cell lymphoma died within one year of diagnosis.

Until recently, diagnosis and management of small-bowel tumours were delayed by the difficulty of access to

Gastroenterology Research and Practice 3

Figure 3: Jejunal hamartoma; the size of the polyp is nicely seen inDBE fluoroscopy.

Figure 4: Jejunal hamartoma, resected specimen.

the small bowel and the poor diagnostic capabilities ofthe available diagnostic techniques. Early use of CE canshorten the diagnostic work-up and influence the subsequentmanagement of these patients [7]. CE appears to be an idealtool to recognise the presence of neoplastic lesions alongthis organ, since it is noninvasive and enables the entiresmall bowel to be visualised. High-quality images of thesmall-bowel mucosa may be captured and small and flatlesions recognised without exposure to radiation [3]. Recentstudies on a large population of patients undergoing CE havereported small-bowel tumour frequency only slightly abovethat reported in previous surgical series (range 1.6%–2.4%)and have also confirmed that the main clinical indicationfor CE in patients with small-bowel tumours is obscuregastrointestinal bleeding. The majority of tumours identifiedby CE are malignant; many were unsuspected and notfound by other methods. However, it remains difficult toidentify pathology and tumour type based on the lesion’sendoscopic appearance. Despite its limitations, CE providescrucial information leading, in most cases, to changes insubsequent patient management [3].

Before the CE and BE era, the small intestine was difficultto access for endoscopic investigation and small intestinaltumours were often diagnosed as late as during surgery. Adelay in diagnosis is common, which may result in the dis-covery of disease at a late stage. An unfortunate consequenceof late diagnosis is a poor outcome of the treatment in theevent of malignancies. A variety of tumours, approximately

Figure 5: Granular cell tumour with ulcers in the ileum.

Figure 6: Cavernous lymphangioma of the jejunum.

40 different histologic types of both benign and malignantsmall intestinal tumours, may arise within the small intestine[6, 11, 12]. Benign lesions that may arise in the small bowelmostly include adenomas, hamartomas, leiomyomas, fibro-mas, and lipomas. Malignant tumours of the small intestineare very rare compared to other gastrointestinal organs butare among those with the poorest prognosis compared withother gastrointestinal malignancies [5]. It is important, thatapproximately half of small intestinal tumours are malignant(42% in our setting).Themost common are adenocarcinomasfollowing by lymphomas, carcinoids, and gastrointestinalstromal tumours (GISTs) Figures 10–12.Thefive-year survivalrates range from 0–28% for adenocarcinomas, 14–30% forlymphomas, 50% for GISTs, and 60% for carcinoid tumours[5]. A small part of small intestinal malignancies comprisesecondary malignancies, usually metastases of the lung,breast and prostate cancer, and malignant melanoma.

According to epidemiologic studies, the most commonmalignant tumours were carcinoid and adenocarcinoma,followed in order by gastrointestinal stromal tumour andmalignant lymphoma. The incidence of small intestinal ma-lignancies is increasing [13].

According to data from the USA, the distribution of his-tologic types of small-bowel malignant tumours is changing,largely because of the increasing incidence of carcinoids.In 1987, the most common histologic types of malignanttumours of the small intestine in population-based registrydata from the Surveillance, Epidemiology and End Results


(a)

(b) (c)

Figure 7: Fibrolipoma of the distals duodenum extends beyond oral jejunum ((a) stalk, (b) body, and (c) head of the polyp).

Figure 8: The fibrolipoma after endoscopic polypectomy.

(SEER) programof theNational Cancer Institute were adeno-carcinoma 45%, carcinoid 29%, lymphoma 16%, and sarcoma10% [14]. Bilimoria et al. published in 2009 that carcinoidtumours surpassed adenocarcinomas as the most commonsmall-bowel tumour (data from the National Cancer DataBase-NCDB) [15]. Between 1985 and 2005, the proportionof patients with carcinoids increased from 28 to 44 percent,while the proportion of adenocarcinoma decreased from42 to 33 percent. The proportion of patients with stromaltumours and lymphomas remained essentially stable (17 and 8percent, resp.) [15]. According to a large European multicen-tre study with capsule enteroscopy fromRondonotti et al., themain primary small-bowel tumour type was gastrointestinalstromal tumour (GIST) (32%) followed by adenocarcinoma(20%) and carcinoid (15%); 66% of secondary small-boweltumours were melanomas [7].

Figure 9: Flat adenoma of the jejunum.

Different risk factors are considered for development ofsmall intestine neoplasms.

Certain hereditary syndromes are associated with anincreased incidence of particular histologic types of smallintestinal tumours. These include the Peutz-Jeghers syn-drome (hamartomatous polyps occurring primarily in thejejunum and ileum), familial adenomatous polyposis andGardner syndrome (adenoma and adenocarcinoma), and vonRecklinghausen disease (paraganglioma). Desmoid tumours,which are often multiple, may be the primary manifestationof Gardner syndrome in the small bowel [12]. Peutz-Jegherssyndrome is an inherited, autosomal dominant disorder dis-tinguished by hamartomatous polyps in the gastrointestinaltract and pigmented mucocutaneous lesions. Prevalence of


Figure 10: Gastrointestinal stromal tumour in the jejunum.

this syndrome is estimated from 1 in 8,300 to 1 in 280,000individuals. Peutz-Jeghers syndrome predisposes sufferersto various malignancies (gastrointestinal, pancreatic, lung,breast, uterine, ovarian, and testicular tumours). Bleeding,obstruction, and intussusception are common complicationsin patients with this disease [16].

Cronkhite-Canada syndrome is a sporadic disease withmultiple polyps in the gastrointestinal tract. Histology findshamartomatous polyps (juvenile type) exhibiting glandularhyperplasia, cystic dilation, mucosal edema, and eosinophilicinflammation. Extraintestinal manifestations are alopecia,dermal hyperpigmentation, onychodystrophy, diarrhoea,protein loosing enteropathy, and/or dysgeusia. Cachexia andcolon cancer are most common [17].

Dietary factors have been suggested to be related tothe risk of small-bowel carcinoma. A study of small-bowelcarcinoma mortality and food intake by the WHO showedcorrelation of carcinoma with per capita daily consumptionof animal fat and animal protein. Saturated fat intake seemsto be a risk factor for small-bowel carcinoma. On the otherhand, there is no association between alcohol intake andrisk of adenocarcinoma of the small intestine [18]. Thereare a number of studies about obesity and small intestinaladenocarcinoma with no clear result. Men have higherincidence rates of small intestinal cancer in most countries[18].

Cigarette smoking, biliary tract diseases (cholecystitisand gallstones), infection with Helicobacter pylori, use ofcorticosteroids, exposure to ionising radiation, and so forthare suspect factors in small intestinal tumourigenesis [18].

Univocal risk factors for individual malignancies wereidentified.

Adenocarcinomas are most common in the distal duo-denum and the duodenojejunal junction. Explanations forthe predilection to the initial part of the small bowel includethe metabolism or dilution of ingested carcinogens in transitthrough the small bowel or interactions of carcinogens withpancreatobiliary secretions [19]. Small intestinal inflamma-tory disorders that predispose patients to adenocarcinomainclude Crohn’s disease (in these patients, tumours couldbe involved in 70% of the terminal ileum), celiac disease,familial adenomatous polyposis, Peutz-Jeghers syndrome,and Meckel’s diverticulum [5, 15, 18]. The risk of adeno-carcinoma in Crohn’s disease is directly related to both

Figure 11: Ileal carcinoid tumour.

Figure 12: Stenosing adenocarcinoma of the jejunum.

the extent of small-bowel involvement and the durationof Crohn’s disease. The cumulative risk of a small-boweladenocarcinoma in patients with small bowel Crohn’s diseaseis 0.2% at 10 years and 2.2% at 25 years of disease [20]. Typicalendoscopic appearance is usually concentric tumour stenosiswith irregular margins and complete bowel obstruction inthe late stage. Polypoid lesions and ulcerations are sometimesseen.

Lymphoma may arise as a primary neoplasm in theintestine or as a component of systemic disease with gastroin-testinal involvement. Primary intestinal lymphomas arisefrom the lymphoid aggregates in the submucosa. The dis-tribution of lymphomas in the small intestine parallels thedistribution of lymphoid follicles, with the lymphoid richileum representing themost common location.The diagnosisof primary gastrointestinal lymphoma is characterised by noperipheral or mediastinal lymphadenopathy, normal whiteand differential blood cell count, and no evidence of liver orspleen involvement [21]. Primary gastrointestinal lymphomais themost common extranodal formof lymphoma; the stom-ach and small bowel are the most common sites. A typicalendoscopic appearance is polypoid mass with ulcerationsand bowel obstruction in the late stage. Bleeding is quite acommon sign, and patients are at risk of spontaneous small-bowel perforation. Small-bowel lymphomas are more oftenfound in patients with celiac disease, Crohn’s disease, AIDS,EBV infection, immunoproliferative disease (IPSID), longterm immunosuppressive therapy (posttransplantation) andafter radiation, and/or chemotherapy [5, 21]. A significant


increase in the incidence of EATL in the United States wasindicated, which may reflect the increasing seroprevalence ofceliac disease and better recognition of rare types of T-celllymphomas [22]. EATL is a rare disease with an incidence of0.1 per 100,000 inhabitants per year, occurring in older age,with a peak incidence in the 7th decade, and nonelevated dur-ing childhood and adolescence. Small intestinal lymphomasand carcinoma are responsible for elevated morality risk inceliac disease. Although uncomplicated celiac disease is twiceas frequent in female patients, EATL is more prevalent inmales [23–25].

Carcinoids, gastroenteropancreatic neuroendocrine tum-ours, constitute a diverse group of neoplasms arising fromthe diffuse neuroendocrine cell system. During the last 2years, a new classification system, the WHO 2010, has comeinto clinical practice together with Tumour Nodes Metasta-ses (TNM) staging and grading systems, developed by theEuropean Neuroendocrine Tumour Society/American JointCancer Committee [26].

Carcinoid is most commonly found in the ileum within60 cm of the ileocecal valve; duodenal or jejunal localisationis rare. Small-bowel carcinoids are likely to be associated withMEN 1. Endoscopically, a small submucosal protrusion withnormal mucosa on the surface is usually seen. Desmoplasticreaction in submucosa is common.

Gastrointestinal stromal tumour (GIST) could be foundelsewhere in the small intestine, but ileal localisation is morecommon. A regular round mass with normal mucosa on itssurface and often central ulceration with or without visiblebleeding is found on endoscopy. Large vessels around thetumour are often seen during surgery.

4. Conclusion

Small intestinal tumours are rare diseases, but approximatelyhalf of them are malignant. A lack of symptoms and difficultdetermination lead to late diagnosis with advanced diseaseand poor prognosis. Because of nonspecific symptoms, itis difficult to make a diagnostic algorithm. Nowadays, thebest way to ensure earlier diagnosis seems to be the useof CE in combination with other new diagnostic (MRI ormultidetector CT enterography) and therapeutic endoscopic(BE) techniques. These tools could lead to earlier diagnosisand treatment of these neoplasms, better survival rate, andcost savings in the end.

Prevention in known risk factors and chronic diseases isobvious.

Acknowledgment

This study was supported by the programme PRVOUK P37/08.

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