Obscure gastrointestinal bleeding due to carcinoid tumours of the small bowel

NORMAN MACHADO and CHRISTOPHER S. GRANT
Department of Surgery, Sultan Qaboos University Hospital, PO Box 38, Postal Code 123, Muscat, Oman

Introduction

Patients and methods

Discussion

References

Patients with obscure gastrointestinal bleeding are often difficult to manage and frequently undergo extensive investigations. The diagnosis is particularly difficult when the bleeding arises from small lesions in the small bowel that is not easily accessible for direct visualisation. We report two patients with obscure gastrointestinal bleeding from carcinoid tumours of the small bowel, highlighting the problems in diagnosis and localisation.

Obscure gastrointestinal (GI) bleeding constitutes 5% of all GI bleeds and are mostly due to vascular anomalies of the colon and small bowel.^1,2 Small bowel tumours contribute only about 5% of the causes of obscure GI bleeds.3 Carcinoid tumours of small bowel are rare, with an estimated incidence of 1.5 per 100 000 people; less than 5% of the tumours bleed, making them a very unlikely cause of GI bleeding.4 We report here two patients who presented with obscure GI bleeding due to carcinoid tumours of the small gut and highlight problems in the diagnosis and localisation of such cases.

A 53-year-old diabetic, hypertensive female, with a previous history of a stroke, was admitted with an episode of acute bleeding per rectum and a haemoglobin of 5.9g/dl. She had been admitted for investigation of recurrent bleeding per rectum 18 months previously, although upper GI endoscopy, colonoscopy, small bowel contrast study, and technetium-tagged red blood cell (Tc-RBC) scan were all normal. Following the series of investigations she was discharged on iron supplements. She underwent further GI investigations, including mesenteric angiography, 6 months later. Again, the tests were negative. On this admission, a repeat Tc-RBC scan showed an uptake in the ileum and mesenteric arteriograms revealed two small areas of localised enhancement with a tumour blush in the ileum (Figure 1). She was transfused and underwent an exploratory operation. The small gut appeared grossly normal apart from an obvious pooling of blood in the terminal ileum. Enteroscopy (using a colonoscope via an ileal enterotomy) confirmed the presence of fresh blood in the lumen. Careful examination of the entire mucosa, after saline irrigation, revealed two ileal submucosal nodules approximately 5 cm apart, each around 5 mm in diameter, with one of them oozing blood from an overlying minute ulceration. The two nodules were resected as a single, 10 cm segment of ileum and an end-to-end anastomosis performed. The histopathological diagnosis of the two lesions was carcinoid tumours. Following this procedure, the patient had no further GI bleeding and was discharged. She had a follow-up meta-iodobenzylguanidine (MIBG) scan that was reported to be normal. She remains well 5 years after the surgery, with no further episodes of GI bleeding.

Figure 1: Technetium labelled RBC scan showing extravasation of radiolabelled blood in a loop of ileum (arrow)

A 48-year-old male patient presented with an 18-month history of anaemia and occasional upper abdominal pain. His haemoglobin level was 7.1 g/dl and the blood analysis showed microcytic hypochromic anaemia. The stool was positive for occult blood on three occasions. He underwent upper GI endoscopy, colonoscopy and a barium meal and follow through, all of which were normal. He was put on iron supplements and followed-up. He presented 3 months later, with three episodes of melaena. Upper GI endoscopy was again normal and a Tc-RBC scan was also negative. The bleeding ceased spontaneously and he refused further investigations. He returned 12 months later with similar complaints. A Tc-RBC scan, on this occasion, showed an uptake in the jejunum and arteriography demonstrated a tumour blush in the jejunum (Figure 2). At laparotomy, a visible, palpable lesion, 1.5 cm in diameter, was found on the anti-mesenteric border of the jejunum 20 cm from the duodenojejunal flexure. Exploration was otherwise normal. The lesion was resected and enteroscopy of the remaining small gut was normal; an end-to-end anastomosis was then carried out. Gross examination of the resected specimen showed a submucosal lesion with a 3 mm diameter mucosal ulceration overlying it; microscopic examination revealed a carcinoid tumour (Figure 3). There was no further bleeding postoperatively and he was discharged. A MIBG scan carried out 12 months after the surgery was negative. The patient remains well 4 years after the surgery with no recurrence of bleeding.

Figure 2: Technetium labelled RBC scan showing abnormal activity in the jejunum (single arrow) with the later images showing extravasated radiolabelled blood in the jejunal loop (double arrows)

Figure 3: Photomicrograph of resected specimen showing ulceration of mucosa (curved arrow) with endocrine type tumour with trabeculae and glandular pattern (straight arrow) characteristic of a carcinoid tumour. (Haematoxylin-eosin stain; original magnification x9)

Most carcinoid tumours derive from the embryologic mid-gut. In a meta-analysis of 3718 collected cases, 45% of the tumours were found in the appendix and 28% in the jejunum and ileum.⁵ Jejuno-ileal carcinoids may be multiple, with a reported incidence of about 28% but in one series of patients with bleeding carcinoids, the incidence was 57%.^6,7 Mid-gut carcinoid tumours are generally advanced at diagnosis unless they are discovered incidentally or present with GI bleeding. The most common clinical presentation of small bowel carcinoids is periodic abdominal pain which appears to be due to intermittent bowel obstruction. The mean duration of symptoms before a diagnosis is made is approximately 2 years.⁸ Gastro-intestinal bleeding is distinctly uncommon as these lesions rarely ulcerate.^2,9 Carcinoids originate deep to the mucosa and, as they grow, they tend first to invade the muscular layer, serosa and mesentry rather than mucosa. Ulceration, therefore, is an uncommon feature. In one series, only 2/209 small bowel carcinoids were found to have ulcerated at autopsy.⁹ In both our patients gross and microscopic ulceration could be identified (Figure 3). Rarely, acute bleeding may result from occlusion of the mesenteric artery in association with large clusters of metastatic nodal lesions involving the vessels at the root of the mesentry.^8,9 It is also speculated, that other than the mechanical narrowing of vessels due to nodes and fibroblastic reaction, the local vasoconstricting effect of high concentrations of serotonin may play a role.⁸

Several GI investigations are often required before a bleeding, small bowel carcinoid tumour is localised, as demonstrated by our own experience. This is largely due to the small size of the lesions.^8,10 In one large series of obscure GI bleeding, patients with small bowel tumours required a median of eight GI investigations before the diagnosis was made.3 Diagnosis of bleeding small bowel carcinoid tumours before surgery is a challenge as most of the cases reported, including our own patients, had neither associated bowel obstruction nor carcinoid syndrome.7 In one report an arteriographically seen ileal lesion was specifically diagnosed as carcinoid because the patient developed a paroxysmal episode of facial flushing during injection of the contrast.¹¹ In collective series, arteriograms demonstrated the site in 57% of bleeding carcinoid tumours.7 Selective arteriograms may pick up an actively bleeding lesion if the rate of bleeding is more than 0.5ml/min.¹² However, even in patients with slow bleeding as in one of our patients, the presence of a tumour blush is useful in localising the lesion.

Although RBC-tagged scintigraphy can detect blood loss of 0.05-0.1 ml/min, the success rate of detection is variable; recent reports give a sensitivity of 97% and specificity of 85%.^13,14 Nuclear scanning with MIBG is more useful in surveillance in the patients with carcinoid tumours and has been reported to visualise 70% of mid-gut carcinoid tumours.¹⁵ A recent technique of somatostatin labelled with technetium which visualises tumours with somatostatin receptors promises to be useful in detecting carcinoid tumours. High-affinity somatostatin receptors seem to dominate in carcinoid tumours which, therefore, may be detected with 100% specificity and 66% sensitivity.¹⁵

Even though nuclear scanning and angiograms may grossly localise a bleeding carcinoid it may still be difficult to identify the lesion at laparotomy, particularly when they are less than 1 cm in size, as demonstrated by our first patient. The usefulness of enteroscopy in such cases has been documented in the past.^2,10 In addition to identifying these small bleeding carcinoids by directly examining the mucosa, it is important to search for coexistent non-bleeding carcinoid lesions as they tend to be multiple. If missed, these could be symptomatic at a later stage. Small lesions can easily be missed in the mucosal folds, particularly, when the lumen is loaded with blood. It is imperative to repeat the enteroscopy examination several times until one is convinced about the findings.

The follow-up of these patients for recurrence, particularly those with lesions of more than 1 cm, should involve biochemical investigations and/or a radionucleide study. Measurements of plasma or urinary serotonin, substance P, chromogranins or Beta human chorionic gonadotrophin may prove useful, but the exact indication for these tests are not, as yet, clear.¹⁶

In summary, small bowel carcinoid tumours that bleed are generally small in size and require several GI investigations, particularly nuclear scanning and angiography to localise them pre-operatively. Detection at laparotomy may also be difficult and enteroscopy may be needed to locate the bleeding lesion and search for co-existent carcinoids.

The authors would like to thank Mrs Helen B. Leopoldo for her secretarial help and typing.

Correspondence: Professor C S Grant, Department of Surgery, Sultan Qaboos University Hospital, PO Box 38, Postal code 123, Muscat , Oman

Obscure gastrointestinal bleeding due to carcinoid tumours of the small bowel:problems in diagnosis and localisation