Surgery for complications of advanced mid-gut carcinoid may be associated with prolonged survival: report of two cases
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1 Surgery for complications of advanced mid-gut carcinoid may be associated with prolonged survival: report of two cases Lenka Humenska, StR Sam O Toole, FY1 Richard Guy, Consultant Department of General Surgery Peterborough District Hospital 1
2 Introduction Carcinoid tumours are neuroendocrine tumours derived from enterochromaffin or Kulchitsky cells, which are widely distributed in the body. The annual incidence of carcinoid tumour is around two cases per 100,000, although the incidental finding of these tumours at post mortem examination - mainly in the small intestine - is much higher (up to 0.5%- 1%) [1]. The overall incidence of carcinoid tumours appears to have increased in the past 3 decades [2], possibly through improved detection [3]. In age-specific incidence rates, a peak between 15 and 25 years and another peak between 65 and 75 years can be found. Under the age of 50, the incidence is approximately twice as high in females as it is in males. At older ages, a male predominance is observed, with a rate double that of women [3, 4]. Complications of mid-gut carcinoid include obstruction, haemorrhage, intussusception, bowel infarction and perforation secondary to mesenteric infiltration by nodal disease. Over 700 reports of complications of carcinoid are reported in the world literature. Two cases of complicated midgut carcinoid requiring surgery are presented. These cases illustrate the often difficult decision making process required in this disease and the potential for prolonged survival following palliative resection. 2
3 Report of Cases Case 1 A 47 year old woman presented as an emergency with a month s history of severe colicky right upper quadrant pain associated with symptoms of flushing and diarrhoea.. There was no history of jaundice or altered bowel habit. On examination the abdomen was soft with right upper quadrant tenderness and voluntary guarding. Full blood count showed a neutrophilia (neutrophils 11.5 x 10 9 / L, white cell count 13.9 x 10 9 / L). C Reactive Protein was not raised and liver function tests were normal. A chest radiograph was unremarkable. An ultrasound scan of the abdomen showed a thin-walled gallbladder without stones and with no evidence of common bile duct dilatation. The liver appeared abnormal with multiple hyperdense lesions visualised in both lobes. A contrast-enhanced CT scan of the chest, abdomen and pelvis confirmed three round lesions in the left lobe of the liver around the falciform ligament with at least one more lesion in the right lobe with the appearance of metastases (Figure 1). There was an abnormal small bowel loop which was irregular and thickened with a relatively increased enhancement and the suggestion of intussusception (Figure 2). There was a nodular irregular thickening along the line of the blood vessels. Metastatic small bowel carcinoid was considered the most likely diagnosis. The colon was normal at colonoscopy and levels of CEA, CA125 and Ca19.9 tumour markers were normal. Her urinary HIAA level prior the surgery was 234 umol/24h. 3
4 The decision was made to proceed to laparoscopy. A right iliac fossa mass was found affecting the caecum and terminal ileum with significant regional lymph node disease, a nodular mass in the pelvis and widespread peritoneal metastases. Examination of a peritoneal biopsy showed sclerotic tissue with tumour cells composed of sheets and islands of monomorphic cells with clumped chromatin and prominent nucleoli. There was also focal microcalcification. Immuno-histochemistry showed positivity for chromogranin and synaptophysion confirming a histological diagnosis of carcinoid. She was treated with subcutaneous Lanreotide 60mg once monthly but abdominal symptoms of intermittent obstruction persisted and she proceeded to laparoscopic right hemicolectomy. This was uneventful without post-operative complications and histopathological examination confirmed the diagnosis of metastatic carcinoid of small bowel origin, 8 out of 11 dissected lymph nodes showing metastatic tumour. Her post-operative urine HIAA level was 92 umol/ 24h and her symptoms of flushing and diarrhoea improved. She was discharged under the care of oncologist and restarted on Lanreotide 60mg once monthly. 4
5 Figure 1 CT showing three low density liver lesions clustered around the falciform ligament. 5
6 Figure 2. CT showing thickened and irregular small loop with relative enhancement suggestive of intussusception. Case 2. A 79 year old man presented with abdominal pain associated with vomiting and diarrhoea. Past medical history included appendicectomy and non-metastatic prostate cancer managed with Zoladex. Metastatic carcinoid tumour had been diagnosed 3 years previously, a CT scan having shown tumour involving the terminal ileum and mesentery with multiple liver metastases, subsequently confirmed on liver biopsy. He had been managed on Lanreotide and the disease was considered stable. 6
7 However, a CT scan 6 months prior to emergency presentation showed tumour infiltrating the duodenum causing some obstruction and with progression of the liver metastases. On examination he was afebrile but tachycardic (heart rate 110/min) and had signs of generalised peritonitis. Blood tests showed a white cell count of 14.4 x10 9 /L (neutrophils 13.4 x 10 9 / L) and a mildly elevated urea (10.6 mmol/ L). Abdominal and chest radiographs were unremarkable. Following discussion with the patient and his family the decision was made to proceed to surgery, despite the potential risk of significant morbidity or mortality. At laparotomy through a midline incision perforation of a 30cm length of infarcted distal ileum was found with free intraperitoneal small bowel content. Small bowel resection was performed and an ileum to transverse colon bypass plus gastrojejunostomy carried out. Postoperatively he made a gradual but complete recovery, bowel function was restored and he was able to tolerate a normal diet. He was discharged after 3 weeks. 7
8 Discussion. Carcinoid tumours were first described in 1907 by Obendorfer and are rare slow-growing, neuroendocrine tumours. Classification of gastrointestinal carcinoid tumours is based on the region of tumour origin, comprising foregut (10% of the total), midgut (75%) and hindgut (15%). Midgut carcinoids may present with abdominal pain (up to 60%), nausea and vomiting (up to 40%), weight loss (up to 30%), intermittent or continuous diarrhoea (up to 20%), blood loss (up to 20%) and carcinoid syndrome ( up to 20%). A significant number are discovered incidentally, usually at laparotomy or appendicectomy [4]. Midgut tumours may present with an acute abdomen in a minority of patients, with clinical features consistent with appendicitis, intestinal obstruction, intestinal perforation, gastrointestinal haemorrhage or mesenteric ischaemia. Alternatively, carcinoid may remain unconsidered until histopathology is obtained following surgery for presumed jejunal, ileal or colonic inflammatory disorders, including Crohn s disease, lymphoma or adenocarcinoma. Also, carcinoid tumours may be found in the midgut or in resected specimens when surgery has been undertaken for other intraabdominal disease, notably carcinoma, borne out by the association of carcinoid with other tumours evident in population-based studies [5]. Intermittent intestinal obstrucion may be caused by fibrosis and shrinkage of the mesentery, with kinking of the small intestine [6]. Furthermore, intestinal ischaemia may result from compression of the main mesenteric vessels by nodal metastases, fibrosis or elastic vascular sclerosis [7, 8]. Haematological, biochemical and radiological investigations should be undertaken as required for general medical assessment and to determine whether the patient is fit enough for surgery [5]. Emergency surgery is likely to be indicated for the acute abdomen and should be directed at removing the immediate threat to life. Aggressive resectional surgery in patients with midgut 8
9 carcinoid tumours may have a place in the management of this disease but the extent of emergency surgery may be limited by the condition of the patient and the extent of intra-abdominal disease [9]. Patients not requiring emergency surgery can be more accurately staged pre-operatively for definitive elective management [10]. Resection of the primary tumour reduces symptoms and improves survival, even when inoperable mesenteric lymph node and liver metastasis are present, as in the cases presented. If possible, mesenteric lymph node metastases should be resected, as this measure alleviates symptoms and may improve survival [11]. Adjuvant medical treatment may be effective in combination with surgery. The combination of octreotide and interferon treatment benefits the patients additionally [11]. 9
10 References 1 Moertel CG, Sauer WG, Dockerty MB. Life history of the carcinoid tumor of the small intestine. Cancer 1961;14: Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97: Hemminki K & Li X. Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer 2001;92: Quaedvlieg PF, Visser O, Lmers CB. Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol 2001;12: Shebani KO, Souba WW, Finkelstein DM, Stark PC, Elgadi KM, Tanabe KK, Ott MJ. Prognosis and survival in patients with gastrointestinal tract carcinoid tumors. Ann Surg 1999;229: Kowlessar OD, Law DH, Sleisenger MH. Malabsorption syndrome associated with metastatic carcinoid tumor. Am J Med 1959;27: Warner TF, O Reilly G, Lee GA. Mesenteric occlusive lesion and ileal carcinoids. Cancer 1979;44:
11 8 Eckhauser FE, Argenta LC, Strodel WE, Wheeler RH, Bull FE, Appelman HD, Thompson NW. Mesenteric angiopathy, intestinal gangrene, and midgut carcinoids. Surgery 1981;90: Makridis C, Oberg K, Juhlin C, Rastad j, Johansson H, Lorelius LE, Akerstrom G. Surgical treatment of mid-gut carcinoid tumors. World J Surg 1990;14: Kulke M, Mayer R. Carcinoid tumors. N Eng J Med 1999;340: Hellaman P, Lundström T, Öhrvall U, Eriksson B, Skogseid B, Öberg K, Tiensuu Janson E, Åkerström G. Effect of surgery on the outcome of the midgut carcinoid disease with lymph node and liver metastases World J. Surg. 2002;26:
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