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Carcinoid Syndrome and Perioperative Anesthetic Considerations Kenneth Mancuso MD (Assistant Professor)A, Alan D Journal of Clinical Anesthesia (2011) 23, 329–341 Review article Carcinoid syndrome and perioperative anesthetic considerations Kenneth Mancuso MD (Assistant Professor)a, Alan D. Kaye MD, PhD (Professor, Chairman)a, J. Philip Boudreaux MD, FACS (Professor)b,c, Charles J. Fox MD (Associate Professor)d,e, Patrick Lang (Medical Student)e, Philip L. Kalarickal MD, MPH (Clinical Assistant Professor)f, Santiago Gomez MD (Clinical Assistant Professor)f, Paul J. Primeaux MD (Clinical Assistant Professor)g,⁎ aDepartment of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA bDivision of Neuroendocrine Surgery and Transplantation, Louisiana State University Health Sciences Center, New Orleans, LA cChairman, Department of Surgery, Ochsner-Kenner Hospital, Kenner, LA 70065, USA dDirector of Perioperative Management, Department of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112, USA eTulane University School of Medicine, New Orleans, LA 70112, USA fDepartment of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112, USA gResidency Program Director, Department of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112, USA Received 10 February 2010; revised 7 December 2010; accepted 8 December 2010 Keywords: Abstract Carcinoid tumors are uncommon, slow-growing neoplasms. These tumors are capable of Carcinoid syndrome; secreting numerous bioactive substances, which results in significant potential challenges in the Octreotide; management of patients afflicted with carcinoid syndrome. Over the past two decades, both surgical and Serotonin medical therapeutic options have broadened, resulting in improved outcomes. The pathophysiology, clinical signs and symptoms, diagnosis, treatment options, and perioperative management, including anesthetic considerations, of carcinoid syndrome are presented. © 2011 Elsevier Inc. All rights reserved. 1. Introduction from neuroendocrine cells and are capable of secreting bioactive substances, most importantly serotonin, histamine, Carcinoid tumors are uncommon, but not rare, slow- and the kinin peptides [1-3]. If these substances reach the growing neoplasms capable of metastasis. They originate systemic circulation without first being metabolized by the liver, they are capable of producing carcinoid syndrome [1]. ⁎ Corresponding author. Tel.: +1 504 988 5904. This syndrome may produce life-threatening perioperative E-mail address: [email protected] (P.J. Primeaux). hemodynamic instability. The syndrome most often occurs 0952-8180/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2010.12.009 330 K. Mancuso et al. with primary tumors that do not drain into the portal system Table 1 Clinical presentation and incidence of Carcinoid or with hepatic metastases (the most common site of syndrome metastasis) because they bypass metabolism in the liver Location Percentage Incidence of Incidence of [1]. The majority of these tumors are located in the of total metastases (%) Carcinoid gastrointestinal (GI) tract, most commonly in the appendix, syndrome (%) rectum, and ileum [1]; however, they also may be found in Foregut the bronchial tree [1]. esophagus b 0.1 —— Improved tools have resulted in an increase in the stomach 4.6 10 9.5 diagnosis of carcinoid tumors [4]. Currently, the reported duodenum 2.0 — 3.4 incidence is between 0.2 and 10/100,000 [1,4-6]. Autopsy pancreas 0.7 71.9 20 results have shown incidental findings of carcinoid tumor to gallbladder 0.3 17.8 5 be as high as 8% [4], indicating that many of these tumors bronchus, lung, 27.9 5.7 13 remain undiagnosed [7]. There is no difference in incidence trachea with regard to either gender or race [1]. There is, however, a Midgut bimodal distribution with respect to age. Patients are jejunum 1.8 58.4 9 typically diagnosed either between 25 and 45 years of age ileum 14.9 58.4 9 Meckel's 0.5 — 13 or over 60 years of age [1]. These tumors are sometimes diverticulum found in children, most commonly in the appendix [8]. The appendix 4.8 38.8 b 1 5-year survival rate is 80% overall, but ranges from 33% for colon 8.6 51 5 patients with sigmoid colon tumors to 99% for those with liver 0.4 32.2 — tumors of the appendix. When distant metastases are present, ovary 1.0 32 50 the 5-year survival rate decreases to 18% to 19% [9,10]. With testis b 0.1 — 50 the introduction of octreotide in 1992, survival rates have Hindgut improved significantly [10]. rectum 13.6 3.9 — Modified from: Jensen RT: Endocrine tumors of the gastrointestinal tract and pancreas. In: Fauci AS, Braunwald E, Kasper DL, et al., editors. Harrison's Principles of Internal Medicine. 17th edn. New York: 2. Background McGraw-Hill Cos.; 2008. p. 2349. Although first reported in 1888, it was not until 1907 that jejunum to mid-transverse colon, and are most likely to Oberndorfer first described these tumors as “carcinoid” produce the classic carcinoid syndrome [24]. Hindgut tumors tumors [11]. They were described as slow-growing, small are found from the mid-transverse colon to the rectum bowel tumors, capable of metastasis, with a generally [23,25], and usually do not present with carcinoid syndrome favorable prognosis. More than 75% of carcinoid tumors [24]. Hindgut carcinoids are more likely to present with originate in the GI tract [12-14]. The lung is the most GI bleeding [23]. There is another classification system common site outside of the GI tract in which carcinoid which assigns the term “carcinoid tumor” only to midgut tumors are found (22% of distant metastases are found in the tumors, and “neuroendocrine tumor of the site of origin” lung) [15,16]. Tumors also have been reported in the to others [26]. genitourinary tract, thyroid, breast [1], pancreas [17], thymus Patients with carcinoid tumors also are at increased risk of [18], and liver [19]. having other co-existing tumors, frequently in the lung, The extent of tumor burden is not necessarily related to esophagus, stomach, colon, prostate, and urinary tract [27]. the clinical course of the patient. Patients with a large tumor The presence of an occult carcinoid tumor may become burden may remain asymptomatic for years, while some of evident during surgery for a non-carcinoid tumor. Incidental those with only minimal disease, in the small bowel findings of carcinoid tumor are often found in younger mesentery, for example, may have significant symptoms of patients, 25 to 45 years of age, during appendectomy, carcinoid syndrome without any liver metastases [7,20-22]. trauma, or cesarean sections. In the older population, over 60 Carcinoid syndrome is most often associated with ileal years of age, findings are often made during vascular surgery tumors with liver metastases that secrete mediators directly or transurethral resection of the prostate [1]. into the hepatic veins [19]. Carcinoid tumors traditionally have been classified by the embryonic site of origin of the tumor, eg, as foregut, midgut, or hindgut [4]. The site of origin affects the clinical 3. Signs and symptoms presentation, secretion of vasoactive substances, signs and symptoms of carcinoid syndrome, and overall survival [23] Due to their slow growth, carcinoid tumors are usually (Table 1). Foregut carcinoids are found from the esophagus asymptomatic and often produce only vague abdominal pain to the duodenum. Midgut carcinoids are found from the that is undiagnosed or misdiagnosed as irritable bowel Carcinoid syndrome and anesthesia 331 syndrome [28]. However, these non-secreting tumors may Table 2 Clinical manifestations of carcinoid syndrome produce symptoms such as intestinal obstruction or hemop- Sign/symptom Frequency Characteristics Involved tysis [19]. Appendiceal carcinoids are usually found mediators incidentally at appendectomy, whereas jejunoileal carcinoids are more likely to present with abdominal pain, obstruction, Flushing 85% - Foregut: Kallikrein, 90% long-lasting, 5-HTP, or signs of carcinoid syndrome [23]. Only 25% of carcinoid purple face and Histamine, tumors actually produce mediators capable of causing neck. Midgut: substance P, symptoms of carcinoid syndrome [19]. Normally the release short-lasting, Prostaglandins of vasoactive substances causes little if any symptoms pink/red. Severe because the liver is able rapidly to inactivate these substances flushing [23]. With larger tumors, the liver's ability to inactivate these associated substances may be overwhelmed [19,29], and carcinoid with hypotension syndrome results. Signs and symptoms of carcinoid and tachycardia syndrome develop only when neuropeptides and amine GI 70% - Secretory diarrhea, Gastrin, substances are released in their active form into the systemic hypermotility 80% nausea, vomiting 5-HTP, circulation. These signs and symptoms often indicate the histamine, PGs, VIPs presence of hepatic, gonadal, bone, or pulmonary metastases, Abdominal 35% Progressive Small bowel as substances produced in these sites bypass metabolism in pain obstruction, the liver [4]. Primary tumors that do not drain into the portal hepatomegaly, circulation, such as bronchial, ovarian, or testicular tumors, ischemia are also capable of producing carcinoid syndrome [1]. Heart failure Although 25% of tumors actively secrete substances right 30% Dyspnea 5-HTP, capable of causing symptoms, less than 10% of people with a substance P carcinoid tumor develop the classic carcinoid syndrome [24]. left 10% Carcinoid syndrome has a clinical spectrum that includes Telangiectasia 25%
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