Characteristics of the Most Common GI Carcinoid Tumors
Appendiceal carcinoids occur in 1 in every 200–300 appendectomies, usually in the appendiceal tip. Most (i.e., >90%) are <1 cm in diameter without metastases in older studies, but more recently 2–35% have had metastases (Table 350-3). In the SEER data of 1570 appendiceal carcinoids, 62% were localized, 27% had regional metastases, and 8% had distant metastases. Approximately 50% between 1 and 2 cm metastasized to lymph nodes. Their percentage of the total number of carcinoids decreased from 43.9% (1950–1969) to 2.4% (1992–1999).
Small-intestinal carcinoids account for approximately one-third of all small-bowel tumors in various surgical series. These are frequently multiple; 70–80% are present in the ileum, and 70% within 6 cm (24 in.) of the ileocecal valve. Forty percent are <1 cm in diameter, 32% are 1–2 cm, and 29% are >2 cm. Between 35 and 70% are associated with metastases (Table 350-3). They characteristically cause a marked fibrotic reaction, which can lead to intestinal obstruction. Distant metastases occur to liver in 36–60%, to bone in 3%, and to lung in 4%. As discussed previously, tumor size is an important variable in the frequency of metastases. However, even a proportion of small carcinoid tumors of the small intestine (<1 cm) have metastases in 15–25% of cases, whereas the proportion increases to 58–100% for tumors 1–2 cm in diameter. Carcinoids also occur in the duodenum, with 31% having metastases. No duodenal tumor <1 cm in two series metastasized, whereas 33% of those >2 cm had metastases. Small-intestinal carcinoids are the most common cause (60–87%) of the carcinoid syndrome and are discussed in a later section (Table 350-6).
Table 350-6 Clinical Characteristics in Patients with Carcinoid Syndrome |Favorite Table|Download (.pdf)
Table 350-6 Clinical Characteristics in Patients with Carcinoid Syndrome
|At Presentation||During Course of Disease|
|Diarrhea ||32–73% ||68–84% |
|Flushing ||23–65% ||63–74% |
|Pain ||10% ||34%|
|Asthma/wheezing ||4–8%||3–18% |
|Carcinoid heart disease present||11%||14–41%|
|Male ||46–59% ||46–61%|
|Mean ||57 yrs||52–54 yrs |
|Range||25–79 yrs||9–91 yrs|
|Foregut ||5–9% ||2–33% |
|Midgut ||78–87% ||60–87% |
|Hindgut ||1–5% ||1–8% |
Rectal carcinoids represent 1–2% of all rectal tumors. They are found in approximately 1 in every 2500 proctoscopies. Nearly all occur between 4 and 13 cm above the dentate line. Most are small, with 66–80% being <1 cm in diameter, and rarely metastasize (5%). Tumors between 1 and 2 cm can metastasize in 5–30%, and those >2 cm, which are uncommon, in >70%.
Bronchial carcinoids account for 1–2% of primary lung tumors. The frequency of bronchial carcinoids has increased more than fivefold over the last 30 years. A number of different classifications of bronchial carcinoid tumors have been proposed. In some studies, lung NETs are classified into four categories: typical carcinoid [also called bronchial carcinoid tumor, Kulchitsky cell carcinoma I (KCC-I)], atypical carcinoid [also called well-differentiated neuroendocrine carcinoma (KC-II)], intermediate small cell neuroendocrine carcinoma, and small cell neuroendocarcinoma (KC-III). Another proposed classification includes three categories of lung NETs: benign or low-grade malignant (typical carcinoid), low-grade malignant (atypical carcinoid), and high-grade malignant (poorly differentiated carcinoma of the large cell or small cell type). The WHO classification includes four general categories: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. These different categories of lung NETs have different prognoses, varying from excellent for typical carcinoid to poor for small cell neuroendocrine carcinomas. The occurrence of large cell and small cell lung carcinoids, but not typical or atypical lung carcinoids, is related to tobacco use.
Gastric carcinoids account for 3 of every 1000 gastric neoplasms. Three different subtypes of gastric carcinoids are proposed to occur. Each originates from gastric enterochromaffin-like cells (ECL cells), one of the six types of gastric neuroendocrine cells, in the gastric mucosa. Two subtypes are associated with hypergastrinemic states, either chronic atrophic gastritis (type I) (80% of all gastric carcinoids) or Zollinger-Ellison syndrome, which is almost always a part of the MEN 1 syndrome (type II) (6% of all cases). These tumors generally pursue a benign course, with type 1 uncommonly (<10%) associated with metastases, whereas type II tumors are slightly more aggressive with 10–30% percentage associated with metastases. They are usually multiple and small and infiltrate only to the submucosa. The third subtype of gastric carcinoid (type III) (sporadic) occurs without hypergastrinemia (14–25% of all gastric carcinoids) and has an aggressive course, with 54–66% developing metastases. Sporadic carcinoids are usually single, large tumors; 50% have atypical histology, and they can be a cause of the carcinoid syndrome. Gastric carcinoids as a percentage of all carcinoids are increasing in frequency [1.96% (1969–1971), 3.6% (1973–1991), 5.8% (1991–1999)].
Carcinoid Tumors Without the Carcinoid Syndrome
The age of patients at diagnosis ranges from 10 to 93 years, with a mean age of 63 years for the small intestine and 66 years for the rectum. The presentation is diverse and is related to the site of origin and the extent of malignant spread. In the appendix, carcinoid tumors usually are found incidentally during surgery for suspected appendicitis. Small-intestinal carcinoids in the jejunoileum present with periodic abdominal pain (51%), intestinal obstruction with ileus/invagination (31%), an abdominal tumor (17%), or GI bleeding (11%). Because of the vagueness of the symptoms, the diagnosis usually is delayed approximately 2 years from onset of the symptoms, with a range up to 20 years. Duodenal, gastric, and rectal carcinoids are most frequently found by chance at endoscopy. The most common symptoms of rectal carcinoids are melena/bleeding (39%), constipation (17%), and diarrhea (12%). Bronchial carcinoids frequently are discovered as a lesion on a chest radiograph, and 31% of the patients are asymptomatic. Thymic carcinoids present as anterior mediastinal masses, usually on chest radiograph or CT scan. Ovarian and testicular carcinoids usually present as masses discovered on physical examination or ultrasound. Metastatic carcinoid tumor in the liver frequently presents as hepatomegaly in a patient who may have minimal symptoms and nearly normal liver function test results.
Carcinoid Tumors with Systemic Symptoms Due to Secreted Products
Carcinoid tumors immunocytochemically can contain numerous GI peptides: gastrin, insulin, somatostatin, motilin, neurotensin, tachykinins (substance K, substance P, neuropeptide K), glucagon, gastrin-releasing peptide, vasoactive intestinal peptide (VIP), pancreatic polypeptide (PP), ghrelin, other biologically active peptides (ACTH, calcitonin, growth hormone), prostaglandins, and bioactive amines (serotonin). These substances may or may not be released in sufficient amounts to cause symptoms. In various studies of patients with carcinoid tumors, elevated serum levels of PP were found in 43%, motilin in 14%, gastrin in 15%, and VIP in 6%. Foregut carcinoids are more likely to produce various GI peptides than are midgut carcinoids. Ectopic ACTH production causing Cushing's syndrome is seen increasingly with foregut carcinoids (respiratory tract primarily) and in some series has been the most common cause of the ectopic ACTH syndrome, accounting for 64% of all cases. Acromegaly due to growth hormone–releasing factor release occurs with foregut carcinoids, as does the somatostatinoma syndrome, but rarely occurs with duodenal carcinoids. The most common systemic syndrome with carcinoid tumors is the carcinoid syndrome, which is discussed in detail in the next section.
The cardinal features from a number of series at presentation as well as during the disease course are shown in Table 350-6. Flushing and diarrhea are the two most common symptoms, occurring in up to 73% initially and in up to 89% during the course of the disease. The characteristic flush is of sudden onset; it is a deep red or violaceous erythema of the upper body, especially the neck and face, often associated with a feeling of warmth and occasionally associated with pruritus, lacrimation, diarrhea, or facial edema. Flushes may be precipitated by stress; alcohol; exercise; certain foods, such as cheese; or certain agents, such as catecholamines, pentagastrin, and serotonin reuptake inhibitors. Flushing episodes may be brief, lasting 2 to 5 min, especially initially, or may last hours, especially later in the disease course. Flushing usually is associated with metastastic midgut carcinoids but can also occur with foregut carcinoids. With bronchial carcinoids the flushes frequently are prolonged for hours to days, reddish in color, and associated with salivation, lacrimation, diaphoresis, diarrhea, and hypotension. The flush associated with gastric carcinoids can also be reddish in color, but with a patchy distribution over the face and neck, although the classic flush seen with midgut carcinoids can also be seen with gastric carcinoids. It may be provoked by food and have accompanying pruritus.
Diarrhea is present in 32–73% initially and 68–84% at some time in the disease course. Diarrhea usually occurs with flushing (85% of cases). The diarrhea usually is described as watery, with 60% of patients having <1 L/d of diarrhea. Steatorrhea is present in 67%, and in 46% it is greater than 15 g/d (normal <7 g). Abdominal pain may be present with the diarrhea or independently in 10–34% of cases.
Cardiac manifestations occur in 11–20% initially of patients with carcinoid syndrome and in 17–56% (mean 40%) at some time in the disease course. The cardiac disease is due to the formation of fibrotic plaques (composed of smooth-muscle cells, myofibroblasts, and elastic tissue) involving the endocardium, primarily on the right side, although lesions on the left side also occur occasionally, especially if a patent foramen ovale exists. The dense fibrous deposits are most commonly on the ventricular aspect of the tricuspid valve and less commonly on the pulmonary valve cusps. They can result in constriction of the valves, and pulmonic stenosis is usually predominant, whereas the tricuspid valve is often fixed open, resulting in regurgitation predominating. Overall, in patients with carcinoid heart disease, 97% have tricuspid insufficiency, 59% tricuspid stenosis, 50% pulmonary insufficiency, 25% pulmonary stenosis, and 11% (0–25%) left-side lesions. Up to 80% of patients with cardiac lesions develop heart failure. Lesions on the left side are much less extensive, occur in 30% at autopsy, and most frequently affect the mitral valve.
Other clinical manifestations include wheezing or asthma-like symptoms (8–18%) and pellagra-like skin lesions (2–25%). A variety of noncardiac problems due to increased fibrous tissue have been reported, including retroperitoneal fibrosis causing urethral obstruction, Peyronie's disease of the penis, intraabdominal fibrosis, and occlusion of the mesenteric arteries or veins.
Carcinoid syndrome occurred in 8% of 8876 patients with carcinoid tumors, with a rate of 1.4–18.4% in different studies. It occurs only when sufficient concentrations of products secreted by the tumor reach the systemic circulation. In 91% of cases this occurs after distant metastases to the liver. Rarely, primary gut carcinoids with nodal metastases with extensive retroperitoneal invasion, pancreatic carcinoids with retroperitoneal lymph nodes, or carcinoids of the lung or ovary with direct access to the systemic circulation can cause the carcinoid syndrome without hepatic metastases. All carcinoid tumors do not have the same propensity to metastasize and cause the carcinoid syndrome (Table 350-3). Midgut carcinoids account for 60–67% of cases of carcinoid syndrome, foregut tumors for 2–33%, hindgut for 1–8%, and an unknown primary location for 2–15%.
One of the main secretory products of carcinoid tumors involved in the carcinoid syndrome is serotonin [5-hydroxytryptamine (5-HT)] (Fig. 350-1), which is synthesized from tryptophan. Up to 50% of dietary tryptophan can be used in this synthetic pathway by tumor cells, and this can result in inadequate supplies for conversion to niacin; hence, some patients (2.5%) develop pellagra-like lesions. Serotonin has numerous biologic effects, including stimulating intestinal secretion with inhibition of absorption, stimulating increases in intestinal motility, and stimulating fibrogenesis. In various studies 56–88% of all carcinoid tumors were associated with serotonin overproduction; however, 12–26% of the patients did not have the carcinoid syndrome. In one study platelet serotonin was elevated in 96% of patients with midgut carcinoids, 43% with foregut tumors, and 0% with hindgut tumors. In 90–100% of patients with the carcinoid syndrome there is evidence of serotonin overproduction. Serotonin is thought to be predominantly responsible for the diarrhea because of its effects on gut motility and intestinal secretion, primarily through 5-HT3 and, to a lesser degree, 5-HT4 receptors. Serotonin receptor antagonists (especially 5-HT3 antagonists) relieve the diarrhea in many, but not all, patients. Additional studies suggest that prostaglandin E2 (PGE2) and tachykinins may be important mediators of the diarrhea in some patients. In one study, plasma tachykinin levels correlated with symptoms of both flushing and diarrhea. Serotonin does not appear to be involved in the flushing because serotonin receptor antagonists do not relieve flushing. In patients with gastric carcinoids the characteristic red, patchy pruritic flush probably is due to histamine release because H1 and H2 receptor antagonists can prevent it. Numerous studies have shown that tachykinins are stored in carcinoid tumors and released during flushing. However, some studies have demonstrated that octreotide can relieve the flushing induced by pentagastrin in these patients without altering the stimulated increase in plasma substance P, suggesting that other mediators must be involved in the flushing. A correlation between plasma tachykinin levels, but not substance P levels, and flushing has been reported. Both histamine and serotonin may be responsible for the wheezing as well as the fibrotic reactions involving the heart, causing Peyronie's disease and intraabdominal fibrosis. The exact mechanism of the heart disease has remained unclear, although increasing evidence supports a central role for serotonin. The valvular heart disease caused by the appetite-suppressant drug dexfenfluramine is histologically indistinguishable from that observed in carcinoid disease. Furthermore, ergot-containing dopamine receptor agonists used for Parkinson's disease (pergolide, cabergoline) cause valvular heart disease that closely resembles that seen in the carcinoid syndrome. Metabolites of fenfluramine, as well as the dopamine receptor agonists, have high affinity for serotonin receptor subtype 5-HT2B receptors, whose activation is known to cause fibroblast mitogenesis. Serotonin receptor subtypes 5-HT1B,1D,2A,2B normally are expressed in human heart valve interstitial cells. High levels of 5-HT2B receptors are known to occur in heart valves and occur in cardiac fibroblasts and cardiomyocytes. Studies of cultured interstitial cells from human cardiac valves have demonstrated that these valvulopathic drugs induce mitogenesis by activating 5-HT2B receptors and stimulating upregulation of transforming growth factor β and collagen biosynthesis. These observations support the conclusion that serotonin overproduction by carcinoid tumors is important in mediating the valvular changes, possibly by activating 5-HT2B receptors in the endocardium. Both the magnitude of serotonin overproduction and prior chemotherapy are important predictors of progression of the heart disease. Atrial natriuretic peptide (ANP) overproduction also has been reported in patients with cardiac disease, but its role in the pathogenesis is unknown. However, high plasma levels of ANP have a worse prognosis. Plasma connective tissue growth factor levels are elevated in many fibrotic conditions; elevated levels occur in patients with carcinoid heart disease and correlate with the presence of right-ventricular dysfunction and the extent of valvular regurgitation in patients with carcinoid tumors.
Synthesis, secretion, and metabolism of serotonin (5-HT) in patients with typical and atypical carcinoid syndromes. 5-HIAA, 5-hydroxyindolacetic acid.
Patients may develop either a typical or, rarely, an atypical carcinoid syndrome. In patients with the typical form, which characteristically is caused by a midgut carcinoid tumor, the conversion of tryptophan to 5-HTP is the rate-limiting step (Fig. 350-1). Once 5-HTP is formed, it is rapidly converted to 5-HT and stored in secretory granules of the tumor or in platelets. A small amount remains in plasma and is converted to 5-HIAA, which appears in large amounts in the urine. These patients have an expanded serotonin pool size, increased blood and platelet serotonin, and increased urinary 5-hydroxyindolacetic acid (5-HIAA). Some carcinoid tumors cause an atypical carcinoid syndrome that is thought to be due to a deficiency in the enzyme dopa decarboxylase; thus, 5-HTP cannot be converted to 5-HT (serotonin), and 5-HTP is secreted into the bloodstream (Fig. 350-1). In these patients, plasma serotonin levels are normal but urinary levels may be increased because some 5-HTP is converted to 5-HT in the kidney. Characteristically, urinary 5-HTP and 5-HT are increased, but urinary 5-HIAA levels are only slightly elevated. Foregut carcinoids are the most likely to cause an atypical carcinoid syndrome.
One of the most immediate life-threatening complications of the carcinoid syndrome is the development of a carcinoid crisis. This is more common in patients who have intense symptoms or have greatly increased urinary 5-HIAA levels (i.e., >200 mg/d). The crises may occur spontaneously or be provoked by stress, anesthesia, chemotherapy, or a biopsy. Patients develop intense flushing, diarrhea, abdominal pain, cardiac abnormalities including tachycardia, hypertension, or hypotension. If not adequately treated, this can be a terminal event.
Diagnosis of the Carcinoid Syndrome and Carcinoid Tumors
The diagnosis of carcinoid syndrome relies on measurement of urinary or plasma serotonin or its metabolites in the urine. The measurement of 5-HIAA is used most frequently. False-positive elevations may occur if the patient is eating serotonin-rich foods such as bananas, pineapples, walnuts, pecans, avocados, or hickory nuts or is taking certain medications (cough syrup containing guaifenesin, acetaminophen, salicylates, serotonin reuptake inhibitors, or l-dopa). The normal range in daily urinary 5-HIAA excretion is 2–8 mg/d. Serotonin overproduction was noted in 92% of patients with carcinoid syndrome in one study, and in another study, 5-HIAA had 73% sensitivity and 100% specificity for carcinoid syndrome.
Most physicians use only the urinary 5-HIAA excretion rate; however, plasma and platelet serotonin levels, if available, may provide additional information. Platelet serotonin levels are more sensitive than urinary 5-HIAA but are not generally available. Because patients with foregut carcinoids may produce an atypical carcinoid syndrome, if this syndrome is suspected and the urinary 5-HIAA is minimally elevated or normal, other urinary metabolites of tryptophan, such as 5-HTP and 5-HT, should be measured (Fig. 350-1).
Flushing occurs in a number of other diseases, including systemic mastocytosis, chronic myeloid leukemia with increased histamine release, menopause, reactions to alcohol or glutamate, side effects of chlorpropamide, calcium channel blockers, and nicotinic acid. None of these conditions cause increased urinary 5-HIAA.
The diagnosis of carcinoid tumor can be suggested by the carcinoid syndrome, recurrent abdominal symptoms in a healthy-appearing individual, or the discovery of hepatomegaly or hepatic metastases associated with minimal symptoms. Ileal carcinoids, which make up 25% of all clinically detected carcinoids, should be suspected in patients with bowel obstruction, abdominal pain, flushing, or diarrhea.
Serum chromogranin A levels are elevated in 56–100% of patients with carcinoid tumors, and the level correlates with tumor bulk. Serum chromogranin A levels are not specific for carcinoid tumors because they are also elevated in patients with PETs and other neuroendocrine tumors. Plasma neuron-specific enolase levels are also used as a marker of carcinoid tumors but are less sensitive than chromogranin A, being increased in only 17–47% of patients.
Treatment: Carcinoid Syndrome and Nonmetastatic Carcinoid Tumors
Treatment includes avoiding conditions that precipitate flushing, dietary supplementation with nicotinamide, treatment of heart failure with diuretics, treatment of wheezing with oral bronchodilators, and control of the diarrhea with antidiarrheal agents such as loperamide and diphenoxylate. If patients still have symptoms, serotonin receptor antagonists or somatostatin analogues (Fig. 350-2) are the drugs of choice.
Structure of somatostatin and synthetic analogues used for diagnostic or therapeutic indications.
There are 14 subclasses of serotonin receptors, and antagonists for many are not available. The 5-HT1 and 5-HT2 receptor antagonists methylsergide, cyproheptadine, and ketanserin have all been used to control the diarrhea but usually do not decrease flushing. The use of methylsergide is limited because it can cause or enhance retroperitoneal fibrosis. Ketanserin diminishes diarrhea in 30–100% of patients. 5-HT3 receptor antagonists (ondansetron, tropisetron, alosetron) can control diarrhea and nausea in up to 100% of patients and occasionally ameliorate the flushing. A combination of histamine H1 and H2 receptor antagonists (i.e., diphenhydramine and cimetidine or ranitidine) may control flushing in patients with foregut carcinoids.
Synthetic analogues of somatostatin (octreotide, lanreotide) are now the most widely used agents to control the symptoms of patients with carcinoid syndrome (Fig. 350-2). These drugs are effective at relieving symptoms and decreasing urinary 5-HIAA levels in patients with this syndrome. Octreotide-LAR and lanreotide-SR/autogel (Somatuline) control symptoms in 74% and 68%, respectively, of patients with carcinoid syndrome and show a biochemical response in 51% and 39%. Patients with mild to moderate symptoms usually are treated initially with octreotide 100 μg SC every 8 h and begun on long-acting monthly depot forms (octreotide-LAR or lanreotide-autogel). Forty percent of patients escape control after a median time of 4 months, and the depot dosage may have to be increased as well as supplemented with the shorter-acting formulation, SC octreotide.
Carcinoid heart disease is associated with a decreased mean survival (3.8 years), and therefore it should be sought for and carefully assessed in all patients with carcinoid syndrome. Transthoracic echocardiography remains a key element in establishing the diagnosis of carcinoid heart disease and determining the extent and type of cardiac abnormalities. Treatment with diuretics and somatostatin analogues can reduce the negative hemodynamic effects and secondary heart failure. It remains unclear whether long-term treatment with these drugs will decrease the progression of carcinoid heart disease. Balloon valvuloplasty for stenotic valves or cardiac valve surgery may be required.
In patients with carcinoid crises, somatostatin analogues are effective at both treating the condition and preventing their development during known precipitating events such as surgery, anesthesia, chemotherapy, and stress. It is recommended that octreotide 150–250 μg SC every 6 to 8 h be used 24–48 h before anesthesia and then continued throughout the procedure.
Currently, sustained-release preparations of both octreotide [octreotide-LAR (long-acting release), 10, 20, 30 mg] and lanreotide [lanreotide-PR (prolonged release, lanreotide-autogel), 60, 90, 120 mg] are available and widely used because their use greatly facilitates long-term treatment. Octreotide-LAR (30 mg/month) gives a plasma level ≥1 ng/mL for 25 days, whereas this requires three to six injections a day of the non-sustained-release form. Lanreotide autogel (Somatuline) is given every 4–6 weeks.
Short-term side effects occur in up to one-half of patients. Pain at the injection site and side effects related to the GI tract (59% discomfort, 15% nausea, diarrhea) are the most common. They are usually short-lived and do not interrupt treatment. Important long-term side effects include gallstone formation, steatorrhea, and deterioration in glucose tolerance. The overall incidence of gallstones/biliary sludge in one study was 52%, with 7% having symptomatic disease that required surgical treatment.
Interferon α is reported to be effective in controlling symptoms of the carcinoid syndrome either alone or combined with hepatic artery embolization. With interferon α alone the response rate is 42%, and with interferon α with hepatic artery embolization, diarrhea was controlled for 1 year in 43% and flushing was controlled in 86%.
Hepatic artery embolization alone or with chemotherapy (chemoembolization) has been used to control the symptoms of carcinoid syndrome. Embolization alone is reported to control symptoms in up to 76% of patients, and chemoembolization (5-fluorouracil, doxorubicin, cisplatin, mitomycin) in 60–75% of patients. Hepatic artery embolization can have major side effects, including nausea, vomiting, pain, and fever. In two studies 5–7% of patients died from complications of hepatic artery occlusion.
Other drugs have been used successfully in small numbers of patients to control the symptoms of carcinoid syndrome. Parachlorophenylanine can inhibit tryptophan hydroxylase and therefore the conversion of tryptophan to 5-HTP. However, its severe side effects, including psychiatric disturbances, make it intolerable for long-term use. α-Methyldopa inhibits the conversion of 5-HTP to 5-HT, but its effects are only partial.
Peptide radioreceptor therapy (using radiotherapy with radiolabeled somatostatin analogues), the use of radiolabeled microspheres, and other methods for treatment of advanced metastatic disease may facilitate control of the carcinoid syndrome and are discussed in a later section dealing with treatment of advanced disease.
Carcinoid Tumors (Nonmetastatic)
Surgery is the only potentially curative therapy. Because with most carcinoids the probability of metastatic disease increases with increasing size, the extent of surgical resection is determined accordingly. With appendiceal carcinoids <1 cm, simple appendectomy was curative in 103 patients followed for up to 35 years. With rectal carcinoids <1 cm, local resection is curative. With small-intestinal carcinoids <1 cm, there is not complete agreement. Because 15–69% of small-intestinal carcinoids this size have metastases in different studies, some recommend a wide resection with en bloc resection of the adjacent lymph-bearing mesentery. If the carcinoid tumor is >2 cm for rectal, appendiceal, or small- intestinal carcinomas, a full cancer operation should be done. This includes a right hemicolectomy for appendiceal carcinoid, an abdominoperineal resection or low anterior resection for rectal carcinoids, and an en bloc resection of adjacent lymph nodes for small-intestinal carcinoids. For carcinoids 1–2 cm in diameter for appendiceal tumors, a simple appendectomy is proposed by some, whereas others favor a formal right hemicolectomy. For rectal carcinoids 1–2 cm, it is recommended that a wide local full-thickness excision be performed.
With type I or II gastric carcinoids, which are usually <1 cm, endoscopic removal is recommended. In type I or II gastric carcinoids, if the tumor is >2 cm or if there is local invasion, some recommend total gastrectomy, whereas others recommend antrectomy in type I to reduce the hypergastrinemia, which led to regression of the carcinoids in a number of studies. For types I and II gastric carcinoids of 1–2 cm, there is no agreement, with some recommending endoscopic treatment followed by chronic somatostatin treatment and careful follow-up and others recommending surgical treatment. With type III gastric carcinoids >2 cm, excision and regional lymph node clearance are recommended. Most tumors <1 cm are treated endoscopically.
Resection of isolated or limited hepatic metastases may be beneficial and will be discussed in a later section on treatment of advanced disease.