GIT

Question 1

What Is Crohn’s Disease?

Answer 1

• Crohn’s disease is one of two chronic inflammatory bowel diseases (IBDs), the other being ulcerative colitis.
• It follows a relapsing, remitting course, usually over many years.
• Unlike ulcerative colitis, which only involves the colon, Crohn’s disease can affect any part of the gastrointestinal tract from the mouth to the anus. Fifty percent of patients have both terminal ileum and colon involvement, 20% have colonic involvement only, and 30% have disease confined to the small bowel. The rectum is typically spared, but 25% of patients have perianal disease [1].
• Crohn’s disease is characterized by a patchy distribution of skip lesions, i.e., diseased sections of the gastrointestinal tract are interrupted by
  uninvolved areas.
• Extraintestinal manifestations of Crohn’s disease are common and not necessarily related to relapses of intestinal disease. Crohn’s disease has a slight female preponderance, is more common in smokers, and usually starts in the second or third decade of life.
• Its incidence is increasing – currently it is 3–20 per 100,000 [2, 3]. It has both environmental and genetic components, e.g., 10% of Crohn’s disease sufferers have a first-degree relative with the condition, and there is a 40–50% rate of concordance among identical twins [4].
• The histological features account for many of the clinical sequelae seen in Crohn’s disease patients. The first thing to note is that in addition to its variable location, inflammation is transmural. Three phenotypic subtypes are described: inflammatory, stricturizing, and fistulizing. Initial inflamma-
  tion can progress to fibrosis and narrowing of the bowel lumen, which may result in bowel obstruction. Deep ulcers, which appear as linear fissures, can penetrate the bowel wall leading to abscess formation or development of fistulae between the bowel, bladder, vagina, uterus, or perineal skin;
  50–80% of patients will eventually require surgery for complications of Crohn’s disease.

Question 2

What Are the Common Classifications of Crohn’s Disease?

Answer 2

• Clinically, the disease is classified according to severity (mild, moderate, or severe), location (upper gastrointestinal, ileocolic, ileal, colonic, or perianal), and phenotype (inflammatory, stricturizing, and fistulizing).
• The Crohn’s Disease Activity Index (CDAI) (Table 24.1) is used for defining severity of disease activity, defining whether or not a patient is in remission, and response to treatment [1, 5].
• Crohn’s disease is deemed to be in clinical remission when CDAI <150, mild when CDAI is 150–220, moderate to severe when CDAI is 220–450, and severe-fulminant when CDAI >450.
• A simplified variant of the CDAI, the Harvey-Bradshaw index (Fig. 24.1) can also be used to grade disease activity

Question 3

What Are the Risk Factors for Aggressive
Disease Activity?

Answer 3

The natural course of Crohn’s disease ranges from that of an
indolent course with long periods of remission to aggressive
and incapacitating disease [7]. Aggressive disease is
considered to be that which has a high relapse rate with
penetrating disease requiring repeat surgeries or multiple
admissions for flare-ups. Age of diagnosis less than 30 years,
involvement of the upper gastrointestinal tract and ileum,
perianal disease, deep ulceration, prior surgery, and
stricturizing or penetrating disease are risk factors for
aggressive disease activity [2].

Question 4

What Medications Can We Expect to See
Prescribed for the Crohn’s Disease Patient?

Answer 4

Glucocorticoids
Enteric-coated budesonide is considered the treatment of
choice for inducing remission in patients with low-risk
disease of the ileum and proximal colon [10]. The aim of
treatment with budesonide is induction of remission within a
12-week period followed by tapering and discontinuation.
Glucocorticoids are also used as first-line therapy in patients
with moderate to severe disease who require a fast treatment
response prior to maintenance treatment with azathioprine or
an anti-TNF agent [10].
5-Aminosalicylates (5-ASA): Sulfasalazine,
Mesalamine
5-ASA formulations can be used for the treatment of mild to
moderate disease when glucocorticoid avoidance is
preferable. It decreases cyclooxygenase enzyme activity and
subsequently decreases the formation of pro-inflammatory
prostaglandins. Sulfasalazine was developed to deliver both
an anti-inflammatory agent, 5-ASA, and anti-bacterial agent,
sulfapyridine [11]. Up to 25% of patients taking sulfasalazine
discontinue taking it due to unwanted effects, e.g., hypersensitivity reactions, bone marrow suppression,
pancreatitis, and pneumonitis [12, 13]. Sulfapyridine is
responsible for many of the unwanted effects of sulfasalazine.
A 5-ASA formulation without the sulfa group, mesalamine,
is tolerated by most patients with sulfasalazine intolerance.
Unlike sulfasalazine, which is only partially absorbed in the
jejunum, mesalamine is rapidly absorbed in the jejunum with
only 20% of drug reaching the terminal ileum and colon
[12]. A number of enterically coated mesalamine formula-
tions have subsequently been developed to increase delivery
to affected areas.
Immunomodulators
The thiopurines (azathioprine and 6-mercaptopurine) are the
most commonly used agents in this category for the manage-
ment of Crohn’s disease. They are typically used for patients
who require glucocorticoids to maintain remission, i.e., they
are glucocorticoid-sparing agents.
Methotrexate
This may be a useful choice for maintenance therapy in
patients who cannot tolerate thiopurines. A clinical response
is usually seen within 3 months and patients are maintained
on glucocorticoid agents with an eventual tapering dose until
this response is achieved.
Antibiotics
The use of antibiotics for the treatment of active Crohn’s
disease is controversial, relating to inconsistencies in the
supporting evidence. A systematic review and meta-analysis
of 10 studies involving 1160 patients found a modest benefit
over placebo for inducing remission [14]. However, the wide
range of antibiotics used made the data difficult to interpret.
The commonest antibiotics used in the treatment of Crohn’s
disease are metronidazole and ciprofloxacin.
Anti-TNF Agents
Sometimes called biologic agents, the commonest anti-TNF
therapies used in Crohn’s disease are the monoclonal anti-
bodies infliximab (Remicade®) and adalimumab (Humira®).
These are usually used in combination with an immunomod-
ulator, e.g., azathioprine, to induce and maintain remission in
patients with moderate to severe disease.
Ustekinumab (Stelara)
This is a monoclonal antibody which is used as a second-line
therapy if anti-TNF agents have been tried unsuccessfully. It
is an interleukin-12 and interleukin-23 antagonist. Unwanted
effects include increased risk of infection, upper respiratory
infection being of particular relevance perioperatively.

Question 5

What Instructions Should Be Given
to Patients with Regard to Discontinuation
of Medications Prescribed for Management
of Crohn’s Disease?

Answer 5

5-ASA is primarily excreted renally. It is reasonable to
discontinue 1 day before surgery in patients with, or at risk
of, decreased glomerular filtration rate.
Immunosuppressive and immune modulating agents, e.g.,
azathioprine, methotrexate, glucocorticoids and the biologic
agents have been implicated in causing postoperative
infection and septic complications [15]. A preoperative drug-
free interval has been proposed as being advisable if feasible
[15]. The following paragraphs will discuss each drug
separately.
For patients taking glucocorticoids preoperatively, it is
preferable that these be discontinued prior to surgery to
minimize complications associated with chronic use. However,
this is rarely possible as it is usually patients with disease
refractory to other medications, and are steroid dependent,
who require surgery. Stopping steroid therapy in this popula-
tion may lead to more severe symptoms such as complete
obstruction. Subsequently, many patients are likely to be on
chronic glucocorticoid therapy and may require surgical stress
dosing. This topic has been explored in detail in Chap. 19. A
recent review on this subject suggests that the patient taking
any dose of glucocorticoid for less than 3 weeks or those tak-
ing prednisone 5 mg daily for any period of time do not need
steroid stress dose administration [16]. There are numerous
practical approaches towards the patient with potential hypo-
thalamic-pituitary-adrenalaxis (HPAA) suppression in the
perioperative period. This includes that which calls for main-
tenance of the usual steroid dose throughout the surgical
period and treating hypotension with rescue dose steroid [16,
17]. A more nuanced approach assesses the risk of HPAA sup-
pression based on the clinical picture and/or the ACTH stimu-
lation test. Patients at high risk of HPAA, e.g., presence of
Cushingoid features, use of prednisone 20 mg/day or greater,
are treated with stress dose steroids; patients at low risk, e.g.,
< prednisone 5 mg/day, do not require stress dosing [16]. An
approach to the dosing required according to surgical type, as
adapted from Liu et al., is provided in Table 24.2 [16]
Azathioprine has been associated with antagonism of
neuromuscular blocking agents [11, 18]. There is also a
theoretical risk of perioperative bone marrow suppression
especially in patients with renal impairment. A cautious
approach in patients with compromised renal function would
be to hold azathioprine on the day of surgery and resume
once renal function does not deteriorate further in the post-
operative period [11].
Continuation of anti-TNF agents is contentious [19].
Some single-center studies have found an increased risk of
infectious complications with preoperative use of anti-TNFα
medications. A meta-analysis of 18 studies found that they
significantly increased postoperative infectious complica-
tions (OR = 1.93) [19, 20]. However, the overall consensus
from retrospective reviews, prospective studies, and meta-
analyses points towards a lack of convincing evidence for
postoperative complications with the preoperative use of
anti-TNFα medications [19].
There are no definitive guidelines regarding periopera-
tive use of ustekinumab. A small cohort study looked at
postoperative complications in patients who had been
treated with ustekinumab within 4 months of surgery
compared with a control cohort of anti-TNF-treated patients
[21]. There were no significant differences in early or late
wound infections, anastomotic leak, or postoperative ileus
between the groups.

Question 6

What Are the Indications for Surgery
in Crohn’s Disease?

Answer 6

Most patients with Crohn’s disease will require surgery at
least once, and some patients require multiple surgical
procedures. Surgery is not curative but may be required for
some of the complications associated with the disease. It is
usually performed for obstructive complications due to
strictures or for complications related to fistulae. Patients
unresponsive to medical therapy or those who are steroid
dependent also require surgery [1]. Urgent/semi-urgent
indications for surgery include uncontrolled bleeding, toxic
megacolon, and dysplasia.

Question 7

Are There Any Specific Concerns That Need
to Be Addressed Preoperatively in This
Patient Population?

Answer 7

Patients undergoing open abdominal surgery are at increased
risk for postoperative pulmonary complications, e.g., atelec-
tasis, pneumonia, respiratory failure, and prolonged mechan-
ical ventilation. Patients with chronic obstructive pulmonary
disease should be assessed and optimized as outlined in
Chap. 14 and patients who smoke should be offered counsel-
ing on stopping. The preoperative visit may also be an opportune time for patient education on breathing exercises such
as incentive spirometry.
Patients with IBD may have chronic anemia from persis-
tent gastrointestinal bleeding, may have active infection, or
can be immunosuppressed from medication. Laboratory
investigations should be directed accordingly.
Patients with ankylosing spondylitis require a thorough air-
way assessment, including range of neck motion evaluation.
The plan for intubation should be discussed with the patient.
Patients requiring a stoma will require counseling and edu-
cation. Preoperative education is associated with fewer stoma-
related postoperative complications and earlier hospital
discharge [22, 23]. Stoma site selection can also be performed
at the preoperative anesthesia visit, ideally in collaboration
between the patient, the stoma nurse, and the surgeon

Question 8

How Is Nutritional Status Assessed
Preoperatively?

Answer 8

Malnutrition is an independent risk factor for postoperative
complications including poor surgical wound healing and
prolonged ventilation. It is seen in up to 70% of patients with
inflammatory bowel disease [24, 25]. Body mass index (BMI),
unintentional weight loss, body fat percentage, and reduced
dietary intake are commonly used clinical measures of
nutritional status. Serum albumin (<30 g/L), prealbumin,
transferrin, total cholesterol, and triiodothyronine (T3) can be
used as surrogate serologic markers of nutritional status [25].
Oral nutritional supplements may be required preoperatively
and if the patient’s caloric needs (which are typically high due
to malnutrition and the need to boost nutritional status before
surgery) cannot be met using oral supplementation, enteral
nutrition through a nasogastric or nasoenteric tube may be
indicated. Guidelines issued by the European Society for
Clinical Nutrition and Metabolism (ESPEN) recommend
delaying surgery for 1–2 weeks if malnutrition is identified in
IBD patients to allow enteral nutrition to be commenced [26].
Our approach is to screen patients with the Canadian Nutrition
Screening Tool [27]. A dietician is consulted if the patient is
flagged with this tool. If there is no weight gain with outpatient
dietician support, enteral nutrition is commenced. The enteral
route is preferred unless there is a strong indication for
parenteral feeding, e.g., complete obstruction.

Question 9

What Perioperative Precautions Should
Be Taken for Venous Thromboembolism
Prophylaxis in the Patient with Crohn’s
Disease?

Answer 9

Patients with IBD having intra-abdominal surgery are at
increased of thromboembolism compared with patients
without IBD and that includes patients having surgery for
abdominal neoplasms. No guidelines have been published
for VTE prophylaxis in this specific population. It is recom-
mended that patients with Crohn’s disease receive VTE pro-
phylaxis based on American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (eighth
Edition), i.e., for laparotomy, 5000u subcutaneous unfrac-
tionated heparin three times daily or 40 mg subcutaneous
enoxaparin once daily [11, 28

Question 10

How Should This Patient Be Educated
Regarding Postoperative Pain Control?

Answer 10

This patient uses opioid analgesia on a regular basis preop-
eratively. Postoperative opioid requirements will likely be
higher than in the opioid naïve patient and she is at risk for
chronic postsurgical pain and chronic postsurgical opioid use
[29, 30]. As a regular cannabis smoker, she may have more
difficulty with postoperative analgesia and may have
increased opioid requirements [31, 32].
A thorough history of opioid consumption is required
including average consumption of “as required” opioids
taken daily, in this case oxycodone. She should be advised to
continue using her fentanyl patch throughout the periopera-
tive period. For more complex surgeries with large fluid
shifts, contingencies need to be made for incomplete absorp-
tion. If this is the case, transdermal fentanyl should be
replaced with equipotent morphine or hydromorphone.
There is evidence to suggest that opioid-tolerant patients are
resistant to local anesthetic nerve blockade [33, 34]. Dosing
of adjunctive opioid and non-opioid analgesia will need to be
adjusted accordingly if a regional anesthesia technique is
used, e.g., epidural analgesia or continuous transversus
abdominis plane nerve blockade.

Question 11

Is There Evidence That NSAID Use Is a Risk
Factor for Disease Exacerbation?

Answer 11

This patient uses opioid analgesia on a regular basis preop-
eratively. Postoperative opioid requirements will likely be
higher than in the opioid naïve patient and she is at risk for
chronic postsurgical pain and chronic postsurgical opioid use
[29, 30]. As a regular cannabis smoker, she may have more
difficulty with postoperative analgesia and may have
increased opioid requirements [31, 32].
A thorough history of opioid consumption is required
including average consumption of “as required” opioids
taken daily, in this case oxycodone. She should be advised to
continue using her fentanyl patch throughout the periopera-
tive period. For more complex surgeries with large fluid
shifts, contingencies need to be made for incomplete absorp-
tion. If this is the case, transdermal fentanyl should be
replaced with equipotent morphine or hydromorphone.
There is evidence to suggest that opioid-tolerant patients are
resistant to local anesthetic nerve blockade [33, 34]. Dosing
of adjunctive opioid and non-opioid analgesia will need to be
adjusted accordingly if a regional anesthesia technique is
used, e.g., epidural analgesia or continuous transversus
abdominis plane nerve blockade

Question 12

Is There Evidence That NSAID Use Is a Risk
Factor for Disease Exacerbation?

Answer 12

NSAIDs are usually associated with aggravation of pre-
existing disease and are occasionally implicated in the devel-
opment of new-onset colitis [35, 36]. A number of studies
and reports examine the association between NSAID use and
worsening of Crohn’s disease, the mechanism likely being
related to cyclooxygenase inhibition and disruption of the
gut epithelium [35, 37]. Results are conflicting; there is some
evidence than infrequent use, i.e., less than 5 times per month
is not associated with disease exacerbation [38, 39].
Conversely, a number of studies find that NSAIDs provoke
existing Crohn’s disease [40, 41]. Unfortunately, most stud-
ies have small subject numbers, are of mediocre quality, and
do not make a meaningful contribution to the dialogue.
Given this paucity of evidence in favor of NSAID use, it may
be prudent to avoid their use when possible. If recourse to NSAID use is deemed necessary, a low dose of drug for a
short period of time is recommended. This should also be
discussed with the colorectal surgery team.

Question 13

What Are the Preoperative Considerations
in a Patient Who Smokes Marijuana
on a Daily Basis?

Answer 13

The chronic effects of smoking marijuana on a daily basis
include cough and chronic obstructive pulmonary disease,
similar to that seen in chronic tobacco smokers (Table 24.3)
[42]. Chronic marijuana smokers may be at higher risk of
developing atheromatous disease due to the relatively
high amount of carbon monoxide in marijuana cigarettes
[43]. Risk of myocardial infarction has been shown to be
elevated 4.8 times over baseline in the 60 minutes after
marijuana use [44]. Consideration should be given to
delaying elective surgery for over 1 hour if this becomes
evident.
Cannabis withdrawal syndrome can develop within
24 hours of cessation for high-dose chronic users and can
takes weeks to fully resolve [45]. Symptoms of withdrawal
include irritability, anger, anxiety, aggression, insomnia,
restlessness, anorexia, and abdominal cramping.
Administration of benzodiazepines and synthetic tetrahydro-
cannabinol (THC) may be useful for improving withdrawal
symptoms [42
Preoperative evaluation should include obtaining a history
of duration, frequency, dose, and route of use. Timing of
most recent use should be noted. Patients exhibiting signs of
acute intoxication in the immediate preoperative period, e.g.,
anxiety, paranoia, psychosis may be subject to more violent
emergence from anesthesia [42]. Cannabis-induced
psychosis resulting from the use of high-potency THC
formulations may present with a similar constellation of
symptoms (fever, tachycardia, hypertension) to that seen in
malignant hyperthermia, serotonin syndrome, neuroleptic
malignant syndrome, or thyrotoxicosis and may be mistaken
for these conditions

Question 14

True/False Questions
1. (a) Crohn’s disease is a relapsing, remitting chronic
inflammatory disease which only involves the colon
(b) Extraintestinal manifestations are rare in Crohn’s
disease
(c) Ankylosing spondylitis is an extraintestinal manifes-
tation of Crohn’s disease
(d) At least 50% of patients with Crohn’s disease will
eventually require surgery for associated
complications
(e) NSAID use is not a risk factor for disease
exacerbation

Question 15

2. (a) Glucocorticoids are frequently used as first line ther-
   apy in Crohn’s disease
   (b) Glucocorticoids should never be discontinued before
   surgery
   (c) Azathioprine is used as a steroid-sparing agent in
   patients who require glucocorticoids to maintain
   remission
   (d) Perioperative continuation of anti-TNF agents is
   strongly associated with postoperative complications
   (e) One of the main indications for surgery in Crohn’s
   disease is steroid dependency

Question 16

What Are Carcinoid Tumors?

Answer 16

• Carcinoid tumors are relatively rare neuroendocrine tumors most commonly arising from the gastrointestinal (GI) tract (60% of carcinoid tumors) followed by the bronchopulmonary system (27%) and most infrequently the kidneys and ovaries [1, 2].
• The breakdown according to location for carcinoid tumors within the GI tract is as follows: small intes-
  tine (34%), rectum (23%), colon (19%), stomach (8%), and appendix (7%) [3]. - The incidence of carcinoid tumor is approximately 2.5–5 per 100,000—this represents 0.49% of all malignancies [1].

Question 17

Do All Patients with a Carcinoid Tumor Have carcinoid Syndrome?

Answer 17

No.
- Carcinoid tumors are capable of secreting a range of GI peptides, e.g., insulin, somatostatin, glucagon, and gastrin as well as vasoactive substances such as serotonin, bradykinin, histamine, and tachykinins. Carcinoid syndrome results from systemic secretion of these vasoactive substances.
- About 10–20% of patients with a carcinoid tumor display symptoms and signs of carcinoid syndrome, i.e., flushing, diarrhea, hypotension, hypertension, and bronchoconstriction [4, 5].
- Flushing and diarrhea are the most common symptoms. Flushing is characterized by being of sudden onset, and can be precipitated by stress, exercise, alcohol, and certain foods or medications (discussed in detail below).
- Most patients with carcinoid syndrome have liver metastases in addition to a primary carcinoid tumor. Normally, serotonin is metabolized to 5-hydroxyindolacetic acid (5-HIAA) for renal excretion. In the presence of hepatic carcinoid metastases, this metabolic pathway is saturated by the large quantities of serotonin produced. More infrequently, a primary neuroendorine tumor in the lung gives rise to carcinoid syndrome without liver metastases.
- In this instance, the vasoactive products produced by the tumor bypass the liver and thus are not inactivated

Question 18

How Do Carcinoid Tumors Present?

Answer 18

Patients may present with the typical symptoms of carcinoid
syndrome, symptoms related to the mechanical effects of a
tumor mass, e.g., bowel obstruction or hepatomegaly, or
symptoms of carcinoid heart disease. Occasionally carcinoid
tumors are discovered incidentally during investigation and
work-up for other conditions.

Question 19

How Is a Diagnosis of Carcinoid Syndrome
Confirmed?

Answer 19

24-hour urinary excretion of 5-HIAA, the end-product of
serotonin metabolism, has a sensitivity and specificity of
over 90% for diagnosis of carcinoid syndrome.

Question 20

What Is Carcinoid Heart Disease?

Answer 20

• Carcinoid tumors can affect the heart in several ways.
• Twenty percent of carcinoid syndrome patients will initially present with cardiac symptoms. Carcinoid heart disease occurs in up to 50% of patients with carcinoid syndrome [6].
• Most patients with cardiac manifestations have hepatic carcinoid metastases. Elevated levels of serotonin and other vasoactive amines can precipitate vasovagal syncope, arrhythmias, and pulmonary hypertension. - Endocardial deposition of plaque-like fibrous tissue in the valves and myocardium of the right side of the heart causes myocardial fibrosis, and tricuspid and pulmonary valve dysfunction. Valvular regurgitation is
  the most common manifestation.
• The left side of the heart is normally spared due to metabolism of excess circulating serotonin by pulmonary monoamine oxidase.
• Left-sided cardiac involvement may indicate an intracardiac shunt, severe or poorly controlled carcinoid activity overwhelming pulmonary metabolism capability, or an endobronchial tumor.
• The incidence of left-sided heart involvement is 5–10% of carcinoid heart disease [1, 6].

Question 21

What Are the Clinical Manifestations of Carcinoid Heart Disease?

Answer 21

Cardiac-specific symptoms are frequently related to tricuspid and pulmonary regurgitation. Mild to moderate tricuspid regurgitation is usually asymptomatic. Patients with severe disease may display symptoms of right heart failure, e.g., peripheral edema, ascites, or painful hepatosplenomegaly.
- Similarly, patients with pulmonary regurgitation can be asymptomatic until the onset of right ventricular dysfunction at which time patients may display exertional dyspnea and fatigue, as well as atrial or ventricular arrhythmias giving rise to palpitations or syncope. Enlargement of the right ventricle can cause tricuspid regurgitation, if not already resent, due to carcinoid fibrous deposits.
- Though valvular involvement is the dominant clinical presentation, atypical presentations of carcinoid heart disease have been reported; coronary artery vasospasm with ST segment elevation, atrial fibrillation, ventricular tachycardia and fibrillation, and cardiac arrest have all been reported as
the primary presenting feature [7–10].

Question 22

What Is a Carcinoid Crisis?

Answer 22

This is a potentially fatal exacerbation of carcinoid syndrome that arises from the uncontrolled release of an overwhelming number of vasoactive hormones. This can be spontaneous or secondary to tumor handling, stress, administration of certain anesthetic agents (Boxes 25.1 and 25.2), or tumor necrosis caused by chemotherapy [1]. It is manifest clinically as intense flushing, edema, severe bronchospasm, and significant hemodynamic instability, including tachycardia, hypotension, or hypertension, which may be refractory to treatmen

Question 23

How Are Carcinoid Tumors Treated?

Answer 23

• Definitive treatment will depend on whether the disease is localized or metastatic.
• The presence of liver metastases is the most important factor affecting survival in patients with GI or pancreatic neuroendocrine tumors [11].
• The liver is the most common site for metastasis due to hematogenous
  spread via the portal venous drainage of the GI tract and pancreas [12].
• Liver metastases have been reported in up to 85% of patients with a primary neuroendocrine tumor, although a more conservative estimate puts the incidence closer to 40% [13, 14].
• Radiographic staging is commonly performed using CT, MRI, or somatostatin receptor imaging. Localized GI and bronchial carcinoid tumors are surgically resected even in the presence of liver metastases. If possible, surgical resection of liver metastases provides the best opportunity for long-term survival.
• However, fewer than 20% of patients with metastatic liver disease are eligible for metastasectomy or partial liver resection, due to wide dissemination of metastases or the expectation that liver volume after resection will be inadequate [11].
• Somatostatin analogs can be used for symptomatic treatment in patients with unresectable liver metastases.
• A variety of liver-directed therapies can be explored when liver disease is unresectable, e.g., thermal ablation, embolization, and cytotoxic chemotherapy [11

Question 24

How Are Patients with Carcinoid Tumors Optimized for Surgery?

Answer 24

-Preoperative evaluation should consist of
(1) determining the presence and/or extent of carcinoid syndrome, i.e., severity of symptoms related to vasoactive peptide release, and
(2) presence and/or extent of cardiac disease.
- Patients with persistent diarrhea require electrolyte and creatinine
measurement with subsequent volume resuscitation and correction of electrolyte abnormalities [15]. The presence of hypoalbuminemia may require nutritional supplementation.
- Abnormally elevated levels of serotonin and other vasoactive
amines are surrogates of tumor burden [1]. Preoperative optimization aims to antagonize these mediators of carcinoid syndrome. The somatostatin analogs octreotide and lanreotide inhibit a wide range of vasoactive hormones by binding to the somatostatin receptors that are expressed in the majority of neuroendocrine tumors [16]. Somatostatin is a peptide hormone
that regulates the endocrine system by inhibiting hormone secretion. These somatostatin analogs can control symptoms in more than 80% of patients with a carcinoid tumor [4]. Monthly depot injections of both octreotide and lanreotide are available and can be titrated for optimal symptom control. In addition to controlling vasoactive mediator release, somastatin analogs
have also been shown to control tumor growth of pancreatic and GI neuroendocrine tumors [17].
Echocardiographic evaluation of valvular and ventricular dysfunction is recommended even in the absence of symp-toms. As outlined above, moderate to severe carcinoid cardiac disease can be asymptomatic

Question 25

How Is Carcinoid Crisis Managed? Can Any
Measures Be Taken Preoperatively
to Prevent the Intraoperative Occurrence
of a Carcinoid Crisis?

Answer 25

Octreotide can be used prophylactically and for the manage-
ment of an evolving carcinoid crisis. Patients with a history
of carcinoid syndrome can be given up to 500 mcg intrave-
nously, as a bolus or by infusion, prior to surgical resection,
and this can be repeated intraoperatively if required.
Octreotide, 100–500 mcg intravenously can also be used to
treat carcinoid crisis. Higher doses may be required in
patients with previous exposure to octreotide and in patients
with carcinoid heart disease [18].
Despite the lack of signs and symptoms indicative of the
presence of carcinoid heart disease, an echocardiogram was
obtained, as recommended. This did not show any valvular
disease. The patient continued not to exhibit any symptoms
or signs of carcinoid syndrome. An electrolyte screen,
creatinine and liver function tests were normal on day before
surgery. The patient proceeded to have an uneventful
ileocolic resection.

Question 26

True-False Questions
1. (a) Most carcinoid tumors originate in the gastrointesti-
nal tract
(b) The stomach is the commonest location in the gastro-
intestinal tract for a carcinoid tumor to occur
(c) The majority of patients with a carcinoid tumor dis-
play symptoms of carcinoid syndrome
(d) Carcinoid syndrome can be diagnosed using 24-hour
urinary excretion of 5-HIAA
(e) Octreotide can be used to prevent the occurrence of
an intraoperative carcinoid crisis

Question 27

(a) Carcinoid heart disease is commonly associated with
carcinoid syndrome
(b) Pulmonary and tricuspid valvular stenosis are the
commonest valvular manifestations of carcinoid
heart disease
(c) The left and right sides of the heart are equally
affected in carcinoid heart disease
(d) Patients with severe carcinoid heart disease display
symptoms of right heart failure
(e) Most patients with carcinoid heart disease have
hepatic carcinoid metastases