# Vasoactive Intestinal Peptide Tumor

Authors: Naveed Natanzi; Mazyar Amini; David Yamini; Shawn Nielsen; Ramin Ram
Journal: Scholarly Research Exchange
 (2009)

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## Abstract

Background and aim.  Vasoactive intestinal peptide tumor is a rare neuroendocrine neoplasm which causes voluminous watery diarrhea via hypersecretion of electrolytes and water from the intestinal mucosa through a vasoactive intestinal peptide-mediated, cyclic AMP-dependent mechanism. The acid base imbalance generated by the loss of water and electrolytes leads to severe dehydration and potential renal failure, which can ultimately result in death if left untreated. This paper aims to review the clinical, histological, radiological, and diagnostic features of this disease as well as the therapeutic modalities in treating this condition.
Methods.  A review of literature was performed using MEDLINE, Pubmed, and Cochrane databases in collection of data using MeSH terms including vasoactive intestinal peptide,  VIPoma, and WDHA.
Results and conclusion.  Vasoactive intestinal peptide tumor is a rare neoplasm associated with significant morbidity and mortality through secretion of water and electrolytes in the gastrointestinal tract. The nonspecific clinical presentation of this neoplasm can pose diagnostic challenges, as these tumors can be easily misdiagnosed as other conditions, ranging from laxative overdose to the presence of a carcinoid secreting tumor. Nevertheless, a number of imaging and laboratory studies can facilitate the correct evaluation and diagnosis of VIPoma. Following proper diagnosis, VIPomas are treated by either medical or surgical modalities depending on the existence and extent of metastasis.


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## Body

## 1. Introduction

WDHA,
a syndrome characterized by watery diarrhea, hypokalemia, and achlorhydia was
first described by  Verner and  Morrison  in 1958 [1].  These classical
clinical findings in WDHA marked the impetus for uncovering the association
with vasoactive intestinal peptide tumors (VIPomas). VIPomas are neuroendocrine
neoplasms arising from the pancreas in 90% of the cases reported, while the
remaining 10% occur in other tissues of neural crest origin [2]. These tumors
excessively secrete vasoactive intestinal peptide (VIP), ahormone which
stimulates adenosine 3′,5′-cyclic phosphate (cAMP) production by the
intestinal tract.  Hypersecretion of VIP
induces a significant increase in cAMP levels, thereby causing massive emission
of water and electrolytes, namely, potassium [1, 2]. The acid-base imbalance
generated by the loss of water and electrolytes leads to dehydration and
potential renal failure, which can ultimately result in death if left untreated
[2].VIPomas can often
pose diagnostic challenges because of the nonspecific clinical presentation.  It can be easily misdiagnosed as several
other conditions, ranging from laxative overdose to the presence of a carcinoid
secreting tumor [3]. Nevertheless, a number of imaging and laboratory studies can
facilitate the correct evaluation and diagnosis of VIPoma.  Following proper diagnosis, VIPomas are
treated by either medical or surgical modalities depending on the existence and
extent of metastasis [4]. Remarkably, 50–60% of the cases
in the literature have metastasized at the time of diagnosis, regardless of the
primary origin of the tumor [2, 3].


## 2. Vasoactive Intestinal Peptide (VIP)

VIP
is a 28-amino acid neuropeptide which stimulates the production of cAMP by the
enteric system. The hormone also releases acetylcholine which induces
relaxation of vascular and nonvascular smooth muscles [1]. VIP is expressed in
neurons of the gastrointestinal tract, respiratory, urogenital tracts, as well
as in the central nervous system, primarily the hypothalamus, hippocampus, and
cortex [1]. However, a number of extrapancreatic neoplasms such as
neurofibromas, neuroblastomas, ganglioneuromas, ganglioblastomas, mastocytomas,
pheochromocytomas, esophageal carcinomas, small cell carcinomas of the lung,
and primary VIPoma of the liver have been reported to produce VIP in a
paraneoplastic process [2].Endogenously
produced at a physiological rate and concentration, VIP is responsible for a
number of functions, including regulation of gastrointestinal secretions.  The hormone functions as a potent stimulator
of adenylate cyclase, which induces the secretion of water and electrolytes by
intestinal mucosa [5]. Furthermore, VIP stimulates alkaline pancreatic juice
and acid secretion, lipolysis, glycogenolysis, pentagastrin secretion, and
inhibits histamine release [1], and is therefore widely considered to be a
major regulator of human intestinal motility [6].Normal VIP levels for a healthy adult range
from 0–30 pmol/L or 0–190 pg/mL [2, 7].  Patients with VIPoma generally have
elevated serum VIP levels ranging from 60 to as high as 2100 pg/mL [7]. Serum levels
greater than 200 pg/mL is considered by several authors as a likely indication
of VIPoma. Elevated
serum VIP can be used to make a preliminary diagnosis of VIPoma when correlated
clinically. Tissue sampling confirms the diagnosis.


## 3. Vasoactive Intestinal Peptide Tumor (VIPoma)

Originating in
amine precursor uptake and decarboxylation (APUD) cells of the
gastroenteropancreatic endocrine system and in adrenal or extra-adrenal
neurogenic sites [1], VIPoma is a rare tumor that stimulates excessive
production of the VIP hormone.  By
elevating VIP production, VIPoma causes symptomatic watery diarrhea through dysregulation
of electrolyte shift in the gastrointestinal tract.Although VIPoma
has also been referred to as pancreatic cholera, it should be clarified that
not all tumors arise from the pancreas. While 90% of known cases of this tumor
arise from pancreatic endocrine cells, the remaining 10% arise from neural
crest-derived tissues such as the pituitary, thyroid, adrenal medulla, and
sympathetic nerve chains [2]. When VIPoma is found in the pancreas, 75% of the
tumors occur in the corpus and cauda, while 25% occur in the pancreatic head,
which may be of radiologic importance for diagnosis and follow-up for treatment
[2]. Adult VIPomas are primarily neuroendocrine islet cell tumors of the
pancreas [1]. The liver is another known source for VIPoma [4]. Interestingly, childhood
VIPomas are more likely to form outside of the pancreas, in ganglioneuromas or
ganglioneuroblastomas, arising from the neural crest tissue of sympathetic
ganglia or the adrenal medulla [2, 5].


## 4. Incidence and Prevalence

The annual incidence
of VIPoma in the United States has been reported as 0.05–0.2 per million
adults [7]. Of the affected adult population, 65% are women and 35% are men,
whereas the pediatric population does not appear to have a gender predilection
[8].


## 5. Clinical Presentation

VIPoma patients
characteristically present with high volume, chronic, and intractable watery
diarrhea causing significant pH and electrolyte imbalances [7]. Furthermore,
there may also be an excessive loss of electrolytes resulting in hypo- or
achlorhydria, hypokalemia, hypercalcemia, and interestingly, hyperglycemia and
suffer clinically from a spectrum of related conditions [9]. The mechanisms of
this diabetogenic effect and the calcium derangements seen with this condition
are poorly understood.  These electrolyte
imbalances often result in many of the observed clinical symptoms: massive diarrhea, ECG abnormalities, muscle
weakness, and renal failure [1].Other symptoms
associated with these neoplasms include abdominal pain, bloating, nausea,
vomiting, skin rash, backache, facial flushing, and lethargy [7].  Furthermore, one author describes an
association of this condition to increased colonic polyps [7].


## 6. Diagnosis

Diagnosis of
VIPoma begins with a thorough history and clinical examination, followed by a
comprehensive metabolic and chemistry panel as well as a VIP level with close
attention to electrolytes such as potassium, sodium, chloride, as well
acid-base disturbances, and glucose levels.Computed
tomography (CT), visceral angiography, magnetic resonance imaging (MRI),
traditional and endoscopic ultrasound (EUS), and nuclear medicine scintigraphy
have all been used to image pancreatic neuroendocrine tumors. Currently, either
CT or MRI is the
imaging modalities of choice in the primary evaluation of VIPomas. During the
mid 1990s, two-phase dynamic incremental CT was considered standard, with a
reported sensitivity ranging from 64–82% [10, 11]. The
role of MRI, however, has quickly gained recognition as an equivalent, if not
superior, modality for diagnosing pancreatic tumors, with a reported
sensitivity of 75–100% [11, 12].
There is also a suggestion that MRI may be superior in imaging tumors less than
2.5 cm in diameter [12] with one retrospective study finding tumors as small as
1 cm in diameter [12].Transabdominal
ultrasonography (US)
has played a limited role in primary detection of pancreatic tumors with a
sensitivity of approximately 60%. There is, however, a clear role for US, and
in particular EUS, in patients undergoing both diagnostic and preoperative evaluations as it
provides high-resolution images of the pancreas and surrounding structures
[13]. In a relatively large prospective trial evaluating the use of EUS,
Anderson et al. found a sensitivity of 93% in detecting pancreatic tumors with
a mean tumor diameter of 1.51 cm [13]. Furthermore, EUS has showed the added
utility of allowing fine needle aspiration to distinguish visualized masses
further aiding in diagnosis, staging, and in determining a management strategy
[14, 15].Visceral
angiography is generally less sensitive than both MRI and CT in localizing
neuroendocrine tumors. With reported sensitivity of approximately 66% [10], the
clinician must weigh the risks of invasive angiography with the benefits of
information gained. In patients with hepatic dominant disease and substantial
symptoms caused by tumor bulk or release of VIP, procedures such as hepatic
artery embolization or chemoembolization may be of benefit [16, 17]. For these
patients, visceral angiography may provide important information preoperatively,
especially in preembolization vascular mapping [10].


## 7. Imaging

Following VIP
level analysis, magnetic resonance imaging (MRI) and computed tomography (CT)
are employed for localization of disease, and aid in biopsy and determining
resectability (see Figure1). Naturally, the sensitivity of these two imaging
techniques improves with increasing tumor size [12, 18]. If the tumor is larger
than 3 cm, there is a 50–80% sensitivity
in its identification via imaging, while one which is smaller than 3 cm can be
detected with a 30–40% sensitivity
[12, 18]. These imaging techniques also yield useful information regarding the
local anatomy of the tumor, presence of metastases, staging, and may ultimately
affect the decision of medical versus surgical management.MRI: MRI scans obtained with permission
from a 32 year-old male with a mass in the region of the tail of the pancreas. (a)
Coronal HASTE image through the plane of the gall bladder fossa demonstrates
multiple liver lesions which are heterogeneous and fully to moderately
hyperintense (arrows). (b) Fat suppressed axial image through the tail of the
pancreas demonstrates a low-attenuation lesion in the region of the tail of the
pancreas which is conspicuous against a background of high signal intensity
pancreas (short arrow). Liver metastasis in the medial segment of the left lobe
of the liver is also observed (long arrow). (c) Preconstrast T1-weighted
axial image at the level of the portal vein demonstrates multiple low-attenuation
lesions throughout the liver (arrows), predominantly located in the left lobe. (d) Early postgadolinium axial T1-weighted image demonstrates
radial enhancement of the multiple liver lesions, suggestive of metastases from
a neuroendocrine tumor. These
images are courtesy of Dr. Richard Semelka of University of North
Carolina, Chapel Hill.
(a)(b)(c)(d)


## 8. Scintigraphy

Additionally, a
more advanced method of detecting islet-cell tumors, including VIPomas, has been reported by
Virgolini et al. [19].  Somatostatin
receptor scintigraphy employs the use somatostatin analogs in binding with the high affinity
receptors overexpressed in a number of such tumors [19]. One such procedure is
known as the octreotide scan. In this procedure, the patient is given a small
amount of a radioactive agent, usually Indium111-labeled octreotide that is
absorbed by the VIPoma [19]. Other markers, beside Indium111-labeled
octreotide, include radiolabelled DOTA-Tyr(3)-octreotide and
DOTA-Tyr(3)-octreotate derivatives which have shown considerable improvement of
imaging results with increased tumor uptake [19]. Of note, the (68)Ga-labelled
DOTA-Tyr(3)-octreotide scan has been demonstrated with promising success for
pancreatic islet-cell tumors, as it has been attributed to its high-affinity
binding to the somatostatin receptor subtype 2 in combination with positron
emission tomography (PET) technology [19]. Finally, there have been reports of
the successful use of iodine-123-VIP scintigraphy, further adding an important
assay to the diagnostic armamentarium [20].
The combination of diagnostic techniques allows more comprehensive staging and guide in the
management of such tumors.


## 9. Other Diagnostic Modalities

Other
diagnostic procedures such as arteriography, endosonagraphy, and venous
sampling can aid in the diagnosis of VIPomas [21, 22]. These processes have
been demonstrated to be effective, and are considered when a diagnosis is
unclear or further anatomical or metastatic information is required.


## 10. Histology

After
imaging studies localize the tumor, sampling of the tissue in the form of a
biopsy or aspirate yields the final and official diagnosis. Histologically, a
VIPoma demonstrates a composition of uniform, small to intermediate-sized cells
in clusters, nests, and trabecular growth patterns with hyperchromatic nuclei and scant
cytoplasm [23]. A few nests may also exhibit psuedorosettes [23].
Immunohistochemistry of this entity typically reveals positive immunoreactivity
for vasoactive intestinal peptide, cytokeratin, neuron specific enolase,
chromogranin, synaptophysin and somatostatin, and negative reactivity for S100,
calcitonin, PSA, CEA, insulin, glucagon, and growth hormone [23].  (See Figure 2).Histology:  (a) this image reveals uniform, small- to intermediate-sized
cells in clusters, nests, and trabecular growth pattern. The cells demonstrate enlarged
hyperchromatic nuclei and scant cytoplasm. A few nests may exhibit
psuedorosettes. (b) Immunohistochemistry of this entity typically reveals
positive immunoreactivity for vasoactive intestinal peptide (VIP). VIPoma also
stains positive cytokeratin, neuron-specific enolase, chromogranin,
synaptophysin and somatostatin, and negative reactivity for S100, calcitonin,
PSA, CEA, insulin, glucagon, and growth hormone(not shown).
(a)(b)


## 11. Staging

Proper diagnosis
and staging of VIPoma are the most principal determinants of treatment
modalities. Due to the relative rarity of VIPoma, even among other
neuroendocrine tumors, this entity is usually discussed together with
somatostatinoma and pancreatic polypeptide cancers in the “miscellaneous”
islet cell carcinoma category, separate from their more common and somewhat
better studied counterparts:
gastrinoma, insulinoma, and glucagonoma [16].


## 12. General Treatment Principles

According to the
most recent recommendations of the National Cancer Institute (NCI), surgery
constitutes the mainstay of therapy, and should be considered standard of care
when tumors are localized and lend themselves to resection. Without metastases,
a single lesion in the head of the pancreas or a small lesion (less than 1.0 cm) in the body or tail of the pancreas can be treated with enucleation if
surgically feasible [16]. For larger lesions in the body or tail or for
multiple pancreatic tumors, distal pancreatectomy [16] or Whipple procedure may
be performed depending upon the intraoperative findings [10].  Metastatic disease to lymph nodes or distant
sites and VIPomas originating in locations other than the pancreas should also
be resected when possible [16]. There is limited data on the utility of
radiofrequency [16, 24] and cryosurgical ablation [16] when disease sites are
not resectable by conventional techniques.In the majority of
patients with pancreatic neuroendocrine cancers, an aggressive surgical
approach is indicated with the intent of cure via complete resection of the
primary lesion and metastases [10]. Surgical cure is less feasible in those
patients with advanced metastatic disease and, therefore, determining the
extent of disease as well as the size and anatomic locations of any metastases plays
a pivotal role in defining a management strategy. For this purpose, surgical
exploration including intraoperative ultrasonography remains essential for the
localization of occult tumors not seen with conventional imaging [10].


## 13. Systemic Therapy

### 13.1. Medical (Nonsurgical)

#### 13.1.1. Chemotherapy

Cytotoxic
chemotherapy for VIPoma attempts to destroy the cancer cells, and is
administered either orally or by injection. Success rates have been relatively
low, however, they improve with combination chemotherapy or in addition to
surgical resection. In patients with unresectable disease, combination
chemotherapy with doxorubicin and streptozocin should be used [25]. Combination
of fluorouracil and streptozocin can be given to patients in whom doxorubicin
is contraindicated [16, 25].
Chlorozotocin, a drug structurally similar to streptozocin, is currently
under investigation in its role in combination with fluorouracil to provide a
regimen which may be more tolerable [25].Though the
treatment effectively terminates cancerous cells, these chemotherapy agents are
not without side effects, such as bone marrow suppression, leukopenia, anemia,
and/or thrombocytopenia leading to an elevated risk of infections, bruising,
and bleeding. Other side effects include poor appetite, vomiting, nausea,
diarrhea, oral sores, hair loss, and fatigue.


#### 13.1.2. Biologic Therapy (Immunotherapy)

Biologic therapy includes administration of alpha
interferon. Treatment by biological therapy is used to relieve symptoms rather
than effectively terminate cancerous cells of VIPoma [26, 27]. Alpha interferon inhibits both tumor growth and the
biochemical response of the tumor cell by limiting hormone release; the
biological treatment agent simulates natural killer cell function by these
mechanisms. Though more than 500 patients have been treated with alpha
interferon, only 11% experienced actual tumor regression, and when compared to
long-acting somatostasin analogs, the two treatments appear to differ primarily
in the area of side effects [26, 27]. In treating these symptoms, alpha
interferon has been noted to have severe potential side effects including fatigue,
depression, and flu-like symptoms [26, 27].


#### 13.1.3. Hepatic Artery Embolization

Hepatic artery
embolization (HAE) is a procedure designed to block the blood supply to the
tumor by sealing off the blood vessels flowing to the affected area [28, 29].  It is used in patients with a
hepatic primary or metastatic involvement.
HAE targets specific sites within the hepatic parenchyma [28, 29].


#### 13.1.4. Somatostasin/Octreotide

Somatostasin
administration has been shown to stop diarrhea and normalize electrolyte and
acid-base imbalances induced by VIP. Octreotide, the most common hormonal
therapy, is administered to relieve symptoms induced by the tumor [30–32].  The hormone, in the form of
sandostatin, can be administered daily via subcutaneous injections or monthly
by intramuscular injections [30–32].Somatostasin and
octreotide, though effective initially in controlling diarrhea, have one major
drawback. They are known to become gradually ineffective as resistance toward
this medication develops. Therefore, these agents are only short-lasting
solutions to combat the symptomatic component of VIPomas [30–32].


#### 13.1.5. Supportive Therapy

Volume loss is a
key concern in VIPoma, and rigorous volume replenishment, and meticulous
electrolyte correction is the mainstay of supportive management of this
condition. Antidiarrheal medications such as loperamide, often in combination
with octreotide, are used in preventing large outputs of diarrhea, especially
in cases where frequent breakthroughs are affecting the patient.


### 13.2. Surgical Approach

Of the treatments
options for VIPoma, surgery is the most common and successful method. Although
excision of VIPoma in undoubtedly the most effective treatment method, this is
not always possible due to the presence of extensive metastasis and/or
significant morbidity associated with collateral surgical impairment during the
procedure.The type of
surgery performed is highly dependent on the location and the size of the
neoplasm. The Whipple procedure is one surgical option. This procedure, which
involves the surgical removal of the pancreas head and part of the small
intestine, bile duct, and stomach, may be required in order to effectively
treat the patient. Following these procedures, the digestive tract and biliary
system are anastamosed [33, 34].
Nevertheless, if the VIPoma is localized to a single organ, such as the
pancreas, localized resections have also produced satisfactory results [33, 34].Partial or
complete pancreatectomy may result in insulin-dependent diabetes mellitus on
account of insulin depletion from pancreatic damage or resection.  These patients should be treated similar to
an insulin-dependent diabetic. Additionally, other endocrine and exocrine hormones replacement must
be considered whenever a pancreatectomy is performed. The stomach and spleen
are not commonly
resected organs as they may be affected by the spread of tumor or related
pathology. Nevertheless, the general side effects of surgery, such as post-op
pain, infection, bleeding, fatigue, and others, should be considered for the
elderly and other patients with limited tolerability for such invasive
procedures [33, 34].


### 13.3. Emerging Therapy

Though currently
considered an investigative treatment technique, researchers have found that
somatostasin-receptor antibodies attached to radioactive isotopes, such as
indium 111, have the potential to treat VIPomas and other neuroendocrine
neoplasms, in a similar fashion used to diagnose this condition (see above Diagnosis
section). The antitumor antibodies are thought to be effective because they
utilize the overexpression of somatostatin receptors in such tumors.


## 13.1. Medical (Nonsurgical)

### 13.1.1. Chemotherapy

Cytotoxic
chemotherapy for VIPoma attempts to destroy the cancer cells, and is
administered either orally or by injection. Success rates have been relatively
low, however, they improve with combination chemotherapy or in addition to
surgical resection. In patients with unresectable disease, combination
chemotherapy with doxorubicin and streptozocin should be used [25]. Combination
of fluorouracil and streptozocin can be given to patients in whom doxorubicin
is contraindicated [16, 25].
Chlorozotocin, a drug structurally similar to streptozocin, is currently
under investigation in its role in combination with fluorouracil to provide a
regimen which may be more tolerable [25].Though the
treatment effectively terminates cancerous cells, these chemotherapy agents are
not without side effects, such as bone marrow suppression, leukopenia, anemia,
and/or thrombocytopenia leading to an elevated risk of infections, bruising,
and bleeding. Other side effects include poor appetite, vomiting, nausea,
diarrhea, oral sores, hair loss, and fatigue.


### 13.1.2. Biologic Therapy (Immunotherapy)

Biologic therapy includes administration of alpha
interferon. Treatment by biological therapy is used to relieve symptoms rather
than effectively terminate cancerous cells of VIPoma [26, 27]. Alpha interferon inhibits both tumor growth and the
biochemical response of the tumor cell by limiting hormone release; the
biological treatment agent simulates natural killer cell function by these
mechanisms. Though more than 500 patients have been treated with alpha
interferon, only 11% experienced actual tumor regression, and when compared to
long-acting somatostasin analogs, the two treatments appear to differ primarily
in the area of side effects [26, 27]. In treating these symptoms, alpha
interferon has been noted to have severe potential side effects including fatigue,
depression, and flu-like symptoms [26, 27].


### 13.1.3. Hepatic Artery Embolization

Hepatic artery
embolization (HAE) is a procedure designed to block the blood supply to the
tumor by sealing off the blood vessels flowing to the affected area [28, 29].  It is used in patients with a
hepatic primary or metastatic involvement.
HAE targets specific sites within the hepatic parenchyma [28, 29].


### 13.1.4. Somatostasin/Octreotide

Somatostasin
administration has been shown to stop diarrhea and normalize electrolyte and
acid-base imbalances induced by VIP. Octreotide, the most common hormonal
therapy, is administered to relieve symptoms induced by the tumor [30–32].  The hormone, in the form of
sandostatin, can be administered daily via subcutaneous injections or monthly
by intramuscular injections [30–32].Somatostasin and
octreotide, though effective initially in controlling diarrhea, have one major
drawback. They are known to become gradually ineffective as resistance toward
this medication develops. Therefore, these agents are only short-lasting
solutions to combat the symptomatic component of VIPomas [30–32].


### 13.1.5. Supportive Therapy

Volume loss is a
key concern in VIPoma, and rigorous volume replenishment, and meticulous
electrolyte correction is the mainstay of supportive management of this
condition. Antidiarrheal medications such as loperamide, often in combination
with octreotide, are used in preventing large outputs of diarrhea, especially
in cases where frequent breakthroughs are affecting the patient.


## 13.1.1. Chemotherapy

Cytotoxic
chemotherapy for VIPoma attempts to destroy the cancer cells, and is
administered either orally or by injection. Success rates have been relatively
low, however, they improve with combination chemotherapy or in addition to
surgical resection. In patients with unresectable disease, combination
chemotherapy with doxorubicin and streptozocin should be used [25]. Combination
of fluorouracil and streptozocin can be given to patients in whom doxorubicin
is contraindicated [16, 25].
Chlorozotocin, a drug structurally similar to streptozocin, is currently
under investigation in its role in combination with fluorouracil to provide a
regimen which may be more tolerable [25].Though the
treatment effectively terminates cancerous cells, these chemotherapy agents are
not without side effects, such as bone marrow suppression, leukopenia, anemia,
and/or thrombocytopenia leading to an elevated risk of infections, bruising,
and bleeding. Other side effects include poor appetite, vomiting, nausea,
diarrhea, oral sores, hair loss, and fatigue.


## 13.1.2. Biologic Therapy (Immunotherapy)

Biologic therapy includes administration of alpha
interferon. Treatment by biological therapy is used to relieve symptoms rather
than effectively terminate cancerous cells of VIPoma [26, 27]. Alpha interferon inhibits both tumor growth and the
biochemical response of the tumor cell by limiting hormone release; the
biological treatment agent simulates natural killer cell function by these
mechanisms. Though more than 500 patients have been treated with alpha
interferon, only 11% experienced actual tumor regression, and when compared to
long-acting somatostasin analogs, the two treatments appear to differ primarily
in the area of side effects [26, 27]. In treating these symptoms, alpha
interferon has been noted to have severe potential side effects including fatigue,
depression, and flu-like symptoms [26, 27].


## 13.1.3. Hepatic Artery Embolization

Hepatic artery
embolization (HAE) is a procedure designed to block the blood supply to the
tumor by sealing off the blood vessels flowing to the affected area [28, 29].  It is used in patients with a
hepatic primary or metastatic involvement.
HAE targets specific sites within the hepatic parenchyma [28, 29].


## 13.1.4. Somatostasin/Octreotide

Somatostasin
administration has been shown to stop diarrhea and normalize electrolyte and
acid-base imbalances induced by VIP. Octreotide, the most common hormonal
therapy, is administered to relieve symptoms induced by the tumor [30–32].  The hormone, in the form of
sandostatin, can be administered daily via subcutaneous injections or monthly
by intramuscular injections [30–32].Somatostasin and
octreotide, though effective initially in controlling diarrhea, have one major
drawback. They are known to become gradually ineffective as resistance toward
this medication develops. Therefore, these agents are only short-lasting
solutions to combat the symptomatic component of VIPomas [30–32].


## 13.1.5. Supportive Therapy

Volume loss is a
key concern in VIPoma, and rigorous volume replenishment, and meticulous
electrolyte correction is the mainstay of supportive management of this
condition. Antidiarrheal medications such as loperamide, often in combination
with octreotide, are used in preventing large outputs of diarrhea, especially
in cases where frequent breakthroughs are affecting the patient.


## 13.2. Surgical Approach

Of the treatments
options for VIPoma, surgery is the most common and successful method. Although
excision of VIPoma in undoubtedly the most effective treatment method, this is
not always possible due to the presence of extensive metastasis and/or
significant morbidity associated with collateral surgical impairment during the
procedure.The type of
surgery performed is highly dependent on the location and the size of the
neoplasm. The Whipple procedure is one surgical option. This procedure, which
involves the surgical removal of the pancreas head and part of the small
intestine, bile duct, and stomach, may be required in order to effectively
treat the patient. Following these procedures, the digestive tract and biliary
system are anastamosed [33, 34].
Nevertheless, if the VIPoma is localized to a single organ, such as the
pancreas, localized resections have also produced satisfactory results [33, 34].Partial or
complete pancreatectomy may result in insulin-dependent diabetes mellitus on
account of insulin depletion from pancreatic damage or resection.  These patients should be treated similar to
an insulin-dependent diabetic. Additionally, other endocrine and exocrine hormones replacement must
be considered whenever a pancreatectomy is performed. The stomach and spleen
are not commonly
resected organs as they may be affected by the spread of tumor or related
pathology. Nevertheless, the general side effects of surgery, such as post-op
pain, infection, bleeding, fatigue, and others, should be considered for the
elderly and other patients with limited tolerability for such invasive
procedures [33, 34].


## 13.3. Emerging Therapy

Though currently
considered an investigative treatment technique, researchers have found that
somatostasin-receptor antibodies attached to radioactive isotopes, such as
indium 111, have the potential to treat VIPomas and other neuroendocrine
neoplasms, in a similar fashion used to diagnose this condition (see above Diagnosis
section). The antitumor antibodies are thought to be effective because they
utilize the overexpression of somatostatin receptors in such tumors.



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*Source: 938325-2009-04-05.xml*