Gastroenteropancreatic tumors, although relatively rare,
present management problems that may last many years, in comparison with the
usually more aggressive adenocarcinomas whose management may encompass a far
briefer span of time. In general, 50% of such tumors are insulinomas, while
gastrinomas comprise 25%, and nonfunctional tumors 20% VIPomas and glucagonomas are the predominant lesions of the remaining 5%.
Clinical diagnosis is usually made on the presence of the classical symptom
complex. In uncertain circumstances or covert presentations, the critical
diagnostic biochemical test is plasma chromogranin A as well as measurement of
the specific peptide.
Localization of the lesion is best undertaken by
111In-pentetreotide imaging (OctreoScan, Mallinkrodt Imaging), although
insulinomas may occasionally not be identifiable in 111In-pentetreotide because
they are somewhat less likely to express somatostatin receptors. Intraoperative
localization of impalpable lesions still remains a problem because the adequate
gamma probe collimators are unavailable. For solitary lesions, surgical
resection is still the ideal therapy. The majority of lesions, however, have
spread, and in such instances, alternative therapy is required. This may
include, but is not limited to, resection, cytoreduction, hepatic
transplantation, chemotherapy, chemoembolization, biotherapy, and symptomatic
treatment with octreotide LAR depot (Sandostatin LAR Depot).
Formal liver resection appears to be of marginal benefit
unless lesions are lobe-specific, and outcome usually reflects surgical
technique rather than the nature of the tumor itself. Hepatic cytoreduction
including cryoablation, and more recently thermoablation, has gained
prominence.[1-3] Current data suggest no major advantage to this technique, and
thermoablation poses some danger if structures such as bile ducts or major
vessels are compromised. Chemoembolization is significantly less invasive, can
be repeated, and appears as efficacious although no rigorous comparisons are
available. Liver transplantation has been of marginal benefit in highly
selected situations, but inadequate data exist to support its formal
introduction into a therapeutic strategy.
A wide variety of cytotoxics have been utilized with
extremely modest outcome, and all are associated with significant side effects
that seriously decrease quality of life.[4,6] More recent agents studied include
etoposide, paclitaxel, and gemcitabine (Gemzar), although insufficient data are
available to determine their final utility. Octreotide LAR depot currently
appears to be among the most promising therapeutic strategies. It may also be
advantageously used alone or in combination with surgery or chemoembolization.
Of note is the fact that octreotide LAR depot may be useful in the management of
gastrinoma patients and may be capable of inhibiting the development of gastric
carcinoids in individuals with the MEN-1 syndrome.[8,9]
Biotherapy using interferon may be useful in unresponsive
patients, although its toxicity remains a concern. Although interferon has
significantly more side effects than octreotide LAR depot, a combination therapy
of the two agents has yielded early promising data. Octreotide LAR depot is also
an important adjunct to surgery in that it decreases postoperative biliary and
pancreatic complications and reduces symptoms. Of particular interest is the use
of octreotide-associated radioisotopic therapy.[10,11] The initial use of indium
has been promising, and although yttrium appears to be more effective, it has
been more often associated with renal problems. Current studies with the
lutetium isotope are considered even more promising, but insufficient experience
renders a final conclusion premature at this time.
Overall, the best gastroenteropancreatic management strategy involves tumor
cytoreduction followed by symptom relief using octreotide LAR depot and specific
tumor ablation, using the least invasive technique possible.
1. Chung MH, Pisegna J, Spirt M, et al: Hepatic cytoreduction
followed by a novel long-acting somatostatin analog: A paradigm for intractable
neuroendocrine tumors metastatic to the liver. Surgery 130:954-962, 2001.
2. Siperstein AE, Rogers SJ, Hansen PD, et al: Laparoscopic
thermal ablation of hepatic neuroendocrine tumor metastases. Surgery
122:1147-1154, 1997; discussion 1154-1155.
3. Bilchik AJ, Sarantou T, Foshag LJ, et al: Cryosurgical
palliation of metastatic neuroendocrine tumors resistant to conventional
therapy. Surgery 122:1040-1047, 1997.
4. Faiss S, Scherubl H, Riecken EO, et al: Drug therapy in
metastatic neuroendocrine tumors of the gastroenteropancreatic system. Recent
Results Cancer Res 142:193-207, 1996.
5. Dousset B, Houssin D, Soubrane O, et al: Metastatic
endocrine tumors: is there a place for liver transplantation? Liver Transpl Surg
6. Schott M, Scherbaum WA, Feldkamp J: Drug therapy of
endocrine neoplasms. Part II: Malignant gastrinomas, insulinomas, glucagonomas,
carcinoids and other tumors. Med Klin 95:81-84, 2000.
7. Claure RE, Drover DD, Haddow GR, et al: Orthotopic liver
transplantation for carcinoid tumour metastatic to the liver: Anesthetic
management. Can J Anaesth 47:334-337, 2000.
8. Angeletti S, Corleto VD, Schillaci O, et al: Single dose
of octreotide stabilize metastatic gastro-entero-pancreatic endocrine tumours.
Ital J Gastroenterol Hepatol 31:23-27, 1999.
9. Shojamanesh H, Gibril F, Louie A, et al: Prospective study
of the antitumor efficacy of long-term octreotide treatment in patients with
progressive metastatic gastrinoma. Cancer 94:331-343, 2002.
10. Waldherr C, Pless M, Maecke HR, et al: Tumor response and
clincial benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl
Med 43:610-616, 2002.
11. Waldherr C, Pless M, Maecke HR, et al: The clinical value of
[90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of
neuroendocrine tumours: A clinical phase II study. Ann Oncol 12:941-945, 2001.