Current Status of Gastroenteropancreatic Tumor Management
Current Status of Gastroenteropancreatic Tumor Management
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 1:111-117, 1995.
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.