| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
EDITORIALS |
From the Departments of Gastrointestinal Oncology (JCY) and Surgical Oncology (J-NV), University of Texas MD Anderson Cancer Center, Houston, Texas.
Correspondence: Address correspondence to Jean-Nicolas Vauthey, MD, Department of Surgical Oncology, UTMD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030; Fax: 713-792-0722; E-mail: jvauthey{at}mdanderson.org
Carcinoid tumors arise from ubiquitous neuroendocrine cells. These tumors are relatively uncommon, but their incidence is rising.1 Our own analysis of the data from the Surveillance, Epidemiology, and End Results (SEER) Program show that the overall incidence of carcinoid tumors (per 100,000 individuals) increased from 0.8 (95% confidence interval [CI], 0.7 to 1.0) in 1973 to 2.9 (95% CI, 2.7 to 3.2) in 1999 (Fig. 1).2 On the basis of the current estimated population of the United States, 290 million, we estimate that 8400 new cases of carcinoid tumors will be diagnosed in this country in 2003.
|
In this issue of Annals of Surgical Oncology, Knox et al.3a describe a case of primary hepatic carcinoid tumor successfully managed with judicious surgical intervention resulting in long-term survival. The authors performed an extensive literature search and identified 48 additional cases of primary hepatic carcinoid tumor. The median survival time in this series was long—10.9 years.
Although the liver is a common site for metastases from carcinoid tumors, it is a rare site for primary carcinoid tumors. The neuroendocrine cells in the liver that give rise to primary hepatic carcinoid tumors have not been well described. We searched the SEER 9 database for all cases of primary hepatic carcinoid tumor diagnosed between 1973 and 1999. Excluding those cases identified at autopsy, we identified 43 cases. The survival in the SEER series that we identified was significantly worse than the survival in the series described by Knox et al. The median survival times for localized, regional, and metastatic carcinoid were 3.2 years, 2.5 years, and 0.8 years, respectively.3 This difference may be caused by several factors. Published reports may have included only the patients with the best outcomes. Patients in the SEER registry may have had inoperable disease or may not have been optimally treated. Finally, patients in the SEER registry may not have had the same rigorous search for occult extrahepatic primary disease as described by Knox et al. in this issue.
Whereas substantial data exist regarding surgical treatment of patients with hepatic colorectal metastases, few data are available to support a standardized algorithm to select patients who will benefit most from surgical resection of hepatic carcinoid tumor. The evaluation, however, should rest on four key points: (1) whether the tumor is primary or secondary (i.e., from the gut, including the bronchial origin, or from the pancreas, from a well-differentiated islet cell carcinoma [formerly also called pancreas carcinoid]); (2) the extent of the associated functional symptoms, if any; (3) the intrahepatic and extrahepatic extent of the tumor; and (4) if it can be obtained, information about the biology of the tumor. Each of these points is discussed below.
Although most hepatic carcinoid tumors are metastatic and associated with a primary tumor in the small bowel (midgut), the differential diagnosis should include metastatic, well-differentiated endocrine neoplasm of the pancreas (islet cell), bronchial carcinoid (foregut), and distal colonic carcinoid (hindgut). We are hesitant, therefore, to designate the primary site of a carcinoid tumor as the liver unless an exhaustive search for an occult primary tumor has been performed. Examination of the small bowel by conventional endoscopic approaches is not feasible. Radiologic imaging of the small bowel is notoriously difficult. Nuclear imaging with 111In-DTPA-D-pentetreotide scintigraphy (Octreoscan) will frequently miss a small primary tumor. A small occult primary tumor in association with extensive hepatic metastases is not uncommon and may eventually be uncovered at the time of hepatic resection or subsequent followup examinations. If no primary tumor is identified at the time of hepatic resection—as occasionally occurs in the case of small endocrine neoplasms of the pancreas—close followup, with imaging may uncover an occult primary tumor within a few years.
Patients with tumors that cause functional symptoms are currently treated with somatostatin or an analog, which usually results in partial or complete symptomatic response. No evidence, however, indicates that hormonal therapy is associated with meaningful response, and the effect of hormonal therapy is cytostatic at best. Therefore, in the absence of effective chemotherapy for carcinoid tumors, all patients who are suitable candidates for complete resection should have surgical resection.4,5 Likewise, patients with uncontrolled functional symptoms associated with carcinoid syndrome should also have surgical resection provided that at least 90% of the tumor can be resected (debulking).6,7 Treatment of carcinoid syndrome with hormonal therapy or hepatic artery embolization, although these options can minimize symptoms, should not be a substitute for timely surgical resection, as surgery for advanced disease (75% hepatic replacement) and palliative (incomplete) resection are associated with a poor prognosis.8 There is debate, however, as to whether asymptomatic patients benefit from debulking procedures.9
Evaluation of the extrahepatic extent of disease can include nuclear imaging studies. Assessment of the intrahepatic extent of disease should include helical computed tomography with thin (5 mm) cuts through the liver and rapid bolus intravenous contrast injection (2 to 5 mL per second) to obtain four sets of images (precontrast, arterial, portal, and delayed phases).10 Bilobar disease is not a contraindication to resection. The main contraindication to surgery is an anticipated incomplete resection (except for patients in whom the intent of resection is debulking). We favor synchronous resection of the primary tumor and the liver metastases unless a staged procedure is required because of extensive mesenteric or hepatic involvement. An extended resection is often performed to achieve complete resection. We commonly perform preoperative portal vein embolization before an extended right hepatectomy to induce hypertrophy of the anticipated liver remnant (segments 2 and 3).11,12 On the basis of our recent experience with extended liver resections, we believe that portal vein embolization is indicated in patients in whom the anticipated liver remnant is <20% of the total estimated liver volume. In patients in whom the dominant disease is located in the left liver, we combine an extended left hepatectomy with resection or radiofrequency ablation of the disease in the right posterior sector (segments 6 and 7).
Perhaps most important in the evaluation of patients with carcinoid tumor being considered for surgery is a multifaceted evaluation of the tumor that provides an estimation of tumor biology. The success story presented by Knox et al. epitomizes the favorable biology: an asymptomatic patient with positive lymph nodes had three resections over 8 years and an additional 7 years of followup without recurrence. Today, there is almost never a need for urgent resection following initial diagnosis. The test-of-time approach advocated for patients with metastatic colorectal carcinoma (waiting time before liver resection)13,14 applies to patients with carcinoid tumors because of the slow disease progression. Liver resection should be avoided for patients with high-grade neuroendocrine subtype. In patients whose disease is not controlled medically and, occasionally for the purpose of downstaging prior to resection, we favor hepatic artery embolization as part of this test-of-time approach.15
In summary, we believe that surgical resection has an important role in the management of hepatic carcinoid tumor. Select patients, including those with a primary carcinoid tumor outside the liver, will experience long-term survival after resection. The four key points outlined herein may assist in the selection of the optimal candidates for surgery.
Received for publication October 6, 2003. Accepted for publication October 17, 2003.
REFERENCES
This article has been cited by other articles:
 |
|
 |
|
  J. C. Yao, A. Phan, P. M. Hoff, H. X. Chen, C. Charnsangavej, S.-C. J. Yeung, K. Hess, C. Ng, J. L. Abbruzzese, and J. A. Ajani Targeting Vascular Endothelial Growth Factor in Advanced Carcinoid Tumor: A Random Assignment Phase II Study of Depot Octreotide With Bevacizumab and Pegylated Interferon Alfa-2b J. Clin. Oncol., March 10, 2008; 26(8): 1316 - 1323. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
