1 Dipartimento di Medicina Interna e Gastroenterologia, 2 Dipartimento Clinico di Scienze Chirurgiche ed Anestesiologiche and 3 Dipartimento Clinico di Scienze Radiologiche ed Istopatologiche, Università di Bologna, Italy
* Correspondence to: Prof P. Tomassetti, Department of Internal Medicine and Gastroenterology, University of Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti, 9, 40138 Bologna, Italy. Tel/Fax: +39-051-6364186; E-mail: paola.tomassetti{at}unibo.it
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Abstract |
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Patients and methods: Eighty-three patients with pancreatic endocrine tumors diagnosed in our department from 1978 to 2003 were studied.
Results: The study included 37 men (44.6%) and 46 women (55.4%). The median age of patients at diagnosis was 55 years (range 1981 years). Fifty-two patients (62.7%) had non-functioning endocrine tumors, 16 (19.3%) had functioning endocrine tumors and 15 (18.1%) had MEN 1 disease with pancreatic involvement. Twenty-seven patients (32.5%) had liver metastases at the time of diagnosis, involvement of the lymph nodes was found in 47 out of 79 patients (59.5%). Forty patients (48.2%) had radical surgery, 20 (24.1%) had palliative surgery and 53 were treated medically. The survival rate was significantly related to the presence of metastases, lymph node involvement, and the type of tumor and treatment.
Conclusions: Tumor resection, the absence of liver and lymph node metastases, and the presence of MEN 1 syndrome are related to a better survival rate. Radical surgery continues to have a central role in the therapeutic approach to endocrine tumors of the pancreas.
Key words: endocrine pancreatic tumor, gastrinoma, multiple endocrine neoplasia, octreotide, surgical procedure
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Introduction |
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The aim of this study was to evaluate the survival rate of patients with endocrine tumors of the pancreas, functioning or non-functioning, as well as associated or not with MEN 1 syndrome. We also evaluated which clinical, radiological and histological variables are associated with the survival rate of these patients. Finally, we evaluated which of the different treatment modalities are associated with the survival rate of patients with pancreatic endocrine tumors.
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Patients and methods |
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The patients enrolled in the study underwent a clinical check-up and abdominal US every 3 months. A CT scan was performed in all patients every 6 months during the first year after diagnosis and every 12 months thereafter. Surgical and medical procedures and survival rates were recorded in the follow-up period.
Statistics
Mean, median, standard deviation, range and frequencies were used as descriptive statistics. Survival curves were computed by using the KaplanMeier method, whereas the MantelCox model was applied in order to identify factors significantly related to survival; the hazard ratios (HR), together with their respective 95% confidence intervals (CI), were also computed. The Wilcoxon signed ranks test was also applied. Statistical significance was defined as two-tailed P values less than 0.05. Statistical analyses were performed by means of the SPSS (Version 8.0 for Windows) statistical package.
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Results |
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Discussion |
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In our study, the 5-year survival rate was 55.3%, which is similar to that reported by other authors (between 35% and 60%) [10, 21
23
].
In our experience, sex, age of patients and localization of the tumor were not significantly related to survival [10, 13
]; size was not related, this finding being in contrast with other reports at least concerning non-functioning pancreatic tumors [10
, 24
, 25
]. One possible explanation is that we could not find an accurate definition of the tumor size that unequivocally affects patient's survival in the literature. As a rule, 34 cm diameter is considered the accepted limit, but there are controversial data [24
, 26
28
]. Moreover, in a recent study in patients with MEN-1, Lowney et al., in agreement with our results, could not find a correlation between the size of the primary tumor and its metastatic potential [29
, 30
]. In our opinion, this discrepancy may be explained by the heterogeneity of the tumors grouped together as NETs. Due to the long period of time considered, it was not possible to separate well- and poorly-differentiated tumors according to the histopathological classification proposed by WHO in 2000. For this reason a careful study of the natural history of each of these neoplasms is required in order to define better the relationship between the features of the tumor and patient survival.
Moreover, in our patients, we could not find a significant relationship between survival and the Ki-67 proliferative index determination which is considered by several authors as a reliable prognostic factor [26, 27
, 31
]. We determined the Ki-67 index only in the last 29 patients studied. The limited number of determinations can affect the relevance of statistical significance.
Regarding patients with metastases, survival was also significantly better in patients without metastases at diagnosis compared with those with metastases at diagnosis and this finding is in agreement with other recent reports. At present, metastases, and in particular liver metastases, are considered the factors that are more highly correlated with the survival rate [10, 13
, 24
].
The overall survival rate in patients who underwent radical surgery was significantly better than in those not operated on and in patients who underwent palliative surgery; our data agree with those of other authors [10, 17
, 21
, 24
]. In addition, patients who underwent palliative surgery did not show a better survival rate with respect to patients not operated on. Moreover, recent reports suggest that conventional contraindications to surgical resection, such as nodal or distant metastases, the hallmarks of advanced malignancy, should be redefined, giving further support to surgical options [32
].
Regarding medical treatment, available data did not show any statistical significance between patients treated with somatostatin analogues and those not treated. However, we have noticed a positive trend concerning survival in treated patients. It is important to stress that medical treatment with somatostatin analogues, available since the 1990s, has produced a rapid disappearance of symptoms due to hormonal hypersecretion in patients with functioning endocrine tumors and an improvement in the quality of life in those with non-functioning ones.
In conclusion, we can suggest that radical surgery continues to have a central role in the therapeutic approach to NETs of the pancreas. The crucial point is an early diagnosis that allows radical surgery when the tumor has not yet metastasized. Of course, our data cannot be proposed as a prognostic model for the treatment of endocrine tumors of the pancreas; we only report our experience on this topic even if we believe that a wider approach to surgical criteria can give better opportunities to patients.
Medical treatment has a precise role in functioning endocrine tumors while, as far as non-functioning tumors are concerned, further studies on a larger number of patients are necessary.
Received for publication April 29, 2005. Revision received June 16, 2005. Accepted for publication June 20, 2005.
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