HIGH-GRADE PANCREATIC NEUROENDOCRINE TUMORS: POSSIBILITIES OF SURGICAL INTERVENTIONS
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Abstract
Objective. To evaluate the immediate and long-term results of surgical interventions for patients with high-grade pancreatic neuroendocrine tumors (pNETs). Material and methods. We performed surgical interventions for 130 patients with pPNETs, and 20 (15%) of them presented an over 20% proliferation index (Ki-67) in tumor cells. In 15 of latter a Ki-67 proliferation index between 20% and 55% was detected (high-grade, highly malignant tumors - grade G3). In the rest 5 patients, with a Ki-67 proliferation index over 55%, low-grade (G3) neuroendocrine tumors, or pancreatic neuroendocrine cancer (pNEC) was diagnosed. The results of surgical procedures were analyzed: distal pancreatectomy, in most cases distal subtotal adrenalectomy and splenectomy, in 15 patients (75%); pancreaticoduodenectomy in 3 patients (15%); and pancreatectomy with angiectomy in 2 patients (10%). Moreover, 15 patients (75%) underwent combined operations with angiectomy, adrenalectomy, transverse colectomy, gastrectomy, ovariectomy, nephrectomy, and partial hepatectomy for synchronous liver metastases. Results. All patients survived surgery, and postoperative complications occurred in 9 of them (45%): gastroptosis, acute postoperative pancreatitis and pancreatic fistula in 10%, 5.5% and 22% of cases, respectively. Two patients (10%) were diagnosed diabetes after pancreatectomy. The 5-year overall survival (OS) for patients with G3 pNETs was 39±17%, and the median survival time was 28 months. For patients with pNEC, the 5-year OS was 40±30%, while the median survival time was not achieved. However, the statistically differences are unreliable (p =0.9). The indicators of disease-free survival for the entire group of patients with high-grade pNETs were 17 ± 10% and 8 months, respectively. The OS after microscopic radical surgery (R0) and cytoreductive surgery (R2) in the groups of G3 pNETs and pNEC indicated statistically insignificant differences (p=0.3 and p=0.6). In the pNEC group, R0 resulted in a 5-year survival rate, while after cytoreductive operations (R2) a 2-year OS was not achieved. In cases of synchronous metastases in the liver at G3 pNETs, after R0 surgery a 2-year survival was achieved; in the subgroup of staged operations (stage 1 - R2 procedure on the pancreas, stage 2 - R0 procedure on the liver), a 5-year survival was achieved. In the pNEC group, after one-stage cytoreductive operation a 2-year survival was achieved. Conclusion. Our data demonstrate a relatively high OS rate for patients with pNETs who underwent pancreatic resections or eradication. For the entire group under consideration, a relatively long period of survival with an existing relapse of the disease is characteristic. There were no significant differences in OS after surgical interventions between patients with G3 pNETs (Ki-67 20-55%) and pNEC (Ki-67 > 55%). Without any possibilities to perform a microscopic radical operation, cytoreductive operation as part of the combined treatment is permissible. Synchronous metastases in the liver are not a contraindication to surgical intervention. In G3 pNETs patients, stage operations (stage 1 - resection of the pancreas, stage 2 - radical removal of metastases in the liver) ensured a 5-year survival. In pNEC patients with synchronous liver metastases, a cytoreductive operation, removal of the primary tumor followed by non-surgical treatment for metastases, resulted in 2-year survival rate.
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