Complete remission of recurrent multiple insulin-producing neuroendocrine tumors of the pancreas with somatostatin analogs: a case report and literature review.

Hyperinsulinemic hypoglycemia is most commonly caused by a single, sporadic insulinoma. Multicentric insulinoma disease (insulinomatosis) as well as metachronous neuroendocrine tumors of the pancreas, known also as neuroendocrine adenomatosis, represent a very rare condition, if not associated with multiple endocrine neoplasia type 1 syndrome (MEN1) or Von Hippel Lindau disease. We report a 9-year follow-up of a 41-year-old woman, initially presenting with hypoglycemic syndrome caused by two insulin-producing tumors, who underwent subtotal pancreasectomy in 2012, with histology compatible with multiple small neuroendocrine tumors. An approximately 1-cm insulin-producing tumor recurred at subsequent biochemical and radiological follow-up, and was cured with the somatostatin analog octreotide as a single treatment, until remission of symptoms and complete regression of the pancreatic lesion achieved after only 16 months of treatment. The possible mechanisms for these findings are discussed and the literature is briefly reviewed.

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis.

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an upregulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition indexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) "Dino Amadori", Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4-13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9-10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9-6.7 months) in underweight patients (BMI ≤ 18.49 kg/m2) and 10.1 months (95% CI: 3.7-28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients.

Paraneoplastic hypocalcemia-induced heart failure in advanced breast cancer: A case report and literature review.

Hypocalcemia is an uncommon clinical symptom of patients with malignant tumors, and a number of factors may be involved in its development. The present study describes the case of a 67-year-old Caucasian female, presenting with severe refractory hypocalcemia and heart failure. The patient was subsequently diagnosed with breast cancer and bone metastases. The paraneoplastic origin of the syndrome was confirmed by its complete resolution once the tumor responded to specific antineoplastic treatments, comprising weekly paclitaxel and aromatase inhibitor administration. The present case report suggested the need for greater awareness of the possibility of paraneoplastic hypocalcemia in breast cancer patients, and suggested that this condition may also contribute to the occurrence of heart failure. The mechanisms potentially responsible for this event were discussed and a brief review of the literature presented.

Metronomic capecitabine in gastroenteropancreatic neuroendrocrine tumors: a suitable regimen and review of the literature.

BACKGROUND: We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented. METHODS: From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29-82) years. The median treatment duration was 8 months. RESULTS: Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively. CONCLUSION: Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.

Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

BACKGROUND: The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). METHODS: Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. RESULTS: Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. CONCLUSIONS: Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

Chromogranin A in gastric neuroendocrine tumours: an immunohistochemical and biochemical study with region-specific antibodies.

The aim of the present study was to investigate ECLomas and enterochromaffin-like (ECL) cell hyperplasia in gastric human mucosa regarding the immunohistochemical expression of chromogranin A (CgA) epitopes and to measure the same CgA epitopes in plasma samples. Eight gastric biopsies from ECLomas, seven of type I and one of type III, and biopsies from one patient showing only ECL cell hyperplasia were included in the study. Our results revealed a varying expression of region-specific CgA epitopes in the ECLomas regarding both the frequency of immunoreactive cells and intensity of immunoreactivity. CgA284-301 (pancreastatin) was not revealed in any neoplasm, whereas CgA361-372 (catestatin) was expressed in all ECLomas. However, the number of immunoreactive cells to vesicular monoamino transporter 2 (VMAT 2) or the commercial monoclonal CgA (CgA250-284) antibodies were generally higher. The plasma concentrations of the region-specific CgA radioimmunoassays differed considerably, with highest concentrations of CgA1-17 and CgA116-130 epitopes and the lowest with the CgA17-37, CgA63-76, CgA238-247 and CgA441-424 epitopes. No relationship was found between tissue expression and plasma concentration of CgA epitopes. In conclusion, this study shows that VMAT 2 and the commercial CgA antibodies seem more useful for histopathological diagnosis of ECLomas than the antibodies to the other CgA regions.

Gastrinoma of the stomach: a case report.

Gastrinomas of the stomach are extremely rare endocrine tumors producing Zollinger-Ellison syndrome. We report here the case of a patient with gastrinoma of the stomach who presented regional and hepatic metastases at the time of diagnosis. The endocrine tumor was discovered incidentally 8 yr after the onset of symptoms related to peptic ulcer, which responded to medical treatment with a proton pump inhibitor. Surgery did not cure the patient, as demonstrated by provocative tests showing serum gastrin responses indicative of residual disease. A long-term treatment with the somatostatin analog lanreotide induced a biochemical response and was associated with a substantially stable disease.