Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours

Abstract

Background: Gastric carcinoid tumours type 1 (GCA1) originate from hyperplastic enterochromaffinlike (ECL) cells secondary to hypergastrinaemia. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. We conducted a multicentre prospective study to assess the effects of long-acting SSA on hypergastrinaemia and ECL-cell proliferation in patients with GCA1. Methods: We studied 15 patients with GCA1 treated with monthly long-acting release octreotide (LAR) (20-30 mg; nZ14) or Lanreotide 90 mg (nZ1) for at least 6 months. Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from both tumours and surrounding mucosa before, and every 6-12 months following treatment. Sections were immunostained for neuroendocrine markers. The cell proliferation index Ki-67, intensity of staining before and after treatment and the degree of gastric wall invasion were also assessed. Results: All patients tolerated treatment well (mean follow-up of 18 months). In 11 patients (73%), a complete disappearance of the tumours at 1 year of treatment was observed on endoscopy, while in three patients (20%), the tumours decreased significantly in number and size. Gastrin levels normalized in 25% of patients, and were reduced by more than 80% in the remaining 75%. Conclusions: Treatment with SSAs in GCA1 leads to a substantial tumour load reduction, with a concomitant decrease of serum gastrin levels. Our data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1.

Neuroendocrine neoplasms of the stomach

“…Thus, gastrin suppression and tumoristatic effect may be achieved using somatostatin analogs (octreotide or lanreotide) in recurrent and multiple lesion type 1 NETs or type 2 (ref. [14][15][16][17][18]20 ). Antrectomy is also an effective procedure for gastrin suppression but debatable by some authors 1 .…”

“…Antrectomy may be indicated in frequently recurring type 1 tumours 12 , but total gastrectomy should be a rather exceptional indication for this type. Tumoristatic effects of somatostatin analogs have been confirmed by a few small clinical studies [13][14][15][16][17][18] . Somatostatin analog (octreotide) was used in our work with good therapeutical effect in 6 patients with recurring small multiple tumour lesions.…”

“…In our opinion, most patients with type 1, with grading G1 (Ki67 ≤ 2%), tumor size ≤ 10 mm, tumours not penetrating through lamina muscularis mucosae and not metastasizing into regional lymphnodes canmostly be treated by endoscopic removal. Antrectomy may be considered for recurrent cases 12 , however, according to some authors, the long-term benefits of antrectomy remain uncertain 15 . Serum chromogranin A levels were increased in both subsamples and did not differ significantly even though type 1 tumours were only localized, small lesions (tumour size was up to 10 mm in diameter in our subsample), and type 3 tumors were generalized with large tumour load.…”

Somatostatin analogs for gastric carcinoids: For many, but not all

“…every 10 d) vs octreotide (200 μg s.c. twice or thrice daily) in 33 patients with carcinoid syndrome, O'Toole et al [51] did not evidence any significant differences with regard to symptom control. Again, both these analogs have been reported to have an antiproliferative effect in vitro [52,53] . Data from uncontrolled prospective and retrospective clinical series [54][55][56] showed tumor shrinkage and disappearance in response to either short-acting SSAs alone or when combined with interferon-α.…”

Nowotwory neuroendokrynne żołądka i dwunastnicy z uwzględnieniem gastrinoma (zasady postępowania rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

“…the test with secretin (2 units/kg bw IV) or calcium gluconate in uncertain cases (*evidence level 3); -assessment of serum gastrin concentration in patients after surgery due to gastrinoma, 3-12 months after the surgery, then follow-up tests every 6-12 months for 3-4 years (*evidence level 5); -determination of serum CgA concentration (*evidence level 5); -in uncertain cases concerning differentiation of the causes of secondary hypergastrinaemia -determination of gastric pH (pH < 2) [34] (*evidence level 4); -in the case of suspected MEN-1 syndrome, screening tests described in section 1: "Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms" should be performed (see p. 79-110). Concomitant MEN-1 syndrome requires confirmation in genetic tests [12] (*evidence level 4).…”