Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms

Abstract

There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni-and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.

Frequency and Prognostic Significance of Intertumoural Heterogeneity in Multifocal Jejunoileal Neuroendocrine Tumours

“…Interestingly, in general, we observed no significant survival differences between our cohort of advanced multifocal SI-NETs and our control cohort of advanced unifocal SI-NETs. This finding is consistent with results from previous studies on SI-NETs [ 14 , 19 , 29 , 30 ]. In line with this general finding, intertumoral variation of WHO grade, SSTR2, serotonin, or CDX2 did not impact patient survival within the group of multifocal tumors or in comparison to unifocal NETs, pointing towards an, at best, limited prognostic relevance of morphological heterogeneity in multifocal SI-NETs and even of multifocality in general.…”

“…We compared the survival characteristics of our multifocal NET series with a cohort of 88 advanced unifocal ileojejunal NETs (UICC stage IV), who underwent resection at the University Hospital Marburg during the same time period. Survival data from some of these patients were part of a previously published collective [ 19 ].…”

Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms

“…Between April 2014 and December 2021, a total of 102 patients with SI-NENs were subjected to surgery at our institution. Some details of these patients, such as pathological data, metastatic progression, long-term survival and prognostic markers have been previously reported [ 6 , 10 ]. In the present study, only patients operated on after 2014 with small bowel resections who were subjected to primary tumor resection with either vessel-sparing lymphadenectomy (VS-LA) or conventional lymphadenectomy (Con-LA) were analyzed.…”

“…Regional lymph node metastases are often larger than the primary tumor(s) and frequently associated with dense desmoplastic fibrosis, leading to mesenteric shrinkage. This condition can cause acute symptoms such as abdominal pain, bowel obstruction and mesenteric ischemia, which may require emergency intervention in up to 25% of cases [ 10 ]. Surgical treatment is the cornerstone of multimodal SI-NEN management and may be curative in cases of complete R0 resection.…”

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

“…It can reveal recurrence and may predict prognosis. A new immunohistochemical marker is the transcription factor insulinoma-associated protein 1 (INSM1), which is more specific for the differentiation of NETs of the pancreas and rectum[ 4 , 35 , 44 , 45 ].…”