Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5376
Peer-review started: April 30, 2019
First decision: June 6, 2019
Revised: June 12, 2019
Accepted: July 19, 2019
Article in press: June 6, 2019
Published online: September 21, 2019
Gastric neuroendocrine neoplasms type 1 (GNENs1) exhibit a generally benign clinical course and have distinct differences in tumour biology and patient outcomes, as compared to other types of GNENs.
Informative clinico-pathological features (size, grade, depth of invasion) are currently used indistinguishably for most GNEN types and remain to be elucidated for GNEN1s in particular in order to determine the risk of lymph node (LN) metastases, disease-specific survival and local recurrence; and guide a more patient-tailored management.
The aim of our study was to compare the rate of LN metastases, disease-specific mortality, and recurrence rates post intervention in patients with GNEN1s undergoing endoscopic or surgical resection with respect to the aforementioned clinico-pathological parameters (size, grade and depth of invasion). Additionally, we aimed to evaluate the rate of procedural complications associated with endoscopic and surgical interventions.
The PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale and in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios with 95%CI were applied for the quantitative meta-analysis.
Although the metastatic propensity of GNEN1 is low (3.3%), tumour size ≥ 10 mm and invasion of the muscularis propria in the gastric wall may be utilized to predict the presence LN. The negative predictive value of tumour size for lesions < 10 mm and that of the absence of muscularis propria invasion with respect to the presence of locoregional LN metastases were as high as 99.2% and 96.9% respectively. Contrary to other GNEN types, tumour grade was not clearly associated with the risk of LN metastases in GNEN1. The disease prognosis is excellent, with a 5-year DSS of 100% in most studies; thus, the presence of LN metastases does not seem to clearly affect survival in GNEN1 patients. Moreover, most studies reported 98-100% 5-year DSS, irrespective of the type of intervention that was undertaken. However, studies reporting long-term follow-up (i.e., >10 years post-treatment surveillance) are lacking; hence, we were not able to provide evidence that prophylactic surgical resection exerts a survival benefit. The complication rates of endoscopic vs surgical resection in the few studies reporting this information were 0.6 and 3.8%, respectively. Finally, scarce data were available with regard to GNEN1 local recurrence after endoscopic or surgical intervention. Although surgery was associated with a lower recurrence rate, recurrence prediction stratified by patient-related parameters was not feasible in our study.
Herein, we have thoroughly investigated patient-related clinico-pathological risk parameters potentially predicting metastatic disease, recurrence following endoscopic or surgical management and disease-specific mortality rates. We confirmed that LN metastases in GNENs1 are relatively rare and that tumour size ≥ 10 mm, as well as the presence of the muscularis propria invasion are associated with an increased risk for LN metastasis. The latter finding suggests that endoscopic ultrasound investigation is very valuable in the work up of these lesions. Finally, surgical resection is linked to a lower risk for local recurrence.
The present study provides a systematic review and meta-analysis of GNEN1 confirming the indolent course of this neoplasm and providing suggestions for future research towards a stratified approach based on patient-tailored parameters in the era of personalized medicine. Foremost, based on our findings, special attention to GNEN1 size and the depth of invasion and making use of diagnostic modalities, such as endoscopic ultrasonography, seem reasonable in clinical practice, and in future studies with long-term follow up in the field of GNEN1.