**3. Gastric neuroendocrine tumours (NETs)**

the risks of multicentric synchronous or metachronous carcinoma [13]. TG is recommended for gastric carcinoma located in the upper third of the stomach, signet ring cell cancers (*linitis plastica*), cancer arising on the background of atrophic gastritis, multicentric cancers, advanced distally located tumours with lymph node metastasis to allow extended lymphadenectomy, invasion of pancreas (which requires pancreaticosplenectomy) and patients with inherited E-cadherin mutation as a prophylactic measure (due to 80% lifetime risk of developing gastric

Laparoscopic gastric cancer surgery is technically demanding and is currently performed more routinely by Asian surgeons. Nevertheless, more and more specialists around the globe are becoming more confident in laparoscopic surgery, and, with the help of technological advancements, usage of laparoscopy will certainly increase [14]. As discussed previously, very early gastric carcinomas are preferably treated by endoscopic resection. However, criteria for endoscopic treatment are very strict, and these methods are more widely used in highincidence countries with high proportion of early cases. Therefore, the most solid indication for laparoscopic surgery is gastric carcinoma located in the distal or middle third of the stomach and limited to submucosa without evidence of lymph node involvement or mucosal cancers not amenable to endoscopic treatment [14]. In case of laparoscopic total gastrectomy, the more widely accepted indication is T1N0 tumour of proximal third of the stomach [14]. There is evidence that laparoscopy is a safe and feasible option even for advanced gastric carcinomas if performed in high-volume specialised centres [1]. A systematic review comprising 3411 patients revealed similar lymph node harvest and long-term survival for laparoscopic distal gastrectomy compared to open approach. Hospital stay, analgetic consumption, postoperative complication rate and blood loss in surgery were all reduced in laparoscopic approach group [1]. Surgeons in Eastern Asia have expanded the use of laparoscopy to advanced cancers even with limited involvement of perigastric nodes [14]. There is still a small amount of high-quality evidence to support these expanded indications [4, 14]. However, one large systematic review analysing 23 studies with 7336 patients was recently published. Authors found comparable 5-year overall survival (*p* = 0.45), recurrence (*p* = 0.08) and gastric cancer-related death rates (*p* = 0.28) between laparoscopic and open gastrectomy groups. These results led them to conclude that laparoscopic gastrectomy was comparable to the open approach and did not worsen oncologic results [15]. To evaluate the role of laparoscopy in advanced gastric cancer, a meta-analysis comprising 11 studies and 1904 patients was performed. A D2 dissection was performed in both open and laparoscopic cases. Researchers found reduced blood loss, morbidity, shorter postoperative ileus and length of hospital stay in laparoscopic group, although the operation time was longer by almost 42 min (*p* < 0.05). No significant difference was noted in lymph node harvest, intrahospital mortality, recurrence rate and 3-year overall survival rates. This indicates that laparoscopy has several advantages in short-term results

While many surgeons perform the so-called laparoscopy-assisted gastrectomy which requires mini-laparotomy incision and extracorporeal anastomosis, several options for totally laparoscopic gastrectomy are available. Even single-port laparoscopy is being performed frequently

cancer) [1, 6, 7, 12, 13].

210 Gastric Cancer

*2.2.4. Laparoscopic vs. open gastrectomy*

and is equivalent from oncologic standpoint [16].

NETs arise from the cells of the diffuse neuroendocrine system that are scattered all around the body and have both neural and endocrine characteristics (**Figure 10**). This is a heterogeneous group of tumours with wide variations in biologic behaviour, clinical picture and optimal management. Despite the fact that these tumours are typically indolent in nature, often

**Figure 10.** Gastric NET. (A) Haematoxylin-eosin, original magnification (OM) 100×. (B) Synaptophysin expression. Immunoperoxidase, OM 100×.

described as slowly growing, they all have malignant potential. Therefore, surgical resection is the only definitive treatment [18].

Gastric NETs (GNETs) are rare tumours, but their incidence is growing. The proportion of GNETs amongst all gastrointestinal NETs also increases. The current incidence is 1–2 per 100,000 persons per year which accounts for 8.7% of all gastrointestinal NETs. This increase of incidence is at least partly related to more widespread use of gastrointestinal endoscopy [18, 19].

There are three to four types of GNETs which differ significantly in terms of biologic behaviour, malignancy, prognosis and optimal treatment [18–20]. Some discrepancy in literature regarding classification of GNETs is noted. Although the latest European Neuroendocrine Tumour Society (ENETS) guidelines still divide GNETs in three types, a further subclassification of type 3 tumours is considered appropriate [20]. A comparison of different GNET types is depicted in **Table 2**.


GNET, gastric neuroendocrine tumour; MEN1-ZES, multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome; N, normal; NET, neuroendocrine tumour; G, grade; NEC, neuroendocrine carcinoma.

**Table 2.** Features of different gastric NETs.

#### **3.1. Type 1 GNETs**

This is the most common type of GNETs (70–80%) and is more frequently seen in female patients. Type 1 GNETs develop from enterochromaffin-like (ECL) cells and are associated with chronic gastric mucosal atrophy caused by *H. pylori* or autoimmune gastritis. These tumours are well differentiated, usually small (<1 cm), multiple, located in the fundus or corpus, limited to mucosa or submucosa and have an excellent prognosis [18–20]. They have a very low mitotic rate and metastatic potential (2–5%) [18, 19]. Pathophysiological mechanism of type 1 GNET development is achlorhydria caused by atrophic gastritis, which stimulates gastrin production, which in turn evokes ECL cell hyperplasia [19].

These tumours are best treated with conservative approach, with surgery reserved for selected cases. In ENETS guidelines, endoscopic surveillance every 1–2 years is recommended for lesions <1 cm without evidence of invasion into the proper muscular layer or metastasis. However, other specialists have recently suggested removal of all visible lesions with biopsy forceps or EMR (>5 mm tumours). This approach has to be compared with the previously mentioned less aggressive management in randomised trials to support its use. Any GNET with size close to 10 mm or threatening proper muscular layer has to be resected to avoid metastatic spread [18–20]. Research has shown superior complete resection rates for ESD compared to EMR in the treatment of GNETs [19].

Surgical resection is recommended for type 1 GNETs that are invading the proper muscular layer (T2), have recurred after endoscopic removal and are poorly differentiated or in case of positive resection margins after endoscopic resection [18–20]. Depending on the location and number of lesions as well as potential involvement of lymph nodes, local excision, partial or total gastrectomy is selected. Antrectomy to reduce hypergastrinemia is questionable and is rarely performed [18, 20].
