**2. Gastric adenocarcinomas**

**1. Introduction**

200 Gastric Cancer

still remains.

*pylori* infection (**Table 1**) [2].

and endoscopic surgical techniques.

**Table 1.** Risk factors of gastric cancer.

Despite significant reduction in incidence, important advances in understanding of tumour biology and improvements of complex management of this disease, gastric cancer is still a major and in many aspects poorly resolved oncological problem. Thus, the title 'silent killer'

Gastric cancer is the fourth most common cancer and second leading cause of cancer death in the world, with nearly a million of new cases in 2012 [1]. There are substantial geographical variations in gastric cancer incidence and survival, with half of all cases diagnosed in East Asia (GLOBOCAN data). This is related to the prevalence of risk factors, mainly *Helicobacter* 

Similarly, stage at diagnosis is also dependent on geographical factors and local screening policies. In most countries, the majority of cases are still diagnosed at an advanced stage (see **Figure 1**). There are many classifications for gastric cancer. Anatomically, it can be divided in true gastric (noncardia) cancers and gastro-oesophageal (cardia) cancers, which differ in epidemiology and surgical treatment [1]. Histologically, the majority of gastric cancers are malignant epithelial tumours, namely, carcinomas (>90%), while neuroendocrine tumours (NETs) and

Surgery is still the only potentially curative treatment of gastric cancer. Despite adequate surgical resection, gastric cancer has a high recurrence rate after operation [4]. Survival parameters have traditionally been higher in Asian countries due to screening and higher proportion of early disease [5]. A 5-year overall survival of 72.3% has been reported in one Korean study, whereas European studies report survival of 28.0–44.3% [2]. To improve these figures, a sys-

Since gastric carcinomas, NETs and GISTs have different characteristics, natural history and prognosis, the cornerstone of treatment, surgical resection, has to be adjusted as well. In this chapter, we discuss the common features and differences in surgical treatment of different gastric cancers according to TNM stage as well as the latest advances in minimally invasive

gastrointestinal stromal tumours (GISTs) rank next by frequency [3].

tematic and evidence-based approach must be used to treat gastric cancer.

**Risk factor Influence and relative risk**

*H. pylori* infection ↑ 3.02 Pernicious anaemia ↑ 6.8 Cigarette smoking ↑ 1.53 Heavy alcohol consumption ↑ 1.20 High dietary salt ↑ 1.07 Dietary fruit and vegetables ↓ 0.81 Carcinomas, representing malignant epithelial tumours, arise from epithelial cells in the most superficial, mucosal layer of gastric wall. Traditionally, carcinomas have been divided, according to Lauren classification, in diffuse and intestinal type (**Figure 2**). The former is poorly differentiated, lacks glands, has a more pronounced genetic component, spreads via transmural and lymphatic route and generally has a worse prognosis. Intestinal type is characterised by glandular structures, well or moderately differentiated tumours with haematogenous spread and more pronounced environmental risk factor influence [6]. More recently, the WHO produced a classification that was in concert with histological division of gut tumours—tubular, papillary, mucinous adenocarcinomas, poorly cohesive carcinoma and rare variants [1]. However, there is very little evidence that the aforementioned classifications have additional prognostic value compared to TNM staging [6]. Therefore, for this practical guide, only TNM stage will be taken into consideration.

**Figure 2.** Types of gastric carcinoma by Lauren classification. (A and B) Intestinal type: (A) gross view in gastrectomy and (B) morphological structure showing adenocarcinoma. Haematoxylin-eosin, original magnification (OM) 100×. (C and D) Diffuse type: (C) gross view in gastrectomy and (D) morphological structure showing signet ring cells. Immunoperoxidase, cytokeratin AE1/AE3, OM 400×.

### **2.1. Early gastric adenocarcinomas**

For very early gastric carcinomas (T1a), endoscopic treatment is possible. Precise patient selection is essential to avoid suboptimal treatment. The target is to identify a subgroup of patients for whom the risk of lymph node metastases is virtually zero [5]. Both Japanese and European guidelines have similar criteria for patient selection for endoscopic treatment [5, 7]:


However, in the guidelines, issued by european society for medical oncology (ESMO), these criteria are necessary to consider endoscopic treatment [III, B], whereas Japanese guidelines state them as an absolute indication for endoscopic resection [5, 7]. This underlines the experience of Japanese doctors in endoscopic treatment of very early gastric cancer. The resection is considered curative when a meticulous pathologic examination of specimen reveals an en bloc resection of a tumour with previously mentioned features, negative resection margins and no lymphovascular invasion [7].

There are two principal methods for endoscopic removal of gastric cancer. In endoscopic mucosal resection (EMR), a saline injection is used to elevate the tumour and is followed by an excision with a snare device using electrocautery [6] (**Figure 3**). This is generally indicated for lesions smaller than 10–15 mm [5].

In endoscopic submucosal dissection (ESD), electrocautery is used to mark the borders of the tumour followed by hydrodissection with epinephrine and indigo carmine. The lesion is then removed en bloc by dissecting the submucosal layer from the proper muscle layer using insulation-tipped electric knife [6, 7] (**Figure 4**).

**2.1. Early gastric adenocarcinomas**

Immunoperoxidase, cytokeratin AE1/AE3, OM 400×.

**1.** Confined to mucosa (T1a)

and no lymphovascular invasion [7].

**2.** Well differentiated

**4.** Diameter of ≤2 cm

**3.** Non-ulcerated

202 Gastric Cancer

For very early gastric carcinomas (T1a), endoscopic treatment is possible. Precise patient selection is essential to avoid suboptimal treatment. The target is to identify a subgroup of patients for whom the risk of lymph node metastases is virtually zero [5]. Both Japanese and European guidelines have similar criteria for patient selection for endoscopic treatment [5, 7]:

**Figure 2.** Types of gastric carcinoma by Lauren classification. (A and B) Intestinal type: (A) gross view in gastrectomy and (B) morphological structure showing adenocarcinoma. Haematoxylin-eosin, original magnification (OM) 100×. (C and D) Diffuse type: (C) gross view in gastrectomy and (D) morphological structure showing signet ring cells.

However, in the guidelines, issued by european society for medical oncology (ESMO), these criteria are necessary to consider endoscopic treatment [III, B], whereas Japanese guidelines state them as an absolute indication for endoscopic resection [5, 7]. This underlines the experience of Japanese doctors in endoscopic treatment of very early gastric cancer. The resection is considered curative when a meticulous pathologic examination of specimen reveals an en bloc resection of a tumour with previously mentioned features, negative resection margins

**Figure 3.** Endoscopic mucosal resection: (1) Localisation of tumour, (2) submucosal injection of saline to elevate the area and (3) electrocautery is applied through snare device to perform resection followed by removal of the lesion.

**Figure 4.** Endoscopic submucosal dissection. (1) Marking borders of the tumour with electrocautery, (2) submucosal injection of a lifting agent, (3) circumferential mucosal incision followed by submucosal dissection with insulationtipped electric knife and (4) haemostasis.

A meta-analysis comparing both methods was performed, and the results indicated significantly higher en bloc and complete histologic resection rates for ESD (odds ratio, OR = 9.69 vs. OR = 5.66, *p* < 0.001). This increased radicality and also resulted in lower recurrence rate (OR = 0.009, *p* < 0.001). On the other hand, perforation rate was significantly higher for ESD (OR = 4.67, *p* < 0.001) [8]. The European Society of Gastrointestinal Endoscopy Guidelines recommend ESD as the standard procedure for most early gastric tumours [IV, B] [5].

Extended criteria for ESD also are known. One Korean study found no statistically significant differences in recurrence rates between absolute indication and extended indication groups (7.7% vs. 9.3%, *p* = 0.524). However, due to the lack of high-quality evidence, these indications remain investigational and will not be discussed in detail here [7].

Surgical resection is indicated in patients with T1 tumours that do not meet the criteria for endoscopic treatment. However, the extent of resection can be reduced compared to more advanced cancers [5]. For patients with clinical T1 and N0 who require surgical resection for middle gastric cancer, a pylorus-preserving gastrectomy can be offered if the distal extent of tumour is at least 4 cm proximal to pylorus (see **Figure 5**). For early proximal gastric tumours, proximal gastrectomy is an option if more than half of the distal stomach can be preserved (**Figure 6**) [4]. As for segmental gastrectomy and local resection under sentinel navigation, these are still considered investigational [7]. If the above-mentioned criteria are not met, early gastric cancer is treated with a standard gastrectomy. In addition, lymphadenectomy is required because of the risk of lymph node metastases due to submucosal invasion. The extent of lymphadenectomy in early gastric cancer will be discussed in the following chapter.

**Figure 5.** Pylorus-sparing gastrectomy.

A meta-analysis comparing both methods was performed, and the results indicated significantly higher en bloc and complete histologic resection rates for ESD (odds ratio, OR = 9.69 vs. OR = 5.66, *p* < 0.001). This increased radicality and also resulted in lower recurrence rate (OR = 0.009, *p* < 0.001). On the other hand, perforation rate was significantly higher for ESD (OR = 4.67, *p* < 0.001) [8]. The European Society of Gastrointestinal Endoscopy Guidelines rec-

**Figure 4.** Endoscopic submucosal dissection. (1) Marking borders of the tumour with electrocautery, (2) submucosal injection of a lifting agent, (3) circumferential mucosal incision followed by submucosal dissection with insulation-

Extended criteria for ESD also are known. One Korean study found no statistically significant differences in recurrence rates between absolute indication and extended indication groups (7.7% vs. 9.3%, *p* = 0.524). However, due to the lack of high-quality evidence, these indications

Surgical resection is indicated in patients with T1 tumours that do not meet the criteria for endoscopic treatment. However, the extent of resection can be reduced compared to more advanced cancers [5]. For patients with clinical T1 and N0 who require surgical resection for middle gastric cancer, a pylorus-preserving gastrectomy can be offered if the distal extent of tumour is at least 4 cm proximal to pylorus (see **Figure 5**). For early proximal gastric tumours, proximal gastrectomy is an option if more than half of the distal stomach can be preserved (**Figure 6**) [4]. As for segmental gastrectomy and local resection under sentinel navigation,

ommend ESD as the standard procedure for most early gastric tumours [IV, B] [5].

remain investigational and will not be discussed in detail here [7].

tipped electric knife and (4) haemostasis.

204 Gastric Cancer

**Figure 6.** Proximal gastrectomy.
