**3.1. Minimal residual disease—definition**

The question is: Which GCLM patients are suitable for surgical intervention?

patients and contraindicating surgical intervention.

defines three adverse prognostic factors:

**1.** Invasion of serosa by primary tumor

**3.** Size of liver metastasis exceeding 50 mm.

**2.** Three and more liver metastases

resection [15].

246 Gastric Cancer

metastasis of GCLM [16].

At present, there is no direct marker available, defining the degree of biological aggressiveness of the tumor (indicating or contra-indicating the surgical treatment), therefore we are left to rely on indirect prognostic factors—number of liver metastases, size of metastatic lesion [8, 72]. Several studies have attempted to identify the prognostic factors defining adverse outlook for

Among these studies, a multicenter study by Japanese authors stands out [15]. This study

The study noted a significant difference in survival between patients without a prognostic factor and patients with one of the three prognostic factors. The authors recommend to consider

Patients with lower number of risk factors had better 3- and 5-year survival following liver

The indication for surgical intervention in GCLM is subject to overall clinical condition of the patient, but liver resection should definitely be contraindicated in the presence of all three

Repeated hepatectomy was performed only in 14.4% of patients, which is significantly lower number of hepatectomies compared to patients with colorectal cancer. This is caused by dif-

Hepatic resection is presently considered and justified only in case of solitary relapsing

The role of chemotherapy in GCLM is not clearly defined. Neo-adjuvant chemotherapy is being brought forward that can be used to differentiate responders from nonresponders.

Several studies assessed the use of RFA in GCLM, recommending it for solitary lesions up to 30 mm in size, located in the periphery of the liver. No clear advantage of RFA compared to

Surgical treatment is not able to provide patients with GCLM a complete cure. Half of the patients had recurrence within 1 year, in spite of R0 resection and careful selection. On the other hand, there was sufficient number of patients with long-term survival. This can be explained by

GCLM patients treated by systemic chemotherapy alone have 1.7% 5-year survival [17].

surgical intervention in the presence of any of the three risk factors.

adverse prognostic factors (no long-term survival was noted) [15].

ferent pathophysiological course of gastric cancer relapse [16].

Surgical intervention is contraindicated in nonresponders [17].

varying tumor sub-populations with differing biological behavior [15].

surgical resection has been shown [18, 72].

Minimal residual diseases are remnant tumor cells that are left after treatment and that cannot be detected by conventional clinical studies. These cells can persist in the primary site or as disseminated tumor cells in proliferative and/or dormant phases [19].

A source of minimal residual disease is considered systemic micrometastatic diseases caused by early dissemination of cancer cells from the primary tumor. These cells have the ability of dormancy [17].

In gastric cancer patients, minimal residual disease is defined as micrometastases and isolated tumor cells (ITC). First, micrometastasis is defined as tumor cell clusters between 0.2 and 2.0 mm in the greatest dimension, whereas ITC are defined as single tumor cells or small clusters of tumor cells less than 0.2 mm in size (seventh Tumour-Node-Metastasis Classification classification) [20].

Cancer stem cells (CSCs) are the cornerstone of micrometastases and define their characteristics and behavior. The clinical implications and/or prognostic significance of the micrometastases are still a matter of debate.
