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Occult Tumor Cells in Lymph Nodes of Patients with Gastric Cancer: A Systematic Review on Their Prevalence and Predictive Role

Background and Aims: The presence of lymph node (LN) metastasis is a key prognostic factor for gastric adenocarcinoma. However, even among patients without LN metastasis (N0), recurrence may occur. In some of these cases, occult tumor cells (OTC) are thought to play an important role. We aimed to determine the prevalence of OTC and its clinical relevance. Methods: We conducted a systematic review of studies in English published until September 2013 that addressed OTC prevalence and/or its clinical relevance. The studies were retrieved from the MEDLINE database. Results: We included 42 studies. The most frequently used methods for detecting OTC were immunohistochemical examination (IHC) and/or polymerase chain reaction (PCR) with a wide range of markers. Using IHC for OTC detection, in patients and in LN, the prevalence varied from 9 to 88% and 0.4 to 42%, respectively. With PCR, it ranged from 17 to 46% in patients, and from 3 to 33% in LN. In the studies assessing the predictive role of OTC in gastric cancer recurrence (n = 24), 8 studies found no statistical association, while 18 concluded that OTC presence was associated with poorer prognosis. However, only 6 studies presented a significantly different 5-year survival rate between patients with and without LN micrometastasis. Conclusions: OTC seems to occur in gastric cancer patients with a variable prevalence, depending on the definition, methods and setting. The majority of the retrieved studies (75%) evaluating the predictive role of OTC conclude that its presence is associated with a worse prognosis.