It can be concluded that CYT+ is a significant predictor of worsened survival. These findings prompted the American Joint Committee on Cancer (AJCC) to reevaluate the staging of patients with gastric cancer to include the evaluation of peritoneal cytology. Based on these data, CYT+ is now classified as an M1 disease, even in the absence of other visible disease [24]. In fact, median overall survival in patients with isolated CYT+ disease is no different than those with gross abdominal metastasis at laparoscopy [25]. Interestingly in the Ribeiro et al. series, no patients with early lesions (≤ T2) were CYT+ [23]. This trend holds true in several subsequent evaluations; similar to evidence presented for staging laparoscopy in general, peritoneal fluid sampling has a lesser effect on therapeutic planning in early stage gastric cancer and may be reserved for only those who present with advanced lesions (Fig. 10.1).

Treating patients with M1_CYT+ disease with chemotherapy has been shown to improve survival (Table 10.2). Badgwell et al. reported a 7-month survival gain (total 16.2 months) over palliation alone [25]. A subsequent trial by Lorenzen et al. showed that 37 % of CYT+ patients were able to convert to CYT−; these responders had improved median survival compared to those who were persistently CYT+ (36.1 months vs 9.2 months) [26] and was again confirmed by Mezhir et al. [27]. Of note in the Lorenzen study however, is that even though the primary lesion may become resectable, perhaps as high as a quarter of the patients with locally advanced gastric lesions may progress from CYT− to CYT+ despite chemotherapy.

Treatment of CYT+ disease remains a novel area of focus [28, 29]. In addition to traditional chemotherapy administration, intraperitoneal chemotherapy has been evaluated. The theory behind this treatment is to eradicate free tumor cells and prevent them from seeding the peritoneum and abdominal viscera. A meta-analysis of three trials showed a trend towards improved overall survival (HR 0.70, p < 0.008), putting this forward as a potential treatment while awaiting further studies [29]. On a more basic hypothesis, a single, but intriguing randomized controlled trial by Kuramoto et al. has evaluated the effect of simply diluting out the free tumor cells by means of extensive intraoperative lavage [30]. In patients with locally resectable CYT+ disease who underwent surgery alone, 5 year overall survival was 0 %, compared to 4.6 % in those who received surgery with intraoperative peritoneal chemotherapy. This was in stark comparison to the 43.8 % survival in the patients who received surgery, 10 L saline lavage of the peritoneum, and intraperitoneal chemotherapy.

Subsequent resection in these patients with complete peritoneal response with chemotherapy remains unclear. In a small subset of patients who converted from CYT+ to CYT− and underwent attempted curative resection, there was no improvement in median disease specific survival when compared to converters who did not undergo resection [27]. A small study by Okabe et al. does however report a survival advantage in highly selected complete responders who go on to obtain an R0 resection. This remains experimental, and at most institutions, patients with M1_CYT+ disease will only undergo resection for palliation of symptoms.