Abstract
Background
Rupture of hepatocellular carcinoma (HCC) releases tumor cells and furthers peritoneal metastasis. The present study investigated the killing effects of distilled water (DW) on HCC cells and the clinical outcomes of patients undergoing liver resection with DW lavage for spontaneously ruptured HCC.
Materials and Methods
Human HCC cells (BEL-7402, SMMC7721) were treated with DW, the morphological changes observed, and cell viability measured. DW-treated HCC cells were also injected intraperitoneally into nude mice, and the formation of tumor nodules and overall survival (OS) measured. The clinicopathological data of 141 consecutive patients undergoing liver resection for spontaneously ruptured HCC during 1998–2011 were retrospectively reviewed.
Results
Fifteen minutes of DW exposure caused complete cell lysis of HCC cells in vitro and completely prevented tumor formation and prolonged survival time in nude mice. Among the 141 patients, the 1-, 3-, and 5-year disease-free survival (DFS) and OS rates in patients administered DW lavage during surgery were 68.9, 24.6, and 6.6 %, respectively, and 95.1, 65.1, and 40 %, respectively, which were significantly higher than those in patients who did not (P < 0.05). DW lavage was an independent predictor of recurrence (odds ratio (OR), 0.34; 95 % confidence interval (CI), 0.23–0.51; P < 0.001) and OS (OR, 0.35; 95 % CI, 0.23–0.53; P < 0.001).
Conclusions
Fifteen minutes of DW lavage can effectively kill HCC cells in vitro and prevent tumor formation in vivo. DW lavage significantly improves long-term outcomes in patients undergoing liver resection for spontaneously ruptured HCC and could be administered intra-operatively when tumor cell liberation is suspected.
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Acknowledgments
This work was funded by the National Natural Science Foundation of China (No. 81172293) and allocated to Dr. Zhi-yong Huang.
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Supplemental Fig. 1
Evaluation of the toxicity of the peritoneal injection of DW. Two milliliters of PBS or DW was injected into the abdominal cavities of 4-week-old male BALB/c nude mice. One week after injection, all mice were killed, and intra-abdominal findings were investigated (n = 3). a No significant differences were observed in the representative macroscopic findings of abdominal organs between the PBS and DW groups. b No significant differences were observed in the representative histological findings of the small intestine or liver between the PBS and DW groups (magnification, ×100). Peritoneal injection of DW did not cause toxicity in mice. PBS phosphate-buffered saline, DW distilled water. (GIF 90 kb)
Supplemental Fig. 2
Inhibition of the establishment of peritoneal dissemination after incubation of SMMC7721 cells with DW. a Representative macroscopic findings in the abdominal cavity. Arrows indicate disseminated nodules. b The mean size, number of disseminated nodules, and tumor incidence were significantly decreased by DW incubation. The OS was significantly worse in the PBS group than in the DW group (n = 10 per group, *P < 0.05; § P > 0.05). PBS phosphate-buffered saline, DW distilled water, OS overall survival. (GIF 81 kb)
Supplemental Fig. 3
Inhibition of the establishment of peritoneal dissemination of SMMC7721 cells by peritoneal injection of DW at the indicated time points. a Representative macroscopic findings in the abdominal cavity. Arrows indicate disseminated nodules. b The mean size, number of disseminated nodules, and tumor incidence were significantly decreased by peritoneal DW injection. The OS was significantly worse in the PBS group than in the DW group (n = 10 per group; *P < 0.05; § P > 0.05). PBS phosphate-buffered saline, DW distilled water, OS overall survival. (GIF 97 kb)
Supplemental Fig. 4
DW lavage improved long-term outcomes of patients in the emergency surgery group and staged surgery group. Comparison of DFS (a) and OS (b) rates between the DW and non-DW groups within the emergency surgery group. Comparison of DFS (c) and OS (d) rates between the DW and non-DW groups within the staged surgery group. (GIF 28 kb)
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Zhou, Sj., Zhang, El., Liang, By. et al. Distilled Water Lavage During Surgery Improves Long-Term Outcomes of Patients with Ruptured Hepatocellular Carcinoma. J Gastrointest Surg 19, 1262–1270 (2015). https://doi.org/10.1007/s11605-015-2797-0
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DOI: https://doi.org/10.1007/s11605-015-2797-0