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Sugarbaker. J Cancer Metastasis Treat 2018;4:7 I http://dx.doi.org/10.20517/2394-4722.2017.67 Page 3 of 16

Tumor cell entrapment hypothesis
- resected gastric cancer -

Serosal invasion Lymphatic invasion Venous invasion
+ + +
Surgical trauma Lymphatic transection Hemorrhage

Free intraperitoneal tumor emboli

*Fibrin entrapment

Inflammatory cell infiltration

Growth factor stimulation

Cancer implant

*Occurs at resection site, on abraided bowel surfaces, and beneath abdominal incision

Figure 1. The tumor cell entrapment hypothesis suggests three mechanisms for microscopic residual cancer cells in patients having an R-0
gastrectomy. (From Sethna et al. [27] with permission)

PREVENTION PROTOCOLS USING PERIOPERATIVE CHEMOTHERAPY WITH GASTRECTOMY
Perioperative intraoperative chemotherapy can eliminate progression of peritoneal implantation after
curative surgery, however, it cannot treat residual disease within lymph nodes. Therefore, an adequate
lymphadenectomy is essential. Intraperitoneal chemotherapy enters the peritoneal nodule by simple diffusion
[28]
so it only penetrates to 1 or 2 mm . It is not effective in lymph nodes. Also, peritoneal nodules larger than 1
or 2 mm have ineffective drug delivery and all visible nodules must be removed prior to treatment.

LITERATURE REGARDING PERIOPERATIVE INTRAPERITONEAL CHEMOTHERAPY FOR
ADVANCED T-STAGE PRIMARY GASTRIC CANCER
There have been randomized and non-randomized trials about adjuvant perioperative intraperitoneal
chemotherapy compared to surgery alone for resectable primary gastric cancer without peritoneal spread.
Sugarbaker et al. published a meta-analysis in 2003 of articles published in English. Xu et al. published
[29]
[7]
[30]
a similar study in 2004. Yan et al. published a summary of randomized control trials about adjuvant
intraperitoneal chemotherapy for resectable gastric cancer in 2007. Feingold et al. published the most
[31]
recent summary of non-randomized and randomized studies in English of CRS and HIPEC and/or EPIC in
gastric cancer.
Yan et al. selected 10 of 13 randomized controlled trials that were judged to be of fair quality to be used
[30]
in the meta-analysis. There was a survival benefit associated with HIPEC [hazard ration (HR) 0.060; 95% CI
0.43-0.83; P = 0.002] or HIPEC with EPIC (HR 0.45; 95% CI 0.29-0.68; P = 0.0002). There was a marginal
benefit with normothermic intraoperative intraperitoneal chemotherapy but no significant improvement in
survival with EPIC alone or delayed postoperative intraperitoneal chemotherapy [Figure 2].