There is no standard treatment for PC from GC. CRS plus HIPEC represent a multidisciplinary approach to this problem. It was first reported in 1988 by Fujimoto et al on 15 patients with PC secondary to advanced GC, with a mean survival of 7.2 ± 4.6 months with acceptable morbidity.22
This new treatment modality gradually gains acceptance in many countries. Although the reported studies use different PCI scoring system to evaluate the extent of PC and different HIPEC approaches, they produce similar results that CRS plus HIPEC is an appropriate treatment option for a selected subgroup of GC patients with PC, and for advanced GC with high risk of developing PC. A systematic review and meta-analysis of 13 acceptable quality randomized controlled trials also have established that HIPEC is associated with marked improvement in survival in advanced GC, in comparison with the current standard treatments.17
As a result, a panel of international experts strongly recommend that CRS plus HIPEC be the current standard treatment for advanced GC.23
Nevertheless, controversy over this treatment modality remains, and more high quality clinical studies are required to clarify the value and the usefulness of this strategy.
In this prospective randomized study, CRS and HIPEC has been demonstrated to provide survival benefit for gastric PC. The median OS was 6.5 months for CRS group and 11.0 months for CRS + HIPEC group. The results were similar to those reported by Glehen et al. (OS 10.3 months) and Yonemura et al. (OS 11.5 months).13
Compared with CRS alone, CRS + HIPEC could extend the OS by nearly 70% (6.5 vs. 11.0 months). This is similar to the 76% improvement of OS (22.2 vs. 12.6 months) favoring CRS + HIPEC in the landmark phase III clinical trial in colorectal PC by the Netherlands Cancer Institute, which has provided level 1 evidence to support HIPEC with CRS for colorectal PC.16
Taking together, these results suggest that in either gastric or colorectal PC, CRS + HIPEC could provide similar survival advantage in selected cases.
Our results also demonstrated that patients with metachronous PC had worse survival than those with synchronous PC, in agreement with Glehen et al.13
The usefulness of CRS + HIPEC was evident for synchronous PC (median OS 12.0 vs. 6.5 months). For metachronous PC, the number was too small for any definite conclusion, although the median OS was shorter in the CRS + HIPEC group (5.5 months) than in the CRS alone group (11.0 months). More studies with greater sample size are required to clarify this issue.
This study demonstrated again the importance of complete cytoreduction for long term survival. Whether patients underwent CRS alone or CRS + HIPEC, CC 0–1 was independently associated with longer survival (Fig. ). Therefore, efforts should be focused on complete CRS.
The synergistic effects of CRS to remove the macroscopic tumor and HIPEC to eradicate microscopic residual diseases are major advantages of this combined approach. However, such a procedure also brings greater risks for major morbidity and mortality. Major complications are directly related to the magnitude of the procedure, including the extent of resections and peritonectomy, the number of anastomoses, the duration of surgery, and the doses of cytotoxic chemotherapeutic drugs used in HIPEC.25
As a result of extensive resection, more blood loss, and more complex gastrointestinal reconstruction, complications become more frequent. To minimize potential complications, all patients in our group required blood, plasma and cryoprecipitation transfusion and large doses of antibiotics during and after operation. All patients were in intensive care for at least 24 h after the procedure. Even in intensified medical and surgical care, complications did occur. In terms of SAE, there were no statistically significant differences in the incidence of SAE between CRS group (11.7%) and CRS + HIPEC group (14.7%). But the CRS + HIPEC group had 3 cases with wound infection and sepsis, possibly as a result of long wound exposure during the lengthy operation. Our results are similar to the 19% grade IV complication rate reported by Sugarbaker et al.26
Our multivariate analysis demonstrated that SAE was an independent factor for worse survival. Therefore, greater efforts should be made to minimize SAE.
Severe hematological adverse events were not encountered in our patients. This could be due to relatively lower doses of mitomycin C and cisplatin used. Although we did not conduct pharmacokinetics studies to monitor the drug metabolism in the perfusion fluid, mitomycin C concentration of 5 μg/ml (30 mg/6000 ml) is still above the cytotoxic concentration, because previous studies have confirmed that 3 μg/ml of mitomycin C in HIPEC for 2 h can kill all GC cells in ascites and on the peritoneal surface.27
In conclusion, this study has found that for synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.