Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer with Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP).

BACKGROUND: Gastric cancer (GC) with peritoneal carcinomatosis (PC) is traditionally considered a terminal stage of the disease. The use of a multimodal treatment, including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), can benefit these patients. Our goal was to evaluate the morbidity and survival outcomes of these patients. METHODS: This is a retrospective, multicenter study from a prospective national database of patients diagnosed with PC secondary to GC treated with CRS and HIPEC from June 2006 to October 2017. RESULTS: Eighty-eight patients from seven specialized Spanish institutions were treated with CRS and HIPEC, with median age of 53 years; 51% were women. Median Peritoneal Cancer Index (PCI) was 6, and complete cytoreduction was achieved in 80 patients (90.9%). HIPEC was administered in 85 cases with 4 different regimens (Cisplatin + Doxorubicin, Mitomycin-C + Cisplatin, Mitomycin-C and Oxaliplatin). Twenty-seven cases (31%) had severe morbidity (grade III-IV) and 3 patients died in the postoperative period (3.4%). Median follow-up was 32 months. Median overall survival (OS) was 21.2 months, with 1-year OS of 79.9% and 3-year OS of 30.9%. Median disease-free survival (DFS) was 11.6 months, with 1-year DFS of 46.1% and 3-year DFS of 21.7%. After multivariate analysis, the extent of peritoneal disease (PCI ≥ 7) was identified as the only independent factor that influenced OS (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.26-4.46, p = 0.007). CONCLUSIONS: The multimodal treatment, including CRS and HIPEC, for GC with PC can improve the survival results in selected patients (PCI < 7) and in referral centers.

Hyperthermic Intraperitoneal Chemotherapy and Recirculation with CO2: A Safe Technique.

INTRODUCTION: Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has evolved as a treatment for peritoneal carcinomatosis in various tumors after a careful and complete cytoreductive surgery, and it demonstrated much better and longer survival than more traditional therapeutic schemas. Our objective has been to examine the safety, efficacy and survival achieved with closed technique with CO2-agitation system Combat PRS® (Peritoneal Recirculation System: PRS). To achieve this, we compared the appearance of adverse events, mortality and survival with the described using classic techniques (open, closed without CO2-agitation) for the treatment of selected patients with peritoneal carcinomatosis; Materials and methods: We studied overall survival, disease-free survival and safety (morbidity and mortality) of the administration of HIPEC through a closed method technique with CO2 recirculation (Combat PRS®) in 482 patients from 11 Spanish hospitals; Results: The mortality of our technique (1.66%) was similar to other published techniques (open, closed). Morbidity exhibited a 9.96% rate of Clavien-Dindo (CD) III/IV complications in 482 patients, which was lower than in other series. Survival (overall survival (OS) and disease-free survival (DFS)) was similar to previously published results: 86% 1y-OS, 54% 3y-OS, 77% 1y-DFS and 31% 3y-DFS; Conclusion: The procedure with closed PRS with CO2 agitation is as safe as standard open and closed procedures for the administration of HIPEC after complete cytoreductive surgery, with similar and very low mortality (1.66%) and lower morbidity (9.96% CD III and IV in our series vs range of 20-40% in the majority of different series); only Kusamura had similar results, with 12% in 205 patients, using the closed technique without CO2 agitation).

HLA-G 3'UTR Polymorphisms Are Linked to Susceptibility and Survival in Spanish Gastric Adenocarcinoma Patients.

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.