Rationale for the administration of systemic 5-FU in combination with heated intraperitonal oxaliplatin.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (OX) is the standard of care for selected patients with peritoneal carcinomatosis of colorectal origin. Because 5-FU is mandatory to improve efficacy of OX when used by systemic route, several teams now empirically combine intravenous (IV) 5-FU with HIPEC OX, but this practice has yet to be supported by preclinical data. Using a murine model, we studied the impact of IV 5-FU on peritoneal absorption of HIPEC OX. METHODS: Under general anesthesia, 24 Sprague-Dawley rats were submitted to 4 different doses of IV 5-FU (0, 100, 400 and 800 mg/m2) and a fixed dose of HIPEC OX (460 mg/m2) perfused at 40 °C during 25 min. At 25 min, samples in different compartments were harvested (peritoneum, portal vein and systemic blood) and the concentrations of 5-FU and OX were measured by high performance liquid chromatography. RESULTS: Peritoneal absorption of OX was significantly higher (17.0, 20.1, 34.9 and 38.1 nmol/g, p < 0.0001) with increasing doses of 5-FU (0, 100, 400 and 800 mg/m2, respectively). Peritoneal absorption of OX reached a plateau between 400 and 800 mg/m2 of IV 5-FU. CONCLUSION: IV 5-FU enhances peritoneal absorption of HIPEC OX. The most efficient dose of IV 5-FU to be used in combination with HIPEC OX seems to be 400 mg/m2.

Second-look surgery plus HIPEC for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Should we resect the initial anastomosis? An observational study.

BACKGROUND: Cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves the overall survival in selected cases of peritoneal carcinomatosis (PC) of colorectal origin. Second-look surgery in asymptomatic patients at high risk of developing PC has shown encouraging results. This study aims at identifying cases in which initial anastomosis should be resected. METHODS: Patients treated by second-look surgery and HIPEC were identified from a prospective database. High-risk was defined as synchronous resected and minimal PC, ovarian metastasis or perforated primary tumor. Patients were divided in two groups based on intra-operative evaluation of the anastomosis: possibly-invaded (PI) and unlikely-invaded (UI). PI was defined as 1) PC away from the anastomosis, 2) nodules resting on the anastomosis 3) anastomotic stenosis or anastomotic thickening. Anastomosis in the PI group were resected. RESULTS: Forty patients were included: 12 in the PI group and 28 in the UI group. Incidence of pathological anastomotic invasion was 42% (5 on 12 patients) in the PI group. In the UI group, 2 patients had anastomotic recurrence, both associated with peritoneal recurrence. Morbidity and mortality was not influenced by anastomosis resection. The presence of suspicious nodules on the anastomosis had a sensitivity of 100% and a specificity of 89% in predicting anastomotic invasion. CONCLUSION: In second-look surgery and HIPEC for colorectal cancer at high-risk of PC, anastomosis should be resected when overlying PC nodules are found. This attitude is supported by high sensitivity of this finding for anastomotic invasion and low morbidity related to anastomotic resection.

Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. AIM: To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. PATIENTS AND METHODS: Patients (n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. RESULTS: All the patients with a PCI ≥ 15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥ 15 (p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥ 15 (p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) (p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥ 15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%). CONCLUSION: A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.