Are there intra-operative hemodynamic differences between the Coliseum and closed HIPEC techniques in the treatment of peritoneal metastasis? A retrospective cohort study

This retrospective cohort study comprised 30 patients with peritoneal metastasis of colorectal origin, who all fulfilled the criteria to undergo CRS and HIPEC at the Regional University Hospital of Malaga, from December 2011 to March 2015. All the patients were assessed, treated, and reviewed by the same surgical team. Most of the patients were originally admitted to our own hospital, with just 3 cases referred from other hospitals in the Malaga area. The study was authorized by the hospital Ethics Committee.

The inclusion criteria for patients to undergo the procedure included the following: an age between 18 and 70 years; patients with peritoneal metastasis with a peritoneal carcinomatosis index (PCI) ≤26; achievement of macroscopically complete surgical cytoreduction or with tumor remains no greater than 2.5 mm, with a completeness of cytoreduction score (CC score) of 0 or 1; patients with a life expectancy greater than 12 weeks and with a performance status (Eastern Cooperative Oncology Group) ≤2; patients with no extra-abdominal tumors, <3 liver lesions that were technically resectable, lack of biliary, and ureteral obstruction; patients in a good general and nutritional state of health, with no severe cardiac, lung, liver, kidney, or neurological condition that could contraindicate the surgery; and patients with no signs of intestinal obstruction and who had an adequate hematologic and hepatic balance. All patients also had to provide specific written informed consent.

The following variables were recorded for each patient:

Intra-HIPEC variables (measured at the end of the cytoreduction, 15 min after starting HIPEC and at the end of the procedure): hemodynamic parameters: O₂ saturation, systolic and diastolic blood pressure, central venous pressure, heart rate, and maximum inspiratory pressure. Intra-abdominal temperature: recorded at 10, 15, and 30 min after starting the procedure. The hemodynamic parameters were measured via continuous invasive monitoring. The intra-abdominal temperature was recorded with thermal sensors incorporated into the devices to administer the hyperthermia.

The outcome measures were perioperative morbidity and mortality as well as contamination episodes.

The HIPEC procedure was done following CRS. After the incorporation in our service of HIPEC, we initially started with the Coliseum technique for 2 years, after which we adopted the closed technique, which we continue to use, mainly because of technical improvements and a lower incidence of operating room contamination by chemotherapeutic agents. For us, the technique is more comfortable and safer, avoiding overflow and contamination of operating room personnel, in addition to which its efficacy has been well documented. The cytostatic agent used in both techniques was oxaliplatin at a dose of 460 mg/m² of body surface area, diluted for perfusion in 2 L/m² of glucose solution at 5%, maintaining the perfusion circuit at a constant flow of 0.5–0.7 L/min at 43 °C for 30 min. We used bidirectional chemotherapy to potentiate the intra-peritoneal oxaliplatin by the intravenous administration of folinic acid 20 mg/m², followed by 400 mg/m² of 5-FU in perfusion for 30 min, infused 1 h before the HIPEC. In both techniques, we used three intra-abdominal thermometers (placed in the areas of the pelvis and diaphragm) to monitor the temperature in the peritoneal cavity during perfusion. We also routinely used a probe with an esophageal temperature sensor to monitor the core temperature of the patient. In the HIPEC Coliseum cases, we used a standard technique (described by Sugarbaker). Abdominal wall suspension is achieved with a suture, creating a Coliseum for the instillation of the peritoneal perfusate placing two inflow and two outflow catheters, with a blood recovery device adapted for HIPEC as an infusion pump (Belmont®). The infusion pump forces the perfusate of chemotherapeutic drugs into the abdomen through a Tenckoff catheter and extracts it through the drains, with an approximate flow rate of 1 L/min. A heat exchanger keeps the infused fluid at 43–45 °C so that the intra-peritoneal fluid is maintained at about 41–43 °C. The perfusate first recirculates between the reservoir and the heat exchanger in order for it to reach the suitable temperature. At this point, full circulation of the perfusate into and out of the peritoneal cavity is established until achieving a minimum intra-peritoneal temperature of 41.5 °C. The chemotherapeutic drug is then included in the circuit, at which stage the perfusion timer is started. The perfusion in the cases that underwent closed HIPEC was done in a closed circuit, with placement of two inflow catheters in close proximity to the retroperitoneum and one more superficial outflow catheter. This technique differs from the open technique in that the skin is completely sutured along the laparotomy so that the perfusion is given in a closed circuit. The position of the patient is varied during the perfusion by inclining the operating table in the Trendelenburg and antiTrendelenburg positions and laterally in order to achieve homogeneous distribution of the heat. In comparison with the open technique, a greater volume of fluid is needed in the closed technique to establish the circuit; in addition to which greater intra-abdominal pressures are obtained during the perfusion. In these cases, we used the chemotherapy infusion pump from Evomed®. After the hyperthermic perfusion, the abdomen is again opened and the anastomoses, stomas, and placement of drains are done. Finally, the abdomen is closed definitively in the standard manner.

All the patients in both groups received the same anesthesia protocol.

All the patients in both groups shared similar demographic, clinical, and therapeutic features (Table 1). The median age of the patients was 52 years (range 33–66 years), with 16 women and 14 men. All the patients had an ECOG of 0. Analysis of the anesthetic risk (ASA) showed that 20 patients were ASA II, followed by 9 with an ASA of III. Only 1 patient was ASA I. In the series, 17 patients had synchronous peritoneal metastasis, with 13 having metachronous metastasis. In these latter, the median time to appearance of the metastasis was 10 months after surgery for the primary tumor (most in stages pT3N2aM0) and the corresponding adjuvant therapy. The median BMI of the series was 25.12 kg/m² (range 19.7–43.9 kg/m²), and the median preoperative PCI was 5.52 (range 0–20). In the Coliseum group, 9 patients received chemotherapy prior to the procedure, while 4 patients in the closed technique group received neoadjuvant therapy.

A total of 30 CRS plus HIPEC procedures were performed. We performed peritonectomy procedures including a large xyphopubic laparotomy, assessing the extension of the peritoneal disease. Staging of the degree of tumor involvement was done with the PCI. All the patients underwent the same surgical procedure, starting with the pelviperitonectomy, resecting the uterus and the adnexa if these were affected, as well as the Douglas pouch. If the rectosigmoid was affected, it was also resected en bloc, with reconstruction of the tract by colorectal anastomosis (or ileorectal in the patients who required total colectomy) with a 29 mm circular stapler. Stomas to protect the anastomosis were done depending on the patient risk factors and the nature of the anastomosis. In the event of implants infiltrating the small intestine and depending on their size, intestinal resections with anastomosis were done or fulguration with the round end of the electro-cauterizer. Cytoreduction of the rest of the peritoneal cavity was then done, systematically performing a complete omentectomy. We always used at least one drain for abdominal aspiration placed in the pelvis, and in those patients who underwent intestinal anastomosis, we placed another aspiration drain nearby.

No statistically significant differences were observed for any of the hemodynamic parameters studied (Fig. 1). The diastolic blood pressure figures varied less during the procedure in the closed technique, being more stable than those with the Coliseum technique. Though the difference was not significant (p = 0.09), there was a certain tendency. The central venous pressure figures varied more during the closed technique compared with the Coliseum technique; again not significantly (p = 0.08) but with a tendency. Finally, the intra-abdominal temperature remained more stable and homogenous during the closed technique throughout the procedure, varying less than with the Coliseum technique; this difference was statistically significant (p = 0.009).

All complications arising during the first 30 postoperative days were recorded, classified according to Dindo-Clavien. The incidence of postoperative complications in the HIPEC Coliseum group was 53% (8 patients), all occurring during the early postoperative period (first 15 days). The complications were grade II: urinary fistula requiring percutaneous nephrostomy, nosocomial pneumonia (2 cases), rhabdomyolysis, and acute pulmonary edema; grade IIIA (2 cases): intra-abdominal abscess treated with percutaneous drainage and hepatic abscess that required percutaneous drainage; and grade IIIB (1 case): abdominal sepsis secondary to bacterial translocation that necessitated urgent re-operation. The incidence of complications in the closed HIPEC group was 13% (2 patients). These were grade II (surgical wound infection) and grade IIIB (acute pulmonary edema and acute respiratory failure that required mechanical ventilation).