Peritoneal carcinomatosis (PC) is, after liver metastases, the second most frequent cause of death in patients with colorectal cancer (CRC). The peritoneal surface is involved in 10%-30%[ ^{1 - 3}] of patients with CRC and in roughly 7%-8%[ ^{3 , 4}] at the time of primary surgery, in 4%-19% of cases during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40%-80% of patients who succumb to CRC[ ⁴]. However, in the 25% of patients with metastatic disease, the peritoneal cavity seems to be the only site of diffusion even after extensive diagnostic investigations[ ⁵].

The PC occurs by a sequence of events: the spreading of cancer cells in the peritoneal cavity, their adhesion to the mesothelial surface and the invasion of the subperitoneal space for proliferation and vascular neogenesis[ ⁷]. The high incidence of tumour implantation on the peritoneal surface in CRC can occur by intraperitoneal tumour emboli as result of serosal penetration, or can be the consequence of surgical management through leakage of the malignant cells from the lymphatic vessels or through their dissemination due to tumour trauma as result of dissection, with subsequent fibrin entrapment and tumour promotion of the entrapped cells[ ⁸].

As reported by Esquivel et al[ ⁶], in the light of a new aggressive approach based on the combination of CRS and HIPEC, the story of peritoneal carcinomatosis can probably be rewritten like the story of colorectal liver metastases.

Perioperative intraperitoneal chemotherapy consists of the intraperitoneal administration of drugs in a large volume of fluid either during the operation or postoperatively[ ¹⁶]. Intraperitoneal chemotherapy can increase local exposure of the peritoneal surface to pharmacologically active molecules, especially those of high molecular weight (Mitomycin C, 5-FU, Doxorubicin, Cisplatin, Paclitaxel and Gemcitabine) resulting in a more uniform distribution throughout the abdominal cavity[ ¹⁶]. This treatment can also be performed under hyperthermic conditions. Hyperthermia, associated with intraperitoneal chemotherapy, presents several advantages; it has a direct cytotoxic effect and enhances the activity and penetration depth of many cytotoxic drugs[ ^{17 - 19}]. Because it is estimated that the optimal target of thermochemotherapy is limited to few millimetres, is mandatory to resect all the macroscopic disease[ ^{20 , 21}]. According to Sugarbaker, the peritoneum can be divided into six parts, so between one and six peritonectomy procedures may be required, including visceral and parietal peritonectomies[ ²²]. Subsequently, when the resection of the cancer is complete, some catheters and suction drains are placed through the abdominal wall to permit perfusion, with open or closed abdomen techniques or with peritoneal cavity expander or a semi-opened or semi-closed technique. The duration of the perfusion varies according to investigators and drugs used, from 30 to 120 min, and a heat exchanger keeps the infused fluid at 46-48°C so that the intraperitoneal fluid is maintained at 41-43°C[ ^{23 , 24}]. When the perioperative intra-abdominal chemotherapy is over, the abdominal cavity must be revisited. As to the timing of bowel anastomoses, pre- or post-hyperthermic chemotherapy, there is no consensus.

In the last decade, an increasing number of prospective studies investigated the effectiveness of the CRS and HIPEC in the management of PC of colorectal origin. Verwaal et al[ ¹⁰] were the first who in 2003 conducted a randomized controlled trial comparing the efficacy of CRS and HIPEC with systemic chemotherapy and surgery. This trial clearly demonstrated longer survival in the combined treatment group with a median survival of 22.3 mo vs 12.6 mo obtained in the control arm. Subsequently, Glehen et al[ ²⁸] in 2004, in a multi-institutional registry study from 28 international treatment centres, showed that the median survival was 19 mo and 3-year survival was 39% after CRS and HIPEC for 506 patients with colorectal peritoneal carcinomatosis. However at present, the clinical outcomes, in the literature, vary considerably: the median survival from 12 to 32 mo, with 1-year, 2-year, 3-year and when reported 5-year survival rates ranging from 65% to 90%, 25% to 60%, 18% to 47% and 17% to 30%, respectively[ ⁴]. Univariate and multivariate analyses of most series of patients with PC of colorectal origin revealed several clinical, surgical and pathologic factors predictive of survival[ ⁴]. Clinical characteristics that have been correlated, in univariate analyses with an improved survival, are female gender, younger age and good clinical performance status[ ⁴]. Surgical factors that have been correlated with survival are the extent of carcinomatosis encountered at laparotomy, the completeness of resection, bowel obstruction, the presence of ascites and the presence and resection of metastatic disease to the liver[ ⁴]. Finally, the pathologic factors that have been correlated with impaired survival include site of the primary tumour, poor tumour differentiation, signet cell histology and lymph node involvement. However, the results of multivariate analyses on the abovementioned clinicopathologic factors were reported in 5 publications; in 4 of these, the extent of disease [measured by Peritoneal Cancer Index (PCI)] and the completeness of resection were the factors most related to treatment success and survival[ ⁴]. Patients with localization in six or seven regions of the abdomen had a poor prognosis, with a median survival of 5.4 mo vs 29 mo in those with a lower number of regions affected[ ⁷]. In a recent retrospective study, in 70 patients, da Silva and Sugarbaker demonstrated, by univariate analysis, that the patients with a PCI < 20 had a median survival of 41 mo compared with 16 mo for patients with PCI > 20 ( P = 0.004)[ ²⁹].