CRS and HIPEC were first described in 1980 [
23]. This procedure involves stripping of the diseased peritoneum (peritonectomy) with multiple visceral resections and is performed with the goal of achieving a maximal cytoreduction of all visible peritoneal lesions within the abdomen. Following the resections, a heated chemotherapy perfusate is administered intraoperatively into the abdomen to chemically sterilize all peritoneal surfaces. HIPEC allows a high local concentration of a cytotoxic drug to be achieved for microscopic cytoreduction of any residual tumor with minimal systemic adverse effects. In addition, hyperthermia has been demonstrated to have a synergistic effect with chemotherapy, thus enhancing the cytotoxicity of the drug [
24].
In the early 1990s, CRS and HIPEC were introduced for CRC patients with PM [
6,
25], and these methods have been reported to improve prognosis with 5-year overall survival rates ranging from 27 to 51% [
7‐
12]. With improved prognosis, recurrence after initial CRS and HIPEC has recently been a topic of discussion [
16]. Most cases of recurrence have been reported to be intra-abdominal, with the liver being the second most frequent site of recurrence after the peritoneum. About 10–20% of patients develop liver metastases after CRS and HIPEC [
15,
16]. Although recent reports suggested that simultaneous hepatectomy for liver metastases with CRS and HIPEC could improve prognosis [
26,
27], metachronous hepatectomy after CRS and HIPEC has been scarcely reported. Sánchez-Velázquez et al. reported a case of caudate lobectomy with inferior vena cava resection for liver metastasis from CRC following CRS and HIPEC for colorectal PM, and the patient showed no recurrence for 18 months after hepatectomy [
28]. In the present study, we presented three cases of metachronous liver metastases from CRC treated by hepatectomy after CRS and HIPEC for PM. All hepatectomies were successfully performed, and no recurrence was detected in cases 1 and 2, although the observation periods were short. In case 3, liver metastases were diagnosed first; although complete remission was achieved once with systemic chemotherapy, early recurrence was found after hepatectomy for liver metastases. Case 3 showed synchronous presentation of hepatic metastases with a primary tumor, which was reported to be a risk factor for recurrence after CRLM resection, implying that the indication for CRLM resection after CRS and HIPEC should be carefully considered when making a decision about the procedure. However, recent advancement of multi-modality treatment for CRC revealed the efficacy of surgical resection even for metastatic lesions including liver, lung, and peritoneum [
29,
30]. Considering these previous reports, surgical approach for liver metastasis after CRS + HIPEC might be justified for better prognosis, although curative and safe resection should be secured.
CRS procedures around the liver include peritonectomy of the bilateral diaphragm and hepatoduodenal ligament, lesser omentum resection, and ablation of the liver surface serosa; therefore, severe adhesion around the liver is expected during reoperation after CRS. In addition, intraabdominal chemotherapy, including HIPEC and early postoperative intraperitoneal chemotherapy, could enhance postoperative adhesion [
24]. In the present three cases, hepatectomy was performed after prior CRS and HIPEC. Adhesion of surrounding organs to the liver surface was broadly observed because the peritoneum around the liver was completely stripped in the previous CRS. However, the adhesions could be dissected as in other abdominal surgeries in which the removal of the peritoneum was not aimed, and hepatectomy could be performed safely. This was probably because of the characteristics of peritoneal healing following a peritoneal injury. Fibrinolytic activity over the peritoneal surface is reported to decrease after damage to the peritoneum, leading to changes in the expression and synthesis of various cellular mediators and in the remodeling of connective tissues [
31]. Thus, for patients with good performance status and with the ability to combat adverse events, hepatectomy for recurrences in the liver, even after previous CRS and HIPEC procedures, may be associated with long overall survival. However, owing to the shortness of the observational period in the present cases, further studies are needed to show the long-term outcomes of hepatectomy for liver recurrences after previous CRS and HIPEC. In addition, the optimal timing of hepatectomy for liver metastasis after CRS + HIPEC including the interval between liver metastasis and CRS + HIPEC and conversion from systemic chemotherapy should be investigated for more efficacious multi-modality treatment to advanced CRC.