In this issue, Becher and al. analyzed 195 patients undergoing CRS and HIPEC for carcinomatosis, mainly of appendiceal and colon origin. They compared patients requiring splenectomy to those who did not with the focus of this report on hematotoxicity. The authors are to be congratulated for the complete laboratory and toxicity data, which are often missing or incomplete in the literature. The number of patients studied is significant, highlighting the familiarity and experience with the procedure at the Wake Forest University School of Medicine, Winston- Salem. Three important points can be gleamed from this study. The splenectomy group required more red blood cells transfusions, had a longer hospital stay and they also had a lower incidence of white blood cell toxicity. There was no significant difference in platelet or plasma requirements. These findings can be explained by the fact that patients requiring splenectomy had a more important tumor burden and thus required a more extensive surgery. The white blood cell nadir post HIPEC was statistically higher in the splenectomy group. Hence, granulocyte colony stimulating factor (G-CSF; filigrastim) was needed in only 29% of the splenectomy group compared to 43% of non-splenectomy patients (P=0.043) following their protocol for its use (13). The authors hypothesized it was predominantly due to the temporarily decrease in the clearance of senescent cells following splenectomy, which results in peripheral leukocytosis. This interesting finding led them to the conclusion that while performing CRS + HIPEC, this could be an additional argument to perform splenectomy.

The effects of splenectomy are well known in the trauma population. It is associated with leukocytosis and thrombocytosis in the postoperative period. The infection rate with encapsulated bacteria is significantly higher if patients are not vaccinated and can put the patient at risk for overwhelming post-splenectomy sepsis (OPSI) which has a mortality of up to 70% (14). Thrombosis and cardiovascular complications have also been noted in post splenectomy populations (15). In addition, the spleen plays a role in immunity, which is incompletely understood. It can be difficult to determine the cause of the elevated white blood cells in the postoperative period. Is it only the physiologic inflammatory response to splenectomy or a prodrome to an undetected infection? Toutouzas found that in the trauma population on the fifth operative day, a leukocyte count (WBC) higher than 15 x 10⁹/L, a platelet count divided by the WBC less than 20 and a injury Severerity Score higher than 16 was predictive of sepsis 97% of the time (16). In a prospective study, Weng confirmed these findings (17). In the context of an extensive procedure like CRS + HIPEC, patients are at high risk for infectious complications and higher WBC can be seen. Perioperative vaccination to prevent OPSI is also very important. Becher and al. applied a thorough vaccination protocol and had no OPSI during their follow up period.

In the gynecology literature, splenectomy as part of CRS has been investigated. Bidus and al. have shown that post splenectomy patients after CRS had a higher platelet and white blood cell counts than for patients with spleen preservation (18). Leukocytosis alone was not a predictive factor for infection. McCann and al. have described a series of 44 splenectomised patients with CRS for ovarian cancer. They found that splenectomy was an independent factor for worse overall survival (19). They hypothesized that increased extent of disease affected the spleen and was also associated with a worse outcome. Another possible explanation relates to the immune function of the spleen. These hypotheses can also be applied to the present article. Magtibay and al. also studied the effects of splenectomy in CRS for ovarian cancer and found no difference in prognosis nor infectious complications (20). He concluded that splenectomy should be part of the cytoreduction when involved by tumor.

The hematologic effects of systemic MMC are important. Its dose limiting toxicity is myelosuppression particularly thrombocytopenia and leucopenia which can occur following only one dose (21). When given intraperitoneal, the systemic effects should be lessened (22). However, myelosuppression still exists with HIPEC (23). Sugarbaker reported 28% grade IV hematologic adverse events with HIPEC, predominantly neutropenia (24). A similar effect is seen with oxaliplatin (25). In the present study, 5 patients died from sepsis with cytopenia, which probably contributed to this outcome. Severe or febrile neutropenia is usually treated with G-CSF. This study raised the interesting fact that transient leukocytosis associated with splenectomy might significantly help reduce the need for G-CSF. This finding holds true for the authors as per their protocol for G-CSF administration, which is, to our knowledge, not a standard practice in the various HIPEC-specialized centers nor easily extrapolated from the established guidelines for use of growth factor support (26). Whether it ameliorates the long-term outcome of these patients remains to be proven. The costs of longer hospital stay and increased transfusion rates would overweight any economic advantage of reduced G-CSF usage in the splenectomized population.