For the last three decades, the prognosis of patients with PM has been improved by multimodal treatment, including complete cytoreduction and HIPEC. This combined therapy has prolonged overall survival rates in carefully selected patients. The prognosis of these patients primarily depends on the extent of the peritoneal disease (PCI), the completeness of cytoreduction, and the histopathologic types (1–5). To achieve complete resection, an extended multivisceral and/or peritoneal resection is usually needed. On the other hand, the degree of small bowel involvement is insistently considered to be a limiting factor to radically eradicate macroscopic tumor burden (8, 20–22). The terminal ileum, as a special part of the small bowel with its own features of anatomical fixity and limited peristaltic movements, is frequently resected in cytoreductive procedures. Besides, the intraperitoneal fluid circulates in a well-defined manner (in the head-caudal-head direction and is controlled by gravity and respiratory movement sequence), which leads to the accumulation of influxing cells on some special anatomic sites such as the ileum (6–8). In light of these findings, the terminal ileum can be affected by tumor nodules irrespective of the extent of the disease. The current study is particularly focused on the outcomes of ileal resection in patients with PM. High PCI, more CC-1 or CC-2 resection, more gastrointestinal anastomosis, more ostomy formation, more blood products, and albumin usage were strikingly in the ileal resection group. In addition, ileum-resected patients had prolonged operative time, high post-operative infection, increased nephrotoxicity, and prolonged hospital stay. C-D grade I-IV morbidity and perioperative mortality were significantly higher in the resection group.
The clinical consequences of functional loss of the terminal ileum and ileocecal valve have been well-documented in the literature: the ileocecal valve acts as a structural barrier for the passage of intestinal contents and provides the required time for efficient absorption of nutrients, electrolytes, and water by slowing intestinal transit time (13). Bile acids, vitamin B12, and fat-soluble vitamins (vitamins A, D, E, and K) are significantly absorbed in the last 100 cm of ileum (9–13). These vitamins are a prerequisite for normal cell division and growth. The loss of these important mechanisms may possibly result in a decline in the physiological reserve and immuncompetence of the patient and may contribute to more infections, more grade I-II and grade III-IV morbidity, and longer hospital stays in the ileal resection group in our series. The ileum is also the main site of bicarbonate and chloride exchange and has an important clinical role in the passive absorption of water and electrolytes. Only the ileum can absorb sodium chloride against steep electrochemical gradients. When the ileal mechanism that provides the exchange of bicarbonate with chloride ions is disrupted, excessive amounts of chloride and hydrogen ions pass into the colon, bicarbonate accumulates in the body and metabolic alkalosis develops. When the decrease in bicarbonate/chloride exchange is accompanied by loss of fluid (diarrhea) and monovalent ions, the kidneys cannot maintain the acid-base balance and alkalosis deepens (13, 23). Considering these unique tasks of the ileum, nephrotoxicity was found to be a statistically significant factor in the ileal resection group in our series. It’s sure that chemotherapeutic agents used during HIPEC also had an important role in nephrotoxicity, but 40 of the 61 (67%) patients who developed nephrotoxicity were patients with ileal resection (p = .027). In this nephrotoxicity group, cisplatin was used in 19 of these patients, cisplatin + mitomycin in 27, oxaloplatin in 8, and other chemotherapeutic agents in 5 patients.
Hence, resection of the ileum may adversely affect overall survival. In our study, the ileal resection group had significantly lower 1-, 3-, and 5-year survival rates (p = .005). Distal small bowel resections are less tolerated than proximal small bowel resections. This important feature is because of the remarkable ability of the ileum to compansate the absorbtive functions of the proximal intestine. Fifty to sixty percent of the mid-jejunum can be resected with few long-term metabolic consequences, however, resection of more than 30% of the ileum is poorly tolerated (24, 25, 26). Loss of these unique functions of the ileum, which are not replaced in the long-term period, may be one of the key factors that negatively affect post-operative morbi-motality and overall survival. In the Cox model, high PCI, complete cytoreduction, intraoperative ES replacement, and post-operative infection were independent prognostic factors of overall survival, whereas ileal resection could not stay in the model. However, the resection of the ileum clearly worsened the overall survival.
To the best of our knowledge, this is the first study reporting outcomes of ileal resection in patients with PM who underwent CRS and HIPEC. It has several inherent limitations. First, it was an observational, retropro mono-center study. Second, there were various histotypes of peritoneal surface malignancies. And also, potential confounding factors from uncontrollable variables may affected the analyses. We are fully aware that ileum-resected patients usually undergo more extensive cytoreductive procedures. Thus, it can be pleonastic to overstress the assessment of the ileum as a risk factor besides the well-known variables. But, we aimed to search for the clinical significance of ileal resection in high volume patient data to improve results to optimize patients’ intensive care and oncologic outcomes.