Postoperative ileus is the most common complication after radical cystectomy. Delayed recovery of intestinal function due to injury stress and anesthesia occurs in most patients after radical cystectomy. In general, the time taken for the recovery of function is less than 24 hours for the small intestine, 24–48 hours for the stomach, and 48–72 hours for the colon. Thus, normally delayed recovery of intestinal function is referred to as physiological postoperative ileus. In contrast, persistent postoperative ileus (usually referred to as postoperative ileus) is defined as non-recovery of intestinal function for more than 7 days postoperatively or the presence of nausea, vomiting, abdominal distension and other symptoms of intestinal obstruction after the recovery of intestinal function. The incidence of postoperative ileus after radical cystectomy is reportedly 4–19%. Postoperative ileus affects patient recovery, increases the length of hospital stay, and greatly increases the medical costs.
The mechanisms of postoperative ileus are listed in the following paragraph. (1) Reduction of intestinal peristalsis induced by vagal nerve stress after surgical trauma; (2) surgical anesthesia and opioids; (3) activation of the innate immune system leading to the release of inflammatory factors; (4) intestinal edema caused by inappropriate fluid replacement or uncorrected hypoproteinemia intra- or postoperatively; (5) disruption of intestinal continuity and hindrance of the recovery of intestinal peristalsis function due to delayed repair of the Cajal interstitial cell network and intestinal nervous system network at the site of trauma; (6) imbalance of gastrointestinal hormones and neuropeptides.
Urinary diversion is necessary after radical cystectomy, and a neobladder or fistula is constructed using intestinal tissue, which increases the burden of intestinal function recovery after radical cystectomy. In addition, the complexity of radical cystectomy and the long duration of surgery and anesthesia may result in a relatively high incidence of postoperative complications. However, the present study found that operation time and lymph node dissection were not risk factors for postoperative ileus. This might be because the present study analyzed patients treated in a single center, and so there was a high consistency of surgical experience and postoperative management. Study has shown that age is a risk factor for postoperative ileus, but our study did not reach the same conclusion. The main reason for these interstudy differences may be that, in our institution, older adults with a poor preoperative general condition generally undergo ureterocutaneostomy without lymph node dissection; thus, intestinal surgery is not required. Furthermore, the introduction of the ‘enhanced recovery after surgery’ protocol may have decreased the influence of age and urinary diversion type on the development of ileus after radical cystectomy.
In the present study, postoperative serum creatinine concentration was a risk factor for postoperative intestinal obstruction. Four possible reasons for this are discussed in the following paragraph. (1) Serum creatinine concentration is an important indicator of renal function. An elevated creatinine level often indicates the deterioration of renal function. Decreased renal excretion may result in an increase in the body fluid load, which may increase the risk of intestinal edema and decrease intestinal peristalsis. (2) Inflammation is an important factor affecting the development of postoperative ileus. Due to the stimulation of intestinal surgery or the intraoperative temperature decrease, pro-inflammatory factors such as histamine, prostaglandin, IL-6, and IL-8 are released locally; monocytes and neutrophils then infiltrate the muscle layer, and the cytokines released by these cells also inhibit the contraction of intestinal muscle. The systemic inflammatory response also plays an important role in the development of postoperative ileus. The presence of tumor necrosis factor (TNF), IL-6, IL-8, and other substances in the plasma postoperatively further leads to local infiltration of inflammatory cells in the intestine[12-14]. However, when the renal function deteriorates, the ability of the kidneys to clear systemic inflammatory mediators (such as IL-6 and TNF) is decreased, which inhibits the clearance of the systemic inflammatory response and promotes the further development of postoperative ileus. The development of postoperative ileus aggravates the systemic inflammatory response, while the increased levels of inflammatory mediators such as IL-8 and TNF further damages the renal function. Thus, a cycle of "deterioration of renal function - aggravation of inflammatory reaction - postoperative ileus - aggravation of inflammatory reaction - deterioration of renal function" is formed; this can lead to the progression from physiological postoperative ileus to postoperative ileus. (3) The deterioration of renal function not only disturbs the body fluid metabolism, but also leads to the accumulation of toxic substances in the body. Among them, nitrogen-containing substances, such as urea, are most closely related to the intestinal tract. These substances are excreted from the blood into the intestinal cavity, where bacteria decompose these substances into ammonia and then convert them into ammonia hydroxide, which eventually leads to the damage of the intestinal epithelial connexin. This may lead to the further penetration of toxic substances and bacteria into the intestinal submucosa, which may cause intestinal inflammation and delay the recovery of intestinal peristalsis[16,17]. (4) In the present study, the postoperative deterioration of renal function had an obstructive cause in some patients. Urinary diversion involves the anastomosis of the ureter and the output tract. If the ureteral stent is blocked or falls off after the operation, this may lead to hydronephrosis. A large number of mechanoreceptors located in the renal pelvis are introduced into the spinal cord via autonomic nerves after they detect the traction caused by hydronephrosis, which results in the dysregulation of sympathetic and parasympathetic nerves, and may lead to intestinal obstruction due to neurological factors. However, further research data are needed to confirm this hypothesis.
The decrease in postoperative serum albumin level was a risk factor for postoperative ileus in the present study. This is consistent with previous research that found that plasma albumin level is a strong predictor of postoperative hospital stay and mortality, and that low postoperative albumin level is a risk factor for complications after radical cystectomy. The reason that a low postoperative serum albumin level is a risk factor for postoperative ileus may be that the pre- and postoperative plasma albumin levels reflect the nutritional status of the patient. Patients with a poor nutritional status have less resistance to surgical trauma and inflammation than patients with a good nutritional status. In addition, hypoproteinemia can cause intestinal edema and subsequent postoperative ileus.
Combined with the above results, we incorporated these indexes into the prediction model, made a nomogram, and proposed a prediction model for predicting whether intestinal obstruction will occur after radical cystectomy. Our prediction model is based on the preoperative creatinine level, postoperative creatinine level, and postoperative serum albumin concentration. According to the model nomogram, we scored to predict the incidence of postoperative ileus. We verifid it by bootstrap correction curve and ROC curve, which proved that our prediction model had good identification ability and accuracy. At present, there is no way to predict and evaluate whether ileus occurs in patients after radical cystectomy. Clinicians often can only wait for patients to have more serious symptoms of ileus or delayed recovery of intestinal function before further examination and intervention. This study provides clinicians with a method to judge the risk of postoperative ileus according to the model, so as to proceed necessary early detection and treatment to better improve the prognosis of patients.
The highlight of this study is that it is found that preoperative creatinine level, postoperative creatinine level, and postoperative serum albumin concentration are the risk factors of postoperative ileus. Based on those findings, a clinical prediction model is constructed and had good prediction and identification ability. Patients with higher scores using this prediction model need to be vigilant about the possibility of subsequent postoperative ileus. However, this study still has some shortcomings that can not be ignored that the sample size included in this study is limited, and it is expected that more samples will be included to enrich this study in the future.