HOSs or high-output syndrome is rarely studied and lacks attention. There is no consensus on the definition of HOSs (HOS) [5, 7, 8, 9, 10]. Dehydration, electrolyte disturbance (hyponatremia, hypochloremia, hypomagnesemia), renal failure and malnutrition (late stage) can occur in high-output ileostomy [5, 7, 8]. HOS increases the risk of readmission of CRC patients. Some scholars defined HOS as stoma output of more than 1500 ml per day for more than two consecutive days [8, 9], while the others advocate that HOS should be defined as the output of more than 2,000 ml per day for more than two or three consecutive days [5, 7]. As the complications are more likely to occur when the daily stoma output exceeds 2000 mL, we adopt the latter standard in our study. HOS can be classified as early (< 3 weeks after initial ostomy surgery) or late HOS (3 weeks after surgery) and this is widely accepted by previous studies.
In our cohort, the incidence of HOSs (114/494) was 23.07%, higher than earlier reports (17%)[7]. Dehydration was the most common symptom of HOS (37.7%), followed by electrolyte disturbance (28.1%), local dermatitis (21.9%), renal dysfunction (5.3%) and malnutrition (7.0%) in long-term HOS. It was reported that the incidence of HOS is 26% in 262 patients with ileostomy during hospitalization, 30% of patients were re-admitted within 30 days after discharge, and 37% of patients with re-hospitalization were due to dehydration [11]. The re-admission risk of ileostomy patients with inflammatory bowel disease was double that of other risk factors (OR 2.04) [12].
Our study found no clear correlation between the occurrence of HOS and gender, age, gross typing, histological grading, location of tumors, lymph node metastasis and TNM staging in patients with colorectal cancer. Preoperative complications of inflammatory bowel disease, diabetes mellitus and neoadjuvant chemoradiotherapy are risk factors for HOS. Inflammation caused by abnormal reaction of intestinal mucosal immune system act as an important role in the pathogenesis of inflammatory bowel disease, and is also the main cause of HOS. Diabetes mellitus occurred in patients with colorectal cancer because of the disorder of glucose metabolism and utilization, such as inappropriate control, of blood sugar or intestinal movements, which may result in large amount of liquid discharge from ileostomy[5]. We found that neoadjuvant concurrent radiotherapy and chemotherapy (CRT) is a risk factor for HOS (HOS). Radiation enteritis caused by neoadjuvant radiotherapy might be responsible for HOS in preoperative CRC patients [13]. As neoadjuvant chemoradiotherapy is mostly carried out simultaneously before operation in our hospital, there is no stratified study of neoadjuvant chemotherapy, radiotherapy alone and neoadjuvant concurrent radiotherapy and chemotherapy. It has been reported that preoperative radiotherapy alone, the distance between the tumor and anal margin, could affect the intestinal function of patients after operation, while chemotherapy alone has no significant effect on intestinal function after operation [14].
Among the related factors of operation, total colectomy and abdominal infection are the risk factors of HOS, but not the operation time, bleeding volume, diuretic application and laparoscopic operation. Diabetes mellitus and total colectomy are high risk factors for HOS, which are consistent with previous study [5]. As it is reported bile acid deficiency is one of the mechanism of total colectomy caused HOS. Total proctocolectomy prevents the reabsorption of bile acids absorbed by the ileocecum, as a result decrease in bile acid pools inhibits lipid absorption. Consequently, unabsorbed long-chain fatty acids arehydroxylated or desaturated by anaerobic intestinal bacteria, triggering the secretion of fluid and electrolytes, which may lead to the development of HOS [5]. Bile acid deficiency may also cause changes in the intestinal flora that increase intestinal drainage [15]. The loss of water absorption by the colon in patients undergoing total colectomy can also lead to high ileostomy output. In our study, we did not find that the use of steroids and diuretics after ileostomy increase the high output of ileostomy, but the use of large doses of diuretics may increase the risk of dehydration.
Generally, half of the EHOS patients required no special drug intervention until recuperation, while the other half required drug intervention [7]. For the treatment and management of HOS, patients should be managed and guided throughout the hospital and after discharge [16]. In addition to basic treatments (such as restricting fluid intake, rehydration and correcting electrolyte disturbance) reducing the secretion of somatostatin and oral intake of loperamide is also effective in reducing discharge. Pieter-Jan Cuyle reported that 17% of patients with ileostomy had high excretion [17]. This complication would affect the implementation or completion of adjuvant therapy. Somatostatin analogues (ranitides, etc.) could reduce the excretion of ileostomy effectively. Routine dosage of loperamide is 20 mg twice daily by mouth, but dosage can be increased if not effective. Alicia Mackowski reported that increasing the dosage of loperamide to 300 mg per day in individual patients can reduce the amount of stoma excretion, without observed abnormality in renal function [18].
This paper is a retrospective study with some limitations. Prospective study should pay attention to the patients with high risk factors HOS, strengthen the supervision and treatment after operation and discharge for reducing the complications of stoma, and facilitate the smooth progress of comprehensive treatment as well as the re-admission rate caused by HOS [19–22].
We followed up with patients who had ileostomy reversal or 1 year after ileostomy by inpatient medical records, outpatient review and telephone follow-up. These data mostly came from patients' observation records in the hospital (including outpatient review) belonging to on-site data collection. Using remote video conference to evaluate ileostomy output, and taking early intervention measures to improve prognosis is a method worth exploring [23]. Multicenter, large sample randomized controlled studies of HOS should be conducted in the future.