The term “intestinal failure” was introduced in the literature in the 1950s and has been used ever since. Because the intestine does not have clear parameters for monitoring its function like other organs, there is no universally accepted definition of intestinal failure, which makes the diagnosis and treatment of intestinal failure more difficult than other organ failures. failure units (IFUs) at Hope Hospital, Salford, with only four beds, to treat patients with complex bowel disease requiring abdominal infection control, intensive monitoring and possibly major surgery. In 1997, it was combined with a sister unit at St Mark’s Hospital in London and received funding from the Department of Health to become a national referral center for the treatment of severe intestinal failure in the U.K. In 1979, Academician Li Jieshou established the first IFUs in China at the Nanjing General Hospital of the Nanjing Military Region. The IFUs, which also had only 4 beds at that time, focused on the most severe cases of intestinal failure – external intestinal fistula. Under the leadership of Academician Lai, after 30 years of hard work, the IFUs in Nanjing General Hospital have grown from 4 beds to more than 100 beds, treating patients with intestinal failure from all over China and overseas, including severe abdominal infections, intestinal fistulas, short bowel syndrome, radiation enteropathy, severe inflammatory bowel disease, severe constipation requiring surgery, complex bowel disease with multiple surgeries, etc., making it one of the largest IFUs in the world. It has become one of the largest IFUs in the international arena. In this 30-year anniversary, we would like to discuss our understanding and treatment experience of intestinal failure, taking into account the literature. I. Definition of intestinal failure The earliest definition of intestinal failure was proposed by Fleming and Remington: intestinal failure is “the reduction of the functional intestine to the point where it is difficult to maintain digestion and absorb nutrients at a minimum”. However, in most cases, this definition actually equates to patients who require prolonged TPN, ignoring those who may only require fluid and/or electrolyte replacement. Later, Nightingale [3] updated the definition of intestinal failure as “the need for nutritional and/or hydration and electrolyte supplementation to maintain the patient’s health and/or growth due to reduced intestinal absorptive capacity”. However, neither definition mentions the cause of intestinal failure, which can be caused by both structural loss of the intestine due to surgical resection and functional loss of the intestine due to intestinal disease itself, and the treatment and prognosis of intestinal failure differs between these two causes. Recently, an international consensus group has proposed a new definition of intestinal failure that encompasses the etiology of intestinal failure. They consider intestinal failure as “loss of intestinal absorption due to intestinal obstruction, intestinal motility disorders, surgical resection, congenital defects, or lesions of the intestine itself, characterized by the body’s inability to meet the protein-energy, fluid, electrolyte, and micronutrient balance. ” . The above definition biases the understanding of intestinal function to the digestion and absorption of nutrients, but the intestine not only has the functions of digestion, absorption and peristalsis, but also immune regulation, hormone secretion and mucosal barrier. Currently, more clinical attention is paid to the intestinal mucosal barrier function, which is a specific function of the intestine, a complex function composed of epithelial/molecular and immune, etc., that prevents intestinal bacteria and toxins from escaping into the body through the intestinal wall. Intestinal bacterial translocation is the redistribution of the intrinsic flora in the intestinal lumen in the internal environment outside the gut. Intestinal bacterial translocation and cytokine production can lead to systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Therefore, the intestine is also known as the center of the stress organ. Enteric-derived infections caused by intestinal bacterial translocation have been one of the important research topics in the medical field in recent years, and therefore, intestinal mucosal barrier function should be given high priority. The incidence of intestinal mucosal barrier dysfunction far exceeds the reduction of intestinal digestive and absorptive area, and in many diseases, especially in cases of severe traumatic stress, it is also more harmful than simple digestive and absorptive insufficiency. Clearly, intestinal mucosal barrier function should be included in the definition of intestinal failure, and this is where the definition of intestinal failure in the literature falls short. “Organ failure” is an issue that has been keenly studied and discussed in clinical practice since the 1970s. At that time, “organ failure” was understood to mean irreversible impairment of organ function. Therefore, in the diagnostic criteria for organ failure as determined by different authors, all indicators were selected at the upper limit of the monitored parameters, resulting in a very high mortality rate in patients diagnosed with “multi-organ failure”, when 3-4 organs reached the diagnostic criteria of “failure”. When three to four organs meet the diagnostic criteria for “failure”, few survive. In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) jointly discussed issues related to infection and multi-organ failure, and recommended that the term “dysfunction” be used instead of the term “multiple organ failure”. In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) jointly discussed the problems related to infection and multi-organ failure, and recommended that the term “dysfunction” should replace “failure”, and that the monitoring parameters should be changed to start from the lower limit of abnormal values, in order to achieve early diagnosis and early treatment, and that the purpose of clinical treatment should be to prevent and stop organs from entering a state of failure. However, in this symposium, there was a lack of clear description of the concept and prevention of intestinal dysfunction. In summary, due to the complexity of intestinal function and the lack of clear functional monitoring indicators, there is no universally accepted definition of intestinal failure, and the replacement of “intestinal failure” by “intestinal dysfunction” is not as accepted as other organ dysfunctions. According to academician Li Jieshou, conceptually, the term “intestinal dysfunction” should be used instead of “intestinal failure”, which is more suitable for clinical needs, and intestinal dysfunction should include digestion, absorption disorders and intestinal mucosal barrier disorders. It is suggested that the meaning of “intestinal dysfunction” should be “impairment of intestinal parenchyma and/or function, resulting in impairment of digestion, absorption of nutrients and/or mucosal barrier function”. It is now believed that gastrointestinal bleeding due to stress ulcer is only a special type of gastrointestinal dysfunction. In the past, intestinal failure could be clinically classified into two major categories according to the primary disease: 1. intestinal dysfunction secondary to intestinal diseases, including inflammatory bowel diseases, extraintestinal fistula, early postoperative inflammatory bowel obstruction, short bowel syndrome, radiation enteritis, etc. 2. intestinal dysfunction secondary to extraintestinal diseases, including severe acute pancreatitis, abdominal infection, trauma, burns, etc. Since the etiology of intestinal failure is very extensive and the severity and duration vary, some scholars have proposed a new classification of intestinal failure in recent years: type I intestinal failure refers to self-limiting intestinal dysfunction after abdominal surgery; type II intestinal failure refers to intestinal dysfunction in critically ill patients, who, in addition to extensive small bowel resection, also have complications of infection, metabolism and nutrition, requiring multidisciplinary comprehensive treatment and metabolic and nutritional Type III intestinal failure refers to chronic intestinal failure that requires long-term or even lifelong nutritional support. Most patients with type I intestinal failure can be treated in hospitals in non-specialized centers, and complete recovery can be achieved without sequelae after a period of rehydration, maintenance of water-electrolyte balance, and enteral/parenteral nutritional support. Type III intestinal failure mainly refers to patients with short bowel syndrome (SBS) who require long-term or even lifelong parenteral nutritional support. It is generally accepted that SBS can be diagnosed when the residual small bowel length is <200 cm, but the definition of SBS based on small bowel length alone seems arbitrary because, firstly, the "normal" small bowel length can vary from 275 to 850 cm, and secondly, this definition does not take into account the function of the residual small bowel, and the degree of intestinal failure in SBS is difficult to quantify objectively. It has been suggested that citrulline levels may serve as a measure of intestinal epithelial cell function and predict the patient's dependence on parenteral nutrition, but its clinical validity needs further confirmation. Recently, an international consensus group has proposed a new definition of "SBS-related intestinal failure" as "a clinical condition secondary to loss of absorptive function caused by surgical resection, congenital defects, or lesions of the intestine itself, and characterized by the inability of the patient to maintain protein-energy, fluid, and nutrient levels through a conventional normal diet. Protein-energy, fluid, electrolyte, and micronutrient balance is maintained." Currently, the extent and characteristics of SBS secondary to nutrient, fluid and electrolyte imbalances can be roughly predicted by the length of the residual small intestine and the lesion and site of resection of the small intestine: patients who retain more than 100 cm of jejunum are usually able to absorb sufficient water and salt from the oral diet to maintain positive intestinal homeostasis; water and salt absorption is greatly diminished in jejunum <100 cm, and intestinal homeostasis analysis suggests a "secretory type", usually requiring parenteral nutritional support; jejunocolonic anastomosis, the colon has a strong ability to absorb water and electrolytes (up to 6L per day), and these patients often do not need parenteral fluid supplementation; jejuno-ileal anastomosis, the remaining ileum can compensate structurally and functionally to increase nutrient absorption, and if the colon is retained If the colon is retained, the jejunum will also undergo functional compensation, increasing its absorption capacity. This process is called "intestinal compensatory process", and many systemic or local nutritional and non-nutritional factors can facilitate this compensatory process. The combination of glutamine, growth hormone and enteral nutrition has shown good results in a limited number of patients with SBS. The ideal treatment for SBS patients with combined intestinal failure is small bowel transplantation. In recent years, the treatment concept of whether to choose parenteral nutritional support or small bowel transplantation for patients with III bowel failure has changed considerably, and the 7th International Small Bowel Transplantation Conference in May 2001 concluded that while the 3-year survival rate for patients with small bowel transplantation alone has reached 70%, the 3-year survival rate for patients with home total gastrointestinal parenteral nutrition (TPN) can reach 90%. Therefore, if patients with irreversible intestinal failure can tolerate parenteral nutrition, parenteral nutrition is still preferred. Patients with intestinal failure who cannot tolerate TPN have a 1-year survival rate of less than 20% and a very poor prognosis. For this group of patients, as well as patients with intestinal failure who are dependent on TPN for life but also have serious complications of TPN (e.g. liver dysfunction), small bowel transplantation is the most ideal treatment option. In recent years, the key technology of small bowel transplantation has been greatly developed, and the survival rate of small bowel transplant patients and transplanted organs has been greatly improved, with the 1-year survival rate of small bowel transplant patients and transplanted organs at Pittsburgh University reaching 92% and 89%, respectively, which has reached the efficacy of home parenteral nutrition, but the cost-effectiveness ratio of small bowel transplantation is clearly preferred over home parenteral nutrition. The cost-effectiveness ratio of small bowel transplantation is significantly better than that of home parenteral nutrition. According to the Global Small Bowel Transplant Registry (ITR), the number of patients treated at home (with nutritional support) prior to small bowel transplantation is much higher than those still in the hospital in recent years, suggesting that the number of stable patients receiving small bowel transplantation has increased significantly, and the postoperative survival rate of these patients (80%-100%) is significantly higher than that of patients still in the hospital (40%-60%). ). Therefore, in recent years, the concept of indications for small bowel transplantation has developed greatly. In July 2005, the 9th International Conference on Small Bowel Transplantation concluded that once a patient cannot rely on intestinal absorption for survival, small bowel transplantation should be performed as early as possible, and both the cost of small bowel transplantation and the surgical effect are better than small bowel transplantation when intestinal failure occurs. It is still controversial whether malignant tumor with intestinal dysfunction is included in the category of intestinal failure. In the UK, patients with combined malignancy are rarely treated for bowel failure and rarely receive home parenteral nutrition (HPN), but malignancy is a major indication for home enteral nutrition (HEN). In the United States, however, tumors have become the second most prominent indication for HPN. Why this difference exists between the UK and the US is unclear. Type II intestinal failure has a wide range of etiologies, including extensive bowel resection, mesenteric vascular embolism, inflammatory bowel disease, intestinal fistula, mechanical or functional intestinal obstruction, with special emphasis on the effect of abdominal infection on type II intestinal failure. These factors can act individually or in combination to cause type II intestinal failure. The combined effect of multiple factors is more common in clinical practice. For example, in one case, an anastomotic fistula followed by abdominal abscess after major small bowel resection and severe infection further worsened the gastrointestinal dysfunction and eventually led to type II intestinal failure. This situation is very common in China, and our IFUs admit patients with intestinal failure from all over the country, most of whom fall into this category. The interaction of multiple factors makes the clinical presentation more complex and the treatment more challenging. Intestinal failure can occur at all levels of the hospital, and many patients referred for intestinal failure are lost due to the lack of specialized IFUs, expertise, and supporting medical equipment. Overseas attempts have been made to establish certain criteria to define which patients need to be referred to specialized IFUs, but there are still many inconveniences in implementing them in China. Since the etiology of type II intestinal failure is diverse and in most cases is the result of a multifactorial interaction, it is important to develop a rational treatment strategy. For example, malnourished patients undergoing intestinal resection complicated by intestinal fistula and abdominal infection need not only infection control, but also nutritional and metabolic support and surgical reconstruction. In these patients, intestinal failure is not only a short bowel syndrome due to extensive small bowel resection and intestinal fistula formation, but there is also secondary impairment of gastrointestinal function by abdominal infection. In these patients, the management of the various etiologies of intestinal failure is clearly chronological and should be prioritized: drainage and removal of abdominal infection should be the first priority, and improvement of intestinal function and nutritional status is possible only if the abdominal infection is controlled; then nutritional support and supplementation of metabolic substrates are required before definitive surgical reconstructive surgery is considered. Overseas guidelines have been formulated for the treatment of type II intestinal failure, called the "Sepsis-Nutrition-Anatomy-Plan" model, referred to as the "SNAP" model. China should also develop corresponding guidelines for the treatment of type II intestinal failure according to its own national conditions. Control of abdominal infections Various causes of intestinal failure may be associated with abdominal infections, the most common of which is intestinal fistula. Abdominal infections are the leading cause of death in patients with intestinal failure. With advances in treatment technology, the outcome of type II intestinal failure has improved significantly, but the proportion of deaths due to abdominal infections has not changed. The impact of abdominal infection on patients with intestinal failure is multifaceted: active infection can cause and exacerbate a variety of gastrointestinal dysfunctions, including nutrient transport, intestinal peristalsis, digestive fluid secretion, intestinal epithelial cell proliferation and regulation, and intestinal mucosal barrier function. Abdominal infection weakens the healing ability of the intestine, and there is little possibility of self-healing of intestinal fistula in the absence of controlled abdominal infection. At the same time, abdominal infection also increases the catabolism of the body and hinders the application of nutritional substrates, which is clinically manifested by the loss of the pro-anabolic effect of insulin (insulin impedance), which is why the therapeutic outcome of patients with abdominal infection can be improved by strict control of blood glucose levels using continuous pumping of insulin. Due to intestinal dysfunction and metabolic changes caused by abdominal infection, even aggressive nutritional support is not effective unless the abdominal infection is promptly controlled, which is the rationale behind the "SNAP" model of managing type II intestinal failure. The possibility of abdominal infection should be suspected in all patients with intestinal failure in whom nutritional support is ineffective. If the abdominal abscess is encapsulated by fibrin and collagen, the patient may sometimes not present with the classic signs of abdominal infection such as hyperthermia or leukocytosis. In this case, certain atypical clinical features such as malignancy, hypoproteinemia, hyponatremia and abnormal liver function often suggest the presence of an occult abdominal infection. Therefore, blood cultures (peripheral veins and central venous catheter tips), urine cultures, incisional smears (including screening for MRSA) and chest X-rays should be routinely performed in all patients with IFUs. CT scan of the abdomen is the most effective means of diagnosing abdominal infection and should be an important part of the diagnostic evaluation of patients with type II intestinal failure [14]. However, if it is necessary to identify whether the effusion is sterile or infectious, ultrasound or CT-guided puncture culture is required. Although with the development of tomographic imaging techniques, CT can replace abdominal plain films as the first-line examination in patients suspected of having intestinal fistula, contrast examinations (including sinus angiography) still have an important complementary role in understanding the intestinal anatomy and abnormal changes. Once an abdominal infection is detected, it should be drained immediately, and percutaneous percutaneous drainage under CT or ultrasound guidance is the first-line option for the management of abdominal or pelvic abscesses. A variety of other pathways, including CT-guided transgastric, transgluteal, transvaginal, and transrectal routes, can be used to obtain good drainage for deep abscesses that cannot be reached percutaneously. Selection of sensitive antibiotics based on the results of drug sensitivity of the puncture fluid culture can be an adjunctive therapy, especially if the patient has systemic infection symptoms such as high fever and leukocytosis. However, antibiotics alone do not make the abscess cavity disappear and must be based on adequate drainage to be effective. If the daily drainage continues to be high after puncture, the possibility of intestinal-abscess endovascular fistula should be considered. Statistically, the probability of intra-abdominal abscesses presenting with intestinal-abscess endovascular fistula is about 15-44%, and most of them are diagnosed at later imaging [15]. Therefore, it is essential to keep the drain in place and to flush it daily depending on the volume and nature of the drainage fluid. Complete resolution of the abscess and spontaneous healing of the fistula may take several weeks, and removal of the drainage tube must wait until the drainage fluid is completely gone and the pus cavity disappears as indicated by a transdigestive sinusogram. There are some abscesses that require surgical drainage: in particular the combination of multiple intertrip abscesses, abscesses communicating with high-flow intestinal fistulas, lack of intestinal continuity or distal obstruction, large anastomotic breaches, or viscous pus. In these cases, imaging-guided drainage may also be attempted first to help control the infection and to provide preoperative nutritional support and evaluation of the intestinal anatomy. There are several surgical options for intestinal fistulas complicated by abdominal infection. Usually, a one-stage resection anastomosis of an intestinal fistula cannot be performed in the presence of an abdominal infection, and an enterostomy proximal to the fistula is a simple and effective surgical approach. Regardless of the surgical approach, adequate drainage of the abdominal cavity and fistula site is the basis for successful treatment. In some particularly critical cases, laparotomy may be performed. Only after the abdominal infection is completely controlled and the patient's nutritional status improves can a reoperation be considered to restore the continuity of the gastrointestinal tract and the integrity of the abdominal wall, a process that often takes several months. V. Nutritional support for type II intestinal failure The focus of nutritional support for type I intestinal failure is to maintain water-electrolyte balance, and complete recovery can be achieved after a period of enteral/parenteral nutritional support. Type III intestinal failure requires long-term or even lifelong nutritional support, and its treatment has been described in many literatures. The clinical focus on nutritional support for type II intestinal failure has several implications: First, most patients with type II intestinal failure have acute malnutrition, and nutritional support is the basis for successful treatment; second, malnutrition in these patients can lead to decreased immune function and delayed wound healing; third, these patients are often in a state of infectious stress and lose a large amount of protein daily. Third, these patients are often in a state of infectious stress and lose a large amount of protein daily, so it is technically difficult to supplement sufficient energy and nitrogen to maintain positive nitrogen balance. The evaluation of the nutritional status of patients with type II intestinal failure must be closely linked to the recording of fluid balance, and currently there is no single indicator that can cover all aspects of nutritional status evaluation. Body weight and BMI are easy objective indicators, but if the patient's fluid balance is unstable (e.g., high stoma flow, edema or early re-feeding in severely malnourished patients), rapid fluctuations in body weight at this time mostly reflect changes in the patient's body fluids rather than changes in the lean muscle mass. Similarly, serum albumin level is also a suitable indicator to reflect nutritional status because (1), inflammatory response itself can make serum albumin level decrease; (2), serum albumin level can be normal even with severe malnutrition; (3), excessive intravenous rehydration can also cause hypoproteinemia. The evaluation of nutritional and fluid balance in patients with type II intestinal failure is a continuous process that must be monitored and adjusted 24 hours a day by specialized health care personnel. There is a long-standing debate about the advantages and disadvantages of EN and PN. In patients with intestinal function, EN is undoubtedly the best mode of nutritional support. However, intestinal obstruction, mucosal lesions, short bowel, and intestinal fistulae limit the use of EN in intestinal failure to varying degrees. In fact, most of the increased complications associated with PN are the result of improper care leading to central venous catheter infections, or of metabolic disturbances and hyperglycemia due to excessive perfusion of parenteral nutrition. The understanding and experience with PN has evolved considerably over the last century, and the survival time of patients who are chronically dependent on PN no longer depends on the implementation of PN, but mainly on the extent of the underlying pathology. Therefore, when considering the optimal mode of nutritional support for intestinal failure, different patients may require different ratios of parenteral and enteral nutritional support, depending on the degree of intestinal failure, to ensure that patients receive adequate amounts of nutritional substrate. In patients with type II intestinal failure, the nutritional substrate provided can not only meet the patient's needs, but also help the patient recover rapidly from the abdominal infection process, which is an important topic for future research and development. It is not uncommon for type II intestinal failure to be combined with hepatobiliary pathology, and such hepatobiliary pathology may originate from the underlying pathology or is most likely a complication of treatment. For example, abdominal infection induces liver dysfunction, while antibiotic treatment applied during infection can also induce or exacerbate liver impairment, and protein-energy malnutrition can also cause hepatic steatosis. The effect of PN on the liver must be taken seriously at this point. In type II intestinal failure, it is sometimes difficult to define how much of the abnormal liver function is due to the underlying pathology and how much is due to nutritional support or pharmacological treatment. It is important to recognize the impact of pharmacologic factors (e.g., high-dose proton pump blockers in the case of short bowel syndrome or growth inhibitors in the case of enterocutaneous fistula) on the liver; and the importance of controlling abdominal infections to improve liver function. From the viewpoint of clinical nutritional support, restricting caloric intake and restoring enteral nutrition are more effective measures to reverse PN-related liver lesions. VI. Development of surgical plan Type II intestinal failure should be considered for long-term treatment planning only after the infection begins to subside and the nutritional status improves, because the presence of persistent infection and malnutrition are the main causes of postoperative complications and death. Regardless of the cause of intestinal failure, a thorough understanding of the patient's residual intestinal anatomy is essential before planning for definitive surgery. Since there are no specific indicators for monitoring the functional intestinal epithelial cell population, only the length of the residual intestine can be used as a rough predictor of whether the patient will be left with a nutritional deficiency after surgery. Therefore, a complete evaluation of the entire small bowel and colon, including oral contrast, barium enema, and sinus angiography, must be performed before considering performing GI reconstruction surgery. Because intestinal contrast can produce artifacts on CT images, imaging should be performed after CT. If intestinal perforation or anastomotic fissure is suspected, water-soluble ion contrast agent is preferable to barium because barium can cause peritoneal inflammatory reaction after entering the abdominal cavity. However, it must also be taken into account that barium is not easily diluted, is more impermeable on imaging, and is more sensitive in showing gastrointestinal fistulas and anatomical structures. In addition, ultrasound, angiography, cholangiography, CT or magnetic resonance imaging are necessary in some cases to obtain adequate information about the anatomy of the GI tract. Some chronic lesions (such as Crohns disease or pseudo-intestinal obstruction) often progress over a long period of time before developing into intestinal failure, while some lesions (such as extensive intestinal necrosis due to superior mesenteric artery thrombosis) often develop overnight into intestinal failure. The surgical planning for these different types of intestinal failure may vary and often requires a multidisciplinary treatment model that includes control of abdominal infection, improvement of nutritional status, determination of intestinal anatomy, and development of definitive therapeutic measures to reduce the incidence of complications and mortality in patients. Intestinal failure is difficult and costly to treat, and clinicians must focus on prevention of intestinal failure. Early diagnosis and treatment of potential intestinal ischemic lesions, avoidance of fistulas and abdominal infections caused by surgical errors, careful surgical treatment to prevent abdominal adhesion formation, and refraining from definitive surgery while abdominal infection or malnutrition is still present to avoid complications and additional intestinal tube loss are all noteworthy issues in the prevention of intestinal failure.