The main treatment method for rectal cancer is surgery, and with the advancement of anatomical understanding and the continuous improvement of surgical instruments, rectal cancer anastomotic surgery has been performed more frequently. As a major complication of anastomotic leakage in rectal cancer surgery, anastomotic leakage has received increasing attention from clinical practitioners at home and abroad, and research has been intensified. To sum up, the current research on postoperative anastomotic leak in rectal cancer mainly covers five aspects, including factors that may lead to anastomotic leak, diagnosis, prevention, treatment and prognosis of postoperative anastomotic leak in rectal cancer, and certain achievements have been made. However, it should be noted that there are still many problems that have not been completely solved, such as the incidence rate varies greatly in different literature reports, which indicates that there is no unified and effective operation standard in prevention. In the future, we should continue to explore the prevention-oriented and combined prevention and treatment, even if the incidence and mortality rate are reduced by 1%, it is of great practical significance. Progress in the prevention and treatment of postoperative anastomotic leak in rectal cancer.
Anastomotic leak is a more serious complication after anastomotic surgery for rectal cancer, and there are two terms “anastomotic leak” and “anastomotic fistula” in the domestic literature. The term “leak” means rupture, which is called “leakage” or “leak” in English literature, and “fistula” refers to an abnormal tube between the deep part of the body and the body surface or organs, such as anal fistula and rectovaginal fistula. The term “fistula” is used in English. In this article, we focus on “fistula” formed by anastomotic rupture after rectal cancer surgery, and also include “anastomotic fistula” in some literature. Studies have confirmed that anastomotic leak is a risk factor affecting the postoperative local recurrence rate and tumor-related survival of rectal cancer patients. The author reviewed the domestic and international literature in the past 10 years, and combined with clinical practice, the progress of its prevention and treatment is summarized as follows.
The surgical anastomosis of rectal cancer is generally low and often has the following characteristics.
(1) The pelvic floor peritoneum is closed during rectal preservation surgery, and the presacral space is separated from the abdominal cavity. Leakage mostly occurs about 1 wk after surgery, when the rectum has adhered to the pelvic wall and surrounding tissues, and once anastomotic leakage occurs, the leakage is often limited to the presacral space.
(2) Adults have about 8 L of digestive juices per day, most of which are reabsorbed in the small intestine and proximal colon.
(3) The leaking fluid is feces, which contains a large amount of bacteria and is very likely to cause local and systemic infections.
1. Diagnostic points of anastomotic leak.
(1) Temperature change: the temperature has been normal after surgery, and then it rises again after 5-7 d or persistently high fever does not subside after surgery.
(2) Blood picture changes: leukocytes and neutrophils are increased.
(3) Changes in signs: rectal irritation signs and signs of peritonitis suggest that leakage has occurred.
(4) Drainage: increased pelvic drainage, cloudy or fecal water-like, and gas from the drainage tube during exhaustion.
(5) Severe patients may have paralytic intestinal obstruction, infectious toxic shock, acute renal failure, etc.
2.Factors that may lead to anastomotic leak.
There are many factors that can cause anastomotic leak, and the following are summarized from past experience.
(1) The risk of anastomotic leakage increases in elderly patients with relatively poor general condition and mostly combined with diseases such as vascular sclerosis and diabetes mellitus, low immune function and poor tissue repair ability.
(2) Obesity: intestinal wall and pelvic wall adipose tissue hypertrophy, poor intraoperative exposure; hypertrophic sigmoid mesentery across the sacral cape mostly has tension compression and affects blood supply; more anastomotic adipose tissue, postoperative liquefaction and formation of leakage; high percentage of diabetes.
(3) Preoperative intestinal preparation is not ideal: when the stool remaining in the proximal colon of the anastomosis passes through the anastomosis, it is easy to increase the tension of the anastomosis and induce infection and anastomotic leakage. Patients with emergency surgery often do not have intestinal preparation, and there is a large amount of intestinal contents in the postoperative intestine, and the pressure in the rectal cavity increases during defecation, causing excessive pressure at the anastomosis during defecation, which can easily lead to anastomotic fistula, incomplete intestinal obstruction exists before surgery, and the intestinal wall is dilated and edematous, which affects anastomotic healing.
(4) Poor systemic nutritional status: Patients with hypoproteinemia are prone to edema and poor repair and healing ability, and the body’s systemic and local tissue resistance to infection is reduced, so the chance of anastomotic leakage is relatively increased.
(5) Poor pelvic drainage: leads to infection around the anastomosis and induces anastomotic leakage.
(6) Unskilled anastomotic technique leads to defects in the anastomosis. For example, the needle distance is too large or too small, resulting in obstruction of anastomotic blood flow or poor suturing; improper use of the anastomosis leads to tissue tearing, incomplete stapling and entrapment of other tissues, etc. The closure of the rectal stump is the key to the success of the anastomosis when using the anastomosis clutch for low colorectal anastomosis. Therefore, we should master the operation of the anastomosis at every step, and be rigorous and meticulous.
(7) High anastomotic tension: Tension can cause spasm or tearing of the anastomotic vessels.
(8) Poor anastomotic blood flow: The healing of the anastomosis depends on a good blood supply at the anastomotic end. Thus, inadequate blood supply to the proximal colonic intestine is mainly due to the high and multiple locations of the free ligated mesentery, which damages the vascular arch of the colonic margin. In contrast, the blood supply to the mesentery of the rectal stump is derived from the inferior rectal artery and the anal artery. However, the variability of the inferior rectal artery is large, and most women are absent. Therefore, the blood supply to the stump after low anterior resection mainly depends on the anal artery, and if the rectal mesenteric is stripped too much the blood supply to the anastomosis is inevitably poor. After ligation of the inferior mesenteric artery, the blood supply to the sigmoid colon, which relies on the marginal artery for blood supply, was found to be significantly decreased by applying laser Doppler flowmetry, thus it is believed that insufficient blood supply to the marginal colonic artery after anastomosis may lead to anastomotic leak.
(9) Systemic diseases such as diabetes mellitus.
(10) Improper placement of postoperative drainage tube to compress the anastomosis.
(11) Improper mastering of surgical indications: With the continuous advancement of basic research on the pathological anatomy of rectal cancer and the application of intestinal anastomosis, the indications for anal preservation in radical rectal cancer surgery have been relaxed, and the distance between the lower edge of the lesion and the anus in Dixon’s operation has been reduced. However, there are more and more complications, and anastomotic leakage is one of the common complications.
(12) Lax intraoperative asepsis leads to perianastomotic infection. Some studies have shown that contamination of the operative field is an independent risk factor affecting the incidence of anastomotic leak.
(13) The occurrence of anastomotic leak is associated with the quantity and quality of matrix collagen in the preoperative colonic tissue and may be related to the abnormal expression of matrix collagenase-13.
(14) Early postoperative diarrhea: It can lead to abdominal distension, intestinal paralysis, and edema of the intestinal wall and anastomosis, contributing to the occurrence of anastomotic leak.
(15) Dukes stage: There was a significant correlation between different pathological stages of tumors and the incidence of anastomotic leak. Further analysis revealed that the incidence of anastomotic leak in patients with Dukes B stage was significantly different from those with Dukes C and D stage (P=0.01,P=0.03), while there was no significant difference in the incidence of anastomotic leak between patients with Dukes C and D stage (P=0.99), and the The reasons for this may be related to the relatively poor systemic condition of patients with Dukes C and D stage, the edema of the intestinal wall of the intestinal segment used for anastomosis, and the poor blood supply to the anastomosis due to the large amount of mesentery to be resected and the high anastomotic tension.
(16) Preoperative application of steroids.
(17) Long operative time.
(18) In addition, it is controversial whether some factors are associated with the development of anastomotic leak. For example, a prospective, controlled study concluded that adjuvant ileostomy did not reduce the incidence of anastomotic leak. In contrast, the results of Peeters et al study were opposite. However, we believe that an adjuvant stoma is clinically valuable because not only does it allow intraoperative flushing of the distal colon, but even if an anastomotic leak occurs postoperatively, a stoma that diverts feces can shorten the treatment time and reduce complications such as infection. In addition, factors such as the implementation of TME surgery, the distance between the anastomosis and the anal verge, gender, age, and tumor size are controversial.
3.Prevention
As a serious postoperative complication, the prevention of anastomotic leak has always been paid much attention, and many doctors have summarized more effective prevention methods in clinical practice.
(1) Good bowel preparation and intraoperative bowel irrigation in cases of intestinal obstruction.
(2) Active treatment of other complications during the perioperative period, control of blood sugar, correction of hypoproteinemia, etc.
(3) Ensure the anastomosis is tension-free and good blood supply. According to Liang Junlin et al, in transanal rectal drag-out anastomosis, as the anastomosis is retracted after anastomosis, certain tension can be relieved, and proximal colon freeing is appropriate, and some other tension-reducing measures are taken to achieve a balance of blood flow and tension, and blood flow should not be sacrificed for tension. This requires the operator to rely on experience to make trade-offs.
(4) Improve surgical skills, reduce the stretching and contusion of tissues, and be familiar with the use of various instruments.
(5) Perform intraoperative protective colostomy in patients with associated predisposing factors, especially in patients with two or more coexisting high-risk conditions.
(6) Intraoperative proximal placement of intestinal catheter: an ileostomy was performed through the ileocecal flap using a 24-gauge balloon catheter to prevent anastomotic leakage after anterior resection for low rectal cancer, and no one of the 25 cases developed anastomotic leakage after surgery with satisfactory results. The myxomatous catheter of F20~22 was placed in the cecum, and the myxomatous catheter was introduced by poking a hole in the abdominal wall corresponding to the cecum stoma. The peritoneum was intermittently sutured around the pulpy layer of the intestinal collaterals and the exit of the catheter in the abdominal wall at the hanging stoma. The catheter was removed 12-15 d after surgery. The effect of preventing anastomotic leakage was satisfactory.
(7) The anastomosis was reinforced by hand suturing after the anastomosis.
(8) Postoperative anal dilation to keep the anal sphincter relaxed and continuous retention of the anal tube in the rectum (across the anastomosis) can effectively reduce the pressure and chemical irritation of the intestinal contents on the anastomosis, which is extremely beneficial to the healing of the anastomosis.
(9) After anastomosis, perform an anastomotic air leak test, put warm saline in the pelvis to submerge the intestinal tube, put a non-invasive intestinal clamp on the proximal colon about 10 cm from the anastomosis, and inject air through the anus by the assistant under the table, so as to dilate the intestinal tube under the clamp, and observe whether there is air bubble overflow from the anastomosis, if there is, try to add a few stitches under direct vision, otherwise a prophylactic ileostomy should be performed.
(10) Intestinal bypass technique: some people remove the free sigmoid colon and rectum together with its mesentery, and the proximal colon is turned out 5 cm, and the sterilized condom is sewn to the mucosa and submucosa of the turned-out colon with 4-0 sheep intestinal thread, and after the anastomosis, the condom is pulled out from the anus and cut along the middle. This method is safe, inexpensive, simple and easy to use.
4.Treatment
Treatment principle: Anastomotic leak that has occurred should be treated at the first time. Low anastomotic leak generally has no direct effect on the stability of the internal environment and nutritional status, and except for serious infections, patients can be cured by active conservative treatment [7]. Local flushing and drainage via drainage tubes supplemented with TPN and transverse colonic dysfunctional leak is the main treatment for anastomotic leak.
Surgical treatment: colostomy and diversion of feces should be aggressively performed in the following cases
(1) Acute diffuse peritonitis.
(2) Estimated large leak that is difficult to heal on its own in the short term.
(3) Significant signs of systemic toxicity.
(4) Old age, poor nutrition, and reduced cardiopulmonary function making it difficult to tolerate prolonged total parenteral nutrition.
(5) The original drainage tube has been removed, and local treatment is difficult. The surgical approach is usually transverse colostomy or ileostomy, but Hartman surgery has also been reported, in which the original anastomosis is severed, the distal intestine of the anastomosis is closed, and the proximal intestine is pulled out for a single tube fistula.
In addition, in recent years, the theory of “rapid treatment” of intestinal leakage has been proposed, which is mainly reflected in.
(1) Following the traditional treatment principles, the original method is improved to promote the rapid self-healing of intestinal leakage.
(2) to completely change the traditional treatment principle, i.e., to perform definitive surgery, i.e., resection and intestinal anastomosis, at the early stage of intestinal leakage.
Non-surgical treatment: Except for the above cases, most cases can be treated conservatively first.
(1) Dietary control: With the continuous improvement of nutritional support therapy, dietary control has become easier. Early fasting, total gastrointestinal nutrition (TPN), or elemental diet with adequate drainage can be used for those who are not suitable for TPN. It should be noted that feeding should be resumed as early as possible depending on the circumstances. Recent studies have shown that 70% of the nutrition required by the intestinal mucosa comes from enteral nutrition, and the use of intravenous nutrition will leave the intestinal mucosa in a starved state, prone to atrophy, and make the intestinal barrier function diminished, in which case it is likely to lead to the translocation of intestinal bacteria or toxins [29]. In contrast, the implementation of enteral nutrition has a protective effect on the intestinal mucosa and can enhance the immune function of the intestinal mucosa. The digestive anastomosis site after colon tumor surgery is very low or there is no anastomosis in the abdominal cavity, so there is no need to worry about the impact on the anastomosis when implementing enteral nutrition, and it is completely possible to feed the patient as early as possible after surgery to improve malnutrition and promote compensation and repair. After the patient’s gastrointestinal function is restored, oral low residue diet can be given, and some intravenous nutrition can be given appropriately, but total parenteral nutrition (TPN) is not recommended. Take an appropriate amount of astringent to promote the early formation of stool, reduce the exudation of the leak, and facilitate the growth and filling of granulation tissue around the leak.
(2) Anti-infection: uncontrolled infection leading to multi-organ dysfunction syndrome is the main cause of death in patients with intestinal leakage, so antibiotics should be applied appropriately at an early stage, including static spot and local flushing, and can be discontinued after adequate drainage and infection control. Long-term application does not shorten the healing time of the leak.
(3) Flushing and drainage: there are more methods of flushing and drainage, and the commonly used methods are: pre-sacral single-tube drainage flushing: before performing anastomosis, the drainage tube is led from the right side of the distal rectum through the perianal area from the pre-sacral area, and the pelvic floor is strictly peritonealized, and the anastomosis is placed outside the peritoneum. Once anastomotic leak occurs, saline and methotrexate are applied to flush from the anterior sacral drainage tube twice or more times a day. Double-cannula flushing plus anal canal drainage: the patient is placed in a semi-sitting position, and the anal canal drainage tube is placed through the anus at a depth of about 2~3 cm just past the contracted external sphincter, avoiding the anastomosis as much as possible; the pre-sacral drainage double-cannula thick tube is connected to negative pressure, and then external compound metronidazole solution (500 mL solution containing chloramphenicol 1.25 g) is flushed through the thin tube continuously, followed by hypertonic saline solution (30 g/L sodium chloride). Afterwards, hypertonic saline solution (30 g/L sodium chloride solution) was applied to reduce the local edema to facilitate the repair of the tissues around the anastomosis. If the drainage fluid becomes clear, the amount of flushing fluid can be gradually reduced and the drip rate slowed down. After about 1 wk, when the pelvic floor fascia gradually adheres firmly and the elastic fiber membrane tube is formed around the lumen of the drainage tube, the double-lumen tube can be gradually withdrawn outward, once every 2 d, 2-3 cm each time, until it is finished and if there is no abnormality, the anal canal drainage can be withdrawn again. Pre-sacral drainage tube flushing with anal tube negative pressure suction method [35]: after it is clear that there is anastomotic leak, fasting is not required, and enteral nutrition, liquid food or less residue food can be given, and attention should be paid not to eat food that produces large pieces of food residue such as vegetables, which may block the suction tube. Anti-inflammatory and supportive treatment is routinely given. A 0.8-1.0 cm diameter myxomatous tube (which is not easily blocked or fixed and not easily dislodged) is inserted into the rectal cavity through the pelvic drainage tube placed at the time of surgery, and an electric negative pressure suction device is attached. With 2-3 kpa negative pressure continuous suction, pelvic drainage tube with saline continuous drip irrigation, drip rate of 60-100 drops/min; can be added twice a day with metronidazole solution, each time 100ml drip irrigation. It takes about 2h for the irrigation fluid to become clear when it is aspirated from the anal tube, and then it can be irrigated regularly, ranging from 4 to 8 times a day; the time of each irrigation also varies, depending on whether the effluent is turbid or not. When the fluid cannot be aspirated, the position can be changed or the anal myxomatous tube can be rotated and often aspirated again. For complete drainage and to prevent the spread of intra-abdominal contamination, the patient is placed in a semi-recumbent or sitting position. Note that if the myotomy tube cannot be aspirated, the drip of fluid from the pelvic drainage tube should be stopped to prevent the spread of intra-abdominal contamination. The healing of the leak is a gradual process. If the inflow and drainage of the irrigation fluid becomes slower and finally no drainage occurs, the leak can be considered closed and the irrigation can be stopped and the myxomycotic tube can be gradually removed from the rectum. Double-tube drainage method: The patient is placed in a lithotomy position, generally without anesthesia, and is first given adequate dilation and then probed for the size and orientation of the anastomotic leak with a dilator. A soft and flexible 0.3~0.5 cm diameter thin Pan’s tube (referred to as anal drainage tube) with multiple lateral holes at the lower end is placed under manual guidance, through the anastomotic leak into the lateral intestinal cavity (in the pelvis) about 3 cm below the anastomosis, and fixed with double butterfly tape. Make sure it is not folded, abdominal drainage tube (a thick Pan’s drainage tube is routinely placed next to the anastomosis in the pelvic cavity after rectal cancer anorectomy) and anal drainage tube are drained by 0.5% metronidazole solution 100-150ml 2-3 times a day. Keep the tube open and negative pressure suction after flushing. The anal drainage tube was removed according to the change of drainage fluid if it was light and did not contain intestinal contents; the abdominal drainage tube was removed according to the disappearance of signs of peritoneal irritation or healing of the anastomotic leak. Transanal sponge negative pressure drainage method: C.F. Nagell et al reported that transanal vacuum drainage was used to treat rectal anastomotic leaks without peritonitis with better efficacy than traditional methods, but the sample size was too small and the actual effect needed further validation. The method was as follows: within 1 d of anastomotic leak diagnosis, a piece of foam sponge (approximately 4 × 2 × 2 cm in size before compression) was placed so that it could pass through the rectum and the anastomotic defect site. The end of one suction tube was cut off and inserted into the sponge and fixed with 2 stitches of 2/0 polypropylene suture. The sponge with the suction tube was placed through the anus and passed over the anastomotic rupture site. The pressure of the suction tube was 125 mmHg intermittent negative pressure. The sponge is changed once every 2-3 days. A small dose of sedation may be given for the first VAC placement. This therapy can be stopped when the pus cavity is smaller than the sponge and covered by granulation tissue. In recent years, some progress has been made in the study of growth hormone and growth inhibitor to promote the healing of intestinal leakage, and there are many reports on this. Growth hormone can effectively inhibit the secretion of digestive juice, thus reducing its leakage from the leak to the outside; growth hormone can improve the expression of liver mRNA, regulate nitrogen balance and promote protein synthesis, thus accelerating the healing of the leak and the growth of intestinal mucosa. It should be noted that some malnourished patients may suffer from severe electrolyte and fluid disorders caused by metabolic abnormalities after oral, enteral or parenteral nutrition refeeding, and this series of symptoms and signs is called refeeding syndrome. Hypophosphatemia is a distinctive feature of refeeding syndrome, and growth hormone may aggravate it, so attention should be paid to electrolyte and ECG monitoring when using it.
5. Prognosis
Graham Branagan et al [51] counted 633 patients with rectal anastomosis, 40 cases of anastomotic leak occurred (6.3%), with a 30 d mortality rate of 10%, significantly higher than the leak-free group (2%).The 5-year cumulative local recurrence rate was 25.1%, significantly different from the leak-free group (10.4%) (P=0.007).The 5-year survival rates were 52.8% and 63.9%, respectively, with no significant difference (P=0.19). The 814 patients who underwent prerectal resection from 1978 to 1996 were followed up, and the prognosis of patients with and without anastomotic leak was analyzed univariately and multifactorially. Of these, 89 (10.9%) had anastomotic leakage. After Kaplan-Meier survival curve analysis, the overall 5-year local recurrence rate of patients was 13.6%. Multifactorial analysis showed that anastomotic leak was an independent risk factor for local recurrence (relative risk ratio 1.7, P=0.0418) and for tumor-related survival (relative risk ratio 1.6, P=0.0172).
In conclusion, certain achievements have been made and many valuable experiences have been accumulated in the diagnosis and treatment of postoperative anastomotic leak in rectal cancer, but there are still many problems that have not been completely solved, for example, the incidence rate varies greatly in different literature reports, which indicates that there is no unified and effective operation standard in prevention. In the future, we should continue to explore the prevention of the disease and combine prevention and treatment, even if the incidence and mortality rate is reduced by 1%, it is also of great practical significance.