Chronic radiation enteritis (CRE) is a common gastrointestinal complication of radiotherapy. More than 1/3 of CRE patients eventually require surgical treatment, but the difficulty of CRE surgery and the high rate of complications and reoperation have long made surgical treatment of CRE a great challenge for surgeons. This paper presents some new thoughts on surgical treatment of CRE based on the experience of more than 300 cases of CRE surgical treatment.
Radiotherapy as an important component of comprehensive tumor treatment has significantly improved the survival rate of tumor patients, but the incidence of radiation enteritis, especially chronic radiation enteritis (CRE), has not been reduced by improved radiotherapy techniques [1, 2]. The main reasons for surgeons to choose surgical treatment of CRE are the difficulty of surgery, many complications, and high mortality. 11 years of surgical treatment of CRE cases in our department has been more than 300 cases, we have summarized our experience in the surgical treatment of 206 cases of CRE [3], on this basis, we would like to discuss some of our thoughts on this issue.
I. Indications for surgical treatment
Radiation enteritis (RE) can be divided into two types: acute and chronic. In the former, the abnormal changes in the structure and function of intestinal tissues are relieved within 4-6 weeks after the end of radiotherapy, and the intestinal mucosal tissues recover and clinical symptoms disappear 3-6 months after the end of radiotherapy. In contrast, clinical symptoms of CRE usually occur 12-24 months after the end of radiotherapy, or in late cases may appear decades after the end of radiotherapy, and in our case we had surgical treatment for intestinal obstruction due to CRE 30 years after the end of radiotherapy [3].
The exact incidence of acute RE is unknown, with 25-75% of abdominal and pelvic radiotherapy patients presenting with acute RE, 55% of whom will be seen for gastrointestinal symptoms [4,5]. The incidence of CRE is 5% with an irradiation dose of 45 Gy, and 50% of patients will develop CRE if the irradiation dose is 65 Gy or more. Of course, there are many factors that affect CRE, with combination chemotherapy being the most common risk factor. However, not all patients with CRE require surgical treatment, and only 1/3 of CRE patients require surgical treatment during the course of the disease [1,6].Common indications for surgical treatment of CRE are intestinal obstruction, bleeding uncontrolled by medical therapy, intestinal perforation with abdominal infection, and intestinal fistula.Meissner et al [7] collected 51 papers of 801 patients with surgically treated CRE, with late complications were intestinal obstruction (71. 3% ), intestinal fistula (16.6%), intestinal perforation (9.7%) and bleeding (2.4%). The indications for surgical treatment in our group of 206 patients with CRE were 142 cases of intestinal obstruction (68.9%), 56 cases of intestinal fistula (27.2%), 12 cases of severe colorectitis (5.8%), 6 cases of intestinal bleeding (2.9%), and 13 cases of others (6.3%) [3].
II. Surgical modalities
The commonly used surgical procedures for CRE are intestinal resection anastomosis, short-circuit anastomosis and colostomy, and surgery for concomitant intestinal perforation, bleeding and fistula. Among them, resection of the diseased intestine in one stage anastomosis or enterostomy (with or without resection of the diseased intestine) + stage II enterostomy is the most common. The former can remove the diseased intestine at one time, but the chance of anastomotic fistula is higher, the surgery is traumatic, avoiding reoperation, restoring intestinal continuity and meeting the requirements of intestinal physiology; while the latter is less traumatic to the patient, and the enterostomy can also avoid anastomotic fistula. Various surgical procedures have their advantages and disadvantages, and a reasonable surgical plan must be selected according to the patient’s general condition and intestinal condition, which is one of the keys to successful surgery. In our group of 206 cases and 229 procedures, there were 142 cases of lesion bowel resection + stage 1 intestinal anastomosis; 57 cases of lesion bowel resection + enterostomy (19 cases of permanent stoma and 38 cases of stage II enterostomy rejection); 14 cases of lesion intestinal collaterals open; and 16 cases of other procedures (9 cases of intestinal alignment, 4 cases of small bowel cannula stoma, and 3 cases of intestinal adhesion release) [3]. In order to make surgeons more targeted in choosing surgical procedures, the following surgical treatments are described separately according to the complications of CRE.
III. Surgical treatment of CRE
1. Surgical treatment of CRE with intestinal obstruction
CRE with intestinal obstruction is the most common reason for surgical treatment. CRE with intestinal obstruction is the most common cause of surgical treatment, but there is no classification of the part of intestinal obstruction in the literature about CRE at home and abroad, in fact, the preoperative clarification of the site of intestinal obstruction is extremely important for the selection of surgical methods. Almost all CRE intestinal obstruction has been discussed in the previous literature for small bowel obstruction [1, 4-7], and it is not uncommon for CRE to be complicated by rectal obstruction or both rectal and small bowel obstruction in clinical practice. If the presence of rectal obstruction cannot be clarified preoperatively, surgical resection of the obstructing small bowel (mostly ileum) alone still cannot resolve the problem of intestinal obstruction.
Bowel resection is the main surgical procedure for small bowel obstruction, and either a stage I bowel resection anastomosis or an enterostomy + stage II bowel anastomosis is performed depending on the patient’s general and intestinal condition. Among our 206 cases and 229 procedures, 180 (78.6%) were bowel resection anastomoses, including 142 intestinal stage I bowel resection anastomoses and 38 bowel resection stage II bowel anastomoses [3]. A common and serious complication of intestinal resection anastomosis is anastomotic fistula, how to prevent anastomotic fistula, two points need to be noted during surgery: (1) choose two healthy intestinal tubes for anastomosis, one end of the intestine is healthy and the other end of the intestine has slight radiation damage, the anastomosis is safe; if both ends of the anastomosis have serious radiation damage, the incidence of anastomotic fistula is high. The rates of poor healing of different sites of bowel resection are 25.5% for ileo-ileal anastomosis, 12% for jejuno-ileal anastomosis, 9.3% for ileo-ascending colon anastomosis, and 4% for ileo-transverse colon anastomosis [7]. Summarizing the surgical treatment experience of more than 300 CRE cases, we found that ileo-ascending colon anastomosis is safer and has a lower incidence of anastomotic fistula than ileo-transverse colon anastomosis, unless the patient has injury to the ascending colon (e.g., patients with right renal tumor or right retroperitoneal tumor treated with radiation), ileo/jejuno-ascending colon anastomosis is usually chosen. Recently, Lefevre et al [8] summarized 20 years of experience in the surgical treatment of 107 cases of CRE also showed that ileal resection is the most important factor in reducing anastomotic fistula and reoperation rate; (2) anastomosis, lateral anastomosis is safer than end-to-side or end-to-end anastomosis, especially the anastomotic lateral anastomosis is preferred.
For patients with small bowel obstruction in poor general condition or proximal intestinal collaterals that are significantly dilated with ischemia, enterostomy and phase II intestinal anastomosis can be chosen. In contrast, proximal colostomy is a wise choice for patients with rectal obstruction. Enterostomy is a common surgical procedure for CRE, accounting for 24.9% of our 229 cases [3]. The choice of enterostomy site needs to pay attention to the following two issues: (1) choose a collaterals stoma without injury, most patients with pelvic radiotherapy, the site of intestinal collaterals injury is sigmoid and/or ileum, ileo/sigmoid stoma is prone to gangrene, stricture, detachment, bleeding, while transverse or descending colonic stoma the above complications are significantly reduced, and (2) choose a peritoneal wall stoma without radiation injury, because the abdominal wall of lower abdomen The same radiological damage also exists, and the same complications will occur as with the improper selection of intestinal collaterals.
As for short-circuiting surgery, it has been used less and less in recent years. The advantage of short-circuiting anastomosis is that it is simple to perform, and the incidence of anastomotic fistula in short-circuiting surgery was thought to be low, but the current study concluded that the incidence of fistula in the anastomotic site is not higher than that in short-circuiting surgery [7]. The risk of hemorrhage, perforation (fistula), obstruction, infection and blind collaterals syndrome is still present and often requires reoperation.
2. Surgical treatment of CRE with intestinal fistula
Both domestic and international studies have shown that enterocutaneous fistulae are the second most frequent cause of surgical complications of CRE, accounting for 27.2% of our 206 cases [3]. The most ideal solution is to remove the diseased small intestine segment where the fistula is located and restore the intestinal continuity, or to remove the diseased intestinal collaterals that are difficult to remove or the patient’s general condition is poor. For those who have difficulty in removing the diseased intestinal collaterals or who are in poor systemic condition, enterostomy and stage II intestinal anastomosis can be chosen.
Due to the contracture of the bladder, the urinary storage function of the bladder is significantly reduced and frequent urination (small bladder) occurs. This can effectively solve the problem of “small bladder”.
In recent years, more and more patients with advanced cervical cancer receive radiation therapy directly without surgery, and the number of cases of rectovaginal fistula brought about by the combination of external and internal radiation therapy applied to some patients has also increased significantly, and the main surgical procedure for such patients is proximal enterostomy.
3. Surgical treatment of CRE with intestinal perforation
The aim of surgery is to control the infection, save the patient’s life and create conditions for secondary surgery to reconstruct the continuity of the digestive tract. In patients with stable vital signs, if the site of a single perforation can be rapidly localized intraoperatively, and the segment of the intestine can be easily resected and at least one intestinal anastomosis without radiological damage can be obtained, definitive surgery can be considered in a single visit, but the complications and mortality of intestinal anastomosis in emergency surgery are significantly higher than in elective surgery [8].
4. surgical treatment of CRE with intestinal bleeding.
For patients with acute intestinal bleeding, the principle of surgical treatment is to stop bleeding, and the ideal solution is to remove the bleeding intestinal collaterals, and whether to perform intestinal anastomosis depends on the patient’s general condition.
IV. Surgical treatment of CRE patients after healing
In a non-randomized controlled study, Gavazzi et al [9] confirmed that the 5-year survival rates of home parenteral nutrition and surgical groups were 90.0% and 68.4%, respectively, but the number of cases in this study was only about ten. Regimbeau et al [6] followed up 109 surgically treated CRE patients for 40 (1-293) months, and 40% of the patients required reoperation during the follow-up. The survival rates of patients with tumor recurrence were 72%, 26% and 19% respectively, and the 5-year survival rates of surgical and non-surgical patients were 71% and 51% respectively.
V. Consideration of several problems in surgical treatment of CRE
1. The timing of surgical treatment of radiation enteritis
Radiation enteritis is divided into two types: acute (within 3-6 months of radiation therapy) and chronic. The clinical manifestations of acute RE, such as abdominal pain, diarrhea and intestinal obstruction, are seen within days after radiotherapy. Unless the patient has complete intestinal obstruction, perforation and uncontrollable bleeding, surgical treatment is not considered in the acute stage. Performing surgical treatment before the disease has stopped not only makes it difficult to distinguish between normal and diseased intestines, but also the so-called normal intestinal collaterals at the time of surgery may gradually evolve into chronic intestinal injury after surgery, with recurrent complications such as intestinal obstruction, perforation, bleeding and intestinal fistula [1, 9].
2. Perioperative nutritional support for CRE
Most patients with CRE have extremely deteriorated systemic conditions with severe malnutrition, disturbances in endostasis, and anemia; therefore, the perioperative management of patients with radiation enteritis is very important, in which nutritional support plays an important role [1-3,8].The objectives of preoperative nutritional support in CRE are (1) to supply sufficient nitrogen and energy to improve the nutritional status of patients and enable them to tolerate complex surgery; (2) to improve organ function and reduce the incidence of postoperative complications; (3) correct endostatic imbalance; (4) promote intestinal mucosal repair; and (5) reduce digestive fluid secretion, thereby reducing the overflow of intestinal fluid from the fistula and reducing infection and inflammation in the tissues adjacent to the intestinal fistula [1]. support is applied at a high rate. Among the 206 CRE patients treated in our surgery, the rate of moderate to severe malnutrition at admission was 55.97%, and 75.98% of patients required preoperative nutritional support, including 44.7% enteral nutrition support, 35.1% total parenteral nutrition support, and 17.2% parenteral combined with enteral nutrition support, and the duration of the three types of nutritional support were 26.22 ± 28.99 d, 15.00 ±13.11d, 25.36±18.06d, and 80% of patients still needed enteral or/and parenteral nutritional support after surgery, and the proportion of home nutritional support after discharge was as high as 51% [3].
3. Differential diagnosis of CRE and with tumor recurrence leading to intestinal obstruction
Most patients with CRE have different degrees of abdominal wall injury, and it is difficult to distinguish between peritoneal implant metastasis and peritoneal radiation injury during physical examination. PET/CT has higher sensitivity in diagnosing tumor recurrence, but it is also difficult to distinguish between CRE or tumor recurrence, both of which are highly manifested as hypermetabolic hyperplastic lesions. Therefore, unless there is clear tumor recurrence or metastasis, surgical treatment can be actively chosen for patients with suspected CRE.
4. Short bowel syndrome after CRE surgery
Short bowel syndrome occurs in 10-19% of patients after CRE surgery [10,11]. Since the residual small intestine is also radiologically damaged to varying degrees after surgery, intestinal absorption and motility are difficult to reach normal levels, and the clinical manifestations of short bowel syndrome are more likely to occur. Lefevre reported that 49.5% of postoperative long-term survival CRE patients rely on parenteral nutrition, and short bowel syndrome is the main cause of this [8]. 5% [11].
5. Recurrence and reoperation after CRE surgery
The reoperation rate of CRE is very high, mainly due to postoperative complications and stoma rejection. In our unit, 206 patients had an average of 1.11 surgeries and a maximum of 5 surgeries [3].Lefevre et al [8] followed up 71 (2-320) months with 2 (1- 5) surgeries, 60.7% of patients were reoperated due to CRE recurrence, and the reoperation rates were 37%, 54%, and 59% at 1, 3, and 5 years postoperatively, respectively. With the increase in long-term survival patients, the issue of CRE reoperation is a priority that deserves adequate attention in the future.
In conclusion, surgical treatment of CRE is a major challenge for surgeons, manifested by the difficulty of surgery, high complications and high mortality, but the quality of life and survival of surgically treated CRE patients are better than conservative treatment, and the selection of appropriate indications for surgery, proper perioperative management and reasonable surgical procedures have the potential to further reduce the complications and mortality of surgical treatment of CRE.