RIPCO is a rare but severe complication after neoadjuvant chemoradiotherapy and sphincter-saving surgery for rectal cancer. It is completely different from a simple anastomotic stricture. In fact, RIPCO is a chronic colonic obstruction in the pelvis due to radiation-induced fibrosis. The colonic stricture above the anastomosis can be as long as 10 cm. This study suggested that BMI, sacral depth, and radiation modalities were associated with RIPCO.
According to the results observed in this study, the clinical manifestation of RIPCO was as follows. First, all patients received sphincter-saving surgery for middle and low rectal cancer following NCRT, and most patients were male. Second, most patients had symptoms and signs of left colonic obstruction after stoma closure, including abdominal distension, megacolon, and a bowel stricture of 3–10 cm. MRI showed the thickened wall of the colon above the anastomosis and the beak sign at the inlet of the pelvis. There were no signs of pelvic recurrence of cancer. Third, most patients could not be cured by endoscopic treatments such as dilation or stent. The majority of patients required a permanent stoma (66.7%) or reconstruction of the anastomosis (22.2%). Fourth, no acute ischemia or clinically significant anastomotic leakage was detected during primary sphincter-saving surgery. Fifth, radiation-induced fibrosis of the colon above the anastomosis was diagnosed by endoscopic or pathological examination.
The present study suggested that the IMRT was associated with RIPCO. A previous meta-analysis of 859 patients from six studies showed that IMRT was associated with lower incidences of ≥ grade 3 acute overall gastrointestinal toxicity, diarrhea, and proctitis compared with 3DCRT [8]. Compared with conventional chemoradiotherapy, IMRT can also significantly reduce the dose distribution to the anal sphincters for patients with rectal cancer [13]. Whether IMRT can decrease the dose distribution to proximal resection margins and radiation injuries need further studies.
A small BMI was associated with RIPCO. There are several potential explanations for the results observed in this study. Optimal radiotherapy delivery is affected by obesity, and the tumor response may be impaired [14]. In the RIPCO group, more patients had a small BMI. It has been reported that autologous fat may play a potential role in the treatment of radiation-induced fibrosis [15]. This study suggested that a BMI less than 21.1 kg/m2 was an independent predictor of RIPCO.
Sacral depth more than 4.1 cm was associated with RIPCO. The stricture colon in a deep sacrum may be easy to form the sacral flexure in an acute angle after primary surgery, with the compression of thickened soft tissues, including bladder, seminal vesicles, muscles, and lateral fascia (Fig. 1E). In addition to radiation injuries of the colon and rectum, adhesions and fibrosis in a narrow pelvis after NCRT and surgery may restrict the dilation space of the colon. Due to radiation-induced fibrosis, the soft tissue may become thicker and compress the neorectum in the pelvis [6]. Hence, a deep sacrum may exacerbate the stenosis and associate with RIPCO.
Most patients with RIPCO were diagnosed after stoma closure, although water-soluble contrast enema was performed before closure. The insufficient display of the colonic lumen may have resulted in the missing diagnosis before stoma closure (Fig. 1G). To decrease the missed diagnosis rate before stoma closure, we recommend that using at least 250 ml of Urografin with sufficient pressure to fill and display the colonic lumen thoroughly during the examination (Fig. 1H). It may help to identify RIPCO and anastomotic leakage before stoma closure. Masaaki also reported a 13% recurrence of anastomosis leakage even though anastomotic healing was confirmed with water-soluble contrast enema before closure. Their study showed that ischemia at the anastomotic site was the main risk factor for recurrent leakage [16]. The PILLAR study suggested that the ICG could change 7.9% of the surgical plan because of the insufficient blood supply above the anastomosis [17]. However, no acute ischemia was detected from proctoscope during primary surgery in our study, and radiation-induced microvascular stenosis or occlusion and chronic ischemia may have led to RIPCO after NCRT and sphincter-saving surgery.
To date, there have been few effective methods to prevent and reverse radiation-induced intestinal fibrosis implemented in the clinic [19]. Hence, some surgeons recommend the addition of extended proximal colectomy and taking down the splenic flexure with the descending colon for anastomosis during primary sphincter-saving surgery. Previous studies suggested that the radiation injuries and fibrosis of proximal resection margins in patients with RIPCO were more severe than those without RIPCO [20, 21]. Therefore, we proposed that a colonic stricture above the anastomosis was “the criminal colon” and should be removed during primary surgery after NCRT. The proposed proximal margin was 19.0 (14.8–25) cm in patients with RIPCO in this study. This was consistent with the previous study. It suggested that radiation injury occurred within 20 cm proximal to rectal cancer [21]. However, whether it is necessary to routinely perform extended colectomy remains controversial.
This study has some limitations. First, this was a retrospective study with a limited number of patients in a single center. There may be selection bias. Second, the records of some important parameters were missing, including the mobilization of the splenic flexure, the length of the proximal bowel, the radiation dose distributions for the proximal margins, the MRI signals, and the radiation injury scores of the proximal margin during primary surgery. Because the sigmoid colon was usually long enough, in this study, we did not mobilize the splenic flexure routinely for all patients and performing an extended colectomy with the descending colon for anastomosis as recommended by experienced surgeons [8, 22]. However, this is one of the very few studies that provided the incidence and the risk assessment, including radiation modalities, for RIPCO. Further studies are needed to assess the radiation injury of the proximal margin and the risk of RIPCO before or during sphincter-saving surgery after NCRT [21]. The results may help with surgical planning and tailored surgery. In addition, to reduce radiation injuries, neoadjuvant therapy with optimal radiation modalities or without radiation in selected patients may decrease the radiation injuries without compromising long-term survival in the future [23, 24]. This study will draw attention to prevention for radiation-induced fibrosis.