CXCL16 inhibits epithelial regeneration and promotes fibrosis during the progression of radiation enteritis.

Radiation enteritis (RE) is a prevalent complication of radiotherapy for pelvic malignant tumors, characterized by severe intestinal epithelial destruction and progressive submucosal fibrosis. However, little is known about the pathogenesis of this disease, and so far, there is no specific targeted therapy. Here, we report that CXCL16 is upregulated in the injured intestinal tissues of RE patients and in a mouse model. Genetic deletion of Cxcl16 mitigates fibrosis and promotes intestinal stem cell-mediated epithelial regeneration after radiation injury in mice. Mechanistically, CXCL16 functions on myofibroblasts through its receptor CXCR6 and activates JAK3/STAT3 signaling to promote fibrosis and, at the same time, to transcriptionally modulate the levels of BMP4 and hepatocyte growth factor (HGF) in myofibroblasts. Moreover, we find that CXCL16 and CXCR6 auto- and cross-regulate themselves in positive feedback loops. Treatment with CXCL16 neutralizing monoclonal antibody attenuates fibrosis and improves the epithelial repair in RE mouse model. Our findings emphasize the important role of CXCL16 in the progression of RE and suggest that CXCL16 signaling could be a potential therapeutic target for RE. © 2022 The Pathological Society of Great Britain and Ireland.

Laparoscopic Proximally Extended Colorectal Resection With Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Late Complications of Chronic Radiation Proctopathy.

Background: Chronic radiation proctopathy (CRP) is a common complication after radiation therapy for pelvic malignancies. Compared with diversion surgery, resection surgery removes the damaged tissue completely to avoid the risks of recurrence and improve patients' outcome. Hence, resection surgery could be an optimal surgical approach when CRP is complicated by late complications. This study aimed to describe a modified surgical procedure of resection surgery and report its preliminary efficacy and safety in treating patients with CRP with late complications. Methods: We retrospectively reviewed the patients who were diagnosed with CRP with late complications and underwent the modified surgical procedure of laparoscopic proximally extended colorectal resection with two-Stage Turnbull-Cutait pull-through coloanal anastomosis (PE-Bacon) between November 2019 and October 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University. Results: A total of 15 patients were performed the modified laparoscopic procedure of PE-Bacon, of which 1 patient underwent conversion from laparoscopic to open operation for intraoperative massive hemorrhage. Overall, the major (Clavien-Dindo III-V) postoperative complications occurred in 1 patient, anastomotic leakage was observed in 2 (13.3%) patients, and anastomotic stricture was observed in 4 (26.7%) patients. No patient had to be reoperated and died. Up to now, at the average follow-up of (524.40 ± 108.39) days, the preoperative symptoms of 93.3% (14/15) patients were relieved, with nine patients achieved complete remission, five patients only suffered minor symptoms. Because of the progression of radiation uropathy, one patient still had a vesicovaginal fistula as pre-operative complication. Colostomy reversal has been performed on 8 (53.3%) patients at an average postoperative duration of 299.5 ± 92.68 days, among whom only 2 patients suffered from major Low Anterior Resection Syndrome (LARS) until now. Conclusions: Laparoscopic PE-Bacon surgery is a safe and feasible surgical procedure for late complications of CRP with low morbidity and high symptom remission rate.

Risk Prediction and Treatment of LE-DVT in Patients with Chronic Radiation Intestinal Injury: A Retrospective Case-Control Study.

BACKGROUND: Chronic radiation intestinal injury (CRII) is the most common complication after pelvic malignancy radiation. Once hemorrhagic CRII patients suffer from lower extremity deep venous thrombosis (LE-DVT), hemostasis and anticoagulation therapy will be adopted simultaneously, but the treatment strategy is a paradox, as the condition is extremely intractable and serious. The aim of this study was to investigate the prevalence of and risk factors for LE-DVT in CRII patients and explore the treatment of hemorrhagic CRII patients with LE-DVT. METHODS: This was a retrospective study, and a total of 608 hospitalized CRII patients after pelvic radiotherapy were included from November 2011 to October 2018. Univariate and multivariate analyses were conducted to investigate the potential risk factors for LE-DVT in CRII patients. Furthermore, the treatment of hemorrhagic CRII patients with LE-DVT was explored. RESULTS: Among the CRII patients, 94 (15.5%) were with suspicious symptoms of LE-DVT in the lower limbs, and 32 (5.3%) were diagnosed with LE-DVT. Among the patients with LE-DVT, 65.6% (21/32) had bleeding simultaneously, and 29 (90.6%) had anemia with 24 (75.0%) having moderate to severe anemia. Multivariate analysis showed that a recent surgical history (≤6 months) (OR = 5.761, 95% CI: 2.506~13.246, p < 0.001), tumor recurrence or metastasis (OR = 3.049, 95% CI: 1.398~6.648, p = 0.005) and the hemoglobin (Hb) level (OR = 0.960, 95% CI: 0.942~0.979, p < 0.001) were significantly associated with the development of LE-DVT. ROC curve analysis showed that the AUC of the merged risk score of the independent risk factors was 0.822 (95% CI: 0.789~0.852), and the optimal Hb cutoff was 82.5 g/L. After colostomy, obvious bleeding remission was rapidly found in 84.6% of hemorrhagic CRII patients with LE-DVT. CONCLUSION: The prevalence of LE-DVT in hospitalized CRII patients was 5.3%. A recent surgical history, tumor recurrence or metastasis and a lower Hb level were independently associated with LE-DVT development in CRII patients. Colostomy could be a good choice for intractable hemorrhagic CRII patients with LE-DVT.

Risk Factors of Delayed Recovery of Gastrointestinal Function After Ileostomy Reversal for Rectal Cancer Patients.

PURPOSE: The aim of this study was to identify the risk factors associated with delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients. METHODS: In this retrospective study, the data of rectal cancer patients who underwent ileostomy reversal from January 2018 to December 2019 at the Sixth Affiliated Hospital of Sun Yat-sen University were assessed to investigate potential risk factors of delayed flatus after ileostomy reversal. RESULTS: A total of 282 patients were eligible for this study. Postoperative first flatus time ranged from 1 to 9 days, of which 58.8% patients presented with delayed flatus that was longer than 3 days. Univariate analysis showed that delayed postoperative flatus was significantly associated with the length of postoperative hospital stay (P<0.001) and postoperative complications (P=0.037). Multivariate analysis showed that intravenous fluid infusion at postoperative day 1 (POD1) (OR=1.001, 95% CI: 1.001-1.002, P=0.001) and duration of stoma ≥6 months (OR=2.005, 95% CI:1.155-3.657, P=0.014) were independent risk factors for delayed flatus. CONCLUSION: Increased intravenous fluid infusion at POD1 and duration of stoma ≥6 months were related to delayed recovery of gastrointestinal function after ileostomy reversal for rectal cancer patients.

Diverting colostomy is an effective procedure for ulcerative chronic radiation proctitis patients after pelvic malignancy radiation.

BACKGROUND: Chronic radiation proctitis (CRP) with rectal ulcer is a common complication after pelvic malignancy radiation, and gradually deteriorating ulcers will result in severe complications such as fistula. The aim of this study was to evaluate effect of colostomy on ulcerative CRP and to identify associated influence factors with effectiveness of colostomy. METHODS: Between November 2011 to February 2019, 811 hospitalized patients were diagnosed with radiation-induced enteritis (RE) in Sun Yat-sen University Sixth Affiliated Hospital, among which 284 patients presented with rectal ulcer, and 61 ulcerative CRP patients were retrospectively collected and analyzed. RESULTS: The overall effective rate of colostomy on ulcerative CRP was 49.2%, with a highest effective rate of 88.2% within 12 to 24 months after colostomy. 9 (31.1%) CRP patients with ulcers were cured after colostomy and 12 (19.67%) patients restored intestinal continuity, among which including 2 (3.3%) patients ever with rectovaginal fistula. 100% (55/55) patients with rectal bleeding and 91.4% (32/35) patients with anal pain were remarkably alleviated. Additionally, multivariable analysis showed the duration of stoma [OR 1.211, 95% CI (1.060-1.382), P = 0.005] and albumin (ALB) level post-colostomy [OR 1.437, 95% CI (1.102-1.875), P = 0.007] were two independent influence factors for the effectiveness of colostomy on the rectal ulcer of CRP patients. CONCLUSIONS: Colostomy was an effective and safe procedure for treating rectal ulcer of CRP patients, and also a potential strategy for preventing and treating fistula. Duration of stoma for 12-24 months and higher ALB level could significantly improve the effectiveness of colostomy on ulcerative CRP patients.