To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown. METHODS: We evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, n = 21) or proximally extended resection (nCRT-E, n = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin. RESULTS: Compared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, P = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, P = 0.039) at the proximal margins compared with the nCRT-C group. CONCLUSIONS: The severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.

Diverting colostomy is an effective and reversible option for severe hemorrhagic radiation proctopathy.

BACKGROUND: Severe chronic radiation proctopathy (CRP) is difficult to treat. AIM: To evaluate the efficacy of colostomy and stoma reversal for CRP. METHODS: To assess the efficacy of colostomy in CRP, patients with severe hemorrhagic CRP who underwent colostomy or conservative treatment were enrolled. Patients with tumor recurrence, rectal-vaginal fistula or other types of rectal fistulas, or who were lost to follow-up were excluded. Rectal bleeding, hemoglobin (Hb), endoscopic features, endo-ultrasound, rectal manometry, and magnetic resonance imaging findings were recorded. Quality of life before stoma and after closure reversal was scored with questionnaires. Anorectal functions were assessed using the CRP symptom scale, which contains the following items: Watery stool, urgency, perianal pain, tenesmus, rectal bleeding, and fecal/gas incontinence. RESULTS: A total of 738 continual CRP patients were screened. After exclusion, 14 patients in the colostomy group and 25 in the conservative group were included in the final analysis. Preoperative Hb was only 63 g/L ± 17.8 g/L in the colostomy group compared to 88.2 g/L ± 19.3 g/L (P < 0.001) in the conservative group. All 14 patients in the former group achieved complete remission of bleeding, and the colostomy was successfully reversed in 13 of 14 (93%), excepting one very old patient. The median duration of stoma was 16 (range: 9-53) mo. The Hb level increased gradually from 75 g/L at 3 mo, 99 g/L at 6 mo, and 107 g/L at 9 mo to 111 g/L at 1 year and 117 g/L at 2 years after the stoma, but no bleeding cessation or significant increase in Hb levels was observed in the conservative group. Endoscopic telangiectasia and bleeding were greatly improved. Endo-ultrasound showed decreased vascularity, and magnetic resonance imaging revealed an increasing presarcal space and thickened rectal wall. Anorectal functions and quality of life were significantly improved after stoma reversal, when compared to those before stoma creation. CONCLUSION: Diverting colostomy is a very effective method in the remission of refractory hemorrhagic CRP. Stoma can be reversed, and anorectal functions can be recovered after reversal.

Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis.

BACKGROUND: Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center. AIM: To assess the long-term efficacy and safety of APC for hemorrhagic CRP. METHODS: This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas. RESULTS: Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm2 (P = 0.035). CONCLUSION: The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm2.

Novel and Effective Almagate Enema for Hemorrhagic Chronic Radiation Proctitis and Risk Factors for Fistula Development.

Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P<0.001) after the enemas. The mean response time was 12 days. No adverse effects were found. Moreover, long-term successful rate in controlling bleeding was 69% and the quality of life was dramatically improved (P=0.001). The efficacy was equivalent to rectal sucralfate, but the almagate with its antacid properties acted more rapidly than sucralfate. Furthermore, we firstly found that moderate to severe anemia was the risk factor of CRP patients who developed rectal deep ulcer or fistulas (P= 0.015). We also found abnormal hyaline-like thick wall vessels, which revealed endarteritis obliterans and the fibrosis underlying this disease. These findings indicate that almagate enema is a novel effective, rapid and well-tolerated method for hemorrhagic CRP. Moderate to severe anemia is a risk factor for deep ulceration or fistula.

Colostomy is a simple and effective procedure for severe chronic radiation proctitis.

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. RESULTS: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. CONCLUSION: Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy.

Formalin irrigation for hemorrhagic chronic radiation proctitis.

AIM: To assess the efficacy and safety of a modified topical formalin irrigation method in refractory hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with CRP who did not respond to previous medical treatments and presented with grade II-III rectal bleeding according to the Common Terminology Criteria for Adverse Events were enrolled. Patients with anorectal strictures, deep ulcerations, and fistulas were excluded. All patients underwent flexible endoscopic evaluation before treatment. Patient demographics and clinical data, including primary tumor, radiotherapy and previous treatment options, were collected. Patients received topical 4% formalin irrigation in a clasp-knife position under spinal epidural anesthesia in the operating room. Remission of rectal bleeding and related complications were recorded. Defecation, remission of bleeding, and other symptoms were investigated at follow-up. Endoscopic findings in patients with rectovaginal fistulas were analyzed. RESULTS: Twenty-four patients (19 female, 5 male) with a mean age of 61.5 ± 9.5 years were enrolled. The mean time from the end of radiotherapy to the onset of bleeding was 11.1 ± 9.0 mo (range: 2-24 mo). Six patients (25.0%) were blood transfusion dependent. The median preoperative Vienna Rectoscopy Score (VRS) was 3 points. Nineteen patients (79.2%) received only one course of topical formalin irrigation, and five (20.8%) required a second course. No side effects were observed. One month after treatment, bleeding cessation was complete in five patients and obvious in 14; the effectiveness rate was 79.1% (19/24). For long-term efficacy, 5/16, 1/9 and 0/6 patients complained of persistent bleeding at 1, 2 and 5 years after treatment, respectively. Three rectovaginal fistulas were found at 1 mo, 3 mo and 2 years after treatment. Univariate analysis showed associations of higher endoscopic VRS and ulceration score with risk of developing rectovaginal fistula. CONCLUSION: Modified formalin irrigation is an effective and safe method for hemorrhagic CRP, but should be performed cautiously in patients with a high endoscopic VRS.

The prognostic role of BRAF mutation in metastatic colorectal cancer receiving anti-EGFR monoclonal antibodies: a meta-analysis.

BACKGROUND: BRAF mutation has been investigated as a prognostic factor in metastatic colorectal cancer (mCRC) undergoing anti-EGFR monoclonal antibodies (moAbs), but current results are still inconclusive. The aim of this meta-analysis was to evaluate the relationship between BRAF mutation status and the prognosis of mCRC patients treated with moAbs. METHODS: Eligible studies were identified by systematically searching Pubmed, the Cochrane Library, Web of Knowledge, and OVID. Risk ratio (RR) for overall response rate (ORR), Hazard ratios (HRs) for Progression free survival (PFS) and Overall survival (OS) were extracted or calculated. Prespecified subgroup analyses were conducted in KRAS wild-type and in different study types. The source of between-trial variation was explored by sensitivity analyses. Quality assessment was conducted by the Hayden's criteria. RESULTS: A total of twenty one trials including 5229 patients were identified for the meta-analysis. 343 patients displayed BRAF mutations of 4616 (7.4%) patients with known BRAF status. Patients with BRAF wild-type (WT) showed decreased risks of progression and death with an improved PFS(HR 0.38, 95% confidence intervals 0.29-0.51) and an improved OS (HR 0.35 [0.29-0.42]), compared to BRAF mutant. In KRAS WT population, there were even larger PFS benefit (HR 0.29[0.19,0.43]) and larger OS benefit (HR 0.26 [0.20,0.35]) in BRAF WT. A response benefit for BRAF WT was observed (RR 0.31[0.18,0.53]) in KRAS WT patients, but not observed in unselected patients (RR 0.76 [0.43-1.33]). The results were consistent in the subgroup analysis of different study types. Heterogeneity between trials decreased in the subgroup and explained by sensitivity analysis. No publication bias of ORR, PFS and OS were detected. CONCLUSIONS: The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients. Additional large prospective trials are required to confirm the predictive role of BRAF status.