[Application of endoscopic tattooing with carbon nanoparticlet in the treatment for advanced colorectal cancer]

Objective: To explore the application of endoscopic tattooing with carbon nanoparticles in the treatment of advanced colorectal cancer (ACRC). Methods: A randomized controlled study was used. Inclusion criteria: (1) age more than 18 years old, and colorectal cancer was found for the first time and confirmed by colonoscopy and biopsy; (2) advanced colorectal cancer (preoperative TNM stage of T3/N1 or above, local unresectable lesion, M1 stage and simultaneously resectable metastatic lesion), and patients agreed to receive neoadjuvant therapy; (3) advanced colorectal cancer (TNM stage of T3/N1 or above) with simultaneous unresectable metastatic lesion, and patients refused operation and consented to chemoradiotherapy. Patients with previous abdominal surgery history, radiotherapy and chemotherapy history, urgent need for surgery or endoscopic stent placement and those with severe allergic constitution were excluded. Based on the above criteria, 120 patients diagnosed with ACRC in No.900 Hospital of the Joint Logistics Team from January 2016 to December 2017 were prospectively enrolled and randomly divided into tattoo group and non-tattoo group by random number table method. Tattoo group were tattooed within 1-7 days before chemoradiotherapy. The labeling location of the lesions: (1) if the colonoscopy could pass smoothly, 4 points were injected into the intestinal wall of the both opposite sides 1 cm cephalad and caudad of the tumor; (2) if the colorectal cavity was severely narrow and the colonoscopy could not pass, only 4 points were injected in 4 quadrants at 1 cm caudad of the tumor. Each injection point was injected with 0.1 ml carbon nanoparticles, and the size of the tumor was measured according to the range of carbon nanoparticles staining. The efficacy was evaluated after 8 weeks of chemoradiotherapy. Patients who were defined to be suitable for operation underwent operation 6 weeks after chemoradiotherapy. The following parameters were compared between two groups: lesion identification time, operation time, blood loss, distance from lesion to distal margin, the rate of first positive margin and the rate of anal sphincter preservation (rectal cancer). Among patients who had been evaluated as having no indication for surgery, those who were effective in chemoradiotherapy continued to receive chemotherapy in the original regimen; if the treatment failed, the chemotherapy regimen was replaced, and the efficacy was finally evaluated after six months [referring to the revised RECIST guidelines (version 1.1)]. Results: Three patients withdrew from this study, and 117 patients were enrolled in this study finally, including 59 cases in tattoo group and 58 cases in the non-tattoo group. There were no significant differences in baseline data between two groups (all P>0.05). All the patients had slight adverse reactions of radiotherapy and chemotherapy before operation, and could tolerate after symptomatic management without interruption of treatment. All the patients in the tattoo group had no discomfort such as fever, abdominal pain, abdominal distention, hematochezia, etc. and the intestinal mucosa could be seen clearly with black staining after being tattooed. A total of 77 patients were evaluated with surgical indications, including 39 cases in the tattoo group (tattoo-operable) and 38 cases in the non-tattoo group (non-tattoo-operatable). There were no significant differences in baseline data between the two groups (all P>0.05). Forty patients without operation indications continued chemoradiotherapy, including 20 cases in tattoo group (tattoo-inoperable) and 20 cases in non-tattoo group (non-tattoo-inoperable), whose differences in baseline data between the two groups were not significant as well (all P>0.05). No obvious edema, necrosis or abscess were found in the tattooed segments and the black spots could be seen quickly and clearly on the serosa of rectum in tattoo-operable patients. As compared to non-tattoo group, tattoo group had significantly shorter lesion identification time [(3.4±1.4) minutes vs. (11.8±3.4) minutes, t=-14.07,P<0.001], shorter operation time [(155.7±44.5) minutes vs. (177.2±30.2) minutes, t=-2.48,P=0.015], less blood loss [(101.3±36.7) ml vs.(120.2±38.2) ml, t=-2.22,P=0.029], shorter distance from lesion to distal margin [(3.7±1.0) cm vs. (4.6±1.7) cm, t=-2.20, P=0.034], while tattoo group had slightly higher rate of anal sphincter preservation [66.7%(16/24) vs. 45.5%(10/22), χ(2)=2.10,P=0.234] and lower rate of first positive resection margin [0 vs. 4.5%(1/22), χ(2)=0.62,P=0.480], but their differences were not significant. There were no significant differences in the degree of tumor differentiation and TNM stage between two groups. Patients without operative indication were evaluated for efficacy of chemoradiotherapy again after half a year. One case of complete response (CR), 8 of partial response (PR), 10 of stable disease (SD) and 1 of progressive disease (PD) were found and the improvement rate was 45.0% (9/20) in tattoo-inoperable patients. No case of CR, 6 of PR, 11 of SD and 3 of PD were found and the improvement rate was 30.0% (6/20) in non-tattoo-inoperable patients. There was no significant difference in the improvement rate between the two groups (P=0.514). Conclusions: Endoscopic tattooing with carbon nanoparticles injection is safe and reliable for colorectal tumor positioning. It can assist rapid detection of lesions during surgery after neoadjuvant treatment, perform accurate resection, significantly shorten the operation time and reduce surgical trauma; can assist colonoscopy accurately to measure the size of the lesions before and after chemoradiotherapy, and increase the means of assessing the efficacy to guide the follow-up treatment plan. This technique is worth clinical promotion and application.