College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Effects of the Four-Herb Compound ANBP on Wound Healing Promotion in Diabetic Mice.

Wound healing is a troublesome problem in diabetic patients. Besides, there is also an increased risk of postsurgical wound complications for diabetic patient. It has been revealed that traditional Chinese medicine may promote healing and inhibit scar formation, while the changes of morphology and physiology of wounds on such medicine treatment still remain elusive. In this study, we first used the ultralow temperature preparation method to produce mixed superfine powder from Agrimonia pilosa (A), Nelumbo nucifera (N), Boswellia carteri (B), and Pollen typhae (P), named as ANBP. Applying ANBP on 40 streptozotocin (STZ)-induced diabetic C57BL/6 mice (4-6 weeks, 20 ± 2 g), we observed that the wound healing process was accelerated and the wound healing time was shortened (14 days, P < .05). Pathological observation using hematoxylin-eosin staining indicated that inflammatory cells were reduced (P < .05) while the thickness of granulation tissue and length of epithelial tongue were increased (P < .05). The vascular density was increased on 7 and 14 days after ANBP treatment. Masson and Sirius red staining showed that, at the early stage of trauma, the expressions of Col I and Col III, especially Col III, were increased in the ANBP group (P < .05). Studies in vitro demonstrated that tubular formation was significantly increased after ANBP treatment on human vascular endothelial cells in a dose-dependent way. Taken together, our studies revealed that ANBP treatment could accelerate wound healing, promote vascularization, and inhibit inflammation, suggesting the potential clinic application of ANBP for diabetes mellitus and refractory wounds.

The four-herb Chinese medicine ANBP enhances wound healing and inhibits scar formation via bidirectional regulation of transformation growth factor pathway.

The four-herb Chinese medicine ANBP is a pulverized mixture of four herbs including Agrimonia Eupatoria (A), Nelumbo Nucifera Gaertn (N), Boswellia Carteri (B) and Pollen Typhae Angustifoliae (P). The combination of the four herbs was first described in Chinese canonical medicine about 2000 years ago for treatment of various trauma disorders, such as hemostasis, antiinflammatory, analgesia, and wound healing, etc. However, the precise mechanisms of ANBP are still unclear. In our study, using rabbit ear hypertrophic scar models of full-thickness skin defect, we showed that local ANBP treatment not only significantly enhanced wound healing by relieving inflammation, increasing formation of granulation tissue and accelerating re-epithelialization, but also reduced scar formation by decreasing collagen production, protuberant height and volume of scars, and increasing collagen maturity. We demonstrated that these effects of ANBP are associated with transforming growth factor (TGF)-ß1-mediated signalling pathways through Smad-dependent pathways. ANBP treatment significantly increased expression of TGF-ß1 and Smad2/3 mRNA at the early stage of wound healing, and led to markedly decrease expression of TGF-ß1 and Smad2/3 compared with the control group after 14 days post-wounding. Taken together, our results defined a bidirectional regulation role of ANBP for TGF-ß1/Smad pathway in promoting wound healing and alleviating scar formation, which may be an effective therapy for human wounds at the earliest stage.