Tumor regression grades:Potential outcome predictor of locally advanced rectal adenocarcinoma after preoperative radiotherapy

AIM:To analyze tumor regression grade(TRG)for prognosis of locally advanced rectal adenocarcinoma(LARA)treated with preoperative radiotherapy.METHODS:One hundred and ninety patients with clinical stageⅡ/ⅢLARA were studied.All patients underwent radical surgery(between 2004 and 2010)after 30-Gy/10-fraction preoperative radiotherapy(preRT).All 190 patients received a short course of preRT and were reassessed for disease recurrence and survival;the slides of surgical specimens were reviewed and classified according to Mandard TRG.We compared patients with good response(Mandard TRG1 or TRG2)vs patients with bad/poor response(Mandard TRG3-5).Outcomes evaluated were 5-year overall survival(OS),5-year disease-free survival(DFS),and local,distant and mixed recurrence.Fisher’s exact test orχ2 test,logrank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes.RESULTS:One hundred and sixty-six of 190 patients(87.4%)were identified as Mandard bad responders(TRG3-5).High Mandard grade was correlated with tumor height(41.7%<6 cm vs 58.3%≥6 cm,P=0.050),yp T stage(75%yp T0-2 vs 25%yp T3-4,P=0.000),and yp N stage(75%yp N0 vs 25%yp N1,P=0.031).In univariate survival analysis,Mandard grade bad responders had significantly worse OS and DFSthan good responders(TRG1/2)(OS,83.1%vs 96.4%,P=0.000;DFS,72.3%vs 92.0%,P=0.002).In multivariate survival analysis,Mandard bad responders had significantly worse DFS than Mandard good responders(DFS 3.8 years(95%CI:1.2-12.2 years,P=0.026).CONCLUSION:Mandard grade good responders had a favorable prognosis.TRG may be a potential predictor for DFS in LARA after pre-RT.

High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis

AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.

Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma

AIM:To examine the correlation of phosphatidylinositol3-kinase(PIK3)CB expression with preoperative radiotherapy response in patients with stageⅡ/Ⅲrectal adenocarcinoma.METHODS:PIK3CB immunoexpression was retrospectively assessed in pretreatment biopsies from 208 patients with clinical stageⅡ/Ⅲrectal adenocarcinoma,who underwent radical surgery after 30-Gy/10-fractionpreoperative radiotherapy.The relation between PIK3CB expression and tumor regression grade,clinicopathological characteristics,and survival time was statistically analyzed.Western blotting and in vitro clonogenic formation assay were used to detect PIK3CB expression in four colorectal cancer cell lines(HCT116,HT29,Lo Vo,and LS174T)treated with 6-Gy ionizing radiation.Pharmacological assays were used to evaluate the therapeutic relevance of TGX-221(a PIK3CB-specific inhibitor)in the four colorectal cancer cell lines.RESULTS:Immunohistochemical staining indicated that PIK3CB was more abundant in rectal adenocarcinoma tissues with poor response to preoperative radiotherapy.High expression of PIK3CB was closely correlated with tumor height(P<0.05),yp T stage(P<0.05),and high-degree tumor regression grade(P<0.001).High expression of PIK3CB was a potential prognostic factor for local recurrence-free survival(P<0.05)and metastasis-free survival(P<0.05).High expression of PIK3CB was also associated with poor therapeutic response and adverse outcomes in rectal adenocarcinoma patients treated with 30-Gy/10-fraction preoperative radiotherapy.In vitro,PIK3CB expression was upregulated in all four colorectal cancer cell lines concurrently treated with 6-Gy ionizing radiation,and the PIK3CB-specific inhibitor TGX-221 effectively inhibited the clonogenic formation of these four colorectal cancer cell lines.CONCLUSION:PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention.

The quality of total mesorectal excision specimen: A review of its macroscopic assessment and prognostic significance

As a surgical procedure which could significantly lower the recurrence rate of cancers, total mesorectal excision (TME) has been the gold standard for middle and lower rectal cancer treatment. However, previous studies have shown that the procedure did not achieve the ideal theoretical local recurrence rates of rectal cancers. Some researchers pointed out it was very likely that not all so-called TME treatments completely removed the mesorectum, implying that some of these TME surgical treatments failed to meet oncological quality standards. Therefore, a suitable assessment tool for the surgical quality of TME is necessary. The notion of 'macroscopic assessment of mesorectal excision (MAME)' was put forward by some researchers as a better assessment tool for the surgical quality of TME and has been confirmed by a series of studies. Besides providing rapid and accurate surgical quality feedbacks for surgeons, MAME also effectively assesses the prognosis of patients with rectal cancer. However, as a new assessment tool used for TME surgical quality, MAME has an only limited influence on the current guidelines and is yet to be widely applied in most countries. The aims of this review are to provide a detailed introduction to MAME for clinical practice and to summarize the current prognostic significance of MAME.