Junjie Peng

Oncological outcome of T1 rectal cancer undergoing standard resection and local excision

Aim  We studied the outcome and prognostic factors for T1 rectal cancer patients undergoing standard resection or transanal excision.

Detection of incidental colorectal tumours with 18F‐labelled 2‐fluoro‐2‐deoxyglucose positron emission tomography/computed tomography scans: results of a prospective study

Aim  This study assessed the clinical significance of incidental colorectal 2‐fluoro‐2‐deoxyglucose (FDG) uptake using 18F‐FDG positron emission tomography/computed tomography (PET/CT) scans and evaluated the importance of colonoscopy when incidental colorectal FDG uptake was observed.

Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29.

PurposeTo assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort.MethodsPatients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients.ResultsA total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module.ConclusionsOur study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.

Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival.

BackgroundThe influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs.MethodsThe demethylation rate of the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3 mRNA was investigated in various colorectal cancer cell lines. A total of 130 colon carcinoma samples were utilized to study the DMR at tumor sites (DMRT) and adjacent normal tissue (DMRN). The correlations between DMRs and clinicopathological variables of patients with colon cancer were studied.ResultsThe TSDR-DMRs varied dramatically among nTregs (97.920 ± 0.466%) and iTregs (3.917 ± 0.750%). Significantly, DMRT (3.296 ± 0.213%) was higher than DMRN (1.605 ± 0.146%) (n = 130, p = 0.000). Higher DMRN levels were found in female patients (p = 0.001) and those with distant metastases (p = 0.017), and were also associated with worse recurrence-free survival in non-stage IV patients (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed that the FOXP3-TSDR status does not have prognostic value.ConclusionMS-qPCR assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of tissue-resident nTregs may have a negative role in anti-tumor effects in patients with colon cancer; however, this role is limited and complicated.

Tolerability and outcomes of radiotherapy or chemoradiotherapy for rectal cancer in elderly patients aged 70 years and older

PurposeTo assess the safety and outcomes of radiotherapy (RT) or chemoradiotherapy (CRT) in elderly patients (≥70) with rectal cancer.MethodsElderly patients aged 70 and older with rectal cancer, who were treated with RT or CRT at a single institution, were retrospectively analyzed. Performance status (KPS and ECOG score) and comorbidity (Charlson comorbidity index) were calculated, and their correlation with treatment toxicity and overall survival were studied. Risk factors for overall survival were investigated using univariate and multivariate survival analysis.ResultsA total of 126 patients with locally advanced disease, local recurrence or synchronous metastasis were included, with a 3-year OS rate of 48.1%. Scheduled dosage of radiation was delivered to 69% of patients. Grade 3 toxicities occurred more often in patients treated with CRT versus RT. The occurrence of grade 3 toxicities was not related to KPS score, ECOG score, number of comorbidities, and Charlson score. Multivariate analysis found that only age and Charlson score were independent prognostic factors for predicting patients’ 3-year OS. The 3-year OS rate was significantly higher in patients with Charlson score <4 vs Charlson score ≥4 (71.1% vs. 26.4%, P=0.0003).ConclusionsAlthough toxicities may be significant, elderly patients with rectal cancer of varied stages can be safely treated with RT or CRT with careful monitoring and frequent modification of treatment. Except for patients’ age, Charlson comorbidity index may be helpful in assessing patients’ outcomes in elderly patients with rectal cancer.

Expression of EGFR, Her2 predict lymph node metastasis (LNM)-associated metastasis in colorectal cancer

BACKGROUND As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) have become efficacious drug targets in this setting. But until now, although above studies suggested that EGFR and Her2 may serve as effective biomarkers for targeted therapy in cancer patients with primary tumor, the information on these biomarkers in colorectal cancer is still limited in metastases. OBJECTIVE The purpose of this study is to evaluate the expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her2) on the lymph node metastasis (LNM) of colorectal cancer (CRC), develop LNM-associated biomarkers for CRC. METHODS Differences in EGFR and Her2 expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in a total of 126 Chinese colorectal carcinoma samples using quantitative real-time PCR analysis and western blot. Confirmation assay with immunohistochemistry (IHC) study was applied in the same samples. The relationship to clinicopathological parameters and prognosis of candidate biomarkers was also examined in the same samples. RESULTS EGFR and Her2 were significantly upregulated in LNM CRC compared to non-LNM CRC, which was confirmed by real-time quantitative polymerase chain reaction, western blot. Similar results were confirmed in the immunohistochemistry (IHC) assay. Overexpression of EGFR and Her2 were significantly associated with LNM (P < 0.001), advanced TNM stage (P < 0.001), increased 5-year recurrence rate (P < 0.001) and decreased 5-year overall survival rate (P < 0.001). Univariate and multivariate analyses indicated that EGFR and Her2 expression were useful independent prognostic factor for recurrence and survival of CRC patients (P < 0.05). CONCLUSIONS EGFR and Her2 might serve as a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of EGFR or Her2 is a potential predict factor to the poor outcome in clinical colorectal cancer.

Prognostic analysis for carcinoid tumours of the rectum: a single institutional analysis of 106 patients

Aim  Rectal carcinoid is a rare rectal tumour with a good prognosis. The aim of this study was to assess its clinicopathological characteristics and prognostic factors in a single institution.

Prediction of Treatment Outcome by CD44v6 After Total Mesorectal Excision in Locally Advanced Rectal Cancer

Background:The purpose of this study was to investigate the significance of CD44 variant 6 (CD44v6) in predicting the treatment outcome of locally advanced adenocarcinoma of the rectum after total mesorectal excision (TME). Methods:Expression of CD44v6 protein was detected using immunohistochemistry in 179 patients with pathologically confirmed stage II or III rectal adenocarcinoma. All patients were treated with TME, and neither neoadjuvant nor adjuvant radiotherapy were used. The correlation between the expression of CD44v6 and other disease-related characteristics with treatment outcome was investigated. Results:The 5-year overall survival and disease-free survival rates were 66.75% and 65.77%, respectively, and the overall locoregional recurrence rate was 8.13% for the entire group of patients. CD44v6 was present in 41.9% of all patients. Multivariate analysis revealed that CD44v6 status and pelvic nodal metastasis were independent risk factors for the rate of distant metastases (P = 0.036 and 0.035, respectively), disease-free survival (P = 0.009 and 0.016, respectively), and overall survival (P = 0.048 and 0.034, respectively). Lymph node metastasis was the only independent risk factor for locoregional recurrence (P = 0.048), and a trend was found for CD44v6 on predicting the locoregional recurrence (P = 0.06) with both stage II and III diseases. CD44v6 is significantly associated with locoregional recurrence in stage III rectal cancer (hazard ratio 6.02, 95% confidence interval 1.25–29.0; P = 0.018), and the overall locoregional recurrence was significantly higher for patients with positive expression of CD44v6 than for those with negative expression (17.63% vs 6.62%; P = 0.026). Conclusion:CD44v6 expression in cancer cells is a sensitive marker for predicting the treatment outcome in patients with stage II and III adenocarcinoma of the rectum after TME and may be used to determine the necessity of adjuvant treatment. However, further investigations are needed to determine the clinical application of CD44v6 and its reliability.

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P = 0.049) and CIMP positive (P = 0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P = 0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P = 0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

Clinicopathologic and molecular features of sporadic microsatellite- and chromosomal-stable colorectal cancers

Background and aimsChromosomal instability (CIN) and microsatellite instability (MSI) are two major causes of colorectal cancers. Recently, a percentage of colorectal cancers were found to be neither CIN nor MSI. This study was performed to explore whether microsatellite- and chromosomal-stable (MACS) colorectal cancers comprise a substantially distinct subtype.Materials and methodsSixty-nine sporadic colorectal cancers were classified into three subsets according to ploidy and microsatellite instability status: CIN+, MSI+, and MACS. Clinicopathologic, genetic, and epigenetic differences among these three groups were investigated by immunohistochemical analysis of p53, APC, hMLH1, and BAX and methylation study of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 with methylation-specific polymerase chain reaction.ResultsThe 69 cases included 49 CIN+, 7 MSI+, and 13 MACS. MACS were found to differ from CIN+ and MSI+ in three aspects. The clinicopathologic features of MACS were similar to MSI+ but distinguished from CIN+. Comparatively, MACS preferred proximal location and poor differentiation (p < 0.05). An immunohistochemical study demonstrated that MACS had a lower rate of loss of hMLH1 or BAX protein than MSI+ and less loss of APC protein than CIN+. In an epigenetic aspect, both MACS and MSI+ had a high rate of CpG island methylator phenotype (46.2 and 42.9%). However, they differed in the presence of hMLH1 methylation (7.7 vs 57.1%, p < 0.05). Otherwise, compared with CIN+, MACS had a more frequent CpG island methylator phenotype and MINT1 methylation (p < 0.05) and relatively more common p16INK4a methylation with marginal significance (p = 0.056).ConclusionMACS sporadic colorectal cancers may compose a unique phenotype with distinct clinicopathologic and molecular characteristics.