Debing Shi

TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer

BackgroundWe have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer.MethodsTPX2 expression was analyzed in human colon cancer cell lines and tumor samples. The effect of TPX2 on cell proliferation, tumorigenesis, and metastasis was examined in vitro and in vivo.ResultsTPX2 was overexpressed in 129 of the 203 (60.8%) colon cancer metastatic lesions, with the expression being significantly higher than that in primary cancerous tissue and normal colon mucosa. Overexpression of TPX2 was significantly associated with clinical staging, vessel invasion, and metastasis. In survival analyses, patients with TPX2 overexpression had worse overall survival and metastasis free survival, suggesting that deregulation of TPX2 may contribute to the metastasis of colon cancer. Consistent with this, suppression of TPX2 expression inhibited proliferation and tumorigenicity of colon cancer cells both in vitro and in vivo. Strikingly, we found that TPX2 knockdown significantly attenuated the migration and invasion ability of colon cancer cells, which was further shown to be mechanistically associated with AKT-mediated MMP2 activity.ConclusionsThese findings suggest that TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease.

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.

Prognostic Nomograms for Predicting Survival and Distant Metastases in Locally Advanced Rectal Cancers

Aim To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment. Materials and Methods A total of 883 patients with stage II–III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS), local recurrence (LR) and distant metastases (DM). Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients. Results The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73]) and 0.68 (95% CI = [0.64, 0.72]) on the original dataset, and 0.76 (95% CI = [0.67, 0.86]) and 0.73 (95% CI = [0.63, 0.83]) on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category. Conclusions The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma

PurposeNeoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC.Methods and materialsPatients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 b.i.d. d1–5 weekly). One cycle of capecitabine (1000 mg/m2 b.i.d. d1–14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation.ResultsBetween October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2–3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3–4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1–2.ConclusionsOur study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical complications. Treatment response was an early surrogate marker and correlated to oncologic prognosis.

Silencing of long non-coding RNA SBDSP1 suppresses tumor growth and invasion in colorectal cancer

Long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. This study was undertaken to examine the expression and biological functions of a novel lncRNA SBDSP1 in colorectal cancer (CRC). Quantitative real-time PCR analysis was used to measure the expression of SBDSP1 in CRC tissues and cell lines. Knockdown of SBDSP1 via short hairpin RNA technology was performed to determine the roles of SBDSP1 in CRC cell growth, colony formation, cell cycle progression, migration, and invasion. The effect of SBDSP1 knockdown on tumorigenesis of CRC cells was investigated in a subcutaneous tumor mouse model. Western blot analysis was done to examine the involvement of signaling pathways in the action of SBDSP1. Notably, SBDSP1 was overexpressed in CRC tissues and cells relative to corresponding normal controls. Moreover, SBDSP1 expression was significantly greater in CRCs with nodal metastasis than in primary tumors (P=0.0259). Downregulation of SBDSP1 significantly inhibited cell proliferation, colony formation, migration, and invasion in SW480 and HCT116 cells, which was accompanied by suppression of Akt, ERK1/2, and STAT3 phosphorylation. SBDSP1-depleted cells showed a G0/G1 cell cycle arrest and deregulation of p21 and cyclin D1. In vivo studies confirmed that SBDSP1 downregulation retarded the growth of HCT116 xenogaft tumors. Altogether, SBDSP1 plays an essential role in CRC cell growth, invasion, and tumorigenesis, largely through inactivation of multiple signaling pathways. Therefore, targeting SBDSP1 may have therapeutic benefits in the treatment of CRC.

Characteristics and Prognostic Significance of Preoperative Magnetic Resonance Imaging-Assessed Circumferential Margin in Rectal Cancer.

Purpose. To study the characteristics and prognostic significance of preoperative magnetic resonance imaging- (MRI-) assessed circumferential margin (CRM) in rectal cancer. Methods. Patients underwent preoperative high resolution pelvic MRI, followed by resection of primary tumor. The relationship between MRI-assessed CRM and pathological CRM (pCRM) was studied, and survival analysis was used to determine the prognostic significance of MRI-assessed CRM. Results. Of all the 203 patients, the total accuracy of MRI-assessed CRM for predicting involvement of pCRM was 84.2%, sensitivity was 50%, and specificity was 86.8%. Anterior tumors were more possible to assess involvement of CRM by MRI, while the false positive rate was significantly higher than lateral or posterior tumor (87.5% versus 50%, p = 0.0002). The 3-year local recurrence, disease-free survival, and overall survival rates were 35.6%, 58.1%, and 85.2% in patients with involved mrCRM, compared with 8.9%, 78.9%, and 92.3% in patients with clear mrCRM. In multivariate analysis, MRI-assessed CRM found an independent risk factor for local recurrence, with a hazard ratio of 3.49 (p = 0.003). Conclusions. High resolution MRI was accurate to assess CRM preoperatively, while anterior tumor should be assessed more cautiously. Involvement of mrCRM was significantly associated with local recurrence regardless of pCRM status.

Poorer prognosis in young female patients with non-metastatic colorectal cancer: a hospital-based analysis of 5,047 patients in China

Purpose To investigate the association of age and sex on survival in non-metastatic colorectal cancer (CRC) patients and to identify groups at high risk for poor outcomes. Materials and methods We performed a retrospective analysis of 5,047 non-metastatic CRC patients from 2008 to 2013. Data regarding age at diagnosis; gender; tumor site; tumor stage; differentiation; lymphatic, neural or vascular invasion; and survival outcomes were collected. Patients were stratified into 10-year age groups (≤35, 36–45, 46–55, 56–65, 66–75, >75) and then further analyzed in three age groups (≤35, 36–75, >75). Disease-free survival (DFS) and overall survival (OS) were evaluated using univariate and multivariate Cox regression models. Results Of the 5,047 eligible patients, 41.3% were female. The tumor stages were balanced between the genders. In the female patients, the tumor stages were similarly distributed among the different age groups, while younger male patients were diagnosed with more advanced disease (P<0.001 for trend). When stratified into three age groups, young females experienced significantly poorer survival than young males (DFS: hazard ratio [HR]=1.85 [1.04–3.30], OS: HR=2.65 [1.11–6.34]). After adjusting for tumor stage, site, differentiated grade and lymphatic or vascular invasion status, females ≤35 and >75 had shorter DFS than patients between 36 and 75 years old (HR=1.57 [1.03–2.38] and HR=1.51 [1.11–2.05, respectively]), while there was no difference in DFS between females ≤35 and those >75. For male patients, older age was associated with poorer OS after the same adjustment. Conclusion Young female CRC patients (≤35 years old) had the poorest DFS and quite poor OS compared to the other age groups. This emphasizes the need for health care providers to have a heightened awareness and to conduct further research when caring for young female CRC patients.

Risk factors of synchronous inguinal lymph nodes metastasis for lower rectal cancer involving the anal canal.

Purpose The aim of the study is to identify the risk factors of synchronous ILN metastasis for lower rectal cancer involving the anal canal. Methods Patients with lower rectal cancer who underwent radical resection at the Fudan University Shanghai Cancer Center were retrospectively analyzed. The synchronous ILN metastasis was defined as the metastasis occurring within 6 months after the diagnosis of rectal cancer. Patients’ gender, age, tumor diameter, dentate line invasion, differentiation level, histological type, depth of invasion, perirectal LN metastasis, lymphovascular invasion or perineural invasion were analyzed in the study. The correlation between synchronous ILN involvement and clinicopathological features were analyzed with Chi-square test/fisher’s exact test. Variables with p<0.05 in univariate analysis were then analyzed in a multivariate logistic model. Odds ratio (OR) along with 95% confidence intervals (95% CI) were calculated. Results A total of 325 patients (182 men and 143 women) with lower rectal cancer met the criteria and were enrolled in the study. Among them, 20 patients (6.2%) had synchronous ILN metastasis. Both univariate and multivariate analysis showed the invasion of the dentate line had a strong correlation with synchronous ILN metastasis with the odds ratio (OR) of 23.558 [95% confidence interval (CI) 6.380–86.982] (p<0.001). The presence of lymphovascular invasion also showed a significant correlation synchronous ILN metastasis with odds ratio (OR) of 5.260 [95% confidence interval (CI) 1.818–15.212] (p = 0.002). Conclusions The invasion of dentate line and lymphovascular invasion are two independent risk factors of inguinal lymph node metastasis for lower rectal cancer involving the anal canal.

Vessel-centered laparoscopic total mesorectal excision via medial approach

Total mesorectal excision (TME) is currently the standard treatment for rectal cancer. This procedure provides significant oncological benefits by reducing local recurrence and increasing 5-year survival. Laparoscopic surgery for colorectal cancer has been steadily developing since its introduction in 1990, and laparoscopic TME (lap TME) is an ideal minimally invasive surgical technique for rectal cancer. Compared with laparotomy, laparoscopic surgery has similar safety, completeness of resection, and prognosis (1,2).

Laparoscopic radical treatment with preservation of left colon artery and superior rectal artery for sigmoid colon cancer

During the classical radical treatment for sigmoid colon cancer, ligation of the inferior mesenteric artery (IMA) at its root is typically performed to achieve better dissection of central and intermediate lymph node groups and improve the surgical outcomes. However, the blood supply to the left colon artery (LCA), sigmoid artery, and superior rectal artery (SRA) is blocked after the ligation at the root of the IMA. Here, we report laparoscopic radical treatment with preservation of the LCA and SRA for sigmoid colon cancer to preservation of blood supply to the anastomosis. The method was indicated to treat cancer at the middle portion of sigmoid colon. In the operation, we careful dissection of IMA exposes the trunk of IMA. The surrounding lymphatic tissue is dissected from the IMA root to its distal end. The LCA is preserved. After IMA divides LCA, 2–5 sigmoid colon arteries are transected one after another at the distal end of the LCA until it further divides into left and right rectal arteries before entering the lateral wall of rectum. The inferior mesenteric vein (IMV) is transected at the lower edge of the pancreas, and the mesorectum is cut open towards the spleen curvature at the lower edge of the pancreas. Other procedures are similar with IMA high ligation surgery. Generally, LCA and SRA can be successfully preserved, and if necessary, the colonic splenic flexure should be mobilized to ensure that there is no tension at the anastomosis. The operation doesn’t significantly prolonged operation, but retrieved comparable lymph node counts with IMA high ligation surgery. Dissection of the lymphoadipose tissues at the root of IMA with the preservation of LCA and SRA is an easily performed surgery. It guarantees further prospective clinical research to compare the anastomosis leakage and oncological outcome with IMA high ligation surgery.