Xu Guan

Exploration of the Optimal Minimum Lymph Node Count after Colon Cancer Resection for Patients Aged 80 Years and Older

The elderly colon cancer (CC) patients are increasing and represent a heterogeneous patient group. The objectives of this study were to identify the features of lymph node examination and to explore the optimal minimum lymph node count after CC resection for patients aged ≥80. Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 65719 CC patients in stage I-III between 2004 and 2012, 26.0% of patients were aged ≥80. The median node count decreased with increasing age, which were 25.5, 20.2, 17.8 and 16.9 for patients aged 20–39, 40–59, 60–79, and ≥80. The rate of ≥12 nodes and the rate of node positivity for patients aged ≥80 were obviously lower than younger patients. Using X-tile analysis, we determined 9 nodes as the optimal node count for patients aged ≥80. Then, we compared the 5-year cancer specific survival (CSS) between patients with ≥9 nodes and <9 nodes. The results showed the 5-year CSSs were improved for patients with ≥9 nodes. Furthermore, the rate of node positivity and survival under the 9-node measure were equal to 12-node measure. Therefore, the lymph node examination should be discriminately evaluated for elder patients, and 9-node measure was available for patients aged ≥80.

Radiotherapy dose led to a substantial prolongation of survival in patients with locally advanced rectosigmoid junction cancer: a large population based study

Radiotherapy is widely applied for locally advanced rectal cancer (RC) to improve both local control and long-term outcomes. However, the efficacy of radiotherapy for rectosigmoid junction cancer (RSC) is still undetermined. Here, we identified 10074 patients who were diagnosed with locally advanced RSC from Surveillance, Epidemiology, and End-Results (SEER) cancer registry. These patients were divided into three subgroups according to different therapy strategies, including surgery alone, surgery plus preoperative radiotherapy and surgery plus postoperative radiotherapy. 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) were obtained. Kaplan–Meier methods and Cox regression models were used to estimate the correlations between prognostic factors and survival outcomes. The 5-year CSSs for RSC patients treated with pre- and postoperative radiotherapy were 72.3% and 72.2%, which were significantly higher than surgery alone (64.8%). The 5-year OSs for RSC patients treated with pre- and postoperative radiotherapy were 71.6% and 71.2%, which were higher than surgery alone (64.0%). In the separate analyses of stage II and III RSC patients, the similar trends were also obtained. In addition, pre- and postoperative radiotherapy were equally identified as valuable prognostic factors for better survival outcomes in RSC patients. Furthermore, the results following propensity score matching also confirmed that the long-term survivals of RSC patients were improved following radiotherapy. In conclusion, locally advanced RSCpatients could obtain potential long-term survival benefits from radiotherapy. A prospective randomized control trial should be performed to further validate the strength of evidence in current study.

Whether regional lymph nodes evaluation should be equally required for both right and left colon cancer

Despite the adequacy of nodal evaluation was gradually improved for colon cancer, the disparity in nodal examination for right colon cancer (RCC) and left colon cancer (LCC) still begs the question of whether 12 nodes is an appropriate threshold for both RCC and LCC. From Surveillance, Epidemiology, and End-Results (SEER) database, we identified 53897 RCC patients and 11822 LCC patients. Compared with LCC patients, RCC patients examined more lymph nodes (18.7 vs 16.3), and more likely to examine ≥12 nodes (P<0.001), whereas RCC patients showed lower rates of node positivity (P<0.001). To balance the nodal disparity between RCC and LCC, we revised the 12-node measure based on different tumor locations. With the X-tile, we determined 15 as the optimal node number for RCC and 11 for LCC. To validate the availability of this revised nodal evaluation, the 5-year cancer specific survival (CSS) was calculated according to the optimal node number in RCC and LCC patients, Coxs regression model were used to further assess the prognostic value of this revised nodal evaluation. The results showed that 5-year CSSs were significantly improved for RCC patients with ≥15 lymph nodes, and also for LCC patients with ≥11 lymph nodes (P<0.001). This revised nodal evaluation could also improve the rate of nodal positivity and long-term survival in both RCC and LCC patients compared with 12-node measure. Therefore, the lymph node examination should be discriminately evaluated for RCC and LCC, instead of using 12-node measure to colon cancer as a whole.

GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer

GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305–0.753] and PFS:HR 0.490, [95% CI 0.336–0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.

Comparison of long-term outcome between hemicolectomy and partial colectomy in the elderly: a large population-based study

Due to large progress has been achieved in surgical techniques, anesthesia and perioperative care, it is accepted that the very elderly colon cancer (CC) patient is not contraindication for surgery. However, it is a controversy that an extended or a less aggressive surgical approach should be performed for this population. Here, we identified 28110 CC patients aged ≥80 from Surveillance, Epidemiology, and End-Results (SEER) database. The surgical approaches included extended hemicolectomy (HC) and partial colectomy (PC). 5-year cancer specific survival (CSS) was obtained. Kaplan–Meier methods and Cox regression models were used to assess the correlations between prognostic factors and long-term survival. The 5-year CSS for patients treated with HC were 45.6%, which were similar to patients who received PC (44.8%), the survival difference has no statistical significance (P=0.087). The result following propensity score matching further confirmed long-term survival were equal between HC and PC. However, patients in AJCC T3/T4 stage and with tumor size ≥5cm could obtain survival benefit from the extended surgery. In conclusion, most of elderly CC patients could not obtain survival benefit from extended resection. Partial colectomy should also be considered as an alternative approach for this group of patients.Due to large progress has been achieved in surgical techniques, anesthesia and perioperative care, it is accepted that the very elderly colon cancer (CC) patient is not contraindication for surgery. However, it is a controversy that an extended or a less aggressive surgical approach should be performed for this population. Here, we identified 28110 CC patients aged ≥80 from Surveillance, Epidemiology, and End-Results (SEER) database. The surgical approaches included extended hemicolectomy (HC) and partial colectomy (PC). 5-year cancer specific survival (CSS) was obtained. Kaplan-Meier methods and Cox regression models were used to assess the correlations between prognostic factors and long-term survival. The 5-year CSS for patients treated with HC were 45.6%, which were similar to patients who received PC (44.8%), the survival difference has no statistical significance (P=0.087). The result following propensity score matching further confirmed long-term survival were equal between HC and PC. However, patients in AJCC T3/T4 stage and with tumor size ≥5cm could obtain survival benefit from the extended surgery. In conclusion, most of elderly CC patients could not obtain survival benefit from extended resection. Partial colectomy should also be considered as an alternative approach for this group of patients.

Current practice patterns of preoperative bowel preparation in colorectal surgery: a nation-wide survey by the Chinese Society of Colorectal Cancer

BackgroundThe optimal preoperative bowel preparation for colorectal surgery remains controversial. However, recent studies have established that bowel preparation varies significantly among countries and even surgeons at the same institution. This survey aimed to obtain information on the current practice patterns of bowel preparation for colorectal surgery in China.MethodsA paper-based survey was circulated to the members of the Chinese Society of Colorectal Cancer (CSCC). The survey responses were collected and analyzed. Statistical analysis was performed for all the categorical variables according to the responses to individual questions.ResultsThree hundred forty-one members completed the questionnaire. Regarding surgical practice, 203 (59.5%) performed > 50% of the colorectal operations laparoscopically or robotically; the use of mechanical bowel preparation (MBP) alone was significantly higher (63.5 vs 31.9%; P < 0.001). The respondents who performed > 200 colonic or rectal resections provided significantly more MBP alone (79.6 vs 39.1%, P < 0.001; 76.6 vs 43.2%, P < 0.001; respectively). Among hospitals with fewer than 500 beds, 52.4% of the respondents used MBP + oral antibiotics preparation (OAP) + enema, a significantly higher percentage than the respondents of hospitals with more than 500 beds (P < 0.001). Nearly 40% of the respondents prescribed OAP in regimens; meanwhile, 74.8% prescribed preoperative intravenous antibiotics.ConclusionsThe study demonstrates considerable variation among members from the CSCC. These findings should be considered when developing multicenter trials and to provide more definitive answers.

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

Background/Aims: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFβ)/SMAD signaling pathway. Methods: RNA sequencing data from the Gene Expression Omnibus database were analyzed using R software. Based on The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort, the clinical significance of MEGF6 was investigated. HCT8R, HCT116, and LoVo CRC cells were transfected with small interfering RNA against MEGF6, and their proliferation and sensitivity to fluorouracil were evaluated with the MTT cell proliferation and colony formation assays. Proteins associated with cell growth were detected by western blot analysis. The apoptosis of cells was evaluated by Annexin V/propidium iodide staining, and transwell assays were performed to assess the involvement of MEGF6 in cell migration. Markers of EMT and TGFβ/SMAD signaling were evaluated by quantitative PCR and western blotting, and the correlation between MEGF6 and these markers was assessed in the TCGA colon and renal adenocarcinoma cohort. Results: The results showed that MEGF6 was upregulated in HCT8R cells. In addition, MEGF6 was significantly overexpressed in tumor tissue and predicted a poor survival in the TCGA-COAD cohort. Moreover, MEGF6 accelerated CRC cell growth and inhibited apoptosis, and promoted CRC metastasis by inducing the EMT. Finally, we found that TGFβ/SMAD signaling triggered the expression of Slug, which regulates the MEGF6-mediated EMT. Conclusions: MEGF6 may serve as an oncogene to promote cell proliferation and inhibit apoptosis. MEGF6 can also accelerate cell migration via TGFβ/SMAD signaling-mediated EMT.

Abnormal Liver Function Induced by Space-Occupying Lesions Is Associated with Unfavorable Oncologic Outcome in Patients with Colorectal Cancer Liver Metastases

An early prediction of prognosis for patients with colorectal liver metastasis (CRLM) may help us determine treatment strategies. Liver function reflects the effect of the overall metastatic burden. We investigated the prognostic value of liver function in CRLM patients. In our study, patients with abnormal LFTs (liver function tests) had a poorer prognosis than did those with normal LFTs (P < 0.05). A multivariate analysis revealed that LFTs was an independent prognostic factor for CRLM. For those patients with abnormal LFTs, novel prognostic contour maps were generated using LFTs, and no positive correlation exists between the values of survival duration and abnormal LFTs. Additionally, the MTVR (metastatic tumor volume ratio) was measured directly by magnetic resonance imaging and was shown to be highly correlated to LFTs by a Pearson correlation analysis. A multivariate logistic regression analysis also demonstrated that the MTVR and hepatectomy were independently predictive of abnormal LFTs. The space-occupying effect of metastatic lesions can cause abnormal LFTs, resulting in a poor prognosis. Biochemical analyses of LFTs at the initial diagnosis of CRLM enable the stratification of patients into low- and high-risk groups; it may help clinicians determine promising treatment strategies.

Reconsideration of the optimal minimum lymph node count for young colon cancer patients: a population-based study

BackgroundCurrently, young colon cancer (CC) patients continue to increase and represent a heterogeneous patient group. The aim of this study was to explore the optimal minimum lymph node count after CC resection for young patients.MethodsWe performed a comprehensive search of the Surveillance, Epidemiology, and End Results (SEER) database, 2360 CC patients aged from 20 to 40 were analyzed. X-tile was used to determine the optimal cut-off point of lymph node based on survival outcomes of young patients. The cancer specific survival (CSS) was estimated with Kaplan-Meier method, the Cox proportional hazards regression model was used to analyse independent prognostic factors and exact 95% confidence intervals (CIs).ResultsUsing X-tile analysis, 22-node measure was identified as the optimal choice for CC patients aged < 40. The 5-year CSS were 85.8% and 80.9% for patients examining ≥22 nodes and < 22 nodes. Furthermore, we identified that examining < 22 nodes was an independent adverse prognostic factor in patients aged < 40. In addition, the revised 22-node measure could examine more positive nodes than the standard 12-node measure in young patients.ConclusionsFor young colon cancer patients, the lymph node examination should be differently evaluated. We suggest that 22-node measure may be more suitable for CC patients aged < 40.Trial registrationRetrospectively registered.

Long-term Effect of Radiotherapy in Rectal Cancer Patients with Mucinous Tumor: A Large Population Based Study

Due to distinct biological behavior of mucinous adenocarcinoma (MAC) and signet ring cell cancer (SRC), the efficacy of radiotherapy on long-term outcome for rectal cancer (RC) patients with mucinous tumors is still unclear. Here, we identified 1808 RC patients with MAC/SRC from Surveillance, Epidemiology, and End-Results (SEER) database from 2004 to 2013. Patients were divided into two subgroups according to different therapeutic strategies, including surgery alone and surgery combined with radiotherapy. Kaplan–Meier methods and Cox regression models were used to access the influence of therapeutic strategy on long-term survival outcomes. The 5-year and 10-year cancer specific survival (CSS) were improved in stage II and III patients who underwent surgery and radiotherapy compared with patients who underwent surgery alone. These results were further confirmed following propensity score matching. In addition, radiotherapy was deemed as independent good prognostic factor in patient with MAC/SRC. In subgroup analysis, the result also demonstrated that long-term survival was improved following radiotherapy. However, there was no prognostic difference between preoperative and postoperative radiotherapy. In conclusion, radiotherapy could improve survival for RC patients with MAC and SRC, but only for patients in stage II and III. This finding supported the application of radiotherapy in clinical practice.