Value of intra-operative Doppler sonographic measurements in predicting post-operative anastomotic leakage in rectal cancer: a prospective pilot study.

BACKGROUND: Anastomotic leakage is a serious surgical complication in rectal cancer; however, effective evaluation methods for predicting anastomotic leakage individual risk in patients are not currently available. This study aimed to develop a method to evaluate the risk of leakage during surgery. METHODS: The 163 patients with rectal cancer, who had undergone anterior resection and low-ligation procedures for Doppler sonographic hemodynamic measurement from April 2011 to January 2015 in Peking University Cancer Hospital, were prospectively recruited. A predictive model was constructed based on the associations between anastomotic leakage and alterations in the anastomotic blood supply in the patients, using both univariate and multivariate statistical analyses, as well as diagnostic methodology evaluation, including Chi-square test, logistic regression model, and receiver operating characteristic curve. RESULTS: The overall anastomotic leakage incidence was 9.2% (15/163). Doppler hemodynamic parameters whose reduction was significantly associated with anastomotic leakage were peak systolic velocity, pulsatility index, and resistance index. The areas under the receiver operating characteristic curve of residual rates of peak systolic velocity, pulsatility index, and resistance index in predicting anastomotic leakage were 0.703 (95% confidence interval [CI]: 0.552-0.854), 0.729 (95% CI: 0.579-0.879), and 0.689 (95% CI: 0.522-0.856), respectively. The predictive model revealed that the patients with severely reduced blood-flow signal exhibited a significantly higher incidence rate of anastomotic leakage than those with sufficient blood supply (19.6% vs. 3.7%, P = 0.003), particularly the patients with low rectal cancer (25.9% vs. 3.9%, P = 0.007) and those receiving neoadjuvant chemoradiotherapy (32.1% vs. 3.7%, P = 0.001), independent of prophylactic ileostoma. Multivariate analysis revealed that insufficient blood supply of the anastomotic bowel was an independent risk factor for anastomotic leakage (odds ratio: 10.37, 95% CI: 2.703-42.735, P = 0.001). CONCLUSION: Based on this explorative study, Doppler sonographic hemodynamic measurement of the anastomotic bowel presented potential value in predicting anastomotic leakage.

Subcutaneous vacuum drains reduce surgical site infection after primary closure of defunctioning ileostomy.

PURPOSE: Surgical site infection (SSI) is the most common complication after primary closure of defunctioning ileostomy. We use a subcutaneous vacuum drain (SVD) in our institution to prevent infection. This study aimed to analyze the risk factors of SSI and to assess the utility of an SVD for preventing SSI in patients undergoing primary closure of ileostomy. METHODS: Patients undergoing ileostomy closure in the Department of Colorectal Surgery, Peking University Cancer Hospital, from September 2006 to March 2013, were included in this study. The clinical features of these patients with or without a subcutaneous drain were reviewed, and the complication rate of SSI was analyzed. The primary endpoints were the incidence and risk factors of SSI, and the secondary endpoints were the rate of overall complications and their management. RESULTS: A total of 245 consecutive patients were enrolled in the study. The overall incidence of SSI was 8.6%. Eighty-five (34.7%) patients received placement of an SVD. The use of SVDs was associated with a significantly lower incidence of SSI compared with primary closure (PC) without an SVD (1.2 vs. 12.5%, p = 0.001). Multivariate analyses showed that the presence of an SVD (odds ratio (OR) 0.063, p = 0.012), total operation time >90 min (OR 4.862, p = 0.002), and postoperative complications (OR 10.576, p < 0.001) were independent risk factors of SSI. CONCLUSIONS: This study shows that an SVD is effective for reducing SSI in patients undergoing PC of ileostomy. Further randomized trials are required to confirm our findings and to compare SVDs with purse-string sutures.

Downregulation of miR-193a-5p correlates with lymph node metastasis and poor prognosis in colorectal cancer.

AIM: To investigate the correlation of miR-193a-5p with lymph node metastasis and postoperative survival of colorectal cancer (CRC) patients. METHODS: A total of 304 formalin-fixed, paraffin-embedded specimens (69 paired cancer and normal tissues, 55 primary tumors of stage III CRC and matched lymph nodes, and 56 primary tumors of stage II CRC) were included in this study. The relative expression levels of miR-193a-5p in the normal mucosa, primary cancer, and metastatic lymph node lesions were measured by quantitative real-time reverse transcriptase polymerase chain reaction. We evaluated the association of its expression with colorectal cancer lymph node metastasis, clinicopathological factors, and patient survival. RESULTS: The relative expression level of miR-193a-5p was significantly lower in CRC tissues than in the normal mucosa (P = 0.0060). The expression levels of miR-193a-5p were lower in primary CRC tissues with lymph node metastases than in those without metastases (P = 0.0006), and decreased expression of miR-193a-5p correlated with advanced lymph node metastatic stage (P = 0.0007). Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had decreased disease-free survival (DFS) (P = 0.0026) and poor overall survival (OS) (P = 0.0003). Interestingly, for the group of patients with lymph node metastases, miR-193a-5p expression was also related to survival. Patients with low miR-193a-5p expression had decreased DFS (P = 0.0262) and poor OS (P = 0.0230). Moreover, multivariate analysis indicated that downregulation of miR-193a-5p was an independent predictor of poor OS. CONCLUSION: Downregulation of miR-193a-5p correlates with lymph node metastasis and poor survival of CRC. miR-193a-5p may be a useful biomarker for CRC diagnosis, metastasis and prognosis prediction.

Expression of HER-2 in rectal cancers treated with preoperative radiotherapy: a potential biomarker predictive of metastasis.

BACKGROUND: Evidence suggests HER-2 overexpression may be predictive of prognosis in colorectal cancer patients, though this remains controversial. OBJECTIVES: This study was performed to assess the prognostic value of HER-2 expression in locally advanced rectal cancer patients after preoperative radiotherapy. PATIENTS AND METHODS: HER-2 expression was evaluated based on immunohistochemical (IHC) staining of resected specimens from 142 mid-to-low rectal cancer patients. Fluorescence in situ hybridization (FISH) was performed to confirm HER-2 overexpression in samples with an IHC score of 2+. Tumor regression grading (TRG) of the primary tumors was determined semiquantitatively using a tumor regression grading scheme advocated in the AJCC Cancer Staging Manual 7 edition. RESULTS: When the total staining intensity was evaluated, 106 samples (74.6%) showed barely-perceptible positivity (0-1+; HER-2--negative), 15 samples (10.6%) showed moderate positivity (2+) and 21 samples (14.8%) showed strong positivity (3+, HER-2 positive). FISH confirmed that 2 cases showing moderate HER-2 positivity (2+) overexpressed HER2. There was no significant difference between the HER-2 positive and -negative groups with respect to age, gender, TRG, TNM stage, downstaging status, lymphovascular invasion or tumor differentiation. A significant correlation was found between HER-2 overexpression and the incidence of distant metastasis (p = 0.005). Subgroup analysis revealed this correlation was not significant (p = 0.247) in the radiation-insensitive (TRG0-2) subgroup, whereas a significant correlation (p = 0.026) between HER-2 overexpression and distant metastasis was found in the radiation-resistant (TRG3) subgroup. Multivariate analysis identified ypN stage (OR = 0.473, p = 0.002)and overexpression of HER-2 (OR = 3.704, p = 0.008) as independent risk factors for distant metastasis. There was no correlation between HER-2 overexpression and disease-free survival or overall survival among the study population. LIMITATIONS: We reported that HER-2 overexpression was correlated with distant metastasis in rectal cancer patients, especially in the radiation-insensitive group. However, there are certain limitations. First, this study was limited due to the fact that the number of rectal patients enrolled was only 142, which is relatively small. Second, HER-2 expression was measured by IHC with a positive ratio around 15%, which is fairly high according to the literature. Also, we collected the tissue samples preoperatively. It would be interesting to know the HER-2 expression levels pre- and postradiotherapy, as well as their correlation with local recurrence or distant metastasis. Finally, in rectal cancer patients, there is little information published on HER-2 and its role in tumor progression and metastasis. Therefore, we are pursuing the regulatory molecule underlined. CONCLUSIONS: HER-2 is overexpressed in around 15% of rectal cancer patients who receive neoadjuvant radiotherapy. Moreover, HER-2 overexpression could be a predictive biomarker of distant metastasis in rectal cancer patients after preoperative radiotherapy, especially patients showing a poor response to neoadjuvant radiotherapy.

Patterns and prognosis of locally recurrent rectal cancer following multidisciplinary treatment.

AIM: To investigate the patterns and decisive prognostic factors for local recurrence of rectal cancer treated with a multidisciplinary team (MDT) modality. METHODS: Ninety patients with local recurrence were studied, out of 1079 consecutive rectal cancer patients who underwent curative surgery from 1999 to 2007. For each patient, the recurrence pattern was assessed by specialist radiologists from the MDT using imaging, and the treatment strategy was decided after discussion by the MDT. The associations between clinicopathological factors and long-term outcomes were evaluated using both univariate and multivariate analysis. RESULTS: The recurrence pattern was classified as follows: Twenty-seven (30%) recurrent tumors were evaluated as axial type, 21 (23.3%) were anterior type, 8 (8.9%) were posterior type, and 13 (25.6%) were lateral type. Forty-one patients had tumors that were evaluated as resectable by the MDT and ultimately received surgery, and R0 resection was achieved in 36 (87.8%) of these patients. The recurrence pattern was closely associated with resectability and R0 resection rate (P < 0.001). The recurrence pattern, interval to recurrence, and R0 resection were significantly associated with 5-year survival rate in univariate analysis. Multivariate analysis showed that the R0 resection was the unique independent factor affecting long-term survival. CONCLUSION: The MDT modality improves patient selection for surgery by enabling accurate classification of the recurrence pattern; R0 resection is the most significant factor affecting long-term survival.

Oncologic outcomes of primary and post-irradiated early stage rectal cancer: a retrospective cohort study.

AIM: To evaluate the oncologic outcomes of primary and post-irradiated early stage rectal cancer and the effectiveness of adjuvant chemotherapy for rectal cancer patients. METHODS: Eighty-four patients with stage I rectal cancer after radical surgery were studied retrospectively and divided into ypstage I group (n = 45) and pstage I group (n = 39), according to their preoperative radiation, and compared by univariate and multivariate analysis. RESULTS: The median follow-up time of patients was 70 mo. No significant difference was observed in disease progression between the two groups. The 5-year disease-free survival rate was 84.4% and 92.3%, respectively (P = 0.327) and the 5-year overall survival rate was 88.9% and 92.3%, respectively, for the two groups (P = 0.692). The disease progression was not significantly associated with the pretreatment clinical stage in ypstage I group. The 5-year disease progression rate was 10.5% and 19.2%, respectively, for the patients who received adjuvant chemotherapy and for those who rejected chemotherapy in the ypstage I group (P = 0.681). CONCLUSION: The oncologic outcomes of primary and post-irradiated early stage rectal cancer are similar. Patients with ypstage I rectal cancer may slightly benefit from adjuvant chemotherapy.

Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy.

AIM: To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. METHODS: Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resectable locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. RESULTS: The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). CONCLUSION: MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.

[Impact of diabetes mellitus on clinicopathological factors and prognosis of patients with colorectal cancer.].

OBJECTIVE: To analyze the impact of diabetes mellitus on the clinicopathological factors and prognosis of patients with colorectal cancer. METHODS: A total of 599 patients with colorectal cancer treated between January 2000 and June 2007 were collected retrospectively. The patients were divided into diabetes mellitus (DM) group and non-diabetes mellitus (NDM) group. The pathologic factors data was compared between the two groups, and the Logistic multivariable analysis was performed. The Cox regression model analysis of prognosis data was applied in 402 patients who underwent radical surgery without preoperative neoadjuvant therapy. RESULTS: A total of 58 cases (9.7%) developed diabetes mellitus. Significant differences was found in the body-weight, age, hypertension between the two groups (P < 0.05), while no significant differences in the pathologic factors, such as tumor differentiation, invasion depth, lymph node involvement, TNM stage and lymphovascular invasion was found between the two groups (P > 0.05). There was no significant correlation between diabetes mellitus and the pathologic factors on the Logistic analysis (P > 0.05). Among the patients underwent radical surgery directly, neither disease progression curve (P = 0.521) nor overall survival curve (P = 0.909) presented significant differences between the two groups. It's not shown that diabetes mellitus was significantly associated with the prognosis of patients with colorectal cancer by using Cox regression analysis (P = 0.991). CONCLUSIONS: Diabetes mellitus does not significantly influence the clinicopathological factors and the prognosis of colorectal cancer in patients receiving radical surgery, and it requires more investigation.

[Comparison of pathologic and clinical characteristics of young and old patients with advanced rectal cancer after neoadjuvant radiotherapy].

OBJECTIVES: To address the difference of pathologic and clinical characteristics of the young and the middle-aged and elderly patients with advanced rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 252 patients undergoing radical surgery from January 2000 to January 2005 were included in this study. The patients were divided into two groups according to the age at diagnosis:young-patient group (< 40 years) and old-patient group (≥ 40 years). The pathologic and clinical materials were collected and the oncologic outcome was compared between the two arms. RESULTS: A total of 252 patients were included in this study, included 54 patients in young-patient group and 198 patients in old-patient group, respectively. There was no significant difference in gender, clinical stage and pretreatment serum carcinoembryonic antigen (CEA) between the two groups. However, the proportion of mucinous and signet-ring cell cancer was significantly higher in young-patient group (20.4% vs. 4.0%, P < 0.05), and furthermore, the proportion of pathologic stage later than IIIA was also significantly higher in the young-patient group (61.1% vs. 42.9%, P < 0.05). There was no significant difference in local recurrence rate between the patients who received neoadjuvant radiotherapy and those who did not in the young-patient group, whereas the difference was observed significant in the old-patient group (3.3% vs. 11.2%, P < 0.05). There was no significant difference in both the disease free survival and overall survival between the two arms (5y-DFS: 63.3% vs. 68.5%, P > 0.05; 5y-OS: 73.5% vs. 72.9%, P > 0.05). CONCLUSIONS: Rectal cancer in young patients has poorer histologic differentiation and more advanced pathologic stage, but the long-term survival is similar to that in middle-aged and elderly patients. The local control effect of neoadjuvant radiotherapy on rectal cancer in young patients still need to be further investigated.

Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer.

AIMS: The CD133 antigen has been identified as a putative stem cell marker in colorectal cancer tissues. According to the cancer stem cell hypothesis, CD133+ cells determine long-term tumour growth and are therefore suspected of influencing clinical outcome. The aim was to investigate the prognostic value of CD133 expression in rectal cancer patients after preoperative radiation and curative resection. METHODS AND RESULTS: The expression of the CD133 stem cell antigen in a series of 73 patients with rectal cancer of various ypTNM stages was analysed by immunohistochemistry on formalin-fixed paraffin-embedded sections. The prognostic value of CD133 expression and other clinicopathological factors was evaluated. On multivariate survival analysis, the proportion of CD133+ cells was a significant (P < 0.05) prognostic factor for adverse disease-free survival and overall survival independent of ypTNM stage, tumour differentiation or lymphovascular invasion. CONCLUSIONS: CD133 stem cell antigen expression correlates with patient survival in rectal cancer, lending support to the current cancer stem cell hypothesis.

Lymphovascular invasion in rectal cancer following neoadjuvant radiotherapy: a retrospective cohort study.

AIM: To investigate the meaning of lymphovascular invasion (LVI) in rectal cancer after neoadjuvant radiotherapy. METHODS: A total of 325 patients who underwent radical resection using total mesorectal excision (TME) from January 2000 to January 2005 in Beijing cancer hospital were included retrospectively, divided into a preoperative radiotherapy (PRT) group and a control group, according to whether or not they underwent preoperative radiation. Histological assessments of tumor specimens were made and the correlation of LVI and prognosis were evaluated by univariate and multivariate analysis. RESULTS: The occurrence of LVI in the PRT and control groups was 21.4% and 26.1% respectively. In the control group, LVI was significantly associated with histological differentiation and pathologic TNM stage, whereas these associations were not observed in the PRT group. LVI was closely correlated to disease progression and 5-year overall survival (OS) in both groups. Among the patients with disease progression, LVI positive patients in the PRT group had a significantly longer median disease-free period (22.5 mo vs 11.5 mo, P = 0.023) and overall survival time (42.5 mo vs 26.5 mo, P = 0.035) compared to those in the control group, despite the fact that no significant difference in 5-year OS rate was observed (54.4% vs 48.3%, P = 0.137). Multivariate analysis showed the distance of tumor from the anal verge, pretreatment serum carcinoembryonic antigen level, pathologic TNM stage and LVI were the major factors affecting OS. CONCLUSION: Neoadjuvant radiotherapy does not reduce LVI significantly; however, the prognostic meaning of LVI has changed. Patients with LVI may benefit from neoadjuvant radiotherapy.

[Expression of epidermal growth factor receptor-2 in Chinese breast cancer patients: a meta-analysis].

OBJECTIVE: To study the expression of cerbB-2 and its clinical biology value in Chinese breast cancer patients by evidence based medical analysis. METHODS: All the published studies about cerbB-2 and breast cancer for the last 10 years were reviewed and standard techniques of meta-analysis to combined with the results of these studies were used to produce a more precise estimate of the prognostic significance expression of cerbB-2. RESULTS: The mean of cerbB-2 positive expression was 50% (95% confidence interval 48%-54%), cerbB-2 positive expression was related with node metastasis, recurrence after surgery and survival time; the RR values were 1.71, 2.14 and 2.32 respectively; tumor size, nuclear grade and pathology type were also the important factors that were related with the expression of cerbB-2, while the expression was not related with age; cerbB-2 was a special and sensitive prognostic factor for breast cancer. CONCLUSION: cerbB-2 can be used as an independent molecular marker for definitive prognosis of breast cancer, as well as a reliable marker for choice of standard and individual therapy.