Changzheng Du

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.

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.

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 7th 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.

Downregulation of SIRT7 by 5-fluorouracil induces radiosensitivity in human colorectal cancer

5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy to treat human cancers, but the underlying mechanisms of this combination treatment remain unclear. Here, we report that NAD+-dependent deacetylase sirtuin-7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal cancer cells sensitive to radiation. We found that SIRT7 downregulation was mediated via a Tat-binding Protein 1 (TBP1) proteasome-dependent pathway. Specifically, TBP1 was dephosphorylated at tyrosine 381 upon 5-FU treatment, which enhanced its direct interaction with SIRT7 and targeted it for degradation. Depletion of SIRT7 in cultured colorectal cancer cells induced radiosensitivity triggering cell death. Interestingly, decreased levels of SIRT7 mediated by 5-FU correlated well with improved therapeutic effect in patients with rectal cancer and with inhibited tumor growth in immune-compromised mice post-irradiation. Taken together, these data suggest that 5-FU induces radiosensitivity via SIRT7 degradation to favor a cell death pathway in targeted cancer cells. Thus, downregulation of SIRT7 could be a promising pharmacologic strategy to increase the effectiveness of chemoradiation therapy in cancer patients.

Prognostic value of microsatellite instability in sporadic locally advanced rectal cancer following neoadjuvant radiotherapy.

This study was conducted to investigate the clinicopathological significance and prognostic value of microsatellite instability (MSI) in locally advanced rectal cancer (LARC) following neoadjuvant radiotherapy.

The expression of chemokine receptors CCR6, CXCR2 and CXCR4 is not organ-specific for distant metastasis in colorectal cancer: a comparative study.

The liver and lung are the organs most commonly affected by metastasis in colorectal cancer (CRC), and the interaction of chemokines and chemokine receptors (CKRs) plays an important role in the metastatic process. The aim of this study was to investigate the organ specificity of CKRs in CRC distant metastasis.

Intermediate-fraction neoadjuvant radiotherapy for rectal cancer.

BACKGROUND: In China, standard neoadjuvant chemoradiation therapy has not been well accepted, not only because of financial constraints but also because of the poorly-tolerated long duration of the regimen. OBJECTIVE: The current study aimed to evaluate the impact of a modified neoadjuvant radiation regimen on the prognosis of rectal cancer patients in China. DESIGN: This was a nonrandomized cohort study evaluating outcomes of patients who chose to undergo preoperative radiotherapy compared with those who chose not to undergo preoperative radiotherapy (controls). SETTINGS: The study was carried out in Peking University Cancer Hospital, a tertiary care cancer center in China. PATIENTS: Records of patients with locally advanced, mid-to-low rectal cancer who underwent total mesorectal excision at Peking University Cancer Hospital from 2001 through 2005 were analyzed in this study. INTERVENTION: Patients who chose preoperative radiotherapy received a total dose of 30 Gy delivered in 10 once-daily fractions of 3.0 Gy each, with at least a 14-day delay of surgery after delivery of the last fraction. MAIN OUTCOME MEASURES: Tumor downstaging was evaluated. Local recurrence, distant metastases, and disease-free and overall survival were analyzed with the Kaplan-Meier method. RESULTS: A total of 101 patients accepted and 162 patients declined the modified preoperative radiotherapy regimen. Of the 101 patients receiving preoperative radiotherapy, 5 (5%) had a complete response, and 50 (50%) achieved TNM downstaging. The local recurrence rate was 5% with preoperative radiotherapy and 18% in the control groups (p = 0.02). Within the preoperative radiotherapy group, 5-year disease-free survival and overall survival rates were significantly higher in patients with T-, N-, or TNM-downstaging than in patients without downstaging. Evaluation of literature reports indicated that clinical safety and effectiveness of the modified protocol are comparable to results of standard neoadjuvant procedures. LIMITATIONS: The allocation to study groups was not randomized, and patient self-selection may have introduced bias, particularly because patients with greater financial means were more likely to choose to undergo the preoperative radiotherapy regimen. CONCLUSIONS: Compared with surgery alone, this modified preoperative radiotherapy regimen is associated with significantly reduced local recurrence and complication rates, with improved survival in patients who show downstaging. The modified protocol offers a clinical outcome equivalent to standard preoperative radiotherapy regimens while offering an alternative for increasing the flexibility of preoperative radiation regimens in China.

Colon cancer with unresectable synchronous metastases: the AAAP scoring system for predicting the outcome after primary tumour resection.

The aim of this study was to develop a prognostic scoring system to predict the outcome of patients with unresectable metastatic colon cancer who received primary colon tumour resection.

The expression of chemokine receptors CXCR3 and CXCR4 in predicting postoperative tumour progression in stages I-II colon cancer: a retrospective study.

Objectives The prognostic significance of chemokine receptors in stage I/II colon cancer is unclear. We assessed the prognostic value of chemokine receptor CXCR3 and CXCR4 in stage I/II colon cancer. Methods 145 patients with stage I/II colon cancer who underwent curative surgery alone from 2000 to 2007 were investigated. Chemokine receptor expression was assessed by immunohistochemistry. The associations between CXCR3, CXCR4 and clinicopathological variables were analysed using the χ2 test, and the relationships between chemokine receptors and a 5-year disease-free survival were analysed by univariate and multivariate analyses. Results The high-expression rates of CXCR3 and CXCR4 were 17.9% (26/145) and 38.6% (56/145), respectively. There were no significant associations between the expressions of CXCR3, CXCR4 and clinicopathological factors including gender, age, tumour location, histological differentiation, pathological stage, lymphovascular invasion and pretreatment serum carcinoembryonic antigen (CEA). The 5-year disease-free survival was not significantly different between low-expression groups and high-expression groups of CXCR3 and CXCR4. Multivariate analysis revealed that serum CEA and a number of retrieved lymph nodes, rather than chemokine receptors, were independent prognosticators. Conclusions CXCR3 and CXCR4 are not independent prognosticators for stage I/II colon cancer after curative surgery.

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.