Zuqing Guan

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.

Downregulation of S100A4 expression by RNA interference suppresses cell growth and invasion in human colorectal cancer cells.

S100A4 protein, a member of the S100 superfamily of calcium-binding proteins, is frequently observed in various types of human cancers, including colorectal cancer (CRC). Our previous investigations have demonstrated that the overexpression of S100A4 is associated with lymph node metastasis and poor prognosis in CRC; however, its biological roles in CRC remain unclear. In the present study, we compared the expression of S100A4 at the mRNA and protein levels in six CRC cell lines, and found that the expression levels roughly coincided with their invasiveness. Using RNA interference, we suppressed S100A4 expression in SW620 CRC cells with highly invasive potential and S100A4 high expression. The specific knockdown of S100A4 strongly suppressed cell growth, migration and invasion activities. Furthermore, employing metastasis-related gene mRNA microarrays, we found four genes to be significantly dysregulated (more than 2-fold) after downregulation of S100A4, including three downregulated genes (MMP9, MMP10 and CDH11) and one upregulated gene (TIMP4). Our present results indicate that S100A4 may positively regulate tumor cell proliferation, invasion and metastasis associated with multiple molecules. Thus, the inhibition of S100A4 might be a potentially novel approach to treatment for CRC.

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.

Standardized pelvic drainage of anastomotic leaks following anterior resection without diversional stomas.

BACKGROUND Anastomotic leakage is a serious complication in rectal cancer surgery. More than one third of rectal cancer patients with low anterior resection (LAR) will receive defunctional stomas during primary operation. METHODS Six hundred thirty-nine consecutive rectal cancer patients, whose tumors were located 5 to 12 cm from the anal verge, were treated with LAR. A standardized pelvic drainage for all these patients and selective irrigation for patients with leakage were conducted, and defunctional stoma was used as a salvage modality. All the anastomoses were all extraperitonealized during primary operations. RESULTS The anastomotic leakage rate was 7.04%. Male gender and location of tumor were found to be risk factors for leakage in patients with LAR. The overall stoma rate was 1.88%. Nearly 75% of leakage could be cured by irrigation-suction without surgical intervention. Severe complications, such as peritonitis, fistula, and obstruction, were strong predictors of irrigation failure. CONCLUSIONS Extraperitonealized anastomosis and pelvic drainage obtained a very low rate of defunctional stoma for LAR. Pelvic irrigation-suction was an effective modality to resolve anastomotic leakage.

Long-term outcome of early-stage rectal cancer undergoing standard resection and local excision

OBJECTIVES To explore the long-term outcome and prognostic factors for early stage rectal cancer patients undergoing standard resection (SR) or local excision (LE). PATIENTS AND METHODS This study included 350 patients with stage I rectal cancer, in which 283 cases (80.9%) received SR, and 67 cases (19.1%) received LE. Survival analyses were performed to compare outcomes of different surgeries. RESULTS The 5-year local recurrence (LR) rate was 14.1% in LE group versus 3.3% in SR group (P= .0004), and the 10-year overall survival (OS) rate was not significantly different between the 2 groups. Multivariate analysis suggested that LE was an independent risk factor for 5-year LR rate and 10-year OS rate. Tumor grade was found related to 5-year LR, and T stage was found related to 10-year OS. Tumor size of 2.5 cm is found as a possible cut-off for predicting 5-year LR rate in LE group, with a sensitivity of 77.8% and a specificity of 75.9%. In patients with LE, the 5-year LR rate for tumors ≥ 2.5 cm was 40%, compared with 4.3% for tumors < 2.5 cm (P = .001). CONCLUSION Local excision in early-stage rectal cancer may result in high local recurrence rate. The procedure is only recommended in highly selective groups of patients. A tumor size of 2.5 cm is a useful criterion for choosing LE rather than SR.

Prognostic significance of apical lymph node metastasis in patients with node-positive rectal cancer

The aim of this study was to assess the effect of apical lymph node (APN) metastasis in predicting prognosis in curatively treated node‐positive rectal cancer. We also investigated the relationship between APN metastasis and the total number of metastatic lymph nodes.

Case report of extrarenal rhabdoid tumor of pelvic retroperitoneum molecular profile of angiogenesis and its implication in new treatment strategy

We report the detailed molecular study of angiogenesis-ralated genes and target therapy of the case of a male 46-year-old patient with extrarenal rhabdoid tumor of pelvic retroperitoneum. The patient was found to have a huge pelvic soft tissue sarcoma and underwent pelvic tumorectomy and appendectomy. The microscopically morphological features and molecular profile by immunohistochemical analysis supported the surgical histological diagnosis of extrarenal rhabdoid tumor. The tumor recurred two weeks after surgery and metastasized to the lung, left abdominal wall and mesenteric lymph nodes. Systemic chemotherapy including ifosfamide, liposomal doxorubicin, Taxol, and cisplatin, concurrently with pelvic radiotherapy (58 Gy of total dose). However, the paitent did not respond to the combination of chemotherapy and radiotherapy. Immunohistochemical staining and fluorescence in situ hybridization of tumor cells indicated negative expression of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) and positive expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). So anti-VEGFR targeted therapy (Bevacizumab) was administered following the fourth course chemotherapy. However, the condition worsened after the administration of the second cycle of Bevacizumab. Multiple organ failure led to the death of the patient. The patient only survived 5 months and 20 days after the surgery of primary tumor.

Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant chemotherapy in female patients with locally advanced colorectal cancer

Aim  In this study we explored the prognostic impact of synchronous bilateral prophylactic oophorectomy in female patients with primary colorectal cancer undergoing radical surgery.

Phase II trial of first-line chemoradiotherapy with intensity-modulated radiation therapy followed by chemotherapy for synchronous unresectable distant metastases rectal adenocarcinoma.

AimsBased on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy.Materials and methodsThirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group).ResultsThe toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4–23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274).ConclusionIt was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy.