Utility of circulating tumor cells in stage II colorectal cancer patients undergoing curative resection.

BACKGROUND: The aim of this study was to determine whether circulating tumor cells (CTCs) have utility as a prognostic biomarker in stage II colorectal cancer (CRC), as well as a biomarker for the selection of patients for adjuvant chemotherapy. METHODS: CTCs were detected in peripheral blood samples obtained from 73 stage II CRC patients, using a negative enrichment and immune-fluorescence in situ hybridization (imFISH) staining method. The follow-up time ranged from 3.5 to 35.9 months, and the clinic-pathologic characteristics and recurrence free survival (RFS) were collected and analyzed. RESULTS: Seventy-three stage II CRC patients were included in this study. The positive rate of CTCs was 65.8% in all patients, 87.5% in recurrent patients and 59.6% in no recurrence patients. The mean RFS was 30.6 months for all patients, 28.7 months for CTC-positive patients and 34.0 months for CTC-negative patients (P=0.043). The mean RFS of CTC-positive and CTC-negative patients with adjuvant chemotherapy were not reached, and those without adjuvant chemotherapy were 27.7 and 33.4 months, respectively. CONCLUSIONS: The level of CTCs may be an effective prognostic factor to predict RFS in stage II CRC patients, and has potential in selecting stage II CRC patients for adjuvant chemotherapy.

Outcomes of trans-anal natural orifice specimen extraction combined with laparoscopic anterior resection for sigmoid and rectal carcinoma: An observational study.

Colorectal carcinoma is currently the third most frequent cancer worldwide. Conventional open surgery was replaced by laparoscopic anterior resection with total mesorectal excision for the treatment of sigmoid and rectal carcinomas; however, it needed an incision to harvest the specimen, which contributed to complications. In 2013, trans-anal natural orifice specimen extraction laparoscopic anterior resection (Ta-NOSE-LAR) to treat sigmoid and rectal carcinoma was performed in our hospital for the first time. The aim of this study was to investigate the outcomes of Ta-NOSE-LAR in sigmoid and rectal carcinoma.Seventy-three patients diagnosed with sigmoid and rectal carcinoma were enrolled between September 2013 and June 2016. Thirty-five patients underwent Ta-NOSE-LAR, whereas the others underwent traditional laparoscopic anterior resection (LAR). We compared the operative data, postoperative complications, pathological evaluation results, and incision-related complications between the 2 groups.Our result showed that the operative time, specimen length, tumor size, amount of total lymph nodes, and lymph node metastasis between the 2 groups were not statistically different. Further, without abdominal scaring for harvesting the specimen, the operative blood loss (49.29 ±â€Š14.63 vs 69.29 ±â€Š13.54 mL, P < .001) and post-operation hospital stay (5.77 ±â€Š0.94 vs 6.76 ±â€Š0.75 days, P < .001) of the Ta-NOSE-LAR group were less than those of the LAR group. Besides, the follow-up data showed that 2 patients were lost to follow-up, and 1 patient had liver metastasis 2 years after surgery in the LAR group, whereas the others showed no regional recurrence, distant metastases, or critical complications.Ta-NOSE-LAR is a valuable and alternative surgical method to treat sigmoid and rectal carcinoma, with the advantages of being a scarless procedure and having a lower post-operation hospital stay duration.

Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients.

Characterization, diagnosis, and treatment of colorectal cancers (CRC) is difficult due to limited biopsy information, impracticality of repeated biopsies, and cancer biomarker fallibility. Circulating tumor DNA (ctDNA) has recently been investigated as a non-invasive way to gain representative gene mutations in tumors, in addition to monitoring disease progression and response to treatment. We analyzed ctDNA mutations and concentrations in 47 early- and late-stage CRC patients using a targetted sequencing approach using a panel that covers 50 cancer-related genes. ctDNA mutations in 37 genes were identified in 93.6% of the patients (n=47). The results showed that TP53, PIK3CA, APC, and EGFR were the most frequently mutated genes. Stage IV patients had significantly higher ctDNA concentration than Stage I patients, and increased ctDNA concentration correlated with increased tumor size. Additionally, ctDNA detection was found to be a greater predictor of disease when compared with five known commonly used tumor biomarkers. The present study supports the use of ctDNA as a liquid biopsy to gain clinical tumor information that may facilitate early diagnosis and treatment and improve CRC patient prognosis.

[Impact of S100P expression on clinical outcomes of gastric cancer patients with adjuvant chemotherapy of oxaliplatin and its mechanisms].

OBJECTIVE: To investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechanisms. METHODS: The expression of S100P was analyzed in 121 resected primary gastric cancer tissues by using tissue array of immunohistochemistry excised from January 2003 to December 2007. The patients received adjuvant chemotherapy with oxaliplatin. The pEGFP-S100P plasmid was constructed and was transfected into BGC823 cell line to establish gastric cancer cell line with over-expression of human S100P, BGC823-S100P. The expression level of S100P was determined by real-time PCR and Western blot assay. The chemosensitivity of BGC823-S100P cell line to oxaliplatin was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. RESULTS: The S100P was positively expressed in 64 tumors (52.9%, 64/121). Although there was no significant relation between the expression of S100P and tumor T staging (P = 0.683), N staging (P = 0.472), M staging (P = 0.770) and differentiation (P = 0.553), Wilcoxon test showed that the 5-year cumulative survival rate of patients with positive S100P expression was significantly higher than that of patients with negative expression (20.3% vs. 3.5%, P = 0.034). Furthermore, overexpressed of S100P was found in the BGC823 cell line, BGC823-S100P. The mRNA and protein level of S100P in pEGFP transfected BGC823-S100P cell lines were significantly higher than those in control group (8.42 ± 1.38 vs. 0.83 ± 0.11 and 3.52 ± 0.48 vs. 0.97 ± 0.19, all P < 0.05). It indicated with MTT assay that the half-inhibitory concentration (IC(50)) to oxaliplatin decreased in BGC823-S100P cells, and was significantly lower than that in vector-only transfected cells [(142 ± 16) mg/L vs. (266 ± 11) mg/L, P = 0.032]. CONCLUSIONS: S100P may also be a potentially novel independent prognostic factor in gastric cancer patients following curative resection. And it could improve the cumulative survival of the patients through enhancing the chemosensitivity of tumor cell line to oxaliplatin.

Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance.

In the present study, we investigated the effect of the taxol resistance gene 1 (TXR1) on taxol resistance in gastric cancer (GC). Immunohistochemistry was performed in order to assess the expression pattern of TXR1 in paraffin-embedded specimens of 107 GC patients who underwent radical D2 gastrectomy with long-term follow-up. In order to determine whether TXR1 expression plays a role in taxol resistance in GC cells, TXR1 was exogenously expressed or knocked down by siRNA in the absence and presence of taxol treatment, and cell proliferation was determined using the MTT assay. TXR1, thrombospondin-1, multidrug resistance protein mRNA and protein expression levels and certain drug resistance-related genes were determined by real time-PCR. There was a significant correlation between TXR1 expression and distant metastasis. Patients whose tissue biopsies tested negative for TXR1 expression had a higher post-operative 5-year survival rate than patients who had TXR1-positive tissue biopsies, even in the advanced cancer group. Exogenous expression of TXR1 in BGC823 cells induced taxol resistance, and siRNA knockdown of TXR1 sensitized human GC cells to taxol. The results show that low expression of TXR1 is correlated with a favorable prognosis in GC patients and that TXR1 likely plays a role in taxol resistance in GC cells.