The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P = 0.028), poorer disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P < 0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P = 0.006, HR: 4.012, 95% CI: 1.130–8.445) and OS (P = 0.028, HR: 3.090, 95% CI: 1.477–10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with synchronous mCRC (all P > 0.05). The present study demonstrated that EGFR expression has prognostic value only for patients with metachronous mCRC. However, KRAS mutation did not have prognostic value in patients with metachronous or synchronous mCRC.
After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed.This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage.The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p < 0.05). The complication rate related to stoma closure was 36.0%. Patients with ileostomy had an increased risk of developing complications (p = 0.017), and early closure of the defunctioning stoma yielded a higher incidence of morbidity (p = 0.006). Multivariate analysis revealed that a time to closure of ≤109 days was an independent risk factor for developing complications (p = 0.007).The optimal timing of stoma reversal is at least 109 days after stoma construction in rectal cancer patients receiving concurrent chemoradiotherapy and low anterior resection.
Two major issues encountered in the surgical resection of low rectal cancers (tumor located <6 cm from anal verge) are tumor-free surgical resection margin and adequate fields of colo-anal pull-through anastomosis. The clinical consequences of ensuring gross tumor-free surgical resection margin by transanal inside-out rectal resection technique were assessed for ultra-low rectal cancer patients. From February 2009 to September 2011, ultra-low anterior resection with a new method of eversion of the rectum through the anal canal after resecting the distal rectum and colo-anal anastomosis extracorporally performed in 30 patients (age range, 41-80 years) was reviewed. All patients received preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) before the surgical resection. The median operating time was 265 min (range, 220-400 min), and the median intraoperative blood loss was 325 ml (range, 80-855 ml). No in-hospital mortality was noted among these patients. R0 resection (tumor-free margin range, 0.9-2.5 cm) was confirmed in all patients by pathologic reports, except one patient with 0.5 cm tumor-free margin. The new surgical technique of transanal inside-out rectal resection and colo-anal pull-through anastomosis for selected patients with ultra-low rectal cancers seems to be a safe and alternative procedure.
We present our preliminary experiences and results for forty consecutive patients with colorectal cancer (CRC) who were treated by robotic surgery.Between May 2013 and September 2014, forty patients with CRC received robotic surgery at a single institution. The clinicopathological features and perioperative parameters were retrospectively analyzed.Of the 40 patients with CRC, 33 (82.5 %) had rectal cancers, and 22 (66.7 %) of those 33 patients also underwent pre-operative concurrent chemoradiotherapy (CCRT). The two most frequent surgical procedures were intersphincteric resection (ISR) with coloanal anastomosis (16/40, 40 %) and lower anterior resection (LAR) (15/40, 37.5 %). Among all 40 patients, the median time to first flatus passage was 2 days. The median time to soft diet resumption was 4 days. The median post operative hospital stay was 7 days. The overall complication rate was 20 % (8/40 patients), of which most of the complications were mild, although one laparotomy was required to check for post-operative bleeding. There was no 30-day hospital mortality, nor conversion to open surgery and laparoscopy.We present our preliminary experiences of robotic colorectal surgery and demonstrate that robotic colorectal surgery is a safe and feasible surgery even when conducted by laparoscopic surgeons with limited experience.
The robotic system has advantages of high-definition three-dimensional vision and articular instruments with high dexterity, allowing more precise dissection in the deep and narrow pelvic cavity. We enrolled 95 patients with stage I-III rectal cancer (adenocarcinoma) who underwent totally robotic-assisted total mesorectal excision (TME) with single-docking technique at a single institution between September 2013 and December 2016. Of the 95 patients, 48 (50.5%) and 30 (31.6%) patients had lower and middle rectal cancers, respectively. Of the 75 (78.9%) patients undergoing preoperative concurrent chemoradiotherapy (CCRT), 27 (28.4%) exhibited pathologic complete response (pCR). Only four (4.2%) patients underwent abdominoperineal resection and the sphincter preservation rate was 95.8%. R0 resection was performed in 92 (96.8%) patients. Circumferential resection margin (CRM) and distal resection margin (DRM) were positive in 2 (2.1%) and 1 (1.1%) patients, respectively. The anastomotic leakage rate was 5.4% (5/95 patients). The overall complication rate was 17.9% (17/95 patients); most of them were mild. No 30-day hospital mortality occurred, and no patients required conversion to open surgery. In 92 patients undergoing R0 resection, 2-year overall survival was 94% and 2-year disease-free survival was 83%. The results demonstrated that totally robotic-assisted TME with the single-docking technique is safe and feasible for patients with rectal cancer, with or without preoperative CCRT. Moreover, favorable pCR rate, R0 resection rate, CRM, DRM, sphincter preservation rate, and short-term oncological outcomes can be achieved by combining this approach with appropriate preoperative CCRT.
The aim of this study was to evaluate the efficacy of helical tomotherapy plus capecitabine as a preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Thirty-six LARC patients receiving preoperative CRT were analyzed. Radiotherapy (RT) consisted of 45 Gy to the regional lymph nodes and simultaneous-integrated boost (SIB) 50.4 Gy to the tumor, 5 days/week for 5 weeks. Chemotherapy consisted of capecitabine 850 mg/m 2 , twice daily, during the RT days. Patients underwent surgery 6–8 weeks after completion of CRT. Information was collected for patient characteristics, treatment response, and acute and late toxicities. Grade 3/4 (G3+) toxicities occurred in 11.1% of patients (4/36). Sphincter preservation rate was 85.2% (23/27). Five patients (14.3%) achieved pathological complete response. Tumor, nodal, and ypT0-2N0 downstaging were noted in 60% (21/35), 69.6% (16/23), and 57.1% (20/35). Tumor regression grade 2~4 was achieved in 28 patients (80%). After a median follow-up time of 35 months, the most common G3+ late morbidity was ileus and fistula (5.7%, 2/35). The study showed that capecitabine plus helical tomotherapy with an SIB is feasible in treatment of LARC. The treatment modality can achieve a very encouraging sphincter preservation rate and a favorable ypT0-2N0 downstaging rate without excessive toxicity.
OV-6 is among the best available markers of liver stem cells. The aim of this study was to investigate OV-6 expression and its clinical implications in colorectal cancer.Expression of OV-6 and its clinical implications were investigated in 94 patients with American Joint Committee on Cancer (AJCC) stage I-III primary colorectal cancer and in 37 rectal cancer patients who had received preoperative chemoradiotherapy. The two main expression patterns of OV-6 were cytoplasmic and membranous. Overexpression of OV-6, which was identified on the basis of overall staining intensity, was associated with perineural invasion, lymphovascular invasion, and early relapses. Membranous OV-6 overexpression was also significantly associated with depth of tumour invasion, AJCC stage, lymphovascular and perineural invasion, and postoperative early relapse. Disease-free survival and overall survival were significantly poorer in patients with high overall OV-6 expression than in those with low overall OV-6 expression (P = 0.015 and P = 0.029, respectively), and significantly poorer in patients with high membranous OV-6 expression than in those with low membranous OV-6 expression (P < 0.001 and P < 0.001, respectively). Membranous OV-6 expression was a more reliable prognostic marker than overall expression.OV-6 is not unique to the hepatobiliary system, and may be a novel prognostic marker in colorectal cancer.
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