Blood content and tumor oxygen level are important biomarkers and prognostic indicators in patients with colorectal cancer (CRC). However, noninvasive measurements of both quantities in human colon are limited. In this study, we extracted the total hemoglobin concentration (THC) and oxygen saturation (StO₂) of normal, premalignant, and malignant colonic tissues in 27 patients using a diffuse reflectance instrument and algorithms based on the diffusion equation. The mean±standard error of THC and StO₂ from all normal sites (n=26) is 93.4±17.1μM and 67.2±3.7%, respectively. THC increased to 136.9±23.8μM and 153.8±38.6μM and StO₂ decreased to 51.3±7.0% and 26.4±6.1% for premalignant and malignant tissues, respectively. The disease-to-normal THC ratios are 3.2±1.1 and 4.4±1.9 and the disease-to-normal StO₂ ratios are 0.7±0.1 and 0.5±0.1 for premalignant and malignant tissues, respectively. These results demonstrate the feasibility of a robust optical method to assess colon THC and StO₂ at all stages of carcinogenesis in vivo so that the angiogenesis and hypoxia of the disease and the therapeutic role can be studied in CRC patients.

Background: To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Methods: Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Results: Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). Conclusions: In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.

By comparing surgical outcomes between primary and delayed resection, we addressed whether and how surgical strategies impacted prognosis of patients with left-sided colorectal cancer underwent emergency curative resection. Between January 1980 and December 2002, a total of 143 patients were identified who presented with obstructive left-sided colorectal cancer and received emergency curative resection in Taipei Veterans General Hospital. Patients were stratified according to the timing of tumor resection into two groups: primary resection and delayed resection. Demographic data of the patients, characteristics of the tumors, and short-term and long-term outcomes were analyzed and compared between the two groups. The demographic data and tumor characteristics did not differ between the two groups except for more rectal cancers in the delayed resection group (P= 0.021). Primary resection group had a higher anastomotic leakage rate (P= 0.017) and a trend toward a higher mortality rate, which did not reach statistical significance (P= 0.063). The median follow-up intervals were similar (60.4vs. 58.3 months;P= 0.79). The median survival tended to be longer in delayed resection group (66vs. 105 months;P= 0.088). Overall five-year and ten-year survival for primary resection were 43.7 and 31.9 percent, respectively, compared with 67.2 and 53.2 percent, respectively, for delayed resection. Delayed resection seems to be a safer procedure and provided a better oncologic outcome compared with primary resection in obstructive left-sided colorectal cancer under emergency situations.

Colonic J-pouch has been constructed to overcome reservoir dysfunction after restorative rectal surgery, whereas no effort has been made for sphincter dysfunction. We conducted a prospective, randomized study comparing surgical and functional outcomes between side-to-end anastomosis and colonic J-pouch after low anterior resection in which the anastomosis was constructed from the abdomen. Fifty-six consecutive patients with middle-to-low rectal cancer undergoing low anterior resection were randomly assigned to side-to-end or colonic J-pouch group preoperatively. Surgical outcomes of all the patients were recorded. Patients underwent functional evaluation, including anorectal manometry and functional assessment, preoperatively and then 3 months, 6 months, 1 year, and 2 years postoperatively. Twenty-four patients in each group completed the study. The demographic data and preoperative functional assessment did not differ between the two groups. There was no significant difference in surgical outcomes with regard to anastomotic height (5 cm), blood loss, protective colostomy, operative time, complications, and adjuvant therapy. Anal pressures showed no significant change postoperatively and during the follow-up period; there were no differences between the two groups. Temporal minor fecal incontinence was noted in the early postoperative period in both groups. With regard to bowel function, a significant reduction of volume of urgency and maximal tolerable volume was found postoperatively in both groups; however, a faster recovery was noted in the colonic J-pouch group. Stool frequency increased significantly after surgery in both groups; however, in contrast to rectal volume, a faster recovery was noted in the side-to-end group. Anastomosis after low anterior resection for middle to low rectal cancer could be performed safely from the abdomen. It minimized sphincter injury and showed good continence preservation. On the other hand, the surgical outcomes and long-term functional results of side-to-end anastomosis were comparable with colonic J-pouch. Side-to-end anastomosis provides an easier, alternative way for reconstruction after restorative rectal surgery.

Purpose: Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC. Experimental Design: CTCs were quantified using EpCAM-positive/CD45-negative immunoselection and flow cytometry in patients with CRC. A mouse model was used to investigate the mechanistic roles of CTCs and interleukin (IL)-17A in metastasis. Results: The number of mesenteric CTCs obtained from stage II patients was higher than that obtained from patients in stages I, III, and IV. In addition, following invasion of orthotopically implanted tumors in our mouse model, we found that CTCs exhibited an increase-then-decrease pattern, accompanied by corresponding changes in serum IL-17A levels and opposing changes in serum granulocyte macrophage colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host immunity. Notably, serum levels of IL-17A were also correlated with disease-free survival in patients with CRC. Conclusions: Our results showed that CTCs and IL-17A could serve as prognostic markers and therapeutic targets for CRC metastasis. Clin Cancer Res; 20(11); 2885–97. ©2014 AACR.