Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS,PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62–0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83–1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795.

Abdominoperineal resection (APR) of advanced lower rectal cancer carries a high incidence of perineal wound infection. The aim of this study was to retrospectively evaluate risk factors for perineal wound infection after APR. The study group comprised 154 patients who underwent APR for advanced lower rectal cancer in our department from January 1990 through December 2012. The following 15 variables were studied as potential risk factors for perineal wound infection: sex, age, body-mass index, American Society of Anesthesiologists score, diabetes mellitus, preoperative albumin level, preoperative hemoglobin level, neoadjuvant chemoradiotherapy(NCRT), surgical procedure (open surgery vs. laparoscopic surgery), operation time, bleeding volume, intraoperative transfusion, tumor diameter, invasion depth, and histopathological stage. Among the 154 patients, 30 (19%) had perineal wound infection. Univariate analysis showed that a hemoglobin level of ≤11 g/dL (p = 0.001) and NCRT (p = 0.001) were significantly related to perineal wound infection. On multivariate analysis including the preoperative albumin level (≤3.5 g/dL) in addition to the above 2 variables, neoadjuvant chemoradiotherapy (NCRT) was the only independent risk factor for perineal wound infection. Perineal wound infection developed in 31% of patients who received NCRT, as compared with 10% of patients who did not receive NCRT. The relative risk of perineal infection in the former group was 4.092 as compared with the latter group (p = 0.0002). NCRT is a risk factor for perineal wound infection after APR in patients with advanced lower rectal cancer.

Adjuvant chemotherapy after resection of colorectal cancer (CRC) lung metastases may reduce recurrences and improve survival. We investigated the effects of adjuvant chemotherapy after curative resection of lung CRC metastases on prognosis. We retrospectively reviewed records of our patients undergoing pulmonary metastasectomy from CRC between January 2000-March 2014. Data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards models. One-hundred (56 men; median age, 66 years) of 128 consecutive patients who underwent complete resection for first lung colorectal metastases were analyzed. Postoperative 5-year rates of overall survival (OS) and relapse-free survival (RFS) were 76% and 41%, respectively. Adjuvant chemotherapy strongly affected RFS and OS by multivariable analysis compared to surgery alone (RFS: HR, 0.49; 95% CI, 0.27-0.88; P = 0.016 and OS: HR, 0.35; 95% CI, 0.14-0.81; P = 0.014). Similar effects of adjuvant chemotherapy occurred in subgroups respectively classified according to number of lung metastases and preoperative serum carcinoembryonic antigen (CEA) level. Adjuvant chemotherapy after curative resection of lung metastases might strongly affect the prognosis of metastatic CRC patients. Even patients with single metastatic lesions and normal preoperative CEA level appeared to receive benefits from such chemotherapy. Narrowing of suitable candidates by predicting the effects of systemic chemotherapy and prospective randomized studies are needed.

Phosphatase of regenerating liver (PRL)-3 was identified as a molecule associated with liver metastasis in colorectal cancer (CRC), although its precise causative role in distant metastasis remains elusive from a clinical point of view. The aim of this study was to promote the mechanistic insight of PRL-3 involvement in liver metastasis in CRC. One hundred and seven CRC patients with resection of the primary lesions were studied for clinicopathological and prognostic association with PRL-3 and were evaluated by immunohistochemistry in univariate and multivariate analyses. Intense immunostaining of PRL-3 was found in Dukes' A (0/26), Dukes' B (0/30), Dukes' C (18/30) and Duke's D (20/21) although the PRL-3 expression could not predict metachronous liver metastasis (MLM) in Dukes' C patients. PRL-3 expression showed an inverse correlation of prognosis in a univariate prognostic analysis (P<0.0001), though a multivariate assay failed to demonstrate PRL-3 relevance as an independent prognostic factor. PRL-3 expression was closely associated with classic prognostic factors such as the pN factor (P<0.0001), H factor-synchronous liver metastasis (SLM) (P<0.0001), pT factor (P=0.0002), preoperative CEA (P<0.0001) and preoperative CA19-9 (P<0.0001). Multivariate logistic regression analysis of PRL-3 expression revealed that the pN factor (P<0.0001), CEA (P<0.0001) and CA19-9 (P<0.0001) were finally remnant as an independent association with PRL-3. However, the H factor (SLM) was eliminated. Our data suggested that liver metastasis by PRL-3 is putatively mediated through lymph node metastasis and elevated tumor markers in the serum and the PRL-3 expression may not represent a direct causative mechanism of liver metastasis.