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A 42-year-old Caucasian man presented with increased stool frequency and dyspeptic symptoms for which he had been prescribed lansoprazole. At colonoscopy he was found to have a 4-cm smooth polypoidal lesion in the transverse colon, adjacent to the hepatic flexure (figure 1). It was determined not to represent an adenoma and a CT colonogram was arranged, which found no extracolonic invasion but shed little further detail on the nature of the lesion in question. Figure 1 A sizeable smooth lesion arising from the epithelium at the transverse colon. A repeat colonoscopy, carried …

Background S100 proteins have been implicated in various aspects of cancer, including epithelial-mesenchymal transitions (EMT), invasion and metastasis, and also in inflammatory disorders. Here we examined the impact of individual members of this family on the invasion of pancreatic ductal adenocarcinoma (PDAC) cells, and their regulation by EMT and inflammation. Methods Invasion of PDAC cells was analysed in zebrafish embryo xenografts and in transwell invasion assays. Expression and regulation of S100 proteins was studied in vitro by immunoblotting, quantitative PCR and immunofluorescence, and in pancreatic lesions by immunohistochemistry. Results Whereas the expression of most S100 proteins is characteristic for epithelial PDAC cell lines, S100A4 and S100A6 are strongly expressed in mesenchymal cells and upregulated by ZEB1. S100A4/A6 and epithelial protein S100A14 respectively promote and represses cell invasion. IL-6/11-STAT3 pathway stimulates expression of most S100 proteins. ZEB1 synergises with IL-6/11-STAT3 to upregulate S100A4/A6, but nullifies the effect of inflammation on S100A14 expression. Conclusion EMT/ZEB1 and IL-6/11-STAT3 signalling act independently and congregate to establish the expression pattern of S100 proteins, which drives invasion. Although ZEB1 regulates expression of S100 family members, these effects are masked by IL-6/11-STAT3 signalling, and S100 proteins cannot be considered as bona fide EMT markers in PDAC.

The serine/threonine kinase Nek2 (NIMA‐related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing inductionofaneuploidyinvitro.Overexpression mayalsoenabletumourprogressionthrougheffects uponAktsignalling, celladhesionmarkersand the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC). Nek2 protein expression was examined in a panel of CRC cell lines using Western blotting and immunofluorescence microscopy. Nek2 and beta‐catenin expression were examined by immunohistochemistry in a series of resected CRC, as well as their matched lymph node and liver metastases, and correlated with clinicopathological characteristics. Nek2 protein expression in all CRC lines examined was higher than in the immortalised colonocyte line HCEC. Nek2 overexpression was present in 86.4% of resected CRC and was significantly associated with advancing AJCC tumour stage and shortened cancer‐specific survival. Elevated Nek2 expression was maintained within all matched metastases from overexpressing primary tumours. Nek2 overexpression was significantly associated with lower tumour membranous beta‐catenin expression and higher cytoplasmic and nuclear beta‐ catenin accumulation. These data support a role for Nek2 in CRC progression and confirm potential for Nek2 inhibition as a therapeutic avenue in CRC. J. Surg. Oncol. . 2014 Wiley Periodicals, Inc.

A 45-year-old man presented with odynophagia, felt in the region of the upper chest. Upper GI endoscopy was normal and proton pump inhibitor therapy ineffective. Oesophageal function tests showed no reflux on 24 h pH monitoring; manometry revealed ineffective oesophageal motility (low-amplitude peristalsis) thought to explain his symptoms. He re-presented 6 years later with worsening odynophagia; repeat endoscopy showed a 1 cm nodule in the proximal oesophagus at 24 cm from the incisor teeth. Endoscopic biopsies showed features of low-grade adenocarcinoma of mucinous/tubular type. He was referred to the network upper GI cancer multidisciplinary team and a decision was made for further endoscopic assessment, after staging CT and positron emission tomography scans did not identify the tumour or any metastases; endoscopic ultrasound (EUS) was not performed. …

The serine/threonine kinase Nek2 (NIMA-related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing induction of aneuploidy in vitro. Overexpression may also enable tumour progression through effects upon Akt signalling, cell adhesion markers and the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC). Nek2 protein expression was examined in a panel of CRC cell lines using Western blotting and immunofluorescence microscopy. Nek2 and beta-catenin expression were examined by immunohistochemistry in a series of resected CRC, as well as their matched lymph node and liver metastases, and correlated with clinicopathological characteristics. Nek2 protein expression in all CRC lines examined was higher than in the immortalised colonocyte line HCEC. Nek2 overexpression was present in 86.4% of resected CRC and was significantly associated with advancing AJCC tumour stage and shortened cancer-specific survival. Elevated Nek2 expression was maintained within all matched metastases from overexpressing primary tumours. Nek2 overexpression was significantly associated with lower tumour membranous beta-catenin expression and higher cytoplasmic and nuclear beta-catenin accumulation. These data support a role for Nek2 in CRC progression and confirm potential for Nek2 inhibition as a therapeutic avenue in CRC.

Introduction Non-anatomic resections (NAR) for colorectal liver metastases (CRLM) have become increasingly common in an attempt to increase resection rates and to enable parenchyma-preserving resections, though some investigators have reported NAR to be associated with higher rates of resection margin positivity and poorer long-term survival than anatomic resections (AR). The aim of this study was to compare surgical outcomes, recurrence and survival in patients treated with NAR and AR. Methods Patients undergoing hepatic resection for CRLM between January 2002 and December 2008 were identified from a prospectively maintained database. Patients were divided into two groups: those who underwent AR and those who underwent NAR. Patients who underwent simultaneous AR and NAR were excluded from analysis. Clinicopathological variables and perioperative outcomes, as well as long-term disease-free and overall survival were compared between the AR and NAR groups, using the χ 2 test, Mann–Whitney U test, logistic regression analysis, log-rank analysis and multivariable Cox regression analysis employing a backwards stepwise model. Results Over the study period 91 patients underwent AR and 77 patients underwent NAR. Perioperative (90-day) morbidity, major morbidity and mortality occurred in 25.0%, 8.3% and 1.8% of cases respectively. There was no significant difference in rates of perioperative morbidity, major morbidity or mortality according to resection type (all p>0.30). There was also no difference in the incidence of positive resection margins between resection types (p=0.413). Overall survival was 48.5% and 36.6% at 3 and 5 years respectively, with disease-free survival of 31.4% and 25.3% at 3 and 5 years respectively. Type of resection was not associated with any significant difference in overall (p=0.430) or disease-free survival (p=0.625) following metastasectomy. Conclusion AR is not superior to NAR in terms of perioperative risk, tumour clearance, time to recurrence or long-term survival following metastasectomy. NAR should remain an integral component of the surgical treatment of CRLM and may enable increasing rates of operability. Furthermore, the preservation of hepatic parenchyma by NAR may enable a larger proportion of patients subsequently developing recurrent metastatic disease to undergo repeat metastasectomy. Competing interests None declared.