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Background: Benchmarking on an international level might lead to improved outcomes at a national level. The aim of this study was to compare treatment and surgical outcome data from the Swedish National Register for Oesophageal and Gastric Cancer (NREV) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA). Methods: All patients with primary oesophageal or gastric cancer who underwent a resection and were registered in NREV or DUCA between 2012 and 2014 were included. Differences in 30-day mortality were analysed using case mix-adjusted multivariable logistic regression. Results: In total, 4439 patients underwent oesophagectomy (2509 patients) or gastrectomy (1930 patients). Estimated resection rates were comparable. Swedish patients were older but had less advanced disease and less co-morbidity than Dutch patients. Neoadjuvant treatment rates were lower in Sweden than in the Netherlands, both for patients who underwent oesophagectomy (68⋅6 versus 90⋅0 per cent respectively; P < 0⋅001) and for those having gastrectomy (38⋅3 versus 56⋅6 per cent; P < 0⋅001). In Sweden, transthoracic oesophagectomy was performed in 94⋅7 per cent of patients, whereas in the Netherlands, a transhiatal approach was undertaken in 35⋅8 per cent. Higher annual procedural volumes per hospital were observed in the Netherlands. Adjusted 30-day and/or in-hospital mortality after gastrectomy was statistically significantly lower in Sweden than in the Netherlands (odds ratio 0⋅53, 95 per cent c.i. 0⋅29 to 0⋅95). Conclusion: For oesophageal and gastric cancer, there are dif

Background: Previous studies suggested a relationship between aspirin use and mortality reduction. The mechanism for the effect of aspirin on cancer outcomes remains unclear. The aim of this study was to evaluate aspirin use and survival in patients with gastrointestinal tract cancer. Methods: Patients with gastrointestinal tract cancer diagnosed between 1998 and 2011 were included. The population-based Eindhoven Cancer Registry was linked to drug-dispensing data from the PHARMO Database Network. The association between aspirin use after diagnosis and overall survival was analysed using Cox regression models. Results: In total, 13 715 patients were diagnosed with gastrointestinal cancer. A total of 1008 patients were identified as aspirin users, and 8278 patients were identified as nonusers. The adjusted hazard ratio for aspirin users vs nonusers was 0.52 (95% CI 0.44-0.63). A significant association between aspirin use and survival was observed for patients with oesophageal, hepatobiliary and colorectal cancer. Conclusions: Post-diagnosis use of aspirin in patients with gastrointestinal tract malignancies is associated with increased survival in cancers with different sites of origin and biology. This adds weight to the hypothesis that the anti-cancer effects of aspirin are not tumour-site specific and may be modulated through the tumour micro-environment.

Purpose: For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. Methods: In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. Results: In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47–0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38–0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13–1.06), although this additional analysis was underpowered for definite conclusions. Conclusions: This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isola

Background: Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. Methods: The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. Results: All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. Conclusions: This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery.

Purpose: Near-infrared (NIR) fluorescence imaging can provide the surgeon with real-time visualization of, e.g., tumor margins and lymph nodes. We describe and evaluate the Artemis, a novel, handheld NIR fluorescence camera.Procedures: We evaluated minimal detectable cell numbers (FaDu-luc2, 7D12-IRDye 800CW), preclinical intraoperative detection of sentinel lymph nodes (SLN) using indocyanine green (ICG), and of orthotopic tongue tumors using 7D12-800CW. Results were compared with the Pearl imager. Clinically, three patients with liver metastases were imaged using ICG.Results: Minimum detectable cell counts for Artemis and Pearl were 2 × 105 and 4 × 104 cells, respectively. In vivo, seven SLNs were detected in four mice with both cameras. Orthotopic OSC-19-luc2-cGFP tongue tumors were clearly identifiable, and a minimum FaDu-luc2 tumor size of 1 mm3 could be identified. Six human malignant lesions were identified during three liver surgery procedures.Conclusions: Based on this study, the Artemis system has demonstrated its utility in fluorescence-guided cancer surgery.

Background:We investigated the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen vs Exemestane Adjuvant Multinational (TEAM) trial.Methods:The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling was performed over the intervals of 0-5 years and >5 years.Results:We observed a strong time dependence of both the IHC4 and Mammostrat scores, with their effects decreasing over time. In the first 5 years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (P<0.05), with increases in R 2 between 5 and 6% and increases in D-statistic between 0.16 and 0.21.Conclusions:Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will benefit from adjuvant chemotherapy.

Introduction. For postmenopausal patients with hormonesensitive breast cancer, outcome is worse with increasing age at diagnosis. The aim of this study was to assess the incidenceof breast cancer recurrence (locoregionalanddistant), and contralateral breast cancer by age at diagnosis. Methods. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were included. Primary endpoints were locoregional recurrence, distant recurrence, and contralateralbreastcancer.Ageatdiagnosiswascategorizedas younger than 65 years, 65-74 years, and 75 years or older. Results. Overall, 9,766 patients were included, of which 5,349 were younger than 65 years (reference group), 3,060 were 65-74 years, and 1,357 were 75 years or older. With increasing age, a decreased administration of radiotherapy after breast conserving surgery (94%, 92%, and 88%, respectively) and adjuvant chemotherapy (51%, 23%, and 5%, respectively) was observed. Risk of distant recurrence increased with age at diagnosis; multivariable hazard ratio for pa

Objective: To determine if composite measures based on process indicators are consistent with short-term outcome indicators in surgical colorectal cancer care. Design: Longitudinal analysis of consistency between composite measures based on process indicators and outcome indicators for 85 Dutch hospitals. Setting: The Dutch Surgical Colorectal Audit database, the Netherlands. Participants: 4732 elective patients with colon carcinoma and 2239 with rectum carcinoma treated in 85 hospitals were included in the analyses. Main outcome measures: All available process indicators were aggregated into five different composite measures. The association of the different composite measures with risk-adjusted postoperative mortality and morbidity was analysed at the patient and hospital level. Results: At the patient level, only one of the composite measures was negatively associated with morbidity for rectum carcinoma. At the hospital level, a strong negative association was found between composite measures and hospital mortality and morbidity rates for rectum carcinoma (p<0.05), and hospital morbidity rates for colon carcinoma. Conclusions: For individual patients, a high score on the composite measures based on process indicators is not associated with better short-term outcome. However, at the hospital level, a good score on the composite measures based on process indicators was consistent with more favourable risk-adjusted short-term outcome rates.

Background: The preventive role of non-steroid anti-inflammatory drugs (NSAIDs) and aspirin, in particular, on colorectal cancer is well established. More recently, it has been suggested that aspirin may also have a therapeutic role. Aim of the present observational population-based study was to assess the therapeutic effect on overall survival of aspirin/NSAIDs as adjuvant treatment used after the diagnosis of colorectal cancer patients. Methods: Data concerning prescriptions were obtained from PHARMO record linkage systems and all patients diagnosed with colorectal cancer (1998-2007) were selected from the Eindhoven Cancer Registry (population-based cancer registry). Aspirin/NSAID use was classified as none, prediagnosis and postdiagnosis and only postdiagnosis. Patients were defined as non-user of aspirin/NSAIDs from the date of diagnosis of the colorectal cancer to the date of first use of aspirin or NSAIDs and user from first use to the end of follow-up. Poisson regression was performed with user status as time-varying exposure.Results:In total, 1176 (26%) patients were non-users, 2086 (47%) were prediagnosis and postdiagnosis users and 1219 (27%) were only postdiagnosis users (total n=4481). Compared with non-users, a survival gain was observed for aspirin users; the adjusted rate ratio (RR) was 0.77 (95% confidence interval (CI) 0.63-0.95; P=0.015). Stratified for colon and rectal, the survival gain was only present in colon cancer (adjusted RR 0.65 (95%CI 0.50-0.84; P=0.001)). For frequent users survival gain was larger (adjusted RR 0.61 (95%CI 0.46-0.81; P=0.001). In rectal cancer, aspirin use was not associated with survival (adjusted RR 1.10 (95%CI 0.79-1.54; P=0.6). The NSAIDs use was associated with decreased survival (adjusted RR 1.93 (95%CI 1.70-2.20; P<0.001). Conclusion: Aspirin use initiated or continued after diagnosis of colon cancer is associated with a lower risk of overall mortality. These findings strongly support initiation of a placebo-cont

Purpose: Some postmenopausal patients with hormone-sensitive early breast cancer remain at high risk of relapse despite endocrine therapy and, in addition, might benefit from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk and may inform treatment decisions. We tested the efficacy of this panel in the Tamoxifen versus Exemestane Adjuvant Multicenter (TEAM) trial. Patients and Methods: Pathology blocks from 4,598 TEAM patients were collected, and tissue microarrays (TMAs) were constructed. The cohort was 47% node-positive, and 36% of patients in the cohort were treated with adjuvant chemotherapy. Triplicate 0.6- mm2 TMA cores were stained, and positivity for p53, HTF9C, CEACAM5, NDRG1, and SLC7A5 was assessed. Cases were assigned a Mammostrat risk score, and distant relapse-free survival (DRFS) and disease-free survival (DFS) were analyzed. Results: In multivariate regression analyses, which were corrected for conventional clinicopathologic markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in estrogen receptor (ER) -positive node-negative patients (n = 1,226) who did not receive chemotherapy (P = .004). Additional analyses in all patients not exposed to chemotherapy, irrespective of nodal status (n = 2,559) and in the entire cohort (n = 3,837) showed Mammostrat scores provided additional information on DRFS in these groups (P = .001 and P < .001, respectively; multivariate analyses). No differences were seen between the two endocrine treatment regimens. Conclusion: The Mammostrat score predicts DRFS for patients treated with exemestane and patients treated with tamoxifen followed by exemestane irrespective of nodal status and chemotherapy. The ability of this test to provide additional outcome data after treatment provides additional evidence of its use in risk stratification of ER-posi

Context: In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. Objective: To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. Design, Setting, and Patients: Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357). Main Outcome Measures: Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. Results: During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [≥75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91-1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P=.06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001). Conclusion: Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality.

In cancer surgery, intra-operative assessment of the tumor-free margin, which is critical for the prognosis of the patient, relies on the visual appearance and palpation of the tumor. Optical imaging techniques provide real-time visualization of the tumor, warranting intra-operative image-guided surgery. Within this field, imaging in the near-infrared light spectrum offers two essential advantages: increased tissue penetration of light and an increased signal-to-background-ratio of contrast agents. In this article, we review the various techniques, contrast agents, and camera systems that are currently used for image-guided surgery. Furthermore, we provide an overview of the wide range of molecular contrast agents targeting specific hallmarks of cancer and we describe perspectives on its future use in cancer surgery.

Introduction: High-tie ligation is a common practice in rectal cancer surgery. However, it compromises perfusion of the proximal limb of the anastomosis. This anatomical study was designed to assess the value of low-tie ligation in order to obtain a tension-free anastomosis. Materials and methods: Consecutive high- and low-tie resections were performed on 15 formalin-fixed specimens, with or without splenic flexure mobilization. If the proximal colon limb could reach the superior aspect of the symphysis pubis with more than 3 cm, the limb would be long enough for a tension-free colorectal anastomosis. Results: In 80% of cases, it was not necessary to perform high-tie ligation as sufficient length was gained with low-tie ligation. The descending branch of the left colic artery was the limiting factor in the other 20% of cases. Resecting half the sigmoid resulted in four times as many tension-free anastomoses after low-tie resection. Conclusion: In the majority of cases, it was not necessary to perform high-tie ligation in order to create a tension-free anastomosis. Low-tie ligation was applicable in 80% of cases and might prevent anastomotic leakage due to insufficient blood supply of the proximal colon limb.

Consensus does not exist on the level of arterial ligation in rectal cancer surgery. From oncologic considerations, many surgeons app

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1 cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.