The 100 most cited articles investigating the radiological staging of oesophageal and junctional cancer: a bibliometric analysis

Objectives Accurate staging of oesophageal cancer (OC) is vital. Bibliometric analysis highlights key topics and publications that have shaped understanding of a subject. The 100 most cited articles investigating radiological staging of OC are identified. Methods The Thomas Reuters Web of Science database with search terms including “CT, PET, EUS, oesophageal and gastro-oesophageal junction cancer” was used to identify all English language, full-script articles. The 100 most cited articles were further analysed by topic, journal, author, year and institution. Results A total of 5,500 eligible papers were returned. The most cited paper was Flamen et al. (n = 306), investigating the utility of positron emission tomography (PET) for the staging of patients with potentially operable OC. The most common research topic was accuracy of staging investigations (n = 63). The article with the highest citation rate (38.00), defined as the number of citations divided by the number of complete years published, was Tixier et al. investigating PET texture analysis to predict treatment response to neo-adjuvant chemo-radiotherapy, cited 114 times since publication in 2011. Conclusion This bibliometric analysis has identified key publications regarded as important in radiological OC staging. Articles with the highest citation rates all investigated PET imaging, suggesting this modality could be the focus of future research

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Staging and patient selection in cancer of oesophagus and the oesophagogastric junction

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Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus

Background: Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal cancer patients treated with neoadjuvant chemotherapy. Patients and Methods: Immunohistochemical expression of p53/p21 and Ki-67 was examined in pretreatment biopsy specimen of 30 patients, in phase II neoadjuvant studies for locally advanced adenocarcinoma of the esophagus, who underwent surgery. Seven patients (23%) had progressive disease. Resection was achieved in all responders (n=23; 77%) and histochemical expression of the above-mentioned proliferating markers was examined in pre-treatment and resection specimens after chemotherapy. Results: Responders had a significantly better survival compared to non-responders (p=0.001). Expression of p53, p21 and high Ki-67 in pre-treatment specimens was 73% (22/30), 63% (19/30) and 30% (10/30), respectively and was not related to response to chemotherapy. However, alteration in expression of p53-positivity in the pre-treatment specimens to p53-negativity in the resection specimens and p21-negativity to p21-positivity in 6 of the 23 (26%) resected tumors was correlated with better response and survival (p=0.011). Conclusion: Data from this study showed that alteration of p53 and p21 expression rather than the initial expression seems to be related to chemotherapy response and overall survival in patients with esophageal adenocarcinoma

Influence of tumor characteristics on the accuracy of endoscopic ultrasonography in staging cancer of the esophagus and esophagogastric junction

Background and Study Aims: Endoscopic ultrasonography (EUS) is the most accurate method of assessing the locoregional extent of cancer of the esophagus and esophagogastric junction. The aim of this study was to evaluate the influence of tumor-related factors such as length and location on the accuracy of EUS in staging these tumors. Patients and Methods: Between January 1997 and September 2002, 280 consecutive patients underwent preoperative EUS for staging cancer of the esophagus and esophagogastric junction. The influence of histopathology, the presence of Barrett's dysplasia or stenosis, and the location and length of the primary tumor on the accuracy of EUS for T, N, and M staging were studied. Results: The overall accuracy rates of EUS for assessing the T, N, and M stages were 73%, 80%, and 78%, respectively. The influence of the tumor's histopathology and the presence of Barrett's dysplasia or stenosis was minimal. The accuracy of EUS was greater in tumors 5 cm or less in size than in tumors larger than 5 cm (82 % vs. 52 % for the T stage, P <0.05; 88 % vs. 59 % for the N stage, P <0.05; and 92 % vs. 56 % for the M stage, P <0.001). The low accuracy of T staging in larger tumors may be due to the exclusion of patients with local unresectability or distant metastases. EUS was also significantly better in esophageal tumors, particularly for identifying celiac trunk metastases (93% vs. 63%; P <0.001). Conclusions: The accuracy of EUS for staging esophageal cancer is lower in tumors larger than 5 cm and in esophagogastric junction tumors than in tumors 5 cm in size or less and in esophageal tumors. These findings should be considered when treatment decisions are being taken

Detection of distant metastases in esophageal cancer with F-18-FDG PET

Standard staging of esophageal and gastroesophageal junction (GEJ) tumors substantially lacks accuracy. The aim of this study was to investigate whether the addition of PET with F-18-FDG is a valuable gain in the initial staging. Methods: Between January 1996 and January 2002, F-18-FDG PET was performed in 74 patients. Conventional staging included CT in all patients and well-performed endoscopic ultrasonography (EUS) in 52 patients. They were compared with F-18-FDG PET with pathology and follow-up of suspicious lesions as the gold standard. Results: PET identified 70 primary tumors (sensitivity, 95%). Sensitivity to identify locoregional metastases was highest for EUS (69%) but was not different for CT and PET (44% and 55%, respectively). PET was able to identify distant nodal disease in 71% (17/24 patients) compared with 29% (7/24 patients) after combined CT/EUS alone (P = 0.021). Sensitivity to detect distant nodal and systemic (M1) disease increased with PET (78% vs. 37%; P = 0.012). PET upstaged 15 patients (15/74; 20%) correctly as M1 disease, missed by CT/EUS, and correctly downstaged 4 patients (5%) from M1 to MO disease. However, false upstaging and downstaging was encountered in 5 (7%) and 3 (4%) patients, respectively. Conclusion: PET improves the currently applied staging of esophageal and GEJ tumors, particularly by ameliorating the detection of M1 disease