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BACKGROUNDSurgeon and hospital factors are associated with the survival of patients treated for rectal cancer. The relative contribution of each of these factors toward determining outcomes is poorly understood.METHODSWe used data from the Surveillance, Epidemiology, and End Results–Medicare database to analyze the outcomes of patients aged 65 years and older undergoing operative treatment for nonmetastatic rectal cancer, diagnosed in the United States between 1998 and 2007. These data were linked to a registry to identify whether the treating surgeon was a board‐certified colorectal surgeon versus a noncolorectal surgeon. Hospital volume and hospital certification as a National Cancer Institute–designated Comprehensive Cancer Centers were also analyzed. The primary outcome of interest was long‐term survival.RESULTSOur data source yielded 6432 patients. Initial analysis demonstrated improved long‐term survival in patients treated by higher‐volume colorectal surgeons, higher‐volume hospitals, teaching hospitals, and National Cancer Institute (NCI)–designated Comprehensive Cancer Centers. Based on an iterative approach to modeling the interactions between these various factors, we found a robust effect of surgeon subspecialty status, hospital volume, and NCI designation. Surgeon volume was not distinctly associated with long‐term survival.CONCLUSIONSPatients treated for rectal cancer by board‐certified colorectal surgeons in centers that are higher volume and/or NCI‐designated Comprehensive Cancer Centers experience better overall survival. These differences persist after adjustment for a broad range of patient and contextual risk factors, including surgeon volume. Patients and payers can use these results to identify surgeons and hospitals where outcomes are most favorable. Cancer 2014;120:2472–2481. © 2014 American Cancer Society.

SummaryPurposeThe distinction between corticotropin (ACTH)‐producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH‐producing pituitary adenomas.Materials and methodsFifty‐five patients with pathology confirmed ACTH‐producing and 44 with nonfunctioning pituitary adenomas were analysed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time–intensity curves were then constructed, and quantitative analysis included: enhancement time, enhancement peak and prepeak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters.ResultsQuantitative analysis showed that tumour PPS in ACTH‐producing adenomas was markedly lower than that in nonfunctioning adenomas (P = 0·0042) and that the PPS of the adjacent pituitary gland was not different (P = 0·2441). The PPS was >3·0 in 59·1% of nonfunctioning adenomas and ≤3·0 in 69·1% of ACTH‐producing adenomas (P = 0·0049). Logistic analysis revealed lower tumour PPS levels (P = 0·0123, OR 1·24, 95% CI: 1·05–1·52) were associated with ACTH‐producing adenomas. The optimal PPS cut‐off determined by ROC analysis was 2·89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak.ConclusionEnhancement parameters in DMRI can help distinguishing ACTH producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH‐producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.

Abstract Adenosine signaling has been implicated in chronic lung diseases such as asthma and chronic obstructive pulmonary disease; however, the specific roles of the various adenosine receptors in processes central to these disorders are not well understood. In this study, we have investigated the role(s) of the A3 adenosine receptor in adenosine-dependent pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A3 receptor (A3R) was found to be expressed in eosinophils and mucus-producing cells in the airways of ADA-deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A3R antagonist, prevented airway eosinophilia and mucus production. Similar findings were seen in the lungs of ADA/A3 double knockout mice. Although eosinophils were decreased in the airways of ADA-deficient mice following antagonism or removal of the A3R, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A3R is needed for the migration of eosinophils into the airways. These findings identify an important role for the A3R in regulating lung eosinophilia and mucus production in an environment of elevated adenosine.

Background— Coronary collateral flow is an alternative source of myocardial perfusion in patients with totally occluded coronary arteries. Clinical evaluation of collateral flow has been limited by the need of invasive measurements. We investigated whether noninvasive coronary computed tomographic angiography can evaluate the angiographic extent of coronary collateral flow. Methods and Results— We enrolled 325 coronary computed tomographic angiography cases with angiographically confirmed chronic total occlusion (median age, 63 years; men 83%). Transluminal attenuation gradient (TAG), which reflects the kinetics of contrast media in coronary artery, of an entire artery as well as of a distal vessel was assessed to evaluate the flow in entire vessel and distal vessel. TAGs were validated against visually assessed angiographic collateral connection and Rentrop grading. TAG of an entire artery increased consistently according to the angiographic extent of collateral flow ( P <0.001). Well-developed collaterals, defined by highest collateral connection and Rentrop grades (n=103), could be predicted by TAG of an entire artery (cutoff, ≥−7.6 Hounsfield units/10 mm; c -statistics, 0.72; sensitivity, 65%; specificity, 73%; positive predictive value, 52%; negative predictive value, 82%). TAG of a distal vessel could discriminate the antegrade (n=143) and retrograde (n=182) flows in distal artery (cutoff, 0.0 Hounsfield unit/10 mm; c -statistics, 0.88; sensitivity, 78%; specificity, 85%; positive predictive value, 87%; negative predictive value, 75%). Conclusions— TAG, an intracoronary attenuation-based analysis of coronary computed tomographic angiography, moderately reflected the functional extent and direction of collateral flow.

Abstract Azadirachta indica, commonly known as neem, has gained worldwide prominence because of its medical properties, namely antitumor, antiviral, anti-inflammatory, antihyperglycemic, antifungal, and antibacterial activities. Despite these promising results, gaps remain in our understanding of the molecular mechanism of action of neem compounds and their potential for use in clinical trials. We investigated supercritical extract of neem leaves (SENL) for the following: molecular targets in vitro, in vivo efficacy to inhibit tumor growth, and bioactive compounds that exert antitumor activity. Treatment of LNCaP-luc2 prostate cancer cells with SENL suppressed dihydrotestosterone-induced androgen receptor and prostate-specific antigen levels. SENL inhibited integrin β1, calreticulin, and focal adhesion kinase activation in LNCaP-luc2 and PC3 prostate cancer cells. Oral administration of SENL significantly reduced LNCaP-luc2 xenograft tumor growth in mice with the formation of hyalinized fibrous tumor tissue, reduction in the prostate-specific antigen, and increase in AKR1C2 levels. To identify the active anticancer compounds, we fractionated SENL by high-pressure liquid chromatography and evaluated 16 peaks for cytotoxic activity. Four of the 16 peaks exhibited significant cytotoxic activity against prostate cancer cells. Mass spectrometry of the isolated peaks suggested the compounds with cytotoxic activity were nimbandiol, nimbolide, 2′,3′-dihydronimbolide, and 28-deoxonimbolide. Analysis of tumor tissue and plasma samples from mice treated with SENL indicated 28-deoxonimbolide and nimbolide as the bioactive compounds. Overall, our data revealed the bioactive compounds in SENL and suggested that the anticancer activity could be mediated through alteration in androgen receptor and calreticulin levels in prostate cancer. Mol Cancer Ther; 13(5); 1067–77. ©2014 AACR.

Objective To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features. Design We studied a cohort of 33 496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28 156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined. Results Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC. Conclusions Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors.