tbuckley/cabot-search huggingface dataset:
Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis
Authors: J E G IJspeert, S A Q Rana, N S S Atkinson, Y J van Herwaarden, B A J Bastiaansen, M E van Leerdam, S Sanduleanu, T M Bisseling, M C W Spaander, S K Clark, G A Meijer, N van Lelyveld, J J Koornstra, I D Nagtegaal, J E East, A Latchford, E Dekker
Journal: Gut (2015)

<h3>Objective</h3> Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. <h3>Design</h3> In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. <h3>Results</h3> In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). <h3>Conclusion</h3> The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.
A relationship between ethics of clinical trials and therapeutic advances in cancer
Authors: B. Djulbegovic, A. Kumar, H. P. Soares, F. Serdarevic, R. J. Wells, J. Fiorica, S. Swann, J. C. Buckner, D. Sargent, I. Hozo
Journal: Journal of Clinical Oncology (2005)

6090 Background: We hypothesized that there is a predictable relationship between equipoise and the outcomes of trials, i.e. the equipoise principle bounds therapeutic advances in a such way that, over time, distribution of successes between experimental and standard treatments is expected to be about equal, reflecting the unpredictability of treatment success for a particular intervention. We tested this hypothesis in randomized controlled trials (RCT) performed by the National Cancer Institute (NCI) sponsored Cooperative Groups (CG), systematically taking into account all factors (publication bias, methodological quality, choice of control intervention) known to affect outcomes. Methods: All completed (published and unpublished) phase 3 RCTs from 6 CGs (563 trials, ∼ 149,000 patients) since 1955 were evaluated. Success of experimental vs. standard treatments was evaluated semi-quantitatively and quantitatively using a meta-analytic technique. Results: Investigator’s preference for experimental vs. standard treatments were 43% and 57%, respectively (p=0.002). Hazard ratio for overall survival was 0.96 [99% CI (0.95, 0.98), p=0.00001] and for event-free survival was 0.92, [99%CI (0.90, 0.93), p=0.0001] slightly favoring experimental treatments but at the expense of increased treatment-related mortality [HR 1.12, 99%CI (1.01, 1.25), p=0.04]. The results adhere to the equipoise hypothesis and were not affected by any factors known to bias outcomes. Conclusions: While many successful treatments are discovered in phase 3 RCTs, innovative treatments in cancer which have progressed to testing in RCTs are, on average, as likely to be inferior or superior to standard treatments. This result was predicted, which amounts to description of the law of therapeutic advances in clinical oncology. If the distribution of the results were significantly skewed to consistently and predictably favor one type of treatments over another, the clinical trial system would come to a halt (patients would naturally request only those treatments that are expected to be superior making randomization impossible). Progress in treating cancer is ultimately determined by the ethical principle of equipoise which should guide clinical research. No significant financial relationships to disclose.
Characterization of unresectable cholangiocarcinoma patients treated with or without chemoradiation.
Authors: Jane Elizabeth Rogers, Van Nguyen, Graciela M. Nogueras-Gonzalez, Christopher H. Crane, Prajnan Das, Sunil Krishnan, Lindsey Law, Milind M. Javle, Ahmed Omar Kaseb, Rachna T. Shroff
Journal: Journal of Clinical Oncology (2015)

403 Background: Curative treatment for cholangiocarcinoma (CC) is surgical resection. Unfortunately, most CC patients (pts) present with unresectable disease in which gemcitabine plus platinum (GEM-P) chemotherapy is the mainstay of treatment (tx). Advanced CC has a dismal prognosis with 5-year survival reported at 5-10 %. Data regarding chemoradiation (CRT) in pts with unresectable CC (uCC) remains limited. Methods: We retrospectively reviewed uCC pts from 1/1/2009 to 7/31/2013. Primary objective: to evaluate the percentage of pts treated with CRT and the median number of chemotherapy cycles given prior to CRT. Secondary objectives: response to first-line tx, progression free survival (PFS) with or without CRT, overall survival (OS) with or without CRT, and duration of CRT control. Inclusion criteria: uCC diagnosis, received tx, and had follow-up at our institution. Exclusion criteria: pts who received liver-directed therapy other than CRT, mixed histology tumors, and a history of other malignancies. Results: 114 pts were included with 62% having intrahepatic CC. Disease control (DC) (response + stable disease) with first-line tx was 75% with 71% receiving GEM-P +/- erlotinib first-line. 65% of pts received CRT with a median of 6 chemotherapy cycles given prior to CRT. DC after CRT was 62% with a median duration of radiation control of 6.4 mths. Median PFS and OS for all pts were 13.4 mths and 27.8 mths, respectively. Median PFS in the CRT group was 14.5 mths versus 11.4 mths in the no CRT group (p = 0.105). Median OS in the CRT cohort was 29.4 mths, while median OS without CRT was 22.4 mths (p = 0.005). Median OS and PFS after CRT for pts with DC on first-line tx were 32.0 months (95% CI = 24-44 mths) and 15.7 mths (95% CI =13.5-18.8 mths), respectively. Pts who progressed on first-line tx and received CRT had a median OS of 23.8 mths (95% CI = 7-30 months) and median PFS of 4.2 mths (95% CI = 2.3-9 mths). Conclusions: Our retrospective review reveals a significant improvement in median OS with CRT in uCC pts. Those with DC on first-line tx showed improvement in PFS and OS with CRT. Patient selection is key with the benefit being highest in pts with DC with first-line tx. Our results warrant further investigation of the role of CRT in uCC.
General practitioners and medical interns' level of knowledge assessment and their commitment to prescribing antibiotic therapy in the treatment of respiratory infections
Authors: Roman Bontsevich, Kristina Vlasova, Lyubov Alekhina
Journal: European Respiratory Journal (2014)

The rational antibiotic (AB) therapy of respiratory infections is one of the most crucial problems in the doctors9 practice. Despite the widespread usage of antibacterial drugs, clinicians are still experiencing difficulties in the prescribing and compensation of treatment with AB.   The objective:  To assess the level of knowledge of general practitioners (GPs) and medical interns (MI) in matters of antimicrobial therapy, to identify the most common AB for the treatment of respiratory infections.   The methods:  there was developed an original questionnaire for surveying physicians. Eleven GPs and twenty-five MI of Belgorod region9s medical institutions took part in the research.   The results:  The question - when it is necessary to change an antibiotic treatment in case of clinical effect absence – was answered correctly in 81.8% and 64% of cases and given by GPs and MI respectively; the question about AB treatment duration was answered by 45.5% of GPs and 56% of MI.  The preferences of GPs and MI on application groups of antibacterial drugs for the treatment of respiratory infections is given to Cephalosporines (100% and 76%), Penicillines (100% and 60%), Macrolides (100% and 56%) and Fluoroquinolones (81.8% and 40%), respectively by AB - Azithromycin (100% and 56%), Ceftriaxone (54.5% and 64%), Amoxicillin/Clavulatate (63.6% and 40%) and Ciprofloxacin (63.6% and 24%), respectively.   The conclusions:  The level of GPs and medical interns9 knowledge in rational antibiotic therapy of respiratory infections is fairly low. It requires conducting additional education programs and measures.
Abstract 15827: Impaired Intrinsic Exercise Capacity Predisposes to Progressive Left Ventricular Remodeling: Role of Microvascular Endothelial Dysfunction and Impaired Glucose Utilization
Authors: Rebecca H Ritchie, Chen H Leo, Chengxue Qin, Erin J Stephenson, Marissa A Bowden, Keith D Buxton, Sarah J Lessard, Donato A Rivas, Lauren G Koch, Steven L Britton, John A Hawley, Owen L Woodman
Journal: Circulation (2012)

Cardiovascular risk factors are increased with low intrinsic aerobic capacity, but the concomitant impact on the progression of left lentricular (LV) morphology and microvascular function remains unresolved. We tested the hypothesis that low intrinsic running capacity (LCR) induces progressive age-dependent LV remodeling compared to high-intrinsic running capacity (HCR), accompanied by impairments in microvascular function, glucose utilization and β-adrenergic responsiveness. Hearts and vessels isolated from female rats selectively bred for either LCR or HCR were studied at 12 and 35wks of age. Control (founder) rats were studied for comparison. Compared to HCR, LCR rats exhibited characteristics of metabolic syndrome, including impaired glucose tolerance (by 14.7±4.3%, P<0.01), elevated plasma insulin (by 61±18%, P<0.05) and bodymass at 12wks; blood glucose was not elevated until 35wks (by 25.8±4.7%, P<0.005). At 12wks of age, LCR rats exhibited LV remodeling (increased cardiomyocyte width and LV collage...
Regorafenib‐induced hand–foot skin reaction with striking epidermal dysmaturation – a new histopathological pattern associated with the use of multi‐kinase inhibitors
Authors: M. Llamas‐Velasco, I. Hegyi, U. Hesterberg, E. Daudén, L. Requena, W. Kempf
Journal: British Journal of Dermatology (2016)
Has the outcome of cholangiocarcinoma in the United States improved? A review of SEER data
Authors: M. S. Beg, R. Komrokji, K. Ahmed, M. M. Safa
Journal: Journal of Clinical Oncology (2008)

15518 Background: Cholangiocarcinoma (CC) remains a therapeutic challenge with surgery often being the only therapeutic option. Recently integration of radiation and chemotherapy has shown promise. Outcome of CC among large population in the United States outside context of clinical trials has not been reported. We examined survival trends of CC patients among a population based registry. Methods: Surveillance, Epidemiology, and End Results (SEER) histology codes C22.1 and C24.0 for intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC) respectively were used to identify cases between 1973 and 2004. SPSS statistical software used for analysis. Kaplan-Meier estimates were used for median overall survival (OS). Variables included were age, race, sex, stage, and year of diagnosis. Results: Between 1973 and 2004 there were 13,676 cases of CC included in the SEER database. Of those 7,113 (52%) were males and 6,463 (48%) were females. Majority cases were white (11,199 (81.9%) while 842 (6.2%) were black. EHCC was more common with 8,308 (60.7%) while IHCC comprised 5,368 (39.3%) cases. Most common histology groups were adenocarcinoma and adenoma with 11,524 (84.3%) cases while the second most common was epithelial neoplasm with 1,057 (7.7%) cases. AJCC staging information was missing in 12,590 (92.1%). In the period 1973–94, 5619 (41.1%) cases were diagnosed, 2720 (19.9%) between 1995–99 and 5337 (39.0%) between 2000–04. Median OS for IHCC and EHCC was 4 and 6 months respectively (p<0.001). Male patients had a median OS of 5 months compared to 6 months in females (p<0.001). Median OS for white and black patients was 5 and 4 months respectively. Interestingly survival in the three time periods defined was very similar (1973–1994 = 5 mo, 1995–1999 = 6 mo and 2000–2004 = 5 mo). In Cox regression analysis year of diagnosis was not an independent predictor of survival while race, primary site and sex were. Conclusions: Outcome of cholangiocarcinoma remains dismal. EHCC has slightly better survival than IHCC. Recent advances in surgical technique, radiation and newer chemotherapeutic agents which has improved survival in many other cancer types has not shown an improvement in cholangiocarcinoma based on this population analysis. No significant financial relationships to disclose.
Inhibition of phorbol ester--induced human epidermal ornithine decarboxylase activity by oral compounds: a possible role in human chemoprevention studies.
Authors: C L Loprinzi, A K Verma, R K Boutwell, P P Carbone
Journal: Journal of Clinical Oncology (1985)

Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.
추계학술대회 초록집 : 대한간학회 학술연구기금 당선과제 발표 ; HBsAg 양성인 간경변 환자의 간세포암종 발생에 있어 음주의 역할과 HBsAg 음성, anti-HCV 음성인 알코올간경변 환자의 간세포암종 발생에 있어 B형간염 바이러스 잠재감염의 의미
Authors: 김주현 ( Ju Hyun Kim )
Journal: Clinical and Molecular Hepatology (2006)
A first-in-human, open-label, phase I/II safety, pharmacokinetic, and proof-of-concept study of ARN-509 in patients with progressive advanced castration-resistant prostate cancer (CRPC).
Authors: D. E. Rathkopf, D. C. Danila, S. F. Slovin, M. J. Morris, J. E. Steinbrecher, Y. Chen, M. Fleisher, S. M. Larson, C. L. Sawyers, H. I. Scher
Journal: Journal of Clinical Oncology (2011)

TPS190 Background: The results of molecular profiling studies show that androgen receptor (AR) overexpression is associated with resistance to conventional anti-androgens such as bicalutamide (Nat Med 10:33-39, 2004). ARN-509 is a novel small molecule AR antagonist that lacks the partial agonist activity seen with bicalutamide in the context of AR overexpression, an in vitro mimic of castration resistance. In addition, ARN-509 reduces the efficiency of nuclear translocation, and impairs AR binding to DNA and AR target gene modulation, thereby inhibiting tumor growth and promoting apoptosis. A phase I/II clinical trial of continuous oral ARN-509 in patients with progressive CRPC with and without prior chemotherapy began in July 2010. Methods: The study is designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor effects of ARN-509 in patients with progressive CRPC. In the dose escalation phase, patients are assigned using standard 3x3 dose escalation criteria to receive oral ARN509 at the following dose levels: 30, 60, 90, 120, 180, 240, and 300 mg. The primary objective is to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ARN-509 that leads to a DLT in a maximum of 30% of patients. Pharmacokinetic (PK) analysis is performed after a single dose of ARN509 in week-1. Correlative studies include circulating tumor cells, optional FDG and FDHT PET imaging, and optional tumor biopsies. Following completion of the dose escalation phase, three expansion cohorts will be enrolled at the RP2D to provide an initial signal of anti-tumor activity with a time to PSA progression endpoint. The three expansion cohorts include: 1) non-metastatic CRPC docetaxel (doc) and abiraterone (abi)-naive (50 patients); 2) mCRPC doc and abi-naive (20 patients); and 3) mCRPC abi pre-treated (10-20 patients). The effect of food on the PK of ARN-509 and the effect of ARN-509 on ventricular repolarization will be evaluated in the expansion phase. The escalation phase is ongoing; enrollment to cohort 4 (120 mg) began in January 2011.DOD/PCF PCCTC trial sponsored by Aragon Pharmaceuticals. NCT01171898.
Abstract 289: The combination of CD40 agonism and PD-L1 blockade enhances anti-tumor immunity in a mouse syngeneic orthotopic pancreatic tumor model
Authors: Nadia Luheshi, Jane Coates-Ulrichsen, James Harper, Gareth Davies, James Legg, Robert Wilkinson
Journal: Cancer Research (2015)

Abstract Infiltration of immunosuppressive myeloid cells into tumors correlates with poorer prognosis in many cancer types. The immunosuppressive effects of these cells help to create a microenvironment that may inhibit responses to T cell-directed immunotherapies. Anti-CD40 agonistic antibodies (αCD40) promote myeloid cell maturation, license cross-presentation of antigens to cytotoxic T cells, and enhance direct macrophage tumoricidal activity. We tested the hypothesis that αCD40 can improve responses to PD-L1 blockade via enhancing anti-tumor immunity in a syngeneic orthotopic mouse model of pancreatic cancer (Pan02). Whilst PD-L1 blockade alone had limited effect on tumor growth, we demonstrated that αCD40 drove antigen presenting cell maturation and systemic immune activation, inhibiting tumor growth and improving overall survival. αCD40 also induced upregulation of PD-L1 both systemically and within the tumor microenvironment. Furthermore, the combination of αCD40 and PD-L1 blockade led to enhanced tumor growth inhibition and improved anti-tumor immunity compared to either monotherapy alone. These data provide further support for the potential benefits of re-educating tumor myeloid cells. Citation Format: Nadia Luheshi, Jane Coates-Ulrichsen, James Harper, Gareth Davies, James Legg, Robert Wilkinson. The combination of CD40 agonism and PD-L1 blockade enhances anti-tumor immunity in a mouse syngeneic orthotopic pancreatic tumor model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 289. doi:10.1158/1538-7445.AM2015-289
Enhancement of Skin Tumorigenesis by Cigarette Smoke Condensate Following β-Irradiation in Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J F McGregor
Journal: JNCI Journal of the National Cancer Institute (1982)

The tumor-promoting ability of cigarette-smoke condensate (CSC) has been demonstrated in rat skin after beta-irradiation. Skin tumors from male albino Charles River CD rats (outbred Sprague-Dawley descended) were classified into 2 groups: carcinomas and other noncarcinoma tumors. A statistically significant increase (P less than 0.01) in tumor yield occurred after CSC treatment that began 2 months after irradiation. This finding confirmed our previously published pilot observation. Extension of the pilot experiment to obtain data on carcinoma yield and an experiment to observe the effects of CSC treatment beginning immediately after irradiation were performed. When CSC treatment began immediately after irradiation, the yield of noncarcinoma tumors was significantly reduced (P less than 0.01), whereas the carcinoma yield increased but statistically not significantly (P = 0.12). The increased yield of noncarcinoma tumors is attributed to a significant increase (P less than 0.01) of acute ulceration caused by CSC on recently irradiated skin. The increase in carcinoma yield resulted from an increase in the rate of conversion of noncarcinoma tumors to cancer. Carcinoma yield was also increased by CSC treatment beginning 2 months after irradiation, but the increase was not significant (P = 0.08). The lack of statistical significance for the carcinoma yields in both experiments may be ascribed to the insufficient number of cancers produced by the treatments. The relative ratios of cancer yields (1.7 and 2.5) did not differ greatly from the 2.2 ratio for the increase of noncarcinoma tumors. The possible relevance of the findings to human carcinogenesis is discussed.
만성 B형 간염환자에서 인터페론 치료후 장기적 관찰
Authors: 연종은(Jong Eun Yeon), 서연석(Yeon Seok Seo), 김윤홍(Yoon Hong Kim), 박상훈(Sang Hoon Park), 권오상(Oh Sang Kwon), 변관수(Kwan Soo Byun), 이창홍(Chang Hong Lee)
Journal: Clinical and Molecular Hepatology (1999)

Background/Aims : Several randomized controlled studies have shown that responders who had treated with interferon alpha for chronic hepatitis B had better rate of sustained loss of HBeAg and HBV DNA than non-responders. These studies also showed that non-responders had higher rates of liver related complication and mortality. But there is very little data on how well sustained responders are and whether the responders eventually lose HBsAg in Korea. The aims of this study were to better define the long term remission of chronic hepatitis B induced by interferon alfa therapy and compare the clinical outcome among the interferon responders and non-responders in Korea. Methods : Sixty-eight patients with chronic hepatitis B who were treated with interferon alfa between 1987 and 1998 were followed up for serologic status (HBsAg, HBeAg, HBV DNA), biochemical tests and liver related complication or mortality. Results : Among 68 patients with chronic hepatitis B who were treated with interferon alfa, 28 (41%) responded to treatment with loss of HBeAg within 1 year of starting treatment. Up to 129 months (mean 58 months) after therapy, responders had higher rate of cumulative clearance of HBeAg at five years than non-responders (100% vs 35.1%, p<0.05). Responders had maintained the normal serum ALT than nonresponders at five years (94% vs 55.6%, p<0.05). Loss of HBsAg was not different between responders and non-responders (5% vs 4%, NS). The rates of liver related complication and mortality did not differ between both groups. Delayed clearance of HBeAg occured in twelve out of forty non-responders (30%). There were no differences in age, baseline ALT, histologic finding of liver biopsy, HBV DNA at the end of first year after study with IFN therapy between the non-responders with and without delayed clearance of HBeAg. Conclusion : Remission in chronic hepatitis B induced by alfa interferon maintained in long duration. But clinical outcomes such as liver related complication, mortality and the elimination of HBV infection have no differences between responders and non-responders. Further studies are needed for the role of interferon therapy in long-term clinical outcome for chronic hepatitis B. (Korean J Hepatol 1999;5:12－21)
Highly Elevated IL-18 Is a Reliable Predictor of Progression to Hemophagocytic Syndrome in the Patients with Langerhans Cell Histiocytosis
Authors: Yasuhiro Ikawa, Raita Araki, Toshihiro Fujiki, Masaki Fukuda, Shintaro Mase, Rie Kuroda, Hideaki Maeba, Shoichi Koizumi, Akihiro Yachie, Ryosei Nishimura
Journal: Blood (2014)