tbuckley/cabot-search huggingface dataset:
PTH-316 Management of colorectal polyp cancers: Abstract PTH-316 Table 1
Authors: PC Sivathondan, N-R Warner, W Hameed, DR McGrath
Journal: Gut (2015)

<h3>Introduction</h3> Management of colorectal polyp cancers is variable, with no clear consensus on whether endoscopic mucosal resection (EMR) or local resection is optimal. We studied the outcome of 42 patients with colorectal polyp cancers in our hospital over a 3year period. <h3>Method</h3> 42 cases of malignant colorectal polyps between May 2012 and May2014 were identified retrospectively from the histology database. Data was collected on polyp morphology and histology including resection margin, tumour grade, lymphovascular invasion and Haggitt/Kikuchi level of invasion. All specimens were examined by a single histopathologist. Adverse oncological outcome was defined as residual tumour at the polypectomy site and/or lymph node metastases in the surgical group and local/distant recurrence in the surveillance group. Post operative morbidity and method and timing of surveillance were documented. <h3>Results</h3> 42 polyps (22 male and 20 female patients, mean age: 68 years, range: 33 to 90 years) were included. 59% of polyps appeared pedunculated at endoscopy with 27% sessile and 14% described as a “lesion.” 5 patients had radiological evidence of metastases. 43% of tumours were visible on imaging with 19% having mesorectal/presacral nodes. 13 patients underwent colonic resection. 8 of those had pedunculated polyps, 5 had sessile polyps. In 7 patients who underwent colectomy, polypectomy or EMR had been performed. Morbidity included 3 stomas (all reversed), 2 anastomotic leaks, 1 wound infection and 1 high output stoma. There were no deaths. Endoscopic resection was the sole treatment in 29 patients; 7 patients with sessile polyps, 17 patients with pedunculated polyps and 5 with “lesions.” Follow up was by imaging only in 15 patients, endoscopy only in 9 patients and a combination of imaging and endoscopy in 11 patients. 6 patients had no follow up. <h3>Conclusion</h3> This study illustrates the varied management of malignant colorectal polyps. It is clear that resection margins adversely affect outcome. A strategy is needed for managing patients with clear resection margins, including nature and timing of follow up. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Williams J. G, <i>et al</i>. Managament of the Malignant colorectal polyp: ACPGBI position statement. Colorectal Dis. 2013;15:1–38 Naqvi S, <i>et al</i>. Management of colorectal polyp cancers. Ann R Coll Surg Engl. 2012;94:574–578
Expression of prostate specific membrane antigen in the neo-vasculature of non-prostate cancers
Authors: J. S. Ross, D. Schenkein, I. Webb, G. Gray, J. Deeds, R. Meyer, A. McDonald, C. Sheehan, K. Gray
Journal: Journal of Clinical Oncology (2004)

3110 Background: Prostate specific membrane antigen (PSMA), a transmembrane folate hydrolase consisting of 750 amino acids, has been consistently detected in normal and hyperplastic prostate tissues, in pre-cancerous lesions and prostate cancer (PCa) using immunohistochemistry and other techniques. The expression of PSMA in Non-PCa is currently being pursued as a target for diagnostic imaging and anti-cancer antibody therapeutics. Methods: PSMA expression was measured on a series of fresh frozen and formalin-fixed paraffin embedded non-PCA malignancies by transcriptional profiling (TP) using cDNA microarrays on nylon membranes, RT-PCR (Taqman), in situ hybridization (ISH), western blotting, dual co-localization immunofluorescence (IF) and immunohistochemistry (IHC) both before and after laser capture microdissection (LCM) using both internal domain (7E11) and external domain (MLN591) antibodies. Results: PSMA mRNA expression was localized to the neo-vasculature in 55% of a series of breast, colon, lung and ovarian cancers using an S-35 labeled probe and ISH. PSMA mRNA expression was localized to the endothelium of the tumor vessels after microdissection using Taqman™ RT-PCR . 40% of the same carcinomas were positive for PSMA immunoreactivity of the tumor vasculature by IHC on frozen sections with the MLN591 antibodyDual IF studies using the MLN591 antibody and anti-CD31 (PECAM-1) localized PSMA expression to the endothelium of neo-vasculature in carcinomas of the breast, colon, lung and ovary, in Wilm's tumors and neuroblastomas. Using the 7E11 antibody on paraffin sections, PSMA staining was observed in 9/10 clear cell renal cell carcinomas, 7/10 infiltrating ductal breast cancers, 6/10 invasive colorectal cancers and 4/10 non-small cell lung cancers. Conclusions: PSMA expression is regularly associated with the neo-vasculature of many non-PCas and co-localizes with endothelial cell markers. Further studies of PSMA in non-PCa as a target for both diagnostic imaging and anti-cancer antibody-based therapies appear warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc.
Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance
Authors: J M Piot, M Royer, A Schmidt-Tanguy, E Hoppé, M Gardembas, T Bourrée, M Hunault, S François, F Boyer, N Ifrah, G Renier, A Chevailler, M Audran, D Chappard, H Libouban, G Mabilleau, E Legrand, B Bouvard
Journal: Blood Cancer Journal (2015)

Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.
Oropharyngeal mucositis prophylaxis in combined radioimmunochemotherapy.
Authors: I. Wildfang, B. Tschechne, J. Borghardt, S. Fanaei, H. Zakaria, S. Luft, W. Jordan
Journal: Journal of Clinical Oncology (2010)

e19613 Background: Our experience with the chemotherapeutic treatment of head and neck cancer especially under concomitant radio- and immunochemotherapy showed that nearly all patients display strong mucositic adverse reactions (grade 3/4) additional to other side effects. In severe cases the oropharyngeal mucositis leads to a therapy interruption or even to a discontinuation caused by secondary local or systemic infections. Mucositis associated pain symptoms also limit the QoL significantly. To prevent or reduce the mucositis and its side effects we treated 129 patients next to our standard antimycotics/ panthenol solution additionally with a polyvinylpyrrolidone (PVP) and sodium hyaluronate containing oral gel (Gelclair). The patient collective contained an unselected group of diverse tumor stages, health status and comorbidities. Methods: 129 patients received the oral gel as a mouth rinsing solution (15 ml) 4 times daily 10 min after antimycotics (1 ml containing 100 mg amphotericin B) and panthenol-solution (10 ml containing 500 mg Dexpanthenol). The treatment started simultaneously with radiotherapy and was discontinued 4 weeks after the end of the radiotherapy. Results: In consequence 117 patients were evaluable. Under this treatment we observed in 96 patients only mild cases of oropharyngeal mucositis. In 16 patients we observed a grade III mucositis and in 5 patients a grade IV mucositis. There were no specific side effects of the oral gel observed and all patients were mostly compliant. In 14 cases therapy had to be interrupted because of a severe mucositis (grade III/ IV). 11 patients had therapy interruptions or discontinuation for other reasons. Conclusions: A prophylactic treatment of head and neck cancer patients receiving a combined radioimmunochemotherapy with a polyvinylpyrrolidone (PVP) and sodium hyaluronate containing oral gel additionally to antimycotics / panthenol seems to effectively reduce most commonly observed mucositis and leads to an improved patient compliance and increases their QoL. Rates of infections and pain symptoms decrease significantly. No significant financial relationships to disclose.
Nephrocystin
Authors: EDGAR OTTO, ANDREAS KISPERT, SILVIA SCHA[Combining Diaeresis]TZLE, BIRGIT LESCHER, CORNELIA RENSING, FRIEDHELM HILDEBRANDT
Journal: Journal of the American Society of Nephrology (2000)

Juvenile nephronophthisis, an autosomal recessive cystic kidney disease, is the primary genetic cause for chronic renal failure in children. The gene (NPHP 1) for nephronophthisis type 1 has recently been identified. Its gene product, nephrocystin, is a novel protein of unknown function, which contains a src-homology 3 domain. To study tissue expression and analyze amino acid sequence conservation of nephrocystin, the full-length murine Nphp 1 cDNA sequence was obtained and Northern and in situ hybridization analyses were performed for extensive expression studies. The results demonstrate widespread but relatively weak NPHP 1 expression in the human adult. In the adult mouse there is strong expression in testis. This expression occurs specifically in cell stages of the first meiotic division and thereafter. In situ hybridization to whole mouse embryos demonstrated widespread and uniform expression at all developmental stages. Amino acid sequence conservation studies in human, mouse, and Caenorhabditis elegans show that in nephrocystin the src-homology 3 domain is embedded in a novel context of other putative domains of protein-protein interaction, such as coiled-coil and E-rich domains. It is concluded that for multiple putative protein-protein interaction domains of nephrocystin, sequence conservation dates back at least to Caenorhabditis elegans. The previously described discrepancy between widespread tissue expression and the restriction of symptoms to the kidney has now been confirmed by an in-depth expression study.
A phase I first-in-human study of REGN910, a fully human and selective angiopoietin-2 monoclonal antibody, in patients with advanced solid tumor malignancies.
Authors: K. P. Papadopoulos, N. G. Chau, A. Patnaik, L. Adriaens, A. S. Lalani, C. Daly, L. L. Siu
Journal: Journal of Clinical Oncology (2011)

TPS159 Background: Angiopoietin-2 (Ang2) is a secreted growth factor that functions as a critical regulator of angiogenesis, blood vessel maturation and integrity of the vascular endothelium. The elevated expression of Ang2 in the vasculature of human tumors, as opposed to very limited expression in normal tissues, makes it an attractive target for interventional antiangiogenic cancer therapy. We have generated a fully-human, Ang2 monoclonal antibody (REGN910) which selectively binds human Ang2 with high affinity and potently blocks signaling through the Tie2 receptor. In preclinical studies, REGN910 treatment significantly inhibits the growth of multiple tumor xenografts, including PC3 (prostate), Colo205 (colorectal) and A431 (epidermoid carcinoma) tumors, and has dramatic effects in reducing the number and/or function of tumor-associated blood vessels in vivo. This report describes an ongoing first-in-human study of REGN910 in patients with histologically or cytologically confirmed diagnosis of advanced solid malignancy and who have previously failed conventional therapeutic options. Methods: This two-center phase I study employs a standard 3 + 3 dose escalation design exploring 4 sequential dose escalation cohorts. Once the recommended phase II dose (RP2D) is determined, an additional 10 patients will be enrolled in an expansion safety cohort, for a planned total enrollment of 34 patients. The primary study objectives are to characterize safety and to determine the RP2D of REGN910 administered intravenously every 2 weeks in patients with advanced solid tumors. Secondary endpoints include characterization of the pharmacokinetics and immunogenicity of REGN910, in addition to exploring preliminary antitumor activity and evaluating correlative pharmacodynamic biomarkers related to REGN910 treatment. Updated enrollment status will be presented.
Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: A single-center experience.
Authors: S. M. Alam, R. S. Fehrmann, D. Olmos, K. Shah, M. Puglisi, D. Sarker, A. Brunetto, S. Postel-Vinay, R. D. Baird, L. R. Molife
Journal: Journal of Clinical Oncology (2010)

2519 Background: Phase I oncology trials are designed to define the maximum tolerated dose and toxicity of new drugs. This study aims to define the risk of toxicity in phase I trials of novel molecularly targeted agents (MTA), as this therapeutic approach is becoming increasingly relevant. Methods: We performed a retrospective analysis of toxicity data from all patients (p) treated in phase I trials. The primary aim was to define the rate of treatment-related grade (g) 3 and 4 toxicities and deaths associated with novel single agent MTAs. Results: 1,145 p were treated within a phase I trial between January 2005 and October 2009. Of these, 727 p were treated with novel MTAs; here we report on complete toxicity data from an initial 173 sequential p treated within 37 trials of agents targeting growth factor receptors, angiogenesis, cell cycle/apoptosis, cytoplasmic signaling proteins, chromatin remodeling/DNA repair, protein folding and degradation and oncolysis. The median age was 60 years (range 24-85); 88 female/85 male. 158 p were ECOG PS 0-1 and 15 PS 2. 40 g3 (rate 23%) and 3 g4 (rate 1.7%) treatment-related events occurred. There was 1 treatment-related death (mortality, 0.6%). 49% of all events were gastrointestinal in origin (nausea and diarrhea), 18% neurological (including fatigue), 13% cardiac (hypertension and ECG changes), and 2% (each) renal, respiratory and cutaneous. 42 of 43 (97.7%) events resolved with dose interruption or dose reduction. Conclusions: Therapy with novel MTAs in the phase I setting is associated with a moderate risk of significant toxicity, though this appears less than in phase I studies involving cytotoxic agents, particularly in relation to g4 toxicity (Horstmann et al, N Engl J Med 2005). The majority of these toxicities were easily managed with dose interruption/reduction. The risk of death is low and in line with that reported in other published series. No significant financial relationships to disclose.
Treatment of unresectable thymoma with neoadjuvant octreotide LAR.
Authors: B. Schalke
Journal: Journal of Clinical Oncology (2010)

e13540 Background: Long-term survival in patients (pts) with thymoma (thym) depends on R0 resection. R0 resection is limited by infiltration or tight adhesion into neighbouring organs. This can result in the inability to resect, pts are left with limited treatment options. Most thym are positive for the somatostatin receptors in the SMS-scintigraphy. Octreotide + prednisolone has been shown to block SMS-receptors and induce thym volume reduction. Methods: Patients with thym WHO type A, B, C where treated in an open, prospective, phase II study with octreotide LAR 30mg every 2 weeks i.m. + prednisolone p.o. 0.6mg/kg/day. Simon two stage design was applied, the planned enrollment is 25 patients with 15 patients in the first phase. Duration of therapy was 24 weeks. Volumetric analysis of tumor volume by computed tomography was performed at week 0/ 6 /12 / 18/ 24. Primary endpoint was tumor volume reduction of > 20%. Secondary endpoint was the safety of the combination. Results: 14 patients have been enrolled as of Dec. 2009, 13 pts. were evaluable, all 13 met the primary endpoint of tumour volume reduction ≥ 20% with a median reduction of 52.61%. The treatment was well tolerated and reported adverse events were associated with the known side effects of prednisolone therapy. Conclusions: Neoadjuvant treatment in patients with thym (WHO A,B,C) with Octreotide LAR 30mg every 2 weeks plus prednisolone appears to be a potential effective treatment option for primary unresectable thym, as it provided reduction in tumour volume and permitted surgical resection in patients thought to be inoperable. Octreotide LAR 30mg + prednisolone therapy was well tolerated. This combination may provide a viable neoadjuvant treatment option for patients with advanced thymand further investigation is warranted. Supported by Novartis/ Germany. No significant financial relationships to disclose.
Association of Admission to Veterans Affairs Hospitals vs Non–Veterans Affairs Hospitals With Mortality and Readmission Rates Among Older Men Hospitalized With Acute Myocardial Infarction, Heart Failure, or Pneumonia
Authors: Sudhakar V. Nuti, Li Qin, John S. Rumsfeld, Joseph S. Ross, Frederick A. Masoudi, Sharon-Lise T. Normand, Karthik Murugiah, Susannah M. Bernheim, Lisa G. Suter, Harlan M. Krumholz
Journal: JAMA (2016)

Little contemporary information is available about comparative performance between Veterans Affairs (VA) and non-VA hospitals, particularly related to mortality and readmission rates, 2 important outcomes of care.
Evaluation of the respiratory function in a population with mild/moderate Parkinson's disease
Authors: Giuseppe Emanuele La Piana, Michele Gennuso, Felice Autera, Flora Agostino, Sabrina Moretti, Vanessa Raimondi, Alessandro Prelle, Alessandro Scartabellati, Stefano Aiolfi
Journal: European Respiratory Journal (2014)

Background : Parkinson9s disease (PD) is a common disabling and progressive neuro-degenerative disorder. Morbility and mortality are frequently associated with pulmonary dysfunction, but there is no conclusive evidence regarding the effective alteration on lung function while awake and during sleep, particularly in the first stages of disease.   Methods : 10 pts (6 M) with a mild/moderate stage of PD (Hoen & Yahr scale score ≤ 2.5); BMI 30±5, Age 66±7 (6 non-smokers, 4 ex smokers), underwent PFT + DL CO  + VC in supine position, MIP, MEP, ABG, ESS and fullnight polisomnography. The next day continuous pulse-oximetry and actigraphy exam for 24 h were recorded, together with cognitive and attention tests.   Results:  We did not find significant alteration in PFT, MIP, MEP, ABG and in daily pulse-oximetry; PSG data showed AHI=9±9 ev/h; RDI=25±17; time spent with SaO2 ‹90% (CT 90)= 3±5; nr. of SaO2dips ›3%/h 7±5 and a low sleep efficiency 55±12; the 24 h actigraphy recording showed a low daily physical activity = 3.4±1.2 h. A correletion was found between RDI and the psycological score, particularly with regards to attention tests (TMTB) (p‹0.05 R 2 =0.62) and global evaluation of frontal function (FAB) (p‹0.05 R 2 =0.59)   Conclusions : We observed a low prevalence of obstructive sleep apnea and hypopneas, and a high prevalence of flow limitation related to arousals (RERAs). Our data suggest a good correlation with RDI and some phycological test scores during the day. The reduction of physical activity during the day could be related to alterated rostral fluid shift and sleep disorders breathing, addressing to new alternative treatment to CPAP in patients with initial PD and SDB.
Does capecitabine plus cisplatin (XP) give advanced or recurrent gastric cancer (AGC) patients higher early tumor shrinkage (ETS) rate than S1 plus cisplatin (SP) with safety?
Authors: Naotoshi Sugimoto, Tetsuhiro Yoshinami, Sachiko Yamamoto, Toshinari Yagi, Fumio Imamura
Journal: Journal of Clinical Oncology (2015)

172 Background: Capecitabine plus cisplatin (XP) is defined as the platform regimen in many global trials (ex: ToGA, AVAGAST) for AGC in first-line setting. But in the Japanese Gastric Cancer Treatment Guideline (4th edition), S-1 plus cisplatin (SP) is mentioned the standard (recommendation 1), XP is considered as recommendation 2. Few reports were existed about the comparison between XP and SP. So we retrospectively compared the efficacy and toxicity of XP and SP for patients with AGC in our hospital. Methods: The selection criteria were pathologically proven AGC (HER2 negative or unknown); no previous chemotherapy; performance status 0-2; able to oral intake; and adequate organ functions. The patients in XP group, capecitabine 1,000mg/m2 was given orally twice daily for 14days followed by a 7-day rest; cisplatin 80mg/m2 on day1 was given by intravenous infusion. In SP group, S1 40mg/m2 was given orally twice daily for 21 days followed by a 14-day rest and cisplatin 60mg/m2 intravenous infusion on day8. Results: The analysis covered 115 patients over the period from May 2008 to June 2014. The median age was 64 years (range 22-81); 76 males and 39 females; PS 0/1/2 score 85/29/1; 31 patients were treated XP and 84 patients were treated SP. Progression-free survival and overall survival were 6.6 and 16.4 months with XP and 6.1 and 13.3 months with SP (no significant difference). The response rates were XP/SP 61%/50%. The ETS (over 20% tumor shrinkage in 6-8weeks) rate were 83% in XP and 61% in SP (p=0.09). The rate of grade 3-4 toxicity in XP/SP were; neutropenia 23%/15%, anemia 16%/20%, nausea 0%/3%, anorexia 3%/ 8%, fatigue 0%/ 4%, hyponatremia 3%/ 0%. There was no treatment death in both groups. Conclusions: It is suggested that XP give AGC patients high ETS rate with safety.
Thyroid Hormones and Experimental Cancer Cachexia&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G Svaninger, P A Lundberg, K Lundholm
Journal: JNCI Journal of the National Cancer Institute (1986)

The relationship between circulating thyroid hormones and nutritional status was studied in sarcoma-bearing inbred C57BL/6J mice and control mice. Supplementation with exogenous thyroxine (T4) was also evaluated. Tumor-bearing animals had depressed levels of circulating thyroid hormones. This was also found in food-restricted (pair-fed and pair-weighed) controls. Plasma levels of thyroid hormones decreased with increased tumor burden. Thyrotropin-releasing hormone caused an increased response of thyroid-stimulating hormone in tumor-bearing animals. Low levels of thyroid hormones in sarcoma-bearing mice were due to depressed hormone production by the thyroid gland rather than to increased clearance rate of hormones. Plasma levels of triiodothyronine (T3) correlated to the amount of whole-body nitrogen among sarcoma-bearing mice and food-restricted controls. Exogenous T4 increased food intake by 20% in sarcoma-bearing mice. The benefit of this was probably counteracted by an increased metabolic rate, since reversal of plasma levels of T3 and free T4 had no net effect on body composition of freely eating sarcoma-bearing mice, although it had a negative effect on body and muscle composition in food-restricted controls. Exogenous T4 did not stimulate tumor growth. The results indicate that low circulating levels of thyroid hormones in experimental cancer cachexia are probably caused by the reduced food intake (anorexia), which is in agreement with findings in clinical cancer. Depression of thyroid hormones is probably a physiological means to reduce energy expenditure and to preserve substrates in progressive cancer disease.