tbuckley/cabot-search huggingface dataset:
OC-001 Endoscopic balloon dilatation for crohn’s disease strictures: a systematic review and meta-analysis
Authors: P Morar, O Faiz, J Warusavitarne, S Brown, R Cohen, D Hind, J Abercrombie, K Ragunath, DS Sanders, I Arnott, G Wilson, S Bloom, N Arebi
Journal: Gut (2015)

<h3>Introduction</h3> Endoscopic balloon dilatation (EBD) is a recognised treatment for symptomatic Crohn’s strictures. Several case studies report its short term and long term efficacy. A systematic analysis of the literature is needed to define overall efficacy and inform future study design. The primary objective was to examine symptomatic response, technical response and adverse events of EBD. The impact of stricture characteristics on outcome was also explored. <h3>Method</h3> A systematic search was performed in accordance with PRISMA guidelines. The quality of individual studies was assessed using the Newcastle-Ottawa Scale. The results were expressed as a per patient analysis using the proportion of patients within a group and a per study analysis using pooled event rates across studies. The random effects model was expressed as forest plots and summative statistics. Heterogeneity across studies was assessed numerically (I<sup>2</sup>). The mean value of pooled outcomes was used to create two groups (&lt; or ≥ the pooled mean event rate [PMER]), to compare the effect of the proportion of patients within each group (e.g. stricture activity and type) on outcome. <h3>Results</h3> Twenty-five studies were included: 1089 patients and 2664 dilatations. The grade for quality ranged from 2 to 6. The proportion of patients with symptomatic and technical response was 63.9% (393/615) and 92.6% (403/435) respectively. The proportion of patients with perforation was 2.6% (18/700). The PMER for symptomatic response was 74.8% (95% CI: 69.9–79.3%; I2: 0%), technical response was 90.6% (95% CI: 87.8–92.8%; I2: 11.7%), complications was 6.4% (95% CI: 5.0–8.2; I2: 4.0%), and perforation was 3% (95% CI: 2.2–4.0%; I2: 0%). The proportion of patients with active strictures demonstrating a &lt; PMER and ≥ PMER for symptomatic response was 73% vs 60% respectively. The proportion of patients with active strictures demonstrating a ≥ PMER and &lt; PMER for perforation was 62% and 36% respectively. The proportion of patients with anastomotic strictures demonstrating a &lt; PMER and ≥ PMER for technical response was 83% and 75% respectively. <h3>Conclusion</h3> EBD for symptomatic Crohn’s strictures shows high efficacy with a low complication rate. Efficacy may be affected by active inflammation and previous surgery. Variation exists in the quality of reporting of the studies. Further well designed comparative studies capturing differential effects of stricture types are needed. <h3>Disclosure of interest</h3> None Declared.
WHO urged to define responsibility during emergencies
Authors: Anne Gulland
Journal: BMJ (2016)

The World Health Organization has been urged to draw up clear lines of responsibility and accountability in its plans for reform in the light of the outbreak of Ebola virus disease.

At this week’s meeting of WHO’s executive board in Geneva, delegates discussed the organisation’s plans after the widespread criticisms of its handling of the epidemic in west Africa. 

Director general Margaret Chan unveiled a new programme to oversee WHO’s work in emergency risk management. Its mission will be to help member states manage these risks and to lead an international, coordinated health response where …
A genotype-directed phase I study of irinotecan in advanced cancer patients
Authors: F. Innocenti, L. Janisch, S. Das, J. Ramirez, L. House, M. L. Maitland, R. Salgia, M. J. Ratain
Journal: Journal of Clinical Oncology (2007)

2502 Background: The risk of severe toxicity of irinotecan is in part related to the presence of common polymorphisms in UGT1A1, which codes for the enzyme responsible for the inactivation of SN-38, the active metabolite of irinotecan. The most common polymorphism in non-Asian populations is an extra TA repeat in the promoter (7 vs. 6), which reduces the enzyme expression. The three most common genotypes are: 6/6 (40–50%), 6/7 (40–50%), and 7/7 (10–15%). The 7/7 genotype confers the highest risk of toxicity, and it has been suggested that dose reduction is appropriate for patients with this genotype. As one published study has suggested that doses up to 500 mg/m 2 q3w can be tolerated by some patients, we hypothesized that higher doses can be safely administered based on genotype by excluding patients with the 7/7 genotype. This study seeks to find the maximum tolerated dose (MTD) in patients with 6/6 and 6/7 genotypes. Methods: Advanced cancer patients (5 SCLC, 4 esophageal, 5 other tumors) have been genotyped for the UGT1A1 polymorphism. 6/6 and 6/7 patients have been treated with 700–850 mg (flat dose, corresponding to about 400–500 mg/m 2 ) of q3w irinotecan. Dose-limiting toxicity (DLT) at cycle 1 is defined as grade =3 nonhematological toxicity, grade 4 neutropenia lasting more than 4 days, and febrile neutropenia. Results: Three 6/6 patients tolerated 700 mg (no grade &gt;2 toxicity). Three additional 6/6 patients have been treated at 850 mg, and one DLT (grade 4 neutropenia lasting more than 4 days) was observed; 3 additional 6/6 patients will be enrolled at 850. Six 6/7 patients have been treated at 700 mg, with only one DLT (febrile neutropenia). Two additional 6/7 patients have been treated at 850, and one DLT (febrile neutropenia) has been observed. Conclusions: Higher doses of irinotecan can be safely administered in patients with selected UGT1A1 genotypes. On the basis of these interim results, a phase II trial in metastatic colorectal cancer patients with 6/6 and 6/7 genotypes has been designed to evaluate the efficacy of higher doses of irinotecan. [Table: see text]
Wood-smoke exposure as a survival predictor in non-small cell lung cancer with response to erlotinib: An open label phase II study
Authors: O. G. Arrieta Rodriguez, E. Tellez, L. Martinez-Barrera, P. Castillo, J. Reyes-Contreras, D. Flores-Estrada, N. Hernandez- Pedro, D. Morales-Espinosa, T. Ceron-Lizarraga, J. De la Garza-Salazar
Journal: Journal of Clinical Oncology (2007)

18029 Background: Erlotinib, a tyrosine kinase inhibitor, has improved survival and quality of life in patients with non-small cell lung cancer (NSCLC) after fist-line or second-line chemotherapy. Asian origin, adenocarcinoma histology, female gender, lack of tobacco use and expression of EGFR are significant independent predictors of response to erlotinib. Although tobacco use is considered a major cause of NSCLC, other factors are involved in its pathogenesis. In underdeveloped countries such as Mexico, wood and other solid fuels are still used for cooking and heating. The physiopathological mechanisms of wood smoke exposure (WSE) as a potential risk factor for the development of NSCLC are still unknown. Methods: 125 patients with the diagnosis of NSCLC with poor performance status and after first or second-line chemotherapy were treated with erlotinib. Clinical and pathological characteristics were associated with response. Results: We found a global response to erlotinib in 39 patients (31.2%; IC 95% 23–39.3), stable disease in 33.6% and progression in 33.6%. Clinical improvement and favorable changes in status performance were observed in 54.4 and 33.6%, respectively. The clinical features associated with response to erlotinib in the univariate analysis were female gender (44 vs 15.7% p=0.001), non-smokers (45.6 vs 19%, p=0.001), adenocarcinoma (33.8 vs 16% p=0.009) and WSE (81 vs 14% p=0.001). Only the histological type (p=0.049) and WSE (p=0.001) were of statistical significance in the logistic regression analysis. The factors associated to an improved progression-free survival (PFS) in the Cox multivariate analysis were: adenocarcinoma histology (7.6 ±0.7 vs 2.7 ±0.4 months, p=0.002), female gender (7.6 ±1.3 vs 3.97 ±1.5, p=0.027) and WSE (8.43 ±0.5 vs 4.8 ±0.9, p=0.011). Conclusions: Conclusion: WSE is associated with response to erlotinib in patients with NSCLC and may indicate an improved PFS. The EGFR mutation is probably involved in the development of NSCLC in non-smokers with WSE. No significant financial relationships to disclose.
Result of childhood acute lymphoblastic leukemia protocol (INCTR) from a developing country
Authors: D. Mukhopadhyay, P. Gupta, S. Mukhopadhyay, P. Chitalkar, S. D. Banavali, S. H. Advani, M. Adde, I. Magrath
Journal: Journal of Clinical Oncology (2007)

20015 Background: Acute Lymphatic Leukemia in children is a curable disease in the range of 80–90 % in developed Countries by aggressive protocol like BFM, St. Judes’. In developing Countries like ours, patients can’t tolerate those aggressive protocol because of Socio- economic and nutritional factors. The less aggressive Protocol like INCTR (International Network for Cancer Treatment &amp; Research) are suitable in developing Countries like ours. The aim of our study was to see outcome of childhood ALL patient with INCTR protocol and tolerability of the protocol in Indian-asian population. Methods: We treated 480 Children (age range 1–25 years, median age of 11 yrs) with INCTR Protocol at Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India, a tertiary cancer centre from Eastern India during period from April ’99 to Dec ’06. There was female preponderance in the study. Fever 283 (58.9%), lymphadenopathy 211 (43.9%) and haepatosplenomegaly 153 (31.8%) were the major clinical presentation. Forty-three (8.9%) patients were present with hyper Leukocytosis. C-ALL phenotype were the largest group though the incidence of the T-ALL were quite high (27.9%). Results: Remission induction were seen in 446 (92.9%) of the patient. In a follow-up period of 88 months (with an average of 54 months) the disease-free survival ( DFS) was 66.8% (321 patients) with an overall survival of 73.9% (355 patients). The isolated bone marrow relapse was seen in majority of the cases 40 (8.33%) and the major relapse was in maintenance and first 6 months of completion of therapy. The major cause of morbidity was infection 316 (65.8%) followed metabolic complications 81 (16.8%), hemorrhage 52 (10.8%), neurologic 10 (2.08%), hepatitis 6 (1.25%) and pancreatitis 5 (1.04%). The major cause of the mortality was infection 75%(360 patients) followed progressive disease 7.91% (38 patients) and Hemorrhage 5.83%( 28 patients). Conclusions: The data of acute lymphatic leukemia from a developing country is encouraging. The protocol was well tolerated by India- asian population. No significant financial relationships to disclose.
In memoriam: Vera Peters.
Authors: S B Sutcliffe, M K Gospodarowicz, P J Fitzpatrick
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.2.239 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8113832 In memoriam: Vera Peters. S B SutcliffexS B SutcliffeSearch for articles by this author , M K GospodarowiczxM K GospodarowiczSearch for articles by this author , P J FitzpatrickxP J FitzpatrickSearch for articles by this author Show More Princess Margaret Hospital, Toronto, Canada. https://doi.org/10.1200/JCO.1994.12.2.239 PDF "In memoriam: Vera Peters.." Journal of Clinical Oncology, 12(2), pp. 239–240© 1994 by American Society of Clinical Oncology
Risk of rash and stomatitis with temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor: A meta-analysis.
Authors: C. Gomez Fernandez, Y. Balagula, S. Wu, X. Su, D. R. Feldman, D. E. Rathkopf, M. E. Lacouture
Journal: Journal of Clinical Oncology (2011)

e15031 Background: Temsirolimus, an mTOR inhibitor, is approved for treatment of advanced renal cell carcinoma (RCC). Maculopapular/acneiform rash and stomatitis are the most common mucocutaneous toxicities. We systematically investigated the overall incidence and risk of rash and stomatitis in patients receiving temsirolimus. Methods: Relevant studies were identified from PubMed database (1999-2010) and abstracts presented at the American Society of Clinical Oncology Conferences between 2004 and 2010. A citation database Web of Science was searched to ensure that no relevant studies were missed. Eligible studies were limited to prospective Phase II-III clinical trials and expanded-access programs in which cancer patients received temsirolimus 25 mg weekly as a single agent. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. Results: A total of 579 patients from 10 clinical trials were available for analysis. The overall incidence of all-grade and high-grade (grade ≥3) rash was 46.7% (95% CI: 37.5- 56.1) and 3.2% (95% CI: 1.9-5.3), respectively. The overall incidence of all-grade and high-grade stomatitis was 44.3 % (CI: 32.1- 57.1) and 3.2% (95% CI: 1.9-5.4). Temsirolimus was associated with significantly increased risk of all-grade rash and all-grade stomatitis (RR=7.8, 95% CI: 4.5-13.6; P<0.001 and RR=11.1, 95% CI: 5.6-22.0; P<0.001) when compared to patients treated with IFN. The risk of high-grade rash and stomatitis was increased (RR=13.2, 95% CI: 0.8-219.8 and RR=13.2, 95% CI: 0.8-218.5) with a trend reaching statistical significance (P=0.07). No significant difference in incidence of all-grade rash between RCC and non-RCC patients was noted (42.6%, 95% CI: 18.4-70.9% vs. 47.6%, 95% CI: 39.2-56.2%, respectively, p=0.75). Similarly, no difference in all-grade stomatitis was observed (36.5%, 95% CI: 14.9-65.4% and 47.8%, 95% CI: 35.8-60.1%, respectively, p=0.47). Conclusions: Cancer patients treated with temsirolimus are at significant risk for developing skin rash and stomatitis. Further studies for prevention and treatment of these untoward toxicities are needed.
The role of preoperative grading of hydronephrosis to predict pathologic outcomes in patients undergoing nephroureterectomy for upper tract urothelial carcinoma.
Authors: Y. Ito, E. Kikuchi, N. Tanaka, A. Miyajima, S. Mikami, M. Jinzaki, M. Oya
Journal: Journal of Clinical Oncology (2011)

e15010 Background: In patients with bladder tumors, the presence of hydronephrosis is associated with advanced disease and is a predictor of poor outcome. However, there is limited information addressing whether a similar relationship exists for UTUC. We analyzed the prognostic impact of the grade of hydronephrosis on disease specific survival and evaluated whether the grade of hydronephrosis could predict worse pathological outcomes preoperatively in cases of UTUC treated surgically. Methods: We identified and retrospectively reviewed 91 patients who were evaluated by multidetector CT and/or MRI images preoperatively and treated by nephroureterectomy at our institution from 2000 to 2009. Ipsilateral hydronephrosis was graded as 0 to 4 by two urological radiologists blinded to the clinical outcomes. The associations between the grade of hydronephrosis and the pathological findings and patient outcomes were analyzed. Results: Of the 91 patients, 67 patients (73.6%) had ipsilateral hydronephrosis preoperatively. The grade of hydronephrosis (grade0,1 vs grade2,3,4) was significantly associated with a tumor located in the ureter (44.4% vs 68.8%, p=0.0307), higher pT stage (≥T3) (11.1% vs 54.7%, p=0.0002) and lymphovascular invasion (LVI) positive (11.1% vs 40.6%, p=0.0014). A higher grade of hydronephrosis (≥grade2) was not associated with 5-year disease specific survival (93.3% vs 77.2%, in the counterpart p=0.1696). In preoperative multivariable analysis controlling for patient age, gender, location, grade of hydronephrosis, clinical stage, urine cytology, and tumor length, a higher grade of hydronephrosis was predictive of pathologcal T stage (≥T3) (HR 4.98 p=0.0228), LVI(+) (HR 6.37 p=0.0022), and grade3 (HR 2.98 p=0.0311). Conclusions: The grade of preoperative hydronephrosis in image analysis was associated with features of aggressive disease and predicted an advanced pathological outcome for UTUC. This information could prove to be useful for selecting candidates for neoadjuvant chemotherapy as well as for making decisions concerning surgical options.
<sup>131</sup>I-MIBG with myeloablative chemotherapy for neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) phase I study
Authors: K. K. Matthay, G. Yanik, J. Tan, J. Huberty, B. Franc, J. G. Villablanca, C. P. Reynolds, S. Groshen, R. C. Seeger, J. Maris
Journal: Journal of Clinical Oncology (2005)

8505 Background: To determine the maximum tolerated dose (MTD) and toxicity of 131I-MIBG with CEM (carboplatin, etoposide, melphalan) and autologous transplant (AT). Methods: 24 children age 1.5–16.9 years with refractory MIBG+ neuroblastoma and no prior AT were entered; 22 were evaluable for toxicity and response. 131I-MIBG was given on day 0, CEM days 14 to 17 (doses reduced for GFR<100), and AT on day 21. 131I-MIBG was escalated in a 3+3 Phase I trial design, stratified by GFR. Results: Dose limiting toxicity (DLT) occurred in 1/6 patients at 12 mCi/kg of 131I-MIBG with Grade 4 hypotension, hypoxia, and acidosis after 131I-MIBG alone, due to bulky tumor, with death prior to CEM. At 15 mCi/kg, 0/3 patients had DLT initially and 2/3 had DLT when the level was expanded, for 2/6 DLT: 1 mucositis with intubation, and 1 veno-occlusive disease (VOD), with recovery. At 18 mCi/kg, there were 2/4 DLT: 1 sepsis that resolved and 1 toxic death from multi-organ failure. The MTD for normal GFR was Level 1 with 12 mCi/kg 131I-MIBG, carboplatin 1500 mg/m2, etoposide 1200 mg/m2, and melphalan 210 mg/m2. In the low GFR cohort, the initial dose level using 12 mCi/kg of MIBG had 1/6 DLT with VOD. Four more patients had VOD that did not reach DLT. A dose reduction for this group was proposed, so the MTD for the low GFR cohort was not finalized. The median whole body radiation dose was 211 cGy (range 111–307). All evaluable patients engrafted: median time for neutrophils >500, 10 (range 8–15) days, and for platelets>20,000, 26.5 (range 10–224) days. Six of 22 patients had complete or partial response at day 56 post-AT. Nine patients improved by MIBG scan, with median relative MIBG score of 0.4 (0–0.9). The event-free survival for all patients at 2 and 3 years is 0.41 and 0.28 ±0.11; survival at 3 years is 0.57±0.11, with median follow up of 34.3 months. Conclusions: The combination of 131I-MIBG with myeloablative chemotherapy is tolerable and effective for resistant neuroblastoma. No significant financial relationships to disclose.
Factors Associated with Functional Recovery among Older Intensive Care Unit Survivors
Authors: Lauren E. Ferrante, Margaret A. Pisani, Terrence E. Murphy, Evelyne A. Gahbauer, Linda S. Leo-Summers, Thomas M. Gill
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Most of the 1.4 million older adults who survive the intensive care unit (ICU) annually in the United States face increased disability, but little is known about those who achieve functional recovery.Our objectives were twofold: to evaluate the incidence and time to recovery of premorbid function within 6 months of a critical illness and to identify independent predictors of functional recovery among older ICU survivors.Potential participants included 754 persons aged 70 years or older who were evaluated monthly in 13 functional activities (1998-2012). The analytic sample included 218 ICU admissions from 186 ICU survivors. Functional recovery was defined as returning to a disability count less than or equal to the pre-ICU disability count within 6 months. Twenty-one potential predictors were evaluated for their associations with recovery.Functional recovery was observed for 114 (52.3%) of the 218 admissions. In multivariable analysis, higher body mass index (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.12) and greater functional self-efficacy (HR, 1.05; 95% CI, 1.02-1.08), a measure of confidence in performing various activities, were associated with recovery, whereas pre-ICU impairment in hearing (HR, 0.38; 95% CI, 0.22-0.66) and vision (HR, 0.59; 95% CI, 0.37-0.95) were associated with a lack of recovery.Among older adults who survived an ICU admission with increased disability, pre-ICU hearing and vision impairment were strongly associated with poor functional recovery within 6 months, whereas higher body mass index and functional self-efficacy were associated with recovery. Future research is needed to evaluate whether interventions targeting these factors improve functional outcomes among older ICU survivors.
Phase I study of topotecan for pediatric patients with malignant solid tumors.
Authors: C B Pratt, C Stewart, V M Santana, L Bowman, W Furman, J Ochs, N Marina, J F Kuttesch, R Heideman, J T Sandlund
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors. PATIENTS AND METHODS In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients. RESULTS Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours. CONCLUSION Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.