tbuckley/cabot-search huggingface dataset:
Combination therapy with methotrexate and 5-fluorouracil: a prospective randomized clinical trial of order of administration.
Authors: A S Coates, M H Tattersall, C Swanson, D Hedley, R M Fox, D Raghavan
Journal: Journal of Clinical Oncology (1984)

Because of biochemical and tissue culture evidence casting doubt on the physiologic relevance of reported synergy afforded by sequential administration of methotrexate (MTX) followed by 5-fluorouracil (5-FU), a randomized controlled clinical trial was conducted in 108 patients with advanced cancer, including 70 with squamous cell carcinoma (SCC) of the head and neck, nine with SCC of other primary sites, 24 with colorectal, and five with gastric adenocarcinomas. Patients were randomized to receive weekly therapy consisting of MTX followed one hour later by 5-FU, or 5-FU followed one hour later by MTX. There was a trend to higher tumor response rates in patients treated with MTX before 5-FU (45% v 33% overall; 65% v 39% in patients with previously untreated head and neck cancer), but these differences were not significant, either by chi-square test or by multivariate stepwise logistic regression. The trend in survival favoring the reverse sequence of 5-FU before MTX was not significant in univariate analyses. Stepwise multivariate Cox model analysis showed that Eastern Cooperative Oncology Group performance status at study entry was the major prognostic factor for survival (P less than 0.001), but among the 70 patients with head and neck cancer, the sequence of drug administration was the only other significant prognostic factor for survival, and favored the sequence of 5-FU followed by MTX (P less than 0.025).
Questions about the reliability of ROCKET-AF anticoagulation data
Authors: Constantinos Christopoulos
Journal: BMJ (2016)

Like Cohen, I also worry about the quality of evidence of the ROCKET-AF trial that led to regulatory approval of rivaroxaban for stroke prevention in non-valvular atrial fibrillation.1

In the warfarin treated control group, the mean time in therapeutic range (TTR) was reported to be …
Abstract 10211: Transient Ischemia Increases Transfection Efficiency of Intracoronary Ad5Luc in Pig Heart In Situ
Authors: Jakob Vinten-Johansen, L. Susan Schmarkey, Rong Jiang, Weiwei Shi, Robert L Engler, Gabor M Rubanyi
Journal: Circulation (2010)

Background: Efficiency of intracoronary adenoviral vector (Ad) uptake in the heart may be impaired by permeability barrier function of the vascular endothelium. Substances that increase vascular pe...
Results of surgery for obstructing carcinomatosis of gastrointestinal, pancreatic, or biliary origin.
Authors: A D Turnbull, J Guerra, H F Starnes
Journal: Journal of Clinical Oncology (1989)

Results of operation for obstructing carcinomatosis of gastrointestinal (GI), pancreatic, or biliary origin were reviewed to assess relief of symptoms, management of re-obstruction, and duration of hospitalization. A retrospective review (1977 to 1986) identified 89 patients, 59 (66%) of whom had tumors originating in the colon, and 19 (21%) in the stomach. Normal bowel function was restored for a median of 102 days in 66 patients (74%) and all but four (94%) were discharged. Forty-one (46%) patients remained unobstructed until death. Twenty-three (26%) were not relieved by operation and died a median of 33 days later (P less than .005). Forty-eight (81.4%) of the 59 colon cancer patients and ten (52.6%) of 19 with gastric cancer (P less than .05) were benefited by the operation, although comparison of duration of function was less striking (P less than .1). In-hospital mortality was 13% and complications occurred in 44%. Obstruction recurred in 38% of those relieved by the initial operation. Normal bowel function was restored in six (46%) of 13 patients undergoing a second laparotomy (median, 158 days) and in six of 13 (46%) treated with nasogastric suction. Obstruction recurred again in four of the latter six patients (median, 39 days). Hospitalization averaged 31 days (median, 25 days) for the first procedure and 41 days (median, 39 days) for patients operated for recurrent obstruction. These results justify laparotomy for intestinal obstruction in known or suspected carcinomatosis, particularly of colonic origin, if performance status is compatible with a reasonable quality of life.
Re: Pilat et al.: High-resolution imaging of the optic nerve and retina in optic nerve hypoplasia (Ophthalmology 2015;122:1330-9)
Authors: Piero Barboni, Giacomo Savini, Valerio Carelli, Nicole Balducci, Chiara La Morgia, Francesco Bandello, Alfredo A. Sadun
Journal: Ophthalmology (2016)
Radiologic–pathologic discordance in biopsy-proven usual interstitial pneumonia
Authors: Kunihiro Yagihashi, Jason Huckleberry, Thomas V. Colby, Henry D. Tazelaar, Jordan Zach, Baskaran Sundaram, Sudhakar Pipavath, Marvin I. Schwarz, David A. Lynch
Journal: European Respiratory Journal (2016)

The aim of this study was to compare the clinical, radiological and histological findings in a large population of subjects enrolled during a multicentre study of idiopathic pulmonary fibrosis, with a focus on discordance between imaging and histologic diagnoses of usual interstitial pneumonia (UIP). Two independent radiologists retrospectively reviewed 241 subjects who underwent high-resolution computed tomography (HRCT) and surgical lung biopsies. HRCT findings were classified as UIP, possible UIP and inconsistent with UIP. Histological findings were classified as definite, probable, possible and not UIP. Of the 241 cases, 102 (42.3%) had HRCT findings of UIP, 64 (26.6%) had possible UIP and 75 (31.1%) were inconsistent with UIP. Among those with UIP on HRCT, 99 (97.1%) had histologically definite or probable UIP (concordant group), and 71 (94.7%) of those with “inconsistent” HRCT features had histologically definite or probable UIP (discordant group). Discordant subjects were slightly younger and less likely to be smokers than concordant subjects, but no survival differences were identified. In this population of patients enrolled with a diagnosis of idiopathic pulmonary fibrosis, 94.7% of those with HRCT findings “inconsistent with UIP” demonstrated histological UIP. This suggests that the term “inconsistent with UIP” is misleading.
Moderate dose-escalation of combination chemotherapy with concomitant thoracic radiotherapy in limited-disease small-cell lung cancer: Prolonged intrathoracic tumor control and high central nervous system relapse rate
Authors: H. van de Velde, J.-F. Rosier, Y. Humblet, L. Bosquée, P. Weynants, J.-L. Canon
Journal: Annals of Oncology (1999)
Predicting an optimal strategy for insulin-like growth factor 1 (IGF1) signaling interference in Ewing's sarcoma (ES).
Authors: A. C. van de Luijtgaarden, Y. M. Versleijen-Jonkers, M. H. Roeffen, U. E. Flucke, B. W. Schreuder, W. T. Graaf
Journal: Journal of Clinical Oncology (2010)

9538 Background: The IGF pathway can be targeted at the ligand or receptor level or at either of the downstream signaling cascades AKT/mTOR and MAPK/ERK. We deduce the optimal target and timing for IGF pathway interference from an examination of (change of) expression, mutual correlations, and prognostic value of potential targets in ES samples taken before and after chemotherapy. Methods: We analyzed tumor material (36 biopsies and 24 resection specimens after neoadjuvant chemotherapy) and follow up data of 41 patients treated at the Radboud University Nijmegen Medical Centre. Immunohistochemical (IHC) staining was done for IGF1, IGF2, IGF binding protein 3 (IGFBP3), IGF1R, phosphorylated AKT (pAKT), -mTOR (pmTOR), and -ERK (pERK). Staining intensity was compared to positive control and scored as absent (0), weak in ≥10% of cells (1) or strong in ≥10% of cells (2). Influence on progression-free (PFS) and overall survival (OS) was tested by the Kaplan-Meier method, change of expression within subjects by Wilcoxon signed rank tests and correlations by Spearman ρ. Results: IHC results (%) are shown in the Table. After chemotherapy, pmTOR expression decreases significantly (p=0.021) and IGFBP3 increases (p=0.005). Correlations exist between IGF1R and pERK (p=0.286, p=0.031), IGF1R and pAKT (p=0.269 p=0.045), pAKT and pERK (p=0.460 p=0.000) and pERK and pmTOR (p=0.273 p=0.038), indicating that both effector cascades are activated. In therapy-naive samples, combined expression of pAKT, pMTOR, and pERK predicts worse PFS (median 11 vs. 32 months, p=0.039) and OS (median 18 vs. 83 months, p=0.023). No other known prognostic factors explain this difference. Conclusions: We detected a cooperation of the AKT/mTOR and MAPK/ERK pathways and identified a prognostic unfavorable subgroup of patients with widely activated signaling cascades. We therefore propose that combined inhibition of these pathways may be an effective treatment for ES patients. Based on IHC results alone, this therapy should be timed before cytotoxic chemotherapy. Biopsy (n=36) Resection (n=24) Intensity 0 1 2 0 1 2 IGF1 14 0 86 0 8 92 IGF2 11 62 27 17 63 21 IGFBP3 25 33 42 9 22 70 IGF1R 25 64 11 21 71 8 pmTOR 67 33 0 87 13 0 pAKT 73 27 0 81 19 0 pERK 58 39 3 78 22 0 No significant financial relationships to disclose.
Transcriptome Analysis of Triple-Negative Breast Cancer Reveals an Integrated mRNA-lncRNA Signature with Predictive and Prognostic Value
Authors: Yi-Zhou Jiang, Yi-Rong Liu, Xiao-En Xu, Xi Jin, Xin Hu, Ke-Da Yu, Zhi-Ming Shao
Journal: Cancer Research (2016)

Abstract While recognized as a generally aggressive disease, triple-negative breast cancer (TNBC) is highly diverse in different patients with variable outcomes. In this prospective observational study, we aimed to develop an RNA signature of TNBC patients to improve risk stratification and optimize the choice of adjuvant therapy. Transcriptome microarrays for 33 paired TNBC and adjacent normal breast tissue revealed tumor-specific mRNAs and long noncoding RNAs (lncRNA) that were associated with recurrence-free survival. Using the Cox regression model, we developed an integrated mRNA-lncRNA signature based on the mRNA species for FCGR1A, RSAD2, CHRDL1, and the lncRNA species for HIF1A-AS2 and AK124454. The prognostic and predictive accuracy of this signature was evaluated in a training set of 137 TNBC patients and then validated in a second independent set of 138 TNBC patients. In addition, we enrolled 82 TNBC patients who underwent taxane-based neoadjuvant chemotherapy (NCT) to further verify the predictive value of the signature. In both the training and validation sets, the integrated signature had better prognostic value than clinicopathologic parameters. We also confirmed the interaction between the administration of taxane-based NCT and different risk groups. In the NCT cohort, patients in the low-risk group were more likely to achieve pathologic complete remission after taxane-based NCT (P = 0.014). Functionally, we showed that HIF1A-AS2 and AK124454 promoted cell proliferation and invasion in TNBC cells and contributed there to paclitaxel resistance. Overall, our results established an integrated mRNA-lncRNA signature as a reliable tool to predict tumor recurrence and the benefit of taxane chemotherapy in TNBC, warranting further investigation in larger populations to help frame individualized treatments for TNBC patients. Cancer Res; 76(8); 2105–14. ©2016 AACR.
PTU-264 Long term survival following resection of colorectal liver metastases – the truth regarding the influence of complications
Authors: AB Fajardo Puerta, FK Welsh, AB Cresswell, TG John, M Rees
Journal: Gut (2015)

<h3>Introduction</h3> The deleterious effect of complications on long term survival following resection of colorectal liver metastases (CRLM) remains controversial. Is it truly the effect of complications <i>per se</i>or simply a reflection of the burden of disease and tumour biology? <h3>Method</h3> From our prospective database of patients resected with CRLM between January 2000 and January 2014 (n = 1457), we used Kaplan-Meier analysis to calculate cancer-specific survival (CSS) and disease-free survival (DFS) for patients with no complications (Group A n = 1084), any complication (Clavien-Dindo I-IV) (Group B n = 373) and major complications (Clavien-Dindo III/IV) (Group C n = 95). In addition, the Basingstoke Predictive Index (BPI), a validated predictor of CSS comprised of primary tumour factors and metastatic disease burden, was calculated for each group. From the BPI, we created case-matched pairs for patients with no complications (Group D n = 456), any complications (Group E n = 154) and serious complications (Group F n = 33) and recalculated CSS and DFS in those groups. <h3>Results</h3> Patients without complications (Group A) had significantly better CSS and DFS compared with patients with complications (Group B) (CSS p = 0.001; DFS p = 0.02) or serious complications (Group C) (CSS p = 0.009, DFS p = 0.045). The median preoperative and postoperative BPI scores were significantly higher for Group B (6 and 7) and Group C (6 and 7) compared to Group A (5 and 6) (p &lt; 0.05). Analysis of case-matched survival showed no difference between patients without complications (Group D) compared to those with complications (Group E) (CSS p = 0.098, DFS p = 0.089) or serious complications (Group F) (CSS p = 0.129, and DFS p = 0.982). <h3>Conclusion</h3> These data show that when the influence of primary tumour biology and metastatic disease burden are corrected for, complications <i>per se</i>do not influence survival after resection of CRLM. <h3>Disclosure of interest</h3> None Declared.
Retrospective analysis of P-STAT6 expression as a predictive marker in primary nervous system lymphoma patients assigned to high-dose methotrexate
Authors: G. G. Altavilla, V. V. Pitini, C. C. Arrigo, G. G. Marabello, C. C. Naro, C. C. Tomasello, M. M. Righi, D. D. la Torre
Journal: Journal of Clinical Oncology (2007)

8059 Background: Recent immunohistochemical data and gene expression values have demonstrated that a majority of Primary Nervous System Lymphoma (PCNSL) express both bcl-6 as well as MUM-1, suggesting an overlapping histogenetic time slot of B-cell differentiation. In addition, an increased expression of P-STAT6 seems to predict short survival in patients (pts.) treated with high-dose Methotrexate (HD-MTX)-based chemotherapy. To investigate the clinical impact of the P-STAT6 expression in this setting we have analyzed P- STAT6 expression in available tumor tissue blocks of 25 PCNSL pts. treated with HD-MTX who have had follow up for at least 2.5 years. Methods: Immunohistochemistry for P-STAT6 was performed using an indirect immunoperoxidase method. Responses were evaluated according to the International Workshop criteria for PCNSL. Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meier Method. Results: 15 male, 10 female; mean age 52.1 years, were included in the analysis. The immunohistochemical analysis showed three different patterns of P-STAT6 expression: 7 pts. had absent P-STAT6 expression and low tumor cellular density (group A); 8 pts. had sparse positive P-STAT6 expression and low cellular density (group B), 10 pts. had strong P-STAT6 nuclear expression in tumor cells and on vascular endothelia and high cellular density (group C). The overall response rates to treatment (CR+PR) were 83% for both group A and B compared to 5% of group C. Furthermore the pts. with intense P-STAT6 expression experienced an impressive early progression (PFS median 2.5 months) and an OS very short (median 10 months). To date pts. of groups A and B have not reached median OS and PFS. Conclusions: PCNSL pts. with intense P-STAT6 expression experienced short survival when treated with HD-MTX- chemotherapy. No significant financial relationships to disclose.
Asthma and psychiatric disorders: a case-control study
Authors: A. Cappai, F. Pinna, F. Manunza, S. Floris, E. Zaccheddu, C. Toscano Carruba, A. Mancosu, S. Palmieri, L. Gambula, W. Orru, F. Argiolas, B. Carpiniello, P Manconi, S. Del Giacco
Journal: Allergy (2011)
Blood Soluble PD-L1 Protein In Aggressive Diffuse Large B-Cell Lymphoma Impacts patient’s Overall Survival
Authors: Thierry Fest, Delphine Rossille, Mélanie Gressier, Delphine Maucort-Boulch, Diane Damotte, Céline Pangault, Steven Le Gouill, Karin Tarte, Thierry Lamy, Noel Milpied
Journal: Blood (2013)
Endoscopic Management of Choledocholithiasis Resulting from a Biliary Metal Stent
Authors: Y.  K.  Cheon, J.  H.  Moon, Y.  D.  Cho, M.  S.  Lee, C.  S.  Shim
Journal: Endoscopy (2003)

A 52-year-old woman was admitted to our institute with abdominal pain in the right upper quadrant and anorexia for a few days. In 1995, she had undergone a lithotripsy using percutaneous cholangioscopy, because of intrahepatic bile duct stones. The patient had refused resection of the left lateral segment of the liver. A self-expandable metal stent covered with polytetrafluoethylene had also been inserted in the stricture site in the left main intrahepatic bile duct, to avoid recurrent cholangitis and intrahepatic bile duct stone. Now, 6 years later, she had developed abdominal pain in the right upper quadrant associated with an elevated serum level of aminotransferase and alkaline phosphatase (aspartate aminotransferase 56 IU/l (normal range 0 - 37 IU/l); alanine aminotransferase 45 IU/l (normal range 0 - 41 IU/l); alkaline phosphatase 643 IU/l (normal range 53 - 128 IU/l). Endoscopic retrograde cholangiopancreatography revealed the dilated extrahepatic bile duct and left intrahepatic bile duct to be without stricture, and also the presence in the distal common bile duct of a large elongated freely mobile filling defect, suggestive of common bile duct stone containing a metal mesh (Figure [1]). After successful endoscopic sphincterotomy, mechanical lithotripsy was performed because of the large size of the stone. The stone was soft and dark brown in color with the metal stent extruding from the ampulla of Vater along with common bile duct stone fragments (Figure [2]). After complete removal of the stone, the serum level of hepatic enzymes returned to normal, and the patient has remained asymptomatic. An intrahepatic biliary stricture may not only limit the clearance of stones but also contribute to the recurrence of stones and cholangitis. Published reports of the intrahepatic use of metallic stents for hepatolithiasis and biliary stricture remain limited. Jeng et al. [1] reported that metallic stent placement seemed to be an effective and well-tolerated treatment for complicated refractory hepatic ductal strictures with hepatolithiasis. The formation of biliary tract stones around surgically introduced foreign material has been well documented. IT is reported that 30 % of recurrent stones after cholecystectomy contained nonabsorbable suture material in their nuclei [2]. Metallic surgical clips have migrated into the biliary tract and acted as a nidus for stone formation [3] [4]. Biliary stasis and bacterial overgrowth resulting in bacterial degradation of bile were contributing factors in the above cases [5].
Abstract 13742: In Body Tissue-engineered Heart Valve (Biovalve) Architecture Based on 3D Printer Molding
Authors: Yasuhide Nakayama, Yoshiaki Takewa, Masami Uechi, Keiichi Kanda, Tsutomu Tajikawa, Tomonori Oie, Masanobu Ono
Journal: Circulation (2013)

Purpose: In body tissue architecture technology, attempted as novel and practical regeneration medicine by us, can prepare a completely autologous heart valve, called Biovalve, consisting of only r...
Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree: series of 106 consecutive patients
Authors: P. Malaguti, M. Milella, A. J. Gelibter, G. Bossone, I. Sperduti, E. Ruggeri, E. Bria, E. Terzoli, P. Marolla, F. Cognetti
Journal: Journal of Clinical Oncology (2006)

14099 Background: Our group recently published a phase II trial of GEM infused at fixed dose-rate of 10 mg/m2/min over 100 min in patients with advanced PDAC and BTC. (Cancer September 15,2005). Given the promising results obtained in the first 40 pts, we expanded the cohort under an observational protocol and this is the report of such experience. Methods: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Results: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m 2 at the fixed dose-rate of 10 mg/m 2 /min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Conclusions: The results obtained with FDR-GEM in a series of 106 consecutive pts confirm previous results obtained in smaller series and suggest that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. FDR-Gem may constitute a viable alternative to standard Gem infusion as first-line treatment in advanced PDAC and BTC. No significant financial relationships to disclose.
Second line BCNU plus CPT-11 chemotherapy in recurrent glioblastoma (GBM): Phase II study of GICNO (Italian Neuro-Oncology Group)
Authors: A. A. Brandes, A. Tosoni, M. Reni, F. Valduga, U. Basso, S. Lonardi, L. M. Pasetto, V. Blatt, S. Monfardini, M. Ermani
Journal: Journal of Clinical Oncology (2004)

1516 Background: In a phase I study the MTD of CPT-11 associated with BCNU was established at 225 mg/m2 for patients (pts) on p450 enzyme inducing anticonvulsants (EIAC). The aim of the present phase II study was to evaluate PFS at 6 months (PFS-6), time to progression (TTP), response rate (RR) and toxicity of associated BCNU and CPT-11. Methods: From August 2001 to October 2003, 42 pts (29 M, 13 F; mean age 53 yrs, range 27–71 yrs) and on EIAC with recurrent/progressive GBM after surgery, radiotherapy and first line chemotherapy with temozolomide, were given chemotherapy with BCNU 100 mg/m2 every 6 weeks on day 1 plus CPT–11 weekly for 4 weeks (starting dose 175 mg/m2), followed by 2-weeks' rest. Second cycle CPT-11 was escalated to 200 mg/m2 if no G2 toxicity was registered. Results: PFS-6 was 30.3% (95% CI: 18.5% - 49.7%) and TTP 17.27 weeks (95% CI: 11.9–23.9). Age <45 years (p=0.024) and response to chemotherapy (p<0.001) were independent prognostic factors. Nine pts (21.4%, 95% CI: 9% - 34%) had a partial response (PR), and 21 (50%, 95% CI: 35% - 65%), stable disease. A total of 130 cycles was delivered (mean 3.1 per pt, range 1–8). The CPT-11 dose was escalated to 200 mg/m2 in 26 cycles (20%), and reduced to 75% in 22 cycles (17%) because G2 diarrhea (59%) and neutropenia ≥G2 (41%) occurred; 2.4% of the pts had G3 neutropenia. Nausea and vomiting were G3 in 4 pts (9.5%), and diarrhea G1–2 in 29 pts (69%) and G3 in 3 pts (7.1%). Therapy was discontinued in 2 pts (4.8%) that had G3 pulmonary toxicity while they were on PR. Overall MST was 11.7 months (95% CI: 7.4-NA). Conclusions: This new regimen is highly active as second line chemotherapy in pts with recurrent GBM with an acceptable toxicity. Further studies are therefore warranted to test it as first line chemotherapy. No significant financial relationships to disclose.
PD-0009 Primary Tumor Location is a Major Independent Prognostic Factor for Mcrc Patients
Authors: Fotios Loupakis, Dongyun Yang, Shibao Feng, Chiara Cremolini, Wu Zhang, Carlotta Antoniotti, Christiane Langer, Herbert Hurwitz, Leonard Saltz, Alfredo Falcone, Heinz Joseph Lenz
Journal: Annals of Oncology (2012)