tbuckley/cabot-search huggingface dataset:
Can we use radiofrequency ablation for liver metastases from colorectal cancer over 25 mm initially but downsized by systemic chemotherapy?
Authors: Leonor Benhaim, Frederique Peschaud, Mostafa El hajjam, Robert Malafosse, Jacques Sellier, Catherine Julie, Alain Beauchet, Philippe Rougier, Bernard Nordlinger
Journal: Journal of Clinical Oncology (2015)

3528 Background: Radiofrequency ablation (RFA) can be a valid treatment for liver metastases from colorectal cancer (CRLM) and is mostly dedicated to metastases unsuitable for surgical resection. Tumor size at the time of the RFA procedure is the main predictive factor for in situ recurrence (ISR) at the ablated zone. However, regardless to tumor size during procedure, the diameter of liver metastases at presentation, before chemotherapy infusion, may be predictive for ISR, although it has never been assessed. The aim of this study was to determine the risk for ISR after RFA for liver metastasis larger than 25mm initially but that have been downsized by preoperative chemotherapy. Methods: We retrospectively reviewed all RFA performed in patients treated for CRLM who had previously received at least one cycle of systemic chemotherapy from January 2004 to December 2012. Each tumor site treated by RFA was studied independently. Metastases were divided into 2 groups according to its size. Group1: ≤ 25mm before and after chemotherapy. Group 2: > 25 mm before chemotherapy; 2A: ≤ 25mm after chemotherapy 2B: > 25 mm after chemotherapy. Results: 133 CRLM were ablated in 83 patients after systemic chemotherapy (median follow-up 21 months). Among those patients, 57 underwent RFA combined with hepatectomy. The rate of 1-year ISR was significantly higher in group 2A than in group 1 (31.8% vs. 15.5% respectively, p = 0.0006). The highest rate of 1-year IRS was 63.6% in group 2B which was significantly higher than in group 1 (p < 0.001) and 2A (p = 0.04). Time to in situ recurrence (TTISR) was significantly shorter in group 2A than in group 1 (HR: 2.89; 95%CI [1.04-8.01], p = 0.004). The shortest TTISR was observed in group 2B. In multivariate analysis, RFA group was the only significant indicator for ISR after RFA (p < 0.001). Conclusions: Initially oversized CRLM do remain beyond the optimal indications for RFA despite downsizing and should be consider as contraindication to RFA procedure. The rate of ISR remains in this situation doubled to that of upfront small liver metastasis reaching 32%.
Keratinocyte-Growth-Factor-Prophylaxis: Positive Effect on Intestinal Mucositis Following Autologous and Allogeneic Peripheral Blood Stem Cell Transplantation in Haemtological Malignancies: A Sequential Cohort Study.
Authors: Wilfried Grothe, Martin Bauer, Andreas Rupprecht, Maximillian Christopeit, Anke Muetherig, Thomas Weber, Sebastian Theurich, Mike Becker, Gerhard Behre
Journal: Blood (2007)
Mutations in the HECT domain of NEDD4L lead to AKT–mTOR pathway deregulation and cause periventricular nodular heterotopia
Authors: Loïc Broix, Hélène Jagline, Ekaterina L Ivanova, Stéphane Schmucker, Nathalie Drouot, Jill Clayton-Smith, Alistair T Pagnamenta, Kay A Metcalfe, Bertrand Isidor, Ulrike Walther Louvier, Annapurna Poduri, Jenny C Taylor, Peggy Tilly, Karine Poirier, Yoann Saillour, Nicolas Lebrun, Tristan Stemmelen, Gabrielle Rudolf, Giuseppe Muraca, Benjamin Saintpierre, Adrienne Elmorjani, Martin Moïse, Nathalie Bednarek Weirauch, Renzo Guerrini, Anne Boland, Robert Olaso, Cecile Masson, Ratna Tripathy, David Keays, Cherif Beldjord, Laurent Nguyen, Juliette Godin, Usha Kini, Patrick Nischké, Jean-François Deleuze, Nadia Bahi-Buisson, Izabela Sumara, Maria-Victoria Hinckelmann, Jamel Chelly
Journal: Nature Genetics (2016)
80% of China’s clinical trial data are fraudulent, investigation finds
Authors: Michael Woodhead
Journal: BMJ (2016)

Just over 80% of clinical trial data submitted to support new drug registrations in China have been revealed as fraudulent or substandard by the country’s drug regulator.

An investigation of data for 1622 new drugs submitted to China’s State Food and Drug Administration (CFDA) for registration said that 1308 of the applications should be withdrawn because they contained fabricated, flawed, or inadequate data from clinical trials.1

In a damning report released on 9 September the CFDA described the findings of widespread fraud as shocking and vowed to crack down on what it described as a “chaotic” situation in the country’s clinical trials industry.

Much of the blame was attributed to the country’s loosely regulated clinical research organisations, which industry insiders claimed operate in …
Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data
Authors: Margarita Pons-Salort, Natalie A. Molodecky, Kathleen M. O’Reilly, Mufti Zubair Wadood, Rana M. Safdar, Andrew Etsano, Rui Gama Vaz, Hamid Jafari, Nicholas C. Grassly, Isobel M. Blake
Journal: PLoS Medicine (2016)

Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s).In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model. Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008-2009 and 2012-2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%-100%] in Nigeria and 84% [95% uncertainty interval 77%-91%] in Pakistan) had >70% population immunity among children <36 mo old. Districts with lower immunity were clustered in northeastern Nigeria and northwestern Pakistan. The accuracy of immunity estimates was limited by the small numbers of non-polio AFP cases in some districts, which was reflected by large uncertainty intervals. Forecasted improvements in immunity for April 2016 were robust to the uncertainty in estimates of baseline immunity (January-June 2015), vaccine coverage, and vaccine efficacy.Immunity against serotype-2 poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization.
Zoledronic acid in M1 patients: HRPC versus hormonal sensitive
Authors: E. Calais da Silva, F. M. Calais da Silva
Journal: Journal of Clinical Oncology (2008)

16120 Background: There is presently clinical evidence that confirms the value of bisphosphonates in the metastatic bone disease. Zoledronic acid is a bisphosphonate that has proved to diminish the skeletal related events (SRE) in metastatic prostate cancer. Methods: We include in the study patients with HRPC and hormonal sensitive M1, with and without pain, with the primary objective of measuring the efficacy of zoledronic acid in these patients. We started Zoledronic acid 4mg i.v. monthly. Results: We evaluated 151 patients, 20 were not evaluable and 131 evaluable with at least 3 administrations. In the group no pain: 40 patients HRPC who had chemotherapy the median follow-up was 19 months (3–44) out of which 26 (65%) remain pain free (3–44 months) and 14 (35%) started pain in average at 11 months (1–28 months). 13 patients hormonal sensitivewho hadhormonotherapy the median follow-up was 14 months (3–45) out of which 11 (85%) remain pain free (3–45 months) and 2 (15%) started pain in average at 8 months (4–12 months). In the group with pain: 63 patients HRPC who had chemotherapy the median follow-up was 15 months (3–50 months) out of which 26 (41%) registered pain palliation (1–46 months) and 37 (59%) no response (3–46 months). 15 patients hormonal sensitive who had hormonotherapy the median follow-up was 13 months (3–49) out of which 5 (33%) registered pain palliation (4–11 months) and 10 (67%) no response (3–42 months). Only 2 patients required administration of Samarium i.v. Mandible bone necrosis 2 cases. Conclusions: Zoledronic acid is an i.v. bisphosphonate effective in the palliation of pain in patients with bone metastases, which produces decrease of pain and analgesic score with a fast response - in average 4 months - and a therapeutic efficacy maintained in average for 8 months. In the group no pain, there is more time with response in the hormonal’s sensitive’s, 85% vs 65%. In the group with pain, there is more time with response in the HRPC group, 41% versus 33%. No significant financial relationships to disclose.
Efficacy and tolerability of Everolimus-Exemestane combination therapy in metastatic breast cancer patients: experience in Real Life
Authors: V. Cocciolone, K. Cannita, A. Tessitore, L. Rinaldi, A. Irelli, A. Dal Mas, G. Calvisi, A. Bafile, E. Alesse, E. Ricevuto, C. Ficorella
Journal: Annals of Oncology (2015)
Utility Of Post Therapy Brain Surveillance Imaging In The Detection Of Primary CNS Lymphoma (PCNSL) Relapse
Authors: Gaelle Fossard, Emmanuelle Nicolas-Virelizier, Philippe Rey, Francois Ducray, Emmanuel Jouanneau, Pierre Faurie, Amine Belhabri, Marie Pierre Sunyach, Catherine Chassagne-Clement, Philippe Thiesse, Catherine Sebban, Pierre Biron, Jean-Yves Blay, Herve Ghesquieres
Journal: Blood (2013)
Phase II study with the combination of capecitabine (C) and vinorelbine (V) in metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes
Authors: L. G. Estevez, N. Batista, P. Sánchez-Rovira, A. Velasco, M. Domine, F. Lobo, J. Oramas, J. Cruz
Journal: Journal of Clinical Oncology (2004)

748 Background: The oral fluoropyrimidine-based prodrug capecitabine and vinorelbine combination has shown promising antitumour activity. Based on this data we conducted this multicentre phase II trial to evaluate the objective response and safety of C and V in patients (pts) with MBC previously treated with anthracycline- and taxane-containing regimens Methods: Women aged >18 with MBC and measurable disease, PS 0–2, with adequate organ functions were enrolled to receive this regimen on a 3 weekly schedule: (C) administered at a dose of 2000 mg/m2 day split-up over 2 daily doses from day 1 to 14 and (V) given at a dose of 25 mg/m2 on day 1 and 8, every 3 weeks until a maximum of 6 cycles Results: A total of 15 pts were enrolled, median age 57 (41–77), PS 0=12 (80%), 1=3 (20%). Postmenopausal 8 (57.1%). The most frequent metastatics sites were liver (53.3%), nodes (40%), lung (40%), bone (13.3%). 53.33% had 2 or more metastatics sites. All pts previously failed to anthracyclines and taxanes chemotherapy regimens. Twelve pts (80%) received the combination as second line and 3 (20%) as first line. 63 cycles were administered with a median of 5 cycles/pt (1–6). Median relative dose intensity was 0.92 [0.51–1.01](V) and 0.90 [0.26–1.03](C). All pts were evaluable for safety. Grade 3–4 haematological toxicities per pts were neutropenia 8/15 (53.3%), leukopenia 2/15 (13.3.0%), thrombocytopenia 1/15 (6.7%); Non-haematological toxicity: hand and foot syndrome reported in 53.3%; grade 3–4: 2/15 (13.3%). nausea-vomiting grade 3–4: 5/15 (33.3%). Ten pts were evaluable for response: overall response rate was 50% (2CR, 3PR), stable disease 2/10 (20%), progressive disease 3/10 (30%). Conclusions: Our preliminary data demonstrate that the combination of capecitabine and vinorelbine shows a promising clinical activity in pts with MBC whose previously failed to taxanes and anthracyclines-containing regimens, with a safe toxicity profile. The study is still ongoing and updated results will be presented. No significant financial relationships to disclose.
Phase I dose-escalation study of novel oral multi-target tumor growth inhibitor (MTGI) ZK 304709 administered daily for 7 days of a 21-day cycle to patients with advanced solid tumors
Authors: J. Graham, K. Wagner, R. Plummer, B. Wiedenmann, J. Cassidy, K. Kowal, C. McCoy, H. Calvert
Journal: Journal of Clinical Oncology (2006)

2073 Background: ZK304709 is a novel MTGI that selectively inhibits activity of Cyclin Dependent Kinases (CDKs) 1, 2, 4, 7, 9, and the tyrosine kinase activity of VEGF-R 1, 2, 3 and PDGF-βR. Methods: Adult patients (pts) with a good performance status (WHO PS ≤2) and a histologically or cytologically confirmed relapsed/refractory solid tumor were eligible. ZK304709 is administered, as a monotherapy, orally on days 1–7 of a 21-day cycle to fasting patients at a starting dose of 15 mg qd. Dose escalation has ranged from 33% - 100% of prior dose, depending on occurrence of drug-related toxicity ≥ grade (gr) 2 (CTC v2.0). Between 3 and 7 patients are to be enrolled per dose level, depending on DLTs that are observed. The primary objective is determination of the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of ZK304709. Secondary objectives include tolerability, pharmacokinetic (PK) profile, and preliminary efficacy. Results: Interim results are available for 22 pts (15 M/7 F, median age 60.5 yrs; range 37–71) treated with ZK304709 at 6 dose levels (15 - 180 mg qd). Patients completed a median of 2 cycles (range 0–8). Common AEs were nausea, vomiting, diarrhea, and lethargy. Two DLT were observed: supraventricular tachycardia and vomiting, but the MTD was not reached. The PK profile shows rapid absorption, with a T max of 2–4 hrs, and a dose-dependent increase in systemic exposure over the 15–90 mg dose range. Disease stabilization for ≥4 cycles has been observed. Conclusions: ZK304709 is rapidly absorbed and has been tolerated on this schedule at doses up to 180 mg qd. The MTD has not been reached, and enrolment is ongoing. These preliminary data demonstrate that oral delivery on this schedule of an agent that inhibits both cell cycle and angiogenesis is feasible. [Table: see text]
Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma
Authors: Elisabeth Naschberger, Andrea Liebl, Vera S. Schellerer, Manuela Schütz, Nathalie Britzen-Laurent, Patrick Kölbel, Ute Schaal, Lisa Haep, Daniela Regensburger, Thomas Wittmann, Ludger Klein-Hitpass, Tilman T. Rau, Barbara Dietel, Valérie S. Méniel, Alan R. Clarke, Susanne Merkel, Roland S. Croner, Werner Hohenberger, Michael Stürzl
Journal: Journal of Clinical Investigation (2016)

Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs.
Endoscopic treatment of post-laparoscopic sleeve gastrectomy leaks using a specifically designed metal stent
Authors: Andrea Tringali, Vincenzo Bove, Vincenzo Perri, Rosario Landi, Pietro Familiari, Ivo Boškoski, Guido Costamagna
Journal: Endoscopy (2016)

<b>Background and study aim</b> Leakage of the surgical suture is the main complication of laparoscopic sleeve gastrectomy (LSG) and is amenable to endoscopic therapy. The aim of this study was to evaluate the efficacy of a specifically designed self-expandable metal stent (SEMS) to seal the leakage. <b>Patients and methods </b>Over a 2-year period, patients referred for the treatment of post-LSG fistulas underwent placement of a fully covered esophagogastric SEMS with a specific design. <b>Results</b> A total of 10 patients were treated after a mean time of 50.9 days from the diagnosis of post-LSG leakage. A total of 11 SEMSs were placed. After stent removal, the leakage was seen to have healed in eight patients. Two patients who were treated with an SEMS with different mesh design, experienced stent migration, which required alternative endoscopic treatment such as the insertion of double-pigtail stents. After a mean follow-up period of 13.4 months, all patients were asymptomatic. <b>Conclusions:</b> Placement of a specifically designed SEMS for the treatment of post-LSG fistulas seems a promising first-line therapy according to this small series.
Seven-Year Follow-up of Patients Receiving Imatinib for the Treatment of Chronic Myelogenous Leukemia by the TARGET System
Authors: Tetsuzo Tauchi, Masahiro Kizaki, Shinichiro Okamoto, Hideo Tanaka, Mitsune Tanimoto, Koiti Inokuchi, Tohru Murayama, Yoshio Saburi, Masayuki Hino, Mitsuru Tsudo, Taizo Shimomura, Yasushi Isobe, Kazuo Oshimi, Kazuo Dan, Kazuma Ohyashiki, Yasuo Ikeda
Journal: Blood (2010)
Magnetic resonance imaging versus mammography for diagnosing ductal carcinoma in situ
Authors: C. K. Kuhl, S. Schrading, E. Wardelmann, M. Braun, W. Kuhn, H. H. Schild
Journal: Journal of Clinical Oncology (2007)

1504 Background: Mammographic screening is considered the mainstay for diagnosing pre-invasive breast cancer (DCIS). However, (over)diagnosis of DCIS has become a major concern. We investigated the sensitivities of high-resolution MRI and of state-of-the-art mammography (Mx) for diagnosing pure DCIS, and compared the biologic profile of MRI-detected versus Mx-detected DCIS. Methods: Prospective study on 5960 consecutive women who were referred to a dedicated breast unit for screening or for diagnostic assessment. Women underwent bilateral mammography with at least 2 views, plus spot compression views where appropriate, and high-resolution bilateral MRI. A total 137 women received the final pathologic diagnosis of having DCIS (no invasion). Of these, 108 (79%) had been referred for regular screening, 14 (10%) for high risk screening, 10 (7%) for follow up after breast cancer, and 5 (4%) for clinical symptoms. We investigated the mode of detection, and the biologic profile of the DCIS (size, nuclear grading, ER/PR and HER2-receptor status). Results: Overall, Mx was positive in 79/137 patients (58%), MRI was positive in 123/137 (90%). In 68/137 (50%), Mx and MRI were concordantly positive. In 3/137 (2%), Mx and MRI were both false-negative. In 11/137 (8%), only Mx was positive, MRI was false- negative. In 55/137 (40%), only MRI was positive, Mx was false negative. Of the 11 DCIS which were only detected by Mx, 1 was high grade, none was ER negative or HER2 positive. Mean VNPI was 4.2. Of the 55 DCIS which were only MRI detected, 41 (78%) were high grade, 14 (27%) were ER negative, 17(33%) HER-2 positive. Mean VNPI was 6.5. Conclusions: Compared to mammography, MRI offers a significantly higher sensitivity for DCIS, in particular for DCIS with adverse biologic profile: Half of the high grade or HER2-positive DCIS were only MRI detected. In turn, DCIS which was only mammography detected had a relatively benign biologic profile. We propose that MRI is helpful for diagnosing biologically (i.e. possibly prognostically) relevant DCIS [Table: see text] No significant financial relationships to disclose.
Drug Price Inflation and the Cost of Assisted Death for Terminally Ill Patients—Death With Indignity
Authors: Veena Shankaran, Richard J. LaFrance, Scott D. Ramsey
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Transparency Associated With Interactions Between Industry and Physicians
Authors: Jack S. Resneck
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal