tbuckley/cabot-search huggingface dataset:
Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib: A single institution experience
Authors: Z. Dubauskas, J. Kunishige, V. G. Prieto, P. Hwu, E. Jonasch, N. M. Tannir
Journal: Journal of Clinical Oncology (2008)

16101 Background: Sorafenib-induced dermatologic toxicity is common and consists primarily of dry skin, maculopapular rash, hand/foot skin reaction, and alopecia. Cutaneous squamous cell carcinoma (SCC) and inflammation of actinic keratosis (AK) were reported in two patients treated with sorafenib (Lacouture et al), but the scope of this observation has not been evaluated. Methods: We reviewed medical records of 131 patients treated with single-agent sorafenib for metastatic renal cell carcinoma (MRCC) at our institution from June 1st, 2005 through April 4, 2007. Results: Seven cases of cutaneous SCC, 2 cases of SCC- (keratoacanthoma) type, 2 cases of focal squamous atypia, and 3 cases of AKs were identified. The median time to development of SCC or AK from the start of sorafenib was 23 weeks (range 4–183). One patient discontinued therapy altogether due to dermatological toxicity, whereas 7 patients discontinued drug due to disease progression and 2 discontinued sorafenib for non-dermatological toxicity. Four patients continue taking sorafenib at reduced doses for non-dermatological toxicity, such as diarrhea and fatigue. One patient, who is still on the drug at a 25% dose reduction developed a second invasive SCC lesion on his forearm six months following the initial resection. Conclusions: These data suggest that there may be an association between sorafenib therapy and the development of cutaneous SCC and inflammation of AK. This adverse event has important therapeutic implications. Full appraisal of this observation in prospective studies is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Oncology, Wyeth Bayer, Pfizer Oncology Hoffman-La Roche, Lilly Oncology, Pfizer Oncology
The detection of circulating tumor cells in patients with renal cell carcinoma using the AccuCyte platform and customized markers.
Authors: Arturo Ramirez, Scott S. Tykodi, Sherry Huang, Nicholas Alan Drovetto, Jackie L. Stilwell
Journal: Journal of Clinical Oncology (2012)

e21148 Background: Enumeration of circulating tumor cells (CTCs) in peripheral blood represents a prognostic marker for select solid tumors. Commercially available technologies for CTC detection rely on enrichment of EpCAM-expressing cells. However, not all tumor histologies demonstrate high constitutive EpCAM expression, including renal cell carcinoma (RCC). New techniques for more complex immunophenotypic characterization of CTCs are therefore of great interest. Methods: The AccuCyte system for characterization of rare blood cell populations retains all nucleated cells for analysis. Fluorochrome-conjugated monoclonal antibodies (mAbs) are added to 3 ml peripheral blood samples processed by density separation with a specialized tube and float. Centrifugation deposits all nucleated cells (Buffy coat) onto a surface designed for imaging with an automated fluorescence microscope. Sensitivity for CTC identification was measured by spiking blood from healthy donors with defined numbers of MDA-MD-453 breast tumor cells analyzed with mAbs to EpCAM and CD45. Peripheral blood samples from 4 patients (pts) with metastatic RCC and whose primary tumor had been resected were analyzed with a mAb specific for the RCC-associated antigen carbonic anhydrase IX (CAIX), as well as mAbs for CD10, EGFR and EpCAM. Results: In 13 blood samples from healthy donors, an average of 89% of spiked-in MDA-MD-453 tumor cells defined as EpCAM + /CD45 - were detected by AccuCyte analysis with linearity from 0 to 139 cells (slope=0.8899; r 2 =0.9351) and a sensitivity of approximately 1 CTC per 10 6 nucleated blood cells. 3 of 4 peripheral blood samples from pts with clear cell RCC contained putative CTCs (range 1-6 cells/ml) defined as CD45 - /CAIX + nucleated cells. 3 CTCs from one patient were also CD10 + or EGFR + . All putative CTCs were EpCAM - . Conclusions: The detection of EpCAM - /CAIX + cells in RCC pts demonstrates the adaptability of the AccuCyte platform for CTC (or other rare blood cell) identification defined by customized markers. Further development of marker panels for CTC analyses in pts with RCC and other tumor histologies as well as automation of image analysis is ongoing.
Neutrophil Infiltration Is Partially Inhibited By EC-18 in the LPS-Induced Acute Lung Injury
Authors: Su-Hyun Shin, Ha-Reum Lee, Nina Yoo, Sun Young Yoon, Myung-Hwan Kim, Cheolwon Suh, Ki-Young Sohn, Heung-Jae Kim, Yong-Hae Han, Saeho Chong, Jae Wha Kim
Journal: Blood (2015)
The Quick Physical Exam
Authors: Robert E. Hirschtick
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
CAPRA: Safety, efficacy, and translational biomarkers of weekly everolimus, carboplatin, and paclitaxel as induction therapy for locally advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Eric Raymond, Christophe Le Tourneau, Michel Gatineau, Jean-Pierre Delord, Jérôme Fayette, Chantal Dreyer, Annemilai Tijeras-Raballand, Sebastien Albert, Muriel Granier, Benoist Chibaudel, Alexandra Hadengue, Nasredine Aissat, Khemaies Slimane, Sandrine J. Faivre
Journal: Journal of Clinical Oncology (2013)

6036 Background: ThePI3K/mTOR pathway is activated in &gt;50% of HNSCC with preclinical synergism between everolimus and carboplatin/paclitaxel. Methods: Patients (pts) with untreated locally advanced HNSCC with ECOG PS&lt;2 received 9 consecutive weekly (w) cycles (cy) of CAPRA combining everolimus (30 mg/w at dose-level 1 then 50 mg/w at dose-level 2) with carboplatin (AUC2) and paclitaxel (60 mg/m 2 ) followed by chemoradiotherapy. Endpoints were safety (CTCv3.0), antitumor activity (RECIST1.1), pharmacodynamic biomarkers on tumor biopsy. Results: A total of 50 pts with stage IV HNSCC (41 males, 9 females, median age 61) were enrolled. Among 7 patients included in the phase I, no dose-limiting toxicity was reported and the recommended dose (RD) of everolimus was 50 mg/w. Safety evaluation in 46 pts treated at RD for 325 cy and a mean number cy/pt of 7.1 (95%CI: 6.3-7.8) showed grade (Gr) 1-2 adverse events consisting of asthenia (50%), nausea/vomiting (28%), alopecia (26%), mucositis (24%), and constipation (20%). Hematological toxicities (Gr1-2/3-4) were neutropenia (35%/39%), anemia (61%/17%), and thrombocytopenia (54%/13%). Everolimus-related Gr3 toxicities were rashes (1pt), pruritus (1pt), dyspnea (1pt), hyperglycemia (2pts), and Gr1-2 hypercholesterolemia (23pts). There was no toxic death. Among 38 pts evaluable for antitumor activity, one pt experienced a complete response (2.6%), 29 pts a partial response (76.3%), and 8 pts a stable disease (21%) for an overall response rate of 79% (no progression reported). Interestingly, 20 major responses (&gt;50% reduction tumor volume) were observed in large necrotic primary tumors/N3 involvement. Efficacy was not correlated to KRAS/BRAF/PI3KCA/EGFR mutations. Significant decreases of Ki67/p-S6K activities were observed in post CAPRA biopsies compared to baseline. Conclusions: Weekly everolimus with carboplatin/paclitaxel as induction regimen was well tolerated with 11% grade 3 and no grade 4/5 toxicity. Translational data showed direct effects of everolimus in tumors. CAPRA yields high rate of objective responses in patients with locally advanced HNSCC. Clinical trial information: NCT01333085.
Early necrosis following concurrent temozolomide and radiotherapy in adult patients with glioblastoma
Authors: M. C. Chamberlain, M. J. Glantz, L. Chalmers, A. Van Horn, A. E. Sloan
Journal: Journal of Clinical Oncology (2006)

1513 Background: Concurrent temozolomide (TMZ) and radiotherapy (RT) is the new standard of care for patients with newly diagnosed glioblastoma GBM). This report is a prospective observational study of surgically confirmed early necrosis in adult patients with GBM treated with concurrent TMZ and RT and post-RT TMZ. Methods: 52 consecutive patients (33 males; 19 females) ages 34 to 69 years (median 60), with newly diagnosed GBM were treated with surgery (complete resection in 40%, incomplete in 33%, biopsy in 27%) followed by concurrent TMZ and RT (median tumor dose 60Gy) followed by planned 6 cycles of monthly TMZ. TMZ was administered as 75mg/m 2 /day for 42 consecutive days with radiotherapy followed by 200mg/m 2 /day for 5 consecutive days every 28 days. Neurological evaluations were performed monthly and cranial MR bimonthly. Results: 26 patients (50%) manifested clinical and neuroradiographic evidence of tumor progression within 6 months of completing RT. 15 patients (28%) underwent reoperation with image verified complete resection. Histopathology was interpreted as necrosis without evidence of tumor in seven patients (13%). Conclusion: The patients in this study with early necrosis suggest a potential and perhaps significant chemo- radiosensitization effect in a subset of patients treated with this regimen of concurrent TMZ and radiotherapy that may predict for durable responses and contribute to the regimens observed benefit in patients with newly diagnosed GBM. Clearly, confirmation of this preliminary observation of unexpected and common early necrosis using concurrent TMZ and radiotherapy in a larger GBM population is required. [Table: see text]
The Supply and Demand of the Cardiovascular Workforce
Authors: Akhil Narang, Shashank S. Sinha, Bharath Rajagopalan, Nkechinyere N. Ijioma, Natalie Jayaram, Aaron P. Kithcart, Varsha K. Tanguturi, Michael W. Cullen
Journal: Journal of the American College of Cardiology (2016)
Fulvestrant in postmenopausal women with metastatic breast cancer progressing on prior endocrine therapy -results from a compassionate use progra
Authors: L. Petruzelka, M. Zimovjanova
Journal: Journal of Clinical Oncology (2004)

730 Background: Fulvestrant (Faslodex) is an estrogen receptor (ER) antagonist with no agonist effects. Here we report results from a compassionate use/named patient program in which postmenopausal women with metastatic breast cancer progressing on at least two prior endocrine therapies were treated with fulvestrant 250 mg. Methods: Fulvestrant 250 mg was given as a single 5 mL intramuscular injection, once-monthly until disease progression (PD). Tumor response was assessed monthly using UICC criteria. Time to progression (TTP) and duration of response (DOR; responding patients only) were defined from start of treatment until PD. Results: Between August 2001 and October 2003, 44 patients (median age 63 years [range 39–91 years]) were treated and followed-up for a median of 28 weeks (range 12–104 weeks). All had received prior endocrine treatment for advanced disease and 50% had received adjuvant endocrine treatment. Thirty patients (68%) had received prior chemotherapy. Most patients (75%) received fulvestrant as 3rd- or 4th-line endocrine treatment for advanced disease. Three patients (7%) had a partial response (PR); at time of analysis PRs were of 40, 76 and 104 weeks duration. Twenty patients (45%) had stable disease (SD) ≥24 weeks giving a clinical benefit (CB) rate (PR + SD ≥24 weeks) of 52%. Median TTP was 22 weeks. Fulvestrant 250 mg was well tolerated with no WHO grade III/IV toxicities observed. Conclusions: Fulvestrant 250 mg has demonstrable efficacy and a good tolerability profile in postmenopausal patients with metastatic breast cancer. More than 50% of patients gained CB from fulvestrant treatment despite most having received 2–3 prior endocrine therapies. No significant financial relationships to disclose.
Reversion to an Embryonic Alternative Splicing Program Enhances Leukemia Stem Cell Self-Renewal
Authors: Frida Linnea Holm, Eva Hellqvist, Cayla N Mason, Shawn Ali, Nathaniel Delos Santos, Christian Barrett, Hye-Jung Chun, Mark D. Minden, Moore Richard, Marco A Marra, Kelly A. Frazer, Anil Sadarangani, Catriona Jamieson
Journal: Blood (2015)
Blockade of p110delta Isoform Activity of Phosphoinositide 3-Kinase Inhibits Blast Cell Proliferation in Acute Myeloblastic Leukemia.
Authors: D. Bouscary, V. Bardet, P. Sujobert, P. Cornillet-Lefebvre, J. S. Hayflick, N. Prie, F. Verdier, B. Vanhaesebroeck, O. Muller, F. Pesce, N. Ifrah, M. Hunault Berger, C. Bertho, G. Guillerm, B. Villemagne, B. Audhui, E. Solary, F. Witz, J. L. Harousseau, C. Himberlin, T. Lamy, B. Lioure, M. C. Bene, J. Y. Cahn, F. Dreyfus, P. Mayeux, C. Lacombe
Journal: Blood (2004)
The pattern and timing of disease recurrence in squamous cancer of the anus: Mature results from the NCRI ACT II trial.
Authors: David Sebag-Montefiore, Roger James, Helen Meadows, Rubina Begum, David Cunningham, John Northover, Jonathan A. Ledermann, Sandra Beare, Latha Kadalayil, Robert Glynne-Jones
Journal: Journal of Clinical Oncology (2012)

4029 Background: Concurrent chemoradiation (CRT) is standard treatment for patients with squamous cell carcinoma of the anus. Although the majority of patients achieve long term disease control, locoregional failure is either detected early (failure to enter complete remission) or at a later date as locoregional recurrence. We explore the pattern and timing of disease recurrence within a phase III trial (ACT II), which mandated standardised radiation fields and doses (50.4Gy in 28 daily fractions). Methods: The UK ACT II trial recruited a total of 940 patients (2000 -2008) and compared cisplatin with mitomycin when combined with 5flurouracil CRT and two cycles of maintenance chemotherapy versus no maintenance using a factorial 2x2 design. Patient characterstics: T1/2 52%, T3/4 46%; N+ 32% N0 62%. The loco-regional response to treatment was assessed by clinical examination at 11, 18 and 26 weeks after CRT. Clinical examination was performed every two months for year 1; 3-monthly for year 2; then 6-monthly for years 3-5. CT scans of chest/abdomen/pelvis were performed at 6,12 24 months. Sites of failure were recorded on a case record form (primary site [PS], inguinal [ING], pelvic nodes [PEL], metastatic [METS]. Results: After a median follow up of 5 years, the crude pelvic failure (PF) rate is 18% (163/924). Of the 163 PF, 133 pts (82%) were pelvic only and 30 (18%) had PF + metastasis. 93% of all pelvic recurrences were detected during the first three years (54% yr 1, 26% yr 2 and 13% yr 3). The pattern was similar for PF only and PF + mets (data not shown). Only 46 (4%) of patients had [METS] as the first disease related event. 117/133 (88%) patients with PF only are evaluable for analysis of the pattern of failure., 53% occurred at the primary site (PS) only, 23% were PS + nodal (5% [ING] 13% [PEL] and 5% [ING+PEL], and 25% nodal only (6% [ING],14% [PEL] and 5% [ING+PEL]). Conclusions: The ACT II trial results with mature follow-up demonstrate a low rate of pelvic failure. Intensive follow up to detect potentially salvageable pelvic failure should be restricted to a maximum of three years in future trials as only 7% of relapses occur beyond this time point.
Decreased level of interleukin-10-producing B cells in patients with pemphigus but not in patients with pemphigoid
Authors: M. Kabuto, N. Fujimoto, T. Takahashi, T. Tanaka
Journal: British Journal of Dermatology (2016)

While the frequency of interleukin (IL)-10-producing B (B10) cells is reported to have an inverse correlation with disease activity in some human autoimmune diseases, the association between B10 cells and autoimmune blistering diseases (AIBD) has not been well evaluated. Although several phenotypes of human regulatory B cells have been proposed, the most appropriate one in AIBD has not been established.To evaluate B10 cells in AIBD including their phenotypes.Peripheral blood mononuclear cells were isolated from 39 patients with AIBD, including 14 with pemphigus and 25 with pemphigoid, and 10 healthy controls. We investigated the frequencies of B10 cells and CD19+ CD24hi CD38hi B cells using flow cytometry.The frequencies of B10 cells and CD19+ CD24hi CD38hi B cells were significantly lower and higher, respectively, in patients with pemphigus compared with healthy controls. Comparing patients with pemphigoid and healthy controls, no significant difference in the frequencies of B10 cells and CD19+ CD24hi CD38hi B cells was observed. B10-cell level in pemphigus was not associated with disease severity but inversely correlated with the required dose of steroid for treatment. While no significant difference in the frequency of IL-10-producing cells among CD19+ CD24hi CD38hi B cells was observed, in CD9+ and CD27- B-cell subsets it was significantly decreased in patients with pemphigus compared with healthy controls.Our results suggest the association of B10 cells with pemphigus but not with pemphigoid. The decrease in B10-cell level in pemphigus is partly caused by the lower production of IL-10 in CD9+ and CD27- B-cell subsets.
Worms in the Eye
Authors: Kyungmin Huh, Jeong Hoon Choi
Journal: New England Journal of Medicine (2016)

A 21-year-old man presented with a 2-week history of itching in his left eye. He reported “seeing worms” in his eye. He underwent thorough irrigation of the conjunctival sac and lacrimal duct. A video shows removal of a worm.
Ruxolitinib therapy and telomere length in myelofibrosis
Authors: G Caocci, M Greco, G Delogu, C Secchi, A Perra, S Ghiani, F Orru, A Vacca, F Galimi, G La Nasa
Journal: Blood Cancer Journal (2016)

Telomeres are specialized structures of repetitive nucleotide sequences that cap the ends of human chromosomes. Their main purpose is to maintain genome stability and integrity, and to protect the cell from progressive DNA shortening during repeated division. Human enzyme telomerase complex maintains the length of telomere repeats.1 Despite the high levels of telomerase activity in cancer cells, telomere shortening can still occur. Some recent reports describe reduced telomere length in myelofibrosis (MF) regardless of hydroxycarbamide therapy, suggesting a possible prognostic relevance for this biomarker.2, 3, 4 As yet, no studies have investigated telomere dynamics following treatment with ruxolitinib, a JAK1/2 inhibitor approved for the treatment of intermediate-2 and high risk MF, primary or post-polycythemia vera (PV) and essential thrombocytemia (ET).5
Safety and effectiveness of a long, partially covered metal stent for endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction
Authors: Yousuke Nakai, Hiroyuki Isayama, Natsuyo Yamamoto, Saburo Matsubara, Yukiko Ito, Naoki Sasahira, Ryunosuke Hakuta, Gyotane Umefune, Naminatsu Takahara, Tsuyoshi Hamada, Suguru Mizuno, Hirofumi Kogure, Minoru Tada, Kazuhiko Koike
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is potentially complicated by bile leak and stent migration. The aim of this study was to evaluate the safety and effectiveness of a long (≥ 10 cm), partially covered metal stent (LP-CMS) for EUS-guided hepaticogastrostomy (EUS-HGS) for malignant biliary obstruction. Both the stent length and the uncovered portion at the proximal end of the LP-CMS are designed to prevent stent migration. <b>Patients and methods:</b> A total of 33 patients undergoing EUS-HGS using an LP-CMS in four centers were retrospectively studied. Technical and clinical success, adverse events, and recurrent biliary obstruction were evaluated. <b>Results:</b> Gastric outlet obstruction (76 %) and surgically altered anatomy (15 %) were two major reasons for EUS-HGS. The technical and clinical success rates were 100 %. The median intragastric stent length was 54 mm. The adverse event rate was 9 %. No stent migration was observed. Recurrent biliary obstruction developed in 24 %, with a median cumulative time to recurrence of 8.5 months. <b>Conclusions:</b> EUS-HGS using an LP-CMS for unresectable malignant biliary obstruction was safe and effective.
Sleep disturbance in patients with advanced cancer: Frequency and factors associated with response to specialist-based outpatient supportive care.
Authors: S. Yennurajalingam, G. Chisholm, S. L. Palla, E. Bruera
Journal: Journal of Clinical Oncology (2011)

9069 Background: Sleep disturbance (SD) is one of the most distressing symptoms in patients with advanced cancer. There is limited data on the effectiveness of treatment and predictors of response. Methods: We reviewed 442 consecutive patients with advanced cancer presenting in the Supportive care clinic for SD. All patients underwent screening for SD (‘+’ defined as ≥3/10) and interdisciplinary assessment and treatment including drug review, counseling, sleep hygiene, and drug therapy (PC). Response was defined as ≥30% improvement from baseline to follow up visit. Baseline patient characteristics, cancer related symptoms (Edmonton symptom assessment scale), delirium (Memorial delirium assessment scale), use of opioids, steroids and anxiolytics/hypnotics, and CAGE score, were analyzed to determine their association with response to PC. Results: The median age was 58 years; males were 53%. The most common cancer types were H&N and lung and GI. (55%). 330/ 442 pts had SD (75 %). Median, mean (SDev) for SD (0=best sleep, 10- worst sleep imaginable) were 5 and 5(3). Sedative use (r-0.16, p=0.002), pain (r - 0.31), fatigue (r-0.31, <0.001), Depression(r-0.25, p<0.001), anxiety (r-0.28, p<0.001), drowsiness (r-0.30, p<0.001) and feeling of wellbeing (r-0.33, p=0.02) are associated with SD at initial consult. The median time between visits was 15 days. SD response was seen in 143/330 (43%) [95% CI 38% to 49%]. Use of medications such as anxiolytics/hypnotics, steroids, opioid dose, pain, depression, anxiety, fatigue and delirium were not predictive of SD response. Higher SD score (OR=1.14 per pt; p=0.01) was associated with response in patients with baseline SD. Conclusions: Frequency and severity of SD is high. Response to interdisciplinary supportive care is low. Further research is greatly needed.