tbuckley/cabot-search huggingface dataset:
Serial transbronchial biopsies in patients with lung cancer after radiation therapy
Authors: Georgia Karpathiou, Vasilis Mihailidis, Alexandra Giatromanolaki, Mihalis Koukourakis, Paschalis Steiropoulos, Efthimios Sivridis, Demosthenes Bouros, Marios Froudarakis
Journal: European Respiratory Journal (2011)

Background: Radiation therapy (RT) may cause lung damage in patients with lung cancer. However, serial microscopic evaluation of human lung parenchyma after irradiation is lacking. Transbronchial biopsy (TBB) is a bronchoscopic sampling tool for a variety of bronchial and pulmonary lesions.

The aim of the present prospective study was to assess lung parenchyma lesions after RT by serial TBBs.

Methods: 14 patients with lung cancer necessitating radiation therapy agreed to participate the study. Of these patients, 12 (85.7%) were assessable. TBB were obtained to the opposite of the tumor lung. Serial TBBs were performed before, just after RT and every 6 months in the first year of follow-up. Evaluation of each specimen was based on the presence of congestion, inflammation, hemorrhage and fibrosis, all these parameters giving a final total score.

Results: A median number of 4 biopsies were taken per patient and per procedure (range 2-6). In 11/12 patients (91%) congestion was present within the period of follow-up. All these patients presented a late evolution of a different degree of fibrosis at their TBB. Total score was before RT =3.1±3, just after RT = 5±1.3 and at 6 months = 6±1.9. Significant difference was observed between before and after RT (p=0.047) and before and at 6 months after RT (p=0.01). Major limitation of the study was the low patient accrual due to the proposed repeated procedures in patients with advanced stage disease and, at the end, poor performance status (overall median survival after RT 8 months).

Conclusion: Our study, although limited in accrual, showed that microscopic evaluation of lung parenchyma is possible with serial TBBs in lung cancer patients after RT.
Definition of giant ventral hernias: Development of standardization through a practice survey
Authors: Guillaume Passot, Laurent Villeneuve, Charles Sabbagh, Yohann Renard, Jean-Marc Regimbeau, Pierre Verhaeghe, Reza Kianmanesh, Jean-Pierre Palot, Delphine Vaudoyer, Olivier Glehen, Eddy Cotte
Journal: International Journal of Surgery (2016)
Phase I safety and pharmacokinetic (PK) study of SU014813 (S) in combination with docetaxel (D) in patients (pts) with solid tumors (STs)
Authors: P. Schöffski, M. de Jonge, H. Dumez, N. M. Brega, A. Abbattista, R. Courtney, J. Verweij
Journal: Journal of Clinical Oncology (2008)

3554 Background: S is an oral, multitargeted tyrosine kinase inhibitor (TKI) of PDGFRs, VEGFR-1 and -2, KIT and FLT3. This phase I study assessed the safety and PK of S in combination with D. Methods: Pts had refractory STs with ECOG PS ≤1. The first cohort received D 60 mg/m2 IV every 3 wks (q3w) and continuous S 50 mg/d. Doses were escalated in serial cohorts of 3–6 pts to determine the maximum tolerated dose (MTD). The MTD was exceeded if >1/3 pts experienced dose limiting toxicities (DLTs) within the first 2 cycles (6 wks) of treatment. Adverse events (AEs) were graded according to NCI CTCAE v.3. Results: 23 pts (32–75 yrs) have been treated to date. All malignant melanoma (MEL) pts had progressed under DTIC/cisplatin ± other agents and all gastrointestinal stromal tumors (GISTs) were resistant to TKIs. All pts had progressive tumors at baseline according to RECIST. Doses ranged from 50–100 mg/d for S and 60–75 mg/m2 for D. Most common tumor types were MEL (n=12), GIST (n=4), sarcoma (n=2) and cancer of unknown primary (CUP; n=2). Most frequent drug-related AEs were alopecia (70%), fatigue, nausea (65%), neutropenia, anorexia and diarrhea (60%). DLTs were observed in 3 pts at the highest doses and in 2/6 at MTD. Unacceptable toxicity, including neutropenic fever (n=5), asthenia (n=1) and neutropenia G4 (n=2), was also observed in 3 of 8 pts in an expanded cohort. Best responses according to RECIST included partial response (n=6, 1 of which unconfirmed), stable disease ([SD]; n=12), progressive disease (n=3) and too early (n=2). Of 12 pts with MEL, objective responses were observed in 4 pts. A further response was seen in CUP. Prolonged SD has been reported for 1 GIST pt who remains on treatment. The number of treatment cycles ranged from 1–22+ in the total population, 1–20+ in treatment-refractory MEL and 5–22+ in GIST. There was no evidence of a PK interaction between S and D based on maximum plasma concentrations and area under the curve. Conclusions: The combination of continuous S 50 mg/d with D 75 mg/m2 q3w in pts with advanced STs is tolerable and active in treatment-refractory MEL, GIST and CUP. No PK drug interaction was observed. Further disease-specific phase II studies are clearly warranted at this dose. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Cancer Risk Factors: An Analysis of Utah Mormons and Non-Mormons&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: D. W. West, Ph.D., J. L. Lyon, M.D., M.P.H., J. W. Gardner, M.D., M.P.H.
Journal: JNCI Journal of the National Cancer Institute (1980)

In a comparison of Mormons and non-Mormons in Utah, more Mormon men and women married spouses of the same faith, were religiously active, were of Northern Europe ancestry, lived in rural areas, had fewer exposures to occupational hazards, were less likely to smoke cigarettes or drink coffee, tea, and alcohol, used fats in cooking, and were more often married that was the cohort of other religions. No differences existed in occupation, but Mormon men had completed more years of schooling. Mormon women were less likely to be college graduates, had fewer sexual partners, had more pregnancies, were older at first pregnancy, were less likely to use birth control pills, had fewer miscarriages and hysterectomies, examined their breasts more often, and had more breast X-rays. For women, there was only a small difference by religion for age at first intercourse and no difference for age at which they began using birth control pills. Religious activity was examined for Mormons, and in most instances inactive Mormons were more like the non-Mormon population in respect to the variables measured.
Brief Communication : Isolation of an Endogenous C-Type RNA Virus From Mus musculus molossinus 2
Authors: Hendrick G. Bedigian, Hans Meier
Journal: JNCI Journal of the National Cancer Institute (1975)

We isolated a type-C RNA virus from the Japanese field mouse, Mus musculus molossinus. M. musculus musculus and M. musculus molossinus are two different subspecies of Mus and thus only distantly related. The virus grew only on cells foreign to the host, was xenotropic, and readily rescued the murine sarcoma (MuSV) genome from a normal rat kidney cell line transformed nonproductively by the Harvey strain of MuSV. The virus banded at a density of 1.16 g/ml and contained an RNA-dependent DNA polymerase.
Glomerular epithelial cells produce endothelin-1.
Authors: A V Cybulsky, D J Stewart, M I Cybulsky
Journal: Journal of the American Society of Nephrology (1993)

Endothelin-1, a vasoactive peptide originally isolated from vascular endothelial cell culture supernatants, has constricting or mitogenic effects on smooth muscle and glomerular mesangial cells. Whether or not cultured rat glomerular epithelial cells synthesize endothelin-1 was assessed. Under basal culture conditions, the synthesis and release of endothelin-1 peptide by glomerular epithelial cells was time dependent, reaching 0.231 +/- 0.017 pg/1,000 cells at 24 h. For comparison, unstimulated bovine pulmonary artery endothelial cells and rat mesangial cells produced 0.982 +/- 0.237 and 0.004 +/- 0.002 pg of endothelin-1 peptide/1,000 cells per 24 h, respectively. In addition to endothelin-1 peptide, unstimulated glomerular epithelial cells expressed preproendothelin-1 mRNA. Transforming growth factor-beta, complement C5b-9, thrombin, and phorbol myristate acetate significantly enhanced endothelin-1 peptide synthesis in glomerular epithelial cells (45, 15, 55, and 25% above basal levels at 24 h, respectively), whereas epidermal growth factor had no effect. Thrombin and phorbol myristate acetate appeared to stimulate endothelin-1 peptide by activating protein kinase C, because the protein kinase inhibitor 1-(5-isoquinolinyl-sulfonyl)-3-methyl-piperazine abolished the thrombin- and phorbol myristate acetate-induced rise in endothelin-1 but had no effect on basal production. The stimulatory effect of thrombin was also markedly diminished in glomerular epithelial cells that had been depleted of protein kinase C by prolonged preincubation with a high dose of phorbol myristate acetate. Thus, glomerular epithelial cells may be an important source of endothelin-1, which might influence glomerular vasoconstriction or proliferation of target cells, particularly in the presence of proinflammatory molecules in the glomerulus.
Night shift, vitamin D and occupational allergies in bakers
Authors: Mario Olivieri, Carlo Alberto Biscardo, Dario Valenza, Giuseppe Verlato
Journal: European Respiratory Journal (2014)

Background.Night work can influence vitamin D level and growing evidence connects vitamin D with allergic diseases.  Aims. To evaluate the effect of working schedule on vitamin D levels in bakers.  Methods.Forty-four bakers, participating in a survey on the prevalence of occupational allergic diseases, underwent a clinical evaluation, including waist-to-hip ratio (WHR) assessment, vitamin D measurement, spirometry, methacholine challenge, SPT to bakery9s allergens, NET evaluation.  Results.Thirty-tree bakers were working at night, while 11 during daytime. Normal vitamin D levels (g30 ng/mL) were observed only in 3 bakers, all of them working during daytime. Median vitamin D level was significantly lower in night workers (15.1 ng/mL, range 4.9-26.3) than in daytime workers (27.1 ng/mL, range 17.8-41.7). Vitamin D deficiency (l20 ng/mL) was observed in 27 night working bakers (82%) but only in one daytime working baker. WHR (Spearman9s rho = -0.406, pl0.01) and the presence of occupational allergic diseases (n=31) were significantly associated with vitamin D levels in univariable analysis.  In multivariable analysis only working schedule was a significant predictor of vitamin D levels (pl0.001). According to a quantile regression model, median vitamin D level in night working bakers was lower by 9.6 ng/mL (95% CI 16.3 – 2.9) with respect to daytime working bakers (p=0.006).  Conclusion.Vitamin D insufficiency is very common in bakers, especially in night workers. The main risk factor of vitamin D deficiency was working at night, while WHR and occupational allergic diseases did not independently affect vitamin D levels in this small sample.
Diagnosis of mediastinal lymphadenopathy: Clinical-radiological methods vs. mediastinoscopy
Authors: Anna Chernihovski, Lilia Lysansky, Vadim Sonkin, Hector I. Cohen, Alexander Gurevich, Edward Altman
Journal: European Respiratory Journal (2014)

Introduction:  Today, mediastinal lymphadenopathy (MLAP) is increasingly detected and diagnosed owing to major technological advances. Nevertheless, efficacy of clinical-radiological methods has not yet been evaluated properly in comparison with cervical mediastinoscopy, considered the gold standard method for diagnosis of MLAP.   Objectives:  To evaluate diagnostic abilities of modern clinical –radiological methods in comparison with mediastinoscopy in patients with MLAP.   Methods:  A retrospective review of 103 patients9 medical documents with MLAP admitted to Western Galilee Hospital from 2001-2012. Of 103 patients 59 male, 44 female; mean age 57 years. Clinical-radiological methods together with mediastinoscopy were employed for diagnosis. Ancillary methods (bronchoscopy with needle biopsy, skin and bone marrow biopsy, etc) were used in 33.3% of MLAP patients. Preliminary clinical-radiological diagnosis of MLAP type was compared with results of mediastinoscopy.   Results:  Preliminary clinical-radiological diagnosis of MLAP type was confirmed by mediastinoscopy in patients with: sarcoidosis -83.9%, bronchogenic carcinoma -82.4%, lymphoma -33.7%, non-specific lymphadenopathy-20.4%. Prompt employment of mediastinoscopy helped establish diagnosis during one-two weeks (51.4%). Mediastinoscopy was performed without complications with diagnostic yield 100%. During patient follow up there were no changes in established diagnosis.   Conclusions:  Clinical-radiological preliminary diagnosis was very effective in patients with sarcoidosis and bronchogenic carcinoma. Lymphoma (early stage) and non-specific enlargement of mediastinal lymph nodes were rather difficult to diagnose without mediastinoscopy.
Pilot study of fixed-dose bevacizumab (200 mg) for solid malignancies
Authors: S. K. Reddy, M. Curti, M. Janis, R. Minow
Journal: Journal of Clinical Oncology (2009)

e14600 Background: We report our initial experience with fixed dose bevacizumab at 200mg (approximately 3mg/kg). Phase I studies suggested that an optimal dose for phase II studies with bevacizumab is 3mg/kg and that circulating VEGF was undetectable at 0.3mg/kg. (Gordon et al. JCO 2001) We proposed a fixed-dose regimen of bevacizumab which we hypothesized would yield equivalent response rates with reduced toxicities and cost versus higher-dose regimens. Patients with advanced malignancies for whom bevacizumab would be indicated were analyzed. Methods: 15 patients were treated with 200mg bevacizumab in combination with antineoplastic therapy. 6 patients had NSCLCa, 8 patients had Colorectal cancer, and 1 patient had BRCA. Results: 15 patients are evaulable for response and have completed a total of 234 doses of bevacizumab (median number of doses =13) with no grade III/IV toxicity, or bevacizumab associated toxicities seen. No grade III or greater hypertension was observed. Proteinuria was not formally assessed, but no grade 3 or greater proteinuria was reported. All patients are evaluable for response with overall response rate of 33% (5/15). With a median follow-up (from the start of bevacizumab) of 452 days (222–1,699 days), median survival has not been reached with only 2 deaths. Conclusions: Fixed dose bevacizumab appears to be effective, less toxic, significantly less expensive and supported by biologic rationale and prior phase I studies and warrants further investigation. Additional patients will be accrued in a prospective phase II trial. [Table: see text]
P73 Referral of hepatitis B surface Ag positive patients to specialist hepatology care: need for improvement
Authors: B Smith, I Brown, D Muir, P Nutter
Journal: Gut (2010)

Introduction  There are a number of obstacles to ensuring appropriate diagnosis and treatment of both hepatitis B and hepatitis C patients. A major potential problem is the failure of onward referral to specialist care following the finding that a patient is HBsAg (+). This is of particular concern due to existing misconceptions relating to supposed “healthy carrier states” and lack of knowledge regarding efficacy of current hepatitis B treatments.  Aim  The aim of this study was to establish what proportion of patients found to be HBsAg (+) by both primary care and hospital clinicians were referred to, and attended specialist hepatology clinics.  Method  All HBsAg (+) results obtained by the virology department at St Mary9s Hospital over a 3 year period from Jan 1 2007 to Dec 31 2009 were identified. Duplicate tests, equivocal serology and unidentifiable patients were removed. The source of the request was recorded: primary care, hospital out-patient, in-patient, Accident and Emergency or ante-natal clinic. The patient administration system at SMH was used to determine how many of these patients attended at least one hepatology clinic at SMH. For patients who failed to attend hepatology clinics the hospital notes were reviewed (when available) to try to establish reasons for lack of onward referral.  Results  Initially 2698 HBsAg (+) results were found. This was reduced to 1094 patients by excluding duplicate requests (including from within hepatology), indeterminate (n=18) and untraceable confidential hospital numbers used by the sexual health clinic (n=459).  The Abstract P73 Table 1 indicates patients tested in primary care were far less likely to reach specialist care, Antenatal patients were the commonest group tested in the hospital setting who failed to reach hepatology clinics (22 patients in total) but they also made up the largest group of patients tested in secondary care. It was not possible to exclude the possibility that some patients may have been attending hepatology clinics outside SMH, but this was not documented in notes as an explanation for lack of referral.  Conclusion  This retrospective review is imperfect and may underestimate the number of hepatitis B carriers reaching specialist care. Nonetheless a major problem clearly is still occurring despite very directive information appearing on virology result slips; the vast majority of patients found to be hepatitis B carriers in the community are not referred for appropriate follow-up. In-hospital referral rates are significantly better. This is consistent with a concerning survey of London GPs regarding knowledge of hepatitis and indications for referral (Taylor  et al Gut  2009; 59 (Suppl1):PTU-072) and indicates the need for improving education in this area.
Phase I study of the MEK1/2 inhibitor selumetinib (AZD6244) hydrogen sulfate in children and young adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs).
Authors: Brigitte C. Widemann, Leigh Jessica Marcus, Michael J. Fisher, Brian D. Weiss, AeRang Kim, Eva Dombi, Andrea Baldwin, Patricia Whitcomb, Staci Martin, Andrea Gillespie, Austin Doyle
Journal: Journal of Clinical Oncology (2014)

10018 Background: Lack of functional neurofibromin in NF1 leads to dysregulated Ras and tumorigenesis. Selumetinib (AZD6244; ARRY-142886), an oral selective inhibitor of MEK1/2, may inhibit PN growth by blocking Ras signaling. Methods: We are conducting a phase 1 trial (NCT01362803) to determine the maximum tolerated dose (MTD) and plasma pharmacokinetics (PK) of selumetinib in patients (pts) 3-18 years old with NF1 and inoperable PNs. The MTD is determined based on cycle (C) 1-3 toxicities. Selumetinib is administered BID on a continuous dosing schedule (1 C = 28 days) at dose level (DL) 1: 20 mg/m2/dose, and 2: 30 mg/m2/dose. Response evaluation with volumetric MRI analysis occurs after C 5, 10, and then after every 6 C (partial response [PR] = ≥20% decrease in the PN volume). Results: Eighteen pts (10 M:8 F, median age 12.9 years, range 5.3-18.5) with a median PN volume of 1204 mL (range 47-10,269 mL) have enrolled. DL2 exceeded the MTD with DLT in 2/6 pts: grade (gr) 3 creatine kinase (CK) elevation (n=1), and gr 3 decrease in left ventricular ejection fraction (n=1). DL1 was tolerated with DLT in 2/12 pts: gr 3 cellulitis (n=1), and grade 3 urticaria (n=1). The most frequent toxicities (all grades) are acneiform rash, asymptomatic CK elevation, nausea, vomiting, abdominal pain, diarrhea, and fatigue. All DLTs have been reversible. Preliminary median (range) selumetinib C1 day 1 PK parameters [DL1 (n=2), DL2 (n=5)] were: Cmax DL1 513 ng/mL (487-539), DL2 841 ng/mL (576-1770); AUC0-24hDL1 2068 (2046-2089) ngxh/mL, DL2 2702 (2088-6008) ngxh/mL; half-life DL1 7.7 h (6.8-8.5), DL2 7.6 h (5.4-9.8). Of 11 pts with ≥ 1 restaging MRI, all had a decrease in PN volume (median maximal decrease 24%, range 8-39), and 3/5 at DL1, and 3/6 at DL 2 had a PR. All pts remain on trial after a median of 9 C (range 4-30). Conclusions: In children with NF1 PNs selumetinib is tolerated at 20 mg/m2/dose BID on a continuous dosing schedule, approximately 50% of the adult recommended dose (75 mg BID). Preliminary activity is observed at DL1 and DL2. Enrollment is being expanded at 25 mg/m2/dose, the MTD in study PBTC-029 for pediatric low grade gliomas, and a phase II trial is in development. Clinical trial information: NCT01362803.
Long-term outcomes of endoscopic resection for early gastric cancer: Appropriate surveillance strategy based on the incidence and patterns of local, metachronous, and extragastric recurrence.
Authors: Eun Ran Kim, Jae J. Kim, Byung-Hoon Min, Yang Won Min, Jun Haeng Lee, Jae Gyu Kim, Poong-Lyul Rhee
Journal: Journal of Clinical Oncology (2014)

2 Background: Endoscopic resection (ER) has been accepted as standard treatment of EGC. However, data about long-term outcomes especially related with recurrence have not yet been enough and appropriate surveillance strategy is not established. We evaluated the patterns and risk factors of recurrence, through evaluating the long-term outcomes of ER for treatment of EGCs comparing conventional and expanded indication criteria. Methods: We performed a retrospective review of prospectively and consecutively collected database of 1,855 EGCs in 1,803 patients [1,409 lesions in the conventional indication (CI) and 446 lesions in expanded indication (EI)] underwent ER for EGCs from April 2000 to June 2011. Results: Local recurrence was occurred from five tumors (0.35%) in the CI group and one tumor (0.22%) in the EI group. The median local recurrence interval was 13.5 months (range 2-34 months). 48 (3.1%) patients developed metachronous EGCs during follow up period. The median duration until metachronous recurrence was occurred, was 27.3 months (range, 12.25-115.29 months). There was not significantly different between metachronous group and non-metachronouos group except sex and histologic differentiation. Extragastric recurrence of tumor occurred from two patients in each of the CI and EI group. The extragastric recurrence interval was 62 months in the CI group and 48 months in the EI group. At that time, endoscopic examination showed no evidence of local recurrence around ESD scar area. Conclusions: The expanded indication of ER for EGCs showed acceptable long-term outcomes. More than 5 years of close follow up is needed and CT should be performed together with endoscopy for surveillance of recurrence after ER for EGC in the conventional indication group as well as the expanded indication group.