tbuckley/cabot-search huggingface dataset:
Transcutaneous Measurements of Oxygen Tension at Edges of Leg Ulcers: Preliminary Communication
Authors: R Mani, F W Gorman, J E White
Journal: Journal of the Royal Society of Medicine (1986)

Using skin-surface sensors, transcutaneous oxygen tension (TcPo2) has been measured at the edges of ulcers and at control sites proximal to wounds on the same legs. TcPo2 at 43 degrees C at the edges of venous ulcers was found to be significantly different (P less than 0.003) from that of arterial and mixed arteriovenous ulcers (P less than 0.05) respectively. TcPo2 on healed skin was higher than at any wound edge. At this temperature TcPo2 was also found to be significantly different (P less than 0.001) on the intact skin of patients with venous disease when compared with measurements at identical sites on healthy controls. In the same group, these TcPo2 values increased with dependency. By contrast, at 37 degrees C TcPo2 was no different between groups (P less than 0.10), nor did it alter with position. This protocol adopted for investigating ulcers enables a quantitative distinction to be made between ulcers of different aetiologies. The differences in TcPo2 between different ulcers and healed skin support the fibrin cuff mechanism which has been suggested as the cause of venous ulceration.
Identification of cancer of unknown primary with gene expression profiling
Authors: H. Li, K. Qu, K. Tokoro, Y. Ren, J. Y. Liu, A. Sferruzza, R. Bender
Journal: Journal of Clinical Oncology (2006)

10052 Background: Patients with metastatic cancer of unknown primary (CUP) generally have a poor prognosis, with a median survival of 2–10 months. Conventional diagnostic approaches for identifying the primary tumor site are successful in only 20%-30% of cases; however, such identification provides prognostic information and helps with selection of tumor-specific therapy, leading to improved survival. Recent studies indicate that gene expression-based classification of CUP is highly successful in predicting the site of origin. We report herein development and validation of a method that determines the site of tumor origin by comparing the gene expression profiles of CUP cases to those in a database created from known tumor types. Methods: RNA extracted from frozen and formalin-fixed, paraffin-embedded (FFPE) tissue wasis purified and amplified using the Paradise Reagent System System (Arcturus, Mountain View, CA). Following reverse-transcription, cDNA products wereare used in a semi-quantitative real-time PCR to detect 87 tumor-associated genes and 5 reference genes in an ABI PRISM 7900HT Detection System (Applied Biosystems, Foster City, CA). Gene expression data wereare then compared to those in a database, composed of gene expression profiles of 571 samples from 39 different tumor types, using k-nearest neighbor analysis to predict the most likely site of tumor origin. Intra- and interassay reproducibility was determined. Frozen and FFPE tissues (n=57) from a well-characterized, independent sample set were also tested in a blinded manner to further validate the method. Results: Based on the real-time PCR cycle threshold, the intra- and interassay reproducibility ranged from 0.1%-4.3% and 0.5%-8.2%, respectively. The primary tumor type was identified in 77% of cases. The assay determined the correct tumor type in 88% (44/50) of the samples. Seven samples were not reported: 3 failed to amplify adequately and 4 had an unacceptably low confidence level. Conclusions: We have shown that gene expression profiling can determine the most likely site of tumor origin. Our data suggest that this new method is able tomay identify the primary site of tumor origin in 77% of CUP cases. No significant financial relationships to disclose.
A dose finding followed by a phase II study of oral UFT (uracil/tegafur) and lv (leucovorin) plus i.v. mitomycin (MMC) in patients (pts) with metastatic colorectal cancer (MCRC): Phase I results
Authors: E. Maiello, M. Lopez, R. V. Iaffaioli, R. Tambaro, G. Paoletti, F. Giuliani, G. Colucci
Journal: Journal of Clinical Oncology (2004)

3709 Background: UFT/LV is an orally available regimen with proven activity in MCRC pts. Two randomized phase III trials (J.Y. Douillard et al., JCO 2002; J. Carmichael et al, JCO 2002) showed equivalent survival and significant safety improvements of UFT/LV when compared to bolus IV 5FU/LV. MMC combined with IV 5FU produces a 33%–39% response rate in pts with MCRC. This multicenter study was performed to evaluate the safety and the activity of UFT/LV in combination with MMC in pts with MCRC. Methods: In the phase I part of the trial DLTs and MTD were identified in order to recommend a dose for the Phase II portion of the study. Cohorts of 3 to 6 pts were treated with MMC (10 mg/m2, IV d1) and LV (90 mg/d, po x 28 d) at fixed doses; the starting dose of UFT was 200 mg/m2/d. Doses of UFT were increased by 50 mg/m2 increments up to 300 mg/m2 x 28 d. Treatment was repeated every 5 weeks. Results: Twelve pts (9 female and 3 male) with pretreated MCRC and measurable disease were enrolled in the Phase I portion of the study. Ten (83%) patients received study treatment in the second line setting, while the two other patients as first and third line, respectively. Median age was 62 years (range 44 -76); PS 0/1/2 in 9/2/1 patients. No DLT's were observed in the first two UFT dose levels (200 and 250 mg/m2/d). Among the first 3 pts enrolled at level 3 (300 mg/m2/d), one pt developed G3 anemia and G2 thrombocytopenia that did not resolve within 14 days. Therefore, 3 additional pts were accrued at this level, with no DLTs being observed. The most common toxicities (NCI-CTC) reported during the first cycle in all 12 pts were as follows: G1 (pts): anemia 2, thrombocytopenia 5, neutropenia 1, vomiting 1, diarrhea 1, fatigue 1, alopecia 1; G2 (pts): thrombocytopenia 1, fever 2, vomiting 2, diarrhea 1; G3 (pts): anemia 1. Overall, the combination of UFT/LV and MMC was well tolerated with no grade 4 toxicity reported. Efficacy data from the phase I portion are pending. Conclusions: The recommended dose for phase II is UFT 300 mg/m2/d x 28, LV 90 mg/d x 28 days and MMC 10 mg/m2 d 1 given every 5 weeks. The phase II portion of the study is currently ongoing. No significant financial relationships to disclose.
논평참조 : 생체 부분간이식 수술 후 C형간염의 임상 양상
Authors: 박정익 ( Jeong Ik Park ), 최건무 ( Kun Moo Choi ), 이승규 ( Sung Gyu Lee ), 황신 ( Shin Hwang ), 김기훈 ( Ki Hun Kim ), 안철수 ( Chul Soo Ahn ), 문덕복 ( Deok Bog Moon ), 정영화 ( Young Hwa Chung ), 이영상 ( Yung Sang Lee ), 서동진 ( Dong Jin Suh )
Journal: Clinical and Molecular Hepatology (2007)

배경/목적: C형간염에 의한 간경변증은 서구에서 간이식 수술의 가장 흔한 적응증 중 하나이고 국내에서도 증가 추세에 있다. 하지만 이식 후 초기부터 높은 C형간염의 재발률 때문에 환자와 이식편의 생존율은 불량하다고 알려져 있다. 이 연구에서는 C형간염 환자들의 생체 부분간이식 수술 이후의 재발의 빈도와 임상경과를 알아보았고, 재발된 환자들의 리바비린(ribavirin)과 인터페론 (pegylated Interferon alpha-2a) 치료의 반응 정도를 분석하였다. 대상 및 방법: 1992년 8월부터 2006년 6월까지 서울아산병원에서 C형간염으로 진단 받고 생체 부분간이식 수술을 시행받은 39명의 환자들을 대상으로 의무기록을 후향 조사하였으며, 추적기간의 중앙값은 24.9개월이었다. 본원에서 Protocol 간 조직생검을 시행하지 않기 때문에 이 연구에서는 C형간염의 재발을 간효소 수치의 증가가 있으면서, HCV RNA값이 1.0×107 IU/mL 이상의 증가 소견을 동반한 때로 정의하였다. 결과: 간세포암종 동반 유무에 따른 C형간염 환자의 생체 부분간이식 수술 후 2년 환자 생존율은 간세포암종을 동반한 경우 81.2%, 동반하지 않은 경우 81.3%로 유의한 차이는 없었고, 2년 이식편 생존율은 간세포암종을 동반한 경우 81.2%, 동반하지 않은 경우 68.2%였으나 통계에서 유의성은 없었다. 추적기간 동안 C형간염 재발로 사망한 경우는 없었다. C형간염의 재발은 39명의 환자들 중 26명 (66.6%)에서 있었다. 재발은 환자의 86.7%가 이식 후 1년 이내에 있었다. 항바이러스치료는 생체 간이식 수술 시행 이후 C형간염 재발 환자 모두에게 시행하였는데, 리바비린과 인터페론 병합요법으로 치료받은 환자 16명 중 9명에서 추적관찰 기간 동안 HCV RNA가 음전되어 유지되었고, 리바비린 단독으로 치료받은 환자 10명 중에서는 음성으로 전환된 환자가 없었다. 재발에 영향을 주는 인자로는 수혜자의 나이를 제외하고는 통계에서 유의한 인자는 없었다. 결론: 생체 부분간이식 수술 후 C형간염이 재발한 환자들에 대해 리바비린과 인터페론의 병합요법의 적극적인 치료를 시행할 수 있다면 보다 향상된 치료 결과를 기대할 수 있을 것으로 생각한다.
Usefulness of multiplex real-time polymerase chain reaction for diagnosing community acquired pneumonia in Japanese adults
Authors: Yutaka Yoshii, Kenichiro Shimizu, Miyuki Morozumi, Nahoko Chiba, Kimiko Ubukata, Makoto Kawaishi, Keisuke Saito, Jun Araya, Katsutoshi Nakyama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2013)

Background: Usefulness of multiplex real-time polymerase chain reaction (RT-PCR) and frequency of macrolide-resistant (MR) Mycoplasma pneumoniae ( M. p ) in Japanese adults are unknown. Aims: To diagnose causative pathogens of community acquired pneumonia (CAP) in Japanese adults with RT-PCR vs. conventional tests (sputum/blood culture, urine antigen for Streptococcus pneumoniae [ S. p ]/ Legionella pneumophila [ L. p ], and paired serum of M. p antibody) and clarify frequency of MR M. p in Japanese adults. Methods: We prospectively enrolled 29 CAP patients ≥20 years old from Sep 2012 to Feb 2013. CAP was defined based on respiratory symptoms and laboratory/chest X-ray findings excluding noninfectious causes. We collected sputum, nasopharyngeal swab, urine, and blood samples of each patient. RT-PCR can identify 6 bacteria and 11 viruses in sputum and nasopharyngeal swab samples. Causative pathogens were identified by each test. MR gene was checked if PCR of M. p was positive. Results: Mean patient age (15 men) was 56 years, and 20 had taken previous antibiotics. Sensitivity was significantly higher in RT-PCR vs. conventional tests (69%, n=20 vs. 41%, n=12; P <0.05). Common causative pathogens by RT-PCR were S. p (n=10), M. p (n=7) and Haemophilus influenzae (n=4), including duplication, with 4 cases of mixed bacterial/viral infection. Four (57%) of 7 M.p patients were MR by RT-PCR. Conclusions: Since many patients had taken previous treatment, sensitivity of conventional tests was low, but RT-PCR was unaffected by this. RT-PCR was useful for CAP in Japanese adults. When M. p is suspected, RT-PCR is especially useful because sensitivity is high and MR can be checked.
Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making.
Authors: B F Cole, P Solal-Céligny, R D Gelber, E Lepage, C Gisselbrecht, F Reyes, C Sebban, D Sugano, C Tendler, A Goldhirsch
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. PATIENTS AND METHODS A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groupe d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly for 18 months. RESULTS After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided a greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. This gain was significant (P &lt; .05) in all cases except for patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. CONCLUSION In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time following disease progression.
Comparison of simultaneous high dose stereotactic radiotherapy with normofractionated radiotherapy in patients with metastatic renal cell carcinoma under systemic therapy.
Authors: Michael D. Staehler, Behr Lisa, Philipp Nuhn, Boris Schlenker, Ralf Wilkowski
Journal: Journal of Clinical Oncology (2015)

467 Background: Conventional radiation therapy (RT) is considered ineffective in metastatic renal cell carcinoma (mRCC). There are data suggesting that this might be related to low doses per fraction and that higher doses could be more effective. We introduced hypofracationated high-dose radiation therapy in patients with an indication for radiotherapy an retrospectively compared the results to patients with a conventional radiation therapy. Methods: We identified 97 pts with mRCC and an indication for radiotherapy of metastatic lesions between 2007 and 2013. All pts underwent simultaneous systemic therapy based on targeted agents and systemic therapy. 83 pts had a hypofractionated high dose stereotactic radiation (HDRT) (5 Gy per fraction, 3 fractions per week, total 45 Gy) while 14 pts underwent conventional normo-fractionated radiotherapy (NDR) (1.8 Gy per fraction) as described elsewhere. Results: Median age was 64.1 years (27-86). 189 metastatic lesions were irradiated. 64% of the pts had clear cell histology, with 14% harboring papillary RCC type II and 11% other subentities. Median overall survival was significantly longer for pts after HDRT was 9.4 months (+/-9.4 months) and 4.5 months (+/- 3.4 months) after NDR (p=0.01). The multivariate cox regression analysis revealed the MSKCC risk score, HDR therapy and the disease free survival as positive predictors for survival. No grade III toxicities were found, with 24% of the patients experiencing grade 1 or 2 side effects, mainly diarrhea and fatigue. Conclusions: In mRCC HDRT with simultaneous systemic therapy is related to a better overall survival than NRT. HDRT in combination with targeted therapy should be regarded the standard of care if RT is indicated.
Small cell lung cancer (SCLC): Intrathoracic lymph node enlargement as an indicator of prognosis
Authors: H. Y. Wong, H. Raftopoulos, A. Rozenshtein, G. D. N. Pearson, J. H. M. Austin
Journal: Journal of Clinical Oncology (2005)

7273 Background: Although radiologic-prognostic correlates for non-SCLC have been extensively studied in the CT era, such correlates for CT assessment of SCLC have received little attention. The purpose of the present analysis was to determine whether assessment of intrathoracic lymph node (LN) enlargement on chest CT scans would allow further stratification of prognosis beyond the classifications of limited-stage and extensive-stage disease. Methods: A retrospective review of chest CT scans was performed for 52 consecutive patients (mean age 69 years old, 32 female, 20 male) from 1998 to 2002 with histologically or cytologically proven SCLC. Three chest radiologists assessed intrathoracic LN enlargement on each CT scan. The presence or absence of extrathoracic metastatic disease and patient survival from time of diagnosis were recorded. Data analysis used the Kaplan-Meier method and multivariate Cox regression model. Results: The number of enlarged intrathoracic LN and evidence of extrathoracic metastasis were each an independent prognostic indicator (p <0.001). As expected, patients without extrathoracic metastasis (limited stage) (n=26) had longer survival than patients with extrathoracic metastasis (extensive stage) (n=26) (median survival 1.6 years versus 0.6 years, p=0.002). In patients without extrathoracic metastasis, those with 0–2 enlarged intrathoracic LN (n=13) had a significantly longer survival than those with 3 or more enlarged intrathoracic LN (n=13) (median survival 3.9 years versus 1.3 years, p=0.03). In patients with extrathoracic metastasis, those with 0–2 enlarged intrathoracic LN (n=11) also had a significantly longer survival than those with 3 or more enlarged intrathoracic LN (n=15) (median survival 1.1 years versus 0.6 years, p=0.02). The primary tumor size was not a statistically significant prognostic indicator. Conclusion: In this retrospective study, the presence and extent of intrathoracic LN enlargement, as assessed by CT scan, correlated significantly with survival in both limited and extensive disease SCLC patients. Chest CT evaluation of the number of enlarged intrathoracic LN allows stratification of prognosis in patients with SCLC. No significant financial relationships to disclose.
Metformin Impact on Progression-Free Survival in Advanced Pancreatic Well-Differentiated Neuroendocrine Tumors (Pwdnets). Retrospective Evaluation in Diabetic Patients Receiving Everolimus Plus Octreotide Lar Treatment
Authors: S. Pusceddu, F.G.M. De Braud, L. Concas, C. Bregant, F. Festinese, L. Giacomelli, E. D'Autilia, B. Formisano, V. Mazzaferro, R. Buzzoni
Journal: Annals of Oncology (2014)
A systematic review of post-lumpectomy radiation therapy regimens
Authors: B. E. Ellerin, J. Seidenfeld, S. C. Formenti
Journal: Journal of Clinical Oncology (2004)

683 Background: Various post-lumpectomy radiotherapy (PLRT) regimens currently are used that differ in: total radiation doses, fractionation schedules, volumes of breast treated, techniques of administration, and duration of treatment. These have not been directly compared or systematically reviewed. Methods: We searched PubMed for publications on PLRT through 2003. We categorized PLRT regimens into eight distinct types according to volume of breast treated (whole or partial). Whole-breast (WBRT) variants were distinguished by duration (six, five, four, or two weeks) and also by total dose and fractionation schedule, while partial-breast (PBRT) variants were distinguished by technique (multiplane vs. balloon brachytherapy vs. conformal external beam therapy), with intensity-modulated radiation therapy (IMRT) as a “dual-use” variant for either WBRT or PBRT. We compared all techniques with respect to five criteria: cost, convenience, cosmesis, complications, and control, using available literature according to its strength of evidence. Where literature was lacking, we supplied next-best institutional information. We assigned a composite cost score to each regimen to reflect technical factors and overall treatment time. We then ranked the regimens according to the five evaluation criteria. Results: The available evidence suggested the following regimens rank highest for each evaluation criterion: for cost, 4-week WBRT; for convenience, 2-week WBRT; for cosmesis and complications, 4, 5, and 6-week WBRT: for control, 6-week WBRT. For all PBRT regimens, inadequate follow-up was available to judge complications and control. Conclusions: Since control is the paramount criterion in PLRT, further follow-up and direct randomized comparisons are necessary for evidence-based decision-making. At this time, control data are most mature for 5-week and 6-week WBRT; these should be recommended to most patients. No significant financial relationships to disclose.
Phase I trials of the oral histone deacetylase (HDAC) inhibitor MGCD0103 given either daily or 3x weekly for 14 days every 3 weeks in patients (pts) with advanced solid tumors
Authors: K. Gelmon, A. Tolcher, M. Carducci, G. K. Reid, Z. Li, A. Kalita, V. Callejas, J. Longstreth, J. M. Besterman, L. L. Siu
Journal: Journal of Clinical Oncology (2005)

3147 Background: MGCD0103 is a novel isoform-selective inhibitor of human HDACs. Deacetylation of histones by HDACs is postulated to inactivate tumor suppressor genes leading to neoplastic transformation. Thus, inhibition of this enzyme might restore normal growth control. Methods: Two Phase I trials of MGCD0103 have been initiated in pts with advanced solid tumors or non-Hodgkin’s lymphoma evaluating safety and tolerability of two schedules. Pharmacokinetics (PK) evaluation and pharmacodynamics (PD) assessments of enzyme activity in buffy coat white cells are being performed in all pts. Results and Conclusion: Twenty-seven eligible pts have been entered at doses ranging from 12.5–27mg/m2. MGCD0103 is orally available and preliminary PK analyses show that the median t1/2 is 8.8 hours. The apparent oral clearances do not change between Day 1 and Day 14 of dosing. The apparent volume of distribution of MGCD0103 is large, averaging about 20-times body volume. Initial PD data suggest that, in some pts, the inhibition of HDAC activity in whole cells extends beyond the plasma half-life of the drug, lasting as long as 24 hours post drug administration. Initial results of a FACS assay measuring histone acetylation also suggest induction and prolonged maintenance of increased acetylation in some pts. All pts are evaluable for toxicity. The most common toxic effects and associated with study drug are: fatigue 20/27 pts (5 gr. 3), nausea 13 pts (1 gr 3), anorexia 8 pts, vomiting 6 pts, and diarrhea 5 pts. No drug-associated chemistry or hematology toxicities have been observed to date. Preliminary efficacy results show 1 patient with previously treated thymic carcinoma has experienced stable disease for 6 cycles on the daily x 14 schedule. Patient accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MethylGene MethylGene MethylGene
Age and Risk of Acute Leukemia
Authors: R G Stevens
Journal: JNCI Journal of the National Cancer Institute (1986)

Previously unavailable time-depth acute leukemia incidence data were obtained from the Connecticut Tumor Registry for the years 1935–82 and for ages 0–84 years at diagnosis. Acute non lymphocytic leukemia (ANLL) incidence has risen over the period of observation. Acute lymphocytic leukemia (ALL) incidence has risen much less dramatically. After adjustment for cohort effects, the age-incidence relationships of the acute leukemias show several remarkable features. Incidence of both ALL and ANLL is higher in males than in females in childhood but not in adulthood. Incidence of ALL is higher than incidence of ANLL in childhood, while the reverse is true in adulthood. After a fall in incidence in young adulthood, both ALL and ANLL show age-incidence curves that are similar to those of most adult carcinomas: Incidence increases as a power of age. These features of the age-risk relationship may reflect the growth characteristics of the normal hematopoietic stem cells at risk, and this growth may be influenced by exposure to infectious agents.