tbuckley/cabot-search huggingface dataset:
T1 G3 bladder cancer: A second-look endoscopic resection can help achieve a correct staging of a <i>“superficial-invasive”</i> tumor
Authors: M. Simone, G. Pomara, C. Milesi, P. Casale, C. Leonetti, F. Francesca
Journal: Journal of Clinical Oncology (2005)

4651 Background: About one third of urothelial bladder cancers is staged as T1. High grade (G3) T1 tumors present elevated recurrence and progression rates, with a metastatic and lethal potential ten times higher in comparison to other Ta-T1 cancers. Standard treatment, encompassing a transurethral resection plus endovesical Bacillus Calmette-Guérin (TUR + BCG), leads to 80% disease-free rates at 5 years. It is yet to be determined if BCG-non responders present a rapid recurrence, residual disease or a previously undetected mioinvasive lesion. A repeat resection reveals residual disease in more than 30%, and muscle invasion in up to 10% of T1 patients. In order to better stage T1 G3 patients we modified our traditional approach, now routinely repeating the endoscopic resection after the first intervention. Methods: 44 consecutive cases of T1G3 were diagnosed by TUR. 36 patients were males and 8 females; median age was 70 years (range 2 - 40). A repeat-TUR was performed four to six weeks after the first procedure. The technique involves a separate resection of: 1. all visible lesions or surgical scar. 2. borders of the resection area. 3. the “resection floor” including the muscular layer. Random biopsies complete the procedure. Results: 43 out of 44 patients were evaluable. In 14 of them (32.5%) no residual disease was demonstrated: treated with BCG, they are all disease-free at a median follow up of 9 months (range 2 - 40). Residual disease was revealed in 29 patients (67.5%): 3 Ta, 6 Tis, 14 T1G3, 6 T2. Thirteen cystectomies were performed: 3 because of infiltrating tumor, 2 due to rapid progression, 8 (T1G3 at 2nd-look) due to multifocal disease, unresponsive to BCG and/or with Tis. After ablative surgery 9/13 patients (69%) revealed a ≥ pT3 tumor; 4 of them (31%) were node positive. Conclusions: Patients primarily diagnosed with T1 G3 BC at TUR often have residual disease or, worse, are understaged; at times, Tis is also present. It seems there is a strong argument for a “second-look” TUR in this setting, to establish a correct diagnosis. Neverthless, many 2nd-look-positive patients are prone to progress despite BCG, thus demonstrating the high potential of aggressiveness of this apparently superficial tumor. No significant financial relationships to disclose.
Paclitaxel poliglumex (PPX) in combination with carboplatin (carb) for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC): Preliminary data
Authors: J. J. Nemunaitis, N. Leighl, W. Miller, Y. Cormier, A. Bernareggi, F. Oldham
Journal: Journal of Clinical Oncology (2005)

7230 Background: PPX (XYOTAX), a macromolecular drug conjugate that links paclitaxel with biodegradable polymer, poly-L-glutamic acid, is water soluble and can be administered as a 10 minute infusion. Eliminating the need for CremophorEL reduces the risk of hypersensitivity reactions, even without premedication. Preclinical and clinical findings show that PPX is relatively stable in plasma; more than 95% of paclitaxel in circulation is present as the inactive conjugate, reducing systemic exposure to high concentrations of free paclitaxel. The antitumor activity of single agent PPX in chemotherapy naïve high-risk patients with NSCLC has been previously reported. In addition, PPX has been successfully combined with standard doses of cisplatin and carb. This multicenter, open label study evaluates the safety and efficacy of PPX in a standard doublet regimen for 1st line treatment of NSCLC. Methods: PPX (210 mg/m2) was administered as a short (10–20 minute) IV infusion followed carb (AUC 6) q3w to chemotherapy-naïve patients (pts) with performance status (PS) 0–2. Pts were treated for up to 6 cycles. Safety was assessed using NCI CTC (v 2). Efficacy assessments were done after every 2nd cycle using RECIST. Plasma samples were collected for pharmacokinetic (PK) assessment of PPX. Results: 74 pts were treated. The median age was 64 (range 32–85). 53% of pts were male. 14% of pts had PS2. Of the 60 pts with efficacy assessment following cycle 2, 9 pts (15%) had partial response and 24 pts (40%) had stable disease as the best response. Adverse event (AE) data are available for 40 pts (see table). No hypersensitivity reactions were observed. Detailed PK data will be presented. Conclusions: Preliminary data suggest that PPX (210 mg/m2) in combination with carb (AUC 6) is active as 1st line treatment for NSCLC. PPX demonstrates easily manageable toxicities and is generally well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics Cell Therapeutics Cell Therapeutics
Determination of clear margin in breast-conserving surgery: Is 1 mm needed?
Authors: J. Geffrelot, F. Toudic Emily, C. Levy, C. Blanc Fournier, C. Segura, O. Switsers, D. Allouache, C. Delcambre, S. Martin, T. Delozier
Journal: Journal of Clinical Oncology (2010)

515 Background: Our aim was to define the role of complete excision and the value of minimal margin on the local control in breast conserving surgery (BCT). Methods: Between 1973 and 2002, 4,832 patients underwent BCT and radiotherapy at our institution. Clinical and pathologic characteristics evaluated were age, tumor size, histological subtype, grade, oestrogen and progesterone receptor status, in situ component, axillary nodal involvement, initial tumor location. Margin status was known in 2,569 patients. They were classified based on initial margin status: negative (more than 1 mm), close (less than 1 mm), positive. Median follow-up was 71 months. Local recurrence free survival was calculated by the Kaplan-Meyer method. A Cox proportional hazards model was used to estimate the risks of local recurrence. Results: The cumulative rate of local recurrence (LR) was 5.3% at 5 years and 10.3% at ten years. In univariate analysis, LR was influenced by margin status, age, histological subtype, grade, in situ component, oestrogen and progesterone receptor status and axillary nodal involvement. LR was not influenced by initial tumor location. The five-year local recurrence rate was 2% in patients with negative surgical margins, 4.6% in patients with close margins and 9% with positive margins (p < 10-4). No difference was observed when the margin was involved by invasive or in situ component. On multivariate analysis, factors associated with and increased risk of LR were: positive margins (HR 2.56 CI 95% [1.44-4.52]). young age (< = 40 years) (hazard ratio [HR]: 3.75 CI 95 % [1.91-7.35]), negative hormonal receptor status (HR: 2.68 CI 95% [1.45-4.95] ), axillary nodal involvement (HR: 1.74 CI 95% [1.01-3]). Conclusions: Margin status is an important risk factor for local recurence. A clear margin with 1 mm of clearance is the condition of a complete excision. No significant financial relationships to disclose.
The Boston State Hospital case: "involuntary mind control," the constitution, and the "right to rot"
Authors: P S Appelbaum, T G Gutheil
Journal: American Journal of Psychiatry (1980)

The recent Boston State Hospital case represents a problematic decision on the right of inpatients to refuse treatment. The authors describe how basic misconceptions of psychopharmacology led to questionable analysis of the constitutional issues at stake. The effects of the decision may seriously impair proper care for the hospitalized mentally ill.
Living with lymphedema - A cancer supportive care Website project
Authors: E. H. Rosenbaum, C. M. Dollbaum, A. Andrews, F. Manuel, M. Goldman, R. Wascher
Journal: Journal of Clinical Oncology (2004)

8231 Background: Lymphedema is a potentially severe and debilitating side effect of cancer surgery and radiation therapy. It adversely affects an estimated 10 to 30% of cancer survivors in both short-term and long-term discomfort, chronic pain, debility, and loss of function in the affected limb. Living with lymphedema presents many challenges, both physically and psychologically. Stress and frustration are compounded by the lack of or conflicting information on cause and therapy. Increased levels of anxiety and depression are often caused by the challenges faced in the workplace, in social situations, and at home. Patients struggle with body image, clothing, limitations in the ability to comfortably use a computer and of impaired sexual function. Optimal management of chronic lymphedema remains unclear at this time. Improved treatments and specialty clinics are being developed at this time. Methods: A pilot questionnaire was developed in September 2002 to evaluate the perceived utility of Living with Lymphedema on CancerSupportiveCare.com. Our website serves on average 2000 pages per month about lymphedema to interested patients, and healthcare providers to over 80 USA and non USA countries (number of hits is not included - the term hit is misleading, e.g. 100 graphics + 1 web page = 101 hits). Results: Online Questionnaire September 2002 –November 2003 146 were patients (88.5%) and 19 professionals (11.5%). Conclusion: By participating in our project a worldwide audience of patients and healthcare personnel derived significant and useful information and insight into lymphedema an often underreported complication of cancer treatment. This Internet-based approach facilitates better understanding of lymphedema through interactions between patients and specialists in a non - threatening and anonymous forum, and is associated with a very high level of patient satisfaction and overall quality of life. No significant financial relationships to disclose.
Correlation between FDG-PET and pathologic response in patients with rectal cancer treated with neoadjuvant chemo-radiotherapy: First results of the Bologna Project
Authors: F. Di Fabio, C. Pinto, S. Fanti, C. Ceccarelli, A. L. Gentile, F. L. Rojas Llimpe, C. Nanni, V. Mutri, N. Cacciari, A. Martoni
Journal: Journal of Clinical Oncology (2005)

3623 Background: The aim of the study was to evaluate the predictive value of FDG-PET in patients (pts) treated with neoadjuvant chemo-radiotherapy (CRT) for rectal cancer in the Bologna Project. Methods: Pts entering the study had histologically-proven rectal adenocarcinoma and stage uT3-T4 N-/+ or uT2 N-/+ with inferior location (<5 cm from the anal margin). Chemotherapy (CT) consisted of a weekly schedule of oxaliplatin (OXA) 60 mg/m2 iv for 6 times and 5-fluorouracil (5FU) 225 mg/m2/die protracted infusion iv d 1–38. Radiotherapy (RT) started the same day as CT and was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy (45 Gy in 25 fractions + a boost of 5.4 Gy in 3 fractions). Rectal surgery with total mesorectal excision was performed 6–8 weeks after the end of neoadjuvant treatment. The FDG-PET was performed at initial diagnosis and 6–7 weeks after the end of CRT (before surgery). The pathological examination of surgical specimens included the tumor regression grade (TRG) evaluation according to Mandard. Results: 15 pts were evaluated between June 2003 and October 2004. Pt characteristics were: 11 men and 4 women; median age 66 years (33–77); median Karnofsky PS 100 (90–100); stage: 1 uT2N-M0, 7 uT3N-M0, 4 uT3N+M0, 2 uT3NxM0 and 1 uT4NxM0. The FDG-PET correctly indentified the primary tumor in all 15 pts at initial diagnosis (100% sensitivity). The baseline (pre-CRT) mean Standardized Uptake Value (SUV) of all 15 pts was 18.6 (range 7–51). Pathological responses were as follows: complete response (pT0N0) with absence of tumor cells (TRG 1) in 3 pts; microscopic focus (pTmicN0) with rare residual cancer cells (TRG 2) in 9 pts; fibrosis outgrowing cancer cells (TRG 3) in 2 pts; cancer cells outgrowing fibrosis (TRG 4) in 1 pt. In 12 pT0N0 + pTmicN0 pts (TRG 1–2) the mean SUV after CRT was 2.7 (range 0–4.7) with 83.0% SUV mean decrease compared to the baseline. In 3 pts with TRG 3–4 the mean SUV after CRT was 5.1 (range 4.3–6.4) with 72.2% SUV mean decrease compared to the baseline. Conclusions: These early results suggest that higher % decrease of SUV before surgery in pts with rectal cancer treated with neoadjuvant CRT may be correlated with pathological response. No significant financial relationships to disclose.
Detection of lymphatic vessel invasion in early breast cancer by the monoclonal antibody D2–40 (podoplanin)
Authors: M. Braun, U. Flucke, M. Debald, M. Pölcher, G. Walgenbach-Bruenagel, K. J. Walgenbach, R. Büttner, W. Kuhn
Journal: Journal of Clinical Oncology (2008)

22042 Background: The purpose of this study was to compare the detection of lymphovascular invasion (LVI) by D2–40 (podoplanin) immunostaining with conventional hematoxylin-eosin (H.E.) staining in early breast cancer. We also aimed to find associations between the detection of D2–40 + LVI and other clinicopathological variables. Methods: Immunohistochemical staining with D2–40 and CD 34 and conventional H.E. staining was performed on consecutive formalin-fixed, paraffin-embedded tissue sections of 254 invasive breast tumors of 247 patients with node negative and node positive early breast cancer. For every tumor, the whole particular section, stained with H.E., CD34 and D2–40 was screened for the presence of lymphatic invasion Correlation with clinico-pathological factors and the eligibility for the prediction of axillary lymph node metastases was assessed. Results: LVI was identified by D2–40 (D2–40+) in 70 out of 254 tumors (28%) as compared to 40 tumors (16%) by routine HE staining (HE+). The increase of LVI detection was significant (p<0.001). Significant correlation was observed between D2–40+ LVI and age, t-stage, nodal status, grading and “triple negative” tumors (ER/PR and HER2neu negative). There was no correlation between D2–40+ LVI and menopausal-status, HER2-status and histological type. Based on multivariate analysis D2–40+ LVI was the strongest predictor for axillary lymph node metastases (OR = 3.489, p=0.0003), followed only by T-stage and grading (OR = 3.167 and 1.953, p=0.0003 and 0.0352). For 5 out of 35 patients (15%) with primary or secondary mastectomy who did not receive adjuvant radio-therapy, management would have changed to postmastectomy radiation in retrospect because of additional detected LVI by D2–40 immunostaining. Conclusions: Immunostaining with the monoclonal antibody D2–40 significantly increased the frequency of detection of lymphatic invasion compared to conventional H.E. staining in early breast cancer. Immunohistochemical detection of LVI by D2–40 might be of value in clinical practice. No significant financial relationships to disclose.
New Inf2 mutations in a large cohort with sporadic and hereditary FSGS and further evidence for variable
Authors: Rasheed Gbadegesin, Peter J Lavin, Gentzon Hall, B Bartkowiak, A Homstad, R Jiang, Wu G Byrd, Kelvin Lynn, Norman Wolfish, Caroline Ottati, Paul Stevens, David Howell, Peter Conlon, Michelle P Winn
Journal: Kidney International (2012)
Skeletal Muscle Diseases: Recent Advances and Some Related Basic Problems
Authors: E BAJUSZ, G JASMIN
Journal: JAMA (1963)

Recent advances in the knowledge of the structure and function of voluntary muscle and some of its diseases are reviewed on the basis of a recently published international symposium. Among the subjects discussed are: the specific metabolic role of various muscle cell constituents (e.g. sarcosomes, microsomes, sarcoplasmic reticulum); the relaxing factor system and the dual (tonic and phasic) innervation of muscle fibres; observations on the physiology of muscle training; the morphologic differential diagnosis of degenerative skeletal muscle diseases; the value of serum enzyme determinations in the early detection of muscular dystrophy and in the identification of dystrophic carriers; the classification and diagnosis of muscular hypotonias of infancy; the role of inactivity and the trophic control of the nervous system in the development of neural (or denervation) atrophies; factors influencing regeneration of muscle fibres; the significance, as a research tool, of the identification of hereditary primary muscle disease in laboratory animals.
Microbubble ultrasound compared to dynamic contrast MRI and CT for the assessment of vascular response to sunitinib in renal cell carcinoma.
Authors: G. A. Bjarnason, J. M. Hudson, C. Bailey, C. R. Lee, R. Williams, B. A. Lloyd, R. Kerbel, G. J. Stanisz, M. Atri, P. Burns
Journal: Journal of Clinical Oncology (2010)

e15039 Background: A novel ultrasound method employing microbubble (MB) contrast offers portable, noninvasive dynamic assessment of tumor blood flow. A MB contrast agent (Definity, Lantheus, Boston) is infused to produce vascular enhancement on nonlinear ultrasound imaging. The MBs, the size of red blood cells, remain intravascular. MBs are disrupted with an ultrasound pulse and the wash-in of new bubbles is imaged. This method, DCE-US, measures blood flow, velocity and vascular volume in multiple planes. Methods: Untreated patients (pts) with metastatic renal cell cancer (RCC) and a large abdominal tumor suitable for imaging were eligible for study and received Sunitinib 50 mg for 4 weeks on a 6-week cycle. DCE-US, contrast enhanced CT and DCE-MRI were performed on the first treatment course at baseline and on day 14. Blood samples for circulating endothelial cells (CECs) were obtained at the same time points. Results: The abdominal tumors imaged in 20 pts were the RCC primary (15pts), local recurrence (2), liver metastasis (1), retroperitoneal nodes (1) and a pancreas metastasis (1). In 16 pts progression free at 2 months, baseline vs. day 14 studies showed a significant (p < 0.05) decrease in blood volume in each of 13/16 pts (81%) on DCE-US, and a significant decrease in Ktrans and kep (Ktrans/ve) in 9/15 pts (60%) and 8/15 pts (53%) respectively on DCE-MRI. By RECIST criteria on CT, 3/16 (19%) and 13/16 (81%) were designated as partial response (PR) and stable disease (SD) respectively. By modified Choi criteria on CT, 8/13 (62%) and 5/13 (38%) were designated as PR and SD respectively. The number of viable CECs decreased in 10/14 (71%) and of apoptotic CECs in 9/14 (64%) pts. In 4 pts that progressed during the first sunitinib course, DCE-US showed a significant increase in blood volume in 1/4, no change in 2/4 and a decrease in 1/4. There was no increase in Ktrans or kep in progressing pts. The coefficient of variation of the same image plane scanned multiple times with DCE-US was 10%. Conclusions: DCE-US at 14 days is at least as good as DCE-MRI and a contrast enhanced CT at predicting progression-free survival at 2 months. This method is reproducible and takes advantage of a non-diffusible tracer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Philips Ultrasound, Supersonic Imagine Inc. Pfizer Lantheus Medical Imaging, Inc., Pfizer
Liberal bias and the five-factor model
Authors: Evan Charney
Journal: Behavioral and Brain Sciences (2015)

Abstract Duarte et al. draw attention to the “embedding of liberal values and methods” in social psychological research. They note how these biases are often invisible to the researchers themselves. The authors themselves fall prey to these “invisible biases” by utilizing the five-factor model of personality and the trait of openness to experience as one possible explanation for the under-representation of political conservatives in social psychology. I show that the manner in which the trait of openness to experience is conceptualized and measured is a particularly blatant example of the very liberal bias the authors decry.
Prognostic significance of autoimmunity during adjuvant treatment of melanoma with interferon: Updated follow-up
Authors: U. Dafni, D. Pectasides, D. Tsoutsos, P. Panagiotou, A. Polyzos, A. Stratigos, C. Markopoulos, M. Mantzourani, D. Bafaloukos, H. Gogas
Journal: Journal of Clinical Oncology (2008)

9024 Background: Immunotherapies with beneficial effect in advanced melanoma have been shown to induce the collateral appearance of autoimmune responses, as thyroid autoantibodies and depigmentation. We have previously reported that the appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with adjuvant interferon is associated with statistically significant improvements in relapse-free and overall survival (RFS and OS) in patients with melanoma. In the current report, follow-up data were updated on October 1st 2007. Methods: Two hundred patients were included in the study. Peripheral blood was obtained prior to initiation of adjuvant interferon at completion of 1 month of intravenous interferon and at 3, 6, 9 months. Serum samples were tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin antibodies by enzyme linked immunosorbant assay (ELISA). Patients were examined for the appearance of vitiligo or other clinical manifestations of autoimmune diseases. The simultaneous prognostic effect of various factors was determined in a multivariate analysis with use of the Cox proportional-hazards model. Autoimmune status was included in the models as a time- dependent variable. Results: At a median follow up of 72 months (95% C.I., 66.8 - 76.3) 128 patients had a relapse and 105 have died. The previously reported median follow-up was 46 months with 115 observed relapses and 82 deaths. The median RFS was 28 months and the median OS was 63 months. Among patients without autoimmunity, the median RFS was 16 months (112 of 148 had a relapse) while among patients with autoimmunity 115 months (16 of 52 had a relapse). Nine out of the 16 relapses in the group with autoimmunity were late relapses observed at the additional follow-up period. The median OS was 37 months among patients without autoimmunity (98 of 148 died) and was not reached among patients with autoimmunity (7 of 52 died). In the univariate and multivariate Cox regression analysis autoimmunity was an independent prognostic factor for improved RFS and OS (p<0.001). Conclusion: The detection of autoantibodies and the appearance of clinical manifestations of autoimmunity remain a significant prognostic marker for RFS and OS with additional follow- up. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough
I chose reconstruction, but not to “look good”
Authors: Stella Duffy
Journal: BMJ (2016)

Stella Duffy flags up problems of concentrating on aesthetics in breast reconstruction surgery. For series information contact Rosamund Snow, patient editor, rsnow@bmj.com I have had breast cancer twice. The first time, when I was 36, I had a wide local excision, followed by chemotherapy and radiotherapy. In 2014, my annual mammogram showed ductal carcinoma in situ in breast tissue left from the original breast conserving surgery in 2000. Since the first cancer I had, naturally, been thinking about the possibility of recurrence. Therefore, it didn’t take long for me to agree to a mastectomy and breast reconstruction. My consultant told me that implants tend not to be recommended for patients whose skin has already been irradiated. I chose a reconstruction for many reasons: