tbuckley/cabot-search huggingface dataset:
The impact of lymphoscintographic drainage to the internal mammary nodes on the management of invasive breast cancer
Authors: A. J. Mirhadi, H. Chang, T. Nahidi, J. R. Hastings
Journal: Journal of Clinical Oncology (2005)

869 Background: Management of the internal mammary lymph nodes for invasive breast cancer has often been a question of much debate. In this study, we sought to determine how frequently there was drainage to the IM nodes as evidenced by lymphoscintigraphy (LSG), and if there was any correlation with location of primary or failure pattern. Also, we sought to determine what proportion of patients who had pathologically positive nodes had evidence of drainage to the IM nodes on initial LSG. Methods: We retrospectively reviewed the data from a single surgeon at our institution from 1998 to 2003 who had breast cancer surgery followed by LSG mapping. Overall, a total of 325 patients were evaluated with stage I-III breast cancer who had surgery followed by sentinel lymph node mapping using LSG. Radiographic LSG reports were analyzed for each patient, and their drainage patterns were recorded, as well as follow-up. Results: There were a total of 325 total patients reviewed. The location of the primary lesions were broken down as follows: 216 in the upper outer quadrant (UOQ), 60 in the upper inner quadrant (UIQ), 14 in the lower outer quadrant (LOQ), 31 in the lower inner quadrant (LIQ). The lymphoscintographic distribution was broken down as follows: 25 had evidence of drainage to the IM nodes, 193 had drainage to the axillary nodes, 7 had drainage to the SC nodes, 2 had contralateral drainage and 98 revealed no SLN on radiographic report. Overall, a total of 61 patients had positive nodes on either SLN biopsy. Of the 25 patients that had drainage to the IM nodes, 12 had a primary located in the UOQ, 4 in the UIQ, 2 in the LOQ and 6 in the LIQ. Of all patients that had positive nodes pathologically, only 3 had evidence of drainage to the IM nodes. Only one patient with evidence of lLSG drainage to the IM nodes had disease progression on follow up. Conclusions: Evidence of LSG drainage to the IM nodes did not represent a large cohort of patients that have had SLN biopsy (7.7%). In addition, having positive nodes on pathologic analysis did not correlate with an increased likelihood of IM drainage. Of these patients, only one had evidence of disease progression. In addition, location of primary did not seem to predict likelihood of drainage to the IM’s. No significant financial relationships to disclose.
Contemporary patients with hemophagocytic lymphohistiocytosis: An institutional experience
Authors: J. A. Niece, N. Ahmad, Z. R. Rogers
Journal: Journal of Clinical Oncology (2007)

20022 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and complex disease whose treatment has improved in the last decade. We report a single institutional experience with HLH to investigate current survival and prognostic significance of common clinical markers at presentation. Methods: Institutional hematology/oncology and pathology databases were searched to identify patients newly diagnosed with HLH, malignant histocytosis or hemophagocytic syndrome from 1995–2006. Patients meeting HLH 2004 diagnostic criteria: fever, cytopenias of &gt;2 cell lines, hypofibrinogenemia, splenomegaly, elevated ferritin, triglycerides, abnormal natural killer cell function and/or soluble interleukin (IL) 2 receptor were included. Labs, age, ethnicity, treatment and outcome were recorded. Univariate analyses were performed. Results: Nine patients (6 female, 3 male) met inclusion criteria. The median age at diagnosis was 3 yrs (range 9 mo-17 yrs). Five patients (56%) were of Hispanic ethnicity. Acute EBV infection was identified in 7 pts (78%) and CMV in 1 (11%). Diagnostic labs revealed median platelet count of 22,000/mm 3 , hyperbilirubinemia in 7 pts median 7.0 mg/dl, and ALT/AST elevation with median 241/180 U/L. Ferritin elevation and hypofibrinogenemia were prominent in all patients with a median ferritin of 9,092 ng/ml (range 345–130,334) and fibrinogen of 96 mg/ml. Soluble IL-2 receptor was markedly elevated; median 6,403 U/ml (range 4551–27,469). Pts were treated as per HLH 1994 or 2004, with a combination of steroids, IVIG, cyclosporine and VP16. At median follow-up of 12 mo (range 2–49) 8 pts are alive: 4 CR (1 after BMT), 4 PR clinically well with abnormal labs. Death from invasive Rhizopus infection during immunosuppressive therapy in 1. There were no predictive variables for survival identified. Conclusion: The 88% survival of these patients treated with modern HLH therapy significantly exceeds the 55% in prior reports. The large proportion of patients of Hispanic ethnicity distinguishes this from prior series. Whether this ethnic difference accounts for improved survival will need to be studied in larger population. HLH is no longer uniformly fatal, and should be actively sought in critically ill children. No significant financial relationships to disclose.
Airways reflux contributes to cough severity and airways inflammation in non-CF bronchiectasis
Authors: Pallavi Mandal, Alyn Morice, James Chalmers, Adam Hill
Journal: European Respiratory Journal (2011)

Objective: To assess the impact of airways reflux on clinical severity and airway inflammation in bronchiectasis.

Method: Patients with bronchiectasis completed the Hull airways reflux questionnaire (HARQ,which has been validated for use in assessing airways refux as a cause of cough). The minimum score was 0 and maximum 70. A score of >13 was indicative of reflux. Patients were followed-up with longditudinal spirometry, sputum culture and Leicester cough questionnaire (LCQ) as a measure of cough severity (3-severe and 21-no cough). Myeloperoxidase (MPO), neutrophil elastase (NE), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were measured from spontaneous sputum samples. Multivariable linear regression was used to determine independent factors associated with cough severity (LCQ).

Result: 187 completed the study. 58.2% were female. Median age was 65 years.

77.5% had reflux using HCQ.

Reflux+ve patients had more severe cough symptoms as per LCQ (15.2 (3.5) vs.19.4 (1.9)), p<0.001. Sputum levels of MPO, NE, IL-8, TNF-α and IL-1β were significantly higher in reflux+ve group (p<0.0001 for all comparisons).

![Figure][1] 



After adjusting for age, gender, co-morbidities, disease severity and chronic colonisation, reflux was independently associated with cough severity (-3.27 standard error 0.81, p=0.0002).

Conclusion: The presence of airways reflux is associated with more severe cough and increased airway inflammation in bronchiectasis.

 [1]: pending:yes
Case 31-2000
Authors: Robert D. Blute, Esther Oliva
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 32-year-old man was evaluated for a lesion of the urinary bladder.The patient had been well until 16 months earlier, when he had an episode of perineal pain associated with painful ejaculation and a brown, curdled ejaculate. There was no hematuria. His condition improved after treatment with ciprofloxacin. He had had no previous genitourinary symptoms except for the long-standing presence of dribbling after voiding.Four months before the evaluation, the patient was seen at this hospital because of urinary frequency of four days' duration, with intermittent passage of small blood clots in the urine, vague discomfort . . .
Lymphoreticular Tumors in Norway and in Other European Countries&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P. Correa, G. T. O'Conor, Helge Stalsberg
Journal: JNCI Journal of the National Cancer Institute (1973)

All histologic diagnoses of malignant lymphoma in Norway in 1968 were reviewed and reclassified according to the criteria of the UICC international lymphoma survey. Of all diagnoses of malignant disease, 3.2% were leukemias and 4.4% were lymphomas including multiple myeloma. Among solid lymphomas, multiple myeloma was the largest category, followed by Hodgkin's disease. The youngest patient with reticulosarcoma was 23 years old. All lymphosarcomas in patients <30 years old were of the poorly differentiated, diffuse variety. Stem cell lymphomas were seen only in individuals >40 years old. Lymphosarcoma was more frequent in rural than in urban areas, and reticulosarcoma was more frequent in urban areas. Only one case of Hodgkin's disease was observed in a child <10 years old, and the highest incidence was among individuals >60 years old. Mixed cellularity (MC) and nodular sclerosis (NS) subtypes both had biphasic incidence patterns with peaks around 30 years of age and in old age. There was a predominance of MC in old age, among males and in rural areas, and a predominance of NS in younger age, among females and in urban areas. The youngest patient with multiple myeloma was 46 years old, and the disease was more frequent in the population >80 years old than all other solid lymphomas combined. Age distributions for lymphosarcoma and lymphatic leukemia were similar. Of all solid lymphomas except multiple myeloma, 20% presented at extranodal sites, most commonly in the stomach, the intestines, and other and unspecified abdominal sites. A review of the literature on the incidence of and mortality from malignant lymphomas in various European countries showed no obvious geographic differences. The recorded mortality from all major types of malignant lymphoma increased during 1950-63 in all European countries, which was ascribed to improvements in diagnosis and registration.
Response to: ‘Lumacaftor/ivacaftor for patients homozygous for Phe508del-CFTR: should we curb our enthusiasm?’ by Jones and Barry
Authors: J Stuart Elborn, Bonnie Ramsey, Claire Wainwright, Michael Boyle
Journal: Thorax (2015)

The commentary on ivacaftor for patients homozygous for Phe508del-CFTR (c.1521_1523delCTT; formerly F508del) ‘Should we curb our enthusiasm?’ by Jones and Barry makes a number of important points regarding the potential impact of ivacaftor/lumacaftor combination in cystic fibrosis (CF).1 However, the view taken by the authors is rather pessimistic regarding the scientific and clinical impact of combination therapy for people with CF. The TRAFFIC and TRANSPORT studies were designed to test the efficacy and safety of this combination in line with regulatory requirements from the Federal Drugs Administration and European Medicines Agency (EMA). The phase III pivotal programme, as noted in the commentary, met its primary end point of improvement in FEV1, with significant changes in secondary end points in the pooled analyses of frequency of exacerbations and quality of life.2 The reduction in exacerbations (39%) and hospitalisations (61%) are clinically important outcomes as frequent exacerbations are associated with accelerated decline in lung function and worse survival.3 ,4 In a study recently published using registry data from patients with the Gly551Asp mutation treated with ivacaftor in the clinic, there is continued benefit in attenuation of the rate of decline in lung function.5 This suggests that the benefits of restoration of cystic fibrosis transmembrane conductance regulator (CFTR) function go beyond initial improvement in FEV1 alone.

The scientific underpinning of combination therapy is that lumacaftor has a correcting effect on mutant Phe508del-CFTR, increasing its …
Clinical experience of using docetaxel-cisplatin in the treatment of advanced ovarian cancer: A Bangladesh perspective
Authors: M. Mokhlesuddin, P. S. Akhter, D. U. Ahmed, M. A. Khan, M. A. Rahman, T. Islam
Journal: Journal of Clinical Oncology (2006)

15070 Background: Docetaxel is an active agent in the treatment of recurrent advanced ovarian cancer. We conducted a multi-center phase II study to evaluate the response rate, toxicity and survival of docetaxel-cisplatin regimen as first-line treatment of advanced ovarian cancer in Bangladeshi population. Methods: Forty chemotherapy-naïve patients of advanced epithelial ovarian cancer were recruited between October 1999 to March 2002. Eligibility criteria included stage Ic-IV patients, age 18–75 years, an ECOG performance status of 0–3 with adequate hepatic, renal and bone marrow function. Docetaxel 60 mg/m 2 as 1 hour IV infusion and cisplatin 75 mg/m 2 were given on day 1 every 3 weeks for a maximum of 6 cycles (average 5 cycles). Tumor responses and toxicities were evaluated by relevant investigations and survival was documented. Results: A total of 40 patients were enrolled. Median age was 44 years (age range 18–75 years). All the patients were evaluable for response. Overall response was observed in 32 patients (80%) with complete response rate 38% (12 patients), partial response rate 62% (20 patients). Stable disease was seen in 5 patients (12.5%) and progressive disease was in 3 patients (7.5%).Two years survival was documented in 62% patients. Toxicities were limited with grade 3 neutropenia in 10 patients (25%) and some non-hematological toxicities (including nausea, vomiting and fluid retention) in twenty-six patients (65%). No severe febrile neutropenia and no events of death were observed. Conclusions: The combination of docetaxel and cisplatin appears to be effective with manageable toxicities in patients with advanced epithelial ovarian cancer in Bangladeshi population. No significant financial relationships to disclose.
Combined Modality Treatment for Osteosarcoma Occurring as a Second Malignant Disease
Authors: Stefan S. Bielack, Beate Kempf-Bielack, Ulrich Heise, Dorothea Schwenzer, Kurt Winkler
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The prognosis of osteosarcoma occurring as a second malignant disease (OS-SMD) is thought to be poor. We attempted to evaluate whether this holds true when OS-SMD is treated with combined modality therapy as developed for primary osteosarcoma and if factors that influence survival might be identified. PATIENTS AND METHODS: All patients with OS-SMD registered at the Cooperative German-Austrian-Swiss Osteosarcoma Study Group (COSS) study center between 1980 and June 1996 were evaluated for patient- and treatment-related factors, local and systemic outcome, and survival. Therapy was to be given according to contemporary COSS protocols for primary extremity osteosarcoma, including surgery and multiagent chemotherapy. RESULTS: Thirty patients with OS-SMD were registered (median latency period, 9 years 2 months). The first malignancies had been retinoblastoma (10 patients), sarcoma (10 patients), lymphoma (five patients), carcinoma (four patients), and medulloblastoma (one patient). Treatment for these malignancies had included radiotherapy in 24 patients, surgery in 20, and chemotherapy in 14. Twelve osteosarcomas were located axially and 18 were located in an extremity; 17 were radiation-related. Twenty-seven patients presented with localized disease; three presented with primary metastases (two skip, one lung). All 30 patients received chemotherapy, 29 with multiple drugs. Twenty-eight patients underwent operation. At 7 years, actuarial overall survival, survival free from osteosarcoma progression, and survival free from progression of any cancer were 50%, 34%, and 30%, respectively. In 24 patients with local tumor control, the corresponding values were 63%, 46%, and 38%. All seven local failures occurred in patients with axial osteosarcomas who did not undergo operation with wide surgical margins. CONCLUSION: Provided that local tumor control is achieved, OS-SMD treated with combined modality therapy may have a prognosis that approaches that of otherwise comparable primary osteosarcoma.
Abstract 16723: Complementation of Mutant Embryos Demonstrates a Cell Autonomous Requirement of Etv2
Authors: Tara L Rasmussen, Camille A Walter, Joel E Rosenberg, Xiaozhong Shi, Mary G Garry, Naoko Koyano-Nakagawa, Daniel J Garry
Journal: Circulation (2014)

Our previous studies have demonstrated that the disruption of  Etv2 , a gene encoding an Ets related transcription factor, resulted in the absence of the endothelial/endocardial lineages. Etv2 is unique in that it has a limited window of expression from E7 to E9. It is unknown whether all endothelial/endocardial progenitors require Etv2 expression or whether this is only a requirement for the initial vasculogenic progenitor/stem cells. We hypothesized that complementation of Etv2 mutant embryoid bodies (EBs) or embryos with wildtype embryonic stem cells (ESCs) would rescue the endothelial defect in a cell autonomous manner and mutant cells would not contribute to vessel development. To address this hypothesis, we co-differentiated mouse wildtype and mutant ESCs with EYFP-labeled wildtype ESCs. We observed that differentiation of wildtype EYFP-ESCs resulted in contributions to the endothelial lineage. Further, co-differentiation of Etv2 mutant and EYFP-labeled ESCs resulted in endothelial cells derived solely from the wildtype EYFP-labeled cells, indicating that the rescue event is cell autonomous. We further addressed this hypothesis using blastocyst complementation  in vivo . We interbred mice hemizygous for two distinct  Etv2  gene disruptions and harvested blastocysts at E3.5. EYFP-labeled ESCs were injected into the blastocoele cavity and transferred into pseudopregnant mice. At E10.5, a day after the death of Etv2 mutant embryos, the developing embryos were analyzed for chimerism and the contribution of EYFP-labeled ESCs to various cell lineages. We observed that the EYFP-labeled ESCs contributed randomly to all lineages in the wildtype or heterozygous Etv2 embryo. However, when the recipient was an Etv2 mutant blastocyst, the EYFP-labeled cells preferentially gave rise to endothelial lineages. These wildtype ES cells rescued the phenotype of mutant embryos in direct correlation with the degree of chimerism. Furthermore, this was a cell autonomous event as unlabeled mutant cells were unable to give rise to endothelium. We conclude that all endothelial progenitors during embryogenesis require Etv2 expression.
Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma
Authors: Mark Bettington, Neal Walker, Christophe Rosty, Ian Brown, Andrew Clouston, Diane McKeone, Sally-Ann Pearson, Barbara Leggett, Vicki Whitehall
Journal: Gut (2015)

Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/carcinoma to better define their features and the pathways by which they progress to carcinoma.A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and immunostained for MLH1, p53, p16, β-catenin and 0-6-methylguanine DNA methyltransferase (MGMT).The median polyp size was 9 mm and 86.5% were proximal. Most were BRAF mutated (92.7%) and 94.0% showed CIMP. Mismatch repair deficiency, evidenced by loss of MLH1 (74.5%) is associated with older age (76.7 versus 71.0; p<0.0029), female gender (70% versus 36%; p<0.0008), proximal location (91% versus 72%; p<0.02), CIMP (98% versus 80%; p<0.02) and lack of aberrant p53 (7% versus 34%; p<0.001) when compared with the mismatch repair-proficient cases. Loss of p16 (43.1%) and gain of nuclear β-catenin (55.5%) were common in areas of dysplasia/cancer, irrespective of mismatch repair status.SSAs containing dysplasia/carcinoma are predominantly small (<10 mm) and proximal. The mismatch repair status separates these lesions into distinct clinicopathological subgroups, although WNT activation and p16 silencing are common to both. Cases with dysplasia occur at a similar age to cases with carcinoma. This, together with the rarity of these 'caught in the act' lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia.
Chemical Evaluation of the Beeswax Pellet Implantation Bioassay Model for Studies of Environmental Carcinogens 2
Authors: I. B. Rubin, M. R. Guerin
Journal: JNCI Journal of the National Cancer Institute (1977)

The release properties of a number of constituents of cigarette smoke condensate in a condensate--beeswax matrix were characterized by an in vitro study. Eighteen compounds that were representative of several classes of condenate components were tested. Equal quantities of condensate and beeswax, mixed with tracer quantities of the 14C-labeled test compounds, were formed into rod-shaped pellets similar to those used for trachea implant studies, and the rate at which the 14C was removed from the pellet by a flowing saline stream was monitored. Results indicated a wide range in the rates of which the test compounds were released from the pellets. The smaller and water-soluble molecules were released rapidly; about 90% of the nicotine and phenol were leached out in the first 24 hours. Larger and less soluble molecules were released slowly or not at all. Only about 10% of the stearic acid and essentially none of the benzo[a]pyrene was released in 28 days. The effects of such an uneven release of components from an implantation of biologically active material in an inert carrier matrix are discussed with regard to bioassay systems.
Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia.
Authors: W L Furman, S D Baker, C B Pratt, G K Rivera, W E Evans, C F Stewart
Journal: Journal of Clinical Oncology (1996)

To determine the maximum-tolerated systemic exposure (MTSE) and exposure-limiting toxicity of continuous infusion topotecan in children with recurrent acute leukemia.Patients received escalating levels of topotecan systemic exposure as measured by steady-state topotecan lactone concentration (Css). Samples obtained within the first 24 hours were measured by high-pressure liquid chromatography (HPLC) for topotecan. A two-compartment model was fit to the data using a Bayesian algorithm. Css was calculated for each patient; if it differed by more than 20% of target, a new dosage was begun within 6 hours. Follow-up concentrations were obtained as well as serial plasma samples postinfusion. Toxicity and evidence of activity were assessed after each course.Thirteen boys and five girls received 23 courses of topotecan. Target Css ranged from 1.0 to 5.3 ng/mL (topotecan doses, 0.5 to 3.3 mg/m2/d). Nineteen of 23 courses were within +/- 20% of target after adjustment (range, 77% to 139%). The MTSE was 4.0 ng/mL, and mucositis was exposure-limiting at 5.3 ng/mL. A significant relation between topotecan lactone Css and the severity of mucositis was observed. Myelosuppression was experienced but was not considered exposure-limiting. One complete response and one partial response were noted.The MTSE for continuous infusion topotecan was 4.0 ng/mL. Responses were noted at Css comparable to those producing responses in a severe combined immunodeficiency (SCID) mouse model. Further studies of topotecan are warranted.